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Comparative performance of the ParaSight F test for detection of Plasmodium falciparum in malaria-immune and nonimmune populations in Irian Jaya, Indonesia.

A comparison was made of the performance of the ParaSight F test (F test) for detection of Plasmodium falciparum in blood from malaria-immune (410 native Irianese) and nonimmune (369 new transmigrants) populations in Irian Jaya, Indonesia, where malaria is hyperendemic and all four species of human malaria occur. There were highly significant differences between populations in the sensitivity (Irianese, 60% versus transmigrants, 84%; P < 0.001) and specificity (Irianese, 97% versus transmigrants, 84%; P < 0.001) of the F test. The test had comparably high levels of sensitivity for Irianese children aged < or = 10 years, both age groups of transmigrants (76-85%), but low sensitivity for Irianese aged > 10 years (40%), among whom only 7% of parasitaemias < 120 per microliter and 69% of those > 120 per microliter were detected. Specificity was comparably high for transmigrant children aged < or = 10 years and both age groups of Irianese (93-98%). The low specificity for transmigrants aged > 10 years (79%) was due to a preponderance of false positives, frequently identified by microscopy as P. vivax. The results suggest that comparison based on microscopy underestimated the performance of the ParaSight F test and that malaria immune status, irrespective of P. falciparum density, may influence the test's sensitivity.

Adult↗

Efficacy and safety of liposomal amphotericin B (AmBisome) for visceral leishmaniasis in endemic developing countries.

Reported are the results of a study to determine the efficacy and safety of liposomal amphotericin B (AmBisome) for treating visceral leishmaniasis (kala-azar) in several developing countries where the disease is endemic (Brazil, India, and Kenya). At each study site, sequential cohorts of 10 patients each were treated with AmBisome at a dose of 2 mg.kg-1.day-1 (2 MKD). The first cohort received regimen 1:2 MKD on days 1-6 and day 10 (total dose: 14 mg/kg). If the efficacy with this regimen was satisfactory, a second cohort received regimen 2:2 MKD on days 1-4 and 10 (total dose: 10 mg/kg); and a third cohort received regimen 3:2 MKD on days 1, 5, and 10 (total dose: 6 mg/kg). In India, regimens 1, 2, and 3 (which were studied concurrently) each cured 100% of 10 patients. In Kenya, regimen 1 cured all 10 patients, regimen 2 cured 90% of 10 patients, but regimen 3 cured only 20% of 5 patients. In Brazil, regimen 1 was only partially curative: 5 of 13 patients (62%). Therefore, 15 patients were administered regimen 4 (2 MKD for 10 consecutive days; total dose, 20 mg/kg) and 13 patients were cured (83%). These results suggest that for the treatment of kala-azar the following doses of AmBisome should be administered: in India and Kenya, 2 mg/kg on days 1-4 and day 10; and in Brazil, 2 mg/kg on days 1-10.

Adolescent↗

Ecology, economics and political will: the vicissitudes of malaria strategies in Asia.

The documented history of malaria in parts of Asia goes back more than 2,000 years, during which the disease has been a major player on the socioeconomic stage in many nation states as they waxed and waned in power and prosperity. On a much shorter time scale, the last half century has seen in microcosm a history of large fluctuations in endemicity and impact of malaria across the spectrum of rice fields and rain forests, mountains and plains that reflect the vast ecological diversity inhabited by this majority aggregation of mankind. That period has seen some of the most dramatic changes in social and economic structure, in population size, density and mobility, and in political structure in history: all have played a part in the changing face of malaria in this extensive region of the world. While the majority of global malaria cases currently reside in Africa, greater numbers inhabited Asia earlier this century before malaria programs savored significant success, and now Asia harbors a global threat in the form of the epicenter of multidrug resistant Plasmodium falciparum which is gradually encompassing the tropical world. The latter reflects directly the vicissitudes of economic change over recent decades, particularly the mobility of populations in search of commerce, trade and personal fortunes, or caught in the misfortunes of physical conflicts. The period from the 1950s to the 1990s has witnessed near "eradication" followed by resurgence of malaria in Sri Lanka, control and resurgence in India, the influence of war and postwar instability on drug resistance in Cambodia, increase in severe and cerebral malaria in Myanmar during prolonged political turmoil, the essential disappearance of the disease from all but forested border areas of Thailand where it remains for the moment intractable, the basic elimination of vivax malaria from many provinces of central China. Both positive and negative experiences have lessons to teach in the debate between eradication and control as alternative strategies. China has for years held high the goal of "basic elimination", eradication by another name, in sensible semi-defiance of WHO dictates. The Chinese experience makes it clear that, given community organization, exhaustive attention to case detection, management and focus elimination, plus the political will at all levels of society, it is possible both to eliminate malaria from large areas of an expansive nation and to implement surveillance necessary to maintain something approaching eradication status in those areas. But China has not succeeded in the international border regions of the tropical south where unfettered population movement confounds the program. Thailand, Malaysia and to an extent Vietnam have also reached essential elimination in their rice field plains by vigorous vertical programs but fall short at their forested borders. Economics is central to the history of the rise and fall of nations, and to the history of disease in the people who constitute nations. The current love affair with free market economics as the main driving force for advance of national wealth puts severe limitations on the essential involvement of communities in malaria management. The task of malaria control or elimination needs to be clearly related to the basic macroeconomic process that preoccupies governments, not cloistered away in the health sector Historically malaria has had a severe, measurable, negative impact on the productivity of nations. Economic models need rehoning with political aplomb and integrating with technical and demographic strategies. Recent decades in Chinese malaria history carry some lessons that may be relevant in this context.

Asia, Southeastern↗

Evaluation of community compliance with annual ivermectin treatment of onchocerciasis in Patigi, Nigeria.

A low community acceptance and compliance with annual ivermectin treatment was recorded in Patigi, Nigeria where ivermectin is being distributed centrally in designated centres for the fifth time. The average community acceptance rate (ACAR) for the treatment period was 53.48% while the community compliance rate (CCR) of 1.9% of the total subjects interviewed was recorded. Absenteeism from treatment was a major reason for non-treatment (average, 34.6%). Inadequate and poor mobilisation was identified as a major reason for the low ivermectin acceptance and compliance with treatment in this community. An intensive mobilisation with health education messages with the inclusion of religious/traditional institutions is advocated.

Adolescent↗

Helminthic infections of urban and rural schoolchildren in Penang Island, Malaysia: implications for control.

The intestinal parasites of schoolchildren from an urban and a rural area on Penang island, Malaysia were compared. Examination of stool samples for helminth eggs showed that helminths found were Trichuris, Ascaris and hookworms. The results indicate that there is no significant difference (p<0.05) between rural and urban schoolchildren as regards to the prevalence of the three species of helminths. An extensive control program targetted at schoolchildren to monitor the helminth problem on the island is suggested.

Ancylostomatoidea↗

Concurrent parasitic infections among patients with onchocerciasis and controls in Sierra Leone, West Africa.

Research was performed into the prevalence of concurrent parasite infection among 23 patients with onchocerciasis and 13 onchocerciasis-negative controls in Sierra Leone, West Africa. Stools, urine sediments and bloodsmears were examined for ova, parasites and microfilariae. Results showed the presence of Hookworm, Schistosoma mansoni, Trichuris trichiura and Ascaris lumbricoides. A positive relationship was found between O. volvulus and Hookworm infection. The effects of polyparasitism on immunodiagnosis and the need for further research is discussed.

Adolescent↗

Malaria genome project and its impact on the disease.

Malaria remains uncontrolled to-date due to lack of effective parasite and vector control strategies. With the completion of the host, parasite and vector genome projects more suitable and effective disease control measures can be achieved. Here we have reviewed the Plasmodium falciparum genome project and its impact on malaria research in future. The parasite genome project has revealed certain metabolic pathways which can be targeted to develop antimalarial drugs. It has also identified large number of potential antigens for the future potential vaccines. Now the researchers in the malaria field can plan to take up the studies, which can yield more fruitful results within the limited financial resources using bioinformatics, proteomics, structural, functional and comparative genomics, etc.

Animals↗

ZOOM: a generic personal computer-based teaching program for public health and its application in schistosomiasis control.

Schistosomiasis, a group of parasitic diseases caused by Schistosoma parasites, is associated with water resources development and affects more than 200 million people in 76 countries. Depending on the species of parasite involved, disease of the liver, spleen, gastrointestinal or urinary tract, or kidneys may result. A computer-assisted teaching package has been developed by WHO for use in the training of public health workers involved in schistosomiasis control. The package consists of the software, ZOOM, and a schistosomiasis information file, Dr Schisto, and uses hypermedia technology to link pictures and text. ZOOM runs on the IBM-PC and IBM-compatible computers, is user-friendly, requires a minimal hardware configuration, and can interact with the user in English, French, Spanish or Portuguese. The information files for ZOOM can be created or modified by the instructor using a word processor, and thus can be designed to suit the need of students. No programming knowledge is required to create the stacks.

Computer-Assisted Instruction↗

Recent advances in biology and immunobiology of Eimeria species and in diagnosis and control of infection with these coccidian parasites of poultry.

Avian coccidiosis, an intestinal disease caused by protozoan parasites of the genus Eimeria, occurs worldwide. It is considered to be one of the most economically important diseases of domestic poultry. For many years, prophylactic use of anticoccidial feed additives has been the primary means of controlling coccidiosis in the broiler industry and has played a major role in the growth of this industry, which now can produce about 7.6 billion chickens annually. However, development of anticoccidial resistance has threatened the economic stability of the broiler industry. Although there has been little effort by the pharmaceutical industry to develop new anticoccidials, the mounting problem of drug resistance of Eimeria species has prompted major research efforts to seek alternative means of control through increased knowledge of parasite biology, host response, and nutritional modulation. As a consequence, important advancements have been made, particularly in defining parasite antigens that have potential use in vaccines, defining the Eimeria genome, understanding the immunology of coccidial infections, and the practical applications of live vaccines. This review describes the progress in these areas, most of which has occurred within the past 10 to 15 years.

Animals↗

Risk factors associated with human cystic echinococcosis in Jordan: results of a case-control study.

The parasites causing cystic echinococcosis (CE) are transmitted to man and domestic animals either directly or indirectly from dogs. High levels of human infection have been frequently described in sheep-rearing areas of the world, where the infection cycles between dogs and sheep through the use of working dogs and the feeding of sheep offal to dogs. A case-control study was undertaken in northern Jordan to examine the epidemiological characteristics of echinococcosis in a Muslim community. Forty-four indigenous Jordanians who had been treated for CE between 1990 and 1996 were contacted and three controls for each case, matched for sex and age, were selected from the Jordanian population. The most important single factor associated with treatment for CE was the main source of domestic water; 42 (95%) of the cases but only 81 (61%) of the controls reported that they used a public, piped, water supply as their principal source of household water [odds ratio (OR) = 13.22; 95% confidence interval (CI) = 2.91-83.7]. The keeping of dogs or close association with dogs or farm animals was not associated with any increased risk of CE. However, individuals who grew their own vegetables had a significantly decreased risk of acquiring CE (OR = 0.30; CI = 0.08-0.98). There was evidence of widespread ignorance of the disease and how it is transmitted.

Animals↗

Cellular responses and cytokine profiles in Ascaris lumbricoides and Trichuris trichiura infected patients.

The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and interferon (IFN)-gamma secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-alpha, IL-12 and IFN-gamma was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P < 0.05), whereas parasite-specific IgE antibody levels were similarly high in infected individuals and in endemic controls. In summary, chronically infected Ascaris and Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-alpha, IFN-gamma and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage.

Adult↗

Molecular characterization of a calcium binding translationally controlled tumor protein homologue from the filarial parasites Brugia malayi and Wuchereria bancrofti.

We have cloned homologues of the mammalian translationally controlled tumor protein (TCTP) from the human filarial parasites Wuchereria bancrofti and Brugia malayi. TCTP genes from B. malayi and W. bancrofti were expressed in a T7 promoter vector as histidine tagged fusion proteins. Both the recombinant B. malayi TCTP (rBm-TCTP) and recombinant W. bancrofti TCTP (rWb-TCTP) have a molecular mass of approximately 28 kDa with the histidine tag. Sequence analyses showed that there is a 98% similarity between the two filarial TCTPs at amino acid levels and are immunologically cross-reactive. Analysis of soluble proteins from various lifecycle stages of B. malayi suggested that the expression of Bm-TCTP might be differentially regulated and occurs in multimeric form. Recombinant TCTP were found to form multimers in solution under non-reducing conditions. The tendency for filarial TCTPs to become multimers was predicted by the presence of the Lupas coiled coil structure in their sequence. Despite the absence of a signal sequence, Bm-TCTP is present abundantly in the excretory/secretions (ES) of microfilariae. Characterization studies showed that both Bm- and Wb-TCTPs are calcium-binding proteins and have histamine-releasing function in vitro. When injected intraperitoneally both the filarial TCTPs induced inflammatory infiltration of eosinophils into the peritoneal cavity of mice suggesting that the filarial TCTPs may have a role in the allergic inflammatory responses associated with filarial infections.

Amino Acid Sequence↗

Selective internalization of choline-phospholipids in Plasmodium falciparum parasitized human erythrocytes.

We have incubated control and Plasmodium falciparum parasitized human erythrocytes with lipid vesicles containing radiolabeled long-chain phosphatidylcholine and sphingomyelin, in the presence of a nonspecific lipid transfer protein. Most of the radiolabeled phospholipids were, immediately thereafter, available for extracellular phospholipases, suggesting that uptake of vesicles as such did not occur. In time, the amount of phosphatidylcholine inserted in the outer leaflet of the host cell membrane of parasitized erythrocytes decreased, indicating that phosphatidylcholine was being internalized in parasitized erythrocytes. The exclusion of sphingomyelin from the internalization process suggests that the removal of phosphatidylcholine from the outer leaflet of the erythrocyte membrane is caused by transbilayer migration, rather than by endocytosis. The extent of phosphatidylcholine internalization indicates that part of it does not remain in the inner leaflet of the host cell membrane, but is taken up by the intraerythrocytic parasite. Individual phosphatidylcholine species, containing 16:0/18:1-, 16:0/18:2- and 16:0/20:4-fatty acids, showed similar extents of internalization, after being incorporated in parasitized erythrocytes by a phosphatidylcholine specific transfer protein.

Animals↗

Hirsutella thompsonii and Metarhizium anisopliae as potential microbial control agents of Varroa destructor, a honey bee parasite.

The potential of Hirsutella thompsonii Fisher and Metarhizium anisopliae (Metschinkoff) as biological control agents of the parasitic mite, Varroa destructor Anderson and Trueman was evaluated in the laboratory and in observation hives. In the laboratory, time required for 90% cumulative mortality of mites (LT(90)) was 4.16 (3.98-4.42) days for H. thompsonii and 5.85 (5.48-7.43) days for M. anisopliae at 1.1 x 10(3) conidia mm(-2). At a temperature (34+/-1 degrees C) similar to that of the broodnest in a honey bee colony, Apis mellifera L., H. thompsonii [LC(90)=9.90 x 10(1) (5.86-19.35) conidia mm(-2) at Day 7] and M. anisopliae [LC(90)=7.13 x 10(3) (2.80-23.45) conidia mm(-2) at Day 7] both showed significant virulence against V. destructor. The applications of H. thompsonii to observation hives resulted in significant mortality of mites, and reduction of the number of mites per bee 21 and 42 days post-treatments. The treatments did not significantly affect the mite population in sealed brood. However, the fungus must have persisted because infected mites were still observed [82.97+/-(0.6)%] 42 days post-treatment. In addition, the fungus was found to sporulate on the host. A small percentage [2.86+/-(0.2)%] of dead mites found in the control hives also showed fungal infection, suggesting that adult bees drifted between hives and disseminated the fungus. H. thompsonii was harmless to the honey bees at the concentrations applied and did not have any deleterious effects on the fecundity of the queens. Microbial control with fungal pathogens provides promising new avenues for control of V. destructor and could be a useful component of an integrated pest management program for the honey bee industry.

Animals↗

Immunisation of mice against neosporosis.

In the present study a murine encephalitis model was used to investigate if protection against neosporosis could be achieved by immunisation. Groups of 10 mice were immunised with a sublethal dose of live Neospora caninum tachyzoites, N. caninum antigens incorporated into iscoms, N. caninum lysate mixed with Quil A, or N. caninum lysate in PBS. Control mice were given Quil A only. Challenge infection with 2.5x10(6) N. caninum tachyzoites resulted in clinical symptoms that remained until the end of the experiment in the controls. In contrast, mice immunised with live parasites or parasite lysate in Quil A only showed mild and transient symptoms. Of nine mice immunised with N. caninum iscoms, seven recovered while two died. Most severely affected were the mice immunised with parasite lysate only; all of them died within 28 days post-infection. Histological examination and scoring of brain lesions gave a significantly lower (P<0.0001) lesion score in mice immunised with live parasites than in controls. The groups immunised with iscoms or lysate and Quil A also had reduced lesion scores (P<0.04 and 0.07, respectively) but not the group given parasite lysate alone. The lesions seen in the latter group differed from those in the other groups. There was less cellular reaction and more tachyzoites indicating an active infection. The N. caninum specific antibody responses and cytokine production (IFN-gamma, IL-4 and IL-5) of splenocytes were analysed at the time of challenge infection. The results suggest a correlation between protection and high levels of IFN-gamma. Also, the immune responses recorded in mice immunised with parasite lysate without adjuvant were relatively weak and more towards the Th2 type, when compared with the other immunisation schedules. This is consistent with the weaker inflammatory response observed in the brains of these mice.

Adjuvants, Immunologic↗

Concerted action of perforin and granzymes is critical for the elimination of Trypanosoma cruzi from mouse tissues, but prevention of early host death is in addition dependent on the FasL/Fas pathway.

CTL and NK cells are critical for resistance to acute Trypanosoma cruzi infection, but are also implicated in the pathology induced by this intracellular protozoan parasite. Here we explore to what extent the two main cytolytic pathways of CTL and NK cells, i.e. the granule exocytosis and the Fas ligand (FasL)/Fas pathways, are responsible for the elimination of parasites from mouse tissues and control of organ pathology. For this purpose we have employed mouse strains with targeted gene defects in one or more components - including perforin, granzyme A and granzyme B, and Fas - of either of the two cytolytic pathways, and we used the highly pathogenic T. cruzi strain Tulahuen. We show that parasites are effectively cleared from infected tissues independently of the FasL/Fas pathway by the concerted action of perforin and the two granzymes. However, prevention of pathology and early host death is critically dependent in addition on an operational FasL/Fas interaction. Thus, in contrast to C57BL/6 (B6) wild-type mice, mouse strains with deficiencies in either the FasL/Fas or the perforin/granzyme pathway similarly suffer from early death, independently of their differential capacity to control parasite growth; this finding indicates that the two cytolytic pathways control distinct but vital processes during infection with T. cruzi.

Animals↗

Controlled test evaluation of the benzimidazole anthelmintic VET 220-S alone or with concomitant trichlorfon treatment against naturally acquired gastrointestinal parasites in ponies.

A controlled test was done in 30 naturally infected ponies to evaluate the antiparasitic activity of the dienbendazole analog VET 220-S given alone or with trichlorfon (TCF) by nasogastric intubation. Six ponies were nontreated; 6 were given VET 220-S (5.0 mg/kg); 6 were given TCF (40 mg/kg); 6 were given VET 220-S (2.5 mg/kg) and TCF (40 mg/kg); and 6 were given VET 220-S (5.0 mg/kg) and TCF (40 mg/kg). All ponies were euthanatized and necropsied 7 or 8 days after treatment. Draschia megastoma, Oxyuris equi, Strongylus vulgaris, S edentatus, and small strongyles were removed efficaciously by all doses of VET 220-S. Habronema muscae and microfilariae of Onchocerca cervicalis were not removed by VET 220-S or TCF. Gasterophilus intestinalis was 97.9% removed by TCF. Pregnant mares in all groups were not adversely affected by treatment, except for 1 mare that had diarrhea after TCF treatment. Parasite eggs per gram and larval culture data agreed with necropsy data.

Animals↗