Identifying, characterizing, and targeting the reservoir of malaria transmission in Southern Tanzania.

Malaria continues to be a leading cause of morbidity and mortality in countries where it is endemic. While dramatic progress has been achieved globally, recent global malaria reports suggested that overall global progress has stalled since 2014. The plateau in improvement, particularly in high transmission settings of Africa, is associated with several factors, including inadequate coverage and use of the interventions, poor health service coverage, changes in vectors bionomics and insecticides resistance to malaria vectors. In addition, many high transmission countries have insufficient community based interventions to reduce malaria morbidity and mortality. Barriers to progress are associated with uncoordinated surveillance systems, low socioeconomic and living standards as well as inadequate adherence of the affected population to interventions. This hinders the efforts to achieve the overall goal of malaria elimination in many malaria endemic settings, highlighting the need for overall health system improvement to allow for innovative control and surveillance techniques. Furthermore, it necessitates a better understanding of malaria transmission dynamics. In order to meet this challenge, we must delve deeper into the underlying malaria transmission dynamics. The proposed PhD project was embedded within a tripartite pilot project between China-United Kingdom-Tanzania. The project was about Malaria control in Rufiji district, Tanzania, that started in September 2015. The overarching goal of the PhD project was to study the dynamics of malaria transmission and evaluate the impact of community-based malaria reactive case detection strategy in strengthening the transmission-reduction of human malaria infections in areas with high coverage of LLINs. To achieve the project's goal, four specific objectives were specified. This matches to the project chapters' conclusions in this thesis. In Chapter three of this thesis, the effectiveness of implementing a community-based testing and treatment plan to reduce the malaria burden in moderate to high transmission areas is analyzed. The "1-3-7" surveillance and response model developed in China, which prompted the development of this initiative and subsequent adoption of the 1,7-malaria Reactive Community-based Testing and Response (1,7mRCTR) approach, is a novel method for implementing the WHO-T3 and surveillance intervention to eliminate malaria. However, the 1-3-7 model is more effective in China, where the goal is to eradicate the disease, than in Tanzania, where the bulk of the population still has moderate to high transmission. The 1,7-mRCTR is locally-tailored for reporting malaria cases on day one and intervention on day seven, with community-based testing and treatment in high-burden areas stratified based on weekly data from health facilities. In the same district, control areas with comparable epidemiology (no 1,7-mRCTR) were selected and monitored for the duration of the project. After two years of implementing the 1.7 mRCTR, the prevalence of parasites in the target areas was reduced by 66 percent above and above the benefit provided by national measures already in place. Despite the fact that new technology and techniques may be required to eradicate malaria in stable transmission areas of Sub-Saharan Africa, this experiment proved that a locally tailored approach could help to expedite malaria control and elimination efforts. In addition, it highlight the opportunities of validating the results and possibilities of scaling up 1,7-mRCTR approach in other settings within Tanzania, and other African countries for accelerating malaria control and elimination across Africa. In chapter four of this dissertation, the household cross-sectional survey data gathered prior to 1,7-mRCTR intervention were used to describe and characterize the malaria prevalence and the associated exposures risk . In the context of the Tanzania Demographic and Health Survey and Malaria Indicator Survey (TDHS-MIS) 2015-16, this study’s findings are discussed. The findings highlight the importance of national malaria monitoring, and its ramifications for present malaria management strategies. The prevalence of malaria varied by ward, ranging from 5.6 percent to 18 percent, with the average prevalence reported by this study (13 percent) being higher than the reported by the RDHS-MIS national (7.3 percent). Based on the findings of this chapter, t is important for the new malaria control plans to be effective in sustaining gains and accelerating progress towards the end goals in the fight against malaria will depend on clearing parasitaemia and ensuring that poverty is eleviated Importantly, programs intended to improve malaria interventions for the currently recognized vulnerable groups should be modified to include other groups observed with highest parasitaemia. Chapter five investigated and assessed one of the extremely sensitive epidemiological study of malaria transmission (host preference by malaria vectors). In addition to being a significant predictor of malaria transmission patterns, this indicator is essential for determining the appropriateness and efficacy of vector control interventions and for predicting malaria transmission patterns. Using the direct host-preference experiment, the host preference of the primary malaria vector species, Anopheles arabiensis and Anopheles gambiae sensu stricto, was examined in two distinct ecological contexts in Tanzania. In contrast to historical accounts, the data indicate that urban An. arabiensis showed a stronger preference for cattle than rural An. arabiensis, but An. gambiae showed no preference for either people or animals under the same conditions. To achieve malaria eradication, we must have a deeper understanding of the prevalent vectors, their feeding behavior in varied ecological situations, and their feeding preferences. This will allow us to more effectively design and implement locally-tailored, high-impact, integrated interventions. Anopheles mosquito species composition, abundance, and spatial-temporal variability must be thoroughly understood in order to optimally exploit high-resolution malaria vector control strategies. Community-based mapping of residual malaria vector densities to support malaria elimination efforts in southeastern Tanzania is discussed in Chapter six. The findings highligth the changing composition of vector species through time, as well as the presence of many malaria vector species at the village scale, which is characterized by a wide spectrum of ecological variation. Human biting rates (HBR) in the study wards ranged from 1.5 to 73 bites per person every night. Characterization of Anopheles vectors indicated disparities between villages and wards in the distribution of Anopheles gambiae s.l., Anopheles funestus, and Anopheles coustani. This study's findings give evidence-based information that is essential for planning and implementing vector control actions in a local setting, complementing the results of Chapter four. In addition, the findings highlight the significance of comprehending and incorporating vector bionomics data into surveillance and response systems in order to successfully implement the ongoing micro-stratification of malaria strata. Surveillance is acknowledged as an intervention and considered instrumental in accelerating global malaria elimination efforts. However, all available evidence to date supports the incorporation of surveillance as in intervention in low endemicity areas, with no evidence comes from moderate to high endemicity areas. Therefore, this PhD project is the first attempt to develop a surveillance and response strategy in moderate to high transmission setting. The findings aline the current Tanzania mid-term review of the national malaria control as well as with the goals Global Technical Strategy 2015-2030 (GTS) and the High Burden to High Impact (HBHI) initiative, which both reiterated the importance of tailoring intervention approaches to the sub-national local context in order to accelerate progress toward malaria reduction and elimination. Behaviour ecology matters and so does evolutionary biology in human-modified environment, the spatial-temporal variation findings in vector composition at a fine scale level of village and the reduced human-biting preference of the primary malaria vectors collected from two distinct characterized with different ecological features is an example illustrating why regular surveys of mosquito compositions and behaviour need to be incorporated in malaria surveillance. Furthermore, support that, in regions with a high malaria incidence, the convention interventions should be maintained, while prioritizing taiolored approach based on the local contex

Suppression of malaria vector densities and human infection prevalence associated with scale-up of mosquito-proofed housing in Dar es Salaam, Tanzania: re-analysis of an observational series of parasitological and entomological surveys.

BACKGROUND In the city of Dar es Salaam, Tanzania, rapid and spontaneous scale-up of window screening occurred through purely horizontal commercial distribution systems without any public subsidies or promotion. Scale-up of window screening coincided with a planned evaluation of programmatic, vertically managed scale-up of regular larvicide application as an intervention against malaria vectors and transmission. We aimed to establish whether scale-up of window screening was associated with suppression of mosquito populations, especially for malaria vectors that strongly prefer humans as their source of blood. METHODS This study was a re-analysis of a previous observational series of epidemiological data plus new analyses of previously partly reported complementary entomological data, from Dar es Salaam. Between 2004 and 2008, six rounds of cluster-sampled, rolling, cross-sectional parasitological and questionnaire surveys were done in urban Dar es Salaam to assess the effect of larviciding and other determinants of malaria risk, such as use of bed nets and antimalarial drugs, socioeconomic status, age, sex, travel history, mosquito-proofed housing, and spending time outdoors. The effects of scaled-up larvicide application and window screening were estimated by fitting generalised linear mixed models that allowed for both spatial variation between survey locations and temporal autocorrelation within locations. We also conducted continuous longitudinal entomological surveys of outdoor human biting rates by mosquitoes and experimental measurements of mosquito host preferences. FINDINGS Best-fit models of Plasmodium falciparum malaria infection prevalence among humans were largely consistent with the results of the previous analyses. Re-analysis of previously reported epidemiological data revealed that most of the empirically fitted downward time trend in P falciparum malaria prevalence over the course of the study (odds ratio [OR] 0·04; 95% CI 0·03-0·06; p<0·0001), which was not previously reported numerically or attributed to any explanatory factor, could be plausibly explained by association with an upward trend in city-wide window screening coverage (OR 0·07; 0·05-0·09; p<0·0001) and progressive rollout of larviciding (OR 0·50; 0·41-0·60; p<0·0001). Increasing coverage of complete window screening was also associated with reduced biting densities of all taxonomic groups of mosquitoes (all p<0·0001), especially the Anopheles gambiae complex (relative rate [RR] 0·23; 95% CI 0·16-0·33) and Anopheles funestus group (RR 0·08; 0·04-0·16), which were confirmed as the most efficient vectors of malaria with strong preferences for humans over cattle. Larviciding was also associated with reduced biting densities of all mosquito taxa (p<0·0001), to an extent that varied consistently with the larvicide targeting scheme and known larval ecology of each taxon. INTERPRETATION Community-wide mosquito proofing of houses might deliver greater impacts on vector populations and malaria transmission than previously thought. The spontaneous nature of the scale-up observed here is also encouraging with regards to practicality, acceptability, and affordability in low-income settings. FUNDING United States Agency for International Development, Bill & Melinda Gates Foundation, Wellcome Trust, and Valent BioSciences LLC

Lidar reveals activity anomaly of malaria vectors during pan-African eclipse

Yearly, a quarter billion people are infected and a half a million killed by the mosquito-borne disease malaria. Lack of real-time observational tools for continuously assessing the unperturbed mosquito flight activity in situ limits progress toward improved vector control. We deployed a high-resolution entomological lidar to monitor a half-kilometer static transect adjacent to a Tanzanian village. We evaluated one-third million insect observations during five nights, four days, and one annular solar eclipse. We demonstrate in situ lidar classification of several insect families and their sexes based on their modulation signatures. We were able to compare the fine-scale spatiotemporal activity patterns of malaria vectors during ordinary days and an eclipse to disentangle phototactic activity patterns from the circadian mechanism. We observed an increased insect activity during the eclipse attributable to mosquitoes. These unprecedented findings demonstrate how lidar-based monitoring of distinct mosquito activities could advance our understanding of vector ecology

Attribution of reductions in malaria prevalence in Dar es Salaam, Tanzania – Authors' reply

We thank Mathieu Maheu-Giroux and Marcia Castro for their Correspondence about our Article.1 Regarding concerns about the stepped-wedge design of the larviciding scale-up in our study, we agree and also note that scale-up was not randomised, but rather introduced earliest to the best-prepared wards. However, such compromises are normal and healthy in pragmatic assessments of effectiveness under realistic programmatic conditions, rather than efficacy under artificially controlled experimental conditions. As acknowledged in the discussion and emphasised in the title, we also agree that evidence for window screening impact is purely observational, and that long-overdue, cluster-randomised, experimentally controlled analyses of well developed delivery practices for both these supplementary vector control measures are urgently needed

Household factors associated with access to insecticide-treated nets and house modification in Bagamoyo and Ulanga districts, Tanzania.

BACKGROUND: Insecticide-treated nets (ITNs) and house modifications are proven vector control tools, yet in most regions, full coverage has not been achieved. This study investigates household factors associated with access to ITNs and house modification in Tanzania. METHODS: Baseline cross-sectional survey data from previous studies on spatial repellants and indoor residual spray evaluation was analysed from 6757 households in Bagamoyo (60 km north of Dar es Salaam) and 1241 households in Ulanga (a remote rural area in southeast Tanzania), respectively. Regression models were used to estimate the associations between the outcomes: population access to ITNs, access to ITN per sleeping spaces, window screens and closed eaves, and the covariates household size, age, gender, pregnancy, education, house size, house modification (window screens and closed eaves) and wealth. RESULTS: Population access to ITNs (households with one ITN per two people that stayed in the house the previous night of the survey) was 69% (n = 4663) and access to ITNs per sleeping spaces (households with enough ITNs to cover all sleeping spaces used the previous night of the survey) was 45% (n = 3010) in Bagamoyo, 3 years after the last mass campaign. These findings are both lower than the least 80% coverage target of the Tanzania National Malaria Strategic Plan (Tanzania NMSP). In Ulanga, population access to ITNs was 92% (n = 1143) and ITNs per sleeping spaces was 88% (n = 1093), 1 year after the last Universal Coverage Campaign (UCC). Increased household size was significantly associated with lower access to ITNs even shortly after UCC. House modification was common in both areas but influenced by wealth. In Bagamoyo, screened windows were more common than closed eaves (65% vs 13%), whereas in Ulanga more houses had closed eaves than window screens (55% vs 12%). CONCLUSION: Population access to ITNs was substantially lower than the targets of the Tanzania NMSP after 3 years and lower among larger households after 1 year following ITN campaign. House modification was common in both areas, associated with wealth. Improved access to ITNs and window screens through subsidies and Behaviour Change Communication (BCC) strategies, especially among large and poor households and those headed by people with a low level of education, could maximize the uptake of a combination of these two interventions

Participatory approaches for raising awareness among subsistence farmers in Tanzania about the spread of insecticide resistance in malaria vectors and the possible link to improper agricultural pesticide use

Background: Insecticide resistance is a key barrier to long-term malaria control, and it may be exacerbated by poor agricultural pesticide use. Current practices, however, do not link public health and agricultural pesticide use. This study investigated the perspectives of farmers and other stakeholders regarding the integration of agricultural and public health measures to address resistance. Additionally, the feasibility of participatory workshops to increase the farmers’ understanding and participation in pesticide stewardship was assessed. Methods: Four themes were investigated: pesticide awareness, practices, and opinions of; insecticide resistance in malaria vectors; the effectiveness of current malaria prevention tools; and the links between agricultural and public health pesticide usage. Participatory workshops and field training were held with entomologists, farmers, and agricultural specialists, focusing on agro-ecosystem practices related to pest control; and local farmers were involved in live-testing for insecticides resistance of local Anopheles mosquitoes. Results: Most farmers (94%) considered pesticides effective, and nearly half of them (n = 198, 46.4%) could identify and name crop pests and diseases, mostly using local names. Three quarters were unaware of mosquito larvae in their fields, and only 7% considered their fields as potential sources of mosquitoes. Two thirds were uninformed of any effects that agricultural pesticides may have on mosquitoes, and three quarters had never heard of resistance in malaria mosquitoes. Experts from various sectors acknowledged that agricultural pesticides might impact malaria control through increasing resistance. They did, however, emphasize the importance of crop protection and advocated for the use of pesticides sparingly and non-chemical approaches. Farmers learnt how to discriminate between malaria vectors and non-vectors, identify agricultural pests and diseases, choose and use pesticides effectively, and conduct resistance tests during the participatory workshops. Conclusion: This study emphasizes the significance of enhancing subsistence farmers’ awareness of mosquito ecology as well as merging public health and agricultural pest management measures. Participatory techniques have the potential to raise stakeholder awareness and engagement, resulting in more effective resistance management

Reduced human-biting preferences of the African malaria vectors Anopheles arabiensis and Anopheles gambiae in an urban context: controlled, competitive host-preference experiments in Tanzania

Background Host preference is a critical determinant of human exposure to vector-borne infections and the impact of vector control interventions. Widespread use of long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS) across sub-Saharan Africa, which protect humans against mosquitoes, may select for altered host preference traits of malaria vectors over the long term. Here, the host preferences of Anopheles arabiensis and Anopheles gambiae sensu stricto (s.s.) were experimentally assessed in the field, using direct host-preference assays in two distinct ecological settings in Tanzania. Methods Eight Ifakara Tent Trap (ITT), four baited with humans and four with bovine calves, were simultaneously used to catch malaria vectors in open field sites in urban and rural Tanzania. The numbers of mosquitoes collected in human-baited traps versus calf-baited traps were used to estimate human feeding preference for each site's vector species. Results The estimated proportion [95% confidence interval (CI)] of mosquitoes attacking humans rather than cattle was 0.60 [0.40, 0.77] for An. arabiensis in the rural setting and 0.61 [0.32, 0.85] for An. gambiae s.s. in the urban setting, indicating no preference for either host in both cases (P = 0.32 and 0.46, respectively) and no difference in preference between the two (Odds Ratio (OR) [95%] = 0.95 [0.30, 3.01], P = 0.924). However, only a quarter of An. arabiensis in the urban setting attacked humans (0.25 [0.09, 0.53]), indicating a preference for cattle that approached significance (P = 0.08). Indeed, urban An. arabiensis were less likely to attack humans rather than cattle when compared to the same species in the rural setting (OR [95%] = 0.21 [0.05, 0.91], P = 0.037). Conclusion Urban An. arabiensis had a stronger preference for cattle than the rural population and urban An. gambiae s.s. showed no clear preference for either humans or cattle. In the urban setting, both species exhibited stronger tendencies to attack cattle than previous studies of the same species in rural contexts. Cattle keeping may, therefore, particularly limit the impact of human-targeted vector control interventions in Dar es Salaam and perhaps in other African towns and cities

Spatially aggregated clusters and scattered smaller loci of elevated malaria vector density and human infection prevalence in urban Dar es Salaam, Tanzania

Background Malaria transmission, primarily mediated by Anopheles gambiae, persists in Dar es Salaam (DSM) despite high coverage with bed nets, mosquito-proofed housing and larviciding. New or improved vector control strategies are required to eliminate malaria from DSM, but these will only succeed if they are delivered to the minority of locations where residual transmission actually persists. Hotspots of spatially clustered locations with elevated malaria infection prevalence or vector densities were, therefore, mapped across the city in an attempt to provide a basis for targeting supplementary interventions. Methods Two phases of a city-wide population-weighted random sample of cross-sectional household surveys of malaria infections were complemented by two matching phases of geographically overlapping, high-resolution, longitudinal vector density surveys; spanning 2010–2013. Spatial autocorrelations were explored using Moran’s I and hotspots were detected using flexible spatial scan statistics. Results Seven hotspots of spatially clustered elevated vector density and eight of malaria infection prevalence were detected over both phases. Only a third of vectors were collected in hotspots in phase 1 (30 %) and phase 2 (33 %). Malaria prevalence hotspots accounted for only half of malaria infections detected in phase 1 (55 %) and phase 2 (47 %). Three quarters (76 % in phase 1 and 74 % in phase 2) of survey locations with detectable vector populations were outside of hotspots. Similarly, more than half of locations with higher infection prevalence (>10 %) occurred outside of hotspots (51 % in phase 1 and 54 % in phase 2). Vector proliferation hazard (exposure to An. gambiae) and malaria infection risk were only very loosely associated with each other (Odds ratio (OR) [95 % Confidence Interval (CI)] = 1.56 [0.89, 1.78], P = 0.52)). Conclusion Many small, scattered loci of local malaria transmission were haphazardly scattered across the city, so interventions targeting only currently identifiable spatially aggregated hotspots will have limited impact. Routine, spatially comprehensive, longitudinal entomological and parasitological surveillance systems, with sufficient sensitivity and spatial resolution to detect these scattered loci, are required to eliminate transmission from this typical African city. Intervention packages targeted to both loci and hotspots of transmission will need to suppress local vector proliferation, treat infected residents and provide vulnerable residents with supplementary protective measures against exposure

Fine scale mapping of malaria infection clusters by using routinely collected health 1 facility data in urban Dar es Salaam, Tanzania

This study investigated whether passively collected routine health facility data can be used for mapping spatial heterogeneities in malaria transmission at the level of local government housing cluster administrative units in Dar es Salaam, Tanzania. From June 2012 to Jan 2013, residential locations of patients tested for malaria at a public health facility were traced based on their local leaders’ names and geo-referencing the point locations of these leaders’ houses. Geographic information systems (GIS) were used to visualise the spatial distribution of malaria infection rates. Spatial scan statistics were deployed to detect spatial clustering of high infection rates. Among 2,407 patients tested for malaria, 46.6% (1,121) could be traced to their 411 different residential housing clusters. One small spatially aggregated cluster of neighbourhoods with high prevalence was identified. While the home residence housing cluster leader was unambiguously identified for 73.8% (240/325) of malaria-positive patients, only 42.3% (881/2,082) of those with negative test results were successfully traced. It was concluded that recording simple points of reference during routine health facility visits can be used for mapping malaria infection burden on very fine geographic scales, potentially offering a feasible approach to rational geographic targeting of malaria control interventions. However, in order to tap the full potential of this approach, it would be necessary to optimise patient tracing success and eliminate biases by blinding personnel to test results