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BackgroundThe use of data in targeting of malaria control efforts is becoming increasingly adopted by national malaria control programmes and is essential for optimal use of resources. This is especially important during public health emergencies such as the COVID-19 pandemic which resulted in reallocation of funding towards containment efforts. This work provides a practical mechanism for prioritizing geographical areas for insecticide-treated net (ITN) distribution during a public health emergency or situations of limited resources. We adopt a GIS-based weighted approach to categorize and rank administrative units based on data inputs that are widely available and can be applied in various country contexts where Plasmodium falciparum transmission is reported. MethodsP. falciparum-specific intervention and prevailing risk factors were used to rank administrative units in Nigeria for prioritization during ITN distributions. Each factor was assigned a unique weight and was multiplied by a value, typically ranging from 1 to 4, based on natural groupings inherent in the data, or the presence or absence of a given intervention. Risk scores for each factor were then summated to generate a composite unique risk score for each administrative unit. This risk score was then translated into a prioritization map which ranks each administrative unit from low to high priority in terms of ITN distribution targeting in situations of limited resources. ResultsA major component that influenced the prioritization scheme was previous ITN depth of coverage, as obtained and spatially interpolated from DHS survey data. The geospatial heterogeneity found among input risk factors suggests that a range of variables and covariates — outside of those that characterize malaria transmission exclusively — should be considered when using data to inform ITN distributions. The approach resulted in identification of regions that should be prioritized in upcoming ITN distributions. ConclusionThe presented approach provides a tool for prioritizing regions for ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted. Its value added can be found in its potential for application in multiple country contexts, expediated timeframe for producing outputs, and its use of systematically collected malaria indicators in informing prioritization.

Background The use of data in targeting malaria control efforts is essential for optimal use of resources. This work provides a practical mechanism for prioritizing geographic areas for insecticide-treated net (ITN) distribution campaigns in settings with limited resources. Methods A GIS-based weighted approach was adopted to categorize and rank administrative units based on data that can be applied in various country contexts where Plasmodium falciparum transmission is reported. Malaria intervention and risk factors were used to rank local government areas (LGAs) in Nigeria for prioritization during mass ITN distribution campaigns. Each factor was assigned a unique weight that was obtained through application of the analytic hierarchy process (AHP). The weight was then multiplied by a value based on natural groupings inherent in the data, or the presence or absence of a given intervention. Risk scores for each factor were then summated to generate a composite unique risk score for each LGA. This risk score was translated into a prioritization map which ranks each LGA from low to high priority in terms of timing of ITN distributions. Results A case study using data from Nigeria showed that a major component that influenced the prioritization scheme was ITN access. Sensitivity analysis results indicate that changes to the methodology used to quantify ITN access did not modify outputs substantially. Some 120 LGAs were categorized as ‘extremely high’ or ‘high’ priority when a spatially interpolated ITN access layer was used. When prioritization scores were calculated using DHS-reported state level ITN access, 108 (90.0%) of the 120 LGAs were also categorized as being extremely high or high priority. The geospatial heterogeneity found among input risk factors suggests that a range of variables and covariates should be considered when using data to inform ITN distributions. Conclusion The authors provide a tool for prioritizing regions in terms of timing of ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted. Its value added can be found in its potential for application in multiple country contexts, expediated timeframe for producing outputs, and its use of systematically collected malaria indicators in informing prioritization.

Diagnosis is often based on the exceedance or not of continuous health indicators of a predefined cut-off value, so as to classify patients into positives and negatives for the disease under investigation. In this paper, we investigate the effects of dichotomization of spatially-referenced continuous outcome variables on geostatistical inference. Although this issue has been extensively studied in other fields, dichotomization is still a common practice in epidemiological studies. Furthermore, the effects of this practice in the context of prevalence mapping have not been fully understood. Here, we demonstrate how spatial correlation affects the loss of information due to dichotomization, how linear geostatistical models can be used to map disease prevalence and thus avoid dichotomization, and finally, how dichotomization affects our predictive inference on prevalence. To pursue these objectives, we develop a metric, based on the composite likelihood, which can be used to quantify the potential loss of information after dichotomization without requiring the fitting of Binomial geostatistical models. Through a simulation study and two applications on disease mapping in Africa, we show that, as thresholds used for dichotomization move further away from the mean of the underlying process, the performance of binomial geostatistical models deteriorates substantially. We also find that dichotomization can lead to the loss of fine scale features of disease prevalence and increased uncertainty in the parameter estimates, especially in the presence of a large noise to signal ratio. These findings strongly support the conclusions from previous studies that dichotomization should be always avoided whenever feasible., Comment: 18 pages, 5 figures, to be published in the journal of Spatial Statistics

Serological markers, combined with spatial analysis, offer a comparatively more sensitive means by which to measure and detect foci of malaria transmission in highland areas than traditional malariometric indicators. Plasmodium falciparum parasite prevalence, seroprevalence, and seroconversion rate to P. falciparum merozoite surface protein-119 (MSP-119) were measured in a cross-sectional survey to determine differences in transmission between altitudinal strata. Clusters of P. falciparum parasite prevalence and high antibody responses to MSP-119 were detected and compared. Results show that P. falciparum prevalence and seroprevalence generally decreased with increasing altitude. However, transmission was heterogeneous with hotspots of prevalence and/or seroprevalence detected in both highland and highland fringe altitudes, including a serological hotspot at 2,200 m. Results demonstrate that seroprevalence can be used as an additional tool to identify hotspots of malaria transmission that might be difficult to detect using traditional cross-sectional parasite surveys or through vector studies. Our study findings identify ways in which malaria prevention and control can be more effectively targeted in highland or low transmission areas via serological measures. These tools will become increasingly important for countries with an elimination agenda and/or where malaria transmission is becoming patchy and focal, but receptivity to malaria transmission remains high.

Background: Wolbachia, a common insect endosymbiotic bacterium that can influence pathogen transmission and manipulate host reproduction, has historically been considered absent from the Anopheles (An.) genera, but has recently been found in An. gambiae s.l. populations in West Africa. As there are numerous Anopheles species that have the capacity to transmit malaria, we analysed a range of species across five malaria endemic countries to determine Wolbachia prevalence rates, characterise novel Wolbachia strains and determine any correlation between the presence of Plasmodium, Wolbachia and the competing bacterium Asaia. Methods: Anopheles adult mosquitoes were collected from five malaria-endemic countries: Guinea, Democratic Republic of the Congo (DRC), Ghana, Uganda and Madagascar, between 2013 and 2017. Molecular analysis was undertaken using quantitative PCR, Sanger sequencing, Wolbachia multilocus sequence typing (MLST) and high-throughput amplicon sequencing of the bacterial 16S rRNA gene. Results: Novel Wolbachia strains were discovered in five species: An. coluzzii, An. gambiae s.s., An. arabiensis, An. moucheti and An. species A, increasing the number of Anopheles species known to be naturally infected. Variable prevalence rates in different locations were observed and novel strains were phylogenetically diverse, clustering with Wolbachia supergroup B strains. We also provide evidence for resident strain variants within An. species A. Wolbachia is the dominant member of the microbiome in An. moucheti and An. species A but present at lower densities in An. coluzzii. Interestingly, no evidence of Wolbachia/Asaia co-infections was seen and Asaia infection densities were shown to be variable and location dependent. Conclusions: The important discovery of novel Wolbachia strains in Anopheles provides greater insight into the prevalence of resident Wolbachia strains in diverse malaria vectors. Novel Wolbachia strains (particularly high-density strains) are ideal candidate strains for transinfection to create stable infections in other Anopheles mosquito species, which could be used for population replacement or suppression control strategies.

Background Environmental factors, especially ambient temperature and relative humidity affect both mosquitoes and malaria parasites. The early part of sporogony is most sensitive and is affected by high temperatures and temperature fluctuation immediately following ingestion of an infectious blood meal. The aim of this study was to explore whether environmental variables such as temperature, together with the presence of the kdr insecticide resistance mutations, have an impact on survival probability and infection rates in wild Anopheles gambiae (s.s.) exposed and unexposed to a pyrethroid insecticide. Methods Anopheles gambiae (s.s.) were collected as larvae, reared to adults, and fed on blood samples from 42 Plasmodium falciparum-infected local patients at a health facility in mid-western Uganda, then exposed either to nets treated with sub-lethal doses of deltamethrin or to untreated nets. After seven days, surviving mosquitoes were dissected and their midguts examined for oocysts. Prevalence (proportion infected) and intensity of infection (number of oocysts per infected mosquito) were recorded for each group. Mosquito mortality was recorded daily. Temperature and humidity were recorded every 30 minutes throughout the experiments. Results Our findings indicate that apart from the effect of deltamethrin exposure, mean daily temperature during the incubation period, temperature range during the first 24 hours and on day 4 post-infectious feed had a highly significant effect on the risk of infection. Deltamethrin exposure still significantly impaired survival of kdr homozygous mosquitoes, while mean daily temperature and relative humidity during the incubation period independently affected mosquito mortality. Significant differences in survival of resistant genotypes were detected, with the lowest survival recorded in mosquitoes with heterozygote L1014S/L1014F genotype. Conclusions This study confirmed that the early part of sporogony is most affected by temperature fluctuations, while environmental factors affect mosquito survival. The impact of insecticide resistance on malaria infection and vector survival needs to be assessed separately for mosquitoes with different resistance mechanisms to fully understand its implications for currently available vector control tools and malaria transmission.

Objective To examine the association between travel (recency of travel, transmission intensity at destination compared to origin and duration of travel) and confirmed malaria in Uganda. Methods Health facility-based case–control study in highland (~2200 m), and highland fringe (~1500 m) areas with adjustment for other covariates. Results In the highland site, patients who had travelled to areas of higher transmission intensity than their home (origin) areas recently were nearly seven times more likely to have confirmed malaria than those who had not (OR 6.9; P = 0.01, 95% CI: 1.4–33.1). In the highland fringe site, there was also a statistically significant association between travel and malaria (OR 2.1; P = 0.04, 95% CI: 1.1–3.9). Conclusions For highland areas, or areas of low malaria transmission, health authorities need to consider internal migrants when designing malaria control programs. Control interventions should include information campaigns reminding residents in these areas of the risk of malaria infection through travel and to provide additional mosquito nets for migrants to use during travel. Health authorities may wish to improve diagnosis in health facilities in highland areas by adding travel history to malaria case definitions. Where routine monitoring data are used to evaluate the impact of interventions on the malaria burden in highland areas, health authorities and donors need ensure that only cases from the local area and not ‘imported cases’ are counted. Objectif Examiner l'association entre le voyage (recence du voyage, intensite de la transmission au lieu de destination par rapport a l'origine et la duree du voyage) et les cas confirmes de paludisme en Ouganda. Methodes Etude cas-temoins dans les etablissements de sante dans les regions montagneuses (~2200 m), et a l'oree des ces regions (~1500 m) avec ajustement pour d'autres covariables. Resultats Dans le site de montagne, les patients qui avaient recemment voyage dans des regions d'intensite de transmission plus elevee que les zones du domicile etaient pres de sept fois plus susceptibles d'avoir un paludisme confirme que ceux qui n'avaient pas voyage (OR = 6,9; p = 0,01, IC 95%: 1,4–33,1). Dans la zone a l'oree des regions montagneuse, il y avait une association statistiquement significative entre le voyage et le paludisme (OR = 2,1; p = 0,04, IC95%: 1,1 a 3,9). Conclusions Pour les zones montagneuses, les autorites sanitaires doivent tenir compte des migrants lors de la conception des programmes de lutte contre le paludisme. Les interventions de lutte devraient inclure des campagnes d'information rappelant les residents dans ces zones du risque d'infection du paludisme suite au voyage et fournir des moustiquaires supplementaires pour les migrants a utiliser lors du voyage. Les autorites sanitaires pourraient ameliorer le diagnostic dans les etablissements de sante dans les zones montagneuses en ajoutant l'histoire de voyage dans les definitions de cas de paludisme. Lorsque les donnees de surveillance de routine sont utilisees pour evaluer l'impact des interventions sur la charge du paludisme dans les zones montagneuses, les autorites sanitaires et les donateurs devraient veiller a ce que seuls les cas de la region et non les «cas importes» sont comptes. Objetivo Examinar la asociacion entre el viajar (cuan reciente habia sido el viaje, la intensidad de transmision en el lugar de destino comparada con la del origen, y duracion del viaje) y malaria confirmada en Uganda. Metodos Estudio casos control basado en la comunidad en areas de tierras altas (~2200 m), y areas limitrofes (~1500 m) con ajuste para otras covariables. Resultados En las tierras altas, los pacientes que habian viajado recientemente a areas con una intensidad de transmision mas alta que la del area de sus hogares tenian casi 7 veces mas probabilidad de tener una malaria confirmada que aquellos que no habian viajado (OR 6.9; p = 0.01, IC 95%: 1.4–33.1). En las areas limitrofes a las zonas altas existia una asociacion estadistica significativa entre el viaje y la malaria (OR 2.1; p = 0.04, IC 95%: 1.1–3.9). Conclusiones En el caso de las areas en tierras altas, las autoridades sanitarias deberian tener en cuenta a los emigrantes cuando disenan los programas de control de malaria. Las intervenciones de control deberian incluir campanas de informacion que recuerden a los residentes en estas areas del riesgo de infeccion por malaria al viajar y proveer redes mosquiteras adicionales para que los emigrantes utilicen durante el viaje. Las autoridades sanitarias podrian mejorar el diagnostico en los centros sanitarios anadiendo el historial de viajes a las definiciones de caso de malaria. En donde se utilicen datos rutinarios de monitorizacion para evaluar el impacto de las intervenciones sobre la carga de malaria en tierras altas, las autoridades sanitarias y los donantes deben asegurarse de que solo se tienen en cuenta los casos de locales y no los “importados”.

Although the control of malaria epidemics has been a priority for the World Health Organization and other agencies for many years, surprisingly little is known about the public health burden of these epidemics. Here, we evaluate the available evidence of the morbidity and mortality impacts of individual epidemics in Africa and examine the problems associated with using these data to estimate the average annual burden of epidemics at national and continental scales. We argue that conventional approaches that are used to assess the burden of epidemics are inadequate, and outline the future steps that are required to produce estimates that are more accurate.

Background Pyrethroid resistance in African vector mosquitoes is a threat to malaria control. Resistant mosquitoes can survive insecticide doses that would normally be lethal. We studied effects of such doses on Plasmodium falciparum development inside kdr-resistant Anopheles gambiae s.s. in Uganda. Methods We collected An. gambiae s.s. homozygous for kdr-L1014S mutation, fed them on blood samples from 42 P. falciparum-infected local patients, then exposed them either to nets treated with sub-lethal doses of deltamethrin or to untreated nets. After seven days, we dissected 692 mosquitoes and examined their midguts for oocysts. Prevalence (proportion infected) and intensity of infection (number of oocysts per infected mosquito) were recorded for each group. Results Both prevalence and intensity of infection were significantly reduced in deltamethrin-exposed mosquitoes, compared to those exposed to untreated nets. With low doses (2.5–5.0 mg/m2), prevalence was reduced by 59 % (95 % CI = 22 %-78 %) and intensity by 41 % (95 % CI = 25 %-54 %). With high doses (10–16.7 mg/m2), prevalence was reduced by 80 % (95 % CI = 67 %-88 %) and intensity by 34 % (95 % CI = 20 %-46 %). Conclusions We showed that, with locally-sampled parasites and mosquitoes, doses of pyrethroids that are sub-lethal for resistant mosquitoes can interfere with parasite development inside mosquitoes. This mechanism could enable pyrethroid-treated nets to prevent malaria transmission despite increasing vector resistance.

BACKGROUND: A universal coverage campaign (UCC) with long-lasting insecticidal nets (LLINs) was implemented in four districts in Midwestern Uganda in 2009-2010. Entomological surveys were carried out to monitor changes in vector density, behaviour and malaria transmission following this intervention. METHODS: Anopheles mosquitoes were collected using CDC light traps quarterly and human landing catch twice a year in four sites. Collections were done at baseline before the campaign and over a three-year period following the campaign. Plasmodium falciparum circumsporozoite enzyme-linked immunosorbent assays were performed. A subset of anophelines were molecularly identified to species, and kdr L1014S frequencies were determined. RESULTS: The prevailing malaria vector in three sites was Anopheles gambiae s.l. (>97 %), with An. funestus s.l. being present in low numbers only. An. gambiae s.s. dominated (> 95 %) over An. arabiensis within A. gambiae s.l. In the remaining site, all three vector species were observed, although their relative densities varied among seasons and years. Vector densities were low in the year following the UCC but increased over time. Vector infectivity was 3.2 % at baseline and 1.8 % three years post-distribution (p = 0.001). The daily entomological inoculation rate (EIR) in 2012 varied between 0.0-0.98 for the different sites compared to a baseline EIR that was between 0.0-5.8 in 2009. There was no indication of a change in indoor feeding times, and both An. gambiae s.l. and An. funestus s.l. continued to feed primarily after midnight with vectors being active until the early morning. Kdr L1014S frequencies were already high at baseline (53-85 %) but increased significantly in all sites over time. CONCLUSIONS: The entomological surveys indicate that there was a reduction in transmission intensity coinciding with an increase in use of LLINs and other antimalarial interventions in areas of high malaria transmission. There was no change in feeding behaviour, and human-vector contact occurred indoors and primarily after midnight constantly throughout the study. Although the study was not designed to evaluate the effectiveness of the intervention compared to areas with no such intervention, the reduction in transmission occurred in an area with previously stable malaria, which seems to indicate a substantial contribution of the increased LLIN coverage.

Malaria epidemics have long been known to recur in the African highlands. Efforts to develop systems of early warning and detection for epidemics are outlined here with special emphasis on the Highland Malaria Project (HIMAL). This project has been conducting research on the operational implementation of a district-based surveillance and epidemic-monitoring system using a network of sentinel sites in four pilot districts of Kenya and Uganda. The potential use of weather monitoring as well as disease surveillance for effective early warning is being investigated.

The aim of this study was to describe spatial and temporal variations in malaria epidemic risk in Ethiopia and to examine factors involved in relation to their implications for early warning and interpretation of geographical risk models. Forty-eight epidemic episodes were identified in various areas between September 1986 and August 1993 and factors that might have led to the events investigated using health facility records and weather data. The study showed that epidemics in specific years were associated with specific geographical areas. A major epidemic in 1988 affected the highlands whereas epidemics in 1991 and 1992 affected highland-fringe areas on the escarpments of the Rift Valley and in southern and north-western parts of the country. Malaria epidemics were significantly more often preceded by a month of abnormally high minimum temperature in the preceding 3 months than based on random chance, whereas frequency of abnormally low minimum temperature prior to epidemics was significantly lower than expected. Abnormal increases of maximum temperature and rainfall had no positive association with the epidemics. A period of low incidence during previous transmission seasons might have aggravated the events, possibly due to low level of immunity in affected populations. Epidemic risk is a dynamic phenomenon with changing geographic pattern based on temporal variations in determinant factors including weather and other eco-epidemiological characteristics of areas at risk. Epidemic early warning systems should take account of non-uniform effects of these factors by space and time and thus temporal dimensions need to be considered in spatial models of epidemic risks.

Background While significant focus has been given to net distribution, little is known about what is done with nets that leave a household, either to be used by others or when they are discarded. To better understand the magnitude of sharing LLIN between households and patterns of discarding LLIN, the present study pools data from 14 post-campaign surveys to draw larger conclusions about the fate of nets that leave households. Methods Data from 14 sub-national post-campaign surveys conducted in Ghana, Senegal, Nigeria (10 states), and Uganda between 2009 and 2012 were pooled. Survey design and data collection methods were similar across surveys. The timing of surveys ranged from 2–16 months following their respective mass LLIN distributions. Results Among the 14 surveys a total of 14,196 households reported owning 25,447 nets of any kind, of which 23,955 (94%) were LLINs. In addition, a total of 4,102 nets were reported to have left the households in the sample: 63% were discarded, and 34% were given away. Only 255 of the discarded nets were reported used for other purposes, representing less than 1% of the total sample of nets. The majority (62.5%) of nets given away were given to or taken by relatives, while 31.1% were given to non-relatives. Campaign nets were almost six times (OR 5.95, 4.25-8.32, p < 0.0001) more likely to be given away than non-campaign nets lost during the same period. Nets were primarily given away within the first few months after distribution. The overall rate of net redistribution was 5% of all nets. Discussion and conclusion Intra-household re-allocation of nets does occur, but was sensitive to current household net ownership and the time elapsed since mass distribution. These factors can be addressed programmatically to further facilitate reallocation within a given community. Secondly, the overwhelming majority of nets were used for malaria prevention. Of the repurposed nets (

Background Malaria epidemics cause substantial morbidity and mortality in highland areas of Africa. The costs of detecting and controlling these epidemics have not been explored adequately in the past. This study presents the costs of establishing and running an early detection system (EDS) for epidemic malaria in four districts in the highlands of Kenya and Uganda. Methods An economic costing was carried out from the health service provider's perspective in both countries. Staff time for data entry and processing, as well as supervising and coordinating EDS activities at district and national levels was recorded and associated opportunity costs estimated. A threshold analysis was carried out to determine the number of DALYs or deaths that would need to be averted in order for the EDS to be considered cost-effective. Results The total costs of the EDS per district per year ranged between US$ 14,439 and 15,512. Salaries were identified as major cost-drivers, although their relative contribution to overall costs varied by country. Costs of relaying surveillance data between facilities and district offices (typically by hand) were also substantial. Data from Uganda indicated that 4% or more of overall costs could potentially be saved by switching to data transfer via mobile phones. Based on commonly used thresholds, 96 DALYs in Uganda and 103 DALYs in Kenya would need to be averted annually in each district for the EDS to be considered cost-effective. Conclusion Results from this analysis suggest that EDS are likely to be cost-effective. Further studies that include the costs and effects of the health systems' reaction prompted by EDS will need to be undertaken in order to obtain comprehensive cost-effectiveness estimates.

Background Malaria epidemics remain a significant public health issue in the East African highlands. The aim of this study was to monitor temporal variations in vector densities in relation to changes in meteorological factors and malaria incidence at four highland sites in Kenya and Uganda and to evaluate the implications of these relationships for epidemic prediction and control. Methods Mosquitoes were collected weekly over a period of 47 months while meteorological variables and morbidity data were monitored concurrently. Mixed-effects Poisson regression was used to study the temporal associations of meteorological variables to vector densities and of the latter to incidence rates of Plasmodium falciparum. Results Anopheles gambiae s.s. was the predominant vector followed by Anopheles arabiensis. Anopheles funestus was also found in low densities. Vector densities remained low even during periods of malaria outbreaks. Average temperature in previous month and rainfall in previous two months had a quadratic and linear relationship with An. gambiae s.s. density, respectively. A significant statistical interaction was also observed between average temperature and rainfall in the previous month. Increases in densities of this vector in previous two months showed a linear relationship with increased malaria incidence. Conclusion Although epidemics in highlands often appear to follow abnormal weather patterns, interactions between meteorological, entomological and morbidity variables are complex and need to be modelled mathematically to better elucidate the system. This study showed that routine entomological surveillance is not feasible for epidemic monitoring or prediction in areas with low endemicity. However, information on unusual increases in temperature and rainfall should be used to initiate rapid vector surveys to assess transmission risk.

Background The accuracy of malaria diagnosis has received renewed interest in recent years due to changes in treatment policies in favour of relatively high-cost artemisinin-based combination therapies. The use of rapid diagnostic tests (RDTs) based on histidine-rich protein 2 (HRP2) synthesized by Plasmodium falciparum has been widely advocated to save costs and to minimize inappropriate treatment of non-malarial febrile illnesses. HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections. Methods In this study, 78,454 clinically diagnosed malaria patients were tested using HRP2-based RDTs over a period of approximately four years in four highland sites in Kenya and Uganda representing hypoendemic to mesoendemic settings. In addition, the utility of the tests was evaluated in comparison with expert microscopy for disease management in 2,241 subjects in two sites with different endemicity levels over four months. Results RDT positivity rates varied by season and year, indicating temporal changes in accuracy of clinical diagnosis. Compared to expert microscopy, the sensitivity, specificity, positive predictive value and negative predictive value of the RDTs in a hypoendemic site were 90.0%, 99.9%, 90.0% and 99.9%, respectively. Corresponding measures at a mesoendemic site were 91.0%, 65.0%, 71.6% and 88.1%. Although sensitivities at the two sites were broadly comparable, levels of specificity varied considerably between the sites as well as according to month of test, age of patient, and presence or absence of fever during consultation. Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies. Patients with high parasite densities were more likely to test positive with RDTs than those with low density infections. Conclusion RDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission. Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied.

Background Blood spots collected onto filter paper are an established and convenient source of antibodies for serological diagnosis and epidemiological surveys. Although recommendations for the storage and analysis of small molecule analytes in blood spots exist, there are no published systematic studies of the stability of antibodies under different storage conditions. Methods Blood spots, on filter paper or glass fibre mats and containing malaria-endemic plasma, were desiccated and stored at various temperatures for different times. Eluates of these spots were assayed for antibodies against two Plasmodium falciparum antigens, MSP-119 and MSP2, and calculated titres used to fit an exponential (first order kinetic) decay model. The first order rate constants (k) for each spot storage temperature were used to fit an Arrhenius equation, in order to estimate the thermal and temporal stability of antibodies in dried blood spots. The utility of blood spots for serological assays was confirmed by comparing antibodies eluted from blood spots with the equivalent plasma values in a series of samples from North Eastern Tanzania and by using blood spot-derived antibodies to estimate malaria transmission intensity in this site and for two localities in Uganda. Results Antibodies in spots on filter paper and glass fibre paper had similar stabilities but blood was more easily absorbed onto filter papers than glass fibre, spots were more regular and spot size was more closely correlated with blood volume for filter paper spots. Desiccated spots could be stored at or below 4°C for extended periods, but were stable for only very limited periods at ambient temperature. When desiccated, recoveries of antibodies that are predominantly of IgG1 or IgG3 subclasses were similar. Recoveries of antibodies from paired samples of serum and of blood spots from Tanzania which had been suitably stored showed similar recoveries of antibodies, but spots which had been stored for extended periods at ambient humidity and temperature showed severe loss of recoveries. Estimates of malaria transmission intensity obtained from serum and from blood spots were similar, and values obtained using blood spots agreed well with entomologically determined values. Conclusion This study has demonstrated the suitability of filter paper blood spots paper for collection of serum antibodies, and provided clear guidelines for the treatment and storage of filter papers which emphasize the importance of desiccation and minimisation of time spent at ambient temperatures. A recommended protocol for collecting, storing and assaying blood spots is provided.

The S108N, C59R, and N51I mutations in the Plasmodium falciparum gene that encodes dihydrofolate reductase, dhfr, confer resistance to pyrimethamine and are common in Africa. However, the I164L mutation, which confers high-level resistance, is rarely seen. We found a 14% prevalence of the I164L mutation among a sample of 51 patients with malaria in Kabale District in southwest Uganda in 2005 and a 4% prevalence among 72 patients with malaria in the neighboring district of Rukungiri during the same year. Surveillance at 6 sites across Uganda during 2002-2004 reported a single case of infection involving an I164L mutant, also in the southwest, suggesting that this is a regional hot spot. The spatial clustering and increasing prevalence of the I164L mutation is indicative of local transmission of the mutant. Targeted surveillance is needed to confirm the extent of the spread of the I164L mutation and to monitor the impact of I164L on the efficacy of antifolates for intermittent preventive treatment of pregnant women and/or infants with falciparum malaria.

Malaria epidemics represent a significant public health problem in the highlands of Africa. Many of these epidemics occur in low resource settings, where the development of an effective system for malaria surveillance has been a key challenge. Between 2001 and 2006, the Highland Malaria Project (HIMAL) established a programme to develop and test a district-based surveillance system for the early detection and control of malaria epidemics in four pilot districts in Kenya and Uganda. An innovative feature of the programme was the devolution of responsibility for the detection of epidemics from the central Ministry of Health to District Health Management Teams. The implementation of the programme offered the opportunity to test both the technical aspects of the system and to examine the practical issues relating to the operation of the programme in the context of the existing health system. To investigate the attitude of key staff towards the programme, and their perceptions of its impact on their working practices, interviews were carried out among 52 health staff at district level and in the Ministries of Health in Kenya and Uganda. The transfer of responsibility for the early detection of epidemics to the districts had resulted in perceptions of individual empowerment among district-based staff. This, together with improved support supervision, was a key factor in sustaining motivation and improved surveillance. The enhanced support supervision also produced capacity benefits that extended beyond improved malaria surveillance. However, these improvements occurred in the context of increased logistical support (the provision of transport, fuel and travel allowances) which the participants believed was essential to the functioning of an effective system. With this proviso, the district-based malaria early warning system was perceived to be manageable, effective and sustainable in the context of the current health system.

To the Editor: In the field of malaria epidemic early warning, there exists an unfortunate but frequently accurate perception that health systems in many affected countries learn of epidemics by way of the popular press rather than through formal disease surveillance systems. Malaria epidemics are often easily recognized (albeit too late) by laypersons (1), but most routine disease surveillance systems lack the ability to provide accurate, timely indications of aberrations in case numbers. The World Health Organization (WHO) has set specific targets for early detection and control of malaria epidemics as part of a wider strategy to cut the global extent of malaria in half by 2010 (2). We describe experiences during a recent epidemic in southwest Uganda and examine the performance of a pilot early detection system.

Although the development of early warning systems for malaria has been advocated by international agencies and academic researchers for many years, practical progress in this area has been relatively modest. In two recent articles, Thomson et al. provide new evidence that models of malaria incidence that incorporate monitored or predicted climate can provide early warnings of epidemics one to five months in advance in semi-arid areas. Although the potential benefits of these models in terms of improved management of epidemics are clear, several technical and practical hurdles still need to be overcome before the models can be widely integrated into routine malaria-control strategies.

This study was conducted to quantify the association between meteorological variables and incidence of Plasmodium falciparum in areas with unstable malaria transmission in Ethiopia. We used morbidity data pertaining to microscopically confirmed cases reported from 35 sites throughout Ethiopia over a period of approximately 6–7 years. A model was developed reflecting biological relationships between meteorological and morbidity variables. A model that included rainfall 2 and 3 months earlier, mean minimum temperature of the previous month and P. falciparum case incidence during the previous month was fitted to morbidity data from the various areas. The model produced similar percentages of over-estimation (19·7% of predictions exceeded twice the observed values) and under-estimation (18·6% were less than half the observed values). Inclusion of maximum temperature did not improve the model. The model performed better in areas with relatively high or low incidence (>85% of the total variance explained) than those with moderate incidence (55–85% of the total variance explained). The study indicated that a dynamic immunity mechanism is needed in a prediction model. The potential usefulness and drawbacks of the modelling approach in studying the weather–malaria relationship are discussed, including a need for mechanisms that can adequately handle temporal variations in immunity to malaria.

The aim of this study was to assess the accuracy of different methods of forecasting malaria incidence from historical morbidity patterns in areas with unstable transmission. We tested five methods using incidence data reported from health facilities in 20 areas in central and north-western Ethiopia. The accuracy of each method was determined by calculating errors resulting from the difference between observed incidence and corresponding forecasts obtained for prediction intervals of up to 12 months. Simple seasonal adjustment methods outperformed a statistically more advanced autoregressive integrated moving average method. In particular, a seasonal adjustment method that uses mean deviation of the last three observations from expected seasonal values consistently produced the best forecasts. Using 3 years' observation to generate forecasts with this method gave lower errors than shorter or longer periods. Incidence during the rainy months of June-August was the most predictable with this method. Forecasts for the normally dry months, particularly December-February, were less accurate. The study shows the limitations of forecasting incidence from historical morbidity patterns alone, and indicates the need for improved epidemic early warning by incorporating external predictors such as meteorological factors.

Background Mass distribution campaigns of insecticide-treated nets for malaria prevention are usually accompanied by intensive behaviour change communication (BCC) to encourage hanging and use of nets. However, data on the effectiveness of these communication efforts are scarce. In preparation for the next round of mass campaigns in Nigeria, a secondary analysis of existing data from post-campaign surveys was undertaken to investigate the influence of BCC on net hanging and use. Methods Surveys were undertaken between 2009 and 2012 in ten states in Nigeria using standardized questionnaires. Two-stage cluster sampling was used to select households in each study site. Outcomes were defined as the effects of BCC message exposure and recall on knowledge, attitudes, perception as well as intentions and actual use. From the univariable analysis, potential confounders and explanatory variables were identified and key effects explored in multivariable linear or logistic regression models; terms in the models were kept if they had a marginal significance with p