Serological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: Results from a secondary analysis of a cluster randomised trial

Wu, Lindsey; Hsiang, Michelle S.; Prach, Lisa M.; Schrubbe, Leah; Ntuku, Henry; Dufour, Mi‐Suk Kang; Whittemore, Brooke; Scott, Valerie; Yala, Joy; Roberts, Kathryn W.; Patterson, Catriona; Biggs, Joseph R.; Hall, Tom; Tetteh, Kevin K. A.; Gueye, Cara Smith; Greenhouse, Bryan; Bennett, Adam; Smith, Jennifer L.; Katokele, Stark; Uusiku, Petrina; Mumbengegwi, Davis R.; Gosling, Roly; Drakeley, Chris; Kleinschmidt, Immo

doi:10.1016/j.eclinm.2022.101272

Cited by 5 publications

(3 citation statements)

References 51 publications

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“…Despite these limitations, the internal consistency between the findings of this secondary analysis and the original trial, which each used different data structures and statistical methods, supports the validity of our findings. Estimates of total effects in this analysis, which pooled across intervention recipients and non-recipients, were consistent overall with those of the original trial, which included all individuals in study clusters (intervention recipients and nonrecipients) (24,40). Additional strengths include pre-specification of spillover analysis methods and use of individual-level, spatially indexed data to measure spillovers.…”

Section: Effects On Malaria Prevalencementioning

confidence: 66%

“…(5) Field staff also collected 250 ml of whole blood in BD Microtainer tubes with EDTA additive (Becton, Dickinson and Corporation, Franklin Lakes, NJ, USA) for serological analyses. Using human plasma, Luminex assays were performed to detect malaria antigens using previously described procedures (6, 7). Field staff recorded the geocoordinates of all sampled households.…”

Section: Methodsmentioning

confidence: 99%

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Targeted malaria elimination interventions reducePlasmodium falciparuminfections up to 3 kilometers away

Benjamin-Chung,

Li,

Nguyen

et al. 2023

Preprint

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Malaria elimination interventions in low-transmission settings aim to extinguish hot spots and prevent transmission to nearby areas. In malaria elimination settings, the World Health Organization recommends reactive, focal interventions targeted to the area near malaria cases shortly after they are detected. A key question is whether these interventions reduce transmission to nearby uninfected or asymptomatic individuals who did not receive interventions. Here, we measured direct effects (among intervention recipients) and spillover effects (among non-recipients) of reactive, focal interventions delivered within 500m of confirmed malaria index cases in a cluster-randomized trial in Namibia. The trial delivered malaria chemoprevention (artemether lumefantrine) and vector control (indoor residual spraying with Actellic) separately and in combination using a factorial design. We compared incidence, infection prevalence, and seroprevalence between study arms among intervention recipients (direct effects) and non-recipients (spillover effects) up to 3 km away from index cases. We calculated incremental cost-effectiveness ratios accounting for spillover effects. The combined chemoprevention and vector control intervention produced direct effects and spillover effects. In the primary analysis among non-recipients within 1 km from index cases, the combined intervention reduced malaria incidence by 43% (95% CI 20%, 59%). In secondary analyses among non-recipients 500m-3 km from interventions, the combined intervention reduced infection by 79% (6%, 95%) and seroprevalence 34% (20%, 45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 37%. Our findings provide the first evidence that targeting hot spots with combined chemoprevention and vector control interventions can indirectly benefit non-recipients up to 3 km away.

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Section: Effects On Malaria Prevalencementioning

confidence: 66%

Section: Methodsmentioning

confidence: 99%

Targeted malaria elimination interventions reducePlasmodium falciparuminfections up to 3 kilometers away

Benjamin-Chung,

Li,

Nguyen

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…multiplexed [8], allowing a range of targets associated with varying kinetics to be integrated and provide a fuller understanding of exposure. These approaches are now being applied to impact evaluations [9,10]. Considering the need to assess elimination strategies in low transmission settings, serology represents an approach to increase the signal to noise ratio and observe historical exposure trends through an attainable sample size.…”

Section: Introductionmentioning

confidence: 99%

Reactive focal drug administration associated with decreased malaria transmission in an elimination setting: Serological evidence from the cluster-randomized CoRE study

Bridges¹,

Miller²,

Chalwe

et al. 2022

PLOS Glob Public Health

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Efforts to eliminate malaria transmission need evidence-based strategies. However, accurately assessing end-game malaria elimination strategies is challenging due to the low level of transmission and the rarity of infections. We hypothesised that presumptively treating individuals during reactive case detection (RCD) would reduce transmission and that serology would more sensitively detect this change over standard approaches. We conducted a cluster randomised control trial (NCT02654912) of presumptive reactive focal drug administration (RFDA–intervention) compared to the standard of care, reactive focal test and treat (RFTAT—control) in Southern Province, Zambia—an area of low seasonal transmission (overall incidence of ~3 per 1,000). We measured routine malaria incidence from health facilities as well as PCR parasite prevalence / antimalarial seroprevalence in an endline cross-sectional population survey. No significant difference was identified from routine incidence data and endline prevalence by polymerase chain reaction (PCR) had insufficient numbers of malaria infections (i.e., 16 infections among 6,276 children) to assess the intervention. Comparing long-term serological markers, we found a 19% (95% CI = 4–32%) reduction in seropositivity for the RFDA intervention using a difference in differences approach incorporating serological positivity and age. We also found a 37% (95% CI = 2–59%) reduction in seropositivity to short-term serological markers in a post-only comparison. These serological analyses provide compelling evidence that RFDA both has an impact on malaria transmission and is an appropriate end-game malaria elimination strategy. Furthermore, serology provides a more sensitive approach to measure changes in transmission that other approaches miss, particularly in very low transmission settings. Trial Registration: Registered at www.clinicaltrials.gov (NCT02654912, 13/1/2016).

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Detection of 4-aminothiophenol with core-shell structured Ag@ZnS as a surface enhanced Raman scattering substrate

Tian,

Pei,

et al. 2023

Journal of Alloys and Compounds

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Serological evaluation of the effectiveness of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia: Results from a secondary analysis of a cluster randomised trial

Cited by 5 publications

References 51 publications

Targeted malaria elimination interventions reducePlasmodium falciparuminfections up to 3 kilometers away

Targeted malaria elimination interventions reducePlasmodium falciparuminfections up to 3 kilometers away

Reactive focal drug administration associated with decreased malaria transmission in an elimination setting: Serological evidence from the cluster-randomized CoRE study

Detection of 4-aminothiophenol with core-shell structured Ag@ZnS as a surface enhanced Raman scattering substrate

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