Evaluating the impact of programmatic mass drug administration for malaria in Zambia using routine incidence data.

BACKGROUND NlmCategory: BACKGROUND content: In 2016, the Zambian National Malaria Elimination Centre started programmatic mass drug administration (pMDA) campaigns with dihydroartemisinin-piperaquine as a malaria elimination tool in Southern Province. Two rounds were administered, two months apart (coverage 70% and 57% respectively). We evaluated the impact of one year of pMDA on malaria incidence using routine data. - Label: METHODS NlmCategory: METHODS content: We conducted an interrupted time series with comparison group analysis on monthly incidence data collected at the health facility catchment area (HFCA) level, with a negative binomial model using generalized estimating equations. pMDA was conducted in HFCAs with greater than 50 cases/1,000 people/year. Ten HFCAs with incidence rates marginally above this threshold (pMDA group) were compared to 20 HFCAs marginally below (comparison group). - Label: RESULTS NlmCategory: RESULTS content: "The pMDA HFCAs saw a 46% greater decrease in incidence at the time of intervention than the comparison areas (incidence rate ratio: 0.536 [0.337-0.852]); however, incidence increased toward the end of the season. No HFCAs saw a transmission interruption." - Label: CONCLUSION NlmCategory: CONCLUSIONS content: pMDA, implemented during one year with imperfect coverage in low transmission areas with sub-optimal vector control coverage, significantly reduced incidence. However, elimination will require additional tools. Routine data are important resources for programmatic impact evaluations and should be considered for future analyses

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

Characteristics of treatment recall by caregivers and observation at study clinics, Western Province, Zambia, 2012.

<p>All standard errors estimated using the Huber–White Sandwich estimator to account for correlated data at the facility level.</p>a<p>Only one child tested with microscopy.</p>b<p>Includes laboratory-confirmed malaria and clinical diagnosis based on symptoms.</p

Modeled diagnosis and treatment coverage based on sensitivity and specificity of caregiver recall across actual intervention coverages in a given community.

<p>Proportions of patients actually experiencing each event at the study clinics are illustrated with red arrows. The solid black line at a 45° angle represents 100% sensitivity and specificity. Estimates for the coverage of these interventions expected from a household survey from caregiver recall with the sensitivity and specificity observed in this study (blue line) were modeled for true intervention coverages (observed at clinic) ranging from 0% to 100% as follows: estimated coverage from caregiver recall = (true coverage at clinic<i>×</i>sensitivity)+[(1−true coverage at clinic)<i>×</i>[1−specificity)].</p

Effectiveness of reactive case detection for malaria elimination in three archetypical transmission settings: a modelling study

Abstract Background Reactive case detection could be a powerful tool in malaria elimination, as it selectively targets transmission pockets. However, field operations have yet to demonstrate under which conditions, if any, reactive case detection is best poised to push a region to elimination. This study uses mathematical modelling to assess how baseline transmission intensity and local interconnectedness affect the impact of reactive activities in the context of other possible intervention packages. Methods Communities in Southern Province, Zambia, where elimination operations are currently underway, were used as representatives of three archetypes of malaria transmission: low-transmission, high household density; high-transmission, low household density; and high-transmission, high household density. Transmission at the spatially-connected household level was simulated with a dynamical model of malaria transmission, and local variation in vectorial capacity and intervention coverage were parameterized according to data collected from the area. Various potential intervention packages were imposed on each of the archetypical settings and the resulting likelihoods of elimination by the end of 2020 were compared. Results Simulations predict that success of elimination campaigns in both low- and high-transmission areas is strongly dependent on stemming the flow of imported infections, underscoring the need for regional-scale strategies capable of reducing transmission concurrently across many connected areas. In historically low-transmission areas, treatment of clinical malaria should form the cornerstone of elimination operations, as most malaria infections in these areas are symptomatic and onward transmission would be mitigated through health system strengthening; reactive case detection has minimal impact in these settings. In historically high-transmission areas, vector control and case management are crucial for limiting outbreak size, and the asymptomatic reservoir must be addressed through reactive case detection or mass drug campaigns. Conclusions Reactive case detection is recommended only for settings where transmission has recently been reduced rather than all low-transmission settings. This is demonstrated in a modelling framework with strong out-of-sample accuracy across a range of transmission settings while including methodologies for understanding the most resource-effective allocations of health workers. This approach generalizes to providing a platform for planning rational scale-up of health systems based on locally-optimized impact according to simplified stratification

Accuracy of caregiver recall of key questions of diagnosis and treatment of malaria, Western Province, Zambia, 2012.

<p>All standard errors estimated using the Huber–White Sandwich estimator to account for correlated data at the facility level.</p>a<p>Among children reported by caregiver to have a fever in the past 2 wk.</p>b<p>Includes laboratory-confirmed malaria and clinical diagnosis based on symptoms.</p><p>CI, confidence interval; FN, false negative; FP, false positive; TN, true negative; TP, true positive.</p