平成2年9月15日

第18巻第3号
総説

The Epidemiology

Snail−bomeandChemotherapy

TrematodeofShistosomiasis

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原Davis 215−228著

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Japan. J Trop Med Hyg Vol 18 No 3 1990, pp. 215‑228

215

Review

THE EPIDEMIOLOGY AND CHEMOTHERAPYOF SCHISTOSOMIASIS AND OTHER
SNAIL‑BORNE TREMATODE INFECTIONSANDREW DAvrs, MD, FRCPE, FFCM, DTM&H
Received June 26 1990/Accepted July 12 1990

Abstract: The differen,t life cycles of the human digenetic parasitic trematodes
Schistosoma japonicum. S. mansoni. S. haematobium. Clonorchis sinensis, various species of

the genera Qpisthorchis and Paragonimus. and those of lesser pathogenic impbrtance,
Fasciolopsis buski. Heterophyes heterophyes and Metagonimus yokogawai, illustrate thecomplexity of the clinic0=epidemiological profiles of these syndromes.

The one factor common to all of infections is the necessity of a primary snail
intermediate host to complete the biological life cycles: some additionally require asecondary intermediate host which may be several species of fresh‑water fish, crustaceans

or aquatic plants. Conversely, the mode of transmission to man varies froin dermal
penetration of infective cercariae in the schistosome infections, to the consumption of
infective metacercariae in raw or undercooked cyprinoid fresh‑water fish in clonorchiasis
and opisthorchiasis and the eating of fresh‑water crabs or crayfish in paragonimiasis or
the ingestion of water caltrop, water chestnut and bamboo in fasciolopsiasis.
Yet, despite these variations, several general common features characterize thedifferent epidemiological cycles:‑
1 . the prevalences of the infections are highest in rural populations, frequently higher inmales, commonly occurring in the younger age‑groups and the distributions all follow
the inverted binomial pattern, itself characteristic of those infections in which there is

no replication of a parasite population within the human host;

2 . an important feature of their propagation is the indiscriminate disposal of humanfaeces in areas deficient in sanitary provisions or in the use of "night soil" where thispractice remains part of the prevailing agricultural pattern;
3 . transmission in all of these infections is via human behavioural variables‑ either
obligatory water‑contact in the case of the schistosomes, or age‑old eating habits in theother trematodiases‑ human attitudes and customs which are extremely difficult toalter and which are often resistant to conventional hea.Ith education;

4 . animal reservoirs of infection are, with the exception of S. haematobium, extremelycommon.
It thus appears inherently improbable that complete eradication of these infections by
the permanent interruption of transmission will be achieved on a global scale‑ at least in

the immediate future and certainly not before the year 2000.

Since schistosomiasis is the major globally‑distributed example of the humantrematode infections, it will be taken as an example of the linkage between
epidemiological analysis and control strategy and will be dealt with in greater detail thanthe other trematode infections which, nowadays; are of greater regional than global
Lately Director, Parasitic Diseases Programme, World Health Organization, Geneva, Switzerland.
Address: Dr. A. Davis, 'Pantiles' Catcott, Bridgwater, Somerset TA7 9HU, United Kingdom

216
significance.

The control of schistosomiasis will be covered under the headings of objectives,
minimal requirements for the planning of control, epidemiological, parasitological andbiologrcal techmques m current use the concept of an "mtegrated" approach with empha‑
sis on population‑based chemotherapy to reduce human morbidity, the importance of thechemotherapeutic "delivery system", the principles of health care and participation in andby the community, the analytical framework necessary for decisions on follow‑up action,
the importance of primary health care in control and the constraints experienced in the

management of operations.
A discussion on the drugs available for chemotherapy of trematode infections isincorporated into the epidemiological section of the control approach.

INTRODUCTION
It has been estimated that parasitic infections are the most widespread of all majordiseases, currently affecting about 3 x 109 people in the world, innumerable domestic animals

and a high proportion of plant growth.
The depressingly high prevalence rates of parasitic infections in man have several
common, yet general determinants, including poverty, inadequate or absent sanitary facil‑
ities, absence of safe drinking water supplies, ignorance of health‑promoting practices, highbirth‑rates and persistent deleterious human behavioural patterns such as indiscriminate
defaecation or urination or unchanging age‑old eating habits. Above all, the prevailingsocioeconomic factors and the existing ecological conditions are favourable to the many
vectors or intermediate hosts that transmit infection to man.
In epidemiological terms, many of the parasitic infections are advancing in the "Third
World", not receding, and this is occurring despite the technological revolution of the 20th
century. The problems lie less in the areas of diagnosis and treatment than in the low priority

which the governments of endemic countries and governing bodies of international organiza‑
tions accord to the control of parasitic diseases when faced with a multiplicity of often

competing health problems, constrained‑ and finite‑ financial resources and an extreme
shortage of skilled and knowledgeable personnel. There exists a great need to convince
governments of the importance of the burdens, in both human and economic terms, resulting
from the chronic sequelae of parasitic diseases.

THE EpIDEMIOLOGY OF THE SNAIL‑BORNE TREMATODE INFECTIONS
The different life‑cycles of the human digenetic parasitic trematodes Schistosoma
japonicum. S. mansoni. S. haematobium. Clonorchis sinensis, various species of the genera
Qpisthorchis and Paragonimus, and those of lesser pathogenic importance, Fasciolopsis buski,
Heterophyes heterophyes and Metagonimus yokogawai, illustrate the complexity of the clinico‑
epidemiological profiles of these syndromes.
The one factor common to all of these infections is the necessity of a primary snail
intermediate host to complete the biological life‑cycle; some additionally require a secondaryintermediate host which may be several species of fresh‑water fish, crustaceans or aquaticplants. Conversely, the mode of transmission to man varies from dermal penetration of

217
infective

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malaria in socioeconomic andpublicisonehealthof themostimportance inwidespreadandtropical andsubtropical areas．

Causedbyacomplexofparasites，transmission

to man isthroughdifferent

speciesof218

fresh‑water snails in a wide variety of habitats. Five different parasites, at least, areepidemiological entities and affect different organ systems and functions of the body (S.
japonicum. S. mansoni. S. haematobium. S. mekongi and S. intercalatum).
People maintain the life‑cycle by contaminating the environment through indiscriminate
defaecation or urination. In some areas, particularly where S. japonicum is endemic, infec‑
tion in animals is important epide. miologically.

The infection is acquired through repeated contact with infected fresh‑water; disease or

morbidity due to schistosomiasis is caused basically by the heavy parasite loads in children

who are in frequent contact with infected water. The chronic forms of disease observed in
adults, including bladder cancer associated with S. haematobium infection, are sequelae toheavy infections acquired in childhood and repeated in adult life. Althotigh mainly a diseaseof rural areas with high levels of poverty, poor housing, substandard hygiene and lack ofsanitary facilities or adequate water supplies, some urban centres in endemic countries may
show high prevalences of schistosomiasis. The risk of spread and the intensification oftransmission of schistosomiasis is well recognized within expanding agricultural, hydroelec‑
tric and other water‑resource development projects in endemic areas. In refugee settlementsof South‑east Asia and Africa, schistosomiasis is recognized as a public health problem.

Now endemic in 74 countries in the world, it is estimated that more than 200 million
persons living in rural and agricultural areas are infected with schistosomiasis and thatbetween 500 and 600 million people are exposed to infection because of poverty, ignorance,
poor housing, substandard hygienic practices and the availability of few, if any, sanitaryf acilities.

In the earlier years of this century, S. japonicum infection in man occurred. in six
countries, but is found today only in China, Indonesia and the Philippines. Infection with S.

mehongi, a close relative of S. japonicum, has been detected in two South‑east Asian
countries.

S. haematobium infections are endemic in 52 eastern Mediterranean and African coun‑tries, while S. mansoni occurs in 53 countries ranging from the Arabian peninsula to Brazil,

Suriname, Venezuela and certain Caribbean islands. In 40 countries, double infections with

S. mansoni and S. haematobium are endemic. S. intercalatum causes a form of humanintestinal schistosomiasis reported infrequently from 6 central or West African countries.
Reports of new locations of infection appear from time to time such as the appearance of S.

haematobium in an irrigation development jn Sao Tom6 and Principe and the recent presenceof S. mansoni in Niger and Oman. Even within ancient areas of endemicity, the spread ofparasitism is not uncommon and a good example is the insidious advancement of S. mansoni
from the Nile Delta up the river to the governorate of Aswan where cases, and snails, arefound. This curious phenomenon is all the more intriguing since S. mansoni has never been
detected south of Cairo from prehistoric times and the association in time of spread with thechanges in water usage patterns induced by the construction of the Aswan High Dam Lake
must make a causal role of the dam at least suspect, if not proven.

The epidemiology of schistosomiasis is not necessarily uniform within an endemic
country and it cannot be compared between countries. For example, water‑resource develop‑
ment schemes cari change the epidemiology from seasonal and highly focal transmission into
intense, widespread and continuous transmission in a surprisingly short space of time.
The summarized epidemiological profiles of the human element of the total picture,

219

which of course involves the snail distributions and species and the ecological backgrounds,
are as follows:

In S. mansoni endemic areas, the prevalence of infection is greatest in the 10‑24 year

age‑range. Prevalence in older age groups remains at higher levels than is the case in S.
haematobium infections. A small proportion of the infected population excretes at least 50%of the total number of eggs contaminating the environment and most of these heavily infected
people are between 10 and 15 years of age. A high proportion of children with elevated S.
mansoni egg counts (over 800 eggs per gram of stooD have enlarged livers and/or spleens,irrespective of the endemicity of malaria.
In S. haematobium the peak prevalence and intensity of infection occurs in children aged
10‑14 years with a rapid diminution in older age groups. As a generalization, 60‑70% of all
infected persons are in the age‑range 5‑14 years. In both children and adults, increasing
haematuria and proteinuria parallel increasing intensities of infection with rising egg outputs.

The well‑known radiological changes which occur range from calcified bladders throughureteral deformities to hydronephrosis tend to be associated with heavy infections in children.

In several studies haematuria detectable by reagent strips occurred in 98‑100% of children
with egg outputs of over 50 eggs per 10 ml urine, thus providing a useful field substitute formicroscopy.
There is no typical age prevalence and intensity distribution in S. japonicum infection.
Bimodal age prevalence curves with peaks in the 10‑14 and 35‑44 years age‑groups have been
re ported.

A STRATEGY FOR CONTROL OF SCHISTOSOMIASIS
The major objective of the prevention and control of schistosomiasis is the reduction ofhuman morbidity and mortality to levels below public health importance. Public healthworkers have frequently feared that unless schistosomiasis transmission has been stopped, acontrol programme cannot be declared a success. That this attitude is unrealistic is not in
doubt; the high endemicity levels existing in many parts of the world, the socioeconomic
deficiencies accompanying the widespread scarcity of sanitary facilities, the general lack ofprovision of rural potable water supplies and the pervading low standards of health education
at even the most elementary levels make it plain that eradication of schistosomiasis is a non‑realistic goal in the immediate future.

A strategy of control of morbidity caused by schistosomiasis can be implemented byincreased emphasis on health education, Iarge‑scale population‑based chemotherapy, provi‑sion of water supplies and sanitation and the integration of control activities into basic healthservices. Health education is promoted at the community level through the health services
in coordination with the general education system. The effective, safe and well‑tolerated
drugs praziquantel, metrifonate and oxamniquine, all given by mouth, are now included inmany national drug lists and drug policies. The capability for diagnosis of parasitic diseases,
including schistosomiasis, should be an essential activity of peripheral health laboratories in'endemic countries. In parallel with reductions in prevalence and intensity of infection, therole of snail control and environmental management, water supplies and sanitation are
becoming more precisely targeted at an achievable level. Reductions of disease due toschistosomiasis can be attained within the known limitations of each endemic country. As the220epidemiology of schistosomiasis varies from one country to another, so will vary the
managerial and operational structures of schistosomiasis control. The simplicity of thecurrent microscopic diagnostic techniques, the ease and safety of standard dosage with orally

given antischistosomal drugs and the limited use of snail control measures as required by
epidemiological criteria derived from precise data collection and analysis permit schis‑tosomiasis control activities to be adapted and introduced at any level of the health caredelivery system.
The basic justfications for control of schistosomiasis, which are always demanded byfinancing bodies or decision makers at the political level are directed towards two primaryconcepts:
1 . The direct reductions in human morbidity and mortality produced by a simple, well‑tried

technology which is affordable even by the poorest countries.
2 . The use of the control of schistosomiasis as a tool in acceptance by rural populations forentry into other health‑related activities, e.g. personal hygiene, environmental sanitationand improvement, health eduction, maternal and child care; in other words, the mechanics
of primary health care. Considerable social benefits can be anticipated from control and,administratively, a not inconsiderable reduction in funds spent on medical care of infected

people will benefit a national health budget, thus allowing a redeployment of resources
towards other immediately pressing problems (Davis, 1989).

CHEMOTHERAPY IN THE CONTROL OF SCHISTOSOMIASIS
Since the most important and immediate control tool for the reduction of humanmorbidity in schistosomiasis is population‑based chemotherapy, it is essential to consider its

use within an epidemiological context and the appreciation that chemotherapy, although
predominant in control, is certainly not the only public health intervention of value.
Whatever strategy variant is adopted, the next step is to proceed to the tactics of attack.

Tactics are less a matter of medical practice than of medical administration within anational, regional or local health service background and this comprises the health delivery
system to the public.
Success in an integrated approach to control depends essentially on an accurate ecologi‑

cal diagnosis, that is, a diagnosis of the hurrian community, its epidemiological and par‑asitological characteristics, the physico‑geographical environmental attributes, the biologi‑
cal properties of the transmitting snails in the broadest sense and man's behavioural attitudes

and customs; these may be crucial to the success or failure of control.
The principles of community health care which can contribute to the control of schis‑tosomiasis have been laid out (Davis, 1981) and comprise:

1 . The use of accurate demographic and epidemiological survey methods to define thenumerator of infections over the population denominator and to describe the age‑specificprevalence and infection‑intensity profiles.
2 . The use of sensitive and specific parasitological techniques to demonstrate and quantify

a specific infection. Nowadays, the cellophane thick smear, the Kato technique, or one ofits numerous modifications, has become a standard diaguostic tool in epidemiologicalstudies and has much to commend it in those schistosome infections where eggs are
excreted in the faeces. In the diagnosis of S. haematobium, recent years have seen the221replacement of simple sedimentation or centrifugal techniques by filtration and currently
urine samples are passed through filter paper, polycarbonate or polyamide by a variety ofsyringes or pumps. The principle common to all is that eggs are retained on the filter andcan be stained and counted. On filters made from polycarbonate or polyamide, staining is

unnecessary.

3 . The necessity of community participation. The pioneering efforts of the Japanese
Organization for International Cooperation in Family Planning, or JOICFP, in the control
of intestinal parasites cannot be too highly praised for the example shown in mobilizing

community participation.

4 . The employment of population‑based chemotherapy. The use of chemotherapy incontrol requires a clear definition of aims, selection of the most appropriate chemother‑apeutic agent, decisions on the dosage and time‑frame to be followed and the organizationof the delivery system.
The aims of chemotherapy are twofold: to eradicate or control the infection in the patientas an individual and, in endemic areas, to benefit the community in which he lives. In theindividual patient, successful treatment will prevent further deposition of eggs by female
fiukes and, since eggs are the pathogenic agents in the tissues, existing lesions will regress andfuture tissue damage will be prevented. For the community, the cessation of egg excretion
will block the egg/miracidium/snail stage of the biological cycle, thus effectively reducing,or, on rare occasions, controlling transmission.

A quiet revolution has occurred in the treatment of schistosomiasis in the last twenty

years. Up to the mid‑1960's, trivalent antimony drugs were the cornerstone of antischis‑tosomal chemotherapy. Since then, niridazole, metrifonate, hycanthone, oxamniquine andpraziquantel have all come into clinical use and this advent of highly effective, well‑tolerated

chemo‑therapeutic agents has provided physicians with flexibility and opportunities for
curative treatment which were simply unheard of 20 years ago.
The major antischistosomal agents in current use are all on the WHO List of Essential
Drugs. One important reservation must be noted; the success of this last generation ofantischistosomals has had the paradoxical effect of reducing the efforts made by the pharma‑

ceutical industry in research on new drugs against schistosomiasis. Two newcomers, amos‑
canate and oltipraz, although highly effective as schistosomicides, have failed to survive
toxicological screens and there are no promising candidates on the horizon. This should beborne in mind for it cannot be claimed that resistance will not appear as a problem in future.

In fact, although resistance to oxamniquine has been documented, fortunately it has not
become a public health problem to date.

INDIVIDUAL ANTISCHISTOSOMAL DRUGS
Praziquantel:

Undoubtedly the most important advance of recent years in anthelmintic chemotherapy
has been praziquantel. With few siguificant side effects, not adverse reactions on liver, renal,

haemopoetic or other body functions, it is highly effective in all schistosome infections, themajority of other snail‑borne trematode infections and a great variety of cestode infections.

Chemically (2‑cyclohexylcarbonyl‑1,2,3,6,7,1lb‑hexahydr0‑4H‑pyrazino [2,1‑aliso‑
qumolme 40ne), this broad‑spectrum anthelmintic was derived from a novel heterocyclic

222

system. Extensive animal experimentation revealed high therapeutic activity over a wide
range of helminths and currently, activity is known to exist in man against all schistosomes,
Clonorchis sinensis. Qpisthorchis spp., Paragonimus spp., Metagonimus yokogawai. Fasciolopsis

buski. Heterophyes heterophyes and the cestodes, Taenia solium. T. saginata. Hymenolepis
nana. Diphyllobothrium latum and D. paclficum. Of particular importance is its effect inhuman cysticercosis, both dermal and neurocysticercosis. A wide variation of therapeutic
results have been reported against Fasciola hepatica and it is ineffective in the humansecondary larval stage of Echinococcus inefections.
In the customary pharmacological screening tests the profiles of action and toxicity weresatisfactory in rats, beagle dogs, sheep and rhesus monkeys. In man, praziquantel is rapidly

absorbed after oral dosage, and, after a pronounced first‑pass biotrahsformation process,metabolites are excreted mainly in the urine. In healthy volunteers, maximum serum
concentrations are reached in one to two hours. By the use of an isotope‑measuring tech‑nique with 14C‑labelled praziquantel and a specific gas chromatographic assay, the elimina‑tion half‑life of the drug from the serum was 1‑1.5 hours and that for praziquantel plus
metabolites was 4‑5 hours. The renal elimination half‑life for praziquantel plus metabolites
was 4 to 6 hours and the cumulative renal excretion of praziquantel within 4 days was over
80% of the dose, 90% of which was eliminated on the first day after 'dosing (Buhring et al.,
1978; Leopold et al.. 1978) .

The results of toxicological studies were reviewed comprehensively by Frohberg (1984)
who noted a lack of systemic toxic effects, a lack of adverse effects on mammals and theirprogeny and a lack of embryotoxicity. Extensive mutagenicity and full carcinogenicity
studies failed to indicate any mutagenic or carcinogenic potential (Bartsch et al., 1978;
Ketkar et al.. 1982).

Praziquantel is active against schistosomes both in vitro and in vivo. In in vitro
experiments, schistosomes instantly become immobile and undergo contraction on contact
with the drug. A serum concentration of 0.3 pg/ml is fully effective; one of 0.1 pg/ml is
without effect. When schistosomes are kept in culture media containing a little protein, allconcentratibns of drug above 0.04 pg/ml are effective. It seems that the contraction of theschistosome musculature is due to an interference by praziquantel with inorganic ion trans‑
port mechanisms, resulting in a decreased influx of K+ but an increase in influx of Ca2+ andNa+ into the worms (Pax et al.. 1978).
In parallel with these biochemical studies, scanning and transmission electron micros‑
copy of S. mansoni after in vitro exposure to ebncentrations of praziquantel ranging from

0‑100 pglml for times varying from 5 to 60 minutes has shown that the drug causes
vacuolisation of the schistosome tegument, finally leading to the disruption of the apicaltegumental layer (Becker et al.. 1980). This appears to be a direct and primary effect ofpraziquantel, not only on schistosomes, but also on cestodes which are sensitive to the drug.
Glucose uptake of schistosomes, and hence lactic acid production, is reduced by praziquantel

and the worm compensates by breakdown of its endogenous glycogen store. Egg formationin the female is inhibited at concentrations as low as 0.001 pg/ml and totally inhibited at 0.01

pglml .
Thus the mode of action of praziquantel can be summarized as an extremely rapid andmajor alteration in energy support systems and neuromuscular functions of the worms atextremely low concentrations (10‑7 M) , followed by tegumental damage, an immunological223

event which presents both internal metabolites and previously hidden ahd inaccessible
antigenic sites to the enveloping blood stream. Phagocytes and gianulocytes are attracted tothe damaged tegument, fibroblastic encapsulation occurs and a rapid total disintegration of
the schistosomes ensues (Senft, 1989). The precise molecular sequence of events remains
under investigation.
Cooperative multicentre clinical trials of tolerance to praziquantel and of its therapeutic

effect against the three common species of schistoso me infecting man were conducted jointly

by the Parasitic Diseases Programme of the World Health Organization and the manufactur‑
ing company (Bayer AG, Federal Republic of Germany) in Africa, Brazil, Japan and thePhilippines. Double‑blind trials of tolerance were followed by clinical trials of efficacy using

a standard trial design and agreed technical protocols, although parasitological methods oftherapeutic assessment varied with the species of infecting parasite (Davis and W.egner, 1979;
Davis et al., 1979; Ishizaki et al., 1979; Katz et al.. 1979; Santos et al.. 1979).

In these trials, praziquantel was well tolerated, produced no changes of biologicalsignificance in a battery of haematological and biochemical monitoring tests or in serial
electrocardiograms or electroencephalograms, and gave cure rates at 6 months after treat‑ment of between 75 and 100% in the various samples of patients.
Virtually all subsequent trials have confirmed the absence of toxic effects of the drug onvital organs, systems, and functions. Side effects of treatment are generally mild anddisappear within 24 hours. The most frequent symptoms reported are epigastric pain or
diffuse abdominal discomfort, nausea, anorexia, Ioose stools or diarrhoea, dizziness, head‑ache, pruritus or an urticarial‑type of skin eruption and fever. Predictably, the proportionof those complaining of side effects varies with the ethnic origin of the patients. Abdominal

pain has occurred in up to 50% of some series but is usually mild and only rarely accompanied

by vomiting. With increasing experience of large‑scale chemotherapy in the last few years
when hundreds of thousands of patients have been treated, three groups of side eff cts can be
distinguished as entities: (1) those related to the gastrointestinal tract as noted above and,in occasional patients with heavy infections with S. mansoni or S. japonicum, the passage ofblood in the stools shortly after treatment (Polderman et al.. 1984) . This is invariably short‑

lived and not aggravated by the giving of another dose of drug. (2) those symptoms related
to the CNS, i.e. headache and dizziness, and (3) general symptoms of fatigue, fever, pruritus,
etc. It should be stressed that in ,the vast majority of treated patients, side effects are mild

and transient and rarely, if ever, require additional treatment.

After many years of experience, cure rates vary between 75 and 100% in different series

where the characteristics of the treated groups may vary considerably and where there may
be a very wide range of intensities of infection as assessed by excretal egg counts. The usual

dosage used in large‑scale campaigus for both S. mansoni and S. haematobium is one oral
dose of 40 mglkg; for S. japonicum, the current popular regimes are total doses of 60 mg/kg
given either as 30 mglkg in two doses in the day or 20 mglkg given as three doses daily atfour‑hour intervals. It is noteworthy that advanced and complicated cases of S. japonicum
or S. n ansoni with ascites and portal hypertension tolerate the drug well.
The great majority of uncomplicated cases of schistosomiasis can be treated in the home,the out‑patient clinic, the rural dispensary or the village or school‑ an immense advancefrom the practices of 20 years ago.

224

Other Antischistosomal Drugs:
Whilst praziquantel acts on all species of schistosome, there are two other drugs which
are monospecific in their effects: metrifonate being active against S. haematobium only andoxamniquine against S. mansoni only. Metrifonate, an organophosphorus ester, was origi‑
nally used as a pesticide and veterinary anthelminthic before its issue in pure form fortherapeutic use in man. Its insecticidal action was due to enzymic inhibition of specificesterases in ganglionar synapses and neuromuscular junctions. In man, treatment is followed
by depression of cholinesterases in both red cells and plasma but there is no correlation

between cholinesterase depression and any post‑treatment symptoms. It appears thatmetrifonate, in man, undergoes a chemical transformation, unrelated to enzymatic metabo‑lism, into dichlorvos (DDVP 2,2‑dichlorovinyl dimethyl phosphate) which is the actual
cholinesterase inhibitory substance. Metrifonate acts as a slow‑release mechanism forformation of DDVP. Although metrifonate has some activity against S. mansoni it is notnormally used for the treatment of this species. It also has activity against hookworms,
ascariasis, trichuriasis, creeping eruption, onchocerciasis and in cysticercosis but is rarely
used since efiicacy is inconstant. The sole activity for use is S. haewatobium infection. Verywidely used in millions of patients, it is well tolerated but suffers from having to be given inthree doses at intervals of 14 days thus producing a large number of "incomplete treatments".
Its virtues lie in its cheapness, its acceptance and a reasonable cure rate of 60‑90% in different

population samples.
Oxamniquine, the other monospecific schistosomicide, has been widely used against S.
mansoni, the only indication for its employment. The therapeutic response varies with theage and thus the surface area of the patient and with the geographic origin of the infection,
there being a distinct difference in response of schistosome strains of African and SouthAmerican origin, the details of which need not concern us here. Highly effective, it was themainstay of the major Brazilian campaigu of the mid‑1970's when many millions of treat‑ments were given. It remains an interesting compound if only because it affects male worms
rather than females and there is a distinct cut‑off point in efiicacy, it being totally without

effect in man against S. haematobium. S. mattheei or S. japonicum.

POPULATION‑BASED CHEMOTHERAPY AND THE DELIVERY SYSTEM
Mass, selective and targeted chemotherapy
It is clear that for the immediate future and perhaps even for decades, emphasis in thecontrol of schistosomiasis in man will be placed on the reduction of human morbidity andmortality implemented through population‑based chemotherapy. It is also clear that chemo‑
therapy is the only agent available for the cure of the countless numbers of individual patients

presenting themselves for health care.
Population‑based chemotherapy is, as the phrase implies, based on target human popula‑tions, the hosts of the schistosomes. These populations must be viewed as epidemiologicalunits and may be composed of total area populations, or several varieties of sub‑populations,e.g. a population of children in a specific age‑range, a whole village population, a populationof plantation workers, etc. Although the term "community" is frequently used as an alterna‑
tive description of a population, the latter is preferable in reminding us of the essential
statistical rigour with which sampling and data analysis must be conducted. Conceptually,

225

at this stage, the' population itself is the referral unit and not the individual' human targets

within the population‑ as is the case when reference is made t6 "targeted" chemotherapy.

Population‑based chemotherapy is implemented via 2 main pathways: through masschemotherapy or, alternatively, through what has become known as selective population
chemotherapy or SPC.
Mass chemotherapy is the ireatment of everyone in a population whether infected or
non‑infected. Since it is rarely practicable to examine everyone in a population except insmall or moderate‑size village levels or in school surveys, mass chemotherapy as a control
tactic is usually applied after various survey sampling procedures and the subsequent action
is based on decisions made on pre‑determined rates of infection and/or levels of intensity of

infection, which naturally vary in the numerous heterogeneous epidemiological settings
encountered. Where prevalences and/or intensities of infection are very high, or where thereis clear evidence of associated morbidity and/or mortality, this is a perfectly feasible tactic

for morbidity control since, as we have seen, the modern antischistosomal drugs are highly
effective and their toxicity to man is many orders of maguitude less than the compounds usedeven as recently as the 1960's, and population acceptance is good.

The alternative population‑based chemotherapeutic approach, selective population
chemotherapy, is the treatment of those infected members of a population only, i.e. selection
is by the demonstration of infection, qualitatively, quantitatively, or both, depending on theobjectives of the programme, the techniques and measurements used in examinations and thecriteria adopted to indicate success‑ or lack of success! This approach implies the measure‑ment, or in this case the diagnosis, of each individual member of a population (or "commu‑
nity") and the delineation of those infected in contrast to those non‑infected.

There are many variants of selective population chemotherapy, e.g. it can be applied to
sub‑targets of infected populations in the so‑called targeted chemotherapy of high‑intensity

infections where the risk of developing manifest disease is greatest, or to particular age‑
ranges where prevalences are known to be higher than in the rest of the population; this issometimes termed "selective group treatment". Yet even these variants remain basically aform of selective population chemotherapy. In certain situations, a combined approach would
constitute the most effective strategy; after mass chemotherapy has lowered prevalence andintensity rates, then selective population chemotherapy could be used in those individuals
exhibiting the residual prevalence on follow‑up examination.
Whatever strategy of chemotherapeutic control is adopted, and this will depend on theepidemiological survey dat , its analysis and the subsequent projections of epidemiologicaltransmission dynamics, the one essential tactical element will be repeated drug administra‑tion. Whereas mathematical models can point to the utility or otherwise of generalizedtactics, the frequency of administration of drugs, the anticipated rates of population cover‑age, the duration of the attack phase, the timing and duration of surveillance and themaintenance of reduced prevalence and intensity levels tend to be area‑specific,
epidemiologically‑specific, health service‑specific and even species‑specific in the various
schistosome infections.

The essential components of any chemotherapeutic delivery system are personnel,
diagnostic technologies and their associated materials, drugs, transport, Iogistical support,

data recording and management apparatus and that elusive characteristic, motivation.
Whilst the optimum method of drug delivery will vary with local conditions; the existing226

infrastructure and its associated personnel should be used whenever possible.

Costs loom large in any strategic or tactical considerations and the proportionate
components of each of the stepS in the chemotherapeutic delivery system never fail to induce

surprise, whether the calculations are based on numbers of specimens examined, yield per
survey or cases detected, costs per person protected or treatment costs‑ which include fixed
costs of salaries of personnel, field allowances, overtime, costs of materials, vehicular trans‑

port and maintenance, and costs of drugs. It is, for example, axiomatic that the lower is theprevalence, the higher is the cost of case‑detection and it is obvious that the best returns interms of value for money are in those situations where prevalences and intensities of infection

are so high that even a restricted sampling procedure followed by mass chemotherapy isindicated.

There is certainly room for an expansion of practical modelling on chemotherapeutic
delivery costs for the actual purchase prices of drugs are but a small fraction of the wholecost element. Even drug costs themselves are amenable to price reductions through bulk
purchase schemes, competitive tenders, importation of bulk raw supplies for local tabletting

and a competent storage and distribution system at local and national levels (Davis, 1985,
1989) .

Thus the introduction of new, safe, efiicient and well‑tolerated drugs has made chemo‑
therapy the most potent currently available tool in the control of schistosomiasis. This
principle can also be extended to the control of the other snail‑borne trematode infections

and large‑scale chemotherapeutic campaigns with praziquantel are already in use in
Thailand against opisthorchiasis and against clonorchiasis in Korea.
Although all of the principles enunciated for schistosomiasis control are applicable to theother trematode infections the outlook is likely to be less favourable since the complicating
human behavioural variables of eating habits are much more difficult to eradicate as age‑old

customs. Additional complicating factors mitigating against success in control are thenumbers of secondary intermediate hosts; Yoshimura (1965) tabulated 89 species of fresh‑water fish or crustaceans in 10 families existing in China, Korea, Japan and Taiwan, and thelarge numbers of animal reservoirs including many mammals although their role in contribut‑
ing to transmission dynamics is less than clear cut.

One terminological warning on the use of the term "drug‑efficacy" should be borne inmind. Estimates of the antischistosomal activities of the drugs in use at the population levelare frequently optimistic. The terms "cure rate" or "parasitological cure" have time‑honour‑
ed and specific meanings in clinical usage and are applied usually to the individual patient.

They imply in this case the termination of an existing schistosome or other trematodeinfection with the permanent cessation of excretion of eggs from the body. This clinical state

can be confirmed only after repeated parasitological examinations, often using concentration
techniques, over an extended time period. In population‑based chemotherapy programmes it
is not possible to undertake repeated parasitological excretal examinations for logistic
reasons and estimates of "cure rates" are thus usually based on the findings of a single post‑

treatment examination; in other words, the estimates are to be used as a guide and not as an
absolute statistic, particularly when a once daily dose of an active drug may not represent thebest pharmacological usage but is instead a compromise forced by the necessity to ensure thelargest population coverage within logistic constraints.

An alternative technical term used in the assessment of drug efiicacy in all helminthic

227

infections is the "egg reduction rate" expressed as a population‑mean figure or in age‑specificterms. This simply represents the calculation of a post‑treatment egg count of either apopulation or a sample and its comparison with the pre‑treatment egg load of the samecommon denominator, all based on a common unit weight of faecal material or the same

volume of urine examined by the same technique on the two occasions. Although thistechnique is frequently used, it suffers, in parallel with the term "cure rate", from several

disadvantages, principally because of the numerous variables that infiuence egg productionand excretion and observer variation in microscopic assessment. It is therefore a rather
indirect reflection of biological events. Neither index can be regarded as totally satisfactoryand great care must be taken in the evaluation of claims of efficacy advanced after clinicalor epidemiological trials, especially where methodological variation existed.
If neither the prevalence nor the intensity of infection is reduced after chemotherapy, anevaluation should be conducted to explore the possibility of (1) drug "failure" I e therapeu

tic failure; (2) Iack of compliance; (3) "resrstance" of the parasite to the drug vrrtually

unknown to date, or (4) "operational failure", an all‑embracing terin covering manydifferent sins of omission or commission. Programme des, ign and evaluation procedures
usually require the assistance of an experienced epidemiologist, statistician and par‑asitologist (WHO, 1987). Firially, it should be recalled that experience during the last two

decades has shown t.hat the major constraining management problems in parasitic disease
control are rarely technical but usually administrative and financial (Mott and Davis, 1986) .

REFERENCES
1 ) Bartsch, H., Kuroki, T., Malaveille, C., Loprieno, N., Barale, R., Abbondandolo, A., Bonatti, S･.,Rainaldi, G., Vogel, E. and Davis, A. (1978) : Absence of mutagenicity of Praziquantel, a neweffective, anti‑schistosomal drug, in bacteria, yeasts, insects and mammalian cells, Mutation
Research, 58 (2/3), 133‑142

2 ) Becker, B., Mehlhorn, H., Andrews, P., Thomas, H. and Eckert, J. (1980): Light and electron

microscopic studies on the effect of Praziquantel on Schistosoma mansoni‑ dicrocoelium‑
dendriticum and Fasciola hepatica tremat.oda in vitro. Ztschr. Parasitenkd.: 63 (2), 113‑128

3 ) Buhring, K.U., Dieckmann, H.W.,･Muller, H., Garbe, A. and Nowak, H. (1978): Metabolism of
Praziquantel in man, Europ. J. Drug. Metab. Pharmacokin., 179‑190
4 ) Davis, A., Biles, J.E. and Ulrich, A.‑M. (1979): Initial experiences with Praziquantel in thetreatment of human infections due to Schistosoma haematobium. Bull. Wld. Hlth. Org., 57 (5),773‑779
5 ) Davis, A. and Wegner, D.H.G. (1979): Multicentre trials of Praziquantel in human schis‑tosomiasis: Design and techniques, Bull. Wld. Hlth. Org., 57 (5), 767‑771
6 ) Davis, A. (1981): Principles of schistosomiasis control in relation to community health care,Artzneimittel Forschung, 31 (3a), 616
7 ) Davis, A. (1985): In: Ascariasis and its public health significance, Eds, Crompton, D.W.T.,

Nesheim, M.C. and Pawlowski, Z.S., 239, Taylor & Francis, London, New York & Philadelphia
8 ) Davis, A. (1989): In: Ascariasis and its prevention and control, Eds, Crompton, D.W.T.,
Nesheim, M.C. and Pawlowski, Z.S., 343, Taylor & Francis, London, New York & Philadelphia9 ) Frohb rg, H. (1984): Results of toxicological studies on Praziquantel, Artzneimittel For‑
schung, 34 (3a) , 1137‑1144

10) Gammell, M.A., Lawson, J.R. and Roberts, M.G. (1986): Control of echinococcus hydatidosis:
Present status of world wide progress, Bull, Wld. Hlth. Org., 64 (3), 333‑339

22811) Ishizaki, T., Kamo, E. and Boehme, K. (1979) : Double‑blind studies of tolerance to Prazi‑
quantel in Japanese patients with Schistosoma japonicum infections, Bull. Wld. Hlth. Org., 57(5), 787‑791

12) Katz, N., Rocha, R.S. and Chaves, A. (1979): Preliminary trials with Praziquantel in humaninfections due to Schistosoma mansoni. Bull. Wld. Hlth. Org., 57 (5), 781‑785
13) Ketkar, M., Althoff, J. and Mohr, U. (1982): A chronic study of Praziquantel in Syrian golden

hamsters and Sprague‑Dawley rats, Toxicology, 24, 345‑350
14) Leopold, G., Ungethum, W., Groll, E., Diekmann, H.W., Nowak, H. and Wegner, D.H.G. (1978) :Clinical pharmacology in normal volunteers of Praziquantel, a new drug against schistosomes
and cestodes, Europ. J. Clin. Pharmacol., 14, 281‑291
15) Mott, K.E. and Davis, A. (1986): Organizational implications of various program strategies.

Discussion paper for World Bank workshop on "Orgamzatron and management of schis
tosomiasis and other tropical diseases control programs", Washington D.C.
16) Pax, R., Bennett, J.L. and Fetterer, R. (1978): A benzodiazepine derivate and Praziquantel:
Effects on musculature of Schistosoma mansoni and Schistosoma japonicum. Arch. fu. pharma‑kol., 304, 309‑315

17) Polderman, A.M., Gryseels, B., Gerold, J.L., Mpamila, K. and Manshande, J.P. (1984) Side
effects of Praziquantel in the treatment of Schistosoma mansoni Maniema, Zaire, Trans. Roy.
Soc. Trop. Med. Hyg., 78 (6), 752‑754
18) Santos, A.TL, Blas, B.L., Nosefias, J.S., Partillo, G.P., Ortega, O.M., Hayashi, M. and Boehme,
K. (1979): Preliminary clinical trials with Praziquantel in Schistosoma japonicum infections in
the Philippines, Bull. Wld. Hlth. Org., 57 (5) , 793‑797

19) Senft, A.W. (1989) : Personal communication
20) World Health Organization (1983): Parasitic diseases programme, internal document, WHOl

SCHIST0/83.68
21) Yoshimura, H. (1965): The life cycle of Clonorchis sinensis: A comment on the presentationin the seventh edition of Craig and Faust's Clinical Parasitology, J. Parasitol., 51 (6) , 961‑966

Japan. J. Trop. Med. Hyg., Vol. 18 No. 3, 1990, pp. 229‑237

229

PLASMODIUM BERGHEI AND YOELII =A CORRELATION OF SURVIVAL PERIODS

AND IMMUNOLOGICAL PARAMETERS
IN BALB/* MICEMAUNG MAUNG Oo*, SUSUMU IKEHARA2, TAKAO NAKAMURA',
SHUJI INOUEI AND YOSHIHIRO HAMASHIMAl
Received May 2 1990/Accepted June 22 1990

Abstract: After inoculation with Plasmodium berghei I¥lLK65, BALB/C nu/nu micesurvived longer than normal BALB/C mice. No such difference was found after infection
with Plasmodium yoelii 17X. The difference in survival periods was not due to a differencein parasitemia level; studies of several immunological parameters revealed that the micethat survived longer showed an increased ability to generate interleukin‑2 and cytotoxic
T Iymphocytes from their spleen cells. The survival period had no relationship with theamount of anti‑malarial antibodies nor the formation of immune complexes. T cellfunctions were generally decreased and natural killer cell activity was raised in all mice
regardless of their different survival periods.

INTRODUCTION
Different species of rodent malaria parasites induce different immunological reactions in
the host. The resulting pathological effects range from mild self‑limiting diseases to rapidly

fatal complicated infections. There is evidence to show that after infection, some species ofmalaria hosts with T cell dysfunction can survive longer than hosts with normal T cellfunctions. BALB/C mice die earlier than nude mice after inoculation with P. berghei NK65
(Waki et al., 1977) or P. berghei ANKA (Finley et al., 1982) . Neonatally‑thyrnectomized oranti‑thymocyte serum‑treated golden hamsters survived longer after infection with malaria
than did normal hamsters (Wright et al.. 1968,; Wright et al., 1971). Malnourished children
were found to saffer more from the less virulent form of P. falciparum infection than well‑nourished children (Edington et al., 1967) . AII these findings suggest that intact T cellfunctions are deleterious to the host after infection with certain species of malaria parasites.

In order to elucidate the immune mechanisms involved in this phenomenon, we first tried tofind experimental malaria models which could be used to demonstrate the role of T cellfunctions in malaria. Secondarily, several immunologjcal reactions were measured todetermine any correlation with the severity of the disease.

1 Department of Pathology, Faculty of Medicine, Kyoto University. Sakyo‑ku, Kyoto 606, Japan,
2 Ist Department of Pathology, Kansai Medical University, Moriguchi City, Osaka 570, Japan.
Address reprint requests to : Susumu lkehara, MD., Ist Department of Pathology, Kansai Medical
University, Moriguchi City, Osaka 570, Japan230

MATERIALS AND METHODSMice
BALB/C or BALB/C nu/nu mice were inoculated through the tail vein with 10' red blood
cells infected with P. yoelii 17X (lethaD or P. berghei NK65. To determine the effect ofdifferent T cell functions on the severity of the illness, we studied the duration of survival andthe mode of increase in parasitemia level among the different groups. For cellular im‑
munological tests, the mice were sacrificed by cervical dislocation, and the spleen cells thencollected aseptically. For serological tests, blood samples were collected by cardiac puncture

and the samples stored at ‑ 70'C for simultaneous assay at a later date.
Serological assays

Anti‑malarial lgG and lgM titres were measured by indirect fiuorescence antibody
technique (Kuvin et al., 1962). Estimation of CICs was performed by Clq solid‑phaseradioimmunoassay using radio‑iodinated protein A (Hay et al., 1976) and purified Clq frompooled human serum (Yonemasu et al., 1971) .
T cell functions

For mitogen response, the mice were sacrificed 3 days after inoculation, and the spleencells then cultured in the presence of 25 pg/ml of PHA or 5 pg/ml of Con A or 25 pg/ml of

LPS. The mitogen reactivity was determined by measuring the incorporation of 3H‑
thymidine into DNA using 96 well microtitre plates. MLR was performed in the same way
using mitomycin C‑treated stimulator cells of C57BL/6J (H‑2b) or C3H (H‑2k) mice.
BALB/C spleen cells (H‑2d) were used as a control. The same stimulator cells were used for
CTL induction. Stimulated cells were cocultured with the target cells EL4 (H‑2b) , X5563 (H‑2k) and P815 (H‑2d) at different ratios. Percentage cytolysis was determined using the 51Cr

release assay method.
Interleukin 2 production

For IL‑2 production, spleen cells were stimulated with Con A for 24 hours. The super‑
natant was assayed for the presence of IL‑2 activity by its ability to support the growth ofan IL‑2‑dependent cell line, CTLL‑2 (Baker et al., 1979) . To measure NK activity, spleencells were passed through a nylon wool column to remove B cells. The resulting cells were
cocultured with different proportions of YAC‑1 cells. Percentage cytotoxicity was measured
using the 51Cr release assay method.

RESULTS
Nude mice survived longer than BALB/C mice after P. berghei infection (p<0.001) but
no such difference existed after P. yoelii infection. The early death was not attributable toa rapid increase in parasitemia level (Fig. 1). There appeared to be no relationship between
anti‑malarial lgG, IgM, and CIC Ievels in the different groups and the death of the host (Fig.
2) . Mice after infection showed decreased responses in both mitogen and allogeneic stimula‑tion, except that of BALB/C response to LPS after P. berghei infection. These changes also
show no correlation with the survival pattern (Figs. 3 and 4) .

231
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MITOGEN STIMULATION

EE P.yoel 17X (btt,al)

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wells without mitogen from those of the stimulated wells.

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Figure 4 MLR results after C57BL/6J and C3H stimulation shown as net

count per minute (cpm) calculated by subtracting the auto‑
stimulated background counts from those of the stimulated wells.

233
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25lj, 12.5c/1 6.25'/, 3.125'/, l.5G2S'h50'/, 25%l.250k 6.25'/, 3.125% 1.5625'/oAmount of Con A supernatant in cultUre
Figure 6 Con A‑induced IL‑2 production i demonstrated as the ability tosupport the growth of CTLL‑2 cell line. A marked increase in thecell growth is seen only in those wells containing a high percentageof the Con A supernatent obtained from the nude mice infected with
P. berghei.

234

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Figure 7 NK activity is shown as the degree of cytolysis against the target
cell line YAC‑1 at various effector: target (E:T) ratios: o ‑ o , NlC
65 infected; A ‑ A , 17X infected; e ‑ e uninfected.

A mild reduction in the generation of CTLS Was observed in all the P. yoelii‑infected

mice. By contrast, among the P. berghei‑infected group, nude mice showed an increased
generation of CTLS whereas normal BALB/C mice showed a reduced response (Fig. 5).
Thus, there seems to be a correlation between the increased ability to induce CTLS in thenude mice and their longer survival. In addition, Con A‑induced IL‑2 production was also
markedly raised in the same group, whereas reduced levels were found in all other groups(Fig. 6) . NK cell activity was raised in all the groups, there being no difference between
long‑lived and short‑lived groups (Fig. 7) .

DrscUSSloN

Many explanations and speculations had been put forward regarding the prolonged
survival of T cell‑deprived hosts after some types of malarial infections, but many of the
hypotheses did not fit with our findings. The results concerning anti‑malarial antibody levels

contrast with the previous thinking that the lack of T‑dependent agglutinins in T cell‑
deprived hosts was responsible for their longer survival (Wright et al.. 1968; Wright et al..

1971). CIC measurements in relationship to survival pattern excluded the possibility of
immune complex‑mediated injury (June et al., 1979; Rest et al., 1979; Adam et al., 1981).
Reduced mitogenic and allogeneic responses agreed with the previous findings of immunosup‑
pression (Lelchuk et al., 1980; Weidauz et al.. 1982).

Nude mice, having a higher NK activity (Herberman et al., 1978), were presumed to235have a resistance to malarial infection. A correlation was demonstrated between susceptibil‑
ity to malaria and NK activity (Eugui et al.. 1979) . However, in our experiment, NK activity

seemed to play no role in the resistance to malarial infection. Increased NK activity has
previously been noted (Ojo‑Amaize et al., 1981; Ojo‑Amaize et al.. 1984).
In contrast, the ability to produce IL‑2 after Con A stimulation was markedly increasedin the group that survived longest. This group also gave more CTLS in response to both H‑2band H‑2k antigens. Increased IL‑2 productivity may in some way confer a protection against
the malignant pathological effects of P. berghei in nude mice. Raised CTL activity may be
the result of the high IL‑2 secretion because IL‑2 has been known to induce the generationof specific CTLS particularly in nude mice (Gillis et al.. 1979; Smith et al.. 1984). The exact

mechanism by which the high level of IL‑2 confers protection needs to be further investigated.

Macrophage hyperactivity in mouse malaria is well documented (Zukerman et al., 1977) .
Increased IL‑1 production by activated macrophages resulting in an increased IL‑2 produc‑tion and then subsequent increase in CTL generation is a possible sequence, which needs tobe confirmed by measuring the IL‑1 productivity of adherent cells.
Our results pave the way to further observations of the varying pathological effects ofdifferent Plasmodium on human patients. Falciparum malaria can cause cerebral complica‑
tions with rapidly fatal outcome whereas vivax infection is benign and uncomplicated. It will
be interesting to observe whether such a difference is associated with an inequality in IL‑2
productivity and/or CTL activity.
Our findings of raised IL‑2 production is further evidence of the presence of functional
T cells in nude mice. Despite the well known fact of their lack of the thymus, nude mice were
found to exhibit some T cell functions if a sensitive assay method was used or after an intense

immunologic stimulus (Loor et al.. 1973; Langhdrne et al., 1983; Ikehara et al.. 1984).

ACKNOWLEDGEMENTS
This work was supported partly by grants from the Ministry of Welfare and Educationin Japan, and partly by the Japan International Cooperation Agency (JICA). Our gratituteis due to Dr. Aung Than Ba Tu (Director‑General of the Department of Medical Research,
Ministry of Health, Myanmar) for his encouragement and for making these studies possible.
We also thank Mr. K. Tsuchida. Ms. K. Kitamura, and Ms. M. Asano for their technicalassistance, and Ms. Aye Aye Win and Ms. S. Ohya for their help in preparing the manuscript.

REFERENCES
1 ) Adam, C., Geniteau, M., Gougerot‑pochdalo, M., Verroust, P., Lebras. J., Gibert, C. and Model‑

maroger, L. (1981) : Cryoglobulins, circulating immune complexes, and complement activationin cerebral malria, Infect. Immun., 31, 530‑5352 ) Baker, P.E., Gillis, S. and Smith, K.A. (1979) : Monoclonal cytolytic T cell lines, J. Exp. Med.,

149, 273‑2783 ) Edington, G.M. (1967): Pathology of malaria in West Africa, Br. Medical Journal., 1, 715‑718
4 ) Eugui, E.M. and Allison, A.C. (1979): Malaria infections in diffetent strains of mice and theircorrelation with natural killer activity, Bulletin of the World Health Organization, 57 (suppl.) ,231‑238

2365 ) Finley, R.W., Mackey, L.J. and Lambert, P.H. (1982): Virulent Plasmodium berghei malaria:
prolonged survival and decreased cerebral pathology in cell deficient nude mice, J. Immunol.,129, 2213‑2218

6 ) Gillis, S., Union, N.A., Baker, P.E. and Smith, K.A. (1979): The in vitro generation andsustained culture of nude mouse cytolytic T‑lymphocytes, J. Exp. Med., 149, 1460‑1476
7 ) Hay, F.C., Nineham, L.J. and Roitt, I.M. (1976): Routine assay for the detection of immune
complexes of known immunologlobulin class using solid phase Clq., Clin. Exp. Immunol., 24,
396‑400
8 ) Herberman, R.B. and Holden, H.T. (1978) : Natural cell mediated immunity, Adv. Cancer Res.,27, 305‑377
9 ) Ikehara, S., Rajendra, N.P., Fernandes, G., Hansen, C.T. and Good, R.A. (1984): Functional T

cells in athymic nude mice, Proc. Natl. Acad. Sci., 81, 886‑888
10) June, C.H., Contreras, C.E., Perrin, L.H., Lambert, P.H. and Meischer, K.A. (1979) : Circulating

and tissue bound immune complex formation in murine malaria, J. Immunol., 122,2154‑2161
11) Kuvin, S.F., Tobie, J.E., Evans, C.B., Coatnex, G.R., and Contacos, P.G. (1962): Antibody
production in human malaria as determined by the fluorescent antibody technique, Science,
135, 1130‑ll31

12) Langhorne, J., Rollwagen, F.M. and Finerty, J.F. (1983): Induction of T cell activity inathymic (nu/nu) mice infected with Tr)panosoma rhodesiense. Cell. Immunol., 81, 180‑186
13) Lelchuk, R. and Playfair, J.H. (1980) : Two distinct types of non‑specific immunosuppression
immurine malaria, Clin. Exp. Immunol., 42, 428‑435
14) Loor, F. and Kindred, B. (1973): Differentiation of T‑cell precursors in nude mice demonstrat‑

ed by immunofluorescence of T‑cell membrane markers, J. Exp. Med., 138, 1044‑l055
15) Ojo‑Amaize, E.A., Salimonu, L.S., Williams, A.1.0., Akinwolere, O.A.O., Shabo, R., Alm, G.U.
and Wigzell, H. (1981) : Positive correlation between degree of parasitaemia, interferon titres,
and natural killer cell activity in Plasmodium falciparum‑infected children, J. Immunol, 127,2296‑2300
16) Ojo‑Amaize, E.A., Vilcer, J., Cochrane, A.H. and Nussenzweig, R.S. (1984): Plasmodium
berghei sporozoites are mitogenic for murine T cells, induce interferon, and activate Natural
Killer Cells, J. Immunol., 133, 1005‑1009

17) Rest, J.R. and Wright, D.H. (1979): Electronmicroscopy of cerebral malaria in golden ham‑sters (mesocrecetus auratus) infected with Plasmodium berghei. J. Pathol., 127, 115‑120

18) Smith, K.A. (1984): Lymphokine regulation of T cell and B cell function, Fundamental
Immunology, (Edited by W.E.Paul. Raven Press, New York) , 559‑576
19) Waki, S. and Suzuki, M. (1977): A stud of malaria immunobiology using nude mice.
Proceedings of the Second Interriational Workshop on Nude Mice, page 3720) Weidauz, W.P. (1982): Malaria and alterations in immune reactivity, Br. Med. Bull., 38, 167‑
17221) Wright, D.H. (1968): The effect of neonatal thymectomy on the survival of golden hamsters
infected with Plasmodium berghei. Br. J. Exp. Med., 49, 379‑384
22) Wright, D.H., Masembe, R.M. and Bazira, E.R. (1971): The effect of antithymocyte serum on
golden hamsters and rats infected with Plasmodium berghei. Br. J. Exp. Pathol., 52, 465‑477
23) Yonemasu, K., and Stroud, M. (1971): Clq. Rapid purification method for preparation ofmonospecific antisera and for biochemical studies, J. Immunol., 106, 304‑313
24) Zukerman, A. (1977): Current status of the immunology of bolld and tissue protozoa; II.
Plamsmodium (A Review), Exp. Parasitol., 42, 374‑446

237

PZαs吻04勉吻66響h初および夕081げi感染BALB／cマウスの生存率と免疫学的パラメータの解析

Maung

Maung

Oo1・池原井上進2・中村

秀治1・濱島敬夫2・

義博1

・PZαs窺04伽郷加㎎h6ぎNK65を，BALB／cならびにBALB／cnu／nuマウスに感染させて寿命を比較すると，胸腺のないnu／nuマウスの方が長生きした。しかしながらP伽解046％吻δ2怨h417Xの感染実験では，寿命に差はなかった。寿命の差は，血中のparasite数によるのではなくて，hostのIL−2の産生能ならびにキラー丁細胞の誘導能の差によることが判明した。

さらに寿命は，抗マラリア抗体価とも血中の免疫複合体値とも相関しなかった。感染後いずれのマウスも，丁細胞機能は一般に低下したが，NK細胞活性は上昇した。

京都大学医学部病理学教室

関西医科大学第1病理学教室

日熱医会誌．，第18巻

第3号

239

1990年，239−245頁

症例報告

マラリア患者の血液所見，特に貧血について
海老沢 功1・小原博2・田辺 清勝3
平成2年4月6日受付／平成2年5月29日受理

はじめに貧血は，マラリアに特徴的所見であるといわれている。しかしマラリア患者は輸入例を散発的にとした。赤血球：1μ1当たり男399万，女349万以
下，血色素：男12．9，女10．9g／4」以下，白血球：1μ」当たり3，900以下と9，600以上，血小板：1μ」当たり11万以下。

みるだけでなので，感染原虫別に貧血の程度を分

2．原虫数の算出：血液1μ1当たりのマラリア

析することは難しい。過去24年間に経験したマラ

原虫数は薄層標本を，1／50M，pH7．2−7．4のリリア患者の血液検査所見を検討し，特に熱帯熱マン酸緩衝液を用いて染色して検査した。白血球

ラリアの貧血とその対策について述べる。

100〜200コを数えるうちに現われるマラリア原

虫数Pを求め，1μ1当たりの白血球数wにp／

患者資料

100，あるいはp／200を掛けて求めた。感染原虫数が多いときは，赤血球1，000コに対する感染原虫

患者は1966年から1989年3月まで我々が直接，数から1μ」当たりの原虫数を算出した。マラリ

あるいは間接に関与したものである。同一患者がア原虫数は，10数コから2，000，000を越えること

再発，あるいは再燃のため複数回入院治療を受けがあるので，統計学的分析には原虫数の対数をたときは，別の症例として分析した。重複感染例

とって比較したが，表には実数で示した。

では，1つの原虫種が優勢で他の原虫種は少数し

3．統計学的処理：各項目についての統計学的処

か感染していないので，優勢種を感染原虫として

理，特に平均値と異常値を示すものの頻度の比較集計した。

検討は，脇本ら（1984）の統計学的解析用ソフト

患者総数419人のうち男395人，女24人で，21−40

歳の男性が約75％を占めていた。病名は熱帯熱マ
ラリア170，主日熱マラリア220，卵形マラリア

23，四日熱マラリア6であった。
熱帯熱マラリア患者のなかには，意識障害，

ウェアを用いて行った。

結果

各検査項目について，平均値，異常値を示すもDIC，腎不全，血色素尿，肺水腫，強度の黄疸などのの割合，それらの感染原虫種による差の検定結を合併した瀕死の症例が24人あり，そのうち14人

果（危険率1％），および異常値の最高あるいは最が死亡した。その他のマラリアでは，重症と判定

低値を表1に示した。各検査項目については，累されたものはなかった。

積百分率をもってその分布を図示した。以下各項目について説明する。

臨床検査と感染原虫数の算出
1．血液検査異常値の基準：下記の数字を異常値
京浜急行川崎診療所
埼玉医科大学医動物学教室
鹿児島大学医学部医動物学教室

1．感染原虫の種類と最大感染原虫数（／μ」）

マラリアで最も大切なのは，血液内原虫数である。原虫数は，通常治療前に最高値を示すが，と240

Table1Comparison of parasite
OVale malaria

IllneSS

falcipartm

statisticalparameters

and

ViVaX

malariamalaria

max．or％ab一

ロ

count

minim．no㎜．

函1×10318．22，138

rbc2×106

3．50

0．98

Hb39／d1

11．0

3．2

wbc4×103

5．98

mean

13．8

69

3．81

1．91

74

12．4

5．8

16．2

25

55．8

76

pltlt5×103

1，pc＝parasite
The

In

the

unit

the

for

Thepercent
The

85

78

count，2，rbc＝red blood

column ofminimum

and

pltlt

is

max，or minim．，thevalues，andtheofabnormalvalues

sign≒indicatesnocomponents

OValemalarianguresfalciparum，vivax andcomparison

mean

of

forwbc％ofofabnormalvaluesPf＞Pv＞Po

63

4．12

3．23

28

Pf〈Pv〈PoPf≒Pv＞Po

62

13．6

11．4

41

Pf＜Pv＜Po

Pf≒Pv≒Po

8，3

40

Pf≒Pv≒Po

Pf≒Pv≒Po

Pf≒Pv

Pf≒Pv

21．3

17

4．83

2．8

359

81

143

perμ」，and thatwbc are bothincludesbothcomparison

group

196

for Hb is

33

blood

cells，5，pltlt＝platelets、

g／d ．

figures for pc are the maximum values，the figures for

for

of

each

2．4

cells，3，Hb＝hemoglobin，4，wbcニwhite
nt皿1ber

in

0．35

2．3

226

pc，rbc，wbc

cell

max．or％ab−
max．or％ab−
meanminim．norm．
minim．norm．

3．24

2．2

blood

maximum

andabno㎜allyhighand

significant difference between thetworbc，Hb and platelets

areminim㎜1values．

low

valuestogether．

groups．

きに治療開始1−2日後に最高値を示すことがある。血液1μ」中原虫数の平均値は，熱帯
熱マラリア18，200，三日熱マラリア3，200，卵

られた。

90

Po8

80

J

70

熱マラリアにおける原虫数の多いことが注目

60

10，000以上の値を示したものは，熱帯熱マ

Pv●

J

れ2，138，000，138，000および3，800で，熱帯

に値する。

ノ
，

︐●

アで1μ」当たり15，12，10。最大値はそれぞ

ρ●一

」
J

●

∂
∂

ノ

Pf

最小値は熱帯熱，三日熱および卵形マラリ

％

100

●

形マラリア350で，統計学的に有意な差が認め

ノ

4

●

4 ，，
50 」
∂

●

●

ラリア61％，三日熱マラリア24％，卵形マラ

40

リア0％であった。100，000を越えるものは，

30

熱帯熱マラリアが25％に対して，三日熱マラ

20

，
，
●

●

リアでは1％にしか見られなかった。以上の比率は，統計学的に有意である。卵形マラリ

2．7

なかった。

当たりの最大原虫数の分布を示す。熱帯熱マ

ノ

10

アでは，20人中5，000を越えるものは1人も

図1には，3種マラリアにおける血液1μ1

ノ●Figure4

3 3．7
4．7 5 5．7 6＞6．3
lo9 parasite count1μ2

l Cumulative percentage of theparasite count in malaria．

highest

ラリアでは，原虫数が少ないものから100万以

Parasite density

上（対数値で6）に広く分布していることがunits． Log3，4，5and6correspond

わかる。四日熱マラリアは，4人しか定量的

is

1，000，10，000，100，000

μ」．Pf，Pv

andPo

expressed in log
and

are

to

1，000，000

perabbreviationsに検査されていない。最高値は6，760，最小値」P伽ηzo4∫z4窺ノa∫6ゆαn4ηz，P、z雇∂砿andは500であった。

o伽」ε．

P，

of

241

2．最小赤血球数

月以内に正常値に戻った。

（／μ」）

3．最低血色素量

マラリア原虫増殖の直接の影響を受けるのは，（g／dJ）

赤血球の減少である。入院直後，あるいは治療開

平均値は熱帯熱く三日熱〈卵形マラリアの順に始前の赤血球数は，血液濃縮のためかえって増加

多くなり，各群の間にはいずれも有意の差があっしており，治療開始数日後の方が低値を示すことた。熱帯熱マラリア患者の最低値は3．2で，この患が多い。何回かの検査の最小値を，その患者の代者は赤血球も98万で最低値を示した。治療前マラ表値とした。治療前1回しか検査していないもの

リア原虫は最高728，500に達し，クロロキン療法て減少しつつあったが，突然血圧降下をきたしては，それを用いた。

赤血球数の平均値は，熱帯熱く三日熱く卵形マ死亡した（海老沢，1981）。

ラリアの順に多くなり，その差は有意であった。

血色素量が9．9以下の低値を示したもの割合は，熱帯熱マラリアの最小値は98万，熱帯熱マラリア

熱帯熱＞三日熱＞卵形と四日熱マラリアの順に多における貧血の強さが明らかである。299万以下のく，その差は有意である。図2Bには熱帯熱，三

強い貧血を示すものの割合も，熱帯熱の方が三日日熱および卵形マラリアの最低血色素量の分布を熱より多く，卵形と四日熱マラリアでは0であっ示す。赤血球の分布に類似した曲線を示している。

た。瀕死の重症と分類した熱帯熱マラリア患者は，四日熱マラリアでは，最小と最大値が8．3と14．2

で，三日熱マラリアと近似した値であった。瀕死

赤血球数が299万以下になったものに多かった。

図2Aに，3群の最小赤血球数の分布を示す。

の重症例になる頻度も，血色素が10以下に下がる

低値を示すものが，熱帯熱マラリアに多いことがものに多い。

明らかである。四日熱マラリアは，卵形マラリア

4．マラリア患者に対する輸血の問題
熱帯熱マラリアでは，赤血球が299万以下になっとほぼ同様の値を示した。

なお赤血球，および次に述べる血色素いずれもマラリア原虫消失後は，貧血の程度により1−3たものは27％・血色素が10以下に下ったものは31％あった。輸血実施の目安は，全身状態と肝炎

％

％

1

A

〇〇

go

∂

go

80

∂
∂
●

80

ロ
．3

70

印

⑩

釦⑳

肖

，ノ

ロ

50

ノ

20

1！
ノノ！

RB・C・，miIIio【／μ8

．

60

30

P・

ク

1．0 1．5 2．0 2．5 3．0 3．5 4．0 4．5

ρ
9

ヨ

佃

ロ

P》

●

70

7σ
の
4
4」
の
4・・

60

10

o

B

10

研》 P。
！ノ
ノノ
ノ 」

●
5．0

5，5

3

2．04，06．08．010．012．014．016．O

Hb，9／d2

Figure2Cumulative percentage of the lowest red blood（A）and hemoglobin concentrations（B）．
See Fig．1for abbreviations Pf，Pv and Po．

cell

comts

242

Table2Falciparum

Case AgeNo．

minim．

max．

＆

rbc

Hb

pc

pltltslost

sex

106／μJ

g／dJ

perμ」

perμ」

days卓

728，500

16，00011

21，55022，0008

cereb．，ren．f．，lng ed．

1

26F

2

45M

minim．

O．85

1．60

3 23M
4 41M
5 29M

39M

7

24

See

5．4

F

footnote

minim．

main complications

DIC，ren．f．，shock，death

2．09

6．1

829，91029，0006

cereb．，conv．，ren．f．，sev．jndc．

2．31

6．9

727，100

33，0008

cereb．，NANB

44，50040，000

8

None

6．7

2．60

8．7

2．63

8 35M
9 52M
卓The

3．2

2．46

6

16

12，400 34，000

8．4

17

Anemia，edem inhepatitis

legs

DIC，cereb．，parap1．，dementia

2．71

8．0

1，536，000

28，0005

DIC，cereb．，ren．f．，sev．jndc．

2．85

8．8

3，520

32，0006

DIC，cereb．，ren．f．，sev．jndc．，deathtolost days

DIC＝disseminatedlungmalaria patients treated with blood transfusion

Table

l

indicate

for abreviations

thenumberofrbc，Hb，pc

anddays passed before

pltlts．

treatment

intravascular coagulation，ren．f．＝renal

wasstartedafter

failure，cereb．＝cerebral

edema，conv．＝convulsion，parapL＝paraplegia，sev．jndc，＝severe

onset

of

illness．

malaria，1ng

ed＝jaundice．

合併の危険を考慮して，決定しなければならない。

卵形と四日熱マラリア患者は合計8人で，最低検討した症例のうち9例が輸血をうけている（表は64，000，最高260，000であった。血小板数はマラ2）。赤血球数はすべて285万以下，血色素は8．8以

リア原虫が流血中より消失すると，1週間前後で下であった。瀕死の重症と判定されたものは，7

速やかに正常値にもどった。熱帯熱，三日熱およ人あった。発病から治療開始までの日数，すなわ

び卵形マラリアにおける最小血小板数の累積百分

ち損失日数（表2脚注参照）は5−17日で，8例

率は，次の報告で示す。

が熱帯熱マラリア治療開始に安全な5日以内を過6．白血球数（／μ ）ぎてから治療を受けている。輸血を受けたが2例

白血球数の増減は，マラリアでは一定していな死亡，1例が輸血後かなり重症なNANB肝炎にい。診断確定時，あるいは治療開始までの白血球罹患した。

数の最高値をとって検討した。3種マラリアの白死亡した症例1は，マラリアの治療にはほぼ成

血球数の平均値に有意な差はなかったが，異常値功したが，輸血の時期が遅過ぎた（海老沢，を示すものの割合（9，600以上と3，900以下）は熱

1981）。症例9はマラリア治療開始の遅れ，DICな

帯熱，三日熱，卵形マラリアの間で有意な差があっ

どが重なって死亡した。

た。熱帯熱マラリアでは，増加するものと減少す

5．最小血小板数（／μ」）

るものの比は1：2，三日熱マラリアでは1：5，

血小板の減少は，マラリアでは頻回に見られる。

卵形マラリアでは異常者8人が全部減少を示した。

血小板数が11万以下になったものは，熱帯熱と三最小値は，熱帯熱マラリア患者の2，200，最大値は日熱マラリア両群とも約80％であるが，3万以下

三日熱マラリア患者の21，300であった。重症熱帯になったのは前者が29％，後者が8％で統計学的

熱マラリアでは，白血球増加例が多かった。

に有意であった。最低値は前者が6，000，後者が16，000であった。血ノ」板数の平均値にも，両群の間に有意の差はなかった。

243

考

察

マラリア患者の血液内原虫の多寡は，感染原虫う。検討した9例の輸血例のなかには，それが不必要であったと考えられるものもあった。輸血後
肝炎合併の危険を考え，早期診断と即効性キニーの赤血球の日齢に対する選択性に左右されるが，ネの点滴静注により，速やかにマラリア原虫を駆熱帯熱マラリア原虫は，赤血球の日齢を問わない

除することに先ず力をいれるべきであろう。

のが特徴である。

マラリアでは白血球は減少することが指摘されマラリア原虫致の統計学的分析で注目されるのており（Perrinθ∫磁，1982），三日熱マラリア患

は熱帯熱マラリアで，最高2，138，000の値を示し

者で一時的に骨髄低形成による汎血球減少を併発て死亡した例を見ると，本症の危険さを痛盛させした症例も報告されている（山川ら，1989）。我々られる。しかし熱帯熱マラリアでも原虫数が10〜のマラリア患者全体では，白血球減少を示したも50の少ない例があったことも，記録しておく必要のは16％であった。白血球減少の頻度は三日熱とがあろう。瀕死の重症と判定されたものや，極端熱帯熱マラリアで同様であり，卵形マラリアだけな貧血例はすべて熱帯熱マラリアに限定されたのが40％の高率を示した。

で，治療上は本症を最も重視すべきである。

白血球増加は，熱帯熱と三日熱マラリアいずれ

感染赤血球の崩壊に直接影響される赤血球数と，にも見られた。白血球増加と予後に関しては死亡

血色素量は同じ順序で減少したが，血小板の減少例を含む瀕死の重症例で42％，それ以外のものでは感染原虫の種類に関係なかった。しかし，そのは2．6％であり有意な差が見られ，Tani8∫認数が異常に少なかったものは，熱帯熱マラリアに（1984）の報告を確認した。しかし瀕死の重症例多かったことは，本症でDICが起きやすいこととでも，白血球減少例が2例あったことも記載に値関連があろう。

しよう。

初診時は脱水のため，血液は濃縮している。さマラリア患者血液には異型リンパ球が出現する

らに血液内マラリア原虫の分布は不平等で（海老が（Kueh沢，1974），静脈血より毛細血管内により多くのマ

いo

and

Yeo，1982），予後には関係がな

ラリア原虫が潜在する。抗マラリア薬で原虫が死滅するとき，感染赤血球も破壊されるので，抹梢

結血液所見から推定するより多くの赤血球が失われ語る。マラリア患者の貧血に関して，感染赤血球の

1）マラリア患者の最大原虫数は，熱帯熱マラリ

崩壊の他に，免疫学的機序の関与と，脾網内系のア＞三日熱マラリア＞卵形マラリアの順に多い。

機能昂進による非感染赤血球の破壊が推定されて熱帯熱マラリアでは最高2，138，000に達した。

いる（Perrin8∫磁，1982）一因であろう。

2）赤血球数と血色素量の減少の度合は，これと小児の熱帯熱マラリアにおける貧血（Abdalla

同じ順序で大きい。両者の最低値は1μ」当たり98

窃磁，1980）に関しては，治療開始後1週間前後

万と3．2であった。

で最低値を示す急性初感染型，はじめから強い貧3）マラリア患者の貧血に対する輸血の時期につ血を示す慢性型とその中間型が記されている。

いては，赤血球が250万，血色素が9近くになった

我々の症例は大部分成人で，ほとんど第1の初感ら考慮すべきであろう。

染型に属していた。入院・治療後マラリア原虫が4）血小板は感染原虫の種類に関係なく減少する

消失する頃には，初診時よりも50〜100万くらい赤が，極端に減少するものは熱帯熱マラリアに多血球が減少することもある。

かった。

マラリア患者の貧血に対する輸血の時期につい

5）白血球数の平均値は，上記3種マラリアで差て定説はないが，赤血球数が250万前後になったがない。白血球減少は全体の16％に認められ，増ら，全身状態を考慮して輸血を考慮すべきであろ加例もあった。

244

文

献

1）Abdalla，S．，Weatheral1，D．J．，・Wickermascinghe，S．N．and

falciparum

Hughes，M．（1980）：The

anemiaofmalaria，Brit．」．HaematoL，46，171−183

2）海老沢 功（1974）：マラリアの病理．臨床病理，22，391−395
3）海老沢 功（1981）：Case study IV．高熱，貧血，腎不全，内科，47，834−836
4）Kueh，Y．K，and Yeo，KL（1982）：耳aematological alterations in acute malaria，Scand．J．
Haemato1．，29，147−152
5）Perrin，L．H．，Mackey，J．and Miescher，P．A．（1982）：The

haematology ofmalaria

in man，Seminar Haematol．，19，70−82
6）Tani，H．，Fujii，H．，Asano，S．and Miwa，S．（1984）： Imported malaria in Japan：
Haematological aspects，Acta Haematol．Japonica，47，903−908
7）脇本和昌，垂水共之，田中 豊（1984）：パソコン統計解析ハンドブック，1．基礎統計編，共立出

版，東京
8）山川 弘，清滝昌哉，服部 豊，小花光夫，松岡康夫，入交昭一郎（1989）：骨髄低形成による汎血球減少を併発した三日熱マラリアの一例，感染症誌．，63，1043−1046

245

HEMATOLOGICAL FlNDINGS IN MALARIA WITH A NOTE ON BLOOD
TRANSFUSION IN SEVERELY ANEMIC PATIENTSISAO EBISAWA*, HIROSHI OHARA AND KIYOKATSU TANABE
Received April 6 1990/Accepted May 29 1990

Parasite count and hematological studies were made on 170 falciparum, 220 vivax and 23
ovale malaria patients to see whether hematological parameters differ in malaria infected bythree different species of malaria parasites, P. falciparum (P.f.), P. vivax (P.v.) and P. ovale(P.o.) The mean and percentage of abnormal values of each parameter were analyzed
statistically. The parasite count was significantly large in the prder of P.f. > p.v.>p.o. The

maximum parasite count of P.f. was 2,138,000 per pl of blood. The mean parasite count forthe 3 species was 18,200, 3,240 and 350 per pl of blood. The red blood cells (rbc) andhemoglobin (Hb) decreased significantly in the same order and the minium rbc count was O.
98 milion per pl and the lowest Hb concentration was 3.2 g/dl in falciparum malaria. The
mean r.b.c. count in P.f., P.v. and P.o. malaria was 3.50, 3.81, and 4.12 million per pl and themean Hb concentration was ll.O, 12.4 and 13.6 g/dl, respectively. The changes, either
increase or decrease, in white blood cells and the decrease of platelets were not significantly

different in P.f., P.v. and P.o. malaria. Nine cases of falciparum malaria were given bloodtransfusion, and its lifesaving merits in severely anemic patients and demerits of NANB
hepatitis were discussed. Early treatment, within 5 days of the onset of illness, with rapidly

acting antimalarial drug was emphasized.

2

3

Keihin Kyuukou Kawasaki Clinic
Department of Medical Zoology, Saitama Medical College
Department of Parasitology, Faculty of Medicine Kagoshima University

日熱医会誌．，第18巻第3号

1990年，247−253頁

、247

症例報告

マラリア患者の血液生化学的所見
海老沢 功1・小原博2・田辺 清勝3
平成2年4月6日受付／平成2年5月29日受理の通りである。LDH：500u／！以上，総ビリルビ

はじめにと急性腎不全，DIC，強度の黄疸，脳症など重い合

ン：L4mg／4」以上，尿素窒素BUN：21mg／
dJ以上，クレアチニン：1．6mg／dJ以上，
SGPT：36u／1以上，SGOT：41u／1以上，血清併症を起こす。前報（海老沢ら，1990）に引き続

総コレステロール：129mg／dJ以下，血清総タン

きマラリア患者の血液生化学的所見を分析，特にパク6．3g／d！以下。

マラリアでは貧血のほか治療開始時期が遅れる

熱帯熱マラリアにおける極端な異常所見を報告す
る。

検査所見
患者資料，検査項目とその異常値の基準
患者資料は前と同じ，各検査項目の異常値は次Table111nessl

Biochemicalparameters

falciparum malaria

statistical

of

blood

vivax

malaria

前報と同じ要領で各検査項目の平均値と異常値を示すものの割合，および感染原虫種による差の検定の結果を表1に示す。さらに異常値の最高，

infalciparum，vivax

andovale malaria

max．or％ab−
max．or％ab−
max．or％ab−
mean
mean
min㎞．norm．
minim，norm．
minim，norm，parameters

mean

．LDH

1，168

15，292

68

TBil

6．2

42．3

59

1．3

BUN

36．5

204

33

Crt

2．4

16．9

SGPT

57．5

SGOT

ovale

malaria

comparison comparisonof mean
of％of
of

each

9τoup

abnormalvalues

35

425

550

22

Pf＞Pv≒Po

Pf＞Pv

6．4

37

1．1

1．4

17

Pf＞Pv≒Po

Pf≒Pv

15．1

26

9

13，4

23

8

Pf〉Pv≒Po

Pf＞PvニPo

30

1．1

1．9

1

1．0

1．1

O

Pf＞Pv≒Po

Pf＞Pv

455

48

29．6

260

16

22．3

58

22

Pf＞Pv≒Po

Pf〉Pv

70．3

653

44

24．9

180

7

23．0

58

11

Pf＞Pv≒Po

Pf＞Pv

Cholesterol

119

50

68

119

51

65

109

79

78

Pf≒Pv≒Po

Pf≒Pv≒Po

Tp

6．1

3．2

53

6．7

5．2

31

6．8

7

Pf＜Pv≒Po

Pf＞Pv≒Po

thecolumn

See

text

shown

for mitsforindicates

no

of

each

5，142

biochemical parameters．In

cholesterol and total
significant

539

difference

protein．The

between

京浜急行川崎診療所
埼玉医科大学医動物学教室
鹿児島大学医学部医動物学教室

the

two

maximumgroups，

6．1

ofmaximumorminimum，minimum

valuesarevalues are sho㎜for other biochemical parameters．≒

248

1

％oo

％

1

oo

，■一●一

go

鳳両

ク

ノノー

ノ●

所

go

80

曜

70

P》・

●

80
70

4■

，

●

60

m 4

」

聞

4

㈹

⑩

」

60

鋤
20

1

卸

A

20

Pf

・

B

虜

10

10

1．02．04．06．010．0⑳．040〉40
Sorum

to糖I

Figure l Cumulative percentage of

and

the

LDH（B）concentrations

Pf，Pv，Po

represento槻」ε．Pv十Po indicate

mixed

纏験・｝

砂！

bilirubin，mg／d2

highestin

serum

malariatotalbilirubin（A）

patients，

P伽吻04伽￠血Zδφσn御3，P加ひ砿and・R

thatofpatients

data

both

groupsofaretogether．

あるいは最低値も表示した。各検査項目の分布は，ア患者のビリルビン量が，広い範囲にわたってい

感染原虫ごとに累積百分率をもって図に示した。

るのが特徴的である（図1A）。しかし異常値を示

以下各項目について説明する。

したものの割合は，熱帯熱と三日熱マラリアで有

1．最高LDH値（u／」）

意の差はなかった。ビリルビン最高値が42．3に達

赤血球中に多量に含まれるLDHは，赤血球の崩壊により血清中に多量に放出される。LDHのした患者は，生前マラリアを全然考慮に入れず，

急性肝・腎不全として全血交換などの治療を受け平均値および異常値を示すものの割合は，熱帯熱

11病日に死亡した。死後剖検を断られ，生検針にの方が三日熱マラリアより高いが，三日熱，卵形

よる肝の屍検により熱帯熱マラリアと診断されたおよび四日熱マラリア間には差がなかった（図1

例である（表2，症例2）。なお総ビリルビンが異B）。LDH最高値が15，290に達した熱帯熱マラリ

常高値を示した例では，直接および間接ビリルビ

ア患者は，11病日に治療を開始された例で，原虫ンも上昇していた。

数は824，100に達し，腎不全を合併，腹膜透析を

3．最高尿素窒素BUN濃度（mg／dJ）

行ったが死亡した（表2，症例1）。

熱帯熱マラリアでは，腎不全は予後に関係する

2．最高血清総ビリルビン濃度（mg／dJ）

重要な合併症である。BUNの平均値および異常

血清ビリルビンの測定は全員に行われず，熱帯値を示すものの割合は，熱帯熱の方が三日熱マラ

熱マラリアでは肉眼的に黄疸が認められたのでそリアより多かったが，三日熱と卵形マラリアではの検査を行った例があり，症例の選択に偏りが差がなかった（図2A）。

あったことは否めない。

BUNが最高204に達した例は，LDHも最高値

血清ビリルビンの平均値は熱帯熱の方が三日熱を示した前述の熱帯熱マラリアの例である。四日

マラリアより高かったが，三日熱，卵形，および熱マラリアで4人中1人33の値を示したものが四日熱マラリアでは差がなかった。熱帯熱マラリあった。本例は36年問四日熱マラリア原虫に感染

249

Table2

Synopsisoffalciparum

malariapatients

withabnormally

high

or

low

biochemicalparametersage，sex

1
27M

2
43M

3
45M

prognosis

died

died

cured

24，100

？

11

rbc2

39M

5
37M

40F

7
24M

cured

died

cured

cured

215，500

259，900

253，700

655，800

8，000

oo

8

7

9

6

8

2．22

2．89

1．60

3．18

4．30

2．65

3．20

Hb3

6．6

8．5

5．4

10．3

7．6

11．1

wbc4

11，600

5，500

5，000

4，700

10，50012，0005，700

LDH15，290

1，750

900

956

1，568

1，130

780

5．7

42．3

0．8

0．3

4．3

20．3

0．2

0．2

BUN

204

177

201

21

Crt

12．8

6．7

16．2

SGPT
SGOT

138

118

491

Tp

6．1

Cholesterol

145

Case

pc1

lost

days

TBil
dir㏄t

Bi1

blood

cells． The

units

for

6

6．5

56

14

1．2

2．4

1．1

63

455

117

11

270

53

222

151

15

4．7

6．4

4．6

191

59

Abbreviations： 1． pc＝parasite
white

4

count，2．rbcニred
pc，rbc

blood

163

653

3．2

333

62

50

cells，3．Hbニhemoglobin，4．wbc＝and wbc are number perμ」．The

unit for Hb isg／dJ．oQ＝untreated．

していた例で，クレアチニンも2．1に上昇，腎結石

均値および異常値を示すものの割合は，いずれもも合併した症例（Tsuchida初磁，1982）であ

熱帯熱の方が三日熱マラリアよりも高い値を示しる。

た。最高値はそれぞれ455と260で肝炎患者に見ら4．最高クレアチニン濃度（mg／dJ）

れるような高値ではなかった（図3A）。SGPTが平均値および異常値を示すものの割合は，いず

最高値を示した熱帯熱マラリア患者は腎機能障害

れも熱帯熱の方が三日熱マラリアより多かった。

が起きず，順調な経過をとって治癒した（表2，

しかし三日熱と卵形マラリアの間には，有意差は症例4）。

なかった。熱帯熱マラリアにおけるクレアチニン

6．最高SGOT（u／1）の分布は，BUNと類似した分布を示している（図2B）。

SGOTの平均値および異常値を示すものの割合は，いずれも熱帯熱の方が三日熱マラリアより

クレアチニンが16．2で2番目に高かった例は，も高い。最高値はそれぞれ653と180である（図3

BUNも201で2番目に高かった。本例の原虫数はB）。SGOTが最高の653を示した症例は，マラリ

215，500に達し，腹膜透析を12回繰りかえして救アの治療を受けず9病日に死亡，原虫数は命できた（三木ら，1979）（表2，症例3）。

253，700に達した。解剖で心筋毛細血管内に成熟

5．最高SGPT（u／」）マラリア原虫が感染した赤血球が，充満していた

マラリア患者にはしばしば黄疸が見られるので，肝機能障害の有無は注目されている。SGPTの平（海老沢，谷，1980）（表2，症例5）。

7．最低血清タンパク濃度（g／dJ）

250
％oo

1

％
100

ノ
！P》＋P。
●

80
70

病

肖

●﹂ ●﹂

90

」

70

1

」
●﹂ ●

50

30

●

⑳
10

10

〜1・
〜勾

B

30

A

20

〜1．0 〜2．0 〜8．0 〉12．0〜1．5 〜4．0 〜12．O

〜120
⑳0
〜60
〜200
BUN，mg／d2

Figure2Cumulative

percentage

Croatinine，mg／d2

ofthe highest（B）concentrations

in

See

Fig．1forfootnotetomalaria

BUN（A）andcreatinine

patients、

abbreviations

％0
0
0 9
0 8

and

庚

Pv十Po．

陶所

1

Pf

ノ7

％

一

プ

ィ所

60
50
⑳
20

B

30

A

10

90 0
8 m 60 50 ㈹ 30 20 10

︐艶；ノ7

垢00

％

1

㈹

㈹

1

1

●

60

屠

SGPT，u／2

Figure3Cumulative
See〜

SGOT，u／percentage（B）activities

㎜噸

欄

棚伽

㎜

欄粥

期噸

団

ガ・

欄粥

欄

in

footnote toofmalariathehighest

SGPT（A）andpatients．

Fig．1forabbreviations

Pf，Pv

and

Po．

SGOT

251

1

％oo

1

十

恥

ノ為

阿︐︐

％oo

％0090807060印⑳302010

％

1

go

go

80

80
Pf十P》十Po

70

A

ノ

60

60

50

50

⑳

㈹

30

30

B

20

ρf十函十Po

70

C

20
10

10
0

0

9

伊

翫κ

乳幡
O e
航砿

﹄m
5門
O O
生S

13610箆≧鐙
Thr6mb㏄yヒ●，X104／μ2

801⑳1602002⑳〉2鵯
Chol●6torol，mg／d2

Figure4Cumulativepercentageofthelowest駝㎜protein（A）andchole3terol（B）concentrations

andthrombocyte

counts（C）in malaria

patients．

Seefootnote to Fig．1for abbreviations Pf and PV＋Po，Pf十Pv十Po
that data of3groups are mixed together as cholesterol andindicate

throlnbocyte count were independent of

infecting parasites．

平均値は熱帯熱の方が三日熱より低く，異常値

考を示すものの割合は，熱帯熱の方が三日熱マラリ

アよりも高い。三日熱と卵形マラリアの患者間には差が見られない（図4A）。

察

マラリアの主たる臨床病態は，マラリア原虫感
染赤血球の崩壊と，成熟した原虫感染赤血球によ3．2の最低値を示した熱帯熱マラリア患者はイる毛細血管の一時的閉塞で，これは特に熱帯熱マ

ンドネシアで感染した女性で，発病当初下痢が持ラリアに強く起こる。これらが重なってDICと強続，原虫数は655，800に達し意識不明になった（杉い血色素血症が起こる。腎糸球体血管も，成熟マ

山ら，1989年）。クロロキン，ファンシダールおよ

ラリア原虫感染赤血球により閉塞され，急性腎不びファンシメフの内服で全治したが，経過中全身全が起こる。毛細血管の閉塞は，この他に全身の浮腫と肺水腫を起こした（表2，症例6）。

臓器で起こる。

8．最低血清全コレステロール（mg／dJ）

以上の病態生理学的機序を，直接あるいは間接マラリアでは，一時的なコレステロールの低下に反映する検査所見LDH，総ビリルビン，尿素窒はよく見られる。しかし熱帯熱，三日熱および卵素，クレアチニン，SGPTとSGOTおよび血清形マラリアでは平均値も，異常低値を示すものの総タンパク量は，感染原虫数が多くなる熱帯熱マ

割合も差がなかった（図4B）。コレステロールがラリアの方が，三日熱や卵形マラリアより異常値

最低値50を示した熱帯熱マラリア患者は腎機能がを示した。これに反してコレステロールと，前報侵されず，順調な経過をとった（表2，症例7）。

で述べた血小板は感染原虫種に関係なく減少した。

ただし極端な異常値は，コレステロールや血小板の検査でも熱帯熱マラリア患者に多く見られた。

以上の生化学的検査所見を見て，マラリアのう252

ち最も危険なのは熱帯熱マラリアであり，生化学

績は，マラリア死亡例や回復期患者の肝生検所見的検査の中ではBUNとクレアチニンが予後をで肝組織の構築が障害されていないことによって占う上で，最も都合よい指標であると考える。腎裏づけられよう。

不全を起こした例では，キニーネの点滴静注によるマラリアの治療と同時に，腹膜あるいは血液透結析を行わねばならない。しかも患者の血液は，感語

染の危険がある病原体を多量に含んでいる。マラ1）赤血球の崩壊に直接ないし間接的に関係する

リア治療に経験あるものと，腎不全対策に慣れている医師達の共同が必要である。このような患者

生化学的検査項目LDH，総ビリルビン，尿素窒素，クレアチニン，SGPT，SGOTは，感染原虫

はまたDICを合併していることがあり，その対策数が多くなる熱帯熱マラリア患者の方が三日熱マも必要である。

ラリア患者より高い値を示したが，三日熱と卵形
マラリア患者の間には有意差はなかった。

SGPT，SGOTの増加に関しては血管内溶血と，血清ビリルビンの増加を起こしやすい疾患で

2）血清総タンパク量は，熱帯熱マラリア患者のあるから，肝機能障害の指標として容易に理解で方が三日熱マラリア患者より低い値を示したが，きよう。今回の調査では発病当初だけでなく，全三日熱と卵形マラリア患者の間には差がなかった。

経過中の最高値をその患者の代表値とした。その

3）コレステロール量は減少はしているが原虫種ため用いた薬剤，例えばファンシダール（サルファによる差は見られなかった。

ドキシンとピリメサミンの合剤）（Reisinger窃

4）熱帯熱マラリアの検査異常最高値はLDH

砿，1989），キニーネの点滴静注などの影響も考慮（15，290），総ビリルビン（42．3），BUNに入れるべきであろう。既存のアルコール性肝障（204），クレアチニン（16．9），SGPT（455），

害があったため，これらの値が高くでた症例も何

SGOT（653），異常最低値はコレステロール

人かあった。岩田ら（1982）が指摘したように，（50），総タンパク（3．2）が示すように，特に溶SGPT，SGOTいずれもウイルス性肝炎患者に見血と腎機能障害の強さが著明である。熱帯熱マラるような高い値は示さなかった。熱帯熱マラリア

リアでは，早期治療，特に重症患者では即効性静患者のSGPTとSGOTが，200を越えるものは

注用キニーネ使用の必要性を痛感する。

それぞれ3．7と7．3％しかいなかった。これらの成

文

1）海老沢

功，谷

献

荘吉（1980）：マラリアの病理所見，日本医事新報（カラーグラフ）．Nα2949，

11

月1日号

2）海老沢

功，小原 博，田辺清勝（1990）：マラリアにおける血液検査所見，特に貧血について，日熱医会誌．，18（3），239−245

3）岩田晃一郎，田辺清勝，鳴戸弘，清水純孝，海老沢功（1982）：マラリア感染患者の肝障害．肝臓，23，909−914
4）三木 亮，上野高次，唐沢英偉，海老沢 功，谷 荘吉，土田基弘（1979）：急性腎不全を合併せる
熱帯熱マラリアの一治験例・最新医学・34，1555−15625）Reisinger，E．C．，Hortsman，R．D．andDietrich，M．（1989）：Tolerance

combination

withsulfadoxine−pyrimethamine intheprophylaxis

ofofmenoquine

alone

and

in

malaria，Trans．Roy．Soc．

Trop．Med．Hyg．，83，474−477
6）杉山秀徳，田辺清勝，島田 馨（1989）：ファンシメフが奏効した重症熱帯熱マラリアの一例，第38回日本感染症学会東日本地方会総会発表，10月 新潟
7）Tsuchida，H．，Yamaguchi，K．，Yamamoto，S．and Ebisawa，1．（1982）：Quartan

ing

splenectomy36years

after

malaria

infection，Amer．J．Trop．Med．Hyg．，31，163−165

follow−

253

BIOCHEMICAL ABNORMALITIES IN MALARIAISAO EBISAWA , HIROSHI OHARA' AND KIYOKATSU TANABE
Received April 6 1990/Accepted May 29 1990

Biochemical parameters of blood were analyzed statistically in the same way as in thegroups of malaria patients mentioned in the accompanying paper. The parameters which
directly or indirectly reflect intravascular hemolysis, i.e., Iactic dehydrogenase (LDH) , total

bilirubin (TBiD , blood urea nitrogen (BUN) , creatinine (Crt) , serum alanine aminotransfer‑ase (SGPT) and serum asparate aminotransferase (SGOT) were elevated in malaria patients
infected by P. falciparum (P.f.) significantly more than in malaria patients infected by P.
vivax CP.v.) or P. ovale (P.o.). The differences in the biochemical parameters of the last twogroups were not significant. The total proteih (Tp) Ievels also showed the same order ofdecrease. Cholesterol (ChoD was decreased equally in malaria patients irrespective of theinfecting parasite species. The maximum values of LDH (15,290 u/1), TBil (42.3 mg/dl),
BUN (204 mg/dl) , Creat (16.9 mg/dl) , SGPT (455 u/1) , and SGOT (653 u/1) and the lowest
figures of Chol (50 mg/dl) and Tp (3.2 g/dl) in Pf malaria indicate the seriousness of thisinfection. The same parameters in vivax malaria are LDH (5,140), TBil (6.4), BUN (26),Creat (1.9), SGPT (260), SGOT (180), Chol (51) and Tp (5.2). The early treatment of
falciparum malaria, within 5 days of the onset of illness, is emphasized to avoid serious
complications.

2
3

Keihin Kyuukou Kawasaki Clinic
Department of Medical Zoology, Saitama Medical College
Department of Parasitology, Faculty of Medicine Kagoshima University

Japan. J. Trop. Med. Hyg., Vol. 18 No. 3 1990, pp. 255‑263

255

Note

THE ORTHODOX MODEL OF HEALTH CARE DELIVERYSERVICES AND THE FATE OF NIGERIA'S 64 MILLIONRURAL DWELLERS= A SEARCH FOR A VIABLE

HEALTH SUPERMARKET
FESTUS IGHAROSA AGBONLAHOR
Received May 14 1990/Accepted July 12 1990

Abstracts This paper is purely theoretical in orientation and seeks to make the pointthat the archtype capitalistic orthodox model of health care delivery services currently
operated in Nigeria, constitutes the greatest clog to human development in the rural area.
In order to bring the discussion to bear, we examined the provisions made for health in thethree national development plan and established how the perpetuation of this model limits
oppotunities in the rural area. The paper winds up making a number of suggestions on
how the health status of these 64 million Nigerians can be improved.

INTRODUCTION
The potential for development is inherent in all human societies, what differ is thehistorically determined pool of strategies and tools which the members are able to mobilize
in certain dimensions (Anikpo, 1984) .

It will be proper to begin this paper by operationalizing the key variables in oursomewhat rude title. Such explanations are however rendered within the context of thispaper.
Orthodox medicine refers to the present model of health care delivery services with allits curative emphasis. We then arrived at the figure 64 million, by finding 80% of our present

estimated population size of 80 million.

PREAMBLE
Not many scholars will dispute the fac; t that the ideological leaning of Nigeria takes afterthat of her capitalist oriented colonial master‑Britain. Capitalism like any other political
ideology favours asymetrical allocation of resources between the rural and urban areas; withan unambiguous tilt towards the latter (Anikpo, 1984) .
The implication of this for economic planning, is that in situations where ‑as in Nigeria‑

few urban centres exist and where the vast majority live in the rural areas, the gains of
economic planning will continue to be elusive. A focus on the health sector aforded theDepartment of Sociology, Bendel State Umversity D M B 14 Ekpoma Nlgena

256

demonstration of this. On the whole, the paper bvilt on the assumption that a healthy nationis contigent on healthy citizenry.
It therefore, Iimits itself to showing how our health planners limit the oppotunities in the'rural areas by perpetuating the orthodox model which encourages uneven allocation of healthresources. Therein lies the thrust of this paper. The paper winds up by looking at how thehealth status of the Nigerian rural dweller can be substantially improved.

THE DEFINITION OF HEALTH
The World Health Organization (1964) defined health as "... a state of domplete physical,

mental and social well being, not merely the absence of disease or mfirmity" Commentmg
on this definition, Lewis (1953) argued that "... in practrce rt rs the presence of disease thatcan be recognised, not the presence of health". Continuing, he noted that there are no positive

indications of health that can be relied upon and on the basis of this, declared healthy,
everyone who is free from any evidence of disease or infirmity.
Nigeria is a former colony of Britain and like her colonial master, operates the orthodox
model of health care delivery services, with all its curative emphasis.
The unfortunate thing about this model is that it has led many third world nations who
were former colonies of these western nations and who still retain the capitalist ideology; into

formulating over‑ambitious health policies that not only fail to capitivate their world view,
but also considered wasteful in terms of cost and in the light of social epidemiological reports.

It should however be stressed that such a model of development which seems to assume that
Nigeria needs replica 'infrastructure' to be as developed as their Euro‑American counterparts
is, to use Anikpo's word, a product of 'misguilded paternalism' and it is neither limited to thehealth sector of our socio‑economic life, nor typical of Nigeria. The implication of theperpetuation of such a false model of development for the health sector, has been a grossinsurfficiency in the health care delivery serices of these nations, while the mass of the people

continue to live in squalor and consequently in disease (Olugbile, 1981; Hill, 1970) .

NATIONAL PLANNING
It is a common knowledge that the goal of economic planning in developing nations like
Nigeria is for the realization of a high standard of living, for a substantial proportion of the

population (Rodney, 1972) . Similarly, Erinosho (198la) has argued that: health planning fordeveloping countries is aimed at ensuring for the average citizen in the population, access to
medical care and other basic facilities, which would enable him/her to attain a resonably highhealth status and long life‑expectancy.
While the authenticity of this goal is not in doubt, analysts have continually stressed thatthe modalities employed are always influenced by the ideological orientation of such coun‑tries. A Iook at the Nigerian economy will facilitate this.

THE NIGERIAN EcONOMY
The economy of Nigeria hinges on an ideological orientation which emphasises acapitalist mode of production (Onimode, 1983). Capitalism like socialism or communism

257

Table 1 Sectorial distribution of investment spending, First
National Development Plan, 1962‑1968 (Secondary source:
Anikpo, 1984)
Sector

Rural

Urban

Rural ‑Urban *Trade & industry

2,6

97 . 1

0.3

Electricity

0.6

97 . 70.5

Comminications
Health0.0

91 . 48.6

3.9

76 . 219 . 9Inf ormation

0,0

37 . 862 . O

Social welface

9.2

90 . 80.0

Water supply

39 . 6

58 . 51.9

4.9

91 . 7

3.4

Total* Under this heading are public expenditure items disagregated intorural and urban component.
Table 2 Sectorial distribution of investment, Second National Develop‑
ment Plan, 1969‑1974 (Secondary source: Anikpo, 1984)
Sector

Rural

Industry

Commerce & finance

Urban

Rural‑Urban

4.7

5.3

0.0

1.6

8.4

0.0

11 . O89 . O

0.0

Communications

0.0

100 . O

0.0

Health6.6

43 . 150 . 4

Electricity

Inf ormation

0.0

53 . O

46 . 1

Labour & social welfare

28 . 266 . 1

5.7

Water & sewage

14 . 760 . 824 . 6

Town & country planning

0.l

81.4

9.4

Total

8.0

79 . 6

12 . 5

breeds industrialization and the latter in turn breeds unequal allocation of resources (Anikpo,

1984). Be that as it may, it is the contention of this paper, that capitalisrn, more than any

other system limits opportunities in the rural area by championing rural neglect. A Iook at
the sectorial distritution of investment in the First, Second and Third National Development
Plan will reveal this.

Table I depicts the sectorial distribution in investment spending in the First National

Development Plan, 1962‑1968. Even a cursory look will reveal the factor of inequality
between the allocation for rural and urban areas. It is of note to point out that a total of lessthan 5% went to the rural sector. This pattern highly contradicts the goals of the First
National Development Plan, which was to raise the rate of economic growth and to have thenation's economy (Olatunbosun, 1975). A Iook at Tables 2 and 3 will show that this trends
has continued unabated.
It will be inconceivable, given the level of our industrialization and the fact that agricul‑

258

Table 3 Sectorial distribution of investment spending in the Third National Develop‑
ment Plan (Source: Anikpo, 1984)

Rural‑Urban

Urban

Rural

SectorIndustry

3.4

8.9

96 . 791 . O

0.0

0.0

Commerce & finance

4.9

2.2

86 . 796 . 88.4

1.0

Electricity

21.9

23 . 978 . l76 . 10.0

0.0

Communications

0.1

0.1

97 . 598 . 42.3

1.5

HealthInf ormation

13 . 3

7.2

50 . O

75 . 736 . 717 . 10.0

0.0

67 . 453 . 232 . 646 . 814 . 7

Social welfare

0.4

0.5

68 . 384 . 831 . 3

Water supply

23 . 6

20 . O

68 . 370 . 68.2

9.4

Sewerage & drainage

0.0

0.0

100 . OlOO . O

100 . O

0.0

Town & country

2.5

1.3

88 . 789 . 3

8.8

9.4

9.9

16 . 416 . 59.0

75 . 674 , 474 . 284 . 37.0

15 . 718 . 7

0.0

0,0

0.0

100 . O

100 . O

0.0

0,0

0,0

0.0

100 . OlOO . O

0.0

0.0

General administration

0.7

0.0

84 . 541.8

14 . 858 . 2

Defence security

0.0

0.0

39 . O

9.2

61 . O90 . 8

Total

4.l

4.6

78 . 458 . 117 . 537 . 3planning

Cooperative & supply

Community development
LabourHousing

The first column under each sector shows planned budget allocation (%) , while the 2ndcolumn shows actual spendings.

ture formed the economic mainstay of Nigeria, during the First National Development Plan
period, to suggest that industrialization influenced the minds of our economic planners. But
let us assume for the purposes of analysis, that it is difficult to establish the extent to which

industrizatibn influenced their minds. What it boils down to is that we have been able toauthenticate the fact that capitalism like socialism or communism favours lopsided allocationof resources between the rural and urban areas.
It therefore, becomes clear that a look at the sectorial distribution alone cannot upholdour contention that capitalism, more than any other political ideology, Iimits opportunities in

the rural areas by promoting urban bias and rural neglect in resource allocation.
What is needed is an examination of the policy implications for urban bias and rural
neglect, of any aspect of our socio‑economic life, the choice of which is highly influenced by
our ideological leaning and least by industrialization. For the purposes of this work, we shallpick on the health sector. This choice is deliberate.

THE HEALTH SECTORThe Nigerian medical system is organised along the capitalistic Euro‑American model.
And like an all‑time capitalist oriented countries, the economies of the United States, Britain

and Sweden are predicated on a regulated free enterprise. In the United States, health careis left wholly in the hands of entrepreneurs, who act as fronts to the various insurance

259

companies which exist to provide coverrage for all aspects of medical care. Under suchdispensation, Erinosho (198lb) noted that the citizenry is left at the mercy of those insurancecompanies which obviously derive great human and material benefits from the sale of healthpolicies. The physicians in this country also derive high income in their practice, whilst thehighest quality care is reserved for the highest bidder.

Health care delivery services in Britain and Sweden on the other hands, take the same
form as that of the United States, except that in the latter, some powerful pressure groups
who feel strongly about state participation in some aspects of their socio‑economic life, havepersuaded their governments to introduce a National Health Insurance Scheme. It is of note
to say that this scheme has made it possible for the poor and the rich to have access to aheavily subsidezed health care delivary services (Erinosho, 198lb) .
In Nigeria, orthodox medicine exist side by side with traditional medicine, event though
the latter is older and yet to be accorded ofiicial recognition.

As a practice that was borne out of the colonial experience, it emphasizes curative,
rather than preventive health services; whereas, social epidemiological researches have madeit crear that most prevailing diseases in Africa are preventable. Futhermore, orthodox
medicine is founded on science and like an archtype scientific practice, Iimits its explanationof diseases causation to physical or biological discontinuity, whereas, the African view of it,

incorporates the physical as well as the psyche realm (Chilivumbo, 1976; Mbiti, 1976; Ndeti,
1976; Oke, 1982).

Two third of the recognised health institutions in Nigeria are owned by the federal

government (Sunday Tribune, 1985). While the other one third is made up of private
T ble 4 The capital programme by activity (health) in the Third National Develop‑
ment Plan (million)

Government
FederalHospital

programmes

Basichealthservices

programmes

Training

programmes

Su pporting
healthTotal

programmes
26 . 960

212 . OOO

51 . OOO

Benue Plateau

12 . 040

12 . 980 *3 . 500

2. 15030 . 670

East Central

36 . 622

17 . 600

4 . OOO

4. 39962 . 621

Kano
Kwara

8. 28918 . 850 *4 . OOO

300

32 . 430

11 . OOO

12 . 100

3 . 500

900

28 . 500

Lagos
Midwestern

24 . OOO

314 . 160

41 . 501

7 . 700 *4 . 100

o. 60053 . 901

20 . 700

10 . 570 *3 . 750

4. 67039 . 690

North Central

5. 20015 . 050 *3 . 500

o. 06023.810N orth Eastern

6. 75022 . OOO

5 . OOO

9. 15042 . 900

N orth Westernll . 357

14 . 310 *4 . OOO

o. 88330 . 550

Rivers22 . 150

6 . 450 *3 . 500

2. 70334 . 805South Easternll . 500

7 . 700

3 . 500

o. 15022 . 250

7. 31022 . 865 *3 . 500

9. 36643 . 041

406.410219 . 175

70 , 050

64 . 293

759 . 928

Western
Total* Allocation includes cost of projects concerning the control of communicable dis‑eases and other preventive activities.

260
hos pitals.

Despite such massive participation by the government, the extent to which treatment is
subsidized is highly questionable given the fact that most of the hospitals are without thenecessary facilities (Newswatch, 1986).

Other problems centre around the urban based nature of orthodox medicine, which
encourages the few number of personel she parades to cluster around urban centres, high costof training paramedical staff etc. A focus on the provision for health under the Third
National Development Plan will establish the above claims.
Table 4 depicts capital programme by activity (health) in the Third National Develop‑
ment Plan period. A total of 759.928 million was allocated to programmes in health sector
during this planning period. Of this sum, a staggering sum of 406.410 inillion was spent on
hospital programmes by both the federal and the then 12 states in the federation. Of theremaining 540.753, a total of 219.175 was spent on basic health services programmes: 51
million by the federal government and 168.075 spent by the federal and state governments on
training and supportive health programmes respectively.
For the porposes of clarification, Iet us quickly say that hospital programmes involve thebuilding, expending or re‑activation of existing hospitals, clinic, maternity etc., while basic

health services programmes are devoted to the eradication of cotnmunicable and otherpreventable diseases. Training programmes involves both the provision of training facilities

and the actual training of paramedical personnel. Supportive programmes on the otherhands, are "chiefly concerned with pharmaceutical and drug manufacturing laboratories,
medical stores, purchase of special vehicles and accomodation for both junior and senior
officers" (see 3rd NDP).
We have seen from Table 4 that the greater proportion of the health budget for the 3rd

National Development Plan period was devoted to executing hospital programmes. These
hospitals are mainly concentrated in the urban areas, where only 20% of Nigeria's 80 million

people live. A Iook at the 1969 United Nations estimate will corraborate this.
Table 5 shows the 1969 United Nations estimate of the total population of rural dwellers

and urban dwellers in Nigeria by year. It is readable from the Table that a total of 89.8%
of Nigeria's 30.4 million people lived in the rural area is 1953, as opposed to l0.2% who

resided in the urban areas. A decade later, she again estimated 80.7% and 19.3% from a
population of 55.7 for the rural and urban dwellers respectively. Despite the reservations
people have expressed about these e'stimates, which they claim was based on the 1953 and1963 controversal head count, many analysts are agreed today, that at least 80% of Nigerians
live in the rural areas (Olugbile and Oyemade, 1981; Newswatch, 1986; Times International,
1986) .

Table 5 The rural and urban population of Nigeria in 1953 and 1963 (Ekanem, 1972)

1953

1963

No, towns

poptilation

Total rural
population

Total urban
population

with 20,000

30 , 402 , ooo

27 , 307 , ooo

3 , 101 , OOO

54(89 . 8%)(10 . 2%)

44 , 943 , ooO

10 , 729 . OOO(80 . 7%)(19 . 3%)

Year Total Nigerian

55 , 672 , ooo

183

261

A Iook at the location for hospital programmes during the Third National Development
Plan period, will authenticate the fact that they are mainly urban based. In line with this,studies have shown that at least 2/3 of the population of Nigeria's doctors are concentrated
in 7 cities, 6 of which are locations for the older univercities; while more than 1/2 of theremaining 30% of available doctors are concentrated in the big towns in the country. The
same urban concentration is als'o true for all other categories of western trained healthpersonnel (Ademuwagun 1969).
The irony of the perpetuation of the orthodox model, is that even our very colonial
orthodox‑approach‑oriented health planners are aware that 95% of our killer diseases arepreventable (3rd NDP).
IMPLICATIONS
The implication of perpetuating the present health model with all its curative emphasis,and numerous urban based hospitals and health personnel was driven home by Erinosho(198la) when he noted that under such an arrangement; the real issue, namely, the provisionof medical care for a substantial proportion of the people in the population inevitably
assumes secondary place in the scheme of things.
Indeed, a situation in which 80% of our 80 million live in the rural areas and are ill‑
provided with medical facilities, cannot be said to be healthy. This view tallies with that
expressed by Anikpo (1984) when he noted that given the biases in the sectoral distributionof investment in the Third National Development Plan: Nigeria's present underdevelopment
seems less surprising since even from a purely economic point of view, the development ofover 80% of the population was never part of the planning process.
Furthermore, if we accept the truism that a healthy nation is contigent on healthy
citizenry and will allow Hill (1970) to persuade us that poverty breeds diseases and vice versa

then we cannot but come to the sad conclusion that the very life‑blood of the 'neglected' 64

million rural dwellers in Nigeria are by the perpetuation of orthodox model, wittingly or

unwittingly sucked, and each of them turned into a misfit agent of development. The
implication of this for the economic rating of this country, is that we shall continue to remain

a developing nation.

DrscUssroN
I have demonstrated in the course of this work, that health planning under capitalism
cannot quarantee adequate health need for a substantial part of the population. This isbecause capitalism generally promotes the interest of the few at the expense of the majority.

What is needed therefore is for us to adapt an ideology under which we can evolve a
health care model that will be geared towards achieving for the average citizen in the
population, access to medical care and other basic facilities, which would enable him or her

to attain a reasonably high health status and long life expectancy. This ideology is theAfrican ideology.
African ideology is solely based on African spiritual communalism. It is neither social‑
ism nor welferism, it is an ideology which embodies the indigenous African principles of live
and let live, collective sharing, common concern for one another; sense of belonging together;

262

social justice; economic progress and viability for all . . . (Onwuachi, 1977) .

It can be argued that Nigeria is still a face‑to‑face society, where relationships with kins

and neighbours matter a lot. This is in line with the values of African spiritual communalism.

An effective way of incorporating the values of African ideology into our health planning, isfor us to formulate health policies that are geared towards the mass of the people.

We can best achieve this by relying on social epidemiological reports, which havecontinually shown that by far the greater, proportion of the prevailling diseases in tropical
Africa, are preventable.

It will therefore be a step in the right direction to increase the emphasis on primary
health care scheme while de‑emphasizing the orthodox model, with all its curative emphasis,
expensive urban based hospital scheme and huge cost of training paramedical personnel (see3rd. NDP).
Analysts like Hill (1970) . Olugbile and Oyemade (1981) have demonstrated that thecontrol of diseases is dependent on the extent to which we can successfully improve thequality of our environment. To this end, it will be wise for us to divert funds that would havebeen going into new hospital scheme, to the provision of pipe borne water, electricity,drainage, waste disposal and adequate schelter ‑for our rural population, who presently lackthese things (Newswatch, 1986) .
It will serve a useful purpose to educate our people, both in the rural and urban areas,on the need to keep a clean environment. Here, the rebirth of the environmental sanitationby the present administration is a welcome development. However, we may still have to train
health educators to meet this end. A major aspect of the duties of these health educators, will
be to demonstrate to the people, especially these is the rural areas, that most diseases havecultural origins and for them to co‑operate with health workers, to abolish such cultural
practices which limit rather than promote life.
It will also help if the government can recognize and integrate the traditional healers into

the mainstream of our health care delivery services. This is the only rational way out. I
therefore agree with Olatunbosun (1975) , when he noted that: the choices before us are clear;

eiter we have a meaningful rural development plan based on equity and social justice, or wemust forefeit a golden oppotunity to achieve a decent level of living for all men, whether inthe urban or rural areas.

REFERENCES
1 ) Ademuwagun, Z.A. (1969): The relevance of Youba Medicine men in public health practice inNigeria, Public Health Reports, 842 ) Anikpo, M. (1984): The peasantry and the dilemma of underdevelopment in Nigeria, Pan Afr.
Soc. Sci. Rev., No. 1
3 ) Chilivumbo, A.B. (1976) : Social basis of illness: a search for therapeutic meaning, Medical
Anthoropology: ed. Grellig J.S. et al.. Paris, Mouton
4 ) Ekanem, 1.1. (1972): The 1963 Nigerian census, a critical appraisas, Ethiope, Benin City5 ) Erinosho, O.A. (198la) : Health planning in Nigeria: a critique, Department of Sociology,
University of lbadan. Ibadan
6 ) Erinosho, O.A. (198lb): The relevance of social sciences to health care delivery services intropical Africa, Department of Sociology, University of lbadan, Ibadan
7 ) First, second and third national development plan, Central Planning Official Federal Ministry263

of Economic Development, Lagos
8 ) Hill, J. (1970) : The Disinherited, Ernst Be,,, London
9 ) Lewis. A. (1953): Health as a social concept, Brit. J. Sociol.

10) Mbiti, J.S. (1976) : African Religions and Philosophy, Heinemann, Nairobi11) Ndeti, K. (1976): The relevance of African traditional medicine in modern medical training
and practice, Medical Anthropology (Grollig, J.S. et al., ed.), Mouton, Paris

12) Newswatch (1986): Feb. lOth13) Nzimiro, I. and Eteng, I. (1978) : Capitalism in Nigerian rural societies: Pan Afr. J. Soc. Res.,

Vol. 114) Oke, E.A. (1982): Traditional health services: an investigation of the providers and the leveland pattern of utilization among the Yoruba: University of lbadan Department of Sociology15) Olatunbosun, D. (1975): Nigeria's neglected rural mojority, Oxford, Ibadan
16) Olugbile, A.O.B. and Oyemade (1981): Health and the environment, a comparative study of the
agricultural and industrial workers in Nigeria, Afr. J. Med. Med. Sci., 10 (3/4)

17) Onimode, B. (1983) : Imperiasm and underdevelopment in Nigeria. Macmillan, Lagos
18) Rodney, W. (1972): How Europe underdeveloped Africa, Tanzania Publishing House, Dar es

Salaam19) Sunday Tribune (1985): March, 3lst20) Times International (1986): 37, June 1621) Weber, M. (1964): The Theory of Social and Economic Organization, (Parsons, T. ed., Free
Press, N.Y.)

22) WHO (1964): Charter, WHO, Geneva

ISSN 0304‑2]46

JAPANESE JOURNAL OF
TROPICAL MEDIClNE AND HYGIENE
September 1990

Vol. 18 No. 3

CONTENTS
Review
Davis, A.

The Epidemiology and Chemotherapy of Schistosomiasis and Other
Snail‑borne Trematode Infections """""'

215‑228

Original article

Oo. M.M., Ikehara. S., Nakamura, T., Inoue, S. and Hamashima, Y.
Plasmodium berghei and yoelii: a Correlation of Survival Periods and

Immunological Parameters in BALB/C Mice """""""""""""""""'

229‑237

Case note
Ebisawa, I., Ohara, H. and Tanabe, K.

Hematological Findings in Malaria with a Note on Blood Transfusion
in Severely Anemic Patients (in Japanese) """"""""'

239‑245

Ebisawa, I., Ohara, H. and Tanabe, K.

Biochemical Abnormalities in Malaria (in Japanese) """""""""'

247 253

Note
Agbonlahor, F.1.

The Orthodox Model of Health Care Delivery Services and the Fate ofNigeria's 64 Million Rural Dwellers: a Search for a Viable HealthSupermarket ････････････････････････････i･････････････････････‑

Japan. J

Trop.

Med. Hyg.

JAPANESE SOCIETY OF TROPICAL MEDIClNE

255 263