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Vector-borne disease problems in rapid urbanization: new approaches to vector control.

Owing to population growth, poor levels of hygiene, and increasing urban poverty, the urban environment in many developing countries is rapidly deteriorating. Densely packed housing in shanty towns or slums and inadequate drinking-water supplies, garbage collection services, and surface-water drainage systems combine to create favourable habitats for the proliferation of vectors and reservoirs of communicable diseases. As a consequence, vector-borne diseases such as malaria, lymphatic filariasis and dengue are becoming major public health problems associated with rapid urbanization in many tropical countries. The problems in controlling these diseases and eliminating vectors and pests can be resolved by decision-makers and urban planners by moving away from the concept of "blanket" applications of pesticides towards integrated approaches. Sound environmental management practices and community education and participation form the mainstay of some of the most outstanding successes in this area. On the basis of these examples, it is argued that the municipal authorities need to apply a flexible methodology, which must be based on the possibilities of mobilizing community resources, with minimal reliance on routine pesticidal spraying. In this way, vector control becomes a by-product of human development in the city environment. This is now a true challenge.

Animals↗

The Gambian National Impregnated Bed Net Programme: evaluation of effectiveness by means of case-control studies.

Two case-control studies, one on mortality and the other on malaria morbidity, were carried out in order to evaluate the impact of the Gambian National Insecticide Bed Net Programme during the second year of intervention and to explore the feasibility of such a study for the evaluation of programme effectiveness. For the mortality study, children 1-9 years old who died during the 1993 rainy season were matched by age and sex with 2 healthy controls from the same village. For the morbidity study, children 1-9 years old attending Fatoto or Jahalia Health Centres in The Gambia and who had fever and parasitaemia > or = 5000/microL were matched by age with a child attending the health centres without fever or parasitaemia. An additional healthy control was recruited from the case's village. No impact of insecticide-treated bed nets on mortality was detected and this was in keeping with the results obtained by prospective surveillance. A protective effect of insecticide-treated nets on malaria morbidity was detected when cases were compared with controls recruited at the health centres. However, this disappeared when cases were compared with controls recruited from the cases' villages. The mortality case-control study suggested that reducing the time between onset of disease and treatment may have an important impact on childhood mortality. In order to calculate programme cost-effectiveness, important for informed resource allocations to be made by health managers, it is essential to obtain evidence of effectiveness. This can be done by means of case-control studies, which are easier to carry out and require fewer resources than prospective surveillance. Nevertheless, it is necessary to be conscious of their pitfalls, particularly of the bias involved in the choice of cases and controls. The measurement of insecticide on the nets of the cases or controls is essential for such studies.

Case-Control Studies↗

Sustainability of pyrethroid-impregnated bednets for malaria control in Afghan communities.

Between 1992 and 1995 a series of studies was undertaken to assess the long-term suitability of pyrethroid-impregnated bednets (PIBs) for malaria control in Afghan refugee communities in two villages in North-West Frontier Province, Pakistan. During 1992, 86% of bednet owners volunteered to have their bednets re-impregnated, and a further 15% of families purchased nets at two-thirds of cost price. From 1992 onwards, 27% of the villagers returned to Afghanistan, and annual house spraying campaigns were introduced to protect those still resident but sleeping without bednets. Within 3 years, these campaigns, together with PIBs, reduced the annual incidence of malaria by 87%, from 597 to 78 cases per 1000 population. Nevertheless, 65% of resident families continued to re-impregnate their nets annually with permethrin. To assess whether PIBs were still being used and were still protective, in view of these reduced transmission rates, we carried out a case--control study in 1994 on febrile or otherwise symptomatic patients presenting at village health centres. Comparison of the slide-positivity rates of PIB users and those without bednets showed that regular usage reduced the odds of contracting falciparum and vivax malaria to 0.22 (95% confidence interval (CI): 0.09-0.55) and 0.31 (95% CI: 0.19-0.51), respectively. There was no evidence of a sex- or age-bias in bednet use or in protective effect. The results indicate that a community-based PIB programme is an appropriate malaria control measure in areas where management or security problems make traditional house-spraying campaigns impossible. A relevant finding for those involved in the monitoring of bednet distribution projects is that the local coverage of bednets and the local impact on malaria, even when introduced to remote areas, can be estimated very cheaply by health centre microscopists who simply catalogue blood film diagnoses according to patients' bednet use practices.

Afghanistan↗

Local transmission of Plasmodium vivax malaria in Singapore.

A localised outbreak involving 19 cases and two carriers of vivax malaria was reported at Dairy Farm from May to June 1996. Epidemiological investigations showed that the outbreak was caused by the introduction of two foreign workers with imported relapsing vivax malaria into this malaria-receptive area. Transmission of infection occurred amongst 17 other foreign workers residing in the locality and two local residents staying at a condominium nearby. The outbreak was rapidly brought under control through active case finding, isolation and treatment of infected persons, epidemic vector control measures, and improved drainage to prevent Anopheles maculatus breeding. Were it not for the very thorough epidemiological investigations in this episode, foreign workers and local residents with a recent travel history would have been misclassified as imported and the outbreak missed. Medical practitioners should always consider the possibility of malaria in a foreign worker presenting with fever and notify the case as soon as the disease is suspected.

Animals↗

Bone marrow-derived macrophages grown in GM-CSF or M-CSF differ in their ability to produce IL-12 and to induce IFN-gamma production after stimulation with Trypanosoma cruzi antigens.

Trypanosoma cruzi is the etiological agent of Chagas' disease in man. Control of parasitism at the beginning of experimental infection depends on cytokine-activated macrophages that synthesize nitric oxide (NO). We investigated macrophage populations derived in the presence of M-CSF (M-MØ) or GM-CSF (GM-MØ) regarding their ability to control intracellular parasitism by T. cruzi and to synthesize IL-12 and NO. Both macrophage populations supported intracellular multiplication of the parasite; when activated by IFN-gamma, GM-MØ exerted better control of parasitism. Stimulation of GM-MØ with T. cruzi or Staphylococcus aureus resulted in IL-12 production and higher levels of NO synthesis in comparison with stimulated M-MØ. Mice immunized with parasite-Ag-pulsed GM-MØ but not with pulsed M-MØ had increased IFN-gamma and IL-2 production in lymph nodes. However, when immunization was followed by infection with live parasites, transient elevation of IFN-gamma production was observed in both GM-MØ- and M-MØ-immunized mice, without reduction of blood parasite levels.

Animals↗

Parasitic disease in amphibians: control by the regulation of worm burdens.

This review considers three case studies based on macroparasites of anurans: (a) natural infections in the permanently-aquatic Xenopus laevis which represent the worm burdens acquired, and the implications for pathology, when hosts are exposed to continuous, year-round, transmission; (b) the desert toad, Scaphiopus couchii, which experiences invasion very briefly each year and provides a simplified system involving only a single significant infection (Pseudodiplorchis americanus); (c) the mesic Bufo bufo which has been the subject of experimental laboratory studies designed to measure the effects of Rhabdias bufonis infection on host growth, physical performance and survival. Experimental manipulation of both Scaphiopus and Bufo provide quantitative data on disease effects of macroparasites, including precise measurements of parasite-induced host mortality. Field data for Xenopus and Scaphiopus show that, despite high initial worm burdens from efficient transmission, infection levels at parasite maturity are modulated below those leading to significant disease. Experimental data for Scaphiopus and Bufo have documented the time-course and magnitude of this decline in intensities, and there is circumstantial evidence for Scaphiopus that this regulation is host-mediated. Immunological studies on Xenopus show that disease effects of the pathogenic Pseudocapillaroides xenopodis are exacerbated in thymectomised hosts and reversed by implantation of thymuses from MHC-compatible donors. Thus, whilst factorial experiments can demonstrate the potential of helminths to cause significant disease and mortality in anuran host-macroparasite interactions, powerful post-invasion regulation of worm burdens appears to exert a strong control of parasite-induced disease in natural host populations.

Animals↗

Haemoglobin inhibits the development of infective promastigotes and chitinase secretion in Leishmania major cultures.

Haemoglobin or blood in the growth medium of Leishmania major inhibited the formation of infective promastigotes and the secretion of chitinases. Inoculation of mice with stationary-phase parasites from control medium caused infections in 20/29 mice, compared to 3/20 mice injected with parasites grown with 10% rabbit blood, or 1/30 mice that received parasites grown with rabbit haemoglobin. The concentration of peanut lectin (PNA) required to agglutinate promastigotes was used as an index of their infectivity, ranging from a high concentration for infective populations to a low concentration for relatively non-infective populations. Agglutination of 50% of the parasites from control medium or from medium containing rabbit haemoglobin required 4.1 micrograms PNA/ml and 0.1 microgram PNA/ml, respectively. Chitinase activities/10(7) parasites decreased from 4.8 units chitinase and 12.5 units N-acetylglucosaminidase (NAGase) in the control to 2.0 units chitinase and 8.5 units NAGase in cultures containing rabbit haemoglobin. Rabbit, human, bovine and pigeon haemoglobins had various inhibitory effects on the activity of chitinases and not on the virulence, as expressed by PNA agglutination. The relevance of the results to the cycle of Leishmania is discussed.

Acetylglucosaminidase↗

beta-Chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi.

In the present study, we describe the ability of Trypanosoma cruzi trypomastigotes to stimulate the synthesis of beta-chemokines by macrophages. In vivo infection with T. cruzi led to MIP-1alpha, RANTES, and JE/MCP1 mRNA expression by cells from peritoneal inflammatory exudate. In addition, in vitro infection with T. cruzi resulted in expression of beta-chemokine MIP-1alpha, MIP-1beta, RANTES, and JE mRNA by macrophages. The expression of the beta-chemokine MIP-1alpha, MIP-1beta, RANTES, and JE proteins by murine macrophages cultured with trypomastigote forms of T. cruzi was confirmed by immunocytochemistry. Interestingly, macrophage infection with T. cruzi also resulted in NO production, which we found to be mediated mainly by beta-chemokines. Hence, treatment with anti-beta-chemokine-specific neutralizing antibodies partially inhibited NO release by macrophages incubated with T. cruzi parasites. Further, the addition of the exogenous beta-chemokines MIP-1alpha, MIP-1beta, RANTES, and JE/MCP-1 induced an increased T. cruzi uptake, leading to enhanced NO production and control of parasite replication in a dose-dependent manner. L-NMMA, a specific inhibitor of the L-arginine-NO pathway, caused a decrease in NO production and parasite killing when added to cultures of macrophages stimulated with beta-chemokines. Among the beta-chemokines tested, JE was more potent in inhibiting parasite growth, although it was much less efficient than gamma interferon (IFN-gamma). Nevertheless, JE potentiates parasite killing by macrophages incubated with low doses of IFN-gamma. Together, these results suggest that in addition to their chemotactic activity, murine beta-chemokines may also contribute to enhancing parasite uptake and promoting control of parasite replication in macrophages and may play a role in resistance to T. cruzi infection.

Animals↗

Malaria, agriculture, and development: lessons from past campaigns.

The author presents in this article a historical-epidemiological evaluation of several anti-malaria campaigns and of the relative contribution of various direct measures employed and indirect factors operating during these campaigns. Approaches and factors that may be essential or at least useful for successful malaria control are identified. The malaria story in Palestine/Israel and the experience of the Tennessee Valley Authority are analyzed in some detail. In both cases, direct anti-malaria measures were versatile and based mostly on reduction of mosquito breeding and elimination of Anopheles larvae. Efficient organization and coordination of anti-malaria efforts, strenuous research and understanding of the vector biology, and accompanying socioeconomic and agricultural development contributed to successful campaigns. Malaria control in other parts of the United States and in Italy is also considered. The World Health Organization global anti-malaria campaign is discussed in the light of these earlier experiences. The study concludes that no single measure is sufficient to control malaria and that future anti-malaria campaigns need to adopt strategies that are flexible, incorporated into local health services, and interrelated with agricultural practices. Moreover, a certain threshold of socioeconomic development, health services infrastructure, and educational level may have to be reached for the successful application and maintenance of direct anti-malaria measures.

Agriculture↗

Immunological control of hepatotoxicity and parasite egg excretion in Schistosoma mansoni infections: stage specificity of the reactivity of immune serum in T-cell deprived mice.

Within seven weeks of infection with 200 Schistosoma mansoni cercariae, T-cell deprived mice have been shown to suffer from extensive microvesicular damage to hepatocytes, and an inability to excrete parasite eggs at the same rate as comparably infected, immunologically intact controls. Administration of serum (CIS) from chronically infected, immunologically intact donors prevented the development of microvesicular cell damage and partially restored egg excretion rates in infected deprived mice. Serum pools obtained from mice injected either with intact S. mansoni eggs or with a homogenate of eggs emulsified in Freund's complete adjuvant (FCA) were as effective as CIS in preventing hepatotoxicity and restoring the rate of egg excretion in infected deprived recipients. The degree of protection of liver tissue afforded by immune sera could be monitored either by histopathological examination of liver sections or by estimation of serum transaminase concentrations, the results from both assays being generally in agreement. Sera from donor mice injected with cercarial or worm antigens in FCA were relatively inactive either in protecting against S. mansoni-induced liver damage or in reconstituting egg excretion rates in infected deprived mice. Serum from donor mice infected with 25 cercariae became hepato-protective between 49 and 53 days after infection of the donors, and the degree of hepatoprotective activity and egg excretion reconstituting capacity in the serum of 25 cercariae-infected donors was shown to increase between 8 and 16 weeks after infection. Increasing the size of infection of the serum donors to 100 cercariae gave only a marginal increase of hepatoprotective activity at 7 weeks when compared with serum donors infected with 25 cercariae for 7 weeks. Liver parenchymal cells of very heavily infected, immunologically intact mice were found to show microvesicular damage similar to that in livers of infected deprived mice, and administration of CIS to these normal mice was histopathologically protective. However, the elevated serum transaminase concentrations obtaining in the infected normal mice were not reduced to any extent by CIS. The results obtained from serum-reconstituted deprived mice are discussed in terms of the contribution they may make to a better understanding of the host-parasite relationship in immunologically intact mice.

Animals↗

Plasma proteins in children with trichuris dysentery syndrome.

AIMS: To determine whether in Trichuris trichiura dysentery there is (1) evidence of a systemic inflammatory response, (2) evidence that the plasma protein disturbance has special characteristics compared with uninfected children in the endemic environment. METHODS: Three groups of children (age 1.6 to 11.4 years) were studied: 53 cases of trichuris dysentery syndrome (TDS), 16 cases of chronic non-secretory diarrhoea not infected with the parasite ("disease controls", DC), and 20 asymptomatic, parasite-free primary schoolchildren (normal controls, NC). C reactive protein, alpha 1 antitrypsin, caeruloplasmin, albumin, total globulin, fibrinogen, fibronectin, ferritin, and transferrin were measured on a single occasion for each. The study was thus a cross sectional descriptive survey for group comparison. Plasma viscosity was measured on admission for TDS and DC and repeated after six weeks and six months for TDS. RESULTS: Plasma C reactive protein, alpha 1 antitrypsin, total globulin, fibronectin, and viscosity were significantly higher in TDS than in NC. DC children also had acute phase protein elevations (C reactive protein, caeruloplasmin, viscosity). However, the increase in caeruloplasmin was specific to the DC group while an increase in fibronectin was specific to the TDS group. Serial measurement of viscosity in TDS showed a modest but significant fall during the six months following treatment. CONCLUSIONS: There is an acute phase response in intense trichuriasis and a specific elevation of plasma fibronectin. Plasma viscosity remains abnormally high six months after treatment, although lower than at diagnosis.

Acute-Phase Proteins↗

The importance of transmission-blocking immunity in the control of infections by apicomplexan parasites.

Transmission-blocking immunity may have great potential for use in the control of diseases caused by apicomplexan parasites. In this review I will describe our work on the application of transmission-blocking immunity to the control of the Eimeria parasite and compare our results to those working on transmission-blocking immunity against Cryptosporidium and Plasmodium. Eimeria causes the disease known as coccidiosis in domestic animals. Coccidiosis is particularly problematic in the chicken industry, mainly due to the crowded rearing conditions under which chicks are raised. In our work we identified, isolated and characterized 3 major gametocyte antigens (230 kDa, 82 kDa and 56/54 kDa) of Eimeria maxima. We used these native glycoproteins to immunize laying hens that, via the egg yolk, provide large amounts of transmission-blocking maternal antibodies to offspring chicks. We demonstrated that hatchlings from immunized hens shed 60-80% fewer oocysts (i.e. the infective stage of the life-cycle of Eimeria) than those from control hens. Such a reduction in oocyst output acts to significantly reduce parasite numbers in the litter of chicks raised in floor pens. This reduction in oocyst output is comparable to that seen using the most effective coccidiostat drugs and is probably sufficient to control coccidiosis under field conditions. Based on our results together with those of other groups working on transmission-blocking immunity against Cryptosporidium and Plasmodium, it appears that this immunological approach holds great promise for the control of apicomplexan parasites that cause diseases in both animals and man.

Animals↗