Hitting a Moving Target: A Model for Malaria Elimination in the Presence of Population Movement

South Africa is committed to eliminating malaria with a goal of zero local transmission by 2018. Malaria elimination strategies may be unsuccessful if they focus only on vector biology, and ignore the mobility patterns of humans, particularly where the majority of infections are imported. In the first study in Mpumalanga Province in South Africa designed for this purpose, a metapopulation model is developed to assess the impact of their proposed elimination-focused policy interventions. A stochastic, non-linear, ordinary-differential equation model is fitted to malaria data from Mpumalanga and neighbouring Maputo Province in Mozambique. Further scaling-up of vector control is predicted to lead to a minimal reduction in local infections, while mass drug administration and focal screening and treatment at the Mpumalanga-Maputo border are predicted to have only a short-lived impact. Source reduction in Maputo Province is predicted to generate large reductions in local infections through stemming imported infections. The mathematical model predicts malaria elimination to be possible only when imported infections are treated before entry or eliminated at the source suggesting that a regionally focused strategy appears needed, for achieving malaria elimination in Mpumalanga and South Africa.     

Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data

Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model.     

The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial

BackgroundMalaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities.ConclusionsDespite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas. Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach. Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01575613","term_id":"NCT01575613"}}NCT01575613     

A Periodically-Forced Mathematical Model for the Seasonal Dynamics of Malaria in Mosquitoes

We describe and analyze a periodically-forced difference equation model for malaria in mosquitoes that captures the effects of seasonality and allows the mosquitoes to feed on a heterogeneous population of hosts. We numerically show the existence of a unique globally asymptotically stable periodic orbit and calculate periodic orbits of field-measurable quantities that measure malaria transmission. We integrate this model with an individual-based stochastic simulation model for malaria in humans to compare the effects of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) in reducing malaria transmission, prevalence, and incidence. We show that ITNs are more effective than IRS in reducing transmission and prevalence though IRS would achieve its maximal effects within 2 years while ITNs would need two mass distribution campaigns over several years to do so. Furthermore, the combination of both interventions is more effective than either intervention alone. However, although these interventions reduce transmission and prevalence, they can lead to increased clinical malaria; and all three malaria indicators return to preintervention levels within 3 years after the interventions are withdrawn.     

The PacELF programme: will mass drug administration be enough?

The Pacific Programme to Eliminate Lymphatic Filariasis is a regional, mass drug administration-based campaign in 22 countries and territories with the aim of eliminating filariasis transmission and alleviating the suffering caused by Wuchereria bancrofti. The challenges to filariasis elimination campaigns based on mass drug-administration alone are reviewed in this article. These challenges together with the previous successes of mosquito control campaigns in eliminating filariasis from regions in the Pacific argue for inclusion of entomology components in the control of filariasis and the monitoring of filariasis elimination programs.     

Domestic Larval Control Practices and Malaria Prevalence among Under-Five Children in Burkina Faso

Introduction

Larval source management has contributed to malaria decline over the past years. However, little is known about the impact of larval control practices undertaken at the household level on malaria transmission.

Methods

The study was conducted in Kaya health district after the 2010 mass distribution of insecticide treated-nets and the initiation of malaria awareness campaigns in Burkina Faso. The aim was to (i) estimate the level of domestic larval control practices (cleaning of the house and its surroundings, eradication of larval sources, and elimination of hollow objects that might collect water); (ii) identify key determinants; and (iii) explore the structural relationships between these practices, participation in awareness-raising activities and mothers’ knowledge/attitudes/practices, and malaria prevalence among under-five children.

Results

Overall, 2004 households were surveyed and 1,705 under-five children were examined. Half of the mothers undertook at least one action to control larval proliferation. Mothers who had gone to school had better knowledge about malaria and were more likely to undertake domestic larval control practices. Living in highly exposed rural areas significantly decreased the odds of undertaking larval control actions. Mothers’ participation in malaria information sessions increased the adoption of vector control actions and bednet use. Malaria prevalence was statistically lower among children in households where mothers had undertaken at least one vector control action or used bed-nets. There was a 0.16 standard deviation decrease in malaria prevalence for every standard deviation increase in vector control practices. The effect of bednet use on malaria prevalence was of the same magnitude.

Conclusion

Cleaning the house and its surroundings, eradicating breeding sites, and eliminating hollow objects that might collect water play a substantial role in preventing malaria among under-five. There is a need for national malaria control programs to include or reinforce training activities for community health workers aimed at promoting domestic larval control practices.     

From intervention to impact: modelling the potential mortality impact achievable by different longlasting, insecticide-treated net delivery strategies

ABSTRACT: BACKGROUND: The current target of universal access to long-lasting, insecticide-treated nets (LLIN) is 80% coverage to reduce malaria deaths by 75% by 2015. So far, campaigns have been the main channel for large-scale delivery of LLINs, however the World Health Organization has recommended that equal priority should be given to delivery via routine antenatal care (ANC) and immunization systems (EPI) to target pregnant women and children from birth. These various channels of LLIN delivery are targeted to children of different ages. Since risk of mortality varies with child age and LLIN effectiveness declines with net age, it was hypothesized that the age at which a child receives a new LLIN, and therefore the delivery channel, is important in optimizing the health impact of a net. METHODS: A simple dynamic mathematical model was developed of delivery and impact of LLINs among children under five years of age and their household members, incorporating data on age-specific malaria death rates, net use by household structure, and net efficacy over time. RESULTS: The presented analysis finds that supplementing a universal mass campaign with extra ANC delivery would achieve a 1.4 times higher mortality reduction than campaign delivery alone, reflecting that children born in the years between campaigns would otherwise have access to old nets or no nets at an age of high risk. The relative advantage of supplementary ANC delivery is still present though smaller if malaria transmission levels are lower or if there is a strong mass effect achieved by mass campaigns. CONCLUSION: These results indicate that LLIN delivery policies must take into account the age of greatest malaria risk. Emphasis should be placed on supporting routine delivery of LLINs to young children as well as campaigns. Lucy C Okell and Lucy Smith Paintain contributed equally.     

Low Parasitemia in Submicroscopic Infections Significantly Impacts Malaria Diagnostic Sensitivity in the Highlands of Western Kenya

Asymptomatic malaria infections represent a major challenge in malaria control and elimination in Africa. They are reservoirs of malaria parasite that can contribute to disease transmission. Therefore, identification and control of asymptomatic infections are important to make malaria elimination feasible. In this study, we investigated the extent and distribution of asymptomatic malaria in Western Kenya and examined how varying parasitemia affects performance of diagnostic methods including microscopy, conventional PCR, and quantitative PCR. In addition, we compared parasite prevalence rates and parasitemia levels with respect to topography and age in order to explore factors that influence malaria infection. Over 11,000 asymptomatic blood samples from children and adolescents up to 18 years old representing broad areas of Western Kenya were included. Quantitative PCR revealed the highest parasite positive rate among all methods and malaria prevalence in western Kenya varied widely from less than 1% to over 50%. A significantly lower parasitemia was detected in highland than in lowland samples and this contrast was also observed primarily among submicroscopic samples. Although we found no correlation between parasitemia level and age, individuals of younger age group (aged <14) showed significantly higher parasite prevalence. In the lowlands, individuals of aged 5–14 showed significantly higher prevalence than those under age 5. Our findings highlight the need for a more sensitive and time-efficient assay for asymptomatic malaria detection particularly in areas of low-transmission. Combining QPCR with microscopy can enhance the capacity of detecting submicroscopic asymptomatic malaria infections.     

A research agenda for malaria eradication: drugs

Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission.     

Application of the GARC Data Logger—a custom-developed data collection device—to capture and monitor mass dog vaccination campaigns in Namibia

Domestic dogs are responsible for 99% of all cases of human rabies and thus, mass dog vaccination has been demonstrated to be the most effective approach towards the elimination of dog-mediated human rabies. Namibia demonstrated the feasibility of this approach by applying government-led strategic rabies vaccination campaigns to reduce both human and dog rabies incidences in the Northern Communal Areas of Namibia since 2016. The lessons learnt using paper-based form for data capturing and management of mass dog vaccination campaign during the pilot and roll out phase of the project (2016–2018) led to the implementation of a simple and accurate data collection tool in the second phase (2019–2022) of the rabies elimination program. In this paper, we describe the implementation of such custom-developed vaccination tracking device, i.e. the Global Alliance for Rabies Control (GARC) Data Logger (GDL), and the integration of the collected data into a website-based rabies surveillance system (Rabies Epidemiological Bulletin—REB) during 2019 and 2020 campaigns. A total of 10,037 dogs and 520 cats were vaccinated during the 2019 campaign and 13,219 dogs and 1,044 cats during the 2020 campaign. The vaccination data were recorded with the GDL and visualized via REB. Subsequent GIS-analysis using gridded population data revealed a suboptimal vaccination coverage in the great majority of grid cells (82%) with a vaccination coverage below 50%. Spatial regression analysis identified the number of schools, estimated human density, and adult dog population were associated with the vaccination performance. However, there was an inverse correlation to human densities. Nonetheless, the use of the GDL improved data capturing and monitoring capacity of the campaign, enabling the Namibian government to improve strategies for the vaccination of at-risk areas towards achieving adequate vaccination coverage which would effectively break the transmission of rabies.     

Stable and Unstable Malaria Hotspots in Longitudinal Cohort Studies in Kenya

Background

Infectious diseases often demonstrate heterogeneity of transmission among host populations. This heterogeneity reduces the efficacy of control strategies, but also implies that focusing control strategies on “hotspots” of transmission could be highly effective.

Methods and Findings

In order to identify hotspots of malaria transmission, we analysed longitudinal data on febrile malaria episodes, asymptomatic parasitaemia, and antibody titres over 12 y from 256 homesteads in three study areas in Kilifi District on the Kenyan coast. We examined heterogeneity by homestead, and identified groups of homesteads that formed hotspots using a spatial scan statistic. Two types of statistically significant hotspots were detected; stable hotspots of asymptomatic parasitaemia and unstable hotspots of febrile malaria. The stable hotspots were associated with higher average AMA-1 antibody titres than the unstable clusters (optical density [OD] = 1.24, 95% confidence interval [CI] 1.02–1.47 versus OD = 1.1, 95% CI 0.88–1.33) and lower mean ages of febrile malaria episodes (5.8 y, 95% CI 5.6–6.0 versus 5.91 y, 95% CI 5.7–6.1). A falling gradient of febrile malaria incidence was identified in the penumbrae of both hotspots. Hotspots were associated with AMA-1 titres, but not seroconversion rates. In order to target control measures, homesteads at risk of febrile malaria could be predicted by identifying the 20% of homesteads that experienced an episode of febrile malaria during one month in the dry season. That 20% subsequently experienced 65% of all febrile malaria episodes during the following year. A definition based on remote sensing data was 81% sensitive and 63% specific for the stable hotspots of asymptomatic malaria.

Conclusions

Hotspots of asymptomatic parasitaemia are stable over time, but hotspots of febrile malaria are unstable. This finding may be because immunity offsets the high rate of febrile malaria that might otherwise result in stable hotspots, whereas unstable hotspots necessarily affect a population with less prior exposure to malaria. Please see later in the article for the Editors'' Summary     

A Realistic Host-Vector Transmission Model for Describing Malaria Prevalence Pattern

Malaria continues to be a major public health concern all over the world even after effective control policies have been employed, and considerable understanding of the disease biology have been attained, from both the experimental and modelling perspective. Interactions between different general and local processes, such as dependence on age and immunity of the human host, variations of temperature and rainfall in tropical and sub-tropical areas, and continued presence of asymptomatic infections, regulate the host-vector interactions, and are responsible for the continuing disease prevalence pattern. In this paper, a general mathematical model of malaria transmission is developed considering short and long-term age-dependent immunity of human host and its interaction with pathogen-infected mosquito vector. The model is studied analytically and numerically to understand the role of different parameters related to mosquitoes and humans. To validate the model with a disease prevalence pattern in a particular region, real epidemiological data from the north-eastern part of India was used, and the effect of seasonal variation in mosquito density was modelled based on local climactic data. The model developed based on general features of host-vector interactions, and modified simply incorporating local environmental factors with minimal changes, can successfully explain the disease transmission process in the region. This provides a general approach toward modelling malaria that can be adapted to control future outbreaks of malaria.     

Assessment of Anopheles salivary antigens as individual exposure biomarkers to species-specific malaria vector bites

The development of parasitological immunity against malaria affects the ability to detect infection, the efficiency of the local human parasite reservoir at infecting mosquitoes, and the response to reintroduction of parasites to previously cleared areas. Observations of similar age-trends in detected prevalence and mean parasitaemia across more than an order-of-magnitude of variation in baseline transmission complicate simple exposure-driven explanations. Mathematical models often employ age-dependent immune factors to match the observed trends, while the present model uses a new detailed mechanistic model of parasite transmission dynamics to explain age-trends through the mechanism of parasite diversity. Illustrative simulations are performed for multiple field sites in Tanzania and Nigeria, and observed age-trends and seasonality in parasite prevalence are recreated in silico, proffering possible mechanistic explanations of the observational data. Observed temporal dynamics in measured parasitaemia are recreated for each location and age-prevalence outputs are studied. Increasing population-level diversity in malaria surface antigens delays development of broad parasitological immunity. A local parasite population with high diversity can recreate the observed trends in age-prevalence across more than an order of magnitude of variation in transmission intensities. Mechanistic models of human immunity and parasite antigen diversity can recreate the observed temporal patterns for the development of parasitological immunity across a wide range of transmission intensities. This has implications for the distribution of disease burden across the population, the human transmission reservoir, design of elimination campaigns, and development and roll-out of potential vaccines.     

Efficiency of Household Reactive Case Detection for Malaria in Rural Southern Zambia: Simulations Based on Cross-Sectional Surveys from Two Epidemiological Settings

Background

Case detection and treatment are critical to malaria control and elimination as infected individuals who do not seek medical care can serve as persistent reservoirs for transmission.

Methods

Household malaria surveys were conducted in two study areas within Southern Province, Zambia in 2007 and 2008. Cross-sectional surveys were conducted approximately five times throughout the year in each of the two study areas. During study visits, adults and caretakers of children were administered a questionnaire and a blood sample was obtained for a rapid diagnostic test (RDT) for malaria. These data were used to estimate the proportions of individuals with malaria potentially identified through passive case detection at health care facilities and those potentially identified through reactive case finding. Simulations were performed to extrapolate data from sampled to non-sampled households. Radii of increasing size surrounding households with an index case were examined to determine the proportion of households with an infected individual that would be identified through reactive case detection.

Results

In the 2007 high transmission setting, with a parasite prevalence of 23%, screening neighboring households within 500 meters of an index case could have identified 89% of all households with an RDT positive resident and 90% of all RDT positive individuals. In the 2008 low transmission setting, with a parasite prevalence of 8%, screening neighboring households within 500 meters of a household with an index case could have identified 77% of all households with an RDT positive resident and 76% of all RDT positive individuals.

Conclusions

Testing and treating individuals residing within a defined radius from an index case has the potential to be an effective strategy to identify and treat a large proportion of infected individuals who do not seek medical care, although the efficiency of this strategy is likely to decrease with declining parasite prevalence.     

Anti-malarial drugs and the prevention of malaria in the population of malaria endemic areas

Anti-malarial drugs can make a significant contribution to the control of malaria in endemic areas when used for prevention as well as for treatment. Chemoprophylaxis is effective in preventing deaths and morbidity from malaria, but it is difficult to sustain for prolonged periods, may interfere with the development of naturally acquired immunity and will facilitate the emergence and spread of drug resistant strains if applied to a whole community. However, chemoprophylaxis targeted to groups at high risk, such as pregnant women, or to periods of the year when the risk from malaria is greatest, can be an effective and cost effective malaria control tool and has fewer drawbacks. Intermittent preventive treatment, which involves administration of anti-malarials at fixed time points, usually when a subject is already in contact with the health services, for example attendance at an antenatal or vaccination clinic, is less demanding of resources than chemoprophylaxis and is now recommended for the prevention of malaria in pregnant women and infants resident in areas with medium or high levels of malaria transmission. Intermittent preventive treatment in older children, probably equivalent to targeted chemoprophylaxis, is also highly effective but requires the establishment of a specific delivery system. Recent studies have shown that community volunteers can effectively fill this role. Mass drug administration probably has little role to play in control of mortality and morbidity from malaria but may have an important role in the final stages of an elimination campaign.     

Malaria Prevalence,Spatial Clustering and Risk Factors in a Low Endemic Area of Eastern Rwanda: A Cross Sectional Study

Background

Rwanda reported significant reductions in malaria burden following scale up of control intervention from 2005 to 2010. This study sought to; measure malaria prevalence, describe spatial malaria clustering and investigate for malaria risk factors among health-centre-presumed malaria cases and their household members in Eastern Rwanda.

Methods

A two-stage health centre and household-based survey was conducted in Ruhuha sector, Eastern Rwanda from April to October 2011. At the health centre, data, including malaria diagnosis and individual level malaria risk factors, was collected. At households of these Index cases, a follow-up survey, including malaria screening for all household members and collecting household level malaria risk factor data, was conducted.

Results

Malaria prevalence among health centre attendees was 22.8%. At the household level, 90 households (out of 520) had at least one malaria-infected member and the overall malaria prevalence for the 2634 household members screened was 5.1%. Among health centre attendees, the age group 5–15 years was significantly associated with an increased malaria risk and a reported ownership of ≥4 bednets was significantly associated with a reduced malaria risk. At the household level, age groups 5–15 and >15 years and being associated with a malaria positive index case were associated with an increased malaria risk, while an observed ownership of ≥4 bednets was associated with a malaria risk-protective effect. Significant spatial malaria clustering among household cases with clusters located close to water- based agro-ecosystems was observed.

Conclusions

Malaria prevalence was significantly higher among health centre attendees and their household members in an area with significant household spatial malaria clustering. Circle surveillance involving passive case finding at health centres and proactive case detection in households can be a powerful tool for identifying household level malaria burden, risk factors and clustering.     

Asymptomatic Plasmodium falciparum Malaria in Pregnant Women in the Chittagong Hill Districts of Bangladesh

Background

Pregnancy is a known risk factor for malaria which is associated with increased maternal and infant mortality and morbidity in areas of moderate-high malaria transmission intensity where Plasmodium falciparum predominates. The nature and impact of malaria, however, is not well understood in pregnant women residing in areas of low, unstable malaria transmission where P. falciparum and P. vivax co-exist.

Methods

A large longitudinal active surveillance study of malaria was conducted in the Chittagong Hill Districts of Bangladesh. Over 32 months in 2010–2013, the period prevalence of asymptomatic P. falciparum infections was assessed by rapid diagnostic test and blood smear and compared among men, non-pregnant women and pregnant women. A subset of samples was tested for infection by PCR. Hemoglobin was assessed. Independent risk factors for malaria infection were determined using a multivariate logistic regression model.

Results

Total of 34 asymptomatic P. falciparum infections were detected by RDT/smear from 3,110 tests. The period prevalence of asymptomatic P. falciparum infection in pregnant women was 2.3%, compared to 0.5% in non-pregnant women and 0.9% in men. All RDT/smear positive samples that were tested by PCR were PCR-positive, and PCR detected additional 35 infections that were RDT/smear negative. In a multivariate logistic regression analysis, pregnant women had 5.4-fold higher odds of infection as compared to non-pregnant women. Malaria-positive pregnant women, though asymptomatic, had statistically lower hemoglobin than those without malaria or pregnancy. Asymptomatic malaria was found to be evenly distributed across space and time, in contrast to symptomatic infections which tend to cluster.

Conclusion

Pregnancy is a risk factor for asymptomatic P. falciparum infection in the Chittagong Hill Districts of Bangladesh, and pregnancy and malaria interact to heighten the effect of each on hemoglobin. The even distribution of asymptomatic malaria, without temporal and spatial clustering, may have critical implications for malaria elimination strategies.     

Quantifying the Impact of Expanded Age Group Campaigns for Polio Eradication

A priority of the Global Polio Eradication Initiative (GPEI) 2013–2018 strategic plan is to evaluate the potential impact on polio eradication resulting from expanding one or more Supplementary Immunization Activities (SIAs) to children beyond age five-years in polio endemic countries. It has been hypothesized that such expanded age group (EAG) campaigns could accelerate polio eradication by eliminating immunity gaps in older children that may have resulted from past periods of low vaccination coverage. Using an individual-based mathematical model, we quantified the impact of EAG campaigns in terms of probability of elimination, reduction in polio transmission and age stratified immunity levels. The model was specifically calibrated to seroprevalence data from a polio-endemic region: Zaria, Nigeria. We compared the impact of EAG campaigns, which depend only on age, to more targeted interventions which focus on reaching missed populations. We found that EAG campaigns would not significantly improve prospects for polio eradication; the probability of elimination increased by 8% (from 24% at baseline to 32%) when expanding three annual SIAs to 5–14 year old children and by 18% when expanding all six annual SIAs. In contrast, expanding only two of the annual SIAs to target hard-to-reach populations at modest vaccination coverage—representing less than one tenth of additional vaccinations required for the six SIA EAG scenario—increased the probability of elimination by 55%. Implementation of EAG campaigns in polio endemic regions would not improve prospects for eradication. In endemic areas, vaccination campaigns which do not target missed populations will not benefit polio eradication efforts.     

Modelling the Impact of Artemisinin Combination Therapy and Long-Acting Treatments on Malaria Transmission Intensity

Background

Artemisinin derivatives used in recently introduced combination therapies (ACTs) for Plasmodium falciparum malaria significantly lower patient infectiousness and have the potential to reduce population-level transmission of the parasite. With the increased interest in malaria elimination, understanding the impact on transmission of ACT and other antimalarial drugs with different pharmacodynamics becomes a key issue. This study estimates the reduction in transmission that may be achieved by introducing different types of treatment for symptomatic P. falciparum malaria in endemic areas.

Methods and Findings

We developed a mathematical model to predict the potential impact on transmission outcomes of introducing ACT as first-line treatment for uncomplicated malaria in six areas of varying transmission intensity in Tanzania. We also estimated the impact that could be achieved by antimalarials with different efficacy, prophylactic time, and gametocytocidal effects. Rates of treatment, asymptomatic infection, and symptomatic infection in the six study areas were estimated using the model together with data from a cross-sectional survey of 5,667 individuals conducted prior to policy change from sulfadoxine-pyrimethamine to ACT. The effects of ACT and other drug types on gametocytaemia and infectiousness to mosquitoes were independently estimated from clinical trial data. Predicted percentage reductions in prevalence of infection and incidence of clinical episodes achieved by ACT were highest in the areas with low initial transmission. A 53% reduction in prevalence of infection was seen if 100% of current treatment was switched to ACT in the area where baseline slide-prevalence of parasitaemia was lowest (3.7%), compared to an 11% reduction in the highest-transmission setting (baseline slide prevalence = 57.1%). Estimated percentage reductions in incidence of clinical episodes were similar. The absolute size of the public health impact, however, was greater in the highest-transmission area, with 54 clinical episodes per 100 persons per year averted compared to five per 100 persons per year in the lowest-transmission area. High coverage was important. Reducing presumptive treatment through improved diagnosis substantially reduced the number of treatment courses required per clinical episode averted in the lower-transmission settings although there was some loss of overall impact on transmission. An efficacious antimalarial regimen with no specific gametocytocidal properties but a long prophylactic time was estimated to be more effective at reducing transmission than a short-acting ACT in the highest-transmission setting.

Conclusions

Our results suggest that ACTs have the potential for transmission reductions approaching those achieved by insecticide-treated nets in lower-transmission settings. ACT partner drugs and nonartemisinin regimens with longer prophylactic times could result in a larger impact in higher-transmission settings, although their long term benefit must be evaluated in relation to the risk of development of parasite resistance.