Serological Markers Suggest Heterogeneity of Effectiveness of Malaria Control Interventions on Bioko Island, Equatorial Guinea

BACKGROUND: In order to control and eliminate malaria, areas of on-going transmission need to be identified and targeted for malaria control interventions. Immediately following intense interventions, malaria transmission can become more heterogeneous if interventions are more successful in some areas than others. Bioko Island, Equatorial Guinea, has been subject to comprehensive malaria control interventions since 2004. This has resulted in substantial reductions in the parasite burden, although this drop has not been uniform across the island. METHODS/PRINCIPAL FINDINGS: In 2008, filter paper blood samples were collected from 7387 people in a cross-sectional study incorporating 18 sentinel sites across Bioko, Equatorial Guinea. Antibodies were measured to P. falciparum Apical Membrane Antigen-1 (AMA-1) by Enzyme Linked Immunosorbent Assay (ELISA). Age-specific seropositivity rates were used to estimate seroconversion rates (SCR). Analysis indicated there had been at least a 60% decline in SCR in four out of five regions on the island. Changes in SCR showed a high degree of congruence with changes in parasite rate (PR) and with regional reductions in all cause child mortality. The mean age adjusted concentration of anti-AMA-1 antibodies was mapped to identify areas where individual antibody responses were higher than expected. This approach confirmed the North West of the island as a major focus of continuing infection and an area where control interventions need to be concentrated or re-evaluated. CONCLUSION/INTERPRETATION: Both SCR and PR revealed heterogeneity in malaria transmission and demonstrated the variable effectiveness of malaria control measures. This work confirms the utility of serological analysis as an adjunct measure for monitoring transmission. Age-specific seroprevalence based evidence of changes in transmission over time will be of particular value when no baseline data are available. Importantly, SCR data provide additional evidence to link malaria control activities to contemporaneous reductions in all-cause child mortality

The prevalence of Plasmodium falciparum in sub-Saharan Africa since 1900.

Malaria transmission is influenced by climate, land use and deliberate interventions. Recent declines have been observed in malaria transmission. Here we show that the African continent has witnessed a long-term decline in the prevalence of Plasmodium falciparum from 40% prevalence in the period 1900-1929 to 24% prevalence in the period 2010-2015, a trend that has been interrupted by periods of rapidly increasing or decreasing transmission. The cycles and trend over the past 115 years are inconsistent with explanations in terms of climate or deliberate intervention alone. Previous global initiatives have had minor impacts on malaria transmission, and a historically unprecedented decline has been observed since 2000. However, there has been little change in the high transmission belt that covers large parts of West and Central Africa. Previous efforts to model the changing patterns of P. falciparum transmission intensity in Africa have been limited to the past 15 years or have used maps drawn from historical expert opinions. We provide quantitative data, from 50,424 surveys at 36,966 geocoded locations, that covers 115 years of malaria history in sub-Saharan Africa; inferring from these data to future trends, we would expect continued reductions in malaria transmission, punctuated with resurgences

Sero-epidemiological evaluation of changes in Plasmodium falciparum and Plasmodium vivax transmission patterns over the rainy season in Cambodia

<p>Abstract</p> <p>Background</p> <p>In Cambodia, malaria transmission is low and most cases occur in forested areas. Sero-epidemiological techniques can be used to identify both areas of ongoing transmission and high-risk groups to be targeted by control interventions. This study utilizes repeated cross-sectional data to assess the risk of being malaria sero-positive at two consecutive time points during the rainy season and investigates who is most likely to sero-convert over the transmission season.</p> <p>Methods</p> <p>In 2005, two cross-sectional surveys, one in the middle and the other at the end of the malaria transmission season, were carried out in two ecologically distinct regions in Cambodia. Parasitological and serological data were collected in four districts. Antibodies to <it>Plasmodium falciparum </it>Glutamate Rich Protein (GLURP) and <it>Plasmodium vivax </it>Merozoite Surface Protein-1₁₉(MSP-1₁₉) were detected using Enzyme Linked Immunosorbent Assay (ELISA). The force of infection was estimated using a simple catalytic model fitted using maximum likelihood methods. Risks for sero-converting during the rainy season were analysed using the Classification and Regression Tree (CART) method.</p> <p>Results</p> <p>A total of 804 individuals participating in both surveys were analysed. The overall parasite prevalence was low (4.6% and 2.0% for <it>P. falciparum </it>and 7.9% and 6.0% for <it>P. vivax </it>in August and November respectively). <it>P. falciparum </it>force of infection was higher in the eastern region and increased between August and November, whilst <it>P. vivax </it>force of infection was higher in the western region and remained similar in both surveys. In the western region, malaria transmission changed very little across the season (for both species). CART analysis for <it>P. falciparum </it>in the east highlighted age, ethnicity, village of residence and forest work as important predictors for malaria exposure during the rainy season. Adults were more likely to increase their antibody responses to <it>P. falciparum </it>during the transmission season than children, whilst members of the Charay ethnic group demonstrated the largest increases.</p> <p>Discussion</p> <p>In areas of low transmission intensity, such as in Cambodia, the analysis of longitudinal serological data enables a sensitive evaluation of transmission dynamics. Consecutive serological surveys allow an insight into spatio-temporal patterns of malaria transmission. The use of CART enabled multiple interactions to be accounted for simultaneously and permitted risk factors for exposure to be clearly identified.</p

Using serological measures to monitor changes in malaria transmission in Vanuatu

BACKGROUND: With renewed interest in malaria elimination, island environments present unique opportunities to achieve this goal. However, as transmission decreases, monitoring and evaluation programmes need increasingly sensitive tools to assess Plasmodium falciparum and Plasmodium vivax exposure. In 2009, to assess the role of serological markers in evaluating malaria transmission, a cross-sectional seroprevalence study was carried out in Tanna and Aneityum, two of the southernmost islands of the Vanuatu archipelago, areas where malaria transmission has been variably reduced over the past few decades. METHODS: Malaria transmission was assessed using serological markers for exposure to P. falciparum and P. vivax. Filter blood spot papers were collected from 1,249 people from Tanna, and 517 people from Aneityum to assess the prevalence of antibodies to two P. falciparum antigens (MSP-119 and AMA-1) and two P. vivax antigens (MSP-119 and AMA-1). Age-specific prevalence was modelled using a simple catalytic conversion model based on maximum likelihood to generate a community seroconversion rate (SCR). RESULTS: Overall seropositivity in Tanna was 9.4%, 12.4% and 16.6% to P. falciparum MSP-119, AMA-1 and Schizont Extract respectively and 12.6% and 15.0% to P. vivax MSP-119 and AMA-1 respectively. Serological results distinguished between areas of differential dominance of either P. vivax or P. falciparum and analysis of age-stratified results showed a step in seroprevalence occurring approximately 30 years ago on both islands, indicative of a change in transmission intensity at this time. Results from Aneityum suggest that several children may have been exposed to malaria since the 2002 P. vivax epidemic. CONCLUSION: Seroepidemiology can provide key information on malaria transmission for control programmes, when parasite rates are low. As Vanuatu moves closer to malaria elimination, monitoring changes in transmission intensity and identification of residual malaria foci is paramount in order to concentrate intervention efforts

Estimating malaria transmission intensity from Plasmodium falciparum serological data using antibody density models.

BACKGROUND: Serological data are increasingly being used to monitor malaria transmission intensity and have been demonstrated to be particularly useful in areas of low transmission where traditional measures such as EIR and parasite prevalence are limited. The seroconversion rate (SCR) is usually estimated using catalytic models in which the measured antibody levels are used to categorize individuals as seropositive or seronegative. One limitation of this approach is the requirement to impose a fixed cut-off to distinguish seropositive and negative individuals. Furthermore, the continuous variation in antibody levels is ignored thereby potentially reducing the precision of the estimate. METHODS: An age-specific density model which mimics antibody acquisition and loss was developed to make full use of the information provided by serological measures of antibody levels. This was fitted to blood-stage antibody density data from 12 villages at varying transmission intensity in Northern Tanzania to estimate the exposure rate as an alternative measure of transmission intensity. RESULTS: The results show a high correlation between the exposure rate estimates obtained and the estimated SCR obtained from a catalytic model (r = 0.95) and with two derived measures of EIR (r = 0.74 and r = 0.81). Estimates of exposure rate obtained with the density model were also more precise than those derived from catalytic models. CONCLUSION: This approach, if validated across different epidemiological settings, could be a useful alternative framework for quantifying transmission intensity, which makes more complete use of serological data

Host choice and multiple blood feeding behaviour of malaria vectors and other anophelines in Mwea rice scheme, Kenya

<p>Abstract</p> <p>Background</p> <p>Studies were conducted between April 2004 and February 2006 to determine the blood-feeding pattern of <it>Anopheles </it>mosquitoes in Mwea Kenya.</p> <p>Methods</p> <p>Samples were collected indoors by pyrethrum spay catch and outdoors by Centers for Disease Control light traps and processed for blood meal analysis by an Enzyme-linked Immunosorbent Assay.</p> <p>Results</p> <p>A total of 3,333 blood-fed <it>Anopheles </it>mosquitoes representing four <it>Anopheles </it>species were collected and 2,796 of the samples were assayed, with <it>Anopheles arabiensis </it>comprising 76.2% (n = 2,542) followed in decreasing order by <it>Anopheles coustani </it>8.9% (n = 297), <it>Anopheles pharoensis </it>8.2% (n = 272) and <it>Anopheles funestus </it>6.7% (n = 222). All mosquito species had a high preference for bovine (range 56.3–71.4%) over human (range 1.1–23.9%) or goat (0.1–2.2%) blood meals. Some individuals from all the four species were found to contain mixed blood meals. The bovine blood index (BBI) for <it>An. arabiensis </it>was significantly higher for populations collected indoors (71.8%), than populations collected outdoors (41.3%), but the human blood index (HBI) did not differ significantly between the two populations. In contrast, BBI for indoor collected <it>An. funestus </it>(51.4%) was significantly lower than for outdoor collected populations (78.0%) and the HBI was significantly higher indoors (28.7%) than outdoors (2.4%). Anthropophily of <it>An. funestus </it>was lowest within the rice scheme, moderate in unplanned rice agro-ecosystem, and highest within the non-irrigated agro-ecosystem. Anthropophily of <it>An. arabiensis </it>was significantly higher in the non-irrigated agro-ecosystem than in the other agro-ecosystems.</p> <p>Conclusion</p> <p>These findings suggest that rice cultivation has an effect on host choice by <it>Anopheles </it>mosquitoes. The study further indicate that zooprophylaxis may be a potential strategy for malaria control, but there is need to assess how domestic animals may influence arboviruses epidemiology before adapting the strategy.</p

Why are anopheline mosquitoes not present in the Seychelles?

<p>Abstract</p> <p>Background</p> <p>Species of anopheline mosquitoes are largely distributed over emerged lands around the world and, within the tropics, few areas are without these insects, which are vectors of malaria parasites. Among the exceptions is the Seychelles archipelago in the western Indian Ocean. However, in the Aldabra island group, located in the extreme western portion of the archipelago, <it>Anopheles gambiae s.l. </it>was introduced, leading to massive proliferation and then elimination, with the most recent autochthonous malaria cases recorded in 1931.</p> <p>Methods</p> <p>In order to re-examine the absence of anopheline mosquitoes in the Seychelles, an entomological field survey was conducted in December 2008 at 17 sites on four granitic islands, including Mahé and Praslin, and ten sites on coralline atolls in the extreme west, including Aldabra.</p> <p>Results</p> <p>No evidence of larval or adult anophelines was found at the surveyed sites, which supports their absence in the Seychelles.</p> <p>Conclusions</p> <p>In the granitic islands of the Seychelles, the climate is favourable for anophelines. However, these islands are protected by their remoteness and prevailing seasonal winds. In addition, stagnant freshwater, required in anopheline larval development, is relatively uncommon on the granitic islands because of the steep slopes. In the southwestern atolls (Aldabra and Providence-Farquhar groups), the presence of a long dry season of up to nine months and the total absence of permanent natural freshwater prevents the breeding of anophelines and their successful colonization. The Seychelles does not have any native land mammals and like in other parts of the world (Antarctica, Iceland, New Caledonia, Central Pacific islands) their absence is associated with the lack of anophelines. This suggests an obligatory relationship for anophelines to feed on terrestrial mammals, without alternative for blood-feeding sources, such as bats, birds and reptiles.</p

Does the spillage of petroleum products in Anopheles breeding sites have an impact on the pyrethroid resistance?

<p>Abstract</p> <p>Background</p> <p>The emergence of <it>Anopheles </it>populations capable of withstanding lethal doses of insecticides has weakened the efficacy of most insecticide based strategies of vector control and, has highlighted the need for further studies on the mechanisms of insecticide resistance and the various factors selecting resistant populations of mosquitoes. This research targeted the analysis of breeding sites and the oviposition behaviour of susceptible and resistant populations of <it>Anopheles </it>in localities of spilled petroleum products. The aim was to establish the possible contribution of oil spillage in the selection of pyrethroid resistance in malaria vectors.</p> <p>Methods</p> <p><it>Anopheles </it>breeding sites were identified and the insecticide susceptibility of the <it>Anopheles gambiae </it>populations mapped in 15 localities of South Western Nigeria. The presence of oil particles as well as the turbidity, the dissolved oxygen and the pH of each identified breeding site was recorded. Data were cross-analysed to correlate the habitat types and the insecticide susceptibility status of emerging mosquitoes. The second phase of this study was basically a laboratory model to provide more information on the implication of the spillage of petroleum on the selection of pyrethroid resistance in <it>An. gambiae</it>.</p> <p>Results</p> <p>Moderate levels of resistance following exposure to permethrin-impregnated papers were recorded with the majority of <it>An. gambiae </it>samples collected in the South Western Nigeria. Data from this study established a link between the constituency of the breeding sites and the resistance status of the emerging <it>Anopheles</it>.</p> <p>Conclusion</p> <p>This study has revealed the segregational occupation of breeding habitats by pyrethroid resistant and susceptible strains of <it>An. gambiae </it>in south-western Nigeria. Compiled results from field and laboratory research point out clear relationships between oil spillage and pyrethroid resistance in malaria vectors. The identification of this factor of resistance could serve as strong information in the management of insecticide resistance in some West African settings.</p

An assessment of the usefulness of a rapid immuno-chromatographic test, "Determine™ malaria pf" in evaluation of intervention measures in forest villages of central India

BACKGROUND: Plasmodium falciparum malaria, is a major health problem in forested tribal belt of central India. Rapid and accurate methods are needed for the diagnosis of P. falciparum. We performed a blinded evaluation of the recently introduced Determine™ malaria pf test (Abbott, Laboratories, Japan) compared with microscopy and splenomegaly in children in epidemic prone areas of district Mandla to assess the impact of intervention measures. METHODS: Children aged 2–10 yrs with and without fever were examined for spleen enlargement by medical specialist by establishing a mobile field clinic. From these children thick blood smears were prepared from finger prick and read by a technician. Simultaneously, rapid tests were performed by a field lab attendant. The figures for specificity, sensitivity and predictive values were calculated using microscopy as gold standard. RESULTS: In all 349 children were examined. The sensitivity and specificity for Determine rapid diagnostic test were 91 and 80% respectively. The positive predictive values (PPV), negative predictive values (NPV) and accuracy of the test were respectively 79, 91 and 85%. On the contrary, the sensitivity and specificity of spleen in detecting malaria infection were 57 and 74 % respectively with PPV of 73%, NPV 59 % and an accuracy of 65%. CONCLUSIONS: Determine™ malaria rapid diagnostic test is easier and quicker to perform and has other advantages over microscopy in not requiring prior training of personnel or quality control. Thus, highlighting the usefulness of a rapid antigen test in assessing prevailing malaria situation in remote areas