Geographical patterns and predictors of malaria risk in Zambia: Bayesian geostatistical modelling of the 2006 Zambia national malaria indicator survey (ZMIS)

BACKGROUND: The Zambia Malaria Indicator Survey (ZMIS) of 2006 was the first nation-wide malaria survey, which combined parasitological data with other malaria indicators such as net use, indoor residual spraying and household related aspects. The survey was carried out by the Zambian Ministry of Health and partners with the objective of estimating the coverage of interventions and malaria related burden in children less than five years. In this study, the ZMIS data were analysed in order (i) to estimate an empirical high-resolution parasitological risk map in the country and (ii) to assess the relation between malaria interventions and parasitaemia risk after adjusting for environmental and socio-economic confounders. METHODS: The parasitological risk was predicted from Bayesian geostatistical and spatially independent models relating parasitaemia risk and environmental/climatic predictors of malaria. A number of models were fitted to capture the (potential) non-linearity in the malaria-environment relation and to identify the elapsing time between environmental effects and parasitaemia risk. These models included covariates (a) in categorical scales and (b) in penalized and basis splines terms. Different model validation methods were used to identify the best fitting model. Model-based risk predictions at unobserved locations were obtained via Bayesian predictive distributions for the best fitting model. RESULTS: Model validation indicated that linear environmental predictors were able to fit the data as well as or even better than more complex non-linear terms and that the data do not support spatial dependence. Overall the averaged population-adjusted parasitaemia risk was 20.0% in children less than five years with the highest risk predicted in the northern (38.3%) province. The odds of parasitaemia in children living in a household with at least one bed net decreases by 40% (CI: 12%, 61%) compared to those without bed nets. CONCLUSIONS: The map of parasitaemia risk together with the prediction error and the population at risk give an important overview of the malaria situation in Zambia. These maps can assist to achieve better resource allocation, health management and to target additional interventions to reduce the burden of malaria in Zambia significantly. Repeated surveys will enable the evaluation of the effectiveness of on-going intervention

Operational strategies of anti-malarial drug campaigns for malaria elimination in Zambia's southern province: a simulation study

BACKGROUND: Malaria elimination requires reducing both the potential of mosquitoes to transmit parasites to humans and humans to transmit parasites to mosquitoes. To achieve this goal in Southern province, Zambia a mass test and treat (MTAT) campaign was conducted from 2011-2013 to complement high coverage of long-lasting insecticide-treated nets (LLIN). To identify factors likely to increase campaign effectiveness, a modelling approach was applied to investigate the simulated effect of alternative operational strategies for parasite clearance in southern province. METHODS: OpenMalaria, a discrete-time, individual-based stochastic model of malaria, was parameterized for the study area to simulate anti-malarial drug administration for interruption of transmission. Simulations were run for scenarios with a range of artemisinin-combination therapies, proportion of the population reached by the campaign, targeted age groups, time between campaign rounds, Plasmodium falciparum test protocols, and the addition of drugs aimed at preventing onward transmission. A sensitivity analysis was conducted to assess uncertainty of simulation results. Scenarios were evaluated based on the reduction in all-age parasite prevalence during the peak transmission month one year following the campaign, compared to the currently-implemented strategy of MTAT 19 % population coverage at pilot and 40 % coverage during the first year of implementation in the presence of 56 % LLIN use and 18 % indoor residual spray coverage. RESULTS: Simulation results suggest the most important determinant of success in reducing prevalence is the population coverage achieved in the campaign, which would require more than 1 year of campaign implementation for elimination. The inclusion of single low-dose primaquine, which acts as a gametocytocide, or ivermectin, which acts as an endectocide, to the drug regimen did not further reduce parasite prevalence one year following the campaign compared to the currently-implemented strategy. Simulation results indicate a high proportion of low-density infections were missed by rapid diagnostic tests that would be treated and cleared with mass drug administration (MDA). CONCLUSIONS: The optimal implementation strategy for MTAT or MDA will vary by background level of prevalence, by rate of infections imported to the area, and by ability to operationally achieve high population coverage. Overall success with new parasite clearance strategies depends on continued coverage of vector control interventions to ensure sustained gains in reduction of disease burden

Changes in the burden of malaria in sub-Saharan Africa.

The burden of malaria in countries in sub-Saharan Africa has declined with scaling up of prevention, diagnosis, and treatment. To assess the contribution of specific malaria interventions and other general factors in bringing about these changes, we reviewed studies that have reported recent changes in the incidence or prevalence of malaria in sub-Saharan Africa. Malaria control in southern Africa (South Africa, Mozambique, and Swaziland) began in the 1980s and has shown substantial, lasting declines linked to scale-up of specific interventions. In The Horn of Africa, Ethiopia and Eritrea have also experienced substantial decreases in the burden of malaria linked to the introduction of malaria control measures. Substantial increases in funding for malaria control and the procurement and distribution of effective means for prevention and treatment are associated with falls in malaria burden. In central Africa, little progress has been documented, possibly because of publication bias. In some countries a decline in malaria incidence began several years before scale-up of malaria control. In other countries, the change from a failing drug (chloroquine) to a more effective drug (sulphadoxine plus pyrimethamine or an artemisinin combination) led to immediate improvements; in others malaria reduction seemed to be associated with the scale-up of insecticide-treated bednets and indoor residual spraying

Community-led Responses for Elimination (CoRE): a study protocol for a community randomized controlled trial assessing the effectiveness of community-level, reactive focal drug administration for reducing Plasmodium falciparum infection prevalence and incidence in Southern Province, Zambia

Abstract Background Zambia is pushing for, and has made great strides towards, the elimination of malaria transmission in Southern Province. Reactive focal test and treat (RFTAT) using rapid diagnostic tests and artemether-lumefantrine (AL) has been key in making this progress. Reactive focal drug administration (RFDA) using dihydroartemisinin-piperaquine (DHAP), may be superior in accelerating clearance of the parasite reservoir in humans due to the provision of enhanced chemoprophylactic protection of at-risk populations against new infections. The primary aim of this study is to quantify the relative effectiveness of RFDA with DHAP against RFTAT with AL (standard of care) for reducing Plasmodium falciparum prevalence and incidence. Methods/design The study will be conducted in four districts in Southern Province, Zambia; an area of low malaria transmission and high coverage of vector control. A community randomized controlled trial of 16 health facility catchment areas will be used to evaluate the impact of sustained year-round routine RFDA for 2 years, relative to a control of year-round routine RFTAT. Reactive case detection will be triggered by a confirmed malaria case, e.g., by microscopy or rapid diagnostic test at any government health facility. Reactive responses will be performed by community health workers (CHW) within 7 days of the index case confirmation date. Responses will be performed out to a radius of 140 m from the index case household. A subset of responses will be followed longitudinally for 90 days to examine reinfection rates. Primary outcomes include a post-intervention survey of malaria seropositivity (n = 4800 children aged 1 month to under 5 years old) and a difference-in-differences analysis of malaria parasite incidence, as measured through routine passive case detection at health facilities enrolled in the study. The study is powered to detect approximately a 65% relative reduction in these outcomes between the intervention versus the control. Discussion Strengths of this trial include a robust study design and an endline cross-sectional parasite survey as well as a longitudinal sample. Primary limitations include statistical power to detect only a 65% reduction in primary outcomes, and the potential for contamination to dilute the effects of the intervention. Trial registration ClinicalTrials.gov, ID: NCT02654912 . Registered on 12 November 2015

Evaluation of interventions aimed at increasing coverage of IPTp (six studies).

a<p>Comparing intervention and control at point of evaluation.</p>b<p>Comparing baseline and point of evaluation for intervention.</p>c<p>Denominator for IPTp 2+: women who have received already one SP dose.</p>d<p>Denominator: women with at least one ANC visit.</p>e<p>Analysis adjusted for clustering.</p>f<p>Information from article enhanced by supplemental data from authors.</p><p>G1, primigravidae; G2, secundigravidae; trim, trimester of pregnancy.</p

Evaluation of interventions aimed at increasing coverage of ITNs (15 studies).

a<p>Comparing intervention and control at point of evaluation.</p>b<p>Analysis adjusted for clustering.</p>c<p>Sample sizes not provided.</p>d<p>Comparing peri-urban and rural women.</p>e<p>ITN use in infants used as a proxy for ITN use by pregnant women, as women share their sleeping places with their newborns in this setting.</p>f<p>ITN use during pregnancy among women who had received a free United Nations Children's Fund ITN during 2001 when they were pregnant and did not previously use an ITN.</p>g<p>Comparison of the poorest quintile versus wealthiest quintile.</p>h<p>Comparing redemption of vouchers issued in urban versus rural health facilities.</p>i<p>ITN use last night among households with a pregnant woman in residence.</p><p>DRC, Democratic Republic of the Congo.</p

Synthesis matrix comparing findings from observational studies with those of intervention studies for ITNs.

<p>Synthesis matrix comparing findings from observational studies with those of intervention studies for ITNs.</p

Data extracted for barriers and determinants by study.

<p>Data extracted for barriers and determinants by study.</p