Mass Testing and Treatment to Accelerate Malaria Elimination: A Systematic Review and Meta-Analysis.

In regions where malaria transmission persists, the implementation of approaches aimed at eliminating parasites from the population can effectively decrease both burden of disease and transmission of infection. Thus, mass strategies that target symptomatic and asymptomatic infections at the same time may help countries to reduce transmission. This systematic review assessed the potential benefits and harms of mass testing and treatment (MTaT) to reduce malaria transmission. Searches were conducted in March 2021 and updated in April 2022 and included cluster-randomized controlled trials (cRCTs) as well as nonrandomized studies (NRSs) using malaria infection incidence, clinical malaria incidence, or prevalence as outcomes. The risk of bias was assessed with Cochrane's risk of bias (RoB2) tool and Risk of Bias Tool in Nonrandomized Studies - of Interventions (ROBINS-I), and the certainty of evidence (CoE) was graded for each outcome. Of 4,462 citations identified, seven studies (four cRCTs and three NRSs) contributed outcome data. The analysis revealed that MTaT did not reduce the incidence (risk ratio [RR]: 0.95, 95% CI: 0.87-1.04; 1,181 participants; moderate CoE) or prevalence (RR: 0.83, 95% CI: 0.67-1.01; 7,522 participants; moderate CoE) of malaria infection but resulted in a small reduction in clinical malaria (RR: 0.82; 95% CI: 0.70-0.95; 334,944 participants; moderate CoE). Three studies contributing data on contextual factors concluded that MTaT is an acceptable, feasible, and cost-effective intervention. Mathematical modeling analyses (n = 10) suggested that MTaT effectiveness depends on the baseline transmission level, diagnostic test performance, number of rounds, and other co-interventions. Based on the limited evidence available, MTaT has little to no impact on reducing malaria transmission.

Targeted Testing and Treatment To Reduce Human Malaria Transmission in High-Risk Populations: A Systematic Review.

As countries approach elimination of malaria, groups with increased exposure to malaria vectors or poor access to health services may serve as important human reservoirs of infection that help maintain transmission in the community. Parasitological testing and treatment targeted to these groups may reduce malaria transmission overall. This systematic review assessed the effectiveness of targeted testing and treatment (TTaT) to reduce malaria transmission, the contextual factors, and the results of modeling studies that estimated the intervention's potential impact. Bibliographic searches were conducted in March 2021 and updated in April 2022, and a total of 1,210 articles were identified. Three studies were included for outcome data: one factorial cluster randomized controlled trial (cRCT) in Kenya (5,233 participants), one cRCT in Ghana (3,046 participants), and one controlled before-and-after cohort study in schoolchildren in Malawi (786 participants). Nine reports were included for contextual factors, and two were included for mathematical modeling. Data on outcomes from the three studies suggested that at the community level, TTaT would result in little to no difference in the incidence of malaria infection (measured via active surveillance), adverse events, and severe AEs. In contrast, the effects of TTaT on prevalence (malaria parasitemia) among those targeted by the intervention were found to include a short-term impact on reducing transmission but little to no impact on transmission for extended periods. Future iterations of this review should ensure consideration for populations proven to host the vast majority of the reservoir of infection in lower-transmission settings to determine the effectiveness of the intervention.

Targeted Drug Administration to Reduce Malaria Transmission: A Systematic Review and Meta-Analysis.

In low- to very low-malaria transmission areas, most infections may be accrued within specific groups whose behaviors or occupations put them at increased risk of infection. If these infections comprise a large proportion of the reservoir of infection, targeting interventions to these groups could reduce transmission at the population level. We conducted a systematic review to assess the impact of providing antimalarials to groups of individuals at increased risk of malaria whose infections were considered to comprise a large proportion of the local reservoir of infections (targeted drug administration [TDA]). A literature search was conducted in March 2021 and updated in April 2022. Two reviewers screened titles, abstracts, and full-text records. The Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of the evidence (CoE) for each outcome. Out of 2,563 records, we identified five studies for inclusion: two cluster-randomized controlled trials (cRCTs) in Uganda and Kenya; one controlled before-after study in Ghana; and two uncontrolled before-after studies in Sri Lanka and Greece. Compared with no intervention, TDA resulted in little to no difference in the prevalence of infection at the population level (risk ratio [RR]: 0.85, 95% CI: 0.73-1.00; one cRCT, high CoE), although TDA likely resulted in a large reduction in prevalence among those targeted by the intervention (RR: 0.15, 95% CI: 0.06-0.38; two cRCTs, moderate CoE). Although TDA may reduce the burden of malaria among those receiving antimalarials, we found no evidence that it reduces transmission at the population level.

Targeted Test and Treat at Point of Entry to Reduce Importation of Malaria Parasites: A Systematic Review.

As countries approach malaria elimination, imported cases of malaria make up a larger proportion of all cases and may drive malaria transmission. Targeted test and treat (TTaT) at points of entry (POEs) is a strategy that aims to reduce the number of imported infections in countries approaching elimination by testing and treating individuals at border crossings. No evidence has been systematically collected and evaluated to assess the impact and operational feasibility of this strategy. This systematic review gathered empirical evidence on the effectiveness of the intervention, contextual factors, and results of modeling studies that estimate its potential impact. Bibliographic searches were conducted in March 2021 and updated in April 2022, and a total of 1,569 articles were identified. All study designs were included, but none of them were intervention studies set up to measure the impact of TTaT at POEs. Seven nonrandomized observational studies were eligible for assessment of outcome data in terms of describing the extent of positive cases among people crossing borders. Also included in the review were three studies for assessment of acceptability and feasibility of the intervention and three for assessment of mathematical modeling. The positivity rates reported in the seven studies ranged between 0.0% and 70.0%, which may be attributable to the different settings and operational feasibility. Overall, there is limited evidence of the effect of TTaT at POEs on the prevalence of infection, and the certainty of the evidence was very low owing to critical risk of bias, serious inconsistency, and serious indirectness.

Development of Systematic Reviews to Inform WHO's Recommendations for Elimination and Prevention of Re-Establishment of Malaria: Methodology.

The basis for an evidence-based recommendation is a well-conducted systematic review that synthesizes the primary literature relevant to the policy or program question of interest. In 2020, the WHO commissioned 10 systematic reviews of potential interventions in elimination or post-elimination settings to summarize their impact on malaria transmission. This paper describes the general methods used to conduct this series of systematic reviews and notes where individual reviews diverged from the common methodology. The paper also presents lessons learned from conducting the systematic reviews to make similar future efforts more efficient, standardized, and streamlined.