Malaria mapping using transmission models: application to survey data from Mali

Geographic mapping of the distribution of malaria is complicated by the limitations of the available data. The most widely available data are from prevalence surveys, but these surveys are generally carried out at arbitrary locations and include nonstandardized and overlapping age groups. To achieve comparability between different surveys, the authors propose the use of transmission models, particularly the Garki model, to convert heterogeneous age prevalence data to a common scale of estimated entomological inoculation rates, vectorial capacity, or force of infection. They apply this approach to the analysis of survey data from Mali, collected in 1965-1998, extracted from the Mapping Malaria Risk in Africa database. They use Bayesian geostatistical models to produce smooth maps of estimates of the entomological inoculation rates obtained from the Garki model, allowing for the effect of environmental covariates. Again using the Garki model, they convert kriged entomological inoculation rates values to age-specific malaria prevalence. The approach makes more efficient use of the available data than do previous malaria mapping methods, and it produces highly plausible maps of malaria distribution.     

A mathematical model for Plasmodium vivax malaria transmission: estimation of the impact of transmission-blocking immunity in an endemic area.

We have developed a multi-state mathematical model to describe the transmission of Plasmodium vivax malaria; the model accommodates variable transmission-blocking/enhancing immunity during the course of a blood infection, a short memory for boosting immunity, and relapses. Using the model, we simulated the incidence of human malaria, sporozoite rates in the vector population, and the level of transmission-blocking immunity for the infected population over a period of time. Field data from an epidemiological study conducted in Kataragama in the south of Sri Lanka were used to test the results obtained. The incidence of malaria during the study period was simulated satisfactorily. The impact of naturally-acquired transmission-blocking immunity on malaria transmission under different vectorial capacities was also simulated. The results show that at low vectorial capacities, e.g., just above the threshold for transmission, the effect of transmission-blocking immunity is very significant; however, the effect is lower at higher vectorial capacities.     

Prevalence and levels of antibodies to the circumsporozoite protein of Plasmodium falciparum in an endemic area and their relationship to resistance against malaria infection

A study on malaria transmission, prevalence of infection and anti-sporozoite antibodies was carried out in Burkina Faso (West Africa). The prevalence and the levels of antibodies to (NANP)3 were found to be related to the entomological sporozoite inoculation rates measured at the same time in a defined area. The major inducer of anti-(NANP)3 antibody production under field conditions is sporozoite inoculation by infected mosquitoes. Levels of antibodies to (NANP)3 vary considerably with age and transmission season. High levels of anti-(NANP)3 antibodies raised under field conditions might offer protection against small inocula of sporozoites.     

广西疟疾媒介的地理分布、生态习性和传疟作用研究

目的研究广西壮族自治区疟疾传播媒介的地理分布、生态习性和传疟作用。方法采用普查和定点调查结合的方法对广西疟疾流行区的传疟媒介进行研究,同时收集相关的历史资料进行回顾性分析。结果广西有78个县(市)发现微小按蚊,15个县发现嗜人按蚊,中华按蚊是全区广泛分布的蚊种;人血指数:微小按蚊在0.0458～0.1390之间,嗜人按蚊在0.2912～0.6330之间。子孢子自然感染率:微小按蚊为0.08%～8.11%,嗜人按蚊为0.25%～1.85%,中华按蚊为0.005%～0.32%,日月潭按蚊为0.06%～3.22%。结论广西传疟媒介有4种,微小按蚊、嗜人按蚊分别是山区和低山丘陵区疟疾的主要媒介,中华按蚊是平原区的媒介,日月潭按蚊是山区疟疾的次要媒介。     

Recent research on impregnated mosquito nets

The present status of impregnated mosquito nets and other impregnated materials is discussed. Research projects which have produced most of the publications on this subject were conducted in areas in Africa with relatively high endemicity of malaria. In these areas, usage of impregnated mosquito nets caused substantial reductions in the sporozoite inoculation rates and some reduction in incidence of malaria attacks. However, there was little or no reduction in parasite rates in the human population. In several countries in Asia and the Pacific, vector control with impregnated mosquito nets has been introduced on a large scale, thus proving its affordability and compatibility with local customs in these countries. Substantial reductions in malaria parasite rates have been obtained in areas with low levels of malaria transmission. In order to develop the vector control method which is most appropriate for each area, much more research is needed on the technical and organizational aspects of vector control with impregnated mosquito nets. Examples are given of data already available as well as an indication of gaps in knowledge which still exist and will need more attention.     

A unique methodology for detecting the spread of chloroquine-resistant strains of Plasmodium falciparum,in previously unreported areas,by analyzing anophelines of malaria endemic zones of Orissa,India

Generally, clinical data is referred to study drug-resistance patterns of Plasmodium falciparum in an area. This is only possible after a clear manifestation of drug-resistance parasites inside the human host, and thereafter detection by healthcare persons. The detection of spread of drug-resistant P. falciparum in a population, before any pathological symptoms detected in humans is possible by analyzing the anopheline vectors, transmitting malaria. In the present study we implemented a new strategy to detect the spread of chloroquine-resistant (CQR) strains of P. falciparum by the major malaria vectors prevalent in selected endemic regions of Orissa, India. We screened P. falciparum positive vectors by using polymerase chain reaction (PCR)-based assay and thereafter detected K76T mutation in the Pfcrt gene, the chloroquine-resistance marker, of parasites present within the vectors. This study showed higher transmission rate of chloroquine-resistant P. falciparum parasites by Anopheles culicifacies and Anopheles fluviatilis. This study will help in assigning chloroquine-resistant P. falciparum sporozoite transmission potential of malaria vectors and suggest that by adopting the mentioned methodologies, we can detect the spreading of the drug-resistant P. falciparum in its transmission. This approach of studying the anophelines during regular vector collection and epidemiological analysis will give the knowledge of chloroquine-resistance pattern of P. falciparum of an area and help in devising effective malaria control strategy.     

Effects of untreated bed nets on the transmission of Plasmodium falciparum, P. vivax and Wuchereria bancrofti in Papua New Guinea

The impact of untreated bed nets on the transmission of human malaria and filariasis in a village in a hyperendemic area of Papua New Guinea was studied. In anopheline mosquitoes, the Plasmodium falciparum sporozoite antigen positivity rate, filarial infection rates and human blood indices dropped significantly after bed nets were introduced. This reduction in human-vector contact did not affect mosquito density as no significant difference in either landing rates or indoor resting catches was found. The number of bed nets in a house and ownership of dogs were factors significantly associated with a reduction in the number of indoor resting mosquitoes. However, the reduction in the P. falciparum sporozoite antigen rate in mosquitoes was not accompanied by a reduction in either malaria parasite or antibody prevalences or titres against the P. falciparum circumsporozoite protein.     

Specific identification of Plasmodium sporozoites using an indirect fluorescent antibody method

The specific identification of plasmodial sporozoites is not possible on morphological grounds. This study presents a serological method for the identification of sporozoite species, indicating the suitability of this approach for detection and determination of sporozoites in wild vectors collected from malaria endemic areas. Specific antisera and monoclonal antibodies prepared against each of two species of rodent malaria (Plasmodium berghei or P. yoelii) were evaluated for their ability to discriminate among sporozoites of different malaria species (P. vivax, P. gallinaceum, P. berghei, P. yoelii) from varied host types. Antisera produced by intravenous immunization of rabbits or mice and hybridoma-produced monoclonal antibodies reacted only with homologous sporozoites in an immunofluorescent antibody test. Antisera produced by intravenous challenge showed no significant difference in reactivity with fresh sporozoites as compared with sporozoites frozen at -80 degrees C for up to six months, whereas antisera produced by infective mosquito bites showed reduced sensitivity to frozen-stored homologous sporozoites and some cross-reactions with heterologous sporozoites. Antisera prepared against the erythrocytic stages of P. berghei or P. yoelii also cross-reacted with sporozoites of all four plasmodia tested, indicating that it is advantageous to use anti-sporozoite antibodies for the identification of malaria sporozoite species by means of serological tests.     

辽宁省嗜人按蚊的生物学特性观察

目的观察我国辽宁省嗜人按蚊在成虫前期的发育时间和传疟能量上与江苏省嗜人按蚊的差异。方法在实验室条件下,采用相同的饲养法和体外人工感染法,分别观察辽宁嗜人按蚊和江苏嗜人按蚊的孵化率、蛹化率、羽化率和蚊胃卵囊阳性率、唾液腺子孢子阳性率等指标。结果辽宁嗜人按蚊和江苏嗜人按蚊卵孵化期平均为3．66d和3．84d。孵化率分别为76．O％和74．3％;幼虫期平均为6．67d和8．26d,蛹化率分别为94．7％和96．0％;蛹期平均为1．60d和1．72d,羽化率分别为97．2％和98．6％;蚊胃卵囊阳性率分别为25．1％和28．1％;唾液腺子胞子阳性率分别为8．4％和10．7％。结论辽宁省的嗜人按蚊在幼虫发育时间和传疟能量上与江苏省嗜人按蚊差异无统计学意义（尸值均〉0．05）。因此,在疟疾流行季节应加强对当地媒介监测,防止疟疾传播。     

A human Phase I/IIa malaria challenge trial of a polyprotein malaria vaccine

We examined the safety, immunogenicity and efficacy of a prime-boost vaccination regime involving two poxvirus malaria subunit vaccines, FP9-PP and MVA-PP, expressing the same polyprotein consisting of six pre-erythrocytic antigens from Plasmodium falciparum.Following safety assessment of single doses, 15 volunteers received a heterologous prime-boost vaccination regime and underwent malaria sporozoite challenge. The vaccines were safe but interferon-γ ELISPOT responses were low compared to other poxvirus vectors, despite targeting multiple antigens. There was no vaccine efficacy as measured by delay in time to parasitaemia. A number of possible explanations are discussed, including the very large insert size of the polyprotein transgene.     

当前嗜人按蚊和中华按蚊传疟作用的比较研究

为了比较嗜人按蚊和中华按蚊的传疟作用,1982~1987年选择安徽、广西,四川、广东四省各1~2个点作系统研究.通过人工感染、昆虫学、寄生虫学等调查表明,嗜人按蚊为髙效媒介,其传疟作用比中华按蚊高20倍,而且是传播恶性疟的主要媒介,凡有嗜人按蚊存在的地区,当地疟疾均较严重。     

The efficiency of sporozoite transmission in the human malarias, Plasmodium falciparum and P. vivax

Reported are malaria sporozoite and inoculation rates over a 1-year period in eight epidemiologically defined villages of different endemicity in Madang Province, Papua New Guinea. In the study, more than 41 000 wild-caught mosquitos were analysed for Plasmodium falciparum and P. vivax sporozoites by ELISA. In a given village the entomological inoculation rates correlated strongly with the prevalences of both these malarial parasites in children. However, the prevalence of P. falciparum infections in children was much higher than that of P. vivax, despite similar inoculation rates for the two species. These data suggest that in Papua New Guinea P. falciparum is more efficiently transmitted than P. vivax from mosquito to man. The increased efficiency of transmission of P. falciparum may be due to the heavier sporozoite densities in wild-caught mosquitos naturally infected with P. falciparum sporozoites that were tenfold greater than the sporozoite densities in mosquitos infected with P. vivax.     

Insecticide-treated materials, mosquito adaptation and mass effect: entomological observations after five years of vector control in Burkina Faso

Insecticide-treated bednets and curtains have been shown to be successful in reducing malaria transmission and child mortality in Africa over periods of up to 2 years. A major concern relating to this approach is that, in time, it will be compromised by the selection of mosquito genotypes that are resistant at the biochemical or behavioural level. We report entomological data from a large area in Burkina Faso where insecticide-treated curtains have been in use for up to 5 years. Longitudinal indoor and outdoor CDC light-trap catches were performed in 4 sentinel villages. In addition cross-sectional surveys using indoor spray catches and outdoor CDC light-trap catches were performed each September in a larger number of villages, including 8 located outside the intervention area. We found no evidence of the selection of mosquito phenotypes that might compromise the intervention. Indoor and outdoor vector densities remained very low after 5 years of intervention, both compared with pre-intervention levels and with concurrent levels outside the intervention area. We found no evidence of a switch to outdoor rather than indoor biting. The proportion of blood meals taken on humans may have decreased but our data are inconclusive on this point. We observed higher vector densities and sporozoite rates at the periphery of the intervention zone than at the centre, which may reflect re-invasion of peripheral villages by mosquitoes from outside the intervention area. In 'real life' programmes, with perhaps patchy, less than optimal coverage, the protection against malaria transmission provided to individuals using insecticide-treated materials may be less than that achieved in the randomized controlled trials which demonstrated an impact of insecticide-treated materials on child mortality.     

Some entomological observations on malaria transmission in a remote village in northwestern Thailand

Anopheline mosquitoes and their relation to malaria transmission were studied during the months of March, May and July in the Karen village of Mae Tha Waw located in the northwestern mountains of Tak Province. Thirteen species were captured on human bait during 80 man-nights of collecting. Four additional species were collected during routine larval surveys. Anopheles minimus and An. maculatus comprised 92.5% of the specimens captured biting man. Anopheles minimus and An. nivipes were implicated as vectors based on the detection of sporozoite infections using enzyme-linked immunosorbent assays for Plasmodium falciparum and P. vivax. Anopheles dirus was rarely encountered and probably played little part in transmission in Mae Tha Waw during the period of study. Information is provided on nightly biting activity, incidence of disease, infectivity and larval bionomics.     

Malaria persistence in Kumaon foothills of District Nainital, Uttarakhand, India

Clinic data depicted a high incidence of malaria in a forest ecotype in the Kumaon foothills of District Nainital, Uttarakhand, India. A study was therefore conducted to determine the risk factors associated with the transmission of malaria from 2002 to 2004. The man-hour densities of Anopheles culicifacies and An. fluviatilis varied from 2 to 139 and 1 to 69, respectively. The sporozoite rate of 0.24% was recorded in An. culicifacies. Sibling species investigation revealed prevalence of species B (53.8%) and C (46.2%) of An. culicifacies and of species T (100%) of An. fluviatilis complexes. The slide positivity rate and slide falciparum rate were 50.4% and 28.3%, respectively. The infant parasite rate was 42.9% and the enlarged spleen rate among the children was 25.95%. The findings revealed the persistence of malaria in the area mainly due to indigenous transmission through the malaria vector An. culicifacies and the inadequacy of intervention measures. Transmission could be curtailed by indoor residual application of malathion.     

Comparative efficacy of pre-erythrocytic whole organism vaccine strategies against the malaria parasite

Despite major efforts over the past 50 years to develop a malaria vaccine, no product has been licensed yet. Irradiated sporozoites are the benchmark for an experimental live-attenuated malaria vaccine that induces potent protection against re-infection in humans and animal models. Lasting protection can also be elicited by parasite attenuation via tailored genetic modification or drug cover leading to renewed interest in whole-organism vaccination strategies. In this study, we systematically compared the protective efficacy of different whole-organism vaccination approaches in the Plasmodium berghei/C57bl/6 rodent malaria model. We applied blood stage parasitemia and quantitative RT-PCR of liver parasite loads as two complementary primary endpoints of a malaria challenge infection. We were able to demonstrate similar potency of genetic attenuation, i.e., uis3(−) and p36p(−) parasites, and prophylactic drug cover, i.e., azithromycin, pyrimethamine, primaquine and chloroquine, during sporozoite exposure in comparison to irradiated sporozoites. Importantly, when animals were covered with the antibiotic azithromycin during sporozoite exposure we observed superior protection. On the other end, immunizations with heat-killed and over-irradiated sporozoites failed to confer any detectable protection. Together, we show that systematic pre-clinical evaluation and quantification of vaccine efficacy is vital for identification of the most potent whole organism anti-malaria vaccine strategy.     

广东省媒介按蚊的子孢子自然感染率调查

近几年，在广东省疟疾流行区的23市县区166个疫点（村）中，以人诱半通宵捕蚊方法进行媒介按蚊调查，共捕获按蚊7种，其中有我省传疟媒介嗜人按蚊、中华接蚊、微小按蚊和日月潭按蚊，分别占捕获按蚊总数的24．0％、48．8％、14．1％和8．1％，其余按蚊占5．0％。而在12个市县36个点（村）中，以牛房全捕法共捕获按蚊11种，上述4种媒介按蚊分别占捕蚊总数的0．3％、26．4％、42．4％和9．5％，其他按蚊占21．4％。全省有11个市县发现嗜人按蚊。历年媒介按蚊及其传疟作用的调查结果表明，我省4种传疟媒介的子孢子自然感染率嗜人按蚊为0．35～0．54％，中华接蚊为0．15～0．93％，微小按蚊为0．23～5．94％，日月潭按蚊为0．05％。     

Spatial targeting of interventions against malaria

Malaria transmission is strongly associated with location. This association has two main features. First, the disease is focused around specific mosquito breeding sites and can normally be transmitted only within certain distances from them: in Africa these are typically between a few hundred metres and a kilometre and rarely exceed 2-3 kilometres. Second, there is a marked clustering of persons with malaria parasites and clinical symptoms at particular sites, usually households. In localities of low endemicity the level of malaria risk or case incidence may vary widely between households because the specific characteristics of houses and their locations affect contact between humans and vectors. Where endemicity is high, differences in human/vector contact rates between different households may have less effect on malaria case incidences. This is because superinfection and exposure-acquired immunity blur the proportional relationship between inoculation rates and case incidences. Accurate information on the distribution of malaria on the ground permits interventions to be targeted towards the foci of transmission and the locations and households of high malaria risk within them. Such targeting greatly increases the effectiveness of control measures. On the other hand, the inadvertent exclusion of these locations causes potentially effective control measures to fail. The computerized mapping and management of location data in geographical information systems should greatly assist the targeting of interventions against malaria at the focal and household levels, leading to improved effectiveness and cost-effectiveness of control.     

In vivo and in vitro susceptibility of Plasmodium falciparum to sulphadoxine/pyrimethamine in Liberia, West Africa

The in vivo response of Plasmodium falciparum to standard treatment with sulphadoxine/pyrimethamine was studied in 19 hospital patients from Yekepa town with hypoendemic malaria and in 28 children, two to nine years old, living in a village with holoendemic malaria. In vitro tests were performed on eight isolates. In the hospital patients all parasites cleared with mean clearance time of 2.2 (range one to three) days and no recrudescence occurred during a 28-day follow-up period. In the village children, despite a high sporozoite inoculation rate, recurrent parasitaemias were only recorded after 28 days, suggesting a rather long-lasting prophylactic effect against reinfection by the drug combination. In vitro, inhibition of parasite multiplication was achieved by 3 X 10(-7) M sulphadoxine and 3.8 X 10(-9) M pyrimethamine.     

Modeling of malaria incidence in Nepal

Background: Malaria is a major cause of morbidity and mortality in Nepal. The magnitude of malaria across the country is alarming and varies with location. Therefore, the present study aimed to model malaria incidence rates during 1998 to 2009 in Nepal. Methods: Data for the study were obtained from Health Management Information System (HMIS), Ministry of Public Health. A negative binomial model was used to fit malaria incidence rates as a function of year and location and provided a good fit, as indicated by residual plots. Results: In total, 83,345 cases of malaria were reported from 1998 to 2009. The mean incidence rate was 0.30 per 1000 population. The models show trends and spatial variations in disease incidence. There was decreasing trend in the incidence rates of malaria (1998-2004), followed by a more moderate upward trend until 2008, when the rate decreases again. Zero malaria incidences occurred in six districts including Humla, Jajarkot, Manang, Kathmandu, Bhakthapur and Solukhumbu districts for over twelve years. Higher incidence occurred in Kanchanpur, Kailali, Bardiya, Kavre, and Jhapa districts for the study period. Conclusion: Malaria is still a public health problem in Nepal. This study showed a steady decreasing trend in malaria incidence but the numbers of cases are still very high. Higher rates were observed in Terai Region and border areas. These findings highlight the need for more systematic and effective malaria control measures on malaria burden areas of Nepal.