Quality and Relevance of Research and

Related Activities at the Gorges Memorial

Laboratory

August 1983

NTIS order #PB87-142238
Library of Congress Catalog Card Number 83-600577

For sale by the Superintendent of Documents,

U.S. Government Printing Office, Washington, D.C. 20402

ii
Foreword

The Gorgas Memorial Institute of Tropical and Preventive Medicine, Inc. (GMI)

and its operating arm, the Gorgas Memorial Laboratory (GML) have been conducting

tropical research, training, and public health activities for more than half a century.

Questions about GMI’s continued existence were raised this spring when the National

Institutes of Health requested no funds for the core support for GML. Gorgas’ existence

is at stake because the core support appropriation by the United States represents about

three-quarters of GMI’s total budget.

The Senate Committee on Appropriations and its Subcommittee on Labor, Health

and Human Services, and Education requested that the Office of Technology Assessment (OTA) examine the quality and relevance of research and related activities of GML.

Such information is needed in order to adequately judge whether the core support should

be terminated. The subcommittee also requested that the General Accounting Office

undertake a concurrent evaluation of four areas: the peer review process at GMI/GML,

the extent of other federally funded tropical medicine research activities, efforts by Gorgas

to broaden its financial base of support, and the possible impacts on U.S. regional relationships if funding was terminated.

This technical memorandum presents the results of OTA’s examination. It reviews

the quality and relevance of activities at GML, based on Gorgas’ publishing record,

an OTA-commissioned survey of GML’s scientific reputation, a critical review of recent articles and current manuscripts, a comparison of GML’s areas of effort with health

problems in tropical America and with scientific opportunity, and a review of past scientific evaluations of GML.

OTA finds that GML’s research and related activities are generally of high quality

and relevance to the region and the United States. The United States receives excellent

benefit for its contribution to GMI/GML. If Gorgas were to close down, the United

States would most likely have to develop a capability to undertake many of the current

activities of GML. OTA finds that there would be both health-related and international

relations repercussions if the United States were to withdraw its support for GML.

Although GMI could be improved in several significant respects, GML is producing

important work of high quality and represents an excellent investment of health funds.

This memorandum benefited from the consultation and review of a large number

of persons in the Federal Government, universities, international health organizations,

and private industry. Key OTA staff involved in the analysis and writing were Hellen

Gelband, Clyde J. Behney, Steven S. Bjorge, and John S. Willems.

/j2?- A %. “

JOHN H. GIBBONS

Director

. . .

Ill
OTA Staff—Quality and Relevance of Research at

Gorgas Memorial Laboratory

H. David Banta, Assistant Director, OTA

Health and Life Sciences Division

Clyde J. Behney, Health Program Manager

and Study Co-Director

Hellen Gelband, Study Co-Director

Steven S. Bjorge, Analyst

John S. Willems, Research Assistant

Virginia Cwalina, Administrative Assistant

Jennifer Nelson, Secretary

Mary Walls, Secretary

Gwenn Sewell, Research Assistant

Contractors

Michael B. Macdonald

The Johns Hopkins University

Richard K. Riegelman

The George Washington University

OTA Publishing Staff

John C. Holmes, Publishing Officer

John Bergling Kathie S. Boss Debra M. Datcher Joe Henson

Glenda Lawing Linda A. Leahy Cheryl Manning
Contents

Page

CHAPTER 1: INTRODUCTION AND BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Organization of the Technical Memorandum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Summary of Findings and Conclusions. ..., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

The Tropics and Tropical Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . .

The Value of Laboratories Located in the Tropics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CHAPTER 2: GORGAS MEMORIAL INSTITUTE AND LABORATORY . . . . . . . . . . . . . . .

Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . .

Activities of GIL...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CHAPTER 3: QUALITY OF RESEARCH AT THE GORGAS MEMORIAL LABORATORY.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . . . . . . . . . . . . . . . . . . . . . . . .

Site Visits by the Fogarty International Center ...,...,. . . . . . . . . . . . . . . . . . . . . . . .

Review of Research Programs. . . . . . . ..., ..., ..., . . . . . . . . . . . . . . . . . . . ..., ..., ...,

Arbovirus Program. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Environmental Assessment Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Diarrheal Diseases Program ., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Sexually Transmitted Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Cancer Registry/Cancer of the Cervix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Publications . . . . . ..., ..., . . . . . . . . . . . . . . ..., . . . . . . . . . . . . . . . . . . . . . ..., . .

Peer Review at the Gorgas Memorial Laboratory, . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . .

Grants and Contracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . . . . . . .

Quality of Research at GML as Seen by Experts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CHAPTER 4: RELEVANCE OF RESEARCH AT GORGAS MEMORIAL LABORATORY

TO HEALTH PROBLEMS IN TROPICAL AMERICA . . . . . . . . . . . . . . . . . . . . . . . .

Tropical Diseases: Description and Status ., ..., . . . . . . . . ..., . . ..., ..., ..., . . . . . .

Acute Respiratory Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Diarrheal and Enteric Diseases . . . . . . . . . . . . . . . . . ..., . . . . . . . ..., ..., . . . . . .

Malnutrition . . . . . . . . . . ..., . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., ..., ..., . . .

Malaria . . . . . . . . . . . . . . . . . . . ..., . . . . . . ..., ..., ..., . . . . ..., ..., ..., ...,

Chagas’ Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Leishmaniasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . . . .

Anthropod-Borne Viral Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Filariasis ..., . . . . . . . . . . . ..., . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . . . . . . . .

Schistosomiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . .

Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Relevance of Research at Gorgas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CHAPTER 5: FINDINGS AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Findings. ..., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...,

Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3

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51

55

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v
Contents—Continued

Page

Appendixes

A. Acknowledgments; Pan American Health Organization Liaison Group;

OTA Health Program Advisory Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

B. Tropical Disease Research Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

C. Bibliography of Publications by the Gorgas Memorial Laboratory Staff . . . . . . . . . . . . . . . . 67

D. Summary of the Telephone Survey on Gorgas Memorial Laboratory . . . . . . . . . . . . . . . . . . 77

E. Glossary of Acronyms and Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Tables

Table No. Page

l. The Gorgas Memorial Laboratory’s Major Accomplishments From 1970 to the Present . . 7

2. Major Accomplishments of the Gorgas Memorial Laboratory, 1929-69 . . . . . . . . . . . . . . . . 8

3. A: Sources of Financial Support for the Gorgas Institute and Laboratory Fiscal Years 1975-82 15

B: Sources of Financial Support for the Gorgas Institute and Laboratory Fiscal Years 1975-82 16

4. Gorgas Memorial Institute of Tropical and Preventive Medicine, Incorporated:

Operating Budgets Fiscal Years 1982 and 1983 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

5. Gorgas Memorial Institute of Tropical and Preventive Medicine, Incorporated:

Projection Fiscal Year 1984 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

6. Gorgas Memorial Laboratory Information on Scientific Staff as of July 1983 . . . . . . . . . . . 20

7. Recent Activities of Gorgas Memorial Laboratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

8. Total Publications of the Gorgas Memorial Laboratory, 1975-83 . . . . . . . . . . . . . . . . . . . . . . 31

9. Gorgas Memorial Laboratory: Publication Location for Articles

Written by Staff; 1980 to July 1983 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

10. Articles and Manuscripts Reviewed for the Office of Technology Assessment

by Richard K. Riegelman, M.D. Ph. D..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

11. Gorgas Memorial Laboratory: Grants and Contracts as of July 1983 . . . . . . . . . . . . . . . . . . 35

Figures

Figure No. Page

l. Gorgas Memorial Institute Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

2. Gorgas Memorial Institute-Proposed Organization Chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Chapter 1

Introduction and Background
Chapter 1

Introduction and Background

The Gorgas Memorial Laboratory (GML) is a

research institution concerned with tropical

medicine and public health, It undertakes both applied and basic research, and performs laboratory,

clinical, and field research activities. GML was

established in 1928 in commemoration of the work

of Gen. William Gorgas in in controlling yellow

fever. The Laboratory is located in Panama City,

Republic of Panama. It is the research arm of the

Gorgas Memorial Institute of Tropical and Preventive Medicine, Inc. (GMI), a (U. S.) domestic,

nonprofit corporation headquartered in Washington, D.C.

INTRODUCTION

GML is a specific subject of evaluation because

of questions concerning its fiscal year 1984 appropriation. GMI is authorized by act of Congress

(Public Law 70-350, as amended) to receive a yearly appropriation, not to exceed $2 million, from

the U.S Government. The original fiscal year 1984

budget request from the Fogarty International

Center (FIC)—the unit of the National Institutes

of Health (NIH) given responsibility for administering the Gorgas budget request—included a

budget request for Gorgas. A subsequent revision

by NIH, of the NIH budget, led NIH/FIC to request no funds at all for core support of GMI.

Because this core support of close to $2 million

is an extremely large percentage of the total GML

budget (see ch. 2), this action effectively meant

that GML would have to close down.

In order to evaluate whether this action was

justified on the basis of the quality of Gorgas’

research and on its success in identifying needs

and conducting research relevant to health concerns of Panama and tropical America* (especially

Central America and the Caribbean), the requesting subcommittee and committee asked both

‘The term tropical America here refers to the southern part of

North America, all of Central America and the Caribbean, and

tropical South America,

This technical memorandum presents the results

of a review of the quality and relevance of research and related activities of GML. The evaluation was conducted at the request of the Senate

Committee on Appropriations and, especially,

its Subcommittee on Labor, Health and Human

Services, and Education. It is part of a broader

OTA assessment of the status of biomedical research and related technology for tropical medicine, also requested by the committee and subcommit tee.

the General Accounting Office (GAO) and the

Office of Technology Assessment

vide relevant information.

The related effort by GAO

topics:

1.

2.

3.

4.

the process of peer review

(OTA) to preexamines four

used by GML

before initiating research projects and after

their completion,

efforts to broaden the financial base of GML,

other federally funded tropical medicine

research activities, and

the possible impact of GML’s closing on

U.S.-Panamanian relations. That report is

scheduled for completion in August 1983.

The OTA effort devotes some attention to the

first of those four topics, but is primarily addressed to issues of:

1.

2.

the quality of GML’s applied biomedical

research projects, epidemiological activities,

maintenance of research animal populations,

and other research-related activities such as

training; and

the relevance of GML’s research and other

activities to the health needs and problems

of Panama, other tropical American countries, the U.S. interests, and to tropical

medicine in general.

3
4

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6

Organization of the Technical

Memorandum

The remainder of this chapter contains a summary of the findings and conclusions of the

technical memorandum and background information on the Tropics, tropical diseases, and the role

of research laboratories located in the Tropics.

Chapter 2 presents descriptive material on Gorgas,

its structure, and past and current research activities. Chapter 3 examines evidence on the quality of GML’s research, public health, and training activities.

The fourth chapter presents descriptions and

brief data on the status of the diseases and health

problems of critical importance to tropical America and of research related to them. Gorgas’s activities are then discussed in the context of these

diseases and conditions. The final chapter presents

the findings and conclusions.

Appendix A presents the acknowledgments,

lists the members of the Liaison Group formed

by the Pan American Health Organization to provide advice to OTA on this project, and lists the

OTA Health Program Advisory Committee. Appendix B is a brief presentation of other current

research activities in tropical health. Appendix C

is a bibliography of publications since 1975 by

GML staff. Appendix D is a summary of the OTA

survey of experts’ opinions concerning Gorgas and

its research quality and relevance. Appendix E

contains a list of acronyms and a glossary of

terms.

SUMMARY OF FINDINGS AND CONCLUSIONS

OTA examined the quality and relevance of

tropical medicine research and related activities

at GML, The evaluation of the quality of an institution such as Gorgas cannot take place without explicit recognition of certain premises:

●

●

●

●

There is an inherent value in supporting

tropical research laboratories in tropical

countries. Field conditions present opportunities that cannot be duplicated by organizations such as NIH.

Evaluations of the quality of research are inevitably, and properly, made partly on the

basis of fairly objective criteria such as

publications record and partly on the basis

of subjective judgments by qualified individuals.

The criteria used to judge quality, although

similar in type, need to be modified and

weighted differently for research performed

in well-equipped, state-of-the-art laboratories

than for field research laboratories.

Relevance is directly dependent on the type

and location of institution, and it should be

examined from each of the appropriate viewpoints (e.g., host country, region, United

States, general advancement of knowledge).

With these premises in mind, OTA examined

the quality of Gorgas’ research against a range of

objective and subjective criteria. There was very

impressive agreement among the results of: 1 ) the

past scientific evaluations of GML, 2) the critical

evaluation of the research design and presentation of articles and manuscripts, 3) the survey of

expert scientific opinion on Gorgas’ quality, 4) interviews with Panamanian health officials and

professionals, 5) the examination of GML staff’s

publications record, and 6) an examination of

GML’s record of competing for grants and contracts. All evidence gathered by OTA led to the

finding that the overall scientific quality of GML

is high, especially when considered in the context

of GML’s status as a research laboratory located

in the Tropics. Quality was, naturally, not

uniformly even.

OTA also found that the large majority of

GML’s research is highly or adequately relevant

to health concerns and problems of Panama, the

tropical American region, U.S. interests, and the

advancement of scientific knowledge and the field

of tropical medicine in general. (Table 1 lists

significant accomplishments of GML in the past

decade; table 2 shows significant activities during the previous period of GML’s history. ) The

evidence for this finding lies, for the first two, in

the match between tropical health problems and

GML research directed at them, and from strongly
7

Table 1 .—The Gorgas Memorial Laboratory’s Major

●

●

●

●

●

●

●

●

●

●

●

●

●

●

●

Accomplishments From 1970 to the Present

Continued yellow fever surveillance and monitoring of

vectors

St. Louis encephalitis and Venezuelan equine

encephalitis vectors and reservoirs

Insect genetic studies using isozyme markers

Transovarial transmission of yellow fever virus in

mosquitoes

Use of Aotus monkey model for testing of therapeutics

Several new viral isolates in area

Screening of antimalarial drugs and identification of

promising therapeutic antimalarial compounds

WHO regional center for bloodmeal analysis

Improved identification of insect vectors: sandflies,

triatomines, blackflies, etc.

Development of cancer registry in the Republic of

Panama

Discovery of high incidence of cervical and penile

cancer in Herrera Province (Republic of Panama)

Studies of sexually transmitted diseases in the

Republic of Panama (the first such studies in Latin

America)

Rapid identification of viral agent in recent epidemics

of conjunctivitis and encephalitis in the Republic of

Panama

Discovery of high HTLV antibodies in the Republic of

Panama

Environmental impact assessment of Tabasara

Hydroelectric project

SOURCE: Gorgas Memorial Laboratory, Office of the Director August 1983

expressed opinions and examples by various Panamanian officials and professionals.

The importance of GML to Panama cannot be

judged solely on the basis of Panama’s monetary

contribution. Panama is going through a difficult

economic period. Even so, the Ministry of Health

has arranged a loan to keep GML in operation

for the remainder of fiscal year 1983. The value

of the land, buildings, and tax-favored status have

never been adequately assessed. And to put the

often criticized direct financial contribution of

$10,000 from Panama in perspective, the research

budget of the Panamanian medical school is reportedly only $20,000. As one official of the U.S.

Department of State expresses it: Each year, the

United States sends a message to Panama and the

region by funding GML and supporting activities

related to the health of U.S. and Panamanian

citizens alike (51).

Activities related to the recent Panama Canal

Treaty process provide a specific example of the

importance of GML to Panama, As part of the

treaty, a Joint Committee on the Environment was

established. Panama turned to GML, as the only

institution in Panama with the necessary skills and

experience, for assistance in relation to environmental protection and human and animal health,

and additionally named Dr. Pedro Galindo, formerly of GML, as the senior Panamanian on the

Committee.

Relevance to U.S. health interests can be found

in the surveillance activities, the training activities,

and the various research activities undertaken

under contract to the U.S. military. There are

about 20,000 U.S. Government employees and dependents in Panama; and many thousands more

in nearby countries. The work of GML is directly relevant to the health of these people.

Gorgas’s contributions in the areas of malaria,

yellow fever, and leishmaniasis illustrate its

relevance to the general advancement of knowledge (see also, tables 1 and 2).

Based on the above evidence, OTA finds that

with some exceptions that occur almost entirely

within the core-funded activities, the research conducted at Gorgas is relevant to the various parties at interest.

Conclusions: OTA concludes that the benefits

of supporting GML justify, on scientific and other

grounds, the relatively small amount of funds required. Quality and relevance are high. Withdrawing core support from Gorgas would probably not even save the amount of the appropriation, since other Federal agencies may need to

either conduct or support research now carried

out at GML.

Gorgas is not ideal; improvements could certainly be made. Some of the shortcomings stem

from its uncertain funding. The prospect of

unstable funding and perhaps closure may have

kept individual scientists [rem joining GML or

becoming visiting scientists there and may reduce

the desire of U.S. universities to collaborate with

GML on research projects.

Another example of the effect of uncertain

funding has been the decision by the U.S. Navy

to hold off on the next scheduled training class,

because the course would extend a few weeks into

fiscal year 1984. It is extraordinarily difficult to
8

Table 2.–Major Accomplishments of the Gorgas Memorial Laboratory, 1929-69

——.

i. Protozoa/ Diseases of Man and Lower Animals:

Malaria:

1933 and subsequently: First long-range, large-scale field

tests of the antimalarial drugs, Atebrine, chloroquine, and paludrine under controlled conditions in

the New World Tropics,

1954: First long-range field tests of DDT house-spraying

to control malaria.

1960: Field demonstration of the effectiveness of weekly

doses of pyrimethamine-primaquine drugs combined with the eradication of Plasmodium falciparum

malaria from a tropical area.

1966: Demonstration that certain common human malaria

parasites could be grown in certain species of

Panamanian monkeys and could be transferred to

man and other monkeys by blood inoculation and

by bites of mosquitoes.

American Trypanosomiasis:

1931: First report of Chagas’ disease in Panama and

discovery of the vectors.

1959: First report of Trypanosoma range/i from man and

wild vertebrates i n Panama and demonstration of the

development of the human strain in the salivary

glands of Rhodnius pallescens.

1965: Demonstration that the Panamanian strain of T.

range/i differs from the South and Central American

strains in its behavior of development i n the insect

vector.

Leishmaniasis:

1965: Incriminate ion of seven wild vertebrates as reservoir

hosts of human Ieishmaniasis.

1966: Demonstration that Ieishhmania infection may commonly occur i n the apparently normal skin of some

feral animals without producing lesions.

1945-68: Recognition of over 70 species of Phlebotomus in

Panama, of which 4 or 5 have been found infected

with Ieishmania.

Animal Trypanosomiasis:

1932: Discovery of the vampire bat transmission of equine

trypanosomiasis.

1932: Discovery of bovine trypanosomiasis in Panama.

Intestinal Protozoa:

1944: First finding of Isopora hominis in Panama.

Il. Helminthic Diseases of Man and Lower Animals:

1934-35: First comprehensive survey of the worm parasites

of equines in Panama.

1966: Finding a new human disease entity caused by

Echinococcus oligarthrus, a little known cestode

parasite of pumas and other large felines; description of the first known human case that terminated

fatally; and demonstration of the life cycle of the

parasite.

—

Ill. Rickettsial Diseases:

1946: First report of Q Fever in Panama.

1 947: First report of murine typhus in Panama.

1 951: First recognition of Rocky Mountain Spotted Fever

in Panama.

IV. Virus Diseases:

1 949:

1 957:

1958:

1960:

1961 :

1963:

1964:

1965:

1968:

First demonstration of the mosquito vectors of

yellow fever in Panama and Central America and the

inauguration of comprehensive studies on vector

ecology and transmission capabilities.

First recovery of St. Louis encephalitis virus and

recognition of human cases in Panama.

First isolation of Ilheus virus in Central America.

First isolation of Changuinola virus from man.

Discovery of four new arboviruses: Madrid, Ossa,

Patios, and Zegla.

First isolation of Wyeomyia subgroup of arboviruses

from man.

Recognition of the first human case of Ilheus

encephalitis.

Finding of crab-hole mosquitoes (Deinocerites) as

hosts for St. Louis encephalitis virus.

First isolation of Vesicular Stomatitis virus (Indiana)

from man in Panama and detection of virus transmission by the use of sentinel monkeys.

V. Medical Entomology:

1929: First elucidation of the human botfly, Dermatobia

hominis, in man.

1 935: First establishment of a laboratory colony of

anopheles albimanus, the main vector of malaria in

Central America.

1 944: First tests of DDT to control phlebotomine sandflies,

1 945: First experimental trials of DDT for the control of

Simulium spp., the vectors of Onchocerca volvulus,

the blinding filariid parasite of man.

1 945: First experiments with DDT for the control of

Culicoides sandflies.

1 945: First observations in Panama on the habits and life

histories of chigger mites (Trombiculidae), potential

vectors of disease.

1966: First comprehensive survey of the ticks and biting

insects of Panama.

V/. Miscellaneous Projects:

1930-54: Comprehensive survey of the poisonous snakes of

Panama and the incidence of snake bites.

SOURCE Willard H Wright, 40 Years of Tfopcal kfe~iClfw Res=cb (wmhlngton, D C Reese Pre;s, 1970)

— — . ——

plan and carry out research related to tropical dis- ●

eases without multiyear budgeting and some as- ●

surance of multiyear funding.

Gorgas itself could improve its standing and its Ž

relevance by:

being more aggressive in its publishing,

by making better use of its Advisory Scientific Board (see ch 5 for examples of possibilities),

by more actively seeking out associations and

collaborations with a range of universities,
9

groups from other countries, and international organizations,

Ž by making strategic plans to move more fully

into the developing areas of modern science

(e.g., work with monoclonal antibodies and

other immunological diagnostics, and biotechnology approaches to vaccine-related

 research and development), and

Ž by making more of an effort to run vigorous

visiting scientist and fellowship programs.

OTA concludes that the only benefit to the

United States of defunding Gorgas would be savings of perhaps significantly less than $2 million

a year, The negative consequences would include

loss of one of the few, high-quality, broadly relevant, tropical research institutions located in a

tropical country. The standing of the United States

in tropical America would inevitably suffer.

BACKGROUND

The Tropics and Tropical Diseases

The Tropics can be roughly considered to include Central America, much of South America,

the South Pacific, southern Asia, and most of subSaharan Africa. Tropical nations are usually

characterized by poverty, substandard drinking

water and sanitation, hot and humid climates,

poor health services, low levels of education, and

in some cases swampy or jungle areas. Annual

per capita income is often extremely low (as low

as or even less than $100). Ir. tropical America,

the average per capita gross domestic product was

$1,500 in 1980. However, the variation is wide,

ranging from nearly $9,000 in the Bahamas and

$2,685 in Barbados (both figures may be deceptive) to $267 in Haiti and $568 in Bolivia (75).

Of the world’s approximately 41⁄2 billion people, about three-quarters live in less developed

countries, most of which are tropical. Of the approximately 600 million population (1980 figures)

of the Western Hemisphere, about 60 percent live

in Latin America, most of which is tropical.

Health status is generally poor, with high rates

of infant mortality (primarily due to malnutrition,

lack of prenatal care, and diarrheal and respiratory infections), widespread infection with debilIronically{ GML is ir: danger of extinction at

the very time that U.S. interest in Latin America

is high, and at a time when tropical medicine has

never been more relevant to U.S. interests.

In summary, OTA concludes that the positive

consequences of U.S. core support of Gorgas

greatly outweigh the amount of funds involved.

Defunding new, followed by an appreciation of

the loss later and a subsequent attempt to reinstate

such a research capability, may result in much

larger required investments, an inability to

recreate successful conditions for quality research,

or both. *

‘In fact, it may be impossible to recreate GMI. or a ~imilar ]nsti t u tion In the current political climate in I.atin America (s 1 )

itating disease, and high mortality and morbidity rates from all diseases except certain chronic

ones associated with a higher standard of living

(such as some cancers).

Any definition of “tropical disease” is arbitrary.

In its strictest sense, perhaps, a tropical disease

is one found—for reasons of physical environment

and climate or the presence of specific disease

vectors—entirely or predominantly in tropical regions.

However, a more realistic, and more useful,

definition includes those diseases or conditions—

such as acute respiratory infection, tuberculosis,

malnutrition, or cholera—that occur or could occur in many regions, but which are considerably

more prevalent in tropical areas because of the

social and economic conditions that characterize

many tropical countries. In countries with very

low per capita gross domestic products, inadequate or unsafe water supplies and sanitation, low

levels of health care services, high levels of illiteracy, and similar conditions, certain diseases

are able to flourish beyond the extent that would

be predicted simply on the basis of climate.

The OTA assessment, including this technical

memorandum, will consider “classic” tropical dis-
10

eases such as malaria that fit the narrower definition, but it will more generally be guided by the

broader definition. Thus, a more appropriate

phrase to describe the subject of the assessment

and the context in which Gorgas will be evaluated

is “medicine and health in the tropics. ”

The direct economic and social impacts of

widespread disease are obvious, but the most

substantial economic impacts may be indirect

ones, affecting a country’s human resources and

productivity. For example, a country whose population has an extremely high prevalence of

debilitating disease loses labor resources, and productivity inevitably suffers.

In addition to the humanistic concern with the

health and quality of life of people in tropical

countries, and in addition to the stake that all

developed countries have in the economic health

and development of developing countries, there

is a smaller, yet definite benefit that can accrue

to the United States through support of tropical

disease research and technology development.

Tropical countries are no longer—if they ever

really were—’’exotic” far off lands seen only by

adventurers. A great many people now travel to

and live in tropical countries, as tourists, in the

diplomatic or military service, or as employees

of U.S. or multinational companies. The number

of such people is most likely increasing. * “The

tropics are coming closer and bringing their diseases with them” (69).

In addition, advances in tropical disease research can represent valuable knowledge in general medical science, particularly in the areas of

infectious disease control, general preventive medicine, and environmental health.

The Value of Laboratories

Located in the Tropics

Laboratories and field stations located in the

Tropics have played a vital role in tropical disease research during this century. There is a certain point at which research taking place in tem-

*The Increasing number of refugees in recent years serves as a

dramatic example of an additional reason for regarding attention

to tropical medicine as an important priority for the United States

perate countries, even though aimed at eventually

eliminating or controlling tropical diseases, can

go no further, regardless of the quality of researchers or institutions. Initially, information

about the occurrence (incidence, prevalence, casefatality rates), natural history, and transmission

of diseases is necessary for the rational design of

strategies to deal with diseases, and this can only

be collected in the field. Finally, the fruits of

research—e.g., drugs and vaccines, vector control programs—must be tested where the diseases

occur: in tropical regions. These are the very

minimum involvements for institutions in the

Tropics.

There is absolutely no substitute for field conditions in tropical countries. This point has been

made to OTA time and again by tropical health

experts in academia, Government research organizations, and the U.S. military.

Apart from research, training in tropical

medicine can only reasonably take place in the

Tropics. Training needs and expertise have traditionally been concentrated largely in the military.

Additionally, professionals with training in tropical medicine are in demand by foreign governments, academic institutions, and voluntary agencies (107).

In addition to benefits to the U.S. population

from knowledge of the control of tropical diseases,

the existing tropical field laboratories benefit the

countries in which they are located. The country’s health science professionals who are involved

in the projects or receiving training raise the level

of sophistication of biomedical research in these

countries, The disease problems studied are of obvious importance to the populations in these countries, and any progress in treatment or control will

benefit them. An additional benefit can be a lessening of the “brain drain” that occurs in many,

especially developing, countries. When a good

quality research institution exists in a country, its

professionals have a place and the opportunity

to work and develop without emigrating and thus

not depriving the country of their skills.

The U.S. Government supports a relatively

small number of laboratories in tropical areas (see

app. B). The Department of Defense operates

eight medical research laboratories in the Tropics.
11

In Latin America, the Centers for Disease Control (CDC) operates the Medical Entomology Research and Training Unit in Guatemala. CDC previously ran a field station in El Salvador, which

has been closed. The United States also supports

tropical health research through contributions to

international development agencies and through

bilateral aid.

Establishing new field laboratories is a difficult

and time-consuming task. Building good relations

with the host country and becoming a productive unit may take years. The decision to eliminate

an existing laboratory should consider that point.

Thus, any evaluation of GML must not only

consider the quality and relevance of its research,

but also its role as a research, training, and public

health unit actualIy located in the Tropics.
Chapter 2

Gorgas Memorial Institute

and Laboratory
. . .

\ - & 7=4-- ---

— — --J --

Photo credits: Gorgas Memorial Laboratory

Front entrance to the Gorgas Memorial Laboratory, in Panama City, Republic of Panama (bottom photo). Photo at top

shows the Laboratory complex in Panama City. At the extreme left is the side of the administrative offices; the lower

connecting structure houses the Library; to the right rear are the research laboratories. The complex also contains

animal buildings and an insect facility (insectory)
Chapter 2

Gorgas Memorial Institute and Laboratory

The Gorgas Memorial Institute of Tropical and

Preventive Medicine, Incorporated (GMI), a private, nonprofit organization, was incorporated

in Delaware and registered in the Republic of

Panama in 1921 as a memorial to Major General

William Crawford Gorgas (47).

The Gorgas Memorial Laboratory (GML),

GMI’s research arm and primary function, was

established in 1928 in the Republic of Panama,

with resources made available by the Governments of the United States and Panama and by

several national and international agencies. The

establishment of GML was made possible by an

act of Congress (Public Law 70-350), which

authorized a permanent annual contribution for

the facility, provided that a site and building were

made available from other sources, and by action

of the National Assembly of the Republic of Panama, which granted land and a building on the

condition that the property be used for a research

laboratory (47),

The contribution made annually by the U.S.

Government to GMI, which constitutes the core

support for the maintenance and operation of

GML, is administered by the Fogarty International

Center (FIC) of the National Institutes of Health

(NIH). Public Law 70-350, as amended, authorizes

Congress to provide up to $2 million for GMI.

In fiscal year 1983 GMI received $1.8 million

through FIC, an increase from the fiscal year 1982

allotment of $1.692 million. Although GMI asked

for $1.9 million in core support for GML in fiscal

year 1984, the latest fiscal year 1984 NIH budget

request targets no funds for GMI (47,115).

GML also receives grants and contracts supporting specific research projects from a variety

of United States, Panamanian, and international

organizations. In fiscal year 1982, total U.S. contributions including research grants from the U.S.

Army, Navy, NIH, and the Agency for International Development totaled approximately

$2,225,200, or 96.9 percent of all direct financial

support for GMI/GML (see tables 3A and 3B).

Panamanian support for GML, which largely

comes in the indirect form of property grants and

a tax-favored status, is more difficult to tabulate.

In 1930, the appraised value of the land donated

by the Republic of Panama was $126,750. Estimates of the current value of the land and facilities

have gone as high as $20 million by one senior

Panamanian official, but no exact figure is available. In 1979, FIC estimated the value of the “inTable 3A.—Sources of Financial Support for the Gorgas Institute and Laboratory Fiscal Years 1975-82

(dollars in thousands)

1975-82

1975 1976 1977 1978 1979 1980 1981 1982 total

U.S Appropriation . . . . . . . . . . . . . . . . . . $ 707.5 $1,360 $1,400.0 $1,400.0 $1,700.0 $1,700.0 $1,800.0 $1,692.0 $11,759.0

National Institutes of Health ... , . . . . 929.1 174.8 228.1 248.4 333.3 255.9 305.1 219.2 2,693.1

Health and Human Service (HEW) . . . . – – – – 4.4 4.7 0.9 – 10.0

U.S. Army . . . . . . . . . . . . . . . . . . . . . . . . 223.4 203.5 111.7 130.2 145.2 187.5 257.8 228.6 1,488.0

U.S. Navy . . . . . . . . . . . . . . . . . . . . . . . . . 35.0 33.8 25.0 25.0 30.0 35.0 35.0 35.0 235.8

AID ., ... . . . . . . . . . . . . . . . . . . . . . . . . 120.0 5.5 – – 8.1 23.3 45.2 — 202.1

Subtotal Federal support . . . . . . . . . $2,015.0 $1,777.6 $1,764.8 $1,803.6 $2,221.0 $2,205.5 $2,444.0 $2,174.9 $16,406.3

Other U.S. support ... , . . . . . . . . . . . . . $ 7.3 $ 4.3 $ 2.7 – $ 58.3 $ 89.5 $ 58.6 $ 50.3 $ 271.1

Total U.S. support. . . . . . . . . . . . . . . . $2,022.3 $1,781.9 $1,767.6 $1,803.6 $2.279.2 $2,295.0 $2,502.6 $2,225.2 $16,677.5

Government of Panama . . . . . . . . . . . . . – $ 59.3 $ 17.2 $ 37.1 $ 1.0 $ 308.4 $251.0 $22.5 $696.5

WHO/PAHO . . . . . . . . . . . . . . . . . . . . . . . $ 7.7 4.4 16.0 36.9 118.2 57.0 47.8 49.0 336.9

World Bank . . . . . . . . . . . . . . . . . . . . . . . — — — 6.8

Wellcome Laboratories . . . . . . . . . . . . . — — — (a) 6.9 1.0 - - 1.0

Total non-U.S. Support. . . . . . . . . . . . $ 7.7 $ 63.7 $ 33.2 $ 80.8 $ 120.2 $ 365.4 $ 298.8 $ 71.5 $ 1,041.3

Total support . . . . . . . . . . . . . . . . . . $2,030.0 $1,845.6 $1,800.8 $1,884.5 $2,399.5 $2,660.4 $2,801.4 $2,296.7 $17,718.7

a Less than $50

15
16

Table 3B.—Sources of Financial Support for the Gorgas Institute and Laboratory Fiscal Years 1975-82

(as of percent)

U.S Appropriation . . . . . . . . . . . . . . . . . .

National Institutes of Health . . . . . . . .

Health and Human Service (HEW) . . . .

U.S. Army . . . . . . . . . . . . . . . . . . . . . . . . .

U.S. Navy . . . . . . . . . . . . . . . . . . . . . . . . .

AID . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Subtotal Federal support . . . . . . . . .

Other U.S. support . . . . . . . . . . . . . . . . .

Total U.S. support . . . . . . . . . . . . . . . .

Government of Panama. . . . . . . . . . . . .

WHO/PAHO . . . . . . . . . . . . . . . . . . . . . . .

World Bank . . . . . . . . . . . . . . . . . . . . . . .

Wellcome Laboratories . . . . . . . . . . . . .

Total non-U.S. Support . . . . . . . . . . . .

Total suppport. . . . . . . . . . . . . . . . . .

1975-82

1975 1976 1977 1978 1979 1980 1981 1982 average

34.9 73.7 77.7 74.3 70.8 63.9 64.3 73.7 66.4

45.8 9.5 12.7 13.2 13.9 9.6 10.9 10.0 16.7

— — — — 0.2 0.2 (a) – 0.1

11.0 11.0 6.2 6.9 6.1 7.0 9.2 10.0 8.4

1.7 1.8 1.4 1.3 1.3 1.3 1.2 2.0 1.4

5.9 0.3 – – 0.3 0.9 1.6 — 1.1

99.3 96.3 98.0 95.7 92.6 82.9 87.2 94.7 92.6

0.4 0.2 0.2 – 2.4 3.4 2.1 2.2 1.5

99.6 96.5 98.2 95.7 95.0 86.3 89.3 96.9 94.1

— 3.2 1.0 2.0 (a) 11.6 9.0 1.0 3.9

0.4 0.2 0,9 2.0 4.9 2.1 1.7 2.1

— . — 1.9

— — — (a) (a) - - (a)

0.4 3,5 1.8 4.3 5.0 13.7 10.7 3.1 5.9

100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0

a Less than 0.05 support.

SOURCE: Gorgas Memorial Institute, 1983,

direct services’’ provided each year by the Panamanian Government to be $175,000.

GMI is required by law to make an annual report to Congress on the activities and expenditures

of the laboratory, The U.S. General Accounting

Office (GAO) audited all GMI/GML financial

statements until 1980 (47).

GML is currently engaged in an effort to cut

costs and broaden its financial base of support.

This issue is being addressed in the related GAO

study, and will not be covered in this technical

memorandum. Plans call for the the closure of

Building 265, which cost an estimated $279,102

to maintain in fiscal year 1982 (see table 4);

however, modifications to accommodate the relocation of the virology program formerly housed

in the building are estimated at a one-time cost

of $250,000 (table 5 shows this figure, as well as

other projected costs for fiscal year 1984).

The Laboratory has just finished terminating

the employment of some 29 of GML’s employees

and staff. The closing of the entire bacteriology

department eliminated three Panamanian scientists with 10 to 22 years tenure at GML (121). GMI

sought relief from the Panamanian Minister of

Health and Minister of Labor from penalty

charges attributable to early termination of Panamanian employees (47), but waivers were not

granted. GMI has established a Development

Committee to explore fund-raising possibilities in

the private sector. Because of the completion of

a number of commissioned projects, revenues

from research grants and contracts dropped from

$995,641 in fiscal year 1981 to $594,224 in fiscal

year 1982. As a result of this decline, the proportion of total funding represented by U.S. core support rose from 64.3 percent of all revenues in fiscal

year 1981 to 73.7 percent in fiscal year 1982.

Of the $1,884,824 spent by GMI/GML over the

12-month period ending July 1983 after the

reduction-in-force, over half ($928,101) went

towards salary costs. Utility charges, including

those for Building 265, came to $413,257. Administrative costs accounted for $130,732, and

another $163,258 was spent to maintain the GMI

office in Washington, D.C. The “direct” nonsalary

research dollars amount for the laboratory was

$209,476 (121).

At its headquarters in Washington. D. C., GMI

is governed by a 47-member Board of Directors,

which includes officials of the Governments of the

United States and Panama, representatives of national and international agencies active in areas

of common interest, and U.S. and Latin American

scientists and professionals. The board meets annually to determine the policies of the organiza-
17

Table 4.—Gorgas Memorial Institute of Tropical and Preventive Medicine, Incorporated:

Operating Budgets Fiscal Years 1982 and 1983

Fiscal year 1982 Fiscal year 1983

Budgeted Actual Program Budget

(1/20/82) unaudited Old New

Revenue:

Contribution by the United States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Research grants and contracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Other. ....,.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Subtotal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Additional revenue required . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total revenue required . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Expenditures:

Core—

Infectious Disease Program

Virology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Bacteriology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Parasitology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Immunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Clinical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Ecology & Epidemiology Program

Ecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Vertebrate Zoology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Entomology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Epidemiology

Vector Biology

Total

Primatology & Laboratory Animals Program

Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Animal Colony . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Education & Technical Support Program

Educational Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Library . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Data Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Administration

Washington, D.C. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Panama . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Maintenance

Panama . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Building 265. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Seniority Premium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total core expenditures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$1,692,000

609,407

2,500

$1,692,000

594,224

10,442

$1,800,000

346,209

10,000

$1,800,000

346,209

10,000

2,303,907

386,888

2,690,795

275,390

105,765

78,515

21,430

71,297

552,397

110,216

42,474

17,000

494

143,839

314,023

46,254

73,546

2,296,666

2,296,666

340,752

110,826

85,053

21,585

81,809

2,156,209

390.930

2,156,209

524,011

2,547,139

383,547

114,741

79,565

35,364

60,366

2,680,220

374,146

183,052

73,920

48,166

67,688

640,025

95,840

39,831

15,801

6,664

158,478

673,583

105,155

41,039

18,029

9,331

139,477

746,972

106,586

41,039

18,029

9,331

139,477

316,614

47,350

81,969

313,031

57,754

85,977

314,462

53,954

88,427

119,800

5,425

57,991

63,416

43,712

161,256

326,647

129,319

4,346

56,829

61,175

36,777

146,242

256,095

143,731

6,139

62,451

68,590

39,551

163,258

313,609

142,381

5,639

71,056

76,695

45,738

163,258

330,765

487,903

232,992

309,693

402,337

269,449

279,102

476,867

277,804

290,583

494,023

290,539

321,011

542,685

25,000

548,551

21,028

568,387

15,000

611,550

2,148,936

Direct grant and contract expenditures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541,859

Total expenditures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2,690,795

Excess revenue over/(under)

expenditures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $ -o2,155,826

445,089

2,600,915

$ (304.249)

2,298,740

248,399

2,431,821

248,399

2,547,139

$ -oSOURCE Gorgas Memorial Institute, 1983.

2,680,220

$ -otion, review the managerial and fiscal operation, manship of the President of GMI, Dr. Leon

approve budgets, and elect officers, Board mem- Jacobs, a Scientist Emeritus of NIH. The 24-members, and advisors. Between meetings, the Board’s ber Advisory Scientific Board, consisting of scienfunctions are delegated to the 9-member Executive tists in various disciplines, is to advise on the

Committee, which meets monthly under the chair- development and review of scientific programs
18

Table 5.—Gorgas Memorial Institute of Tropical

and Preventive Medicine, Incorporated:

Projection Fiscal Year 1984

Revenue:

Contribution by the United States . . . . . . . . . $1,899,000

Research grants and contracts . . . . . . . . . . . . 300,000

Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10,000

Subtotal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . -2,209,000

Additional revenue required . . . . . . . . . . . . . . 18,000

Total revenue required . . . . . . . . . . . . . . . . . ‘ 2,227,000

Expenditures:

Core—

Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . 180,509

Microbiology . . . . . . . . . . . . . . . . . . . . . . . . . . 276,237

Tropical Ecology . . . . . . . . . . . . . . . . . . . . . . . . 326,553

Applied Pharmacology . . . . . . . . . . . . . . . . . . . 165,699

Administrative Services & Training—

Panama ....., . . . . . . . . . . . . . . . . . . . . . . . . 913,553’

Administration—Washington, D.C. . . . . . . . . . 177,000

Total core expenditures . . . . . . . . . . . . . . . . 2,039,551

Direct grant and contract expenditures. . . . . 187,449

Total expenditures . . . . . . . . . . . . . . . . . . . . ‘2,227,000

Excess revenue over/(under) expenditures . . . . $ -oalnclude~ $250,000 for an~iclpated facilities remv’tlon

SOURCE:Gorgas Memorial Institute, 1983

ORGANIZATION

The organization of research activities of GML

is currently undergoing change. Previously (and

still officially) GML was divided among four scientific programs (see fig. 1). The Infectious

Diseases Program was divided into Virology, Bacteriology, Parasitology, Immunology, and Clinical sections. The Ecology and Epidemiology Program was responsible for Vertebrate Zoology,

Entomology, Epidemiology, and Vector Biology.

Animal Models, Primate Biology, and Animal

Colony research were under the Primatology and

Laboratory Program. Education and Technical

Support programs handled the Library, PhotoLaboratory, and Educational sections. In additon,

GML maintained administrative and data processing sections.

Tentative plans for departmental reorganization have been drawn up, but will not be implemented until GML’s financial situation is more

secure (121). The new organization will include

divisions for epidemiology, laboratory sciences

(e.g., immunology, parasitology, serum bank),

environmental biosciences (e. g., vector bionomics, ecology), clinical therapeutics (e.g., animal

and, if plans are fulfilled, to serve as an editorial

review board for GML staff’s scientific manuscripts. * The officers, members, and advisors

serve without compensation (47).

In 1972, the Middle American Research Unit,

which had been in existence since about 1960 in

the Canal Zone as an offsite laboratory of the National Institute of Allergy and Infectious Diseases

(NIAID), was merged with GML. At the end of

fiscal year 1975, NIAID concluded its support for

the work formerly done by this unit with a resulting loss of senior personnel and financial support for GML (11 O).**

● See the GAO report for a review of the activities of the Advisory

Scientific Board.

* *Because of a deteriorating political situation, the Centers for

Disease Control was forced to close its own Central American

Research Center located in El Salvador in 1981 and relocate to a

smaller research and training unit in Guatemala (53).

models, clinical investigation), and support services (library, administration, etc. ). Figure 2 illustrates the proposed organization.

The interdisciplinary scientific staff of six

Americans, nine Panamanians, and one Peruvian

includes entomologists, arbovirologists, parasitologists, and other specialists (see table 6). One

U.S. Navy medical officer and one Navy Ph. D.

parasitologist are currently on GML’s scientific

staff. The director of GML, Raymond H. Watten, M. D., previously the commanding officer at

the Navy’s Medical Research Unit in Cairo, oversees a total of 94 staff members and employees

(121).

GML is strategically located for studies of disease transmission and movement in tropical

America. Panama is a crossroad of transportation in the region and GML itself is in close proximity to the field. GML also benefits from an

available supply of Aotus monkeys, a simian

valuable for the study of human malaria (110).

The U.S. Fish and Wildlife Service classifies the

Aotus as an animal which could become endangered by international trade.
19

Figure 1. –Gorgas Memorial Institute Organization (currently official, but in process of being changed)

I

Gorgas Memorial Institute

I

Data Processing Gorgas Memorial Laboratory Administratio n

Biostatician I Director Administrator

(Reeves) Raymond H. Watten Alvaro E Paredes ”

1 1 I

1 1 r 1 m I

Finance-De La Lastra b

I

Personnel-(Paredes)

L I

i

Assistant Director Maintenance Nelson’

Rolando E, Saenz

I

Supplies-( Paredes)

Infectious Disease

Program

Bacteriology

Kourany (Vasquez)

i

Parasitology

Sousa”

(Bawden)

1

Immunology

(Johnson’”] (Saenz)

m

Ecology and Epidemlology

Program

i

Ecology

Reeves* (1)

(Petersen)

Vertebrate Zoology

n Mendez’

Entomology:

- (Reeves) (1)

(Christensen)

i

Epidemlology, (Reeves)

(Saenz)

Primatology & Laboratory

Programs I

G%El

EE!zl

F==l

m

Education & Technical I

Support Programs

I

EEl

● Chief

** Volunteer

( ) Secondary Duty

(1) Acting

Adjunct Associates:

Ministry of Health:

Dr. Evelia Quiroz

U.S. Navy:

Dr. Frank S. Wignall

Dr. Monte Bawden

Administrative Assistant:

HMC Charles R. Miranda

SOURCE Gorqas Memor, al lnstll~te J ~11 { 1982

24-122 0 - 83 - 4
20

Figure 2.—Gorgas Memorial Institute-Proposed Organization Chart

Gorgas Memorial Institute

I

Gorgas Memorial Laboratory

Laboratory Environmental Clinical support

Epidemiology Sciences Biosciences Therapeutics Services

Data Processing Parasitology Vector Bionomics C. Investigation Administration

Immunology Ecology Animal Models Finance

Virology zoology Animal Resources Maintenance

Tissue Culture Education

Serum Bank Library

Tentative Departmental

Reorganization - July/63

SOURCE Gorgas Memorial Laboratory, 1983

Table 6.—Gorgas Memorial Laboratory Information on

Scientific Staff as of July 1983

Watten, Raymond H., M.D. (U. S.)

Director

Saenz, Rolando E., M.D. (Panamanian)

Assistant Director

Adames, Abdiel J., Ph. D. (Panamanian)

Ecologist-Entomologist

Christensen, Howard A., Ph. D. (U. S.)

Entomologist

Dutary, Bedsy C., Ph. D. (Panamanian)

Arbovirologist

Escajadillo, Alfonso, D.V. M. (Peruvian)

Medical Veterinarian

Justines, Gustave, Ph. D. (Panamanian)

Virologist

Kourany, Miguel, M. P. H., Ph. D. (Panamanian)

Bacteriologist

Mendez, Eustorgio, Ph. D. (Panamanian)

Vertebrate Ecologist

Ore, Gladys, M.S. (Panamanian)

Microbiologist

Peralta, Pauline, Ph. D. (U. S.)

Virologist

Petersen, John L., Ph. D. (U. S.)

Insect Geneticist

Reeves, William C., M.D. (U. S.)

Medical Virologist

Rossan, Richard N., Ph. D. (U. S.)

Parasitologist-Primatologist

Sousa, Octavio E., Ph. D. (Panamanian)

Parasitologist

Vasquez, Manuel A., M.D. (Panamanian)

Physician-Microbiologist

SOURCE” Office of the Director, Gorgas Memorial Laboratory, July 1983,
ACTIVITIES OF GML

The activities at GML can be characterized as

basic and applied biomedical research, public

health and medical services, and training, Projects

use the laboratory, the clinic, and the field as

bases. Neither the types of activities nor the areas

where they are carried out are entirely categorical

or mutually exclusive. The border between basic

and applied research, for instance, is not a clean

line. Basic biomedical research, as used in this

paper, refers to work that seeks to advance the

state of knowledge about the vital processes that

underlie the normal functioning of organisms and

their malfunctioning in disease. Applied biomedical research draws upon basic information to

develop means of prevention, treatment, and cure

of disease (4).

At the two ends of the research spectrum, the

distinction is clear. Observing and characterizing

the physical and metabolic behavior of a malarial

parasite is basic research. Using the information

gained in that way to design an intervention, e.g.,

a vaccine or drug therapy, is applied research.

Further down the line, e.g., testing the drug or

vaccine in nonhuman primates, a major line of

research at Gorgas, the work falls farther toward

the applied end of the spectrum. A clinical trial

of the intervention in humans is a final step before

research turns to practice. Even during a clinical

trial, however, observations can be made that

would fit the definition of basic research, in furthering the basic knowledge of normal and abnormal human functioning. Marking the checkpoint between basic and applied research in the

process described is all but impossible, and to

spend a great deal of time attempting to do so is

unproductive.

Many projects at GML have both research and

service components. About 1,000 patients per

year are treated in the clinic, providing an important service to the community. Observations of

those patients are an important source for learning about the natural history and treatment of diseases, many of which cannot be adequately studied elsewhere.

GML began as a traditional tropical medicine

research institute concentrating on studies of

malaria, trypanosomiasis, and leishmaniasis. In

recent years, attention has been increasingly

directed to arboviruses and their vectors (110).

Currently, GML also is involved in research projects concerning sexually transmitted diseases,

specific cancers, and ecological studies (see table

7 for a more detailed listing of areas of activity).

In the past, GML has been called on to serve as

a reference center for the region (76). GMI also

offers “Medicine in the Tropics, ” a 6-week tropical

medicine training program offered primarily to

physicians from the U.S. Navy, intended to prepare the medical officers for operational assignments in tropical areas. GML also hosts predoctoral and postdoctoral students and scientists. In

1981, students came from Venezuela, Costa Rica,

Panama, and the United States; in 1982, from

Kenya, Hungary, Argentina, Brazil, Cuba, Panama, and the United States. In the past 12 months,

GML lists these training figures (121):

30 Students, Medicine in the Tropics (6-week course)

25 Visiting scientists

1 Postdoctoral student

2 Predoctoral students

3 Bachelor-level students

6 Trainees and graduate students

GML has working relationships with the Medical Entomology Research and Training Unit in

Guatemala, the Centers for Disease Control, NIH,

Louisiana State University (LSU), Johns Hopkins

University, and other academic and scientific institutions. Most of these arrangements are “inforreal, ” but GML has a Memorandum of Agreement

with LSU, Yale University, Johns Hopkins, and

the University of Panama (121).
22

Table 7.—Recent Activities of Gorgas Memorial Laboratory

Area of activity Active/recent Funding

Animal colonies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Care and maintenance of experimental animals

Applied pharmacology:

Malaria drug testing (Aotus studies) (also under Malaria) . . . . . . . . . . . . . . . . . .

Rabies, clinical trial to identify best minimal

dose of human diploid vaccine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Arboviruses (various):

Arbovirus survey in Tabasara River Basin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Various projects relating to characterization of arboviruses

and investigating outbreaks

Aseptic meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Blackflies:

Vector competence of S. quadrivittatum for O. volvulus . . . . . . . . . . . . . . . . . . .

Blackfly control in Fortuna Hydroelectric project

Species bionics; intervention at breeding sites

Blood meal analysis:

Feeding habits of known and potential vectors . . . . . . . . . . . . . . . . . . . . . . . . . .

Campylobacter:

Survey of this important cause of diarrhea in Panama . . . . . . . . . . . . . . . . . . . .

Cancer:

Human T-cell Ieukemia virus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Cervical and penile cancer in Herrera Province. . . . . . . . . . . . . . . . . . . . . . . . . . .

Association with HTLV; and with herpes simplex

Cervical cancer and Herpes simplex . . . . . . . . . . . . . . . . . . . . ... , . . . . . . . . . . . .

Cell culture lines:

Culturing of Sloth kidney cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Culturing of haemogogus equinus cells

Chagas’ disease:

Study of risk of infection and human manifestations of Chagas’ disease

transmitted by R. pallescens (Central Panama) and T. dimidiata

(Western Panama) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Biological and Isozyme characterization of

T. cruzi and T. range/i strains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Clinical diagnosis and treatment (approximately 1,000 cases per year) . . . . . . . .

Data Processing:

National Cancer Registry (Panama) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Cervical cancer project

National serologic survey

Bayano Lake clinical surveillance project

Malaria chemotherapy project

STD Project

Environmental Impact Assessment:

Tabasara Hydroelectric Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Fortuna River . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Influenza and clinical diagnostic virology

services and surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Leishmaniasis:

Identification of vector special; identification of reservoir (porcupine) . . . . . . .

Isozyme electrophoresis diagnosis of strain and species of Leishmania

and identification of Ieishmaniasis vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Library:

Reference service and collection available to staff and

outside researchers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Malaria:

In Vitro cultivation of infectious agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Antimalarial Drug Testing in Aotus monkey. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Phlebotomus fever:

Serologic surveys of U.S. troops and Panamanians for Chagres and

Punta Toro Fevers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Comparison of Punto Toro and Rift Valley Fevers . . . . . . . . . . . . . . . . . . . . . . . .

Identification of amplifying host vertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Retinochoroiditis due to Toxoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Serum Bank Reference Collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

A

A

R

R

R

R

A

R

A

A

A

A

A

A

A

A

R

R

A

A

A

A

R

A

R

R

R

R

A

Core

U.S. Army contract

Core, with MOH

Contract

Core

Core, with Johns

Hopkins University

Core

Core

Core

Core

and WHO TDR

and NCI grant

Core, with McMaster

University

Core

WHO TDR grant (partial)

Core

Core, with MOH

Core, plus miscellaneous

Contract

Contract

Core, with MOH

Core and WHO

Core and WHO

Core and grant

Panama

AID grant

TDR grant

TDR grant

from

U.S. Army contract

Core

Core

Core

Core

Core
23

Table 7.— Recent Activities of Gorgas Memorial Laboratory-Continued

Area of activity Active/recent Funding —

Sexually transmitted diseases (STDS):

Gonorrhea—survey of prostitutes on prevalence and

penicillin resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Epidemiology of STDS in Panama (prevalence; maternal STD

and effect on pregnancy outcomes) . . . . . . . . . . . . . . . . . . . . . . .

Shigellosis:

Study of drug resistance in shigella isolates. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

St. Louis encephalitis (SLE):

Study of how virus is maintained in the tropics . . . . . . . . . . . . . . . . . . . . . . . . .

Studies with olivaceous cormorant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Susceptibility to infection of Panamanian vector with three geographic

isolates of SLE virus . . . . . . . . . . . . . . . . . . .

Virulence testing and RNA fingerprinting of Panamanian SLE

virus isolates . . . . . . . . . . . . . . . . . . . . . . .

Training:

Medicine and health in the Tropics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Triatoma Colony maintained for xenodiagnosis . . . . . . . . . . . . . . . . . . . . . . . . . .

Trypanosomiasis ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Venezuelan equine encephalitis (VEE):

Search for epizootic virions from enzootic strains . . . . . . . . . . . . . . . . . . . . . . .

Vertebrate zoology

Survey of Mammalian Fauna of Panama. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Long-term survey of rodents (zoogeography) . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Studies of Ectoparasites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Yellow fever:

Monitoring of animal reservoirs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Monitoring of epizootics in Spider monkeys

Monitoring of variations in vectors’ ability to transmit virus. . . . . . . . . . . . . . . .

Genetic studies of jungle vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Longevity and age structure of Sylvan Yellow fever vectors. . . . . . . . . . . . . . . . NIH grant

KEY AID—U S Aqency for International Development, MOH–Panamanian Ministry of Health NC1—National Cancer Institute NIH—National Institutes of health, TDR–

.

R

A

R

R

R

R

R

A

A

A

A

R

A

A

A

A

R

R

Core

Core, with MOH

Core

NIH grant

NIH grant

NIH grant

NIH grant

U.S. Navy

Core

Core and WHO grant

Core

Core

Core

Core

Core

Core

NIH grant

Special Programme for Research and Tralnlng in Tropical Diseases (WHO), WHO—World Health Organizat!on

SOURCE Off Ice of Technology Assessment, 1983 Information provtded by Gorgas Memorial Laboratory WHO and Gorgas Memorial Laboratory flscai year 1981 and

1982 reports
Chapter 3

Quality of Research at the

Gorgas Memorial Laboratory
Chapter 3

Quality of Research at the

Gorgas Memorial Laboratory

INTRODUCTION

The Gorgas Memorial Laboratory (GML) engages in a wide range of public health, research,

and training activities. Gorgas scientists work in

the laboratory, in the field, and in the medical

clinic. GML performs applied and basic research,

and provides public health services in those settings. (See ch. 2 for a description of current

activities. )

This chapter examines the quality of research,

training, and public health activities at GML.

Ideally, assessing the quality of the work at GML

would be accomplished by a review of each project in each program. A multidisciplinary team of

scientists would visit GML, speak with investigators, review research protocols, procedures, and

publications, and evaluate the physical plant. An

overall rating would then be made, pointing out

strong and weak points. Such a thorough review

would serve as the basis for recommending

changes in current programs, and to point out

areas with future potential. OTA was unable to

take such an approach.

Another avenue for assessing the quality of

GML activities, and one that was suggested to the

Office of Technology Assessment (OTA) by a

number of people, is to compare GML activities

and its record of productivity with that of a

similar institution. The logical choices for such

a comparison might be, e.g., Institute of Nutrition of the Caribbean and Panama, International

Laboratory of Research on Animal Diseases, the

Department of Defense (DOD) medical research

units, or the Centers for Disease Control’s former

field station in El Salvador. Even these institutions, however, are very different from GML in

their administrative structures and their research

agendas. While it was possible with the time available and information at hand to make gross comparisons of GML and DOD budgets, it was not

possible to make adequate comparisons of the

quality of scientific activities.

For its review, OTA relied on:

1.

2.

3.

4.

5.

the record of past scientific review of GML’s

programs;

a review of recent publications by GML

researchers, including an in-depth analysis

of a selection of active manuscripts and

published articles;

an assessment of peer review at GML;

a review of recent grants and contracts held

by GML; and

the results of a telephone survey, commissioned by OTA, of experts familiar with

GML.

OTA is aware that this type of assessment is

not definitive. It relies heavily on circumstantial

evidence about quality (e. g., number of publications), some unsubstantiated opinions about quality (e. g., comments from the telephone survey),

and the opinions of site visitors in previous years.

As discussed above, other, more detailed methods

of assessment are possible which would both give

a better reading of the state of GML activities and

serve as a guide for future directions. Such an

assessment could be valuable to GML as well as

its funding agencies, and might be considered as

a GML priority for the near future.

SITE VISITS BY THE FOGARTY INTERNATIONAL CENTER

The Fogarty International Center (FIC) at the other in 1980 (111). In 1978, a review of all proNational Institutes of Health (NIH) has conducted grams was carried out by a team with representtwo site visits to GML, one in 1976 (110) and the atives from FIC and the Gorgas Memorial Institute

24-122 0 - 83 - 5

27
28

(GMI) Executive Committee and Advisory Scientific Board. These are the only comprehensive program reviews that have taken place in recent

years, A scheduled site visit for 1983 has been

postponed due to the uncertainties surrounding

GML’s future (57). Before those site visits, committees of GMI’s Advisory Scientific Board had

conducted reviews of the virology and parasitology programs in. 1973 and 1974, respectively.

The FIC site visits were conducted by multidisciplinary teams which evaulated the scientific activities at GML. The charge of the 1980 fiveperson team was:

. . . an examination of the scientific programs of

the Laboratory as to their quality, adequacy, and

relevance in furtherance of the mission of the

laboratory, to provide advice and to make recommendations as to any alterations in priorities and

program or project implementation that seemed

indicated, and in the final analysis to arrive at

some composite judgment as to the value of the

scientific work relative to the investment by the

U.S. Government.

In addition to reviewing the research programs,

the site visit report comments on administrative

operations and GML’s program in tropical medicine training.

Both FIC site visit reports were strongly positive

about the overall operation of GML, while identifying weaknesses and areas of unused potential.

The 1980 report concludes:

The core long-range program emphases of the

GML on parasitology, arbovirology, and ecologic

studies continue to be of scientific importance,

relevant to the health concerns of the United

States, Panama, and the region, and appropriate

to the unique location and facilities offered by

GML.

The overall quality of research conducted by

GML is of high standard, nationally (United

States) and internationally. As with any institution undertaking a broad spectrum of projects,

there are unevennesses that necessitate periodic

review and reevaluation, especially in terms of

priority relative to available resources. The Team

felt that, in general, this [review and reevaluation]

was being done conscientiously and well. It would

emphasize, as the previous FIC review did, that

GMI actively continue to support the GML Director in this respect through regular site visits by

members of the Executive Committee and/or the

Advisory Scientific Board.

The 1980 report noted a strengthening and consolidation of research activities since the previous

(1976) site visit. A major factor facilitating that

improvement was the relatively stable funding

through the core grant, after several years of

“uncertainty and adjustments” associated with

GML’s absorption of the former NIH Middle

America Research Unit (MARU). At this time, adjustments are continuing, as described in chapter

2. Equilibrium has not yet been reached, and the

research programs may be affected to some degree, particularly in terms of long-range planning,

until the reorganization is complete.

Review of Research Programs

The FIC team critiqued each program as to its

quality and relevance, and developed specific

recommendations for each. The findings and

recommendations of the 1980 site visit report are

summarized below.

Parasitic Infections

Programs in leishmaniasis, trypanosomiasis,

malaria, and toxoplasmosis are critiqued separately. In general, these diseases are considered to be

important in Panama. The site visit report,

however, pointed out the need for refocusing

some of the studies.

The report stressed the unique availability of

large numbers of patients with Ieishmaniasis, and

the potential for expanding and redirecting efforts

in clinical investigations. Ongoing research with

a known major animal reservoir of leishmaniasis,

the two-toed sloth, is promising, and could also

be more carefully focused.

GML has conducted research on Chagas’ disease (American trypanosomiasis) for many years.

Although GML is in possession of a large pool

of clinical data, little has been published. The site

visitors suggested that a major contribution to understanding the importance of Chagas’ disease in

Panama could result from analysis and publication of clinical observations. GML had made some

interesting observations about treatment of
29

Chagas’ disease with metronidazole, which the site

visit team thought worthy of followup by other

laboratories. Studies of vectors and animal reservoirs, and longitudinal prevalence studies in one

population had provided interesting information,

but the goals of those projects required reevaluation.

Malaria

The main activities in malaria research are drug

testing for the U.S. Army, in Aotus monkeys.

This work is considered important, but the site

visitors recommended expanding the scope of malaria research to make greater use of the expertise and resources at GML.

Toxoplasmosis

Toxoplasmosis is a major cause of chorioretinitis (inflammation of parts of the eye) in Panama, and as such is important, although, according to the site visit report “not of the highest priority. ” While the site visit team thought contributions could be made toward understanding toxoplasmosis, “the principal focus of the project as

described seems somewhat lacking in relevancy.”

Arbovirus Program

Yellow fever, Venezuelan equine encephalomyelitis, and St. Louis encephalitis are the major arboviral diseases studied at Gorgas, though GML

retains the capability to investigate and evaluate

outbreaks of other diseases.

Yellow Fever

The site visit report deemed the yellow fever

surveillance “one of the most important programs

of GML. ” Panama is the key location for early

detection of spreading yellow fever from Colombia into Central America. Gorgas has developed

a proven method for surveillance of wild howler

and spider monkeys, the animal reservoirs of yellow fever. At this time there is no alternative

method. The report favored continuation of monitoring seasonal variations in known mosquito

vectors of yellow fever, and expanded efforts in

studying transmission of yellow fever.

Venezuelan Equine Encephalomyelitis (VEE)

Past efforts in VEE research have produced useful information. The site visit report suggests expanding in this area,

St. Louis Encephalitis (SLE)

Comments on the SLE research program indicate that they are headed in productive directions

and the work should be continued.

Environmental Assessment Program

Assessments of two major hydroelectric

schemes have been carried out under contract to

the Panamanian power authority. Although very

different in nature from most of the activities taking place at GML, these assessments were considered successful and useful by the site visitors.

They concluded:

In addition to their technical and social importance, such environmental assessment projects can

help provide a model for similar studies in other

parts of the developing and developed world. Furthermore, they can readily be perceived by the

public as dealing with actual concerns of that

country’s society, We feel that more than

anything else in recent years, these projects in

Panama have probably helped improve the image of the GML in the eyes of Panamanians.

Diarrheal Diseases Program

Several projects in diarrheal diseases were in

progress at the time of the site visit. They were

of variable quality and relevance, according to

the report. For instance, a project demonstrating

the efficacy of oral fluid therapy in the treatment

of dehydration secondary to acute diarrhea duplicated research done elsewhere, but the project

appeared to be beneficial nonetheless. The report

states:

Although the merits of the project as original

research are relatively low, the project served as

an educational effort of considerable importance.

A study of travelers’ diarrhea in Panamanian

visitors to Mexico was considered of only secondary importance and not central to the mission of

GML.
30

At the time of the site visit, a collaborative arrangement with the Johns Hopkins University

School of Medicine had produced worthwhile results in studying the incidence of acute diarrheal

disease in the San Bias Islands with respect to the

availability of water. However, the Hopkins unit

was not refunded beyond 1980 and the research

was terminated.

Sexually Transmitted Diseases

Studies in sexually transmitted diseases (STDS)

were carried out in collaboration with the Panamanian Ministry of Health. They have focused

on the epidemiology and etiology of STDS, and

have led to further studies bearing on the very

high rate of cervical cancer in Panama. The site

visit report commented that STD research was of

“secondary importance” to the other major programs in parasitology, arbovirology, and environmental impact studies.

Cancer Registry/Cancer of the Cervix

GML has worked with the Panamanian national cancer registry in epidemiologic studies of cervical cancer. Analysis of registry data indicated

that Panama has one of the highest rates of cervical cancer in the world, and that geographic

clusters in certain provinces have extremely high

rates. Though not considered of the highest priority by the site visitors, they rated the work of high

quality and recommended that it be continued.

Training

The site visit team was enthusiastic about the

excellence of training provided in the “Medicine

in the Tropics” course. To be more consistent with

the mission of GML, however, it was suggested

that Panamanians be included in the course on

a regular basis* and that GML take over the direction of the course entirely, rather than the director being a U.S. Navy assignee. They concluded:

. . . it appears that the training capabilities and

opportunities offered by GML, including the Lister Hill fellowships of GMI itself, warrant wider

notice in the scientific community.

● According to the Director of GML, only one or two Panamanians take the 6-week course each session (121).

Publications

Research and scientists are often judged on their

publication records. The number of publications,

the journals in which they are published, and the

number of other authors who later cite the papers

are some objective, though indirect, indicators of

quality. However, there are no fixed standards

against which to make a judgment of excellence.

Research activities, in general, are aimed toward

publishing results, while public health service activities do not have publication as a primary goal.

Even in research, each field of study and type of

research varies greatly, and may result in a different array of publications. Long-term field surveillance studies may result in a major publication only after several years. Clinical observations

may be published as case reports after only a single visit.

Environmental assessments are performed under contract to development agencies or companies, and may result in few external publications,

though they may be quite successful. Surveillance

activities are routine until something is found. In

Panama, yellow fever outbreaks have occurred

every 8 or 9 years, but surveillance must go on

continuously.

Given the above perspective, OTA examined

the GML publication record by looking at the

number of publications in recent years and the

journals in which they were published, and by

evaluating the quality of a sample of recent

publications and active manuscripts.

Number of Publications

and Journals of Publication

Over the years of its existence, GML researchers

have been authors or coauthors of about 950

published scientific papers, about 200 of them

since 1975. (App. C lists publications since 1975. )

Though it is impossible to rate the number of

publications on a meaningful, objective scale,

GML’s record is indicative of continuous publishing activity. Table 8 shows the number of publications by GML staff by year. Whether more

publications should have been expected is a

subjective matter. A comparison of GML scientists’ publishing record to that of six of the
31

. ————.— .-— .— —

Table 8.—Total Publications of the Gorgas Memorial

Laboratory, 1975-83

Year Total articles appearing

1975 .., . . . . . . . . . . . ... , . . . . . . . 34

1976 . . . . . . . . . . . . . . . . . . . . . . . . . 18

1977 . . . . . . . . . . . . . . . . . . . . . . . . . 14

1978 . . . . . . . . . . . . . . . . . . . . . . . . . 7

1979 . . . . . . . . . . . . . . . . . . . . . . . . . 16

1980 . . . . . . . . . . . . . . . . . . . . . . . . 24

1981 . . . . . . . . . . . . . . . . . . . . . . . . . 10

1982 . . . . . . . . . . . . . . . . . . . . . . . . . 17

1983 (to date) ..., . . . . . . . . . . . . . 6

SOURCE Office of Technology Assessment, 1983 Based on data provided by

Gorgas Memorial Laboratory, Offlce of the Director, Raymond Watten,

July 1983

centers supported by the Rockefeller Foundation’s

Great Neglected Diseases program shows GML

to be at an acceptable but rather low level.

GML scientists should certainly give more attention to publishing the results of their work, and

GMI/GML management should be aggressive in

urging such activity (the Director of GML and

the President of GMI have indicated they share

this view).

GML researchers publish in a variety of scientific journals. Table 9 1ists the journals in which

papers have appeared since 1980. These are largely refereed journals, meaning that papers are scrutinized in some formal way before acceptance, and

generally there is some competition for publication.

In most cases, Gorgas investigators were the

principal authors (listed first among the authors,

and generally taken to mean that the ideas and

most of the work can be attributed to that individual). Publications appear in both English and

Spanish language journals. In general, papers of

direct relevance to medical practice in tropical

America appear in Spanish language publications

(e.g., Revista Medica de Panama). Those of more

global interest have appeared in journals with

more international circulation (e.g., The American Journal of Tropical Medicine and Hygiene).

An example of a subject of interest both locally

and internationally is oral dehydration therapy of

infantile diarrhea. On the basis of clinical research

carried out at GML, a paper was published in 1980

in Revista Medica de Panama (6). The research

and resulting publication was of great value to

local physicians in demonstrating the value of oral

Table 9.— Gorgas Memorial Laboratory: Publication

Location for Articles Written by Staff; 1980 to July 1983

Number of

Journal or other location: publications

American Journal of Tropical

Medicine and Hygiene . . . . . . . . . . ... . . .

Revista Medica de Panama . . . . . . . . . . . . . . .

Revista Medica de la Caja

de Seguro Social . . . . . . . . . . . . ... ...

Applied and Environmental Microbiology . .

Infection and Immunity . . . . ... . . . . . .

American Museum of Novitates ., . . . . . . . . .

Journal of Medical Virology, , . . . . . . . . . . . . .

Journal of Medical Entomology . . . . . . . . . .

Mosquito News . . . . . . . . . . . . . . . . . . ...

Epidemiological Bulletin . . . . . . . . . . . . . . . .

Ecological Entomology . . . . . . . . . ... , . . .

Bulletin of the WHO . . . . . . . . . . . . . . . . . . . .

Revista de Biologica Tropical . . . . . . . . ... .

Journal of Pacific Insects . . . . . . . . . . . . . . . .

Transactions of the Royal Society of

Tropical Medicine and Hygiene . . . . . . . .

Entomological and Ecological Studies ...

International Journal for the

Study of Animal Problems . . . . . . . . . . . . .

Journal of Infectious Diseases . . . . . . . . . .

Journal of the National Cancer Institute . . .

Journal of Wildlife Diseases . . . . . . . . . . . . .

New England Journal of Medicine ., . . . . . . .

Journal of Economic Entomology . . . . . . .

Revista Medico Cientifica . . . . . . . . . . . . . . .

Annals of Internal Medicine. . . . . . . . . ... .

Mosquito Systematic . . . . . . . . . . . . . . .

PAHO Workshop ... , . . . . . . . . . . ... .

BOOKS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Bacteria/ Infections of Humans

Pediatric Cardiology

Presentations at Symposia/Conferences . . . .

Total articles appearing . . . . . . . . . . . . . . . .

15

13

3

2

2

2

2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

3

. 64

SOURCE Off Ice of Technology Assessment, 1983 Data from Office of the Dlrec

tor, Gorgas Memo;ial Laboratory, Raymond Watten, July 1983

rehydration. Subsequently, the same research

served as a basis for the Panamanian arm of a controlled study of oral dehydration therapy of children in the United States and Panama, which was

published in the New England Journal of Medicine

(95). An editorial accompanying the article (12)

highlighted the importance of this work, making

the point that “Western-trained pediatricians

. . . have created major impediments . . . to the

promulgation of oral-dehydration treatment . . .

Indeed, local herb doctors, quick to recognize the

value of oral dehydration, have often been more

helpful than their Western-trained colleagues in

disseminating the concept of oral dehydration. ”

The contribution of GML in this case was to facilitate a “technology transfer” to medical practice in the developed world.
32

Quality of Articles

OTA commissioned a review, * summarized

here, of five currently active manuscripts and four

recently published articles written by Gorgas staff

members (the articles and manuscripts are listed

in table 10). The articles are not necessarily a representative sample of the total GML output. They

were selected by OTA to cover as diverse a group

of topics as possible, subject to the practical constraint of what was available immediately. The

review assessed the process of the research, including the adequacy of study design, extent of

data collection, and methods of presenting the

research findings. Presented below is an examination of the overall features which characterize the

research reports, and assessment of the methods

of presentation of the data.

● The review was carried out for OTA by Richard K. Riegelman,

M. D., Ph. D., author of Studying a Study; Testing a Test, and a

member of OTA's Health Program Advisory Committee. This section is based entirely on that review.

Table 10.—Articles and Manuscripts Reviewed

for the Office of Technology Assessment

by Richard K. Riegelman, M. D., Ph. D.

Articles

1. Christensen, H., and DeVasquez, A. M., “The Tree-Buttress

Biotope: A Pathobiocenose of Leishmania braziliensis,”

American Journal of Tropical Medicine and Hygiene

31(2):243-251, 1982.

2. Dietz, E., Galindo, P., and Johnson, K., “Eastern Equine

Encephalomyelitis in Panama: The Epidemiology of the

1973 Epizootic,” American Journal of Tropical Medicine

and Hygiene 29(1) :13;1-140, 1980.

3. Dietz, W., Peralta, P., and Johnson, K., “Ten Clinical Cases

of Human Infection With Venezuelan Equine Encephalomyelitis Virus, Subtype l- D,” American Journal of Tropical

Medicine and Hygiene 29(2):329-334, 1979.

4 .Young, M., Baerg, D., and Rossan, R., “Studies With induced Malarias in Aotus Monkey s,” Institute Animal

Sciences 25(6):1 131-1137, 1976.

Manuscripts

5. Petersen, J., “identification of Phlebotomine Sand Flies

(Diptera: Psychodidae) by Cellulose Acetate Electrophoresis” (in press).

6. Piesman, J., Sherlock, l., and Christensen, H., “Triatomine

Density and Host Availability” (in press).

7. Seymour, C., Kramer, L., and Peralta, P., “Experimental St.

Louis Encephalitis Virus Infection of Sloths and Cormorants” (in press).

8 .Seymour, C., Peralta, F)., and Montgomery, G., “Serologic

Evidence of Natural Togavirus Infections in Panamanian

Sloths and Other Vertebrates” (in press).

9 .Seymour, C., Peralta, P., and Montgomery, G., “Viruses

Isolated From Panamanian Sloths’ ’-(in press).

SOURCE: Office of Technology Assessment, 1983,

Overall Features of the Articles and Manuscripts

The articles and manuscripts reviewed reflect

a wide spectrum of scientific activities. These activities include:

●

●

●

●

●

●

●

●

study of a naturally occurring epidemic with

potential for human transmission;

development of new animal models for

studying human disease;

investigations of the mechanisms for transmission and reservoirs of disease in their natural field environment;

laboratory investigations designed to assess

the susceptibility of animal hosts as intermediaries in the transmission of human disease;

reporting on a series of human cases of disease collected over more than 15 years;

development of a new technique for performing enzymatic studies on disease vectors;

field studies of the effect of a human living

environment on the transmission of disease;

and

correlation of biochemical genetic characteristics of disease vectors with the epidemiology

of disease.

Important features of these investigations include the ability to collect and coordinate data

from a variety of sources. The ability of the investigators at GMI to bring together data from

a variety of sources is demonstrated in these studies in at least the following ways.

●

●

●

correlation of their laboratory investigations

with findings from their field research and

knowledge of the epidemiology and natural

history of disease;

cooperation with other laboratories, including CDC and a number of U.S. university, public health, and military programs;

ability to respond to a naturally occurring

epidemic, collecting data requiring cooperation with public health control programs,

hospitals, and correlation with laboratory investigations; and

ability to collect and test large numbers of

disease vectors from a variety of natural environments.

The majority of the investigations represent unrelated studies. Three of the investigations how-
33

ever, include coordinated studies using two- and

three-toed sloths found in the Panamanian forests,

These three studies reflect the ability of investigators at the laboratory to:

●

●

●

Ž

●

collect a large spectrum of species of birds

and mammals from a variety of natural environments;

track the natural history of disease by placing radio transmitters on selected animals and

recapturing them for sequential testing;

perform viral isolation and serological testing

needed to correlate with the epidemiology

and natural history of disease found in the

Panamanian forests;

relate the field and laboratory findings to

human disease potential; and

use knowledge gained from earlier studies to

improve the design and performance of subsequent studies.

Presentations of Data

Background and Hypotheses.—The authors

frequently introduce their presentations by a succinct discussion of their study’s purpose and its

relationship to existing knowledge. These introductions are well referenced and place the studies

in a context which does not require the reader to

have a previous detailed knowledge of the field.

The study hypotheses are usually clearly stated

and their relationship to previous studies are, on

the whole, well outlined.

Study Methods.—The authors of the field

laboratory studies provide detailed discussions of

the location of their collections and the methods

of preservation and preparation of their materials.

The experimental studies provide an adequate description of the study methods, including references to the specific techniques employed. These

presentations appear to fulfill the essential criteria

that other investigators are provided adequate information to attempt to reproduce the findings.

When judgments as to technique and criteria

for positive results are required the authors appropriately present the justifications for their

choice. When the methods themselves possess limitations in their ability to measure the intended

phenomena, the authors clearly identify these limitations,

Results.—The authors present the results of

their studies in adequate detail. They consistently present and acknowledge their failures and the

limitations of their results as well as presenting

their positive findings. This practice should add

to the value of these investigations by identifying areas for further research, appropriately limiting the conclusions, and preventing other investigators from pursuing unproductive approaches.

The statistical methods used in the articles require only basic methods. However, the methods

used are appropriate and appear to be properly

employed.

When interpreting the results of their studies

the authors usually present a variety of potential

explanations for their findings, including the explanation they favor.

In presenting their results, the authors generally

are able to relate their findings to current scientific thinking as well as their implications for immediate disease prevention or control. The articles

often suggest areas for further investigations.

Summary

In summary, the articles and manuscripts reviewed reflect a high level of expertise in designing and carrying out scientific research. The investigators demonstrate an ability to collect and

coordinate data from a variety of sources, present data in an analytical manner, and build on

and contribute to the worldwide scientific literature. The authors are able to take advantage of

the unique features of their setting and experiments to contribute to knowledge of basic and applied biological science.
34

PEER REVIEW AT THE GORGAS MEMORIAL LABORATORY

One of the questions being addressed by the

General Accounting Office (GAO) is about the

peer review process at GML. Thus, this memorandum will not discuss peer review except for some

comments on the relationship of peer review to

the quality of research. By peer review, OTA is

considering basically the process by which decisions are made to fund research projects with internal (core grant) money and the process of

evaluating internal research. Research funded

through grants and contracts is subject to peer

review by the funding agencies, e.g., NIH and the

World Health Organization (WHO). In those

cases, GML is competing with other research

organizations for support. In a sense, GML staff

are competing with each other for core funds to

support their projects that are not under grants

or contracts. A peer review system for research

proposals, and reviews of ongoing and completed

work are mechanisms used to allocate resources

according to merit and to assure that research

quality is acceptable.

It is not uncommon for internal peer review

systems to be less rigorous than externally funded

systems. For instance, at NIH, researchers on the

campus do not submit proposals through the same

system that funds extramural research. Researchers within each institute do go through a formal

process for allocation of intramural research

funds, but review is basically within the institute

itself. Proposals and protocols are not scrutinized

by outside experts, but, at specified intervals outsiders do evaluate the work that goes on within

institutes.

OTA gained some insight into the peer review

process at GML through the telephone survey

about Gorgas. There was a general lack of agreement about whether a peer review process—either

GRANTS AND CONTRACTS

The record of an institution or a researcher can

be measured in the number and dollar value of

grants and contracts awarded from external

sources. Externally funded projects are more likely

to review research proposals, protocols, or results—does in fact exist. It is clear that even if a

process has been set up on paper, it does not function effectively on a regular basis.

The fact that GML does not seem to have a

well-known system for allocating money within

the organization is something that requires consideration in future plans. A truly internal system,

such as NIH uses, may not be the best plan for

GML. Institutes in NIH have a large core of individuals with knowledge in a specific field. For

instance, all researchers at the National Cancer

Institute are knowledgeable about some aspect of

cancer. There is a large number of people there

to provide adequate review of internal research

proposals,

At GML, investigators are unique in education,

training, and research areas. It would probably

be difficult and perhaps not so effective to have

only GML staff review each other’s proposals and

research results, though that is also desirable. The

main peer review body could be drawn from the

Advisory Scientific Board, which has good scientific representation from the relevant disciplines.

A model for how such a group might operate is

the peer review process of the Plum Island (New

York) Animal Disease Center of the U.S. Department of Agriculture, In that case, there are five

non-Government consultants who visit once each

year (but may be called to visit in the interim if

necessary). The consultants are selected by the

laboratory director and are responsible directly

to that person. The consultants produce a report

assessing all programs. The consultants’ expenses

for the visit are paid (98). Paying for travel is even

more critical for GML, since travel to Panama is

relatively expensive.

to undergo vigorous peer review than are those

funded internally by an institution. (See “Peer

Review at the Gorgas Memorial Laboratory, ”

above. ) This is a particularly appropriate measure
35

for researchers in the United States, where there

is a relatively large amount of money available

for research, though competition is quite keen.

Most of the research at GML is funded through

the core grant, rather than through competitive

grants and contracts. Addressing this, the 1980

Fogarty Site Visit Report states:

In these times of financial constraint everywhere, the Team does not feel that too many expectations should be held out that project grants

and contracts could or even should supplant the

necessity for the maintenance of adequate core

support.

A number of past and current projects have received grant or contract funding from sources

other than the core grant, including the WHO

Special Programme for Research and Training in

Tropical Diseases (see app. A), the U.S. Army and

Navy, NIH, and private foundations, Table 11

lists current, completed, newly approved, and

Table 11 .—Gorgas Memorial Laboratory: Grants and

Contracts as of July 1983

Current grants:

U.S. Army Drug Evaluation Contract

U.S. Navy Training Project

WHO/TDR Triatomine Blood Meal Contract

WHO Clinical Trial for Evaluation of Leishmaniasis Therapy

WHO Isozyme Lutzomyia—Sand Flies

NIH/Yale Arbovirus—Yellow Fever

WHO/TDR Chagas’ Disease

UNDP/World Bank/WHO Leishmaniasis in Honduras

Completed and or terminated grants/contracts:

Tabasara Hydroelectric Environmental Impact Study

NIH/NCl Cervical Cancer Study

NIH/NIAID Epidemiology of St. Louis Encephalitis

AID In Vitro Malaria Culture

WHO/TDR Control of Simuliids

Approved contracts:

Panamanian Ministry of Health/lnteramerican Development

Bank—Malaria and Leishmaniasis

NIH/NCl Epidemiology of Human T-Cell Lymphoma Virus

WHO/PAHO Epidemiology of Childhood Respiratory Illnesses

in Panama

Pending grants:

Rapid Early Serodiagnosis of Leptospirosis by Detection of

Antigen in Body Fluids of Infected Persons

Epidemiologic Assessment of Preventable Illness in

Honduran Refugee Camps

Effects of Two Arbovirus in the Development of Panama

Regional Reference Center for Studies on New World

Phlebotomine Sand Fly Host Feeding Patterns

ausually because of lack of funding

SOURCE Gorgas Memor!al Laboratory, Off Ice of the Director, July 1983

pending grants and contracts. There are some

grants and contracts in every GML program.

The fact that GML has competed successfully

for research money is evidence that the quality

of research is equal to other research projects

funded by those agencies at other institutions.

Support for new projects by these funding bodies

is also dependent on successful past performance,

giving some assurance that GML is considered dependable. An official at the National Cancer Institute (32) was very positive about Gorgas’ ability

to carry out a newly approved epidemiologic

study involving human T-cell lymphoma virus,

based on their past work. He also mentioned that

GML is the obvious choice as a coordinating

center for a possible future collaborative study of

cervical cancer in several countries in the region.

Quality of Research at GML

as Seen by Experts

Several questions in the telephone survey that

was commissioned for this technical memorandum (see app. D for a more detailed discussion

of the survey results) addressed the quality of

research and training at GML. In response to a

general question, “How would you rate the work

of GML?” most of the 23 experts interviewed

reacted positively. Some programs were rated excellent, including the work in virology (especially in arboviruses), malaria, medical entomology,

trypanosomiasis and leishmaniasis, cancer, STDS,

and environmental studies. Other programs, bacteriology, for instance, were rated lower.

A commonly held sentiment was that the quality of work varies from program to program, with

many strong points and some weak points, but

that such a state of affairs was to be expected in

an institution that has been in existence for so

long. In some areas the work has become routine,

with slow but steady progress. Some work was

described as not very original, but, technically

good. Presumably this refers to such activities as

serotyping of viruses, which is of public health

importance, and is done routinely at GML, but

is not necessarily innovative.

Several people made the point that judgments

about quality of research must be tempered by

24–1 2’? () - 83 - 6
36

consideration of the conditions under which work

is done—field conditions make for a much different situation than that encountered at NIH.

Particularly in light of working conditions in the

Tropics, GML was rated highly.

The uncertainty of financial support affects the

quality of research, according to a number of experts. Lacking a secure future, it is difficult to attract top scientists to work at any institution. In

addition, the researchers already there are hampered in planning for all but the most immediate

research.

There was a diversity of opinion about whether

the quality of research at GML has changed appreciably over the years. Research emphases have

changed and the whole field of scientific research

has changed so greatly that such a judgment is

difficult to make. Of those who did answer, some

felt there was no change, others a change for the

better (variously since World War II, to within

the last 11/z years). A number noted a general decline in research quality over the years, all of those

respondents relating the decline to uncertain funding.

The experts contacted were asked about the

quality of tropical medicine training offered at

GML. Most gave it a high rating. The unique setting was considered the most important asset in

the training programs. The opportunities for clinical experience were particularly important for the

military. In this regard two respondents referred

to a comment of General Douglas MacArthur’s

that in the Philippines he needed three divisions

to do the work of one, since two would be in the

hospital with malaria or dengue. The disease

ecology is such in. Panama that similar opportunities for learning about tropical diseases do not

exist in many other places. One expert mentioned

that training in Puerto Rico, for instance, would

not be as valuable as that at GML. A few people

said that the training had gone downhill during

the past few years because of financial constraints.

Summary

The research carried out at GML over the years

has been of generally high quality. OTA’s analysis, the survey of expert opinion, the critical

review of articles and manuscripts, and past site

visits are all in agreement on this general conclusion. As is the case in any institution with a long

history, there are strengths and weaknesses. Research emphases have shifted over the years, and

the quality has varied as well. The results of the

telephone survey confirm that most of the major

programs are strong and of good quality, and that

there are fewer weak points.

However, mechanisms to assure continued high

quality of research are not in evidence. There is

a lack of an effective peer review process for

allocating money to research projects funded by

the core grant. While grants and contracts funded

externally have passed through a competitive

process designed to assure high quality, internally generated and funded projects do not necessarily receive the same degree of scrutiny. Another

example of a potential problem area is collaboration with other high-quality institutions. GML

must become more aggressive in seeking and in

strengthening interaction and collaboration with

scientists and institutions from other countries

(especially the United States). And, as mentioned,

GML could make a larger effort to publish study

results.

OTA finds that GML is carrying out research

of high quality, and that the institution enjoys a

generally solid reputation in the field of tropical

medicine research. The most serious threat to

maintaining good research is continuing uncertainty about future financial support.
Chapter 4

Relevance of Research at Gorgas

Memorial Laboratory to Health

Problems in Tropical America
Re

——

Chapter 4

Ievance of Research at Gorgas

Memorial Laboratory to Health

Problems in Tropical America

This technical memorandum considers the term

tropical diseases to refer both to those classically

defined as tropical diseases, such as schistosomiasis, and to those in a broader definition of the

term, such as tuberculosis and malnutrition (see

ch. 1). Socioeconomic status (e. g., malnutrition,

poverty) defines the Tropics and, to a very large

degree, tropical diseases, Otherwise life in urbanized tropical America presents the same hazards to health as life in North America or Europe.

The intimate relationship between health status

and economic and social progress means that

some health problems in tropical America will

only succumb to long-term socioeconomic advancement, yet tropical diseases, by their enormous impact on health status, simultaneously and

seriously affect the economies of tropical countries. The six tropical diseases singled out by the

World Health Organization (WHO) for special

programmatic research support—malaria, schistosomiasis, filariasis, trypanosomiasis, leishmaniasis, and leprosy—together affect between 700

million to 800 million people. The first three each

affect more than 200 million people worldwide

(5).

The resulting amount of human suffering and

disability is enormous. This argues for urgent

humanitarian action where feasible interventions

exist. Significant costs are involved in treating

such diseases and in implementing public health

programs for their prevention and diagnosis, even

though health services are usually underfunded

and inadequate in most of the less developed

countries. However, the most substantial economic impacts may be the indirect ones affecting a

country’s human resources and productivity.

Health problems in the region of tropical America cover a broad range because of the great variations in climate, geography, socioeconomic conditions, and culture. Modernization, population

growth, and rapid rural-to-urban migration cause

many diseases of the developed world to have

growing significance in tropical and developing

America, especially among affluent, middle-aged,

and urbanized persons. For example, heart disease, stroke, diabetes, cancers, and accidental injuries are all emerging as major causes of morbidity and mortality in statistics for the Latin

American and Caribbean regions. *

Even as diseases of the developed world acquire

increasing importance as major causes of mortality in tropical America, the nonfatal diseases

caused by parasitic and infectious agents remain

a critical drag on developmental progress and the

quality of life. Furthermore, in the developing

countries, life expectancy at birth is much lower

than in the developed world. This is a direct result

of high infant and childhood mortality. The major killers of infants and children are three groups

of diseases: diarrheal and enteric infections (fecalborne), respiratory infections and measles, and

malnutrition.

This chapter will first describe some of the major tropical diseases and conditions of ill-health

of tropical America. Following that, the Gorgas

Memorial Laboratory’s (GML) research and related activities will be discussed in light of the information on regional health problems and research needs.

Evaluation of research relevance quickly becomes subjective. Research by its nature is openended. If science administrators and researchers

could predetermine all lines of productive research, they would do so. The reality is often a

simpler hope—for good judgment and good luck.

*Caution is necessary, however, in interpreting these statistics,

because they derive from health care systems that are weighted

(because of the training of physicians, the availability of health facilities, the logistical problems of data collection, etc. ) towards the

diagnosis and recording of acute, traumatic, or degenerative disease

presentations in urban areas.

39
40

In evaluating the relevance of research at GML, nities, and the relationship of GML’s research to

OTA depended on identified health problems and those health problems and research needs.

needs, resulting research questions and opportuTROPICAL DISEASES: DESCRIPTION AND STATUS

Acute Respiratory Infections

Acute respiratory infections (ARI) area major

cause of mortality in children under 5 and the

elderly. The group includes many viral and bacterial infections: influenza (myxoviruses, type A,

B, C), parainfluenza (paramyxoviruses), measles

(paramyxovirus), respiratory syncytial viruses,

adenoviruses, rhinoviruses, Streptococcus pneumonia and other bacteria, chlamydia (congenital),

and mycoplasma. Influenza and pneumonia are

among the top five causes of death in children

under 5 in every country of the Pan American

Health Organization (PAHO) region (75). In addition to the serious mortality risk for the very

young and the very old, these infections are a

tremendous social burden in terms of work productivity lost and demands on the health care

system by all age groups.

These infections are aggravated in conditions

of malnutrition and substandard living conditions,

and in combination with other infectious diseases.

A principal epidemiological factor of ARI transmission is close, overcrowded associations that

promote inhalation of aerosolized pathogens by

coughs, sneezes, and personal contact.

For most of these diseases there is no treatment

other than symptomatic and supportive relief,

though bacterial infection can be effectively

treated with antibiotics. Vaccinations for measles,

whooping cough, and diphtheria are feasible and

promoted under the Expanded Program on Immunization of WHO. Vaccines against influenza

and pneumococcal pneumonia are available but

have reduced usefulness in developing countries:

Pneumococcal vaccine is not very effective in

children under 2 years old; influenza vaccines

must be renewed periodically according to the currently prevalent strain.

Improved access to health care is a critical factor, but also needed are field-based epidemiological studies. ARI control is largely ignored in most

developing countries. This is a function of difficult

diagnosis (of the etiologic agent), lack of effective treatment, lack of definition as a tropical disease, and as an entity worthy of focused research.

Longitudinal studies on the epidemiology of ARI

using rapid diagnostic techniques are needed.

These studies could simplify the prevention and

treatment of ARI by precisely identifying the important etiologic agents in geographic areas and

by determining the risk factors which make ARI

mortality so high. Practical management of ARI

depends on differential diagnosis of viral from

other bacterial, chlamydial, and mycoplasmal

agents for which specific treatments are effective.

With risk factors defined, intervention against

them could be initiated. At the same time, such

studies would produce baseline prevalence data

for subsequent evaluation of intervention measures taken.

Diarrheal and Enteric Diseases

Diarrheal diseases are the leading cause of death

in children under 5 years of age in over half the

countries of Latin America and one of the top five

for all other countries. Data from several countries indicate that the typical child below 5 years

of age experiences four to eight diarrheal episodes

annually. In some countries, up to 45 percent of

all hospital visits during the months of highest

diarrhea prevalence are due to childhood diarrhea,

and case fatality rates as high as 40 percent have

been recorded (76).

A comparison of death rates in children under

1 year of age is startling. For North America

(United States and Canada), the mortality rate in

infants in 1979 was 21.9 per 100,000; for Latin

America it was 914.6 per 100,000, 40 times higher,

almost 1 in 100 infants dying of diarrheal disease.

Because underreporting from rural areas is still

a problem, it is likely that the statistical number

of diarrheal cases will increase as health services

are extended to rural populations.
41

Diarrheal diseases constitute a clinical syndrome of varied etiology, all of which are transmitted by human feces. These include bacilli, viruses, and parasitic and helminthic parasites, such

as shigellae, salmonella, Escherichia coli, Campylobacter, Yersinia, rotaviruses, amoeba, giardia, ascaris, and ancylostoma. Poliomyelitis is

also a fecal-borne disease.

Rotaviruses, which in recent years have been

found responsible for almost half of infant diarrheas in the developing world, were first detected

in humans in 1973. Serologic studies have shown

that by the age of 2 years, nearly all children have

had the infection. A Guatemala community

study indicated that rotavirus accounted for 10

to 20 percent of all diarrhea there.

Escherichia coli is a second important cause

worldwide of diarrheal disease. Only certain

strains which are classified in three groups cause

disease: enterotoxigenic E. coli, enteroinvasive E.

coli, and enteropathogenic E. coli. Each group has

a distinctive physiological and pathological symptomatology. Serotyping based on bacterial cell

wall antigens is a second classification system.

Other important diarrheal pathogens are Shigellae, Salmonellae (both typhoid and nontyphoid), Campylobacter, Entamoeba histolytica

(amebiasis), and Giardia lamblia (giardiasis).

Although acute diarrheal diseases remain a

leading cause of childhood morbidity and mortality in most of the Americas, prospects for their

control are steadily improving. Intensive research

in recent years into almost all aspects of diarrheal

disease has led to a number of breakthroughs and

technical innovations, such as oral dehydration

therapy (ORT), which has become the main strategy of the WHO/PAHO diarrheal disease control program. Therapeutic studies continue to

document the effectiveness of this simple, safe

method which uses a single specific orally administered water solution of electrolytes and

glucose. An ORT trial project begun in 1978 in

Costa Rica has proved an effective lifesaver in

both bacterial and rotaviral infant diarrhea

(70,72,83). A recent study (95) demonstrated that

even in well-nourished children in developed

countries, ORT is a safe and effective treatment

for acute diarrhea (regardless of etiologic agent)

and could replace the use of intravenous fluids

in the majority of such children.

In addition to ORT, four other major strategies

comprise the diarrheal disease control program:

1) improved child care practices, including promotion of breastfeeding, proper weaning, and personal hygiene; 2) health education; 3) improved

water supply, environmental sanitation, and food

hygiene; and 4) epidemiologic surveillance. A

medium- to long-term objective is to integrate

diarrheal disease activities into existing primary

health care systems.

With the growing evidence of rotavirus importance in diarrheal disease, further epidemiologic,

clinical, and basic research is needed. A major objective now is to develop a vaccine for humans.

Such a vaccine exists for animals. Immunological

diagnostic testing exists which can be utilized for

field studies of prevalence and incidence in geographic localities.

Childhood mortality is the highly visible tragic

aspect of enteric disease, but the chronic and

debilitating effects of these parasitic and infectious

diseases (e.g., chronic anemia due to intestinal

hookworm) rob a nation of productivity, vitality, and initiative. WHO estimates there are at least

650 million people in the world with roundworm

(ascariasis), 450 million people with hookworm

(ancylostomiasis), 350 million people with amoebiasis, and 350 million people with whipworm

(trichuriasis) (99). Fecal-oral transmission is the

common denominator of all these diseases. Lack

of safe and adequate water supply and of proper

excreta disposal, two of humankind’s most basic

needs, are the critical deficiencies that promote

these diseases. In rural Latin America, 68 percent

of the population lack access to water supply service, and 98 percent lack sewage service of any

type. In urban areas, 22 percent lack access to

water supply service, and 57 percent have no sewage service.

Malnutrition

Malnutrition is a primary cause of death of

children under 5 years of age in Latin America.

Though not a disease per se, it is so intimately

involved in disease processes and ill-health to warrant specific mention in this overview. The Inter-
42

American Investigation of Mortality in Childhood

showed that low birth-weight (2,500 g or less) and

nutritional deficiency were the direct cause of 6

percent of deaths ‘before age 5 and an associated

cause in 57 percent of all deaths (85). Death is the

final outcome in a chain of events that begins before birth and then involves the pernicious interaction of malnutrition and infectious disease. Maternal malnutrition (together with maternal age and

parity, two other determinants in infant mortality (86)); produces premature birth and low weight

at birth, both serious risk factors for the newborn.

Infants who survive the neonatal period tend to

thrive for the first 6 months of maternal feeding,

but then come to risk from varying degrees of

kwashiorkor and marasmus, the two poles of protein-energy malnutrition. According to Gueri (48),

in a great majority of cases the problem results

not from lack of food in the home but rather from

maldistribution of food within the household,

from lack of knowledge about child feeding, from

an unsanitary physical environment conducive to

infectious diseases (particularly gastroenteritis)

that increase the child’s energy requirements while

decreasing its appetite, from early replacement of

breastfeeding with highly diluted and contaminated milk formulas, and in some cases from sheer

neglect.

Though malnutrition as a primary cause of

morbidity and mortality is less prevalent in

adolescents and adults, it still must be considered

a major contributing factor in infectious diseases.

Immunologic defense mechanisms are seriously

compromised by malnutrition. The synergistic interaction of malnutrition and disease is well documented. For example, Scrimshaw, Taylor and

Gordon (101) observed that, except where populations are malnourished, or otherwise uncommonly susceptible to disease, the incidence of tuberculosis is significantly lower than would be expected by the widespread presence of the tubercule baccilus. Mortality due to measles was 274

times higher in Ecuador than in the United States

in 1960-61, a time before the development of immunization to the disease (85). Thus in all analysis

of tropical health problems, protein-energy malnutrition must be considered a contributing cause

in the disease process, and as a primary cause in

children under 5 years old.

Important research and intervention experiments have been carried out under the auspices

of PAHO. The principal research centers are the

Institute of Nutrition of Central America and

Panama (INCAP), the Caribbean Food and Nutrition Institute (CFNI), and the Latin American

Center for Perinatology and Human Development.

Malaria

Malaria is a disease caused by a protozoan

blood parasite transmitted by various anopheline

species of mosquitoes. It is one of the most widespread and destructive diseases in the world and

has made a resurgence in the last decade with a

more than two-fold increase in world prevalence

(127,128). The incidence of malaria in developed

nations, such as England and the United States,

has also been increasing due to imported cases.

Estimated malaria incidence worldwide is 300 million cases per year. In 1982, 702,000 confirmed

cases were reported from the Americas. These

statistics are large but undoubtedly underreported, because the disease is contracted in rural

areas remote from medical facilities. An estimated

64.9 million people live in areas of tropical

America where the risk of contracting malaria persists. The countries of worst malaria incidence are

Haiti, Guatemala, Honduras, El Salvador, Colombia, Bolivia, and Brazil.

The resurgence of malaria in the last decade is

a setback due to the failure of the global eradication campaign based on DDT house-spraying and

supplementary mass drug distributions. Early successes led to overconfidence that ignored the complexity of a disease caused by four different species

of parasite and transmitted by many different species of mosquito vectors, each with peculiar behavior patterns in widely varying ecological and

sociological settings. The serious consequences of

that failure are insecticide-resistant mosquito vectors and drug-resistant strains of the parasite.

Malaria research is in a new period of vigorous

activity, like most of parasitology. Molecular biologists, geneticists, and biochemists have begun to

apply their research skills to the many important

questions that were ignored during the eradication era. Metabolic studies can identify parasite-
4 3

specific enzyme pathways that can be exploited

to kill the parasite without harming the human

host, Membrane research can reveal how the

parasite finds, attaches to, and invades red blood

cells yielding important clues for drug therapy and

vaccine research. Recent clinical studies have suggested better ways of preventing and treating cerebral malaria, an often fatal complication of severe

malaria infection.

The spread of drug-resistant malaria (by the

species Plasmodium falciparum ) is of great concern worldwide. Regular monitoring of local parasite strains is necessary to keep abreast of therapeutic changes that may be needed, both in type

of drug and dose. In Latin America, serious drugresistance has still not moved north of the Panama

Canal. Renewed effort to develop new drugs is

producing results, but takes years to move from

laboratory screening through animal testing to human trials.

Vector biology studies are critical to any rational mosquito-control effort. Cytogenetic

research which analyzes insect chromosomes has

identified species complexes that were previously unrecognized by conventional taxonomy. As

an example, Anopheles gambiae, the notorious

malaria vector in Africa, is now known to be a

complex of several distinct species all identical to

the unaided eye. Cytogenetic differentiation of the

various species has explained the different behavior patterns of the A. gambiae complex and defined the important vector species. Research on

physiological resistance mechanisms can aid the

development of better insecticide methods. Behavioral resistance, the avoidance of insecticides by

insects, is important for two opposite reasons—

the killing effect is reduced, but transmission may

still be interrupted, if vectors avoid human

habitations.

Field- and community-based studies are needed

to assess the impact of antimalarial interventions.

The ecological impact of vector intervention is

critically important. The selection of insecticideresistant vectors has seriously handicapped current control efforts. The effect of antimalarial activities on population immunity levels still needs

clarification. Studies in the past have clearly

documented the immediate impact of antimalarial

projects on morbidity and mortality, but not the

long-term consequences when projects cease or

fail. Other studies need to evaluate the importance

of sociological and human behavioral factors and

the usefulness of health education, community

self-help, and volunteer collaborators.

Significant progress is being made on the development of a vaccine against malaria, including

the identification of surface antigens and their production by bacteria. If animal testing confirms the

feasibility of immunization against this parasite,

extensive human and field trials will be required,

before there is widespread usage of vaccines in

the control of this disease. The wide usefulness

of a vaccine is also debated considering the many

difficulties associated with implementing other

disease immunization campaigns.

Chagas’ Disease

Chagas’ disease (American trypanosomiasis) is

caused by a protozoan parasite of the blood and

tissues and transmitted by reduviid bugs (“conenosed” or “kissing” bugs), common blood-sucking

insects in the Americas. It is a disease of poor rural

areas with substandard housing that provides harboring sites for the bugs to live and breed. About

150 species of mammals have been incriminated

as reservoir hosts, including dogs, cats, guinea

pigs, rats, opossums, and other rodents and marsupials. The parasite has two life stages in the

mammalian host, one that circulates in the blood

and another that proliferates intracellularly in

tissues.

In 1974, WHO estimated that out of 50 million

exposed, a total of 10 million persons were infected with the Chagas’ disease parasite Trypanosoma cruzi (discovered by Carlos Chagas of

Brazil). Studies in Brazil have shown Chagas’ disease to be a significant cause of mortality in those

under 45 years of age (84) and a heavy social

burden due to high rates of hospitalization (with

unsatisfactory outcome) and disability assistance

(78).

After initial infection by the reduviid bug, the

acute phase of the disease varies in severity according to age. Cardiac arrhythmias, myocardial

insufficiency and collapse, or central nervous
44

system damage may result in death. The younger

the individual, the greater the severity. Mortality is high in children under 2 years of age, while

adults may show no symptoms. The acute stage

may resolve completely in a few weeks or months,

or may pass into a subacute or chronic stage.

There is no effective cure. Long-term sequelae are

cardiomyopathy leading to heart failure and

grotesque enlargement of the digestive tract (megaesophagus and megacolon).

The transmission threat in rural areas is great,

but transmission by blood transfusion is also a

major problem for blood banks in Latin America.

The disease is found in every country of the

Western Hemisphere, except Canada and the Caribbean. Opossums and other mammals harbor the

disease in the Southern United States, and a small

number of indigenous human cases have occurred

in recent years (e.g., two in California in 1982).

Control measures concentrate on insecticide

spraying of houses and upgrading of housing construction (adobe, mud, cane, thatch, or otherwise

poorly constructed rural homes with cracks in the

walls are the usual harborage of the insect vector).

An effective drug cure is a critical research need.

With a therapeutic drug in hand, a simple effective test for early diagnosis would be essential—

the long-term effects once they appear are irreversible. Vaccine research is underway, but this

disease has a complicating factor—the long-term

pathology seems to result from the body’s immune

response reacting against the parasite and crossreacting to its own heart and nerve tissue. Vector bionomics remain important research topics

for defining transmission areas, vector behavioral

characteristics, and improved control measures.

Leishmaniasis

Leishmaniasis is a disease with three clinical

presentations depending on the leishamanial parasite species. In each case, the protozoan parasite

species is transmitted by bloodsucking phlebotomine sandflies. Cutaneous leishmaniasis is a selflimiting and usually self-resolving sore at the point

of infection. Mucocutaneous leishmaniasis is

caused by a different Leishmania species that

begins as a sore but commonly metastasizes and

proliferates in the nasal and pharyngeal mucous

membranes. Gross destructive disfigurement of

the nasal passages occurs. Visceral leishmaniasis

(kala-azar) is a third type of disease in which

spleen, liver, bone marrow, and lymph glands are

the sites of parasite proliferation. Fatal outcome

in children is common.

The disease exists in all Latin American countries except Chile, and in some the number of cases

is increasing because of agricultural colonization

in jungle areas, In the late 1970’s, cutaneous

leishmaniasis seriously impeded a Bolivian scheme

to relocate people outside the overcrowded altipiano. Many of the colonists abandoned their

land. More than 60 percent of those who did said

that leishmaniasis was their reason for returning

to the mountains. It has also significantly hampered both oil exploration and roadbuilding in

several Andean countries (76).

Epidemiologically, most forms of the disease

are transmitted to humans from animals in the

jungle (zoonoses), representing a health hazard

to anyone working there, and rendering control

unsatisfactory or impracticable.

Specific treatment is now limited to antimony

compounds that are not always effective and often

have adverse toxic side-effects. Another disadvantage is that they require daily injections over 10

to 20 days, which makes them impractical for patients living in remote and inaccessible areas.

Hospitalization for such a period is not only expensive but also a major inconvenience to the patient who cannot afford to leave work or farm

for an extended period. For these reasons, improved treatment of the tens of thousands of existing cases is a priority research goal. PAHO/

WHO currently has a structured effort to develop

new therapeutic drugs. Allopurinol is a promising compound of current research activity (119).

In other PAHO investigations of leishmaniasis

epidemiology, a seroepidemiologic survey in

Panama revealed an apparent focus of leishmaniasis transmission without clinical infection.

Completely subclinical leishmaniasis was previously unknown and may be important to vaccine

development. Rapid species diagnosis of leishmanial sores may be soon possible by a recently

published technique of DNA hybridization (124).
This would permit early treatment of the destructive mucocutaneous form of the disease, as well

as facilitate precise epidemiologic field studies.

Arthropod-Borne Viral

Diseases (Arboviruses)

This large group of diseases is caused by viruses

(currently about 80 in humans) defined by ecological, epidemiological, and clinical parameters.

Strictly speaking, arboviruses replicate in and are

transmitted by arthropods (predominantly mosquitoes, but also ticks, sandflies, midges and

gnats). There are some arbovirus- like diseases

whose vector is still unidentified and some whose

early epidemiological profile incorrectly suggested

arthropod transmission; their symptoms (e. g.,

Argentinean and Bolivian hemorrhagic fevers)

must be differentiated from those of true arboviruses. The number of arboviruses is growing rapidly as research resolves the etiologic agent of

many fevers and brain inflammations (encephalitis) of unknown origin and elucidates transmission cycles. Examples of arboviruses include:

yellow fever, dengue fever, eastern equine

encephalitis (EEE), western equine encephalitis

(WEE), St. Louis encephalitis (SLE), Venezuelan

equine encephalitis (VEE), California encephalitis

(CE), Colorado tick fever, Chagres fever, and

Oropouche fever. (Locality names denote the

source of first isolation; range of each is far

wider. )

Clinically these diseases are classed in four

groups (6): I) acute central nervous system disease usually with inflammation of the brain

(encephalitis), ranging in severity from mild asep

-

tic meningitis to coma, paralysis, and death (WEE,

EEE, CE/LaCrosse encephalitis, SLE); 2) acute

benign fevers of short duration, many resembling dengue with and without a rash (exanthem),

although on occasion some may give rise to a

more serious illness with central nervous system

involvement or hemorrhage (yellow fever, dengue, VEE, Oropouche); 3) hemorrhagic fevers, including complications of acute febrile diseases

(previous group), with extensive hemorrhagic involvement, frequently serious, and associated

with shock and high-fatality rates. One of them,

yellow fever, also causes liver damage and jaundice; 4) polyarthritis and rash, usually without

fever and of variable duration, benign, or with

arthralgic sequelae lasting several weeks to

months.

Most of these infections are diseases of animals

(zoonoses) accidentally transmitted to man,

though epidemics can occur with man; the principal source of vector infection, In 1981, an

epidemic of dengue fever swept through Cuba

with 344,208 cases and 158 deaths. The 1977-80

pandemic of dengue in the Caribbean and Central America caused a half-million cases.

Laboratory diagnosis can identify arboviruses

and define antigenically similar groups, but great

geographic and climatic diversity is found in each

serologic grouping. This emphasizes the complexity and challenge of arbovirus research and control. There is no cure for these diseases, only

symptomatic and supportive relief. Early diagnosis of serotype has three important values: to differentiate ambiguous presenting symptoms; to anticipate life-threatening complications, as in

yellow fever and dengue fever; and to target the

type of vector which then determines control

strategies. Current control efforts rely on identifying epidemic outbreaks early in order to institute

vector-control measures such as insecticide fogging. However, disease surveillance is not well

developed in many tropical countries of the

region.

Only yellow fever has an effective vaccine.

There are experimental vaccines for certain strains

of dengue fever, VEE, and WEE. The general utility of arbovirus vaccination is doubtful, though,

because of the complexity involved. The wide variety of arboviruses, most occurring only sporadically in humans, and without inducing crossimmunity, raise many questions about implementation and bring the realization that vaccination

is unlikely to be a panacea. Vector control will

remain the primary intervention method. Entomologic research on vector bionomics together

with surveillance of sentinel populations (animal

reservoirs and vectors) are activities for emphasis.

Especially important is elucidation of the vectorbridge concept—the factors permitting transmission of these zoonoses to humans when the principal vector arthropod is not a human-biter.
46

Yellow fever was the first arbovirus disease of

the Tropics to be recognized and elucidated. It was

William Gorgas who eradicated the disease from

the Panama Canal Zone and Cuba in the early

1900’s. Further success was recorded throughout

Latin America against urban yellow fever, such

that no cases were documented in the Americas

for the past four decades. Jungle yellow fever,

however, remains a major threat in tropical America. It is the same virus maintained by transmission through a number of jungle mosquitoes with

monkeys and possibly certain marsupials serving

as reservoirs. Recent research has demonstrated

that transovarial transmission (passage of the

virus from the female mosquito to the egg) occurs in vectors of yellow fever (26) (and other arboviruses). Thus, the mosquito may function not

only as a vector, but also as a reservoir. Human

cases are associated with man invading the jungle

habitat. In recent years, however, an outbreak in

Colombia appeared where there were no apparent

known vectors or reservoirs and in Trinidad

where no cases had been detected for almost 20

years. The possibility of unknown reservoirs or

vectors is of concern. Aedes aegypti the vector

of urban yellow fever remains abundant throughout the hemisphere (including the United States),

posing a persistent threat of epidemic outbreaks

in large population centers.

The disease occurs in periodic cycles stretching

over several years which depend on the buildup

of nonimmune individuals in a population who

are then swept by an epizootic of the virus leaving an immune population of survivors.

Vaccination of human populations near endemic jungle areas is one strategy. Surveillance of

monkey populations and jungle mosquitoes by

sampling for virus isolation is an important control measure that gives early warning to institute

remedial action.

Dengue fever is a. disease caused by four different serotypes of the dengue flavivirus. In recent years large epidemics of this virus have swept

the Caribbean and Central America. In 1981, the

first indigenous cases in the United States since

the 1940’s occurred. The virus is endemic in the

Caribbean and is transmitted by mosquitoes of

the genus Aedes, including the common urban

vector Aedes aegypti which is found as far north

as St. Louis, Mo, It breeds in small containers of

water such as discarded tires, cans, and jars. A

serious, sometimes fatal, complication of dengue

fever is dengue hemorrhagic fever (or dengue

shock syndrome).

Oropouche fever is emerging as a very important type of arbovirus disease, because of its debilitating symptoms that reduce productivity due

to convalescence. The virus is transmitted by biting

midges (Culicoides spp. ) in urban and periurban

areas. There is probably also a silent transmission cycle in forested areas.

Filariasis

Several species of filarial nematode worms can

inhabit the skin, other tissues, or the lymphatic

system causing disease in humans. These parasites

are transmitted by bloodsucking insects. In Latin

America only two worms are considered public

health problems, Wuchereria bancrofti and Onchocerca volvulus.

The bancroftian filariasis was introduced from

Africa. It is transmitted by several species of mosquitoes including common household pest species.

The adult worms live in the lymphatic system and

cause pathology depending on the immune response of the host. Inflammation and gross obstruction results in varying degrees of swelling of

the lymph glands up to frank elephantiasis of the

legs, breasts, or scrotum. Adult worms release immature forms (microfilariae) that circulate in the

blood which then infect feeding mosquitoes to

complete the transmission cycle. Chemotherapy

and vector control are currently imperfect and

need more research.

Onchocerciasis is also known as river blindness,

because the blackflies (Simulium spp. ) that transmit it live and breed in or near waterways. The

disease occurs in well-defined parts of Africa and

in the Americas, in discrete foci in Guatemala,

Brazil f Colombia, Ecuador, Mexico, and Venezuela. Ecuador’s onchocerciasis focus was only

discovered in 1980. A Panamanian blackfly has

recently been shown to be a potential vector of

O. volvulus.
The adult worm lives in the tissues of the body

and often forms large nodules where an intertwined clump of worms localizes. Microfilariae

released by the adults migrate through the body

in the subcutaneous tissues where they can be

picked up by feeding black flies. If microfilariae

reach the eye, lesions and blindness can result.

Control measures focus on vector control and

blindness prevention (imperfectly achieved by

chemotherapy and nodule removal),

Schistosomiasis

This debilitating disease is caused by a fluke.

The worm-like adult parasite lives in the human

host’s bloodstream, Eggs are deposited in the

blood vessels and escape into the bowel or bladder, or lodge in other organs, where they produce

inflammation and scars. The complex lifecycle involves excretion of the eggs into water sources,

an intermediate snail host in which proliferation

occurs, and an immature stage that can penetrate

the unbroken skin of persons who enter infected

water. Three major species of the fluke occur

worldwide, only one in the Americas, Schistosoma mansoni, which was introduced from Africa.

S. mansoni is now established in suitable snail

hosts in more than half the States of Brazil, where

10 million people are believed infected, in Surinam, where 10,000 people are probably infected,

and in parts of Venezuela, where 10,000 more

people are thought to have the infection. Foci in

the Caribbean occur in the Dominican Republic,

Guadaloupe, Martinique, and St. Martin. A few

cases have been detected in Montserrat. The disease is declining in Puerto Rico and Saint Lucia

due to intervention measures (76).

Chemotherapy against the disease is effective

and relatively safe. Total and complete coverage

in endemic areas can be difficult to achieve requiring other measures to complement control efforts, particularly attention to water and excreta

sanitation and anti-snail treatment of breeding

sites (mollusciciding against the snail host).

Schistosomiasis is spreading worldwide due to

water impoundment and irrigation projects which

create and expand suitable environmental conditions for snail hosts and increase human-snail contact. Areas where large hydroelectric dams are

being built especially in South America deserve

special surveillance and assessment.

Leprosy

Leprosy is a chronic bacterial disease that continues to be an important public health problem

in the Caribbean and Latin America. A quartermillion cases are registered in the region, perhaps

twice that number are prevalent. As case-finding

and notification improved, reported incidence increased with extension of anti-leprosy efforts. Depending on the host’s immunologic response, leprosy can range from the benign tuberculoid form

with localized skin lesions and some nerve involvement to the malign lepromatous form that

causes spreading lesions which become nodular

and disfiguring, destruction of the nose, involvement of the vocal cords and eyes, and severe nerve

damage. Over half the cases in Latin America are

the lepromatous form.

Research on the epidemiology of leprosy is still

needed. A number of useful drugs are now available for treatment. Drug-resistant strains of

Mycobacterium leprae have resulted in recommendations for combination chemotherapy which

will shorten the treatment period. If organized and

administered well, this will lighten the workload

of health services, improve patient compliance,

and result in better prognosis. Vaccination against

the disease is in human trials but still years from

routine use. The PAHO-associated Pan American

Center for Research and Training in Leprosy and

Tropical Diseases (CEPIALET) in Caracas, Venezuela, carries out a full research agenda on

leprosy, as does the U.S. Public Health Service

in Carville, La. Other philanthropic institutions

provide support to leprosy control either directly to the countries or through PAHO.

Tuberculosis

Tuberculosis is a mycobacterial disease transmitted mainly by airborne droplets. The lungs are

first involved, after which infection can spread

to all parts of the body. Though the disease is

decreasing slowly in the Americas, it is still a

serious problem in most countries of the region.
48

Even countries such as Canada and the United

States, with highly developed coverage for diagnosis and treatment, have significant numbers due

to immigrants from tuberculosis-prevalent areas.

Control methods based on BCG (bacille Calmette-Guerin) vaccination, diagnosis from those

with productive cough and treatment for those

with sputum positive, is the policy of PAHO and

the health ministries of Latin America.

BCG vaccination of uninfected persons can produce high resistance to tubercule bacilli, nonetheless, the protection conferred has varied greatly

in field trials. Because some trials have shown high

protection, BCG is still recommended in areas of

high-transmission risk. The resolution of the question of BCG effectiveness needs further evidence.

Cancers

Cancers deserve mention in the context of this

technical memorandum. They are already one of

the leading causes of death in Latin America. This

is an unhappy indicator of progress against other

causes of mortality, because to die of most cancers, one must survive past middle age.

Epidemiologic research has identified varying

patterns of site-specific prevalence in the region.

This points out areas for research on risk factors

as possible causes. Extremely high rates of cervical cancer and penile cancer, compared to the rest

of the world, occur in several of the Latin American countries, including Panama.

RELEVANCE OF RESEARCH AT GORGAS

The relevance of GML research maybe evaluated in comparison to the health problems of

Panama, the tropical Americas, the United States,

and to biomedical research in general. The broad

range of pressing health problems in Latin America and the modest amounts of research support

available dictate that careful stewardship and rational integration of resources and activities take

place so that research programs do not overlap

unproductively and that the restricted resources

are used efficiently.

Historically, GML has concentrated on vectorborne parasitic and infectious diseases. Consequently, it is not surprising to note that GML has

no active research program on malnutrition, leprosy, or tuberculosis. These health problems,

however, are under active research and study by

other institutions in the region. For example, malnutrition is the focus of a longstanding agenda of

research and intervention studies by INCAP in

Guatemala, by CFNI in Jamaica, and others.

Leprosy research is carried out by CEPIALET in

Venezuela, and the U.S. Public Health Service in

Carville, La., while PAHO and philanthropic institutions also provide other support for research

and intervention in several countries of the region.

Tuberculosis research and training is also funded

by PAHO. Thus, a lack of GML activities in these

areas, by itself, does not indicate low relevance.

On diarrheal disease, GML has researched

Campylobacter-caused diarrhea in Panama which

was found to be very prevalent in hospitalized

cases. Another recent study examined epidemiologic features of Norwalk virus and Escherichia

coli. This work complements other diarrhea

disease work in the region, such as rotavirus

research by INCAP and the Caribbean Epidemiology Center.

A recent GML collaborative clinical study of

oral dehydration therapy (95), published in the

New England Journal of Medicine and also in

Spanish in the Revista Medica de Panama, documented the wide applicability of this technique

that was highlighted by an accompanying editorial (12). Thus, GML exploited the availability of

a health problem to expand basic scientific understanding, to test clinical therapy, and to disseminate the knowledge in Latin America and the

United States.

Malaria research utilizes the GML monkey colony to test experimental drugs. The spread and

multiplication of drug-resistant malaria is a cause

for concern throughout the world emphasizing the

need for discovery and testing of new therapeutic

drugs. GML research has identified several promising compounds. This work is not only relevant

to the countries with high-malaria prevalence, but
4 9

also to the U.S. military, which in fact supports

much of this research.

The Aotus monkey also appears to be a good

animal model for leishmaniasis, which has been

used at GML to test therapeutic treatment with

allopurinol (119) of this disfiguring, sometimes

fatal, disease. The GML monkey colony constitutes a resource to conduct screening of promising anti-leishmanial drugs.

Cancer is a growing concern in Panama, as well

as the rest of Latin America, to which GML has

responded by assisting in the development of a

cancer registry utilizing the computer facility at

GML. One result is the identification of a focus

of strikingly high prevalence of cervical and penile

cancers. Continuing research has since examined

various epidemiological parameters, and has also

shown a very high prevalence of a cancer-associated virus (HTLV) in this population. This is

being investigated under a grant from the National

Institutes of Health (NIH) and the National Cancer Institute (NCI). This work appears to be highly

relevant to the region and especially to Panama.

This finding was corroborated by the Minister of

Health of Panama (34).

Epidemiological capability at GML is available

to assist in epidemic outbreaks, such as occurred

in 1981, with aseptic viral meningitis and with

acute hemorrhagic conjunctivitis. GML’s laboratory expertise for diagnosis of viruses complemented these investigations. GML maintains one

of the few viral diagnostic capabilities in the

tropical Americas. This type of activity is very

important to Panama and the region.

Current research on Chagas’ disease is surveying the human populations in two geographical

areas of Panama in which different vector species

transmit the T. cruzi parasite to determine epidemiological differences in the transmission

cycles, This is under a grant from WHO.

Arbovirus research, especially on the vectors

and reservoirs, is a major GML activity. A large

effort is expended to monitor jungle yellow fever,

using a system developed by GML, in the belief

that surveillance can give early warning of

epidemic potential. Urban yellow fever has not

occurred for several decades in Latin America, but

the vector Aedes aegypti is abundant throughout

the region, including the United States. When an

epizootic of jungle yellow fever flares, there is a

probability of spillover transmission to humans,

but, worst of all, would be involvement of A .

aegypti in the transmission. Furthermore, there

still remain questions about reservoirs and vectors of this disease. For Panama and Latin America, the relevance is obvious. For the United

States, too, the relevance is not just theoretical

or abstract. There are 20,000 U.S. Government

employees and dependents in Panama, another

20,000 U.S. citizens in neighboring Costa Rica

(51).

St. Louis encephalitis is another focus of arboviral research. GML is attempting to elucidate

how the virus is maintained in tropical areas, the

vectors and reservoirs, in order to expand knowledge of this arboviral disease that is prevalent

throughout Latin America and the United States.

Research on insect vectors and animal reservoirs of other diseases is carried out as well at

GML. Two important functions of entomologic

field studies are discrimination of vector and

nonvector species in various localities of actual

and potential transmission (different species have

varying transmission capabilities in different habitats), and elucidation of vector behavior and bionomics (e. g., biting times, resting habits, insecticide susceptibilities) in order to develop intervention strategies and to understand the interaction

of host, parasite, and vector. Work at GML has

recently demonstrated that a common blackfly of

Panama, Simulium quadrivittatum, can function

as a vector of onchocerciasis, though the disease

is currently unknown there, Endemic foci of this

disease occur in neighboring countries, thus the

disease could spread. Recent work at GML demonstrated that transovarial transmission of yellow

fever occurs in one of the mosquito vectors. Thus,

the vector may also function as a reservoir of the

virus, that may explain the persistence of the virus

in the absence of disease in animal hosts. Identification of reservoir hosts is an important adjunct

activity. Reduction of disease is sometimes feasible through control of animal hosts (e.g., China

claims to have reduced leishmaniasis through control of dogs that harbor the parasite. ) These activities have relevance to possible intervention in
50

Panama and the region, as well as to basic understanding of disease processes.

GML maintains a reference capability (available to the region as a WHO Collaborative

Research Center) for the identification of blood

meals in suspected insect vectors. This is used to

determine host-preference from field-collected

specimens throughout the region.

Investigation by isozyme electrophoresis’ of

disease vectors is carried out by GML. Identification of these biochemical markers improves the

differentiation of vectorial status, especially where

species complexes are involved. GML is examining sandfly vectors of leishmaniasis. Isozyme identification was also developed to differentiate the

Leishmania species isolated from cutaneous sores.

This can diagnose the mucocutaneous type before

the destructive pathology develops.

Recently, ecological studies on the effects of impoundment of the Bayano River on insect populations and arbovirus activity have been carried out

on contract. Also, environmental and disease impact assessments were carried out in connection

with the Tabasara Hydroelectric Project. Relevance seems obvious given that the work was carried out under contract with a third party (the

Government of Panama), but the relevance is

several-fold:

1.

2.

the scientific merit and addition to scientific

knowledge;

that environmental concern is being addressed and promoted in a developing country;

*Isozyme electrophoresis is a method of separating and identifying variant proteins in apparently similar organisms which then permits differentiation and classification. This is most useful when it

correlates with geographic, pathogenic, or other varying characteristics of the organisms.

3.

4.

related to the development of environmental concern in Panama is the significant role

that environmental preservation plays in the

continued function and maintenance of the

Panama Canal, a gravity-flow, natural watershed-fed navigational waterway; and

that GML was contracted, recognizing it as

a body of expertise, within Panama, competent to do the work,

GML’s work in sexually transmitted diseases

(STDS) has focused on forms of STD that are of

high prevalence in Panama, as well as surrounding countries of the region. STDS are epidemic in

tropical America, as they are in the rest of the

world, but very little public health activity is currently underway in Latin America or the Caribbean:

With the exception of the four nations mentioned above [Canada, United States, Costa Rica,

Cuba], few countries have been able to carry out

well-organized STD control efforts. Although

most countries have developed guidelines and

standards for diagnosis and treatment, few programs to carry them out exist, especially outside

large cities (76).

GML research on STDS in tropical America is

an early and unique effort. For a problem of large

magnitude with very little current information or

other research underway, relevance to the needs

of Panama and the region seems to be very high.

GML physicians see about 1,000 patients each

year. These are people suffering from a variety

of tropical diseases for which GML can provide

expert and specialized services lacking among

local physicians and clinics. This clinical service

not only adds to the research effort at GML but

also supplies a superb and unique teaching facility, and evidently creates much good will among

the general, and health professional, population

in Panama.
SUMMARY

Overall, the work of GML appears to have high

relevance to tropical Latin America, especially to

Panama, to tropical disease research in general,

and to the United States’ interests. Not every activity of GML has obvious relevance. * Nonetheless, the Office of Technology Assessment finds

that there is no major problem relating to the

relevance of GML’s areas of research. This finding is supported by the information presented

above, by the personal statements of officials of

*Clearly stated objectives and goals for the institution, as well

as individual projects, together with regular, at least annual, formalized intramural review procedures could improve this situation.

Panama’s Ministry of Health and other health professionals in Panama, by award of grant and contract funding of research projects by NIH, the

Department of Defense, WHO, and the Government of Panama, by Fogarty International Center

(FIC) site visit reports, and by NIH/FIC testimony

before congressional committee. *

*House of Representatives, Committee on Appropriations, 98th

Congress: Subcommittee on the Departments of Labor, Health and

Human Services, Education, and Related Agencies, Appropriations

for 1984, National Institutes of Health, Part 4B, April 1983,

pp. 1635-37, 1641-43.
Chapter 5

Findings and Conclusions
Chapter 5

Findings and Conclusions

.—— ———— .—— —— .—.———-——— . —-. ——-.

FINDINGS

Previous chapters have presented information

on the quality and relevance of tropical medicine

research at the Gorgas Memorial Laboratory

(GML). At the same time, they were designed to

provide enough information about tropical diseases, tropical disease research, and research

criteria so that research policy makers could place

GML’s quality and relevance in the context of the

goals and capabilities of any comparable organization.

Gorgas cannot be compared to the National Institutes of Health (NIH). Neither can Panama’s

medical research system be compared to that of

the United States. The differences depend on more

than simply size. For example, the disease patterns

differ, the level and organization of health care

delivery differ, and availability of equipment and

collaborating scientists differ. Field conditions

both create obstacles and present opportunities

that cannot be duplicated by an organization such

as NIH.

OTA thus finds that the evaluation of the quality of an institution such as Gorgas cannot take

place without explicit recognition of certain premises. The following are the premises assumed by

OTA during this evaluation:

●

●

●

There is an inherent value in supporting tropical research laboratories in tropical countries. These benefits (see the last section of

ch. 1) extend to the tropical country, tropical

regions in general, and to the country supporting the activities.

Evaluations of the quality of research are inevitably, and properly, made partly on the

basis of fairly objective criteria such as

publications record and partly on the basis

of subjective judgments by qualified individuals.

The criteria used to judge quality, although

similar in type, need to be modified and

weighted differently for basic research or research performed in well-equipped, state-ofthe-art laboratories than for field research

laboratories.

Relevance is directly dependent on the type

and location of institution, and it should be

examined from each of the appropriate viewpoints (e.g., host country, region, United

States, general advancement of knowledge).

With these premises in mind, OTA examined

the quality of GML’s research against a range of

objective and subjective criteria. There was very

impressive agreement among the results of: 1) the

past scientific evaluations of GML, 2) the critical

evaluation of the research design and presentation of articles and manuscripts, 3) the surve y of

expert scientific opinion on GML’s quality, 4) interviews with Panamanian health officials and

professionals, 5) the examination of the GML

staff’s publications record, and 6) an examination

of GML’s record of competing for grants and contracts. All evidence gathered by OTA led to the

finding that the overall scientific quality of GML

is high, especially when considered in the context

of its status as a research laboratory located in

the Tropics. Quality was, naturally, not uniformly even, but it also appears that the Gorgas Memorial Institute’s and GML’s management is

aware of unevenness and is attempting to make

improvements.

Relevance is more difficult to judge, but in general OTA found that the large majority of GML’s

research is highly or adequately relevant to health

concerns and problems of Panama, the tropical

American region, U.S. interests, and the advancement of scientific knowledge and the field of tropical medicine in general (see tables 1 and 2 in ch.

1). The evidence for this finding lies, for the first

two, in the match up between tropical health

problems and GML research directed at them, and

from strongly expressed opinions and examples

by the Panamanian Minister of Health (who is a

former Dean of the Panamanian School of Medicine), his Deputy Minister, the medical director

of Panama’s Childrens’ Hospital (a former Min55
56

ister of Health and former head of Social Security in Panama), and numerous officials of the Pan

American Health Organization.

The importance of GML to Panama cannot be

judged solely on the basis of Panama’s monetary

contribution. Panama is going through a difficult

economic period. Even so, the Ministry of Health

has arranged a loan to keep GML in operation

for the remainder of fiscal year 1983. The value

of the land, buildings, and tax-favored status have

never been adequately assessed. And to put the

often criticized direct financial contribution of

$10,000 from Panama in perspective, the research

budget of the Panamanian medical school is reportedly only $20,000 (34).

As one official of the U.S. Department of State

expresses it: Each year, the United States sends

a message to Panama and the region by funding

GML and supporting activities related to the

health of U.S. and Panamanian citizens alike (51).

Activities related to the recent Panama Canal

treaty process provide a specific example of the

CONCLUSIONS

OTA concludes that the benefits of supporting

GML justify, on scientific and other grounds, the

relatively small amount of funds required. Quality

and relevance are high. Withdrawing core support from GML would probably not even save

the amount of the appropriation, since other

Federal agencies, such as the Department of Defense, may need to either develop their own capabilities to conduct research now carried out at

GML or to fund similar research at other tropical

medicine research centers.

Gorgas is not ideal; improvements could certainly be made. Some of the shortcomings stem

from its uncertain funding. As mentioned earlier,

the prospect of unstable funding and perhaps closure may have kept individual scientists from joining GML or becoming visiting scientists there and

may reduce the desire of U.S. universities to collaborate with GML, on research projects, As an

example, two highly qualified entomologists from

the United States discussed with GML the possibility of their coming to GML for a period. Uncerimportance of GML to Panama. As part of the

treaty, a Joint Committee on the Environment was

established. Panama turned to GML, as the only

institution in Panama with the necessary skills and

experience, for assistance in relation to environmental protection and human and animal health,

and additionally named Dr. Pedro Galindo, formerly of GML, as the senior Panamanian on the

Committee.

Relevance to U.S. health interests can be found

in the surveillance activities, the training activities,

and the various research activities undertaken under contract to the U.S. military. Gorgas’ contributions in the areas of malaria, yellow fever, and

leishmaniasis illustrate its relevance to the general

advancement of knowledge.

Based on the above evidence, OTA finds that

with some exceptions that occur almost entirely

within the core-funded activities, the research conducted at GML is relevant to the various parties

at interest.

tainties over the budget and the very future of

GML have resulted in not being able to join GML,

although one is still considering doing so.

The point about uncertainty should be placed

in perspective: most research scientists operate

under some degree of uncertainty about future

funding. In GML’s case, the uncertainty applies

to the very existence of the entire institution.

Thus, the uncertainty is a matter of degree

(though perhaps a significant one), and not a

situation unique to GML.

Another example of the effect of uncertain

funding has been the decision by the U.S. Navy

to hold off on the next scheduled training class,

because the course would extend a few weeks into

fiscal year 1984.

Gorgas itself could improve its standing and its

relevance by:

• being more aggressive in its publishing;

● by making better use of its Advisory Scientific Board (e.g., in planning for research di-
5 7

rections, as part of a more formal and effective peer review process and as visiting consultants);

by more actively seeking out associations

with universities and collaborations with a

range of groups from other countries and international organizations;

by making strategic plans to move more fully

into the developing areas of modern science

(e.g., work with monoclinal antibodies and

other immunological diagnostics, and biotechnology approaches to vaccine-related

research and development*);

by making more of an effort to run vigorous

visiting scientist and fellowship programs;

and

similar types of actions that should be considered by GMI/GML at a very near date.

Gorgas has also done a rather poor job of letting Congress, Panama, and the public know how

much it is doing and what its capabilities are. Its

financial base should be broadened. Alternately,

or in combination with broadening, some change

in the structure (e. g., an international arrangement of support) of GMI/GML might be undertaken. Any such step should be taken carefully,

in view of the importance of GML and its activities (e.g., its disease surveillance work) to the

United States.

OTA concludes that the only benefit to the

United States of defunding Gorgas would be saving of perhaps significantly less than $2 million.

The negative consequences would include loss of

one of the few, high-quality, broadly relevant,

● The contributions of the International Laboratory of Research

on Animal Diseases in Kenya to the molecular biology of African

trypanosomes is an example where a field unit has done important

work at the forefront of science (68). Other good examples are the

centers supported by the Rockefeller Foundation’s Great Neglected

Diseases Program.

tropical research institutions located in a tropical

country. The Army’s malaria research would be

hurt, as would disease surveillance in the Central

American region. The U.S. ’S standing in Panama,

and perhaps more broadly in tropical America,

would inevitably suffer. For example, the lead

editorial on July 7, 1983, in Panama City’s leading

newspaper spoke emotionally of the “incomprehensible budget policies” of the United States in

regard to defunding Gorgas.

Ironically, GML is in danger of extinction at

the very time that U.S. interest in Latin America

is high, and at a time when tropical medicine has

never been more relevant to the United States.

Health aspects of the increased numbers of

refugees in the United States, an increased amount

of international travel, and the growth of multinational corporations located in tropical regions are

examples of this heightened relevance.

Loss of the training activities at Gorgas would

not only hurt the U.S. Navy but would also

preclude the desirable possibility of expanding

such training in tropical medicine to include more

visiting physicians and students in health sciences*

from the United States and to increase the number

of Panamanians and others attending.

In summary, OTA concludes that the positive

consequences of U.S. core support of Gorgas

greatly outweigh the amount of funds involved.

Defunding now, followed by an appreciation of

the loss later and a subsequent attempt to reinstate

such a research capability, may result in much

larger required investments, an inability to recreate successful conditions for quality research,

or both.

*For example, GML and Yale University have an ongoing program whereby students of Yale’s School of Medicine go to GML

for 2- to 3-month periods for experience in research and clinical

aspects of tropical medicine.
Appendixes
Appendix A

Acknowledgments;

Pan American Health

Organization Liaison Group;

OTA Health Program Advisory Committee

ACKNOWLEDGMENTS

The development of this technical memorandum was greatly aided by the advice and review of a number

of people in addition to the Pan American Health Organization Liaison Group, and the Health Program Advisory Committee. OTA staff would like to express their appreciation especially to the following individuals:

Thomas Aitken

Yale University

Maj. Richard G. Allen

United States Army Medical

Research Command

Karen Bell

National Academy of Sciences

Mark S. Beaubien

Fogarty International Center

Mark Boyer

Harvard University

Louise Brinton

National Cancer Institute

Gloriella Calvo

The Gorgas Memorial Institute

Cdr. Patrick Carney

Navy Research &

Development Command

Richard Cash

Harvard University

Barnett Cline

Tulane University School of Medicine

William Collins

Centers for Disease Control

Joseph A. Cook

The Edna McConnell Clark Foundation

Gustave Dammin

Harvard University

William Dietz

Clinical Research Center

Col. Carter Diggs

Walter Reed Army

Institute of Research

Jose Renan Esquivel

Medical Director

Children’s Hospital

Panama City

Phyllis Eveleth

Fogarty International Center

Allan Fleener

General Accounting Office

Gaspar Garcia de Paredes

Minister of Health

Republic of Panama

Robert J. A. Goodland

The World Bank

Co], Michael Groves

Walter Reed Army

Institute of Research

Sherman Hinson

U.S. Department of State

Rod Hoff

Harvard University

Donald Hopkins

Centers for Disease Control

Abraham Horowitz

Pan American Health Organization

Lee Howard

Pan American Health Organization

Leon Jacobs

The Gorgas Memorial Institute

Geoffrey Jeffries

Centers for Disease Control

Karl M. Johnson

Fort Detrick

William Jordan

National Institute of Allergy

and Infectious Diseases

Irving Kagan

Centers for Disease Control

Robert Kaiser

Centers for Disease Control

Cpt. James F. Kelly

Commanding Officer

Naval Medical Command

Dieter Koch-Weser

Harvard University

Richard Kreutzer

Youngstown State University

Austin J. MacInnis

Editor, the Journal of Parasitology

University of California, Los Angeles

Arnold Monto

University of Michigan

Russell Morgan

National Council for

International Health

Ladene Newton

Centers for Disease Control

Clifford Pease

Agency for International Development

Martha G. Peck

Executive Director

Bourroughs-Wellcome Fund

CO]. C. J. Peters

USAMRIID

Medical Division

William C. Reeves

Gorgas Memorial Laboratory

D. S. Rowe

The World Health Organization

Special Programme for Research and

Training in Tropical Diseases

Ira Rubinoff

Smithsonian Tropical

Research Institute

Col. Phillip K. Russell

Director

Walter Reed Army Institute

of Research

61
6 2

Rolando E. Saenz

Gorgas Memorial Laboratory

Warren R. Sanborn

Portable Rapid Diagnostic

Technology, Inc.

John E. Scanlon

American Society of Tropical

Medicine and Hygeine

Robert E. Shope

Yale Arboviral Research Unit

Reuel A. Stallones

University of Texas

Ronald St. John

Pan American Health Organization

Jose Teruel

Pan American Health Organization

Paul Tiggert

Gorgas Memorial Institute

Ronald Vogel

University of Arizona

Kenneth Warren

The Rockefeller Foundation

Raymond H. Watten

Director

Gorgas Memorial Laboratory

Thomas Weller

Harvard University

Karl A. Western

National Institute of Allergy

and Infectious Diseases

Kerr L. White

The Rockefeller Foundation

Roy Widdus

National Academy of Sciences

Frank S. Wignall

United States Navy

Phillip Winter

Walter Reed Army Institute

of Research

Martin Wolfe

U.S. Department of State

Martin Young

University of Florida

PAN AMERICAN HEALTH ORGANIZATION LIAISON GROUP

OTA would like to thank the members of the group formed by the Pan American Health Organization to

provide advice on OTA’s study of the Gorgas Memorial Laboratory and the main project on the status of research

for

Dr.

Dr.

Dr.

Dr.

tropical medicine in tropical America.

Gloria Coe, Ph. D.

Liaison Group Coordinator

Francisco J. Lopez-Antunano Dr. Gabriel Schmunis

Fernando A. Beltram Hernandez Dr. Juan Cesar Garcia

George Alleyne Dr. Rafael Cedillos

Pedro Acha Mr. Jorge Pena Mohr
63

HEALTH PROGRAM ADVISORY COMMITTEE

Sidney S. Lee (Committee Chair)

Michael Reese Hospital and Medical Center

Carroll L. Estes Frederick Mosteller

Department of Social and Department of Health Policy

Behavioral Sciences and Management

School of Nursing School of Public Health

University of California, San Francisco Harvard University

Dorothy P. Rice

Rashi Fein Department of Social

Department of Social Medicine and Behavioral Sciences

and Health Policy School of Nursing

Harvard Medical School University of California, San Francisco

Richard K. Riegelman

Melvin A. Glasser George Washington University

Health Security Action Council-Committee School of Medicine

for National Health Insurance

Walter L. Robb

Medical Systems Operations

Patricia King General Electric

Georgetown Law Center Milwaukee, Wis.

Frederick C. Robbins

Joyce C. Lashof Institute of Medicine

School of Public Health

University of California, Berkeley Rosemary Stevens

Department of History

Margaret Mahoney and Sociology of Science

The Commonwealth Fund University of Pennsylvania
Appendix B

Tropical Disease Research Activities—

This appendix is a brief profile of tropical medicine

research support, concentrating primarily on activities

with which the United States is involved, either

through direct research activities or by block contributions, but also containing several examples of other

supporting organizations. Table B-1, at the end of this

appendix, summarizes the tropical medicine research

funding levels of the organizations covered. This discussion should not be regarded as a comprehensive review. For example, many U.S. universities maintain

tropical biomedical research programs. In addition,

most developed and some developing countries have

national agencies or institutes which in some way fund

tropical disease research. These are not covered. For

more detail on the range of support for tropical medicine research, see the General Accounting Office report

on Gorgas, to be completed in August 1983.

Multinational Programs

The United Nations Development Program/World

Bank/World Health Organization Special Programme

for Research and Training in Tropical Disease (TDR)

has targetted six specific diseases for biomedical

research: malaria, schistosomiasis, filariasis, African

and American trypanosomiasis, leishmaniasis, and leprosy. Essentially a grant institution, TDR also funds

projects on vector biology and control, biomedical sciences, epidemiology, and social and economic research

(126). Of the more than $30 million spent by TDR in

1981, approximately $5.6 million went to research

activities in the Americas (77). Total U.S contributions

to the TDR in 1982 were more than $5 million, approximately 22 percent of all TDR fundings (105).

The Pan American Health Organization (PAHO),

regional office of the World Health Organization,

sponsored 131 research projects during 1980-81 for a

total of $5.2 million. Direct monetary contributions

from PAHO/WHO comprised 32 percent of that sum,

the remainder coming from the 30 institutions, international organizations, agencies, and governments that

collaborate with PAHO. Research efforts were primarily directed towards the diarrheal diseases, a reflection

of the Special Programme for the Control of Diarrheal

Disease. PAHO-funded programs also researched

other infectious diseases, parasitic diseases, foot and

mouth diseases and vesicular stomatitis, zoonoses,

nutrition, and other areas (77), In 1982-83, U.S. contributions to PAHO of $57.1 million constituted 61.3

percent of the organization’s funding (18).

PAHO maintains nine centers, including the Caribbean Epidemiology Center (CAREC) located in Portof-Spain, Trinidad, the Institute of Nutrition of Central America and Panama (INCAP) in Guatemala City,

the Caribbean Food and Nutrition Institute in Kingston, Jamaica, and the Pan American Center for Research and Training in Leprosy and Tropical Diseases,

in Caracas, Venezuela (76), PAHO provides scientists

and researchers to each of the centers, and with the

exceptions of INCAP, which is semi-independent, and

CAREC, which receives moneys from 19 different

countries and institutions, the centers are primarily

PAHO- funded. It is important to note that the centers

are by no means exclusively devoted to research.

CAREC, for example, provides extensive training, epidemiological surveillance, and laboratory services for

much of the English-speaking Caribbean (100).

United States Agencies

The majority of Agency for International Development (AID) funding for tropical diseases research

comes from its Office of Health. In fiscal year 1982

the office allotted $5.8 million for research in malaria

immunology and vaccine development, $5 million to

the TDR, and $1.9 million as part of the core support

for the International Center for Diarrheal Diseases Research/Bangladesh, The AID Africa Bureau spent approximately $1.3 million on the biomedical research

components of three projects—onchocerciasis control,

combatting communicable childhood diseases, and

schistosomiasis activities in the Cameroons and the

Sudan. The remainder of AID’s tropical diseases activities, some $1 million, was channeled through the

Office of the Science Advisor for collaborative research

between U.S. universities and developing countries.

All AID funding may be considered “extramural,” with

moneys given out on a competitive basis to universities, profit, and nonprofit institutions (79).

Nearly all tropical diseases research at the National

Institutes of Health (NIH) is carried out at the National

Institute of Allergy and Infectious Diseases (NIAID).

NIAID spent more than $9.5 million in fiscal year 1982

for research on trypanosomiasis, schistosomiasis, leishmaniasis, malaria, filariasis, and leprosy. The General

Tropical Medicine Program spent $7.7 million for research involving virology, bacteriology, vector pathogens, and other disciplines; NIAID’s General Parasitology Program expended an additional $3.5 million.

The NIAID International Collaboration in Infectious

64
65

Diseases Research (ICIDR) Program allies institutions

in tropical countries with universities in the United

States for joint research on specific diseases. The

ICIDR fiscal year 1982 budget was $2.2 million. Another $800,000 was directed towards NIAID Tropical

Research Units (112). Approximately $9.5 million of

the NIAID’s Tropical Medicine Program expenditures

went towards intramural research, including salaries

and administrative costs. Extramural research accounted for the remaining $25 million, awarded to institutions around the world on a competitive grant

basis. The NIAID Tropical Medicine and fiscal year

1982 total came to $34.8 mi]lion.

Also within NIH, the Fogarty International Center

administers the appropriation of the Gorgas Memorial

Institute (as the core support for the Gorgas Memorial

Laboratory).

The Department of Defense (DOD) is active in areas

of research into diseases which pose a threat to

American troops stationed in tropical regions. Activities within DOD are coordinated by the Medical

Research and Development Commands of the Army

and Navy. Within the Army, tropical disease research

is managed by the Research Area Manager for Military

Disease Hazards; the Infectious Diseases Program

Manager oversees the Navy’s activities. In fiscal year

1983, DOD expenditures are estimated at $31.2 million, more than half of which ($17.6 million) was directed towards “basic” research (2).

The Walter Reed Army Institute of Research is the

center for most of the Army’s tropical disease activities. In the Navy, the Naval Medical Research Institute is the major U.S.-based center for tropical diseases research. Infectious diseases research includes a

wide range of tropical diseases. The Army’s antimalarial drug development program and the Navy’s

vaccine effort are part of the Department’s emphasis

on malaria. In addition, the United States Army maintains tropical medicine research units in Brasilia,

Kenya, Malaysia, and Thailand. The Naval Medical

Research Units are located in Manila, Jakarta, Lima,

and Cairo. In fiscal year 1983 DOD funding for these

overseas units came to $9.7 million. The department’s

overall tropical disease program total of $31.2 million

does not include salary or housing expenses for military personnel, which fall into other areas of DOD

obligations; however civilian salaries, local employees,

maintenance, and supplies do come out of tropical disease program budgets.

The Centers for Disease Control (CDC) (of the U.S.

Public Health Service) does not have an autonomous

tropical disease program, but conducts tropical disease

research primarily through its Center for Infectious

Diseases and its Parasitology Division. CDC also

serves as a worldwide resource center and is frequently

called on by tropical countries to provide emergency

assistance. The Medical Entomology Research and

Training Unit in Guatemala is funded by CDC. In

fiscal year 1983, total CDC tropical diseases research

funding, including salaries, administration, and other

costs, came to an estimated $5.5 million (53).

Other Institutions

The following are a few examples of non-U. S. Government supporters of tropical medicine research and

related activities.

Through its Tropical Diseases Research Program,

the Edna McConnell Clark Foundation funds a variety of research projects in both developed and developing countries. Primarily concerned with schistosomiasis, the foundation’s program awarded approximately

$2.5 million for more than 60 competitive grants during fiscal year 1982, and accounted for 18 percent of

all Clark Foundation activity (27).

The Great Neglected Diseases of Mankind (GNO),

a major component of the Rockefeller Foundation

Health Sciences Program, examines vaccine and drug

development, improvement of diagnostic testing, and

appropriate targeting of therapy. The GND Network

currently maintains 14 units at institutions around the

world. These units, primarily universities, carry out

research projects concentrating on malaria, schist osomiasis, and diarrheal diseases; furthermore, in 1982

the units trained a total of 84 researchers from developed and developing countries. The GND program

cost came to $1.9 million in 1982 (90).

The International Development Research Centre

(IDRC), an Ottawa-based public corporation created

by the Canadian Parliament, disbursed approximately $4.9 million Canadian on tropical medical research

grants to institutions in 1982 from its Health Sciences

Division. The grants went for projects ranging from

sexually transmitted diseases to malnutrition to

leprosy. The division also provided additional funding

for some health care delivery and water supply and

sanitation projects in tropical countries. Along with

its four other divisions, IDRC issued $36.5 million in

grants during 1982 (56).

In London, a portion of the profits profits from the

Burroughs-Wellcome pharmaceutical company go to

the Wellcome Trust. During 1980-82, the Trust

distributed 3.6 million pounds Sterling (roughly $6 million U. S., approximately 15 percent of the Trust’s total

allocations) for research and fellowships for investigation into cerebral malaria, schistosomiasis, leishmaniasis, rabies, and other tropical medicine concerns.

About 30 percent of these funds were used to help run
66

the Trust’s Tropical Units in India, Brazil, Thailand, Burroughs Wellcome Fund, an entirely separate entiKenyaJ and Jamaica. Approximately 20 percent of the ty supported by profits from the U.S. branch of the

allocations were used for special lectures and fellow- company, awarded $406,000 in support of molecular

ships with the remaining sO percent awarded to re- parasitology research in fiscal year 1982. This sum

searchers and research institutions around the world represented 18 percent of the Fund’s awarded grants

on an individual project basis (122). In addition, the during that period (80).

Table B-1 .—A Profile of Funding for Tropical Medical Research

Millions

Organization of dollars Year Reference

World Health Organization:

Special Programme for Research and Training

in Tropical Diseases (TDR) . . . . . . . . . . . . . . . . . . . . . . 23.832 81 102

Pan American Health Organization . . . . . . . . . . . . . . . . . 5.2 80-81 77

Agency for International Development. . . . . . . . . . . . . . 15.0 FY82 79

National Institutes of Health:

NIAID . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.856 FY82 111, 112

Fogarty International Center . . . . . . . . . . . . . . . . . . . . 1.8 FY83 114

Department of Defense. . . . . . . . . . . . . . . . . . . . . . . . . . . 31.246 FY83 2

Centers for Disease Control . . . . . . . . . . . . . . . . . . . . . . 5.5 FY83 53

Edna McConnell Clark Foundation . . . . . . . . . . . . . . . . . 2.573 82 27

Great Neglected Diseases Program . . . . . . . . . . . . . . . . 1.9 82 89

International Development Research Centre. . . . . . . . . 4.2a

82 56

Burroughs-Wellcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.6b80-82 80, 122

a Approximately equal to 4.9 million Canadian dollars.

b Approximately equal to $600,000 U.S plus 3.6 million pounds Sterling.

NOTE: The definitions of tropical diseases and tropical disease research activity used in compiling these data are not uniform.

For example, CDC totals include activity in research which is not covered by the Department of Defense. TDR//WHO totals

are for research and development and research capability strengthening only. The DOD data are only restricted to those diseases

which are of concern to American troops stationed in tropical countries, As part of the Department of State, AID contributes

funds for tropical disease research to both the TDR/WHO and the PAHO; these funds then lose their “American” label, In

addition, more than $1 million was given by AID to NIAID. Only 32 percent of PAHO activities came directly from PAHO/WHO,

the remainder coming from matching contributions from local governments.
Appendix C

Bibliography of

Publications by the Gorgas

Memorial Laboratory Staff —— ——. - ——

LISTA DE LAS PUBLICACIONES DEL

LABOR ATORIO CONMEMORATIVO GORGAS

DE 1975 A 1979‘

(EN LOS 50 ANOS DE SU FUNDACION )

CON ADICIONES PARA 1980

Prof. Manuel Victor De Las Casas ++

753*

754

755*

756*

757*

Blandón R, Edgcomb JH, Guevara JF, Johnson CM: Electcardiographic Changes in Panamanian Ruttus rattus Naturally Infected by Trypanosoma cruzi. Am Heart J 88 (6):

758-764, 1974

Kourany M, Martinez R: La Situacion de la Shigelosis en Panama” (Parte B, pp. 7 1-73). En: Simposio Sobre Disenteria

Shiqa en Centroamerica (Ciudad de Guatemala, 27 y 28 de

julio de 1971), Washington, D.C: OPS, 1974 (Publicacion

Cientifica No. 283)

Bacrg D.C: Boreham MM: Experimental Rearing of Chagasia

bathana (Dyar) Using Induced Mating, and Description of

the Egg Stage (Diptera: Culicidae). J Med Entomol 11(5):

631-632, 1974

Bacrg DC, Boreham MM: Anopheies neivai Howward Dyar &

Knab: Laboratory observations on the Life Cycle and Description of the Egg Stage (Diptera: Culicidae). J Med Entomol 11(5): 629-630, 1974

Boreham MM, Baerg DC: Description of the Larva, Pupa and

Egg of Anopheles (Lophopodomyia) squamifemur Antunes

with Notes on Development (Dipterea: Culicidae). J Med

Entomol 11 (5): 564-569, 1974

+

++

+

Segundo Suplemento. La presentation de esta bibliografia (Nos. 753 at 846) difiere de

nuestra Bibliografia Basica y sus Suplementos en que, para ahorrar espacio, se suprimio la sangria y se usaron tanto has abreviaturas como el estilo de la Seccion de Materia del CIM, normas adoptadas por la Revista Medica de Panama.

Bibliotecologo Medico del Laboratorio Conmemorativo Gorgas y Profesor de Bibliotecologia en la Facultad de Filosofia, Letras y Educacion, de la Universidad de Panama.

El asterisco que sigue al numero de una pubticacion indica que, al memento de pre

parar esta bibliografia, hay disponibles reimpresos de la misma

67
68

*

*

tc

. “

g

-a.+

2

P-
783*

784

785

786

787*

788*

789*

790*

791

792

793

794

795 *

Wood DE, S{Jus~ OE: Tr-ypano~oma cruzi: Eliects of h?hotinius prolix us I;,xtracts on in ~’itro Development. Rev Lnstituto Aled Trop Sao L’aulo 18(2): 93-96, 1976

Alarc6n Seg(wia S, Andrade ZA, Bloom BR, Wood DE:

Imrnunologia de la Enfermedad de Chagas. Boletin OSP

80 (3): 235-253, 1976. Tambi4n publicado en inglis bajo el

titulo: Inlmunolo&W fo Chagas’ Disease. Bulletin of the World

Ilc-alth Organization, 54(5): 459-492, 1974.

hlindez E: “Panama’s Golden Frog”. (Section 5, pp. 92-95)

En: 1+’ilcilifc ’75; The World Conservation Year-book, ed. por

Nigel Sitwell, London: Danbury Press. 1975

Hcrrer A: “Bartonellosis”. (Chapter 30, pp. 256-259) En:

Tropicai ,i!edicine. 5ed. Por George W. Hunter III, J. Clyde

Swartzwelder y David F. Clyde. Philadelphia: Saunders, 1976

Rossan RN, Baerg DC: Demonstration of Exoerythrocytic

Stages of PLzsrrzodium vzvax in Saimiri sczureus. Trans Royal

Soc Trop Med Hyg 69(5-6): 471-472, 1975

Rossan RN, Baerg DC, Young MD: Five Species of Panamanian Monkeys as New Experimental Hosts for Plasm odiurn simium. J Parasitol 61(4): 768-769, 1975

Sousa OE, Dawson GA: Trypanosoma Infections in the Marrnoset (Saguinus geoffroyi) from the Panama Canal Zone.

Am J Trop Med Hyg 25(3): 407-409, 1976

Kourany M, Bowdre L, Herrer A; Panamanian I’orest hCunmals as Carriers of Salmonella. Am J Trop Med Hyg 25(3):

449-455, 1976

Young hlD: “hlalaria” (Chapter 38, pp. 353-396) En: Tropical .tledicine. 5ed. Por G. W. Hunter, J. C. Swartzwelder y

D. F. Clyde. Philadelphia: Saunders, 1976

Yunker CE, Brennan JM, Hughes LC, Philip CB, Clifford CM,

Peralta PH. Vogel J: Isolation of Viral and Rickettsial Agents

from Panamanian Acarina. J Med Entomol 12: 25(J-255, 1975

Varma hiGR, Pudnes M, Leake CJ, Peralta PH: Isolation in a

Mosquito (’Aedes pseudoscutellaris) Cell Line (Mos. 61 ) of

Yellow l’ever Strains from Original Field Material. lntervirology 6 :50-56, 1975-1976

Nelson TW: Quantitative observations on Feeding Behavoir

in Saguinus geoffroyi (Callithricidae, Primates). Primates

1’(2): 223-226, 1975

Baerg DC, Rossan RN : Plasm odium vzuax Tissue Stage in

Saguinus geo~~royi. Trans Royal Soc Trop Med Hyg 70(2):

167-168, 1976

796

797

798

799

800

801

802*

803*

804*

805 *

806

\$’ebb PA, Justines G, Johnson Khl: lnfcction of Wild and Laboratory Animats with hl~chupo and Latino Viruses. Bull

\$’HO 52: 493-499, 1975

Tesh RB, Peralta PH, Shope RE, Chaniotis BN, Johnson KM:

.%ntigenic Relationship Among Phlebotomus Fever Group

Arboviruses and their Implications for the Epidemiology

of Sand fly Fever. Am J Trop Itfed Hyg 24(1): 135-144,

1975

Reeves WC, Peters CJ, hloon TE, Purcell RH: Familial Clustering of Hepatitis B. Surface Antigen Among Panamanian

Lndians. J Infect L)is 131(1): 67-70, 1975

Chaniotis BN: A New hlcthod for Rearing Lutzomyti trapzifoi (Diptera: Psychodidae), with observations on its Development and Behavior in the Laboratory. J Med Entomol

12(2): 183-188, 1975

Reeves WC, Peters C.J, Purcell RH: The Epidemiology of IIepatitis B Antigen and ‘Antibody Among P~amaniar-Cuna 1ndians. Am J “rrop hled Hyg 24(5): 873-875,1975

L)ietz Jr. WH, Porcell 0, hloon TE, Peters CJ, Purcell RH:

Igftl Levels and Ighl-hlcdiated Immune Responses k Patients

with Acute Hepatitis A, Acute IIepatitis B and Chronic HB

Antigenaemia. Clin Exp Immunol 23(1 ): 69-72, 1976

Christensen HA, Herrcr A: Neotropicai Sand Flies (Diptera:

Psychodidae), Invertebrate Hosts of Endotrypanurn schaudinni (Kinetoplastida: Trypanosornatidae). J Med Entomol 13

(3): 299-303, 1976

}’oung hll), Baerg I)c, Russa.n RN: Studies with Induced

Nlalarias in Ao tus .Ili)nkt’ys. L~boratory Animal Science

26 (6) : 1131-1137, 1976

Rossan RN, Bacrg DC: L.iboratory and I“eral IIybridization

of A teles geog,q-oyi punarntmsis Kellog and Goldman 1944

and A. fusciceps robu~tus Allen 1914 in Panama. Primates 18

(l): 235-237, 1977

Zimmerman JH, Newson 1lD, Iioopcr GR, Christensen HA:

A Comparison of the F,gg Surface Structure of Six Anthropophilic Phlebotornine Sand E-lies (Lutzomyia) with the Scanning Electron hlicr.~scope (Diptcra: Psychodidae). J Nled

Lntonlol 23(4-5): 574-579, 1977

L)awson GA, Dukelow WR: Reproductive Characteristics of

k’ree-Ranging Pandnmlian ‘1’m]ar]ns (Saguirzus o<dipus geoj

Jroyi). J hled Primatol 5: 266-275, 1976
807*

808”

809

810

811

812*

813*

814*

815*

816

817

818

819

820*

Justines G, Sousa OE: Survival 01 Arboviruses in Trypanosome-Infected Triatomines. Am J Trop I’vied Hyg 26

(2): 326-328, 1977

Mindez E: Mammalian-Siphonapteran Associations, the Environment, and Biogeography of Mammals of Southwestern

Colombia. Quaestiones Entomologlcae, 13: 91-182, 1977

Kourany M: Obtenci6n y Manejo de Muestras pat-a Exi.rnenes

Microbioiogicosde ias Enfermedades ‘1’ransmls:bles. Washington, D.C: OPS, 1976 (Publicaci6n Cientffica No. 326), 147p.

Johnson KM: Status of Arenavirus Vaccines and their Application. Bull WHO 52,: 729-735, 1975

Johnson Khf: The Arenaviruses: Some Priorities for Future

Research. Bull WHO 52: 761-763, 1975

Miles CT, Foster WA, Christensen HA: Mating Aggregations

of Male L.utzomyti Sand flies at Human Hosts in Panama.

Trans Royal Soc Trop Med Hyg 70(5-6): 531-532, 1976

Sousa OE, Adames AJ: Geographical Extension in a New

Ecological Association of Panstrongylus humeraiis (Ilemiptera: Reduviidae), Natural Host of Trypanosoma cru.zi in

Panama. J Med I.lntomol 13(6): 748-749, 1977

Johnson CM: Un Caso de Meningoencefalitis Primaria Amibiana. Rev M&d Panan-ui 2(3): 141-144, 1977

Wendehake de Junca C, Lu,ciani de Rivas G, Sousa OE: Determinacibn de la Dosis Media Letal (DL 50) y 10S Efectos

de las Radiaciones Gamma Sobre Rhodnius proiixus y R .

neglectus (Hemiptera: Reduviidae). Rev Med Panami 2(3):

218-222, 1977

Edgcomb JH, Johnson CM: American Trypanosorniasis (Chagas’ Disease). Chapter 1 of Section 7: Diseases Caused by Protozoa, pp. 244-251. En: Pathology of Tropical and Extraordinary Dzseases, ed. por Chapman H. Bindt’ord y Daniel H. Connor. Washington, D.C: AFIP, 1976

Edgcomb JH, Walker DH, Johnson CM: Klossiella in the Opossum. Veterinary Pathol 13(4): 315-318, 1976

Blandon R, Guevara JF, Johnson CM: En fermedad de Chagas

Aguda en Nines, Sintomatologia y Tratamiento. Rev Med Panami’1(3): 153-162, 1976

Sousa OE: Las Especies de Echinococcus Rudolphi, 1801 y

su Biologia. Rev Med Panamii 2 (3): 163-179, 1976

Martinez R, Vasquez MA, Kourany M: Aspectos Epidemio16gicos de la Brucelosis en la Poblac~n de Alto Riesgo e n

Panamii. Boletin OSP 83(2): 140-145, 1977

821 *

822

823

824*

825*

826

827*

828*

829

830

831 *

832

Galindo P: Experienclas Epidemiolbgicas en el Proyecto Bayano. Plerus 7( 1-2): 81-89, junlo - dicicmbre, 1973 (sic).

Trabajo prcsentado por el Dr. Pedro Galindo, Director del Laboratorio Conmemorativo Gorgas, en el Seminario Sobre Planificacibn Ambiental para el Area del Caribe ceiebrado en Panamd, Reptiblica de Panamti, de abril 9 a 11-1975, en colaboracibn con el Programa de Planificaci6n Ambiental de la Es-

~~~la Graduada de Pl~Lifica~iLIl clc id Universiciad de Puerto

Rico. INota: Las fechas son correctas ]

Constantine W, Galindo P, Jenkins DW, Niijera JA, Walton

BC, Zalma V: Impactos de la Construcci6n de la Presa de Itaipu sobre la Salud Pfiblica en Paraguay; Informe de un Grupo

de Estudio. Washington, D.C: OPS, 1977. 65p.

Vitale Gary: Cuficotdes Breeding Sites in Panama. Mosq

News 37(2): 282, 1977

Adames Aj. Evaluaci6n Ambiental y Efectos del Proyecto

Hidroel~ctrico Fortuna; Informe l’inal. En: Revista Lotert’a,

Nos. 254-255-256, abril-mayo-junio, 1977

M4ndez E, Del Pino Encalada R: The Presence of Euhoplopsylus glacia/is exoticus in Ecuador (Siphonaptera: Pulicidae).

Pacific Insects 2 7(2-3): 257-260, 1977

Read RG: Microclimate as Background Environment for

Ecological Studies of Insects in a Tropical Forest. J Applied

hleteorol 16(12): 1282-1291, 1977

Kourany M, V&quez MA, Saenz R: Edwardsiellosis in Man

and Animals in Panama: Clinical and Epidemiological Characteristics. Am J Trop Med Hyg 26(6): 1183-1190, 1977

Galindo P: Los Arbovirus de Panami. Rev Med Panamii 3(l):

1-41, 1978

Sienz RE: Itleningitis por Cryptococcus neoformans en Panami. Rev hfed Panami 3(2): 89-104, 1978

Kourany hl: Edwardsiella turda un Nucvo Organismo pan Panama Asociado con In fecciones en cl Hombre. Rev Med Panam~ 3(2): 157-167, 1978

L6pez-Antunano k’J, Palmer TT: Sensitivy of Duffy Negative

Erythrocytes in .4 otus hlonkeys to Pfasmodium vivax. Trans

Royal Soc Trop hled Hyg 72(3): 319, 1978

I)aly J\$’, Brown GB, .flens.ih-Dwumah Ikl, ,Myers CW: Classification of Skin Alkaloids from Ncotropical Poison Dart

k’rogs (Dendrobatidae). Toxicon 16: 163-188, 1978
833

834*

835*

836*

837

838

839

840

841*

842*

843

Iicncfricks LD, W’ood DE, Hajduk ILIE: Haemoflagellates:

Commercially Available Liquid Nledia for Rapid Cultivation.

Parasitology 76 (3): 309-316, 1978

Herrer A, Chllstensen 11A: A Review of Dermatropic Species

of Lezs/tmant’u Present in Panama. Colloques Intemationaux

du Centre Natiomd de la Recherche Scientifique, No. 239,

75-82, 1978

Christensen HA, Herrer A : The Use of Phlebotomine

%mdflies in Xenodiagnosis. Colloques Internationaux d u

Centre National de la Recherche Scientifique, No. 239 ,

129-130, 1978

Read RG, Adames AJ, Galindo P: A Model of Microenvironment and Man-Biting Tropical Insects. Environmental Entomol 7(4): 547-552, 1978

Ma NSF, Rossan RN, Kelley ST, Harper JS, Bedard MT, Jones TC: Banding Patterns of the Chromosomes of Two New

Katyotypes of the Owl Monkey, Aotus, Captured in Panama.

J Med Primatol 7: 146-155,1978

Brenes Madrigal RR, Sousa OE, A@lar Bonilla M, Achit SM:

Primer Caso de Hidatidosis Hepdtica Humana en Costa Rica.

Rev Cubana Med Trop 29: 5-8, 1977

Kourany M: Papel del Laboratorio en el Manejo y Vigilancia

Epidemio16gica de las Diarreas, pp. 3140. En: !%mimzrio Sobre Nuevas Tendencies para el Dtignbstico y Tratumiento del

St’na!rome Dzizrreico para Centroam&rica y Panamd; Documento de Trabajo y Recomendaciones, Guatemala, 24-28 de noviernbre de 1975, Washington, D.C: OSP, 1977. 90p

Dawson GA, Composition and Stability of Social Group of

the Tamarin, Saguinus oedipus geo~~royi, in Panama: Ecological and Behavioral Implications, pp 23-37. En: The Biology

and Conservation of the Callitrichzdae, ed. por Devra G. Kleiman. A Symposium Held at the Conservation and Research

Center, National Zoological Park, Smithsonian Institution,

August 18-20, 1975, Washington, D.C: Smithsonian Institution Press, 1977

Kreutzer RD: A Mosquito with Eight Chromosomes: Chagasia bathana Dyar, Mosq News 38(4): 554-558, 1978

Walton BC: Racial Differences in Espundia. Ann Trop Med

Paritol 73(l): 23-29, 1979

M4ndez E: Las Aves de Caza de Panarmi. Panam~: Editora

Renovaci6n, 1979. 290p.

844*

845 *

846

\r&iqucz Alf%, Kouran>, \l: Resistcnci.1 de Ids Sdmonelds ii lx+

Ihogas Antimicrobiamis en PantmIA, 1964-1974. Rev ~lcd Pan~~ 4 (~): 58-68, 1979

Nlindez E: Kelacibn de 10S Vampires y otros h!urciilagos con

AlgUIMS khfcrmedades en Pananui. Rev ilfed Panarmi 4 (2):

80-89, 1979

I)ietz ]r WH, Pcralta PH, .]ohnson Khl: Ten Clinical Cases of

~ium~ Infection with Venezuelan Equine EncephalomyeIitis Virus, Subtype I-D. Am J ‘rrop Med Hyg 28(2): 329-334,

1979.

ADDENDA – 1980

Conmensorando 50 aiios de la aparicion de nuestra prim era publication.

(Los numeros son asignados a las publicaciones en el mismo &den en quc estas van llegando a la Bibliotheca de] Laboratorio Conmemorativo Gorgas)

847. * hltndez, E., y Lemke, T. O.-1979.

Description of a New Species of’ Bat Flea from Colombia

(Siphonaptera: Ischnopsyllidae).

Proceedings of the Entomological Society of Washington,

81 (4): 657-662.

848. * Kreutzer, R. D.-1979

Esterase Isozymes in the hlosquito Culex (Alclanoconion)

erra ticus.

hfosquito News, 39 (3): 500-505.

849. Dawson, G.- 1979

The Use of Time and Spec-e by the Panamanian Tamarin,

SaL~inu~ oedipus.

Folia %-imato16gica, 31 (4):253-284.

850. Christensen, H. A., y Ilcrrer, A.- 1979.

Susceptibility of Sand Flies (Diptera: Psychodidae) to

Trypanosom atidae from Two-Toed Sloths (Edcntata:

Brady podidae).

Journal of Medical Entomology, 16 (5):424-427.

851. * Herrer, A., Telford, Jr., S. R., y Christensen, H. A.- 1979

Lcishmaniu brasili[’nsis; Dissemination of Panamanian

Strains in Golden Ilamsters.

Experimental Parasitology, 48(3): 359-363.

852. * Anthony, R.I,., Johnson, C. M., y Sousa, O.E.-l 979

Use of Micro-Elisa for Quantitating An,ibody t o

Trypanosoma cruzi and Trypanosoma rangeii,

American Journal of Tropical Medicine & Hygiene, 28:

969-973.
853. *

854.

855.

856.

857. *

858.

859.

860.

861.

k’wn, A., y Nlindez, L.- 1!)79

Coendalqej panamtwsis, ~.n., sp. n. from the Porcupine in

Panama (Astigmata: Imb.il@dae).

International Journal of Acarolo~~r, 5(4):27 1-274.

Dictz Jr., W.Il., Galindo, p., y JOhn~~Jn, K.M.- 1980

Eastern Equine Encephalom>’litis in Panama: The

Epidemiology of the 1973 Epizootic.

American Journal of Tropical hledicine & Hygiene, 29

11 \.1 QQ 1 A n

( L ) .1 J.)- 1 -rU.

Christensen, H. A., Whitlaw, Jr., J. T., Chaniotis, B. N., y

Visquez, A.M. de-1980

Sylvatic Hosts of Rhodnius pallescens (Hemiptera:

Reduviidae) Nymphs in the Panama Canal Zone.

Journal of Medical Entomology, 17(2): 182.

Christensen, H. A., y Hermr, A.,-1980

Development of a Panamanian Strain of Leishmania

mexican in Co-indigenous Lutzornyia sanguinaria and Lu.

gomezi (Diptera: Psychodidae).

Journal of Medical Entomology, 17(2): 188-189.

Anthony, R. L., Christensen, 11. A., y Johnson, C. M.-198O

hlicro Enzyme-Linked Immunosorbent Assay (ELISA)

for the Serodiagqosis of New World Leishmaniasis.

American Jounal of Tropical Medicine and Hygiene,

29(2 ): 190-194.

Kreutzer, R. D., y Christensen, ILA.-198O

Characterization of Leishrnaniu Spp. by Isozirne

Electrophoresis.

~American Journal of Tropical Medicine and Hygiene, 29

(2): 199-208.

Benenson, A. S.-1979

El Laboratorio Conrnemorativo Gorgas, Resultado del

Esfuerzo y de la Colaboraci6n de Dos Naciones y de Dos

Pueblos.

Revista hlddica de Panama, 4(3): 139-142.

Trapido, H.- 1979

Carrie y Espiritu de Iierbert C. Clark, MD, o Cinco Lustros

de Historia del Laboratorio Conmemorativo Gorgas.

Revista hlidica de Panama, 4(3):15 1-158.

Young, hl.D.- 1979

El Laboratorio Conmemorativo Gc~rgas y la Fiebre

Amarilla Selvatica en Panam~ (1949-1979).

Revista Itlidica de Panami, 4(3): 159-181.

862.

863.

864. *

865.

866.

867. *

868. *

869.

870. *

87 1.*

Young, hl.D.- 1979

El Liiboratorio Conmemorativo Gorgas y Ias lnvestigaciones Sobre 1a Malari:i (1964- 1974).

Revista NILdica de Panarn&, 4(3): 182-194.

Fairchild, G. B.-1979

La Entomologia en Panama Durante la Primera hlitad del

Siglo.

Revista hlddica de Panamd, 4(3): 195-210.

Sousa, O. E., Sousa, F.G. de, y Blanchette, E.-1979

Observaciones Sobre la Ultra Estructura de la Larva

Echznococcus oligarthrus (Diesing, 1862).

Revista hlddica de Pana.rmi, 4(3):2 11-227.

Quiroz R., E., Romero, A., Phillips, L. A., G6mez R., B., y

Reeves, W. C.-1979

Dengue en Centroam{rica.

Revista hlidica de Panama, 4(3):228-235.

Vald&s, P. F., Britton, R., Reeves, W. C., y Benenson, A. S.- 1979

Cincer del Cuello Uterino en Pan ad,

Revista Mtdica de Pananwi, 4(3):236-245.

.Adames, A. , Peralta, P. H., Siienz, R., Johnson, C. M., y

Galindo P.-1979

Brote de Encefalomielitis Equina Venezolana (VEE) Durante la Formaci6n del Lago Bayano en Panarmi, 1977.

Revista hlddica de Panami, 4(3):246-257.

hltndez, E., y Sousa, 0. E.-1979

Identificaci6n y Distribuci6n de 10S Triatominos de Panamd (Hemiptera: Reduviidae).

Revista hl{dica de Pana.mi, 4(3):258-280.

G6mez R., B., Quiroz R., E., Peralta, P. H., Sdenz, R. E.,

Brandaris, C., y Reeves, W. C.-1979

Influenztt en Panarnii, 1977-1979.

Rewsta Nlddica de Panamii, 4(3):281-286.

Justines, G., Peralta, P. H., y Fdbrega, P.-1979

Nl&todo para la Detecci6n de Placas o Areas de Crecimiento del Virus Selv~tico de la Fiebre Amarilla y para

Distinguir entre 10S Anticuerpos Inducidos por la Vacunaci6n de 10S Individuos y por la Infecci6n N’atural.

Revista hlt%ica de Panami, 4(3):287-294.

Saenz, R. E., Peralta, P. H., Reeves, W. C., Ermocilla, R. B., y

Anguizola, B.- 1979

Cases Clinicos de la Epidemia de Fiebre Amarilla Selv~tica Ocurrida en Panami L)urante 1974.

Revista hlddica de Panami, 4(3):295-302.
73

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co m r- r0 0 co -W 03 cc
Calisher, C. H., Lazuick, J. S., Justines, G., Francy, D. B.,

Monath, T. P., Gutierrez V. E., Sabattini, M. S., Bowen,

G. S., Jakob, W. L. (1980). “Viruses Isolated From

Aedeomya squamipennis Mosquitoes Collected in Panama,

Ecuador and Argentina: Establishment of the Gamboa

Serogroup. “ Am J Trop Med Hyg. 30:219-223.

Christensen, H. A., Vasquez, A. M. (1980). ‘ ‘Host Feeding Profdes of Rhodm”us pallescens (llemiptera: Reduviidae) in Rural

Villages of Central Panama. Am J Trop Med Hyg

30:278-283.

Rossan, R. N., Christensen, H. A., Harper, J. (1980). “Adaptation of a Nigerian Strain of P~asmodium fhlciparum to

Panamanian Aotus trivirgatus. ” Am J Trop Med Hyg

30:289-290.

Mendez, E. (1980). ‘ ‘Las Miasis Centroamericanas y 10S Dipteros

que Ias Producen. Rev Med Panama 6: 146-159.

Fain, A., Mendez, E. Lukoschus, F. S. (1980). “Archemyo6ia

Blearchemyobia latipdis spec. nov. (Acax-1”, Prostigmata, Muobiidae) Parasitic on Maruspials in Panama and Brazil. Rev

Biolo~”a Trop 29:77-81.

Davidson, Jr., D. E., Ager, A. L., Brown, J. L., Chapple, F. E.,

Whitmire, R. E., Rossan, R. N. (1980). “New Tissue

Schizontocidal Antimalarial Drugs. ” Bull WZYO. 59:463-479.

Lukoschus, F. S., Scheperboer, G., Mendez, E., and Fain A.

(1980). ‘‘Eudusbabekia (Synoecomyobia) artibei Subgen.

Nov., Sp. Nov. (Acm”na: Postigmata: Myobiatidae) Infesting

the Physllostomid Bat Artibeus phaeotis in Panama. ‘J Pacific

Insects 23:478-486.

Kreutzer, R. D., Sousa, O. E. (1980). “Biochemical Characterization of Trypansomoa spp. by Isoyzme Electrophoresis. Am

J Trop Med Hyg 30:308-317.

Justines, G., Ore, G., Alvarez, O. (1980). “Venezuelan Equine

Encephalitis Virus. Horse Virulence of P-676 and MF-8 Small

and Minute Plaques. Am J Trop fvfed Hyg 30:444-448.

Kourany, M., Telford, S. R. (1980). “Lizards in the Ecology of

Salmonellosis in Panama . Appl Environ Microbiol

41: 1248-1253.

Dutary, B. E., LeDuc, J. W. (1981). “Transovarial Transmission of Yellow Fever Virus by a Sylvatic Vector, Haemagogus

equinus. Trans Roy Soc Trop Med Hyg 75(l): 128.

De Icaza, M. M., Johnson, C. M. (1981). ‘‘Un caso de Peritonitis

Granulomatosa causada por Huevos de Ascaris lumbrimides ‘‘ _Rev .&fed Pmna.ma 6(2): 160-153.

Justines, G., Ore, G., Fabrega, P., Ma.rN, R. A., Wong, N. (1981).

‘‘Presencia de Anticuerpos contra la Rubeola en Comunidades

Urbanas y Rurales de Panama, v Evalucion de 10S Resultados

de Prue- bas de Nueraloizacion e Inhibition de la

Hemaglutinacion. Rev Med Panama 6: 176-182.

Pinheiro, F. P., Freitas, R. B., Travassos de Rosa, J. F., Gabbay, Y. B., Mello, W. A., LeDuc, J. W. (1981). “An Outbreak of Mayaro Virus Disease in Belterra, Brazil. 1. Clinical

and Virological Findings. ‘‘ AmJ Trop Med Hyg 30:674-681.

LeDuc, J. W., Pinheiro, F. P., Travassos da Rosa, A. P. A. (1981).

‘‘An Outbreak of Mayaro Virus Disease in Belterra, Brazil.

III. Epidemiology. “ Am J Trop Med Hyg 30:682-688,

Hoch, A. L., Peterson, N. E., LeDuc, J. W., Pinheiro, F. P.

(1981). “An Outbreak of Mayaro Virus Disease in Belterra,

Brazil. III. Entomology and Ecology Studies. ” Am ,J Trop

Med Hyg 30:689-698.

Mendez, E., Delgaco, F., Miranda, D. (1981). “The Coyote (Canis

latrans) in Panama. Intl J Study Animal Problems

2:252-255.

Petersen, J. L. (1981). ‘ ‘Use of 1sozyme Electrophoresis in Black

Fly Systematic, In: Application of’ Genetics and Cytology

in Insect Systematic and Evolution, ed. by M. E. Stock. A

Symposium held at the National Meeting of the ESA in Atlanta, Georgia, 1-2 Dec. /8O. Moscow, Idaho: Forest, Wildlife

and Range Experiment Station, U. of Idaho, 1981, pp. 85-93.

Petersen, J. L. (1981). ‘ ‘Population Genetics of Some New World

Simuliidae. ” In: Recent Developments in the Genetics of Insect Disease Vectors, Steiner, W. W., ed. proceedings of a

symposium held at Bellagio Study and Conference Center,

Bellagio, Italy (April 20-24, 1981).
75

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. . . . - %

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f

Peters, C. J., Johnson, K. M., Reeves, W. C. (1982). ‘ ‘Hepatitis

B in Families. ” Ann Int Med 97(5):787.

Kourany, M., Martinez, R., Vasquez, M. A. (1983). “Indices

de Enterobactierias Patogenas y Parasitism Intestinal en

Poblaciones de la Region del Rio Bayano antes del Embalse.

Rev Med Panama 8(1):32-43.

Sousa, O. E., Wolda, H., Batista, F. (1983). “Triatominos Encontrados en el Ambiente Selvatico de la Isla Barro Golorado.

Rev Med Panama 8(1):50-55.

Mendez, E. (1983). ‘‘Estado Actual de la Fauna de Mamiferos de

Panama. ” Rev Med Panama 8(1):72-79.

Kourany, M. (1983). ‘‘A Medium for the Isolation and Differentiation of Vibrio parahaemolyticus and Vibro alginolyticus

From Seawater and the Marine Environment, Appl Environ

Microbiol 45(1):310-312.

Peterson, J. L. (1983). ‘ ‘Book Review: Cytogenetics and Genetics

of Vectors, ed. by R. Pal, J. B. Kitzmiller and T. Kanda.

Am J Trop Med Hyg 32(l): 198-199.

Walton, B. C., Harper III, J., Neal, R. A. (1983). “Effectiveness

of Allopurinol Against Lesihmania braziliensis panamensis

in Aotus trivirgatus. Am J Trop Med Hyg 32(1):46-50.
Appendix D

Summary of the Telephone Survey

on Gorgas Memorial Laboratory

Conducted July 13-17, 1983

.— — — — ——— —. — — —————

Michael B. Macdonald, under contract to OTA,

conducted a telephone survey of experts knowledgeable about the Gorgas Memorial Laboratory (GML).

OTA supplied Mr. Macdonald with a list of approximately 70 potential interviewees. He attempted to contact each of them, and was able to complete 23 interviews. (The individuals contacted are among those included in the Acknowledgments for this memoranalum. )

The original list of potential interviewees was compiled by OTA staff. It included the names of individuals known to have specific knowledge of GMI/GML.

The names were gathered during the previous 2

months of preliminary work on this technical memorandum. During that process, solicitations were continually made for additional people who would have

useful information on this subject. Names were added

to the list regardless of whether biases of the individuals were known or unknown to OTA, and regardless of the nature of those biases. The wide range

of responses, positive and negative, gives some assurance that a spectrum of viewpoints was expressed,

though OTA does not claim the survey to be global

or entirely representative of opinion about Gorgas.

Most of those contacted by Mr. Macdonald had

some firsthand knowledge of Gorgas. They had either

worked there, collaborated with Gorgas investigators,

participated in site visits, or had experience with

Gorgas grants or contracts. Nearly all those who participated in the survey are technical specialists in

tropical diseases, including experts in infectious diseases (mainly arboviruses and other viruses); malaria,

leishmaniasis, helminthic, and other parasitic diseases;

traditional tropical disease and cancer epidemiology;

vector biology; microbiology; nutrition; and the general fields of clinical research, tropical medicine, preventive medicine, and international health.

Ten of the participants hold positions in U.S. academic institutions, five are in the military, six are

employed by other U.S. Government departments

(Department of Health and Human Services and Department of State), and two are with an international

health organization.

The results of the survey are summarized in the remainder of this appendix. Opinions and quotes are not

attributed to specific individuals.

1. How would you rate the work of

GML?

The respondents generally rated the quality of work

at GML high. Most felt that some programs were excellent, especially the work on arboviruses, malaria,

and medical entomology, while other programs, such

as the bacteriology, were of lower quality. Three

respondents said that GML has done excellent work.

The most solid endorsement came from one who said

that it was “outstanding, the best in the world. ” Two

others who have spent many years in tropical medicine

stressed that the location of GML makes it an excellent

site for training, as a place for visiting scientific groups,

and for field situations that are not available elsewhere.

Other responses were less enthusiastic but still generally positive, Some programs were considered excellent, others less so. One person commented, “Like

any large institution which has existed for many years,

it has its weak points, but on a scale of 1 to 5, I would

give it a 4 (high). ” Another offered a similar rating.

He felt that while some of the research may not be original, it is technically very good.

Certain programs, including the entomology, virology, and malaria work got high marks. Other programs that were rated as excellent were the cancer and

sexually transmitted diseases programs, trypanosomiasis and leishmaniasis studies, and the ecology and environmental studies.

One respondent said that while the arbovirus and

ecology studies were excellent, some of the other programs were “mediocre. ” Another individual commented, “some of the work was excellent, some routine, but you can expect that in any institution that

has existed for so many years. ”

The bacteriology and some parasitology programs

were sometimes said to be the weakest points. Two

respondents characterized some of the parasitology

studies as slow but steady.

77
78

Many chose to qualify their answer and said that

one must consider the setting when rating the work

of GML. The field conditions make it a much different

situation than that of the National Institutes of Health

(NIH), for instance. One person commented, “I would

rate the work as high. As a person who has worked

in the field for many years, I know what tropical

medicine work is like. Its only weak point is the

decrease in support which makes it difficult to attract

top scientists. ” Another also rated the work as “undersupported.”

2. How should GML be judged?

The quality of publications and GML’s impact on

the public health oft he region were the most frequently

offered criteria for evaluation. Other responses included judging how GML fared in grant competition;

on the productivity of researchers; on the reputation

of the staff; on the training provided at GML; and by

the contributions to progress against specific diseases.

Those respondents with the most experience in the

field stressed that one should not make a direct comparison between an institution such as GML and university or NIH laboratories. Some felt that it should

be judged on a regional basis, in comparison to laboratories in other countries in the region. One individual pointed out that because many of the programs are involved in vector control, it is inappropriate to look simply at short-term output. The

benefits of surveillance accrue in the long term.

3. Has the quality of research

changed over the years?

Most of the participants agreed that this was a difficult question, since the emphasis of the research has

changed. Many chose not to answer. Three thought

that there was no change. Two said there had been

a positive change. Four others said that there were fluctuations in the quality of research, but through all of

the fluctuations, some programs, such as entomology,

continued to meet a very high standard.

A number of people responded that there has been

a general decline in the quality of the research over

the years. All of those who said that there has been

a decline blamed the uncertain funding, citing an inability to buy sophisticated equipment or attract topnotch scientists.

4. Are you aware of the Peer Review

Process at GML?

Few had any knowledge of the peer review process

at GML. There was a general lack of consensus about

whether such a process exists. It seems that respondents felt that sometimes the peer review process was

operating, while at other times it was not, possibly

depending on who was in charge. One person commented that a process exists, but it needs strengthening.

5. What is the relevance of GML

to research in: Panama, Latin America,

the United States, and Biomedical

Research in general?

In various ways, GML research is perceived to be

relevant to Panama, the region, and the United States.

A number of individuals noted that Panama benefits

from activities such as the surveillance field studies and

the environmental impact assessments of hydroprojects.

Another respondent, familiar with the cancer research, noted that GML has been a great help in increasing the sophistication of Panamanian cancer

researchers.

In terms of the region, GML served as a serum and

data bank during the recent dengue epidemic. It was

also the only laboratory in the region that was capable

of looking into the resurgence of yellow fever.

Another aspect of its importance as a regional center

is that it is a place where researchers in Central and

South America can call and receive answers in Spanish.

Everyone contacted mentioned that GML is particularly important to the United States, specifically for

the military. Since NIH no longer has its own laboratory in Central America, it is the only place for the

military to commission work in the region.

One respondent said that if GML did not exist, then

the military would have to build its own tropical laboratory.

Many respondents stressed the potential impact of

GML work. Some said it should be more closely linked

to the Panamanian Ministry of Health, that it should

be a leader in the region and that it could be more productive. One respondent, however, felt that political

barriers presently limit its importance as a regional

center.
79

6. What is the value of the training in

tropical medicine carried out at GML?

Most of those who commented gave GML training

a high rating. They felt that it was a unique setting

and very important to maintain, since there are so few

other places available for training in tropical medicine.

One person said that a training center in a place such

as Puerto Rico, for example, would not be as valuable

because of a different disease ecology. Two respondents offered the same quote by General Douglas MacArthur that in the Philippines he needed three divisions to do the work of one, since two would always

be in the hospital with malaria or dengue.

Not all of the responses to this question were positive. Two felt that the level of training had gone downhill over the past few years because of financial constraints. Another felt that the trainers were not sophisticated enough. He noted that there were more Panamanians involved in the training now and that the program was hurt when NIH cut back on funding for

young American scientists to go to GML. A third negative opinion was offered by a university scientist who

felt that there should be more civilians involved in

training programs at GML.

7. What is the value to research of the

animal population kept at GML?

Nearly all of the responses to this question were very

positive about the animal populations. This question

evoked the most immediate and strongest reactions of

any on the survey. The colonies were variously termed

“Crucial, Critical and Unique, cannot be duplicated

elsewhere. ” One noted that this function is becoming

even more important with the increasing prevalence

of malaria strains resistant to current drugs. A number

of respondents noted that it was much more cost effective to keep the colonies in Panama than in the

United States. Besides malaria, the colonies are very

important in the study of diseases such as trachoma

and hepatitis.

One person stressed that the work on antimalarial

must be carried out. He said that if GML cannot do

it then the Army would have to build its own lab to

screen the antimalarial drugs. Others concurred that

this was one of the most important functions of GML.

“The screening of antimalarial must continue. ” “The

monkey colonies are invaluable to our study of human

malaria. ” It was mentioned that to an outsider the colonies seem to be dull and routine work, but they provide a very important service.

One who is quite knowledgeable about malaria felt

the value of the Aotus population had declined over

the years and that there was some difficulty in meshing

the colony to current research needs. He felt that the

colony was not reaching its potential.

In addition to the monkey colony, it was menioned

that the wild animals in the area also provide a very

valuable resource for the study of disease ecology of

such diseases as leishmaniasis, the arboviruses, and

Chagas’ disease.

8. Do you have any suggestions for

change?

Nearly all respondents had suggestions for change:

stabilization of funding and increased funding were the

most common answers.

It was felt that the constant budget problems eroded

the confidence of the staff and GML’s attraction to top

scientists. One respondent who had worked there for

many years said that it was demoralizing to hear at

every weekly meeting that, “Funding might be cut next

week. ” He said that uncertain funding was a major reason for failing to attract top university scientists. One

said that GML cannot continue in such a precarious

financial position and that it should either be funded

properly or closed. Others felt that GML/GMI should

look for more international support and operate more

like the cholera research institution in Dacca or the

International Laboratory of Research on Animal Diseases in Kenya.

Another respondent suggested that GML should collaborate more with labs in the United States, but

bureaucratic changes would be needed for travel

money and arrangements for cooperative agreements

with other institutions.

Some felt that major changes should be made in the

management structure of GML/GMI, expressing the

opinion that even with solid core support, they would

not be able to compete with other tropical medicine

units. “The current direction must change” noted one

individual. The need for a strong executive was recognized by many other respondents. One felt that they

should pay the high salary needed to get a good director in the United States and in Panama. Two other scientists with many years of experience in tropical medicine felt also that it was important to develop closer

ties to the region.

Other suggestions were for more long-range planning, a firmer peer review process and pruning the

dead wood. Two felt that there should be closer links

to basic science and a greater use of more sophisticated

immunologic and diagnostic techniques.
80

9. What do you think is the overall value

of GML?

All the respondents, without exception, felt that it

would be a terrible mistake to lose GML. “For better

or worse, it is the only one we have, and we are better off with something than nothing, If it did not exist

[the military] would have to build one there.” It is a

resource that cannot be duplicated. “It is irreplaceable

in the panorama of tropical disease research related

to Latin America and the United States. ” A number

of other respondents noted the unique setting of GML.

“While it does have its weaknesses, it would be a terrible mistake to let it go. “ “The relative cost is peanuts

compared to the benefits, and it would be insane to

reduce our limited involvement in the area. ” “If lost

now, we would never get it back. ”

Many spoke in terms of GML’s potential. One felt

that GML’s value now was only marginal but that it

could be great, if it had stable funding.

GML is also viewed as a front line defense against

certain diseases that could spread to the United States.

Panama Canal forms a barrier to many diseases at this

point. But now that the Pan American Highway is

opening up it is even more essential that diseases such

as foot and mouth disease, swine fever, yellow fever,

Venezuelan and eastern equine encephalitis be confined

at this point.

Besides its importance in traditional tropical medicine, GML is very important in cancer research in the

region. It is unique in that it is capable of doing

sophisticated cancer research in a place which is in the

process of modernization.

GML was also felt to be very important politically.

It would be an affront to Panama if we pulled out as

it is a very important indicator of U.S. concern with

nonpolitical problems in the region. The general feeling was that with the current direction of events in the

region, GML is becoming more important than ever,

if constructive changes are made.
Appendix E

Glossary of Acronyms and Terms — — — — r

Glossary of Acronyms

AFRIMS —Armed Forces Research Institute of

Medical Sciences

AID —Agency for International

Development (U.S. Department of

State)

ARI —acute respiratory infections

BCG —bacille Calmette-Guerin Vaccination

CAREC —Caribbean Epidemiology Research

Center (PAHO)

CCCD —Combatting Communicable

Childhood Diseases (AID)

CDC –Centers for Disease Control (PHS)

CE/LAS —California Encephalitis/LaCrosse

Encephalitis

CEPIALET —Pan-American Center for Research

CFNI

DOD

DRG

EEE

EPI

FIC

GAO

GMI

GML

GND

HHS

HTLV

and Training in Leprosy and Tropical

Diseases (PAHO)

—Caribbean Food and Nutrition

Institute (PAHO)

—U.S. Department of Defense

–Division of Research Grants (NIH)

—eastern equine encephalitis

—Expanded Program on Immunization

(WHO)

–Fogarty International Center (NIH)

–General Accounting Office (U.S.

Congress)

—Gorgas Memorial Institute of

Tropical and Preventive Medicine,

Inc.

—Gorgas Memorial Laboratory (of

GMI)

—Great Neglected Diseases of Mankind

(Rockefeller Foundation)

–U.S. Department of Health and

Human Services

—human T-cell leukemia virus

ICDDRB —International Center for Diarrheal

Disease Research/Bangladesh

ICIDR —International Collaboration in

Infectious Diseases (NIAID)

IDRC —International Development Research

Centre (Canadian)

ILRAD —International Laboratory of Research

on Animal Diseases

INCAP —Institute of Nutrition of the

Caribbean and Panama (PAHO)

IRG –Internal Review Group (NIH)

MARU —Middle American Research Unit

(NIAID)

MERTU/G—Medical Entomology Research and

Training Unit in Guatemala (CDC)

NAMRU —Naval Medical Research Unit

NCI –National Cancer Institute (NIH)

NIAID —National Institute of Allergy and

Infectious Diseases (NIH)

NIH –National Institutes of Health (PHS)

ORT —oral dehydration therapy

O TA —Office of Technology Assessment

(U.S. Congress)

PAHO —Pan American Health Organization

PHS –U.S. Public Health Service (HHS)

SLE —St. Louis encephalitis

STD —sexually transmitted diseases

TDR —United Nations Development

Program/World Bank/World Health

Organization Special Programme for

Research and Training in Tropical

Diseases

UNDP —United Nations Development

Programme

USAMRU —United States Army Medical Research

Unit

VEE —Venezuelan equine encephalitis

WEE —western equine encephalitis

WHO —World Health Organization

WRAIR —Walter Reed Army Institute of

Research

YARU —Yale Arboviral Research Unit (Yale

University)

81
82

Glossary of Terms*

acute: Having a sudden onset, sharp rise, and short

course; not chronic.

Aedes (ah-ee’dez): A genus of mosquitoes. A. aegypti, the tiger mosquito, is a common urban species

that breeds near houses and transmits urban yellow

fever and dengue fever.

amebiasis (am-ee-bi’ah-sis): Infection by amebae, especially, infection with Entamoeba histolytica, an

intestinal parasite, characterized by diarrhea with

blood and mucous and also causing abcesses in the

intestine and liver (sometimes called amebic dysentery). See AMEBA.

ameba (ah-me’bah), also, amoeba: A protozoan; a

minute single-celled life form. One species, Entamoeba histolytica, is a parasitic pathogen producing

amebiasis in man. See AMEBIASIS.

ancylostomiasis (an-ki’los-to-mi’ ah-sis): Infection with

Ancylostoma duodenale, the human intestinal hookworm. Causes chronic anemia.

Anopheles gambiae (a-nof’a-leez gam-bee’ee): A species of mosquito in Africa that transmits malaria;

also, a group of closely related species of mosquitoes. See SPECIES COMPLEX.

antigen (an’ti-jen): Any substance that stimulates the

production of antibodies.

Aotus (ay-oftus): A genus of monkey; the owl

monkey.

arbovirus (ar’bo-vi-rus): An abbreviation for arthropod-borne virus, virus transmitted by arthropods.

Argentinean hemorrhagic fever: An acute, sometimes

fatal disease caused by a virus, transmitted through

contamination by urine or feces of infected rats.

Characterized by chills, fever, severe headache,

hemorrhagic symptoms, shock, kidney involvement, and necrologic involvement.

arthropods (ar’thro-podz): Invertebrate animals of the

phylum Arthropoda that includes insects, ticks,

spiders, and crustaceans.

arthropod-borne: Transmitted by arthropods.

ascariasis (as-kah--ri’ah-sis): An infection with worms

of the genus Ascaris, especially, Ascaris lumbricoides, the human intestinal round worm, characterized by intestinal pain and diarrhea.

*SOURCES:

1. The American Heritage Dictionary of the English Language, W. Morse

(cd. ) (Boston, Mass.: Houghton Mifflin Co., 1976).

2. Control of Communicable Diseases in Man, Mth ed , A. S. Benensen (ed )

(Washington, DC.: American Public Health Association, 1981).

3. Dorland’s Illustrated Medical Dictionary, 25th ed. (Philadelphia: W. B.

Saunders, 1974).

4. Office of Technology ,4ssessment, U.S. Congress, Washington, D.C.

s Roper, N., Pocket ,tfedical D~ctionary, 13th ed, (Edinburgh, Scotland:

Churchill Livingstone, 1978).

aseptic meningitis (a-sep’tik men-in-ji’tis): Viral-caused

inflammation of the membranes surrounding the

brain and spinal cord.

bacille Calmette-Guerin, abbr. BCG: An attenuated

(weakened) strain of tuberculosis bacteria used to

vaccinate against virulent tuberculosis.

bacillus (ba-sil’us), pl. bacilli: Any of various rodshaped, aerobic bacteria of the genus Bacillus.

bacteriology (bak-tir’ee-ol’o-ji): The scientific study of

bacteria.

bacterium (bak-tir’ee-um), pl. bacteria: Any of numerous unicellular micro-organisms (class Schizomycetes), occurring in a wide variety of forms, existing

either as free-living organisms or as parasites, and

having a wide range of biochemical, often pathogenic, properties.

bilharzia (bil-har’zi-ah): See SCHISTOSOMIASIS.

bilirubin (bi-li-roo’bin): A pigment largely derived

from the breakdown in the spleen of hemoglobin

from red blood cells.

Bolivian hemorrhagic fever: An acute, sometimes fatal

disease caused by a virus, transmitted through contamination by urine or feces of infected rats, occurring in Bolivia. Characterized by chills, fever, severe

headache, hemorrhagic symptoms, shock, kidney

involvement, and necrologic involvement.

California encephalitis: An acute encephalitis caused

by an arbovirus, transmitted by mosquitoes.

Campylobacter (kam’pil-o-bak’ ter): A genus of

bacteria, one of which, C. jejuni, causes an acute

diarrheal disease.

cellulose acetate electrophoresis: A type of isozyme

electrophoresis. See ISOZYME; ISOZYME ELECTROPHORESIS.

cervical cancer (ser’vi-kal): Cancer of the cervix (the

neck of the uterus).

Chagas’ disease (sha’gus): Infection by Trypanosoma

cruzi, transmitted by reduviid bugs. Discovered and

described by Carlos Chagas of Brazil, Characterized

by an acute course in children with fever, encephalitis, and inflammation of the heart muscle (often

life-threatening or fatal), and a chronic course in

adults leading to heart disease and heart failure.

Widely distributed in Central and South America.

Also called American trypanosomiasis. See TRYPANOSOMIASIS.

Chagres fever: A febrile disease caused by an arbovirus, transmitted by phlebotomine sandflies. Also

called “Panama fever. ”

chemotherapy (kee-mo-ther’a-pi): The use of specific

chemical agents to arrest the progress of, or eradicate, disease in the body without causing irreversible injury to healthy tissues.

chorioretinitis (kawr-i-o-ret-in-it’ is): Inflammation of

the choroid and retina of the eye.
chronic: Lingering, lasting, as opposed to acute.

Colorado tick fever: A febrile disease without rash

caused by an arbovirus, transmitted by a tick, occurring in the Rocky Mountain region of the United

States.

cytogenetics (si’to-je-net’iks): Laboratory examination,

usually microscopic, of chromosomes.

dengue fever (deng’gee): An acute febrile disease

caused by an arbovirus, transmitted by mosquitoes

of the genus Aedes, characterized by fever, severe

pains in the head, eyes, muscles, and joints, and a

skin eruption. Occurring in Japan, Southeast Asia,

the South Pacific, India, the Caribbean, Middle and

South America. Sometimes called “breakbone fever. ”

dengue hemorrhagic fever: Life-threatening complications of dengue infection; syn. DENGUE SHOCK

SYNDROME. See DENGUE FEVER.

dengue shock syndrome: Life-threatening complications of dengue infection; syn. DENGUE HEMORRHAGIC FEVER. See DENGUE FEVER.

diarrhea (dy-a-ree’a): Pathologically excessive frequency and fluidity of fecal discharges. Adj., diarrheal.

diphtheria (dif-theer’ee-a): An acute infectious disease

caused by the bacterium Corynebacterium diphtheria. Characterized by grey, adherent, false membrane growing on mucous surface of the upper respiratory tract. Locally there is pain, swelling, and

may be suffocation. Systemically the toxins attack

the heart muscle and nerves.

DNA hybridization: Laboratory method for species

and strain identification based on matching of DNA

from an unknown organism with DNA from known

organisms.

eastern equine encephalitis, abbr. EEE: An arbovirus

disease of horses and mules, possibly other vertebrates, with a reservoir of infection in birds, transmitted by mosquitoes. Can be transmitted to humans and cause death. Occurring in the United

States in a region extending from New Hampshire

to Texas to Wisconsin, in Canada, Mexico, the Caribbean, and parts of Central and South America.

Characterized by encephalomyelitis.

elephantiasis (el-ef-an-ti’a-sis): The swelling of a limb,

usually a leg, as a result of lymphatic obstruction,

followed by thickening of the skin and subcutaneous

tissues. A complication of filariasis in tropical countries. See FILARIASIS.

encephalitis (en-sef-a-li’tis): Inflammation of the brain.

encephalomyelitis (en-sef’-al-o-mi-e-li’ tis): Inflammation of the brain and spinal cord.

endemic (en-dem’ik): The constant presence or persistence of a human disease or infectious agent within

a given geographic area. Cf. EPIDEMIC; ENZOOTIC.

enteric (en-ter’ik): Pertaining to the intestine.

entomology (en-to-mol’o-ji): The science dealing with

insects.

enzootic (en-zo-ot’ik): The constant presence or persistence of an animal disease or infectious agent

within a given geographic area. Cf. ENDEMIC; EPIZOOTIC.

epidemic (ep-i-dem’ik): The occurrence of a human illness in excess of usual frequency in a particular area.

Cf. ENDEMIC; EPIZOOTIC.

epidemiology (ep-i-de-mi-ol’ o-ji): The scientific study

of the distribution and occurrence of diseases and

health conditions.

epizootic (ep-i-zo-ot’ik): The occurrence of an animal

disease in excess of usual frequency in a particular

area. Cf. EPIDEMIC; ENZOOTIC.

Escherichia coli (esh-er-ik’i-a ko’ii): A species of bacteria; motile, rod-shaped bacterium which is ubiquitous in the intestinal tract of vertebrates. Some

strains are pathogenic to humans, causing intestinal

disease and diarrhea.

etiology (ee-ti-ol’o-ji): The scientific study of disease

causation; the causation of a disease.

filariasis (fil-a-ri’a-sis): Infection with Filaria, parasitic

thread-like worms, found mainly in the tropics and

subtropics, transmitted by mosquitoes. Adults of

Wuchereria bancrofti and Brugia malayi live in the

lymphatic system and connective tissues, where they

may cause obstruction, but the embryos (microfilariae) migrate to the blood stream. Completion of

the lifecycle is dependent on passage through a mosquito. See ELEPHANTIASIS.

genus (jen’us): The taxonomic category next greater

than species.

granulomatous (gran-u-lom’ah-tus): Composed of

tumor-like mass or nodule of tissue, due to inflammatory process associated with an infectious disease,

such as tuberculosis.

helminth (hel’minth): Parasitic worm. Adj. helminthic.

hemorrhage: The escape of blood from a blood vessel.

hemorrhagic fever: Severe complication of some viral

diseases involving internal or external bleeding.

host: Human or other living animal, including birds

and arthropods, that affords subsistence or lodgment to an infectious agent under natural conditions.

human T-cell leukemia virus, abbr. HTLV: A recently identified virus that induces a specific type of cancer of the blood-forming organs.

immunity (i-my oo’ne-ti): Nonsusceptibility, or relative

resistance, to a specific infection, due to antibodies

produced against that specific antigen.

immunology (im’yoo-nol’o-ji): The scientific study of

immunity. Adj., immunologic, immunological.
84

incidence (in’se-dens): The frequency of new occurrences of disease within a defined time interval. Incidence rate is the quotient of new cases of a specified disease divided by the number of people in a

population in a defined period of time.

inflammation (in-flam-ma’shun): The reaction of living tissues to injury, infection, or irritation; characterized by pain, swelling, redness, and heat.

influenza (in-floo-en’za): An acute viral infection of

the nasopharynx and upper respiratory tract.

in vitro (vi’tro): In glass, as in a test-tube.

in vivo (vi’vo): In living tissue.

isozyme (i’so-zime): Two or more forms of the same

enzyme having, identical chemical function but differing physical structure, which can be separated

and identified,

isozyme electrophoresis (i’so-zime el-ek-tro-for-ee’ sis):

Laboratory method of separating isozymes (cf. )

based on their migration distance in an electric field

applied across a standardized inert material (polyacrylamide gel, agarose gel, or cellulose acetate).

jaundice (jawn’dis): A condition characterized by

yellow appearance due to raised bilirubin level in

the blood resulting from: 1) obstruction in the biliary

tract, 2) excessive rupture of red blood cells, 3) toxic or infective damage of liver cells.

kwashiorkor (kwash-ee-or’kor): A nutritional disease

produced by persistent deficiency in essential dietary

protein. Characteristic features are anemia, wasting,

edema, potbelly, depigmentation of the skin, loss

of hair or change of hair color. Untreated, it progresses to death.

LaCrosse encephalitis: An acute encephalitis caused by

an arbovirus, transmitted by mosquitoes. Closely

related to California encephalitis.

Leishmania (leesh-may’ni-a): A genus of flagellated

parasitic protozoans causing several clinical diseases.

See LEISHMANIASIS.

leishmaniasis (leesh-man-i’a-sis): Infection by

Leishmania, transmitted by sandflies. Cutaneous

leishmaniasis is a skin ulcer caused by L. mexicana

(New World) or L. tropica (Old World). Mucocutaneous leishmaniasis is an ulceration of the nose

and throat caused by L. braziliensis, occurring in

tropical America. Visceral leishmaniasis, also called

kala-azar, is a generalized and internal disease

caused by L. donovani (New and Old World).

leprosy (lep’ra-si): A chronic, infectious, granulomatous disease occurring almost exclusively in tropical

and subtropical regions, caused by the bacillus

Mycobacterium leprae, and ranging in severity from

noncontagious and spontaneously remitting forms

to contagious, malignant forms with progressive

anesthesia, paralysis, ulceration, nutritive disturbances, gangrene, and mutilation. Also called “Hansen’s disease. ”

leptospirosis (lep-to-spi-ro’ sis): Disease caused by spirochete (finely coiled bacterium), commonly transmitted in water contaminated by urine of infected

animals, Characterized by inflammation of the spinal cord, the nervous system, and liver.

lifecycle: The progressive stages of development of an

organism.

lymphatic system (lim-fa’tik): The system of vessels

in the body that carry lymph fluid.

lymph glands (limf-glanz): The organs at various

points of the lymphatic system that filter the lymph

fluid.

malaria: A disease caused by protozoan parasites that

infect red blood cells, transmitted by mosquitoes of

the genus Anopheles. Four species of the parasite

cause disease in humans: Plasmodium falciparum,

P. vivax, P. malariae, and P. ovale. P. vixax and

P. ovale have a persistent stage in the liver that

causes relapses. Many other species infect monkeys,

rodents, birds, and reptiles. Characterized by fever,

chills, and sweating that occur at intervals depending on the time required for development of a new

generation of parasites in the body. See PLASMODIUM FALCIPARUM.

marasmus (ma-raz’mus): Wasting away of the body

due to gross lack of calories in the diet.

measles (meez’lz): An acute infectious disease caused

by a virus, Characterized by fever, a blotchy rash,

and inflammation of mucous membranes.

metabolic: Pertaining to metabolism, the series of

chemical changes in the living body by which life

is maintained.

metastasize (me-tas’ta-syz): Tranfer of a disease from

one part of the body to another, usually by blood

or lymph, leading to secondary growth or lesions.

molluscicide (mol-lusk’i-side): Any chemical agent

used to kill molluscs, especially snails.

morbidity: Disease or illness.

mortality: Death,

onchocerciasis (on-ko-ser-ki’a-sis): An infection of humans with Onchocerca worms, transmitted by the

bite of blood-sucking blackflies (Simuliidae). Adult

worms become encapsulated in subcutaneous nodules. Immature worms (microfilariae) migrate in the

tissues and can cause “river blindness” if reaching

the eye. Occurring in western Africa and discrete

foci in tropical America.

oral dehydration therapy: The treatment of fluid-loss

due to diarrhea by a specific water solution of electrolytes and glucose taken by mouth,

Oropouche fever (or-o-poosh): An arbovirus disease

transmitted by biting midges (Culicoides spp. ).
Characterized by fever, headache, aches and pains,

and occasionally encephalitis. Found in Trinidad

and Brazil, but recognized range in tropical America

is expanding. Occurrence is primarily rural or forest,

but explosive urban and suburban outbreaks occur.

parasitology (par-a-sit-ol’o-ji): The scientific study of

parasites.

pathogen (path’o-jen): A disease-producing agent.

pathological: Of or pertaining to disease processes.

Phlebotomus (fle-bot’o-mus): A genus of sandflies,

many of which are vectors of leishmaniasis. Adj.

phlebotomine.

physiological: In accordance with natural processes

and normal function of the body.

Plasmodium falciparum (plaz-mo’de-um fal-sip’arum): One of the four species of protozoan parasites

causing malaria in humans. Only P. falciparum

causes life-threatening complications; only species

with drug-resistant characteristics. See MALARIA.

pneumoccocal (nyoo-mo-kok’al): Referring to the

bacterium, Diplococcus pneumonia, that causes

pneumococcal pneumonia.

pneumonia (nyoo-mon’ya): Inflammation of the lung,

usually the lower respiratory tract.

poliomyelitis (po’lee-o-my’a-li’tis): An infectious viral

disease occurring mainly in children and in its acute,

more virulent form attacking the central nervous

system and producing paralysis, muscular atrophy,

and often deformity. Transmitted by the oral-fecal

route.

prevalence (prev’a-lens): The number of existing cases

of a disease in a defined population at a particular

time.

protozoa (pro-to-zo’a): Unicellular organisms, the

smallest type of animal life. Adj. protozoan, protozoal.

protozoology (pro-to-zo-ol’o-ji): The scientific study

of protozoa. Adj. protozoologic.

reduviid (re-du’vi-id): Belonging to the family

Reduviidae, winged, “true” bugs (Order Hemiptera),

including blood-sucking vectors of Chagas’ disease.

See CHAGAS’ DISEASE.

reservoir: Any person, animal, arthropod, plant, soil

or substance (or combination of these) in which an

infectious agent normally lives and multiplies, on

which it depends primarily for survival, and where

it reproduces itself in such manner that it can be

transmitted to a susceptible host.

rotavirus (ro-ta-vi-rus): Any of a group of viruses

(round in shape) causing gastroenteritis in infants

and children.

St. Louis encephalitis, abbr. SLE: An arbovirus disease transmitted by mosquitoes, with the reservoir

of infection in birds. Can be transmitted to humans

and cause death. First observed in Illinois in 1932.

Occurring in most of the United States, Trinidad,

Jamaica, Panama, and Brazil. Mild cases characterized by aseptic meningitis; severe infection usually

marked by acute onset, headache, high fever, coma,

convulsions, and paralysis.

schistosomiasis (shis’to-so-mi’a-sis): An infection of the

human body by worms of the genus Schistosoma

(“blood flukes”), from drinking or bathing in infected water. Infected humans pass eggs in urine or

feces (depending on parasite species) into water

source. Immature form (miricidia) hatchs and infects

suitable snail host. After multiplication, intermediate form (cercariae) is shed from snail into water,

where penetration of human skin occurs. Adult

worm develops in human, localizing in veins of

bladder or intestine. Schistosoma mansoni occurs

in Africa, the Caribbean, and Brazil; S. japonicum

occurs in the Far East; in both, adult worms localize

in veins of intestine; deposited eggs cause tissue scarring of intestine and liver; S. haematobium occurs

in Africa and the Middle East producing the urinary

form as adult worms localize in veins of the bladder; characterized by obstruction due to scar formation, inflammation, and possibly cancer. Also

called “bilharzia. ”

sequelae (se-kwel’ee): The pathological consequences

of a disease.

seroepidemiologic: Pertaining to a branch of epidemiology that studies antigens from humans to delineate

epidemiologic patterns of a disease. See EPIDEMIOLOGY; SEROLOGY.

serology (se-rol’o-ji): The scientific study of sera (the

fluid portion of blood). Adj. serologic, serological.

sexually transmitted diseases: A group of infectious

diseases defined by transmission through intimate

contact, including gonorrhea, syphilis, chancroid,

lymphogranuloma venereum, granuloma inguinale,

chlamydia, herpes simplex, trichomonas, as well as

hepatitis virus and intestinal parasites such as giardia, entamoeba, ascaris, and trichuris.

species: A taxonomic subdivision of a genus. A group

of individuals having common characteristics distinguishing them from other categories of individuals of the same taxonomic level. Always carries the

implication of reproductive isolation, i.e., members

of a species only reproduce successfully with one

another,

species complex: A group of two or more closely

related insect species that can only be differentiated

by cytogenetic analysis or cross-breeding experiments.

strain: A group of organisms of the same species (cf. )

having a distinctive quality or characteristic (bio-
86

chemical, pathogenic, or other feature) that can be

differentiated, but not different enough to constitute

a separate species.

subacute: Mild or moderately severe. Often the stage

between the acute and chronic phases of disease.

symptomatic: Of or pertaining to the symptoms,

rather than the causes of a disease.

symptomatology: The branch of medicine concerned

with symptoms. The combined symptoms typical

of a particular disease.

therapeutic: Dealing with the treatment of disease.

toxoplasmosis (toks-o-plas-mo’sis): Infection by the

protozoal parasite Toxoplasma gondii. Many mammals can harbor the parasite which encysts in tissue

after ingestion (oral-fecal route), but only in cats is

the lifecycle completed, with the infective form shed

in feces. Characterized by lesions of the central nervous system, which may lead to chorioretinitis,

blindness, brain defects, and death.

trachoma (tra-ko’mah): A chronic, infectious disease

of the eye caused by the bacterium Chlamydia trachomatis, characterized by inflammation, pain, watery eye, then scarring, and finally blindness.

triatomine (tri-a-to-meen): Pertaining to the genus Triatoma, blood-sucking bugs important as vectors of

Chagas’ disease See CHAGAS’ DISEASE.

trichuriasis (trik-u-ri’ah-sis): Infection with the intestinal parasitic whipworrn, Trichuris trichiura.

Trypanosoma (tri-pan-o-so’ma): A genus of parasitic

protozoans. Their lifecycle alternates between

blood-sucking arthropods and vertebrate hosts. See

TRYPANOSOMIASIS.

trypanosomiasis (tri-pan’a-so-my’a-sis): Disease produced by infection with Trypanosoma. In man this

may be with Trypanosoma cruzi, transmitted by

blood-sucking reduviid bugs in the Americas (also

called Chagas’ disease); or with T. rhodesiense in

East Africa or T. gambiense in West Africa, both

transmitted by the tsetse fly, causing “sleeping sickness.” See CHAGAS’ DISEASE.

tubercle bacillus (tu’ber-kl ba-sil’es): A bacillus causing tuberculosis; usually refers to Mycobacterium

tuberculosis, the principal cause of human tuberculosis.

tuberculosis (tu-ber-ku-lo’sis): An infectious disease

caused by any of several species of mycobacteria.

Usually begins with lesions in the lung, but can metastasize to other parts of the body.

vector: A carrier of disease; usage commonly refers

to arthropods or rodents.

vector bionomics: The relationship between organisms

and their environment.

vector-borne: Transmitted by a vector.

vector control: Intervention aimed at disease reduction by action against vectors.

Venezuelan equine encephalitis, abbr. VEE: An arbovirus disease of horses and mules, possibly other

vertebrates, with a reservoir of infection in birds,

transmitted by mosquitoes. Can be transmitted to

humans and cause death. Endemic in northern South

America, Trinidad, Middle America, Mexico, and

Florida. Characterized by severe headache, chills,

fever, pain in muscles and eyes, nausea and vomiting, possibly with severe central nervous system

complications leading to convulsions, coma, and

death.

western equine encephalitis, abbr. WEE: An arbovirus

disease of horses and mules, possibly other vertebrates, with a reservoir of infection in birds, transmitted by mosquitoes. Can be transmitted to humans and cause death. Occurring in Western and

Central United States and Canada and in scattered

areas further east. Characterized by encephalomy -

elitis.

whooping cough: Pertussis; an infectious respiratory

disease of children with attacks of coughing which

reach a peak of violence ending in an inspiratory

whoop. Caused by Bordetella pertussis, Prophylactic vaccination is responsible for a decrease in case

incidence.

yellow fever, abbr. YF: An acute febrile disease caused

by an arbovirus, transmitted by mosquitoes. Characteristic features are fever, jaundice, black vomit,

and anuria (absence of urine excretion). Jungle/sylvan yellow fever is maintained in monkey reservoir

hosts; urban yellow fever refers to transmission with

human reservoir hosts.

zoonosis (zo-on-o’sis): An infection or infectious disease transmissible under natural conditions from

vertebrate animals to man,

-

1.

2.

3.

4.

.5.

6.

7.

8.

9.

10.

11.

12

13.

14.

15.

16

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