A practical approach for geographic prioritization and targeting of insecticide-treated net distribution campaigns during public health emergencies and in resource-limited settings.

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.

Correction to: Monitoring changes in malaria epidemiology and effectiveness of interventions in Ethiopia and Uganda: Beyond Garki Project baseline survey.

Please be advised that one of the author names is incorrectly spelled in the published article: 'Irene Kyomuhagi' should be 'Irene Kyomuhangi'.

Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa.

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.

Effect of environmental variables and kdr resistance genotype on survival probability and infection rates in Anopheles gambiae (s.s.).

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.

Insecticide resistance patterns in Uganda and the effect of indoor residual spraying with bendiocarb on kdr L1014S frequencies in Anopheles gambiae s.s.

BACKGROUND: Resistance of malaria vectors to pyrethroid insecticides has been attributed to selection pressure from long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), and the use of chemicals in agriculture. The use of different classes of insecticides in combination or by rotation has been recommended for resistance management. The aim of this study was to understand the role of IRS with a carbamate insecticide in management of pyrethroid resistance. METHODS: Anopheles mosquitoes were collected from multiple sites in nine districts of Uganda (up to five sites per district). Three districts had been sprayed with bendiocarb. Phenotypic resistance was determined using standard susceptibility tests. Molecular assays were used to determine the frequency of resistance mutations. The kdr L1014S homozygote frequency in Anopheles gambiae s.s. was used as the outcome measure to test the effects of various factors using a logistic regression model. Bendiocarb coverage, annual rainfall, altitude, mosquito collection method, LLIN use, LLINs distributed in the previous 5 years, household use of agricultural pesticides, and malaria prevalence in children 2-9 years old were entered as explanatory variables. RESULTS: Tests with pyrethroid insecticides showed resistance and suspected resistance levels in all districts except Apac (a sprayed district). Bendiocarb resistance was not detected in sprayed sites, but was confirmed in one unsprayed site (Soroti). Anopheles gambiae s.s. collected from areas sprayed with bendiocarb had significantly less kdr homozygosity than those collected from unsprayed areas. Mosquitoes collected indoors as adults had significantly higher frequency of kdr homozygotes than mosquitoes collected as larvae, possibly indicating selective sampling of resistant adults, presumably due to exposure to insecticides inside houses that would disproportionately affect susceptible mosquitoes. The effect of LLIN use on kdr homozygosity was significantly modified by annual rainfall. In areas receiving high rainfall, LLIN use was associated with increased kdr homozygosity and this association weakened as rainfall decreased, indicating more frequency of exposure to pyrethroids in relatively wet areas with high vector density. CONCLUSION: This study suggests that using a carbamate insecticide for IRS in areas with high levels of pyrethroid resistance may reduce kdr frequencies in An. gambiae s.s.

Travel and the emergence of high-level drug resistance in Plasmodium falciparum in southwest Uganda: results from a population-based study.

BACKGROUND: The I164L mutation on the dhfr gene confers high level resistance to sulfadoxine-pyrimethamine (SP) but it is rare in Africa except in a cluster of reports where prevalence >10% in highland areas of southwest Uganda and eastern Rwanda. The occurrence of the dhfr I164L mutation was investigated in community surveys in this area and examined the relationship to migration. METHODS: A cross-sectional prevalence survey was undertaken in among villages within the catchment areas of two health facilities in a highland site (Kabale) and a highland fringe site (Rukungiri) in 2007. Sociodemographic details, including recent migration, were collected for each person included in the study. A total of 206 Plasmodium falciparum positive subjects were detected by rapid diagnostic test; 203 in Rukungiri and 3 in Kabale. Bloodspot samples were taken and were screened for dhfr I164L. RESULTS: Sequence analysis confirmed the presence of the I164L mutations in twelve P. falciparum positive samples giving an estimated prevalence of 8.6% in Rukungiri. Of the three parasite positive samples in Kabale, none had I164L mutations. Among the twelve I164L positives three were male, ages ranged from 5 to 90 years of age. None of those with the I164L mutation had travelled in the 8 weeks prior to the survey, although three were from households from which at least one household member had travelled during that period. Haplotypes were determined in non-mixed infections and showed the dhfr I164L mutation occurs in both as a N51I + S108N + I164L haplotype (n = 2) and N51I + C59R + S108N + I164L haplotype (n = 5). Genotyping of flanking microsatellite markers showed that the I164L occurred independently on the triple mutant (N51I, C59R + S108N) and double mutant (N51I + S108N) background. CONCLUSIONS: There is sustained local transmission of parasites with the dhfr I164L mutation in Rukungiri and no evidence to indicate its occurrence is associated with recent travel to highly resistant neighbouring areas. The emergence of a regional cluster of I164L in SW Uganda and Rwanda indicates that transmission of I164L is facilitated by strong drug pressure in low transmission areas potentially catalysed in those areas by travel and the importation of parasites from relatively higher transmission settings.

The impact of behaviour change communication on the use of insecticide treated nets: a secondary analysis of ten post-campaign surveys from Nigeria.

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 < 0.2. To quantify the effects from BCC, a treatment effect model was used with an inverse-probability weight regression adjustment. RESULTS: More than half of the respondents (58.4 %; 95 % CI 56.0, 60.7) had heard a message about net use or hanging during or after the distribution campaign, with media cited as the most common source of information. Attitude towards net use was positively linked to the number of messages recalled and was overall better in the northern study sites. The number of messages recalled was also the strongest predictor of knowledge (p < 0.001). All BCC outcomes showed a significant increase in net use, which was strongest for the confidence to take action regarding nets with an overall effect of 17 %-point increase of net use comparing poor and excellent confidence levels. Intention to use every night increased net use by 15 %-points and discussing net use in the family by 8 % points. All these effects were statistically significant (p < 0.001). CONCLUSIONS: Multichannel BCC campaigns as well as other media were effective in contributing to an increase in net culture, hanging and use, particularly by vulnerable groups.

Application of Serological Tools and Spatial Analysis to Investigate Malaria Transmission Dynamics in Highland Areas of Southwest Uganda.

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.

Exposure to deltamethrin affects development of Plasmodium falciparum inside wild pyrethroid resistant Anopheles gambiae s.s. mosquitoes in Uganda.

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/m(2)), prevalence was reduced by 59% (95% CI = 22%-78%) and intensity by 41% (95% CI = 25%-54%). With high doses (10-16.7 mg/m(2)), 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.

Monitoring changes in malaria epidemiology and effectiveness of interventions in Ethiopia and Uganda: Beyond Garki Project baseline survey.

BACKGROUND: Scale-up of malaria interventions seems to have contributed to a decline in the disease but other factors may also have had some role. Understanding changes in transmission and determinant factors will help to adapt control strategies accordingly. METHODS: Four sites in Ethiopia and Uganda were set up to monitor epidemiological changes and effectiveness of interventions over time. Here, results of a survey during the peak transmission season of 2012 are reported, which will be used as baseline for subsequent surveys and may support adaptation of control strategies. Data on malariometric and entomological variables, socio-economic status (SES) and control coverage were collected. RESULTS: Malaria prevalence varied from 1.4 % in Guba (Ethiopia) to 9.9 % in Butemba (Uganda). The most dominant species was Plasmodium vivax in Ethiopia and Plasmodium falciparum in Uganda. The majority of human-vector contact occurred indoors in Uganda, ranging from 83 % (Anopheles funestus sensu lato) to 93 % (Anopheles gambiae s.l.), which is an important factor for the effectiveness of insecticide-treated nets (ITNs) or indoor residual spraying (IRS). High kdr-L1014S (resistance genotype) frequency was observed in A. gambiae sensu stricto in Uganda. Too few mosquitoes were collected in Ethiopia, so it was not possible to assess vector habits and insecticide resistance levels. ITN ownership did not vary by SES and 56-98 % and 68-78 % of households owned at least one ITN in Ethiopia and Uganda, respectively. In Uganda, 7 % of nets were purchased by households, but the nets were untreated. In three of the four sites, 69-76 % of people with access to ITNs used them. IRS coverage ranged from 84 to 96 % in the three sprayed sites. Half of febrile children in Uganda and three-quarters in Ethiopia for whom treatment was sought received diagnostic tests. High levels of child undernutrition were detected in both countries carrying important implications on child development. In Uganda, 7-8 % of pregnant women took the recommended minimum three doses of intermittent preventive treatment. CONCLUSION: Malaria epidemiology seems to be changing compared to earlier published data, and it is essential to have more data to understand how much of the changes are attributable to interventions and other factors. Regular monitoring will help to better interpret changes, identify determinants, modify strategies and improve targeting to address transmission heterogeneity.

Association between recent internal travel and malaria in Ugandan highland and highland fringe areas.

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.

Costs of early detection systems for epidemic malaria in highland areas of Kenya and Uganda.

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.

Variations in entomological indices in relation to weather patterns and malaria incidence in East African highlands: implications for epidemic prevention and control.

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.

Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands.

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.

District-based malaria epidemic early warning systems in East Africa: perceptions of acceptability and usefulness among key staff at health facility, district and central levels.

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.

Emergence of a dhfr mutation conferring high-level drug resistance in Plasmodium falciparum populations from southwest Uganda.

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.

Response to malaria epidemics in Africa.

Malaria epidemics affect nonimmune populations in many highland and semi-arid areas of Africa. Effective prevention of these epidemics is challenging, particularly in the highlands where predictive accuracy of indicators is not sufficiently high to allow decisions involving expensive measures such as indoor residual spraying of insecticides. Advances in geographic information systems have proved useful in stratification of areas to guide selective targeting of interventions, including barrier application of insecticides in transmission foci to prevent spread of infection. Because rainfall is associated with epidemics in semi-arid areas, early warning methods based on seasonal climate predictions have been proposed. For most areas, response measures should focus on early recognition of anomalies and rapid mass drug administration. Vector control measures are useful if abnormal transmission is highly likely and if they can be selectively implemented at the early stages of an outbreak.

Early warning systems for malaria in Africa: from blueprint to practice.

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.

The uncertain burden of Plasmodium falciparum epidemics in Africa.

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.

Malaria epidemic early warning and detection in African highlands.

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.