Economic evaluation of postdischarge malaria chemoprevention in preschool children treated for severe anaemia in Malawi, Kenya, and Uganda: A cost-effectiveness analysis.

Background: Children hospitalised with severe anaemia in malaria-endemic areas are at a high risk of dying or being readmitted within six months of discharge. A trial in Kenya and Uganda showed that three months of postdischarge malaria chemoprevention (PDMC) with monthly dihydroartemisinin-piperaquine (DP) substantially reduced this risk. The World Health Organization recently included PDMC in its malaria chemoprevention guidelines. We conducted a cost-effectiveness analysis of community-based PDMC delivery (supplying all three PDMC-DP courses to caregivers at discharge to administer at home), facility-based PDMC delivery (monthly dispensing of PDMC-DP at the hospital), and the standard of care (no PDMC). Methods: We combined data from two recently completed trials; one placebo-controlled trial in Kenya and Uganda collecting efficacy data (May 6, 2016 until November 15, 2018; n=1049), and one delivery mechanism trial from Malawi collecting adherence data (March 24, 2016 until October 3, 2018; n=375). Cost data were collected alongside both trials. Three Markov decision models, one each for Malawi, Kenya, and Uganda, were used to compute incremental cost-effectiveness ratios expressed as costs per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were performed to account for uncertainty. Findings: Both PDMC strategies were cost-saving in each country, meaning less costly and more effective in increasing health-adjusted life expectancy than the standard of care. The estimated incremental cost savings for community-based PDMC compared to the standard of care were US$ 22·10 (Malawi), 38·52 (Kenya), and 26·23 (Uganda) per child treated. The incremental effectiveness gain using either PDMC strategy varied between 0·3 and 0·4 QALYs. Community-based PDMC was less costly and more effective than facility-based PDMC. These results remained robust in sensitivity analyses. Interpretation: PDMC under implementation conditions is cost-saving. Caregivers receiving PDMC at discharge is a cost-effective delivery strategy for implementation in malaria-endemic southeastern African settings. Funding: Research Council of Norway.

Post-discharge morbidity and mortality in children admitted with severe anaemia and other health conditions in malaria-endemic settings in Africa: a systematic review and meta-analysis.

BACKGROUND: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also remain at increased risk of mortality for several months after hospital discharge. We aimed to compare the risks of morbidity and mortality among children discharged from hospital after recovery from severe anaemia versus other health conditions in malaria-endemic settings in Africa. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, and Cochrane Central from inception to Nov 30, 2021, without language restrictions, for prospective or retrospective cohort studies and randomised controlled trials that followed up children younger than 15 years for defined periods after hospital discharge in malaria-endemic countries in Africa. We excluded the intervention groups in trials and studies or subgroups involving children with sickle cell anaemia, malignancies, or surgery or trauma, or those reporting follow-up data that were combined with the in-hospital period. Two independent reviewers extracted the data and assessed the quality and risk of bias using the Newcastle Ottawa Scale or the Cochrane Collaboration's tool. The coprimary outcomes were all-cause death and all-cause readmissions 6 months after discharge. This study is registered with PROSPERO, CRD42017079282. FINDINGS: Of 2930 articles identified in our search, 27 studies were included. For children who were recently discharged following hospital admission with severe anaemia, all-cause mortality by 6 months was higher than during the in-hospital period (n=5 studies; Mantel-Haenszel odds ratio 1·72, 95% CI 1·22-2·44; p=0·0020; I2=51·5%) and more than two times higher than children previously admitted without severe anaemia (n=4 studies; relative risk [RR] 2·69, 95% CI 1·59-4·53; p<0·0001; I2=69·2%). Readmissions within 6 months of discharge were also more common in children admitted with severe anaemia than in children admitted with other conditions (n=1 study; RR 3·05, 1·12-8·35; p<0·0001). Children admitted with severe acute malnutrition (regardless of severe anaemia) also had a higher 6-month mortality after discharge than those admitted for other reasons (n=2 studies; RR=3·12, 2·02-4·68; p<0·0001; I2=54·7%). Other predictors of mortality after discharge included discharge against medical advice, HIV, bacteraemia, and hypoxia. INTERPRETATION: In malaria-endemic settings in Africa, children admitted to hospital with severe anaemia and severe acute malnutrition are at increased risk of mortality in the first 6 months after discharge compared with children admitted with other health conditions. Improved strategies are needed for the management of these high-risk groups during the period after discharge. FUNDING: Research Council of Norway and US Centers for Disease Control and Prevention.

Equity impact analysis of medical approaches to cardiovascular diseases prevention in Tanzania.

Primary medical prevention of cardiovascular disease (CVD) has received low priority in Tanzania, despite evidence of the rising prevalence of CVD risk factors. Different guidelines have been proposed for medical CVD prevention, including the European Society of Cardiology (ESC) and the World Health Organization (WHO) guidelines, which recommend medical prevention for all individuals based on the consideration of single CVD risk thresholds. A third alternative is differentiated risk thresholds according to age. This paper compares the WHO and the differentiated risk threshold by age approaches against a baseline of no medical CVD prevention and a best scenario identical to the ESC approach in Tanzania. Assuming fixed budgets, we evaluate the guidelines according to three outcome measures, namely: efficiency, inequality and the combination of efficiency and inequality. We ran a Markov analysis for an estimated Tanzanian population at risk of CVD employing a 40 years time horizon to estimate the total expected costs and CVD deaths associated with provision of the different guidelines. The results were then used to calculate three outcomes: life expectancy at age 40 as a proxy for efficiency, the Gini coefficient (a measure of inequality), and the achievement index (which combines concerns of efficiency and inequality). Our results suggest that higher life expectancy (28.3 vs. 26.6 years) and more equally distributed health (Gini coefficient of 0.22 vs. 0.24) could be attained if medical CVD prevention was based on the differentiated risk threshold approach compared to the WHO single risk threshold, when the total cost of these approaches is the same. Preventing CVD based on differentiating risk thresholds by age seems to be the better alternative when concerns of both efficiency and inequality are considered important. However, further research on the country-specific distribution of CVD risk levels and budget impact analysis are important to assess the feasibility of its implementation.

Cost-effectiveness of medical primary prevention strategies to reduce absolute risk of cardiovascular disease in Tanzania: a Markov modelling study.

BACKGROUND: Cardiovascular disease (CVD) is a growing cause of mortality and morbidity in Tanzania, but contextualized evidence on cost-effective medical strategies to prevent it is scarce. We aim to perform a cost-effectiveness analysis of medical interventions for primary prevention of CVD using the World Health Organization's (WHO) absolute risk approach for four risk levels. METHODS: The cost-effectiveness analysis was performed from a societal perspective using two Markov decision models: CVD risk without diabetes and CVD risk with diabetes. Primary provider and patient costs were estimated using the ingredients approach and step-down methodologies. Epidemiological data and efficacy inputs were derived from systematic reviews and meta-analyses. We used disability- adjusted life years (DALYs) averted as the outcome measure. Sensitivity analyses were conducted to evaluate the robustness of the model results. RESULTS: For CVD low-risk patients without diabetes, medical management is not cost-effective unless willingness to pay (WTP) is higher than US$1327 per DALY averted. For moderate-risk patients, WTP must exceed US$164 per DALY before a combination of angiotensin converting enzyme inhibitor (ACEI) and diuretic (Diu) becomes cost-effective, while for high-risk and very high-risk patients the thresholds are US$349 (ACEI, calcium channel blocker (CCB) and Diu) and US$498 per DALY (ACEI, CCB, Diu and Aspirin (ASA)) respectively. For patients with CVD risk with diabetes, a combination of sulfonylureas (Sulf), ACEI and CCB for low and moderate risk (incremental cost-effectiveness ratio (ICER) US$608 and US$115 per DALY respectively), is the most cost-effective, while adding biguanide (Big) to this combination yielded the most favourable ICERs of US$309 and US$350 per DALY for high and very high risk respectively. For the latter, ASA is also part of the combination. CONCLUSIONS: Medical preventive cardiology is very cost-effective for all risk levels except low CVD risk. Budget impact analyses and distributional concerns should be considered further to assess governments' ability and to whom these benefits will accrue.

Cost-effectiveness of dihydroartemisinin-piperaquine compared with artemether-lumefantrine for treating uncomplicated malaria in children at a district hospital in Tanzania.

BACKGROUND: Dihydroartemisinin-piperaquine (DhP) is highly recommended for the treatment of uncomplicated malaria. This study aims to compare the costs, health benefits and cost-effectiveness of DhP and artemether-lumefantrine (AL) alongside "do-nothing" as a baseline comparator in order to consider the appropriateness of DhP as a first-line anti-malarial drug for children in Tanzania. METHODS: A cost-effectiveness analysis was performed using a Markov decision model, from a provider's perspective. The study used cost data from Tanzania and secondary effectiveness data from a review of articles from sub-Saharan Africa. Probabilistic sensitivity analysis was used to incorporate uncertainties in the model parameters. In addition, sensitivity analyses were used to test plausible variations of key parameters and the key assumptions were tested in scenario analyses. RESULTS: The model predicts that DhP is more cost-effective than AL, with an incremental cost-effectiveness ratio (ICER) of US$ 12.40 per DALY averted. This result relies on the assumption that compliance to treatment with DhP is higher than that with AL due to its relatively simple once-a-day dosage regimen. When compliance was assumed to be identical for the two drugs, AL was more cost-effective than DhP with an ICER of US$ 12.54 per DALY averted. DhP is, however, slightly more likely to be cost-effective compared to a willingness-to-pay threshold of US$ 150 per DALY averted. CONCLUSION: Dihydroartemisinin-piperaquine is a very cost-effective anti-malarial drug. The findings support its use as an alternative first-line drug for treatment of uncomplicated malaria in children in Tanzania and other sub-Saharan African countries with similar healthcare infrastructures and epidemiology of malaria.