Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa.

BACKGROUND: Increasing insecticide costs and constrained malaria budgets could make universal vector control strategies, such as indoor residual spraying (IRS), unsustainable in low-transmission settings. We investigated the effectiveness and cost-effectiveness of a reactive, targeted IRS strategy. METHODS: This cluster-randomised, open-label, non-inferiority trial compared reactive, targeted IRS with standard IRS practice in northeastern South Africa over two malaria seasons (2015-17). In standard IRS clusters, programme managers conducted annual mass spray campaigns prioritising areas using historical data, expert opinion, and other factors. In targeted IRS clusters, only houses of index cases (identified through passive surveillance) and their immediate neighbours were sprayed. The non-inferiority margin was 1 case per 1000 person-years. Health service costs of real-world implementation were modelled from primary and secondary data. Incremental costs per disability-adjusted life-year (DALY) were estimated and deterministic and probabilistic sensitivity analyses conducted. This study is registered with ClinicalTrials.gov, NCT02556242. FINDINGS: Malaria incidence was 0·95 per 1000 person-years (95% CI 0·58 to 1·32) in the standard IRS group and 1·05 per 1000 person-years (0·72 to 1·38) in the targeted IRS group, corresponding to a rate difference of 0·10 per 1000 person-years (-0·38 to 0·59), demonstrating non-inferiority for targeted IRS (p<0·0001). Per additional DALY incurred, targeted IRS saved US$7845 (2902 to 64 907), giving a 94-98% probability that switching to targeted IRS would be cost-effective relative to plausible cost-effectiveness thresholds for South Africa ($2637 to $3557 per DALY averted). Depending on the threshold used, targeted IRS would remain cost-effective at incidences of less than 2·0-2·7 per 1000 person-years. Findings were robust to plausible variation in other parameters. INTERPRETATION: Targeted IRS was non-inferior, safe, less costly, and cost-effective compared with standard IRS in this very-low-transmission setting. Saved resources could be reallocated to other malaria control and elimination activities. FUNDING: Joint Global Health Trials.

Impact of a clinical decision rule on antibiotic prescription for children with suspected lower respiratory tract infections presenting to European emergency departments: a simulation study based on routine data.

BACKGROUND: Discriminating viral from bacterial lower respiratory tract infections (LRTIs) in children is challenging thus commonly resulting in antibiotic overuse. The Feverkidstool, a validated clinical decision rule including clinical symptoms and C-reactive protein, safely reduced antibiotic use in children at low/intermediate risk for bacterial LRTIs in a multicentre trial at emergency departments (EDs) in the Netherlands. OBJECTIVES: Using routine data from an observational study, we simulated the impact of the Feverkidstool on antibiotic prescriptions compared with observed antibiotic prescriptions in children with suspected LRTIs at 12 EDs in eight European countries. METHODS: We selected febrile children aged 1 month to 5 years with respiratory symptoms and excluded upper respiratory tract infections. Using the Feverkidstool, we calculated individual risks for bacterial LRTI retrospectively. We simulated antibiotic prescription rates under different scenarios: (1) applying effect estimates on antibiotic prescription from the trial; and (2) varying both usage (50%-100%) and compliance (70%-100%) with the Feverkidstool's advice to withhold antibiotics in children at low/intermediate risk for bacterial LRTI (≤10%). RESULTS: Of 4938 children, 4209 (85.2%) were at low/intermediate risk for bacterial LRTI. Applying effect estimates from the trial, the Feverkidstool reduced antibiotic prescription from 33.5% to 24.1% [pooled risk difference: 9.4% (95% CI: 5.7%-13.1%)]. Simulating 50%-100% usage with 90% compliance resulted in risk differences ranging from 8.3% to 15.8%. Our simulations suggest that antibiotic prescriptions would be reduced in EDs with high baseline antibiotic prescription rates or predominantly (>85%) low/intermediate-risk children. CONCLUSIONS: Implementation of the Feverkidstool could reduce antibiotic prescriptions in children with suspected LRTIs in European EDs.

Donor aid mentioning newborns and stillbirths, 2002-19: an analysis of levels, trends, and equity.

BACKGROUND: Global aid for reproductive, maternal, newborn, and child health has stagnated in recent years, and aid mentioning newborns or stillbirths has previously represented a very small proportion of aid for reproductive, maternal, newborn, and child health. Neonatal survival targets have been set by 78 countries, and stillbirth prevention targets have been set by 30 countries, to address the 4·4 million newborn deaths and stillbirths globally. We aimed to generate novel estimates of current levels of, and trends in, aid mentioning newborns and stillbirths over 2002-19, and to assess whether the amount of aid disbursed aligns with the associated mortality burden. METHODS: For this analysis, we did a manual review and coding of the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System database from 2002 to 2019 using key search terms for aid mentioning newborns and stillbirths. We compared these findings with estimates of aid for reproductive, maternal, newborn, and child health for 2002-19 based on the Muskoka2 method. Findings are presented in 2019 US$ according to the OECD's Development Assistance Committee deflators, which account for variation in exchange rates and inflation in donor countries. FINDINGS: We identified 21 957 unique records in the 2002-19 period. Aid mentioning newborns and stillbirths comprised approximately 10% ($1·6 billion) of reproductive, maternal, newborn, and child health funding overall in 2019 ($15·9 billion), with a small decrease in value between 2015 and 2019. 1284 (6%) of 21 957 records and 3·4% ($535 million) of their total value mentioned aid focused only on newborn health. Ten donors contributed 87% ($13·7 billion) of the total value of aid mentioning newborns and stillbirths during 2002-19. Aid mentioning newborns and stillbirths was inequitably allocated in the least developed countries (as defined by the UN), ranging from $18 per death in Angola to $1389 per death in Timor-Leste. Stillbirths were not mentioned in any funding in 2002-09, and they were only mentioned in 46 of 21 957 records in 2010-19, comprising $44·4 million of aid disbursed during this period. INTERPRETATION: Aid mentioning newborns and stillbirths is poorly matched to their corresponding mortality burden (representing 10% of aid for reproductive, maternal, newborn, and child health overall, yet accounting for approximately 50% of mortality in children <5 years) and across recipient countries (with substantial variation in the amount of aid received per newborn death and stillbirth between countries with similar health and economic needs). Our findings indicate that aid needs to be better targeted to populations with the highest mortality burdens, creating greater potential for impact. FUNDING: John D and Catherine T MacArthur Foundation, Bill & Melinda Gates Foundation, ELMA Philanthropies, Children's Investment Fund Foundation UK, Lemelson Foundation, and Ting Tsung and Wei Fong Chao Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Investigating point-of-care diagnostics for sexually transmitted infections and antimicrobial resistance in antenatal care in Zimbabwe (IPSAZ): protocol for a mixed-methods study.

INTRODUCTION: Sexually transmitted infections (STIs) can cause serious morbidity, including pelvic inflammatory disease, and adverse pregnancy outcomes. In low/middle-income countries, limited laboratory infrastructure has resulted in a syndrome-based approach being used for management of STIs, which has poor sensitivity and specificity, leading to considerable underdiagnosis and overtreatment. The WHO has called for development and evaluation of strategies to inform replacement of syndromic management by diagnostic testing.The aim of this project is to evaluate a strategy of point-of-care testing for six STIs in antenatal care (ANC) in Zimbabwe. METHODS AND ANALYSIS: A prospective interventional study will be conducted in ANC clinics in Harare province, Zimbabwe. One thousand pregnant women will be recruited when registering for routine ANC. Alongside routine HIV and syphilis testing, participants will be offered an integrated screening package including testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and hepatitis B. All individuals with STIs will receive treatment, partner notification services, risk reduction counselling and referral if needed according to national guidelines. Gonorrhoea samples will be cultured and tested for antimicrobial resistance as per WHO enhanced gonococcal antimicrobial surveillance programme guidelines.The primary outcome measure is the composite prevalence of CT, NG, TV, syphilis and hepatitis B. A mixed-methods process evaluation and economic evaluation will be conducted to understand the acceptability, feasibility and cost-effectiveness of integrated STI testing, compared with standard of care (syndromic management). ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Research Council of Zimbabwe, the Biomedical Research and Training Institute Institutional Review Board, and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings and shared with participating communities and with national and international policymaking bodies. TRIAL REGISTRATION NUMBER: NCT05541081.

Modelling the cost-effectiveness of introducing subsidised malaria rapid diagnostic tests in the private retail sector in sub-Saharan Africa.

BACKGROUND: Over the last 10 years, there has been a huge shift in malaria diagnosis in public health facilities, due to widespread deployment of rapid diagnostic tests (RDTs), which are accurate, quick and easy to use and inexpensive. There are calls for RDTs to be made available at-scale in the private retail sector where many people with suspected malaria seek care. Retail sector RDT use in sub-Saharan Africa (SSA) is limited to small-scale studies, and robust evidence on value-for-money is not yet available. We modelled the cost-effectiveness of introducing subsidised RDTs and supporting interventions in the SSA retail sector, in a context of a subsidy programme for first-line antimalarials. METHODS: We developed a decision tree following febrile patients through presentation, diagnosis, treatment, disease progression and further care, to final health outcomes. We modelled results for three 'treatment scenarios', based on parameters from three small-scale studies in Nigeria (TS-N), Tanzania (TS-T) and Uganda (TS-U), under low and medium/high transmission (5% and 50% Plasmodium falciparum (parasite) positivity rates (PfPR), respectively). RESULTS: Cost-effectiveness varied considerably between treatment scenarios. Cost per disability-adjusted life year averted at 5% PfPR was US$482 (TS-N) and US$115 (TS-T) and at 50% PfPR US$44 (TS-N) and US$45 (TS-T), from a health service perspective. TS-U was dominated in both transmission settings. CONCLUSION: The cost-effectiveness of subsidised RDTs is strongly influenced by treatment practices, for which further evidence is required from larger-scale operational settings. However, subsidised RDTs could promote increased use of first-line antimalarials in patients with malaria. RDTs may, therefore, be more cost-effective in higher transmission settings, where a greater proportion of patients have malaria and benefit from increased antimalarial use. This is contrary to previous public sector models, where RDTs were most cost-effective in lower transmission settings as they reduced unnecessary antimalarial use in patients without malaria.