bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Toxoplasma gondii infection in a nonhuman primate
Authors: Araujo Fausto G. , Wong Ming M. , Theis Jerold , Remington Jack S.
Published: May 2017

The experiments reported in this paper were performed in order to develop a nonhuman primate model for the study of toxoplasmosis. Forty-eight Macaca arctoides monkeys were tested by the Sabin-Feldman dye test and 9 (18.7%) were positive (≥1:4). Eight had a titer of 1:4 and one a titer of 1:2,048. Eight seronegative animals were experimentally infected with either cysts or trophozoites of Toxoplasma gondii using subcutaneous. intravenous and oral routes of inoculation. The immune response was monitored by the dye and IgM-fluorescent antibody tests and the skin test. Serological responses varied with size of inoculum, form of the parasite inoculated and route of inoculation. The skin test was positive in all animals 15 weeks after infection. Parasitemia was demonstrated by mouse inoculation in four animals during the first 10 days after infection but not thereafter. T. gondii was demonstrated in mice which had been inoculated with brain and heart of one monkey sacrificed 10 weeks after infection and from another which died of unrelated causes 30 weeks following infection, indicating that the serological response observed was due to active invasion and multiplication of the parasite. Since the response of this species to infection with Toxoplasma is not dissimilar to that of man, this model may be useful to study various aspects of toxoplasmosis.
Tumor-like lesion of the brain caused by Trypanosoma cruzi
Authors: De Queiroz Aristides Cheto
Published: May 2017

A 62-year-old man with a 2-year history of pruritus and erythematous skin lesions developed neurological symptoms 3 weeks before death. Autopsy studies revealed an isolated tumor-like lesion of the brain caused by leishmanial forms of Trypanosoma cruzi. Search for parasites in organs other than the brain was negative. This is believed to be the first report of an isolated cerebral infection by T. cruzi, identified in post-mortem histological preparations.
Course of development of Leishmania enriettii infection in immunosuppressed guinea pigs
Authors: Lemma Aklilu , Yau Percy
Published: May 2017

The course of development of L. enrietti infection in normal and immunosuppressed guinea pigs was studied. The leishmanial lesion in normal guinea pigs is confined and self-limiting, but in immunosuppressed animals it metastasizes and diffuses to various parts of the body, particularly the extremities. Successful immunosuppression for such studies can be achieved by administering antilymphocytic antiserum, cyclophosphamide, or whole-body irradiation. All such immunosuppressants must be continuously applied to lower the total white blood cell count to about 2.000/ml and maintain it at that level.
Some epidemiological considerations of scrub typhus (Rickettsia tsutsugamushi) in a natural focus in the Zambales Mountains, Luzon, Republic of the Philippines
Authors: Reisen William K. , Pollard Thomas J. , Tardy Walter J.
Published: May 2017

Reports of six cases of scrub typhus in USAF personnel at the 3614th Combat Crew Training Squadron, Clark Air Base, Philippines during the rainy seasons of 1969 and 1970 prompted an investigation into the scrub typhus potential of the field training area. Rickettsia tsutsugamushi was isolated from Rattus rattus mindanensis; two vector species, Leptotrombidium (Leptotrombidium) akamushi and L. (L.) deliense, were collected. The focus fulfilled all of the basic requirements for the natural maintenance of this disease.
Granuloma of the liver due to Enterobius vermicularis: Report of a case
Authors: Little M. D. , Cuello Carlos Jose , D'Alessandro Antonio
Published: May 2017

A solitary granuloma containing eggs of Enterobius vermicularis was incidentally found in the liver of a 54-year-old man in Colombia. This is only the second report of pin-worm granuloma in the liver of man.
Experimental infection in man with Plasmodium malariae
Authors: Collins William E. , Contacos Peter G. , Chin William
Published: May 2017

Two strains of Plasmodium malariae, one from the Philippines and the other from Nigeria, were studied in 23 volunteers. In infections induced by the intravenous inoculation of parasitized blood, the peak parasitemias of from 1,400 to 27,000 per mm3 were attained on from the 13th to the 28th days of patent parasitemia. The median day of maximum parasitemia was 16 days. Neither strain in man readily infected mosquitoes. Transmission was obtained to six volunteers via the bites of Anopheles freeborni mosquitoes infected by feeding on owl monkeys. The prepatent periods ranged from 24 to 33 days with a mean of 27.5 days. Both strains of malaria were cured by treatment with 600 mg (base) chloroquine. Treatment of the Philippine strain with quinine sulfate (30 grains per day for 5 days) was also curative. The failure of the sporozoite induced infections to relapse after treatment with blood schizontocides suggests that P. malariae does not possess a fixed-tissue relapse mechanism.
Pathology of the testis and epididymis in the late phase of experimental Chagas's disease
Authors: Ferreira Affonso L. , Rossi Marcos A.
Published: May 2017

The present investigation was undertaken to study changes in the testis and epididymis in the late phase of experimental Trypanosoma cruzi infection in guinea pigs. Testicular and epididymal atrophy were observed in infected animals. Histopathological alterations were observed in the seminiferous epithelium, involving inhibition of the process of spermatogenesis beyond certain stages (kinetic data) and morphological changes mainly in the primary spermatocytes. In the testis the disturbances were restricted to focal areas. The epididymis of infected animals showed marked tubular atrophy and the contents of the epididymal tubules closely reflected the state of the seminiferous epithelium. A marked diminution of ganglion cells in the juxtaprostatic pelvic autonomic ganglia of experimentally infected guinea pigs could be displayed by quantitative studies of serial sections. Application of the osmic acid-zinc iodide technic allowed observations on the autonomic fibers and their endings in the epididymis. Degenerative lesions in the fibers, ascribable to the destruction of neurons in the juxtaprostatic ganglion, were observed in infected animals. Our experimental results were consistent with the hypothesis that the destruction of nerve cells in the juxtaprostatic pelvic autonomic ganglion is the main factor in the pathological changes, which may be classified as “post-chagasic orchiopathy and epididymopathy.”
Blast transformation of lymphocytes in amebiasis
Authors: Savanat T. , Viriyanond Pithaya , Nimitmongkol Nitaya
Published: May 2017

Peripheral blood lymphocytes from 21 out of 23 patients with amebic liver abscesses and 1 patient with amebic cervicitis were stimulated in vitro by an aqueous extract of Entamoeba histolytica to undergo blast transformation as measured by their ability to incorporate tritiated thymidine. The response was specific, since lymphocytes from all of 15 healthy individuals and 9 out of 10 patients without amebiasis did not show blastogenic response. The degree of blast transformation varied from one patient to the other, the magnitude of response being high in 7, medium in 9, and low in 6. The ability of lymphocytes to transform in the presence of the antigen did not appear to be related to the number of precipitating bands as measured by the immunoelectrophoresis test, indicating that blast transformation was not directly correlated with the humoral immune response.
Immunization with a zoophilic strain of Schistosoma japonicum: A re-evaluation of the Formosan strain of S. japonicum in rhesus monkeys
Authors: Murrell K. Darwin , Yogore M. G. , Lewert R. M. , Clutter W. G. , Vannier W. E.
Published: May 2017

The zoophilic Formosan strain of Schistosoma japonicum has been reported to be very effective in immunizing rhesus monkeys against the pathogenic Japanese strain. Before its potential as a human vaccine could be evaluated, more information was needed on its protective properties against other pathogenic strains, on its ability to decrease clinical disease and on the amount of pathology resulting from its use. Rhesus monkeys given five immunizing exposures to the Formosan strain had significant reductions in quantitative egg excretions and in worm fecundity after challenge with the Philippine strain. Three of 4 such monkeys had greatly reduced worm burdens. The prepatent period was extended almost a week in immunized monkeys. Evidence is offered that fecal egg counts should not be used as a definitive criterion of immune status. Unimmunized monkeys challenged with the Philippine strain experienced a leucocytosis and hyperglobulinemia (IgG) at the onset of egg excretion, neither of which occurred in immunized monkeys. Quantitative egg counts in tissue digests demonstrated that immunization did not significantly reduce the number of eggs trapped in the liver. Granulomas in the liver and intestinal tissues were comparable in immunized monkeys and their controls. Liver and spleen to body weight ratios and serum enzyme levels were not altered either by immunization or by challenge. Immunization alone induced dermal immediate hypersensitivity reactions in all monkeys and circulating specific reaginic antibody detectable by P-K testing in 6 of 8 monkeys. Challenge with the Philippine strain resulted in reaginic antibody in all instances 60 days later. Circumoval precipitins were detected not only in monkeys harboring adult worms, but also in those exposed to only the immunizing infection. A marked eosinophilia resulted from multiple exposures to the Formosan strain. All monkeys exposed only to the Formosan strain had worms at autopsy, including mature egg-laying females. These latter animals displayed liver granulomas. These results indicate the Formosan zoophilic strain of S. japonicum can immunize partially but not completely against challenge with a pathogenic strain.
Effect of hycanthone, niridazole, and antimony tartrate on schistosome motility
Authors: Senft A. W. , Hillman G. R.
Published: May 2017

The use of a photoactivated, computerized monitor of schistosome motility is described. The effect of antimony tartrate, niridazole, and hycanthone on parasite activity in vitro has been determined. This effect was measured both directly and following stimulation with serotonin. It was found that accurate dose response curves to three common anti-schistosome drugs could be obtained. These show that antimony tartrate and niridazole suppress worm motility at doses from 10-3 to 10-5 M concentration. Hycanthone decreases worm activity at high dosage (10-3 to 10-4 M) but has a strongly stimulatory effect at 10-5 to 10-7 M concentration. The possibility that hycanthone acts by virtue of serotoninergic or anticholinergic functions is discussed.
Susceptibility of adult Biomphalaria glabrata to Schistosoma mansoni infection
Authors: Richards Charles S.
Published: May 2017

In previous studies true-breeding stocks of Biomphalaria glabrata were derived testing 100% or 0% susceptible as juveniles to a Puerto Rican strain of Schistosoma mansoni. When adults of these genetic stocks of B. glabrata were exposed to miracidia of the same strain of S. mansoni, snails of some of the juvenile-susceptible stocks were found to have become refractory at maturity. True-breeding snail stocks of three susceptibility types were derived by selection and self-fertilization through several generations: juvenile and adult refractory, juvenile and adult susceptible, and juvenile-susceptible/adult-refractory. Crosses demonstrated that the adult insusceptibility observed in some of the juvenile-susceptible stocks was determined by a single dominant gene, with the character showing simple Mendelian inheritance. Snails of a fourth susceptibility type showed juvenile susceptibility but modification of adult susceptibility, with unpredictable infection frequencies and delayed parasite development. Clonal stocks of the various susceptibility types, with their lineage recorded in diagrams, are identified for use in other experimental studies.
Complement profile in leprosy
Authors: Petchclai Bencha , Chutanondh Rochana , Prasongsom Sopaporn , Hiranras Supaporn , Ramasoota Teera
Published: May 2017

We investigated complement in leprosy to detect its possible role in pathogenesis. Complement components, C3 proactivator (C3PA), CH50 and anticomplementary activity (AC) were determined in sera collected from lepromatous and tuberculoid leprosy. C3 was found increased in lepromatous leprosy and highly increased C3PA was found in both groups. Changes in other components lacked specific pattern. Increases in C3PA levels are believed to be due to aggregation of the increased serum immunoglobulins. C3 levels and CH50 levels in the present study agree with those in other reports. Development of AC occurred in lepromatous sera even during 2 days of storage at –80° C. AC found among freshly collected sera was probably due to aggregated immunoglobulins. The present study serves as a groundwork for future investigations.
Further observations on the primary paranasal aspergillus granuloma in the Sudan: A morphological study of 46 cases
Authors: Veress Béla , Malik Osman A. , El Tayeb Ahmed A. , El Daoud Sayed , Mahgoub El S. , El Hassan Ahmed M.
Published: May 2017

The morphological changes in 46 cases of primary paranasal aspergillus granuloma seen in the Sudan are described. Histologically, three groups can be differentiated: 1) a proliferative type, characterized by the presence of pseudotubercles in a fibrous tissue stroma; 2) an exudative-necrotizing type, consisting of large foci of edematous necrosis; and 3) a mixed group, where proliferation and necrosis exist side by side. Fungal hyphae are seen both within the giant cells and lying free in the stroma. Three factors seem to play a part in the pathogenesis of this disease: a) the climatic conditions, inducing recurrent inflammation of the nasal sinuses; b) the ability of the fungus and its toxic metabolites to cause damage; and c) an immunological process produced by the fungal antigens. The latter is supported by the finding of fibrinoid necrosis of collagen, vascular alterations, and formation of pseudotubercles.
Epidemiology of the acute fevers of unknown origin in South Vietnam: Effect of laboratory support upon clinical diagnosis
Authors: Berman Steven J. , Irving George S. , Kundin William D. , Gunning Jean-Jacques , Watten Raymond H.
Published: May 2017

Acute fevers among American servicemen in South Vietnam were studied for a two-year period. The population included 524 patients with an acute fever of unknown origin (acute FUO) of at least four days' duration, and 269 patients who were given a tentative diagnosis of leptospirosis, scrub typhus or an arbovirus infection. Fifty-four per cent of the clinical diagnoses were serologically confirmed and 31 % of the patients with acute FUO were found to be infected with these same agents. Leptospirosis accounted for 20% of these acute fevers; scrub typhus and Japanese encephalitis were also common. Results of viral isolations and serologic testing for enteroviruses, rickettsiae, Toxoplasma, and influenza virus were of limited usefulness in the remaining patients. A correlation between the etiology of the acute FUO, seasonal incidence and environmental exposure was established. Epidemiologic data and laboratory reinforcement of clinical impressions resulted in a marked improvement in the accuracy of the attending physician's clinical diagnoses as the study progressed.
Endod extract, a plant-derived molluscicide: Toxicity for mosquitoes
Authors: Spielman Andrew , Lemma Akilu
Published: May 2017

A butanol extract of the soapberry plant, Phytolacca dodecandra (endod), is toxic at about 1 part per million to second and third instar Aedes, Culex, and Anopheles mosquitoes. Ova and pupae are not affected and adults die only after ingestion of concentrated endod. Endod extract is considerably more toxic than rotenone and about 100 times as active as a commercial saponin preparation. It is about twice as toxic as DDT when applied against DDT-resistant larval A. aegypti; 20 times less toxic for DDT-susceptible C. pipiens, and 40 times less toxic for DDT-susceptible A. quadrimaculatus. The concentration of endod required to kill mosquitoes is less than that which kills snails and fish.
Comparative histopathology of two strains of Bolivian hemorrhagic fever virus infections in suckling hamsters
Authors: Terrell Timothy G. , Stookey James L. , Spertzel Richard O. , Kuehne Ralph W.
Published: May 2017

The histopathology of Machupo virus infection in intracerebrally inoculated suckling hamsters was studied and compared to the histopathology of a virus isolated from a case of hemorrhagic fever from Cochabamba, Bolivia. Both virus isolates were pathogenic for suckling hamsters; however, Machupo virus killed the hamsters earlier than Cochabamba virus. Lesions were most commonly observed in liver and lymphoid and central nervous systems. The lesions varied in incidence, time of occurrence and severity. A nonsuppurative encephalitis which developed in the Cochabamba-virus-infected hamsters was not a consistent finding in the animals inoculated with Machupo virus.
Response of Plasmodium Falciparum Infections to Pyrimethamine-Sulfadoxine In Thailand
Authors: Rieckmann Karl , Suebsaeng Laksami , Rooney William
Published: May 2017

The results of this study in Thailand indicate that the early response of falciparum infections to a single dose of pyrimethamine-sulfadoxine is influenced by the developmental stages of the parasite present at the time of treatment. Parasite clearance is slower when young rings predominate at the time of treatment. This should be taken into account when considering the clinical management of patients and the comparative efficacy of antimalarials in clearing parasites from the peripheral blood. The 36–48 hr delay in schizonticidal action observed after treatment of febrile infections and the associated decline in blood concentrations of pyrimethamine suggest that a single dose may not be the ideal way of administering this drug combination and may encourage the emergence of drug-resistant parasites.
A Radioimmunoassay for the Diagnosis of Malaria
Authors: Avidor Boaz , Golenser Jacob , Schutte Chris H. J. , Cox Geoff A. , Isaacson Margaretha , Sulitzeanu Dov
Published: May 2017

A newly developed radioimmunoassay for the diagnosis of malaria has been tested in South Africa. The radioimmunoassay is an antibody binding-inhibition assay, based on a monoclonal antibody (D5) cross-reacting with Plasmodium berghei and P. falciparum. Washed solubilized red blood cells were incubated with the antibody and the residual binding activity was tested on antigen-coated microtiter plates. A sample was considered positive if it inhibited binding of the antibodies to an extent exceeding that of the microscopically negative blood samples. Blood was collected on 3 separate occasions from a total of 530 individuals living in a malaria-endemic area and was examined by radioimmunoassay and microscopy. Group I, consisting of 194 samples, yielded 12 samples positive by microscopy and 10 of these (83%) were also positive by radioimmunoassay. One sample in this group was “positive” in the radioimmunoassay but negative on microscopy (false positive). In the 320 samples of group 2, 13 were positive by microscopy and 6 (46%) by radioimmunoassay. Group 3, which included 16 samples preselected as positive by microscopic examination and 16 controls, was examined after 4 weeks storage at −20°C. Twelve samples (75%) were positive by radioimmunoassay. Tests carried out to determine the effect of blood storage on the activity of the antigen indicated that activity was preserved with little loss over a 3-month period.
Immunological Studies in Amebiasis: Isotypic Characterization of Specific Antibodies by Enzyme-Linked Immunofiltration Assay
Authors: Pinon Jean-Michel , Poirriez Jean , Remy Gerard , Lepan Herve
Published: May 2017

Fifty sera from 17 cases of invasive amebiasis (15 hepatic localizations, ameboma, 1 diffused colic localization) were studied by enzyme-linked immunofiltration assay (ELIFA). IgM and IgE anti-Entamoeba histolytica were detected in 10 and 15, respectively, of the 17 patients studied. IgM and IgE antibodies were found simultaneously in 10 cases; these 2 isotypes were only recognized twice in the same serum by the same antigenic components. During post-therapy monitoring, in less than 90 days IgE or IgM-Ab regressed completely in half the cases. If they appeared or reappeared after the third month, prognosis was bad. In addition to its value for diagnosis and prognosis, the ELIFA allowed us to detect the functional antigenic components revealed more particularly by some IgG, IgM, IgE, or IgA antibodies.
The Electrophoretic Isoenzyme Patterns of Strains of Entamoeba Histolytica Isolated in Two Major Cities in Canada
Authors: Proctor Eileen M. , Wong Quantine , Yang Jim , Keystone Jay S.
Published: May 2017

The isoenzyme patterns of 92 isolates of Entamoeba histolytica from British Columbia and 28 from Ontario were determined. Seropositivity for E. histolytica was assessed by indirect hemagglutination and enzyme-linked immunosorbent assay in the one center and by ELISA and amebic gel diffusion in the other.

In both British Columbia and Ontario nonpathogenic zymodemes I and III were most common. A newly described isoenzyme pattern was identified in Ontario. Only 9 of 120 zymodeme patterns identified were found to be pathogenic strains of E. histolytica. Pathogenic isolates were strongly correlated with clinical symptoms and seropositivity.
In Vitro Cultivation of Third Stage Larvae of Wuchereria Bancrofti to the Fourth Stage
Authors: Franke Eileen D. , Riberu Wiwiek , Wiady Iwa
Published: May 2017

Third stage larvae of Wuchereria bancrofti obtained from laboratory-infected mosquitoes grew and molted to the fourth stage in vitro. The culture medium which supported the best growth and development consisted of a 1:1 mixture (v/v) of two commercially available cell culture media, NCTC 135 and Iscove's modified Dulbecco's medium supplemented with 10% human serum or plasma and an antibacterial/antimycotic mixture. Cultures were incubated at 37°C in an atmosphere of either 5% or 8% CO2 in air. After 35 days of culture, 65% to 100% of the larvae were fourth stage. They were motile and in excellent morphological condition with development of the reproductive system in males and females. This culture system will provide an important tool for biochemical and immunological studies.
Preparation and Use of Monoclonal Antibodies for Identifying Crimean-Congo Hemorrhagic Fever Virus
Authors: Blackburn Nigel Keith , Besselaar Terry Gail , Shepherd Alasdair James , Swanepoel Robert
Published: May 2017

Seven monoclonal antibodies were prepared against a South African strain of Crimean-Congo hemorrhagic fever (CCHF) virus and were found to be directed against viral nucleocapsid protein. Five of the monoclonal antibodies reacted to high titer in indirect immunofluorescence (IF) tests and enzyme-linked immunosorbent assays (ELISA) with 22 strains of CCHF virus and failed to cross-react with the closest antigenic relative of CCHF, Hazara virus, or with 4 other nairoviruses which need to be distinguished from CCHF virus in Africa. These antibodies, used in the IF technique, readily detected antigens induced by all strains of CCHF virus included in the study in cell culture monolayers and mouse brain tissue, which represent the systems commonly used for isolation of CCHF virus. The IF technique with monoclonal antibodies constitutes a rapid and specific means of identifying newly isolated strains of CCHF virus.
Uncertainties in the epidemiology and control of schistosomiasis
Authors: Gryseels B.
Published: May 2017

In this paper, gaps in our understanding of the dynamics of infection, transmission, pathology, and control of schistosomiasis, and the possible contribution of modeling are briefly discussed. The measurement of prevalences and intensities of infection by egg counts has shortcomings; a recently developed model of egg count variations contributes to a better interpretation of survey data, and suggests that true prevalences and worm loads in endemic communities may be considerably underestimated. The question as to whether schistosome populations are regulated by host-dependent or transmission-related factors is still being debated; recent scientific advances and operational control experiences tend to favor the first mechanism, with important implications for control and research strategies. However, there is still a lack of field data to feed models of the dynamics of transmission. We still know little about the dynamics and even the importance of schistosomiasis morbidity, although more objective data are now becoming available through ultrasound studies. Models of the development of early- and late-stage morbidity could substantially contribute to more cost-effective strategies of passive and active chemotherapy. Modeling can also contribute to a better understanding and improvement of results of ongoing control efforts, particularly concerning the impact of repeated chemotherapy, and its complex interaction with many biological and social factors on infection, transmission, and morbidity.
Immunity and morbidity in infection due to Schistosoma haematobium
Authors: Hagan Paul
Published: May 2017

It has been suggested that immunologic factors, rather than transmission factors, may play a particularly important role in the regulation of schistosome populations. Support for this view comes from several studies of the epidemiology of Schistosoma haematobium infection, although evidence is accumulating from both field and laboratory studies that immunity in schistosomiasis need not be a concomitant immunity. Correlations between immunologic parameters such as peripheral blood eosinophil counts and specific anti-worm immunoglobulin E (IgE) antibody levels, and apparent resistance to reinfection following chemotherapy have been reported and used as evidence in favor of the existence of an acquired immunity. Specific anti-worm IgG4 subclass blocking antibodies have also been described. The relationship between infection intensity and morbidity may not be as simple as has hitherto been assumed, especially since the methods used to generate data on the prevalence and intensity of infection have serious limitations that may only be overcome with improved or alternative sampling techniques.
Dynamic modeling of epidemiologic patterns of schistosomiasis morbidity
Authors: Medley G. F. , Bundy D. A. P.
Published: May 2017

This paper uses preliminary mathematical models to examine how the dynamic relationship between schistosomiasis infection and disease is altered by chemotherapy. Two types of morbidity are examined: an acute form that is proportional to current infection intensity and that resolves after treatment, and a chronic form that represents accumulated experience of infection and that does not resolve after treatment, or resolves according to some delay function. The analyses indicate that nonlinearities in the age and frequency distributions of infection intensity have a marked impact on the patterns of morbidity. They also suggest that treatment close to the age of maximum infection intensity (i.e., children of schoolage) is most effective in controlling morbidity in the community as a whole. These models are preliminary, and their further development to include more realistic assumptions in relation to field data is discussed.
Different approaches to modeling the cost-effectiveness of schistosomiasis control
Authors: Guyatt H. L. , Tanner M.
Published: May 2017

The limited economic resources available for health care in developing countries necessitates the involvement of cost analysis in the planning of any control intervention. A number of studies have undertaken cost-effectiveness analysis of schistosomiasis control, and the methodologies utilized in both cost and effectiveness evaluation are discussed. In attempting to relate cost to effectiveness, most studies have utilized static models expressing effectiveness in terms of coverage (drug delivery) or cure rate (infection prevalence reduction). These immediate output measures do not consider the long-term impact of control nor the effect on disease. An alternative approach is to use a model of the transmission dynamics of the parasite to permit evaluation of the long-term impact of control. An example of a population dynamic approach to cost-effectiveness analysis that can assess the impact of treatment on infection and disease due to the intestinal nematodes is presented to illustrate the potential of this approach in modeling the cost-effectiveness of schistosomiasis control.
Doctoral training of African scientists.
Authors: Doumbo O K , Krogstad D J
Published: May 2017

There are two principal rationales for doctoral training of African scientists in health: 1) these scientists are essential for the nations of sub-Saharan Africa to define and implement their own health priorities, and 2) the research they perform is essential for development. However, this training is difficult because of its expense (> $20,000 per year), because many developed country mentors are unaware of the realities of research in sub-Saharan Africa, and because major differences in salary provide a financial disincentive to return. We describe a training strategy that reduces attrition because it is linked to the investigators' responsibilities before and after training, and to home country priorities. This strategy requires a close relationship between the developing country (on-site) and developed country (off-site) mentors, with joint participation in the selection and funding process, followed by course work and short-term, independent projects off-site that lead to a thesis project in the developing country, and subsequently to a defined professional position in the developing country after completion of the doctoral degree. For this strategy to succeed, the developed country mentor must have both field experience and investigative expertise; the developing country mentor must have an understanding of modern biology, as well as clinical and epidemiologic experience. In addition, we would like to emphasize that the long-term retention of these talented, highly-trained individuals requires a similar long-term commitment by their developed country mentors, well beyond the short term of most research funding.
Human antibody responses to Trypanosoma cruzi 70-kD heat-shock proteins.
Authors: Krautz G M , Peterson J D , Godsel L M , Krettli A U , Engman D M
Published: May 2017

Heat-shock proteins of the 70-kD (hsp70) family are targets of humoral and cellular immune responses following bacterial or parasitic infections, including Chagas' disease. In the present study, we measured antibodies in human sera reactive with hsp70s from the cytoplasm (cy-hsp70), mitochondrion (mt-hsp70), and endoplasmic reticulum (grp78) of Trypanosoma cruzi. Of the three hsp70s tested, only grp78 detected T. cruzi infection in more than 90% of nontreated (NT) patients, with cy-hsp70 and mt-hsp70 detecting only 78% and 25% of NT patients, respectively. Reactivity of leishmanial sera was 77% with cy-hsp70, 13% with grp78, and 5% with mt-hsp70. Therefore, considering sensitivity and specificity, the best candidate for T. cruzi serodiagnosis is grp78. Combination of grp78 with a T. cruzi 24-kD flagellar calcium binding protein (FCaBP) increased the diagnostic sensitivity from 90% to 97% but increased leishmanial reactivity from 3% to 8%. To determine whether hsp70s are useful for discriminating between cured and noncured patients treated with trypanocidal drugs, we tested sera from treated noncured (TNC) patients and cured patients who have positive conventional serology, termed treated dissociated (TD). The cy-hsp70 and grp78 reacted with 74% and 68% of TNC patient sera, respectively, but these antigens did not discriminate TNC from TD patients (52% and 45% positive, respectively). The mt-hsp70 was detected by sera from few TNC patients (18%) and no TD patients. Although individual hsp70s were not useful for determining the effect of trypanocidal drugs on T. cruzi infection in individual patients, the majority of TNC patient sera (70-80%) reacted with two or three of the hsp70s. In contrast, no TD sera reacted with all three hsp70s, and 40% did not react with any of the hsp70s, indicating that the number of hsp70s detected decreases following successful treatment. Considered together, these results show that grp78 has potential as a diagnostic antigen and that absence of reactivity to all three hsp70s may be indicative of effective treatment.
The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector.
Authors: Hogh B , Gamage-Mendis A , Butcher G A , Thompson R , Begtrup K , Mendis C , Enosse S M , Dgedge M , Barreto J , Eling W , Sinden R E
Published: May 2017

Using serum or infected blood from Danish volunteers and Plasmodium falciparum-infected Mozambican patients, respectively, the impact of curative doses of chloroquine and pyrimethamine/sulfadoxine upon infectivity of P. falciparum to Anopheles arabiensis and An. gambiae or of P. berghei to An. stephensi was studied. Both treatments cleared circulating P. falciparum gametocytes within 28 days. Before this clearance, chloroquine enhanced infectivity to An. arabiensis, whereas pyrimethamine/sulfadoxine decreased infectivity. Patients harboring chloroquine-resistant parasites as opposed to -sensitive ones were 4.4 times more likely to have gametocytes following treatment. In contrast, pyrimethamine/sulfadoxine-resistant parasites were 1.9 times less likely to produce gametocytes. In laboratory infections using replicated P. berghei or P. falciparum preparations, serum from chloroquine-treated, uninfected, nonimmune volunteers enhanced gametocyte infectivity with increasing efficiency for 21 days following treatment, whereas pyrimethamine/sulfadoxine significantly suppressed infectivity. The observed enhancement in infectivity induced by the use of chloroquine combined with increased gametocytemias in chloroquine-resistant strains may in part explain the rapid spread of chloroquine resistance in endemic populations.
A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG antivenoms for Bothrops snake bites in Uraba, Colombia. The Regional Group on Antivenom Therapy Research (REGATHER).
Authors: Otero-PatiÃ±o R , Cardoso J L , Higashi H G , Nunez V , Diaz A , Toro M F , Garcia M E , Sierra A , Garcia L F , Moreno A M , Medina M C , CastaÃ±eda N , Silva-Diaz J F , Murcia M , Cardenas S Y , Dias da Silva W D
Published: May 2017

The therapeutic efficacy and the incidence of early antivenom reactions (EARs) were compared in a clinical trial performed in 79 patients bitten by Bothrops sp. in UrabÃ¡, Colombia. Patients were randomized into three groups according to the antivenom administered: A (n = 30, Butantan polyspecific, pepsin-digested Bothrops antivenom); B (n = 27, Butantan polyspecific, whole IgG Bothrops antivenom); and C (n = 22, Colombian commercial, monovalent, whole IgG Bothrops antivenom). The groups were comparable in all clinical and epidemiologic aspects; 33 patients had mild, 22 moderate, and 24 severe envenoming. At the doses used (two, four, and six vials [10 ml/vial] for mild, moderate, and severe envenomings, respectively) there were no differences between the antivenoms in restoring normal hemostatic parameters within 24 hr. The evolution of local envenoming was comparable in the three groups. Serum venom/antivenom kinetics determined by ELISA showed a complete clearance of venom levels 1 hr after treatment in mild/moderate envenomings. In severe cases, venom levels remained detectable up to 24 hr and recurrence of antigenemia was observed in some cases. Antivenom concentrations remained at high levels up to 24 hr of treatment. The incidence of EARs was significantly different in the groups: A (36.7%), B (11.1.%), and C (81.8%). There were no life-threatening anaphylactic reactions. We conclude that the efficacy of the three antivenoms was similar in neutralizing human Bothrops envenomings and that the production of whole IgG antivenoms by caprylic acid fractionation is a good alternative for reducing the incidence of EARs.
Early clinical response to different therapeutic regimens for human brucellosis.
Authors: Malik G M
Published: May 2017

Seventy-three cases of acute brucellosis were studied in relation to fever duration and hospital stay following different drug combinations, including gentamicin plus cotrimoxazole, rifampicin plus doxycycline, rifampicin plus cotrimoxazole, rifampicin plus tetracycline, streptomycin plus doxycycline, doxycycline plus cotrimoxazole, tetracycline plus cotrimoxazole, and tetracycline plus streptomycin. No statistical significant difference was found between these combinations regarding early clinical response in human brucellosis.
Short report: detection of Leishmaniavirus in human biopsy samples of leishmaniasis from Peru.
Authors: Saiz M , Llanos-Cuentas A , Echevarria J , Roncal N , Cruz M , Muniz M T , Lucas C , Wirth D F , Scheffter S , Magill A J , Patterson J L
Published: May 2017

Leishmaniavirus is a double-stranded RNA virus that persistently infects some strains of the protozoan parasite Leishmania. There is considerable interest in the possibility that the presence of this virus alters parasite phenotype and may affect disease pathogenesis. If so, the virus marker could provide a valuable prognostic indicator for human leishmaniasis, particularly in those cases caused by New World parasite strains. The virus has been detected in cultured L. braziliensis, L. b. guyanensis, and L. major. To date there has been no information as to the extent of infection in samples prior to culturing in the laboratory. This study demonstrates, through the reverse transcription-polymerase chain reaction, that Leishmaniavirus exists in human biopsy samples of leishmaniasis prior to manipulation in culture.
Transmission intensity and Plasmodium falciparum diversity on the northwestern border of Thailand.
Authors: Paul R E , Hackford I , Brockman A , Muller-Graf C , Price R , Luxemburger C , White N J , Nosten F , Day K P
Published: May 2017

Genetic analysis of the number of Plasmodium falciparum genotypes per infected person in regions of holoendemic and hyperendemic malaria suggest that in areas of lower transmission intensity, significantly fewer parasite genotypes per infected person should be found. A predominance of single clone infections in the human population could generate the controversial clonal population structure proposed for P. falciparum by Tibayrenc and others. Characterization of P. falciparum from individuals on the Thai-Burmese border, an area of hypoendemic transmission, revealed a higher number of genotypes per infected person than that predicted. Possible reasons for this observation are discussed, with particular attention paid to human migration and multidrug resistance.
Prognostic factors of green pit viper bites.
Authors: Rojnuckarin P , Mahasandana S , Intragumthornchai T , Sutcharitchan P , Swasdikul D
Published: May 2017

Clinical features of green pit viper bites vary from asymptomatic to fatal bleeding. Antivenin promptly reverses the coagulopathy but has considerable adverse side effects. In this study, potential clinical predictors of severe outcomes (wound necrosis, wound infection, and systemic bleeding) and antivenin allergy were determined in 271 moderate to severe cases of green pit viper bites by multivariate analysis. The incidences of systemic bleeding, wound necrosis, secondary infection, and antivenin allergy were 17.3%, 6.6%, 5.5%, and 20.8% respectively. The predictors of systemic bleeding were the combination of thrombocytopenia and prolonged venous clotting time and bite sites away from digits. A bite on the fingers or toes was a risk factor for skin necrosis (P = 0.03). Systemic absorption of the venom from digits may be poor, resulting in severe local but mild systemic effects. The presence of blisters often led to necrosis and secondary infections (P = 0.0037 and P = 0.0006, respectively). Although negative skin test results do not exclude the possibility of antivenin allergy, positive results indicate a high risk (P = 0.016) requiring special precautions.
Variant- and strain-specific immunity in Saimiri infected with Plasmodium falciparum.
Authors: Fandeur T , Chalvet W
Published: May 2017

Variant- and strain-specific immunity to malaria in Saimiri monkeys infected with homologous O and R variants of the Palo Alto strain (FUPSP) of Plasmodium falciparum or by various heterologous divergent strains were studied. Following homologous reinfections, the primary immune response in monkeys was effective only against the same variant type but not against the other variant, which differed only by antigens exposed at the surface of the infected red blood cell. In contrast, after two successive inoculations with a single variant type, a variant transcending immunity developed to both O and R parasite populations. The immunity against FUPSP in monkeys repeatedly infected with various combinations of heterologous strains, including Sal I, Tanzania, Camp, FUPCP, FCH4, FVO, and FUPCDC parasites was less effective, resulting at best in protecting the monkey against fulminating infection. However, in several cases, previous or concomitant heterologous infections modified the course of virulent infection by FUPSP parasites, indicating a significant degree of cross-protection between the strains. Therefore, in this model, while variant- and strain-specific antigens are important components of acquired immunity to malaria, the monkey immune response to infection transcends phenotypic antigenic variation and strain diversity.
Pentoxifylline as an ancillary treatment for severe falciparum malaria in Thailand.
Authors: Looareesuwan S , Wilairatana P , Vannaphan S , Wanaratana V , Wenisch C , Aikawa M , Brittenham G , Graninger W , Wernsdorfer W H
Published: May 2017

Pentoxifylline, an inhibitor of tumor necrosis factor, has been evaluated as an antimalarial agent in combination with artesunate in 45 patients with severe falciparum malaria. Patients were admitted to the intensive care unit at the Hospital for Tropical Diseases in Bangkok, Thailand, and randomly assigned to treatment for 72 hr with a combination of intravenously administered artesunate and 1) placebo, 2) low-dose pentoxifylline (0.83 mg/kg/hr), or 3) high-dose pentoxifylline (1.67 mg/kg/hr). All 45 patients had one or more manifestations of severe malaria such as cerebral malaria (n = 18), renal failure requiring hemodialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n = 30). The overall severity was comparable in the three groups. Clinical outcome was assessed with respect to the parasite clearance time and the fever clearance time in all patients. In addition, a number of subsidiary outcome variables were examined in specific subgroups, including the recovery time from coma for patients with cerebral malaria, the duration of intubation in patients with respiratory distress, the number of hemodialysis treatments needed for patients with acute renal failure, and the number of units of blood administered to patients requiring transfusion. Concentrations of tumor necrosis factor were reduced in all three groups at 48 hr after treatment. No significant differences among the three treatment groups were found for any of the outcome variables examined. We conclude that the addition of pentoxifylline to artesunate therapy for severe malaria produced no evident clinical benefit.
Seroprevalence of lymphocytic choriomeningitis virus in Nova Scotia.
Authors: Marrie T J , Saron M F
Published: May 2017

An ELISA system was used to determine the rate of seropositivity to lymphocytic choriomeningitis virus (LCMV) among a random sample of 505 Nova Scotians. Twenty (4%) were positive. Complete questionnaire data were available on all 20 seropositive subjects and on 449 seronegative subjects. Seventeen (85%) of the seropositive subjects were females (P = 0.03). It is concluded that infection with LCMV is present in Nova Scotia and females are more likely to be infected than males.
Malaria risk factors in an endemic region of Sri Lanka, and the impact and cost implications of risk factor-based interventions.
Authors: Gunawardena D M , Wickremasinghe A R , Muthuwatta L , Weerasingha S , Rajakaruna J , Senanayaka T , Kotta P K , Attanayake N , Carter R , Mendis K N
Published: May 2017

In an 18-month study of malaria in a population of 1,875 residents in 423 houses in an endemic area in southern Sri Lanka, the risk of malaria was found to be 2.5-fold higher in residents of poorly constructed houses than in those living in houses of good construction type. In residents of poorly constructed houses but not in others, the risk was even greater when the house was located near a source of water that could act as a potential breeding place for malaria vector mosquitoes (P = 0.0001). Based on previous findings that confirmed that house construction type was itself a risk determinant, and not merely a marker of other behavioral factors, we have estimated the potential impact of two feasible interventions to reduce the risk of malaria: 1) the imposition of a buffer zone of 200 meters around bodies of water from which houses of poor construction were excluded, which was estimated to lead to a 21% reduction of the malaria incidence in the overall population and a 43% reduction in the relocated community; and 2) the conversion of houses of poor construction type located in the buffer zone to those of a good construction type, which was estimated to lead to a 36% reduction in the incidence rates in the whole population and a 76% reduction in the residents of houses whose construction type was improved. Taking into consideration the cost to the Government of malaria prevention, we estimated the worth of a Government's investment in improving house construction type. The investment in housing was estimated to be offset in 7.2 years by savings to the Government on malaria costs alone, and beyond this period, to bring a return on the Government's investment by way of savings to the malaria control program.
Use of monoclonal antibodies prepared against Schistosoma mansoni hatching fluid antigens for demonstration of Schistosoma haematobium circulating egg antigens in urine.
Authors: Nibbeling H A , Kahama A I , Van Zeyl R J , Deelder A M
Published: May 2017

A panel of 17 monoclonal antibodies (MAbs) against Schistosoma soluble egg antigens (SEAs) was produced from BALB/c mice immunized with antigens secreted/excreted by Schistosoma mansoni eggs. In this study, we demonstrate that 16 MAbs were reactive with S. haematobium SEA in addition to S. mansoni SEA. The MAbs were tested as potential immunodiagnostic reagents in a homologous sandwich ELISA format to detect circulating soluble egg antigens (CSEAs) in serum and urine samples of S. mansoni- or S. haematobium-infected individuals. When samples of S. mansoni-infected individuals were tested, none of these MAbs performed as good as the previously described S. mansoni-specific 114-5B1-A and 114-4D12-A MAbs. However, 11 MAbs (of the IgM isotype) detected CSEA in urine samples of S. haematobium-infected individuals. Three MAbs, 290-2E6-A, 291-3D5-A, and 291-5D5-A, were selected for a pilot study with 47 urine samples of S. haematobium-infected individuals from Kenya. The CSEA levels detected with each of these ELISAs showed a significant correlation with urinary egg counts (Spearman rho > 0.37, P < 0.01) and with each other (Spearman rho > 0.74, P < 0.001). Based on the 92% specificity and 90% sensitivity of the assay, the ELISA using MAb 290-2E6-A was found to be the most promising assay for immunodiagnosis of S. haematobium infections.