Optimal population-level infection detection strategies for malaria control and elimination in a spatial model of malaria transmission

Mass campaigns with antimalarial drugs are potentially a powerful tool for local elimination of malaria, yet current diagnostic technologies are insufficiently sensitive to identify all individuals who harbor infections. At the same time, overtreatment of uninfected individuals increases the risk of accelerating emergence of drug resistance and losing community acceptance. Local heterogeneity in transmission intensity may allow campaign strategies that respond to index cases to successfully target subpatent infections while simultaneously limiting overtreatment. While selective targeting of hotspots of transmission has been proposed as a strategy for malaria control, such targeting has not been tested in the context of malaria elimination. Using household locations, demographics, and prevalence data from a survey of four health facility catchment areas in southern Zambia and an agent-based model of malaria transmission and immunity acquisition, a transmission intensity was fit to each household based on neighborhood age-dependent malaria prevalence. A set of individual infection trajectories was constructed for every household in each catchment area, accounting for heterogeneous exposure and immunity. Various campaign strategies (mass drug administration, mass screen and treat, focal mass drug administration, snowball reactive case detection, pooled sampling, and a hypothetical serological diagnostic) were simulated and evaluated for performance at finding infections, minimizing overtreatment, reducing clinical case counts, and interrupting transmission. For malaria control, presumptive treatment leads to substantial overtreatment without additional morbidity reduction under all but the highest transmission conditions. Selective targeting of hotspots with drug campaigns is an ineffective tool for elimination due to limited sensitivity of available field diagnostics

Measurement of malaria transmission and impact of malaria control interventions using health facility and community-based routine reporting systems

Globally malaria still remains the most important parasitic disease of public health interest. In the recent past, most endemic countries have deployed and scaled up both preventive and curative interventions to reduce malaria transmission and, ideally, eliminate it. This has lead to global reductions in both mortality and incidence of malaria. These declines have been attributed to the reinvigoration of the global malaria control agenda by the explicit ambition of achieving elimination, which has lead to an increase in funding for national control programmes to increase coverage of preventive interventions, field compatible diagnostic tools for confirming parasite infection, and increased access to effective treatment. As a result of declines in malaria transmission, the focal nature of malaria transmission has become much more evident and has lead to consideration of surveillance as a key intervention for malaria control/elimination in its own right. Surveillance systems have been well established in most formal health facilities but the incorporation of these systems at community level and operationalised by community health workers (CHWs) still remains limited. Additionally, these few examples of CHW-implemented surveillance systems have been typically only reporting indicators of malaria infection burden, without capturing indicators of intervention availability, deployment, coverage and utilisation, thus representing a missed opportunity for routine monitoring and evaluation of impact of interventions in “real time” to inform program planning and implementation. The study was established as part of a multi-country study under the Malaria Transmission Consortium Project whose primary objective was to develop and evaluate new or improved methods for measuring malaria transmission. Thus the overall goal of this study was to demonstrate how malaria transmission, and impact of interventions, could be routinely measured through a novel longitudinal community based surveillance system (CBSS) operationalised by modestly paid CHWs. The CBSS included both passive and active surveillance activities using field – compatible test kits for in situ parasitological detection of malaria infections, based on which confirmed cases were treated with anti-malarial drugs, coupled with a detailed questionnaire on access and use of malaria control interventions and population characteristics. Passive surveillance was achieved conventionally whenever community members self-reported to the CHWs and active surveillance was achieved through monthly active visits to all households in their catchment populations to offer testing and treatment. In addition to recording detailed details of each patient contact in a paper patient register, weekly summaries of selected data elements were submitted by the CHWs using a mobile phone platform via short messaging system (SMS). The detailed reference data recorded in the patient register was then used to monitor malaria infection dynamics in the study population, evaluate the impact of preventative measures, such as indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) and validate the electronic summaries submitted via SMS. Overall, the CBSS did not routinely capture all malaria infections in the study population and was insufficient to eliminate the human parasite reservoir. This was primarily due to limited study participant participation with the monthly active testing and treatment offered by the CHWs. However, the CBSS clearly demonstrated the incremental and residual impact to supplementation of pyrethroid-treated LLINs with non - pyrethroid insecticides applied by IRS in areas where the dominant malaria vector is highly resistant to pyrethroids. The adequacy of the SMS reports submitted by the CHWs confirms the great potential of mobile phone technology for facilitating and improving the effectiveness of community based reporting. Despite its limitations, the CBSS successfully provided programmatically relevant information regarding malaria infection dynamics across the large study area at a very affordable cost. The CHWs demonstrated their ability to not only provide treatment services but also adequately report their findings both electronically and on paper. CHWs are primarily tasked with providing routine health services at community level but clearly also have a valuable auxiliary role to play in “real time” surveillance of malaria, and most probably a range of other diseases. If the full potential of CHWs as agents of health surveillance can be realized, control programme progress can be measured through spatial and temporal mapping of transmission with greater sensitivity and at finer scales than is possible with health facilities alone, to enable improved, better-informed program planning, resource allocation and implementation

Malaria elimination campaigns in the Lake Kariba region of Zambia: a spatial dynamical model

Background As more regions approach malaria elimination, understanding how different interventions interact to reduce transmission becomes critical. The Lake Kariba area of Southern Province, Zambia, is part of a multi-country elimination effort and presents a particular challenge as it is an interconnected region of variable transmission intensities. Methods In 2012-13, six rounds of mass-screen-and-treat drug campaigns were carried out in the Lake Kariba region. A spatial dynamical model of malaria transmission in the Lake Kariba area, with transmission and climate modeled at the village scale, was calibrated to the 2012-13 prevalence survey data, with case management rates, insecticide-treated net usage, and drug campaign coverage informed by surveillance. The model was used to simulate the effect of various interventions implemented in 2014-22 on reducing regional transmission, achieving elimination by 2022, and maintaining elimination through 2028. Findings The model captured the spatio-temporal trends of decline and rebound in malaria prevalence in 2012-13 at the village scale. Simulations predicted that elimination required repeated mass drug administrations coupled with simultaneous increase in net usage. Drug campaigns targeted only at high-burden areas were as successful as campaigns covering the entire region. Interpretation Elimination in the Lake Kariba region is possible through coordinating mass drug campaigns with high-coverage vector control. Targeting regional hotspots is a viable alternative to global campaigns when human migration within an interconnected area is responsible for maintaining transmission in low-burden areas

Near-term climate change impacts on sub-national malaria transmission

Abstract The role of climate change on global malaria is often highlighted in World Health Organisation reports. We modelled a Zambian socio-environmental dataset from 2000 to 2016, against malaria trends and investigated the relationship of near-term environmental change with malaria incidence using Bayesian spatio-temporal, and negative binomial mixed regression models. We introduced the diurnal temperature range (DTR) as an alternative environmental measure to the widely used mean temperature. We found substantial sub-national near-term variations and significant associations with malaria incidence-trends. Significant spatio-temporal shifts in DTR/environmental predictors influenced malaria incidence-rates, even in areas with declining trends. We highlight the impact of seasonally sensitive DTR, especially in the first two quarters of the year and demonstrate how substantial investment in intervention programmes is negatively impacted by near-term climate change, most notably since 2010. We argue for targeted seasonally-sensitive malaria chemoprevention programmes

Modelling of Malaria Risk, Rates, and Trends: A Spatiotemporal approach for identifying and targeting sub-national Areas of High and Low Burden

While mortality from malaria continues to decline globally, incidence rates in many countries are rising. Within countries, spatial and temporal patterns of malaria vary across communities due to many different physical and social environmental factors. To identify those areas most suitable for malaria elimination or targeted control interventions, we used Bayesian models to estimate the spatiotemporal variation of malaria risk, rates, and trends to determine areas of high or low malaria burden compared to their geographical neighbours. We present a methodology using Bayesian hierarchical models with a Markov Chain Monte Carlo (MCMC) based inference to fit a generalised linear mixed model with a conditional autoregressive structure. We modelled clusters of similar spatiotemporal trends in malaria risk, using trend functions with constrained shapes and visualised high and low burden districts using a multi-criterion index derived by combining spatiotemporal risk, rates and trends of districts in Zambia. Our results indicate that over 3 million people in Zambia live in high-burden districts with either high mortality burden or high incidence burden coupled with an increasing trend over 16 years (2000 to 2015) for all age, under-five and over-five cohorts. Approximately 1.6 million people live in high-incidence burden areas alone. Using our method, we have developed a platform that can enable malaria programs in countries like Zambia to target those high-burden areas with intensive control measures while at the same time pursue malaria elimination efforts in all other areas. Our method enhances conventional approaches and measures to identify those districts which had higher rates and increasing trends and risk. This study provides a method and a means that can help policy makers evaluate intervention impact over time and adopt appropriate geographically targeted strategies that address the issues of both high-burden areas, through intensive control approaches, and low-burden areas, via specific elimination programs

Some aspects of the epidemiology and chemotherapy of African trypanosomiasis

Trypanosomiasis affects man and his domestic Livestock in 10 million km2 of tropical Africa. It is a major constraint to the economic development of animal production in Zambia in one third of which mixed farming is rendered impracticable. In this study an attempt has been made to investigate the epidemiology of animal trypanosomiasis in Zambia and to evaluate the efficiency of the currently used drug regime for the control of the disease. Further, the prevalence of infected domestic livestock in selected areas of the country and the efficacy of two anti-trypanosomal drugs Berenil and Samorin were investigated. It was found that the incidence of bovine trypanosomiasis is high. Trypanosoma vivax infections in one of the areas surveyed became more prevalent as distance from the tsetse-belt increased. There was an apparent increase in the incidence of T. brucei infections in cattle and five clinical cases of such infections are described. Treatment of calves with either Berenil (diminazene aceturate) or Samorin (isometamidium chloride) either 24 hours or 21 days after infection with T. vivax or T. congolense subsequently resulted in a relapsing parasitaemia. This is the first time that relapsing T. congolense and T. vivax infections following Berenil or Samorin treatment have been described in Zambia. Further investigation of the effects of Berenil on T. brucei infections in mice demonstrated that the source of relapsing infection was the brain. This finding has relevance to trypanosomiasis of domestic animals in which Berenil is a commonly used drug and also to human trypanosomiasis which, in the late stages of the disease, affects the central nervous system. The study indicated that the efficacy of current chemotherapeutic regime in Zambia should be critically examined and that more information on the incidence of animal trypanosomiasis is required

Community Case Management of Fever Due to Malaria and Pneumonia in Children Under Five in Zambia: A Cluster Randomized Controlled Trial

In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective. BACKGROUND. Pneumonia and malaria, two of the leading causes of morbidity and mortality among children under five in Zambia, often have overlapping clinical manifestations. Zambia is piloting the use of artemether-lumefantrine (AL) by community health workers (CHWs) to treat uncomplicated malaria. Valid concerns about potential overuse of AL could be addressed by the use of malaria rapid diagnostics employed at the community level. Currently, CHWs in Zambia evaluate and treat children with suspected malaria in rural areas, but they refer children with suspected pneumonia to the nearest health facility. This study was designed to assess the effectiveness and feasibility of using CHWs to manage nonsevere pneumonia and uncomplicated malaria with the aid of rapid diagnostic tests (RDTs). METHODS AND FINDINGS. Community health posts staffed by CHWs were matched and randomly allocated to intervention and control arms. Children between the ages of 6 months and 5 years were managed according to the study protocol, as follows. Intervention CHWs performed RDTs, treated test-positive children with AL, and treated those with nonsevere pneumonia (increased respiratory rate) with amoxicillin. Control CHWs did not perform RDTs, treated all febrile children with AL, and referred those with signs of pneumonia to the health facility, as per Ministry of Health policy. The primary outcomes were the use of AL in children with fever and early and appropriate treatment with antibiotics for nonsevere pneumonia. A total of 3,125 children with fever and/or difficult/fast breathing were managed over a 12-month period. In the intervention arm, 27.5% (265/963) of children with fever received AL compared to 99.1% (2066/2084) of control children (risk ratio 0.23, 95% confidence interval 0.14–0.38). For children classified with nonsevere pneumonia, 68.2% (247/362) in the intervention arm and 13.3% (22/203) in the control arm received early and appropriate treatment (risk ratio 5.32, 95% confidence interval 2.19–8.94). There were two deaths in the intervention and one in the control arm. CONCLUSIONS. The potential for CHWs to use RDTs, AL, and amoxicillin to manage both malaria and pneumonia at the community level is promising and might reduce overuse of AL, as well as provide early and appropriate treatment to children with nonsevere pneumonia.United States Agency for International Development (GHSA-00-00020-00) with Boston University; President's Malaria Initiativ

Exploring the use of routinely-available, retrospective data to study the association between malaria control scale-up and micro-economic outcomes in Zambia

Additional file 1. Additional tables that share additional results of the generalized propensity score matching analysis, as well as a table covering malaria control coverage at the district level

Evaluation of the burden of unsuspected pulmonary tuberculosis and co-morbidity with non-communicable diseases in sputum producing adult inpatients

A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre. In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706-25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected. A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study