Impact of aerial humidity on seasonal malaria: an ecological study in Zambia.

BACKGROUND: Seasonal patterns of malaria cases in many parts of Africa are generally associated with rainfall, yet in the dry seasons, malaria transmission declines but does not always cease. It is important to understand what conditions support these periodic cases. Aerial moisture is thought to be important for mosquito survival and ability to forage, but its role during the dry seasons has not been well studied. During the dry season aerial moisture is minimal, but intermittent periods may arise from the transpiration of peri-domestic trees or from some other sources in the environment. These periods may provide conditions to sustain pockets of mosquitoes that become active and forage, thereby transmitting malaria. In this work, humidity along with other ecological variables that may impact malaria transmission have been examined. METHODS: Negative binomial regression models were used to explore the association between peri-domestic tree humidity and local malaria incidence. This was done using sensitive temperature and humidity loggers in the rural Southern Province of Zambia over three consecutive years. Additional variables including rainfall, temperature and elevation were also explored. RESULTS: A negative binomial model with no lag was found to best fit the malaria cases for the full year in the evaluated sites of the Southern Province of Zambia. Local tree and granary night-time humidity and temperature were found to be associated with local health centre-reported incidence of malaria, while rainfall and elevation did not significantly contribute to this model. A no lag and one week lag model for the dry season alone also showed a significant effect of humidity, but not temperature, elevation, or rainfall. CONCLUSION: The study has shown that throughout the dry season, periodic conditions of sustained humidity occur that may permit foraging by resting mosquitoes, and these periods are associated with increased incidence of malaria cases. These results shed a light on conditions that impact the survival of the common malaria vector species, Anopheles arabiensis, in arid seasons and suggests how they emerge to forage when conditions permit.

mHAT app for automated malaria rapid test result analysis and aggregation: a pilot study.

BACKGROUND: There are a variety of approaches being used for malaria surveillance. While active and reactive case detection have been successful in localized areas of low transmission, concerns over scalability and sustainability keep the approaches from being widely accepted. Mobile health interventions are poised to address these shortcomings by automating and standardizing portions of the surveillance process. In this study, common challenges associated with current data aggregation methods have been quantified, and a web-based mobile phone application is presented to reduce the burden of reporting rapid diagnostic test (RDT) results in low-resource settings. METHODS: De-identified completed RDTs were collected at 14 rural health clinics as part of a malaria epidemiology study at Macha Research Trust, Macha, Zambia. Tests were imaged using the mHAT web application. Signal intensity was measured and a binary result was provided. App performance was validated by: (1) comparative limits of detection, investigated against currently used laboratory lateral flow assay readers; and, (2) receiver operating characteristic analysis comparing the application against visual inspection of RDTs by an expert. Secondary investigations included analysis of time-to-aggregation and data consistency within the existing surveillance structures established by Macha Research Trust. RESULTS: When compared to visual analysis, the mHAT app performed with 91.9% sensitivity (CI 78.7, 97.2) and specificity was 91.4% (CI 77.6, 97.0) regardless of device operating system. Additionally, an analysis of surveillance data from January 2017 through mid-February 2019 showed that while the majority of the data packets from satellite clinics contained correct data, 36% of data points required correction by verification teams. Between November 2018 and mid-February 2019, it was also found that 44.8% of data was received after the expected submission date, although most (65.1%) reports were received within 2 days. CONCLUSIONS: Overall, the mHAT mobile app was observed to be sensitive and specific when compared to both currently available benchtop lateral flow readers and visual inspection. The additional benefit of automating and standardizing LFA data collection and aggregation poses a vital improvement for low-resource health facilities and could increase the accuracy and speed of data reporting in surveillance campaigns.

Improving the efficiency of reactive case detection for malaria elimination in southern Zambia: a cross-sectional study.

BACKGROUND: Reactive case detection (RCD) seeks to enhance malaria surveillance and control by identifying and treating parasitaemic individuals residing near index cases. In Zambia, this strategy starts with passive detection of symptomatic incident malaria cases at local health facilities or by community health workers, with subsequent home visits to screen-and-treat residents in the index case and neighbouring (secondary) households within a 140-m radius using rapid diagnostic tests (RDTs). However, a small circular radius may not be the most efficient strategy to identify parasitaemic individuals in low-endemic areas with hotspots of malaria transmission. To evaluate if RCD efficiency could be improved by increasing the probability of identifying parasitaemic residents, environmental risk factors and a larger screening radius (250 m) were assessed in a region of low malaria endemicity. METHODS: Between January 12, 2015 and July 26, 2017, 4170 individuals residing in 158 index and 531 secondary households were enrolled and completed a baseline questionnaire in the catchment area of Macha Hospital in Choma District, Southern Province, Zambia. Plasmodium falciparum prevalence was measured using PfHRP2 RDTs and quantitative PCR (qPCR). A Quickbird™ high-resolution satellite image of the catchment area was used to create environmental risk factors in ArcGIS, and generalized estimating equations were used to evaluate associations between risk factors and secondary households with parasitaemic individuals. RESULTS: The parasite prevalence in secondary (non-index case) households was 0.7% by RDT and 1.8% by qPCR. Overall, 8.5% (n = 45) of secondary households had at least one resident with parasitaemia by qPCR or RDT. The risk of a secondary household having a parasitaemic resident was significantly increased in proximity to higher order streams and marginally with increasing distance from index households. The adjusted OR for proximity to third- and fifth-order streams were 2.97 (95% CI 1.04-8.42) and 2.30 (95% CI 1.04-5.09), respectively, and that for distance to index households for each 50 m was 1.24 (95% CI 0.98-1.58). CONCLUSION: Applying proximity to streams as a screening tool, 16% (n = 3) more malaria-positive secondary households were identified compared to using a 140-m circular screening radius. This analysis highlights the potential use of environmental risk factors as a screening strategy to increase RCD efficiency.

Spatio-temporal monitoring of health facility-level malaria trends in Zambia and adaptive scaling for operational intervention.

Background: The spatial and temporal variability inherent in malaria transmission within countries implies that targeted interventions for malaria control in high-burden settings and subnational elimination are a practical necessity. Identifying the spatio-temporal incidence, risk, and trends at different administrative geographies within malaria-endemic countries and monitoring them in near real-time as change occurs is crucial for developing and introducing cost-effective, subnational control and elimination intervention strategies. Methods: This study developed intelligent data analytics incorporating Bayesian trend and spatio-temporal Integrated Laplace Approximation models to analyse high-burden over 32 million reported malaria cases from 1743 health facilities in Zambia between 2009 and 2015. Results: The results show that at least 5.4 million people live in catchment areas with increasing trends of malaria, covering over 47% of all health facilities, while 5.7 million people live in areas with a declining trend (95% CI), covering 27% of health facilities. A two-scale spatio-temporal trend comparison identified significant differences between health facilities and higher-level districts, and the pattern observed in the southeastern region of Zambia provides the first evidence of the impact of recently implemented localised interventions. Conclusions: The results support our recommendation for an adaptive scaling approach when implementing national malaria monitoring, control and elimination strategies and a particular need for stratified subnational approaches targeting high-burden regions with increasing disease trends. Strong clusters along borders with highly endemic countries in the north and south of Zambia underscore the need for coordinated cross-border malaria initiatives and strategies.

Scientific Findings of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

For a decade, the Southern and Central Africa International Center of Excellence for Malaria Research has operated with local partners across study sites in Zambia and Zimbabwe that range from hypo- to holoendemic and vary ecologically and entomologically. The burden of malaria and the impact of control measures were assessed in longitudinal cohorts, cross-sectional surveys, passive and reactive case detection, and other observational designs that incorporated multidisciplinary scientific approaches: classical epidemiology, geospatial science, serosurveillance, parasite and mosquito genetics, and vector bionomics. Findings to date have helped elaborate the patterns and possible causes of sustained low-to-moderate transmission in southern Zambia and eastern Zimbabwe and recalcitrant high transmission and fatality in northern Zambia. Cryptic and novel mosquito vectors, asymptomatic parasite reservoirs in older children, residual parasitemia and gametocytemia after treatment, indoor residual spraying timed dyssynchronously to vector abundance, and stockouts of essential malaria commodities, all in the context of intractable rural poverty, appear to explain the persistent malaria burden despite current interventions. Ongoing studies of high-resolution transmission chains, parasite population structures, long-term malaria periodicity, and molecular entomology are further helping to lay new avenues for malaria control in southern and central Africa and similar settings.

Policy Implications of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe.

The International Centers of Excellence for Malaria Research (ICEMR) were established by the National Institute of Allergy and Infectious Diseases more than a decade ago to provide multidisciplinary research support to malaria control programs worldwide, operating in endemic areas and contributing technology, expertise, and ultimately policy guidance for malaria control and elimination. The Southern and Central Africa ICEMR has conducted research across three main sites in Zambia and Zimbabwe that differ in ecology, entomology, transmission intensity, and control strategies. Scientific findings led to new policies and action by the national malaria control programs and their partners in the selection of methods, materials, timing, and locations of case management and vector control. Malaria risk maps and predictive models of case detection furnished by the ICEMR informed malaria elimination programming in southern Zambia, and time series analyses of entomological and parasitological data motivated several major changes to indoor residual spray campaigns in northern Zambia. Along the Zimbabwe-Mozambique border, temporal and geospatial data are currently informing investigations into a recent resurgence of malaria. Other ICEMR findings pertaining to parasite and mosquito genetics, human behavior, and clinical epidemiology have similarly yielded immediate and long-term policy implications at each of the sites, often with generalizable conclusions. The ICEMR programs thereby provide rigorous scientific investigations and analyses to national control and elimination programs, without which the impediments to malaria control and their potential solutions would remain understudied.

Sustained Malaria Transmission despite Reactive Screen-and-Treat in a Low-Transmission Area of Southern Zambia.

Malaria elimination strategies are designed to more effectively identify and treat infected individuals to interrupt transmission. One strategy, reactive screen-and-treat, starts with passive detection of symptomatic cases at health facilities. Individuals residing within the index case and neighboring households are screened with a malaria rapid diagnostic test (RDT) and treated if positive. However, it is unclear to what extent this strategy is effective in reducing transmission. Reactive screen-and-treat was implemented in Choma district, Southern Province, Zambia, in 2013, in which residents of the index case and neighboring households within 140 m were screened with an RDT. From March 2016 to July 2018, the screening radius was extended to 250-m, and additional follow-up visits at 30 and 90 days were added to evaluate the strategy. Plasmodium falciparum parasite prevalence was measured using an RDT and by quantitative PCR (qPCR). A 24-single nucleotide polymorphism molecular bar-code assay was used to genotype parasites. Eighty-four index case households with 676 residents were enrolled between March 2016 and March 2018. Within each season, parasite prevalence declined significantly in index households at the 30-day visit and remained low at the 90-day visit. However, parasite prevalence was not reduced to zero. Infections identified by qPCR persisted between study visits and were not identified by RDT. Parasites identified within the same household were most genetically related; however, overall parasite relatedness was low and similar across time and space. Thus, despite implementation of a reactive screen-and-treat program, parasitemia was not eliminated, and persisted in targeted households for at least 3 months.