The "ComPAS Trial" combined treatment model for acute malnutrition: study protocol for the economic evaluation.

BACKGROUND: Acute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child's weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM. METHOD: This is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant. DISCUSSION: We hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies. TRIAL REGISTRATION: ISRCTN 30393230 , date: 16/03/2017

Water, sanitation and hygiene interventions and the prevention and treatment of childhood acute malnutrition: A systematic review.

Undernutrition is more prevalent among children living in unsanitary environments with inadequate water, sanitation and hygiene (WASH). Despite good evidence for the effect of WASH on multiple infectious diseases, evidence for the effect of WASH interventions on childhood undernutrition is less well established, particularly for acute malnutrition. To assess the effectiveness of WASH interventions in preventing and treating acute childhood malnutrition, we performed electronic searches to identify relevant studies published between 1 January 2000 and 13 May 2019. We included studies assessing the effect of WASH on prevention and treatment of acute malnutrition in children under 5 years of age. Data were extracted by two independent reviewers. We included 26 articles of 599 identified references with a total of 43,083 participants. Twenty-five studies reported on the effect of WASH on prevention, and two studies reported its effect on treatment of acute malnutrition. Current evidence does not show consistent associations of WASH conditions and interventions with prevention of acute malnutrition or with the improvement of its treatment outcomes. Only two high-quality randomized controlled trials (RCTs) demonstrated that improved water quality during severe acute malnutrition treatment improved recovery outcomes but did not prevent relapse. Many of the interventions consisted of a package of WASH services, making impossible to attribute the effect to one specific component. This highlights the need for high-quality, rigorous intervention studies assessing the effects of WASH interventions specifically designed to prevent acute malnutrition or improve its treatment

Comparative study of the efficacy and tolerability of dihydroartemisinin - piperaquine - trimethoprim versus artemether - lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon, Ivory Coast and Senegal

<p>Abstract</p> <p>Background</p> <p>The ACT recommended by WHO is very effective and well-tolerated. However, these combinations need to be administered for three days, which may limit adherence to treatment.</p> <p>The combination of dihydroartemisinin - piperaquine phosphate - trimethoprim (Artecom^®, Odypharm Ltd), which involves treatment over two days, appears to be a good alternative, particularly in malaria-endemic areas. This study intends to compare the efficacy and tolerability of the combination dihydroartemisinin - piperaquine phosphate - trimethoprim (DPT) versus artemether - lumefantrine (AL) in the treatment of uncomplicated <it>Plasmodium falciparum </it>malaria in Cameroon, Ivory Coast and Senegal.</p> <p>Methods</p> <p>This was a randomized, controlled, open-label clinical trial with a 28-day follow-up period comparing DPT to AL as the reference drug. The study involved patients of at least two years of age, suffering from acute, uncomplicated <it>Plasmodium falciparum </it>malaria with fever. The WHO 2003 protocol was used.</p> <p>Results</p> <p>A total of 418 patients were included in the study and divided into two treatment groups: 212 in the DPT group and 206 in the AL group. The data analysis involved the 403 subjects who correctly followed the protocol (<it>per protocol </it>analysis), i.e. 206 (51.1%) in the DPT group and 197 (48.9%) in the AL group. The recovery rate at D14 was 100% in both treatment groups. The recovery rate at D28 was 99% in the DPT and AL groups before and after PCR results with one-sided 97.5% Confidence Interval of the rates difference > -1.90%. More than 96% of patients who received DPT were apyrexial 48 hours after treatment compared to 83.5% in the AL group (p < 0.001). More than 95% of the people in the DPT group had a parasite clearance time of 48 hours or less compared to approximately 90% in the AL group (p = 0.023). Both drugs were well tolerated. No serious adverse events were reported during the follow-up period. All of the adverse events observed were minor and did not result in the treatment being stopped in either treatment group. The main minor adverse events reported were vomiting, abdominal pain and pruritus.</p> <p>Conclusion</p> <p>The overall efficacy and tolerability of DPT are similar to those of AL. The ease of taking DPT and its short treatment course (two days) may help to improve adherence to treatment. Taken together, these findings make this medicinal product a treatment of choice for the effective management of malaria in Africa.</p

Economic evaluation of a reduced dosage of ready‐to‐use therapeutic foods to treat uncomplicated severe acute malnourished children aged 6–59 months in Burkina Faso

Abstract Ready‐to‐use therapeutic foods (RUTF) used to treat children with severe acute malnutrition (SAM) are costly, and the prescribed dosage has not been optimized. The MANGO trial, implemented by Action Contre la Faim in Burkina Faso, proved the non‐inferiority of a reduced RUTF dosage in community‐based treatment of uncomplicated SAM. We performed a cost‐minimization analysis to assess the economic impact of transitioning from the standard to the reduced RUTF dose. We used a decision‐analytic model to simulate a cohort of 399 children/arm, aged 6–59 months and receiving SAM treatment. We adopted a societal perspective: direct medical costs (drugs, materials and staff time), non‐medical costs (caregiver expenses) and indirect costs (productivity loss) in 2017 international US dollar were included. Data were collected through interviews with 35 caregivers and 20 informants selected through deliberate sampling and the review trial financial documents. The overall treatment cost for 399 children/arm was $36,550 with the standard and$30,411 with the reduced dose, leading to $6,140 (16.8$15.43 saved/child treated). The cost/consultation was $11.6 and$9.6 in the standard and reduced arms, respectively, with RUTF accounting for 56.2% and 47.0% of the total. The savings/child treated was $11.4 in a scenario simulating the Burkinabè routine SAM treatment outside clinical trial settings. The reduced RUTF dose tested in the MANGO trial resulted in significant cost savings for SAM treatment. These results are useful for decision makers to estimate potential economic gains from an optimized SAM treatment protocol in Burkina Faso and similar contexts

Predictive factors of cytomegalovirus seropositivity among pregnant women in Paris, France.

Cytomegalovirus (CMV) is the most frequent cause of congenital infection. The objective of this study was to evaluate predictive factors for CMV seronegativity in a cohort of pregnant women in Paris, France.Pregnant women enrolled in a prospective cohort during the 2009 A/H1N1 pandemic were tested for CMV IgG antibodies. Variables collected were age, geographic origin, lifestyle, work characteristics, socioeconomic status, gravidity, parity and number of children at home. A multivariate logistic regression model was used to identify independent predictive factors for CMV seropositivity.Among the 826 women enrolled, 389 (47.1%) were primiparous, and 552 (67.1%) had Metropolitan France as a geographic origin. Out of these, 355 (i.e. 57.0%, 95% confidence interval (CI): [53.6%-60.4%]) were CMV seropositive: 43.7% (95% CI:[39.5%-47.9%]) in those whose geographic origin was Metropolitan France and 84.1% in those with other origins (95% CI:[79.2%-88.3%]). Determinants associated with CMV seropositivity in a multivariate logistic regression model were: (i) geographic origin (p<0.001(compared with Metropolitan France, geographic origins of Africa adjusted odds ratio (aOR) 21.2, 95% CI:[9.7-46.5], French overseas departments and territories and other origin, aOR 7.5, 95% CI:[3.9-14.6], and Europe or Asia, aOR 2.2, 95% CI: [1.3-3.7]); and (ii) gravidity (p = 0.019), (compared with gravidity = 1, if gravidity≥3, aOR = 1.5, 95% CI: [1.1-2.2]; if gravidity = 2, aOR = 1.0, 95% CI: [0.7-1.4]). Work characteristics and socioeconomic status were not independently associated with CMV seropositivity.In this cohort of pregnant women, a geographic origin of Metropolitan France and a low gravidity were predictive factors for CMV low seropositivity. Such women are therefore the likely target population for prevention of CMV infection during pregnancy in France

Proximate determinants of tuberculosis in Indigenous peoples worldwide: a systematic review

Summary: Background: Indigenous peoples worldwide carry a disproportionate tuberculosis burden. There is an increasing awareness of the effect of social determinants and proximate determinants such as alcohol use, overcrowding, type 1 and type 2 diabetes, substance misuse, HIV, food insecurity and malnutrition, and smoking on the burden of tuberculosis. We aimed to understand the potential contribution of such determinants to tuberculosis in Indigenous peoples and to document steps taken to address them. Methods: We did a systematic review using seven databases (MEDLINE, Embase, CINAHL, Global Health, BIOSIS Previews, Web of Science, and the Cochrane Library). We identified English language articles published from Jan 1, 1980, to Dec 20, 2017, reporting the prevalence of proximate determinants of tuberculosis and preventive programmes targeting these determinants in Indigenous communities worldwide. We included any randomised controlled trials, controlled studies, cohort studies, cross-sectional studies, case reports, and qualitative research. Exclusion criteria were articles in languages other than English, full text not available, population was not Indigenous, focused exclusively on children or older people, and studies that focused on pharmacological interventions. Findings: Of 34 255 articles identified, 475 were eligible for inclusion. Most studies confirmed a higher prevalence of proximate determinants in Indigenous communities than in the general population. Diabetes was more frequent in Indigenous communities within high-income countries versus in low-income countries. The prevalence of alcohol use was generally similar to that among non-Indigenous groups, although patterns of drinking often differed. Smoking prevalence and smokeless tobacco consumption were commonly higher in Indigenous groups than in non-Indigenous groups. Food insecurity was highly prevalent in most Indigenous communities evaluated. Substance use was more frequent in Indigenous inhabitants of high-income countries than of low-income countries, with wide variation across Indigenous communities. The literature pertaining to HIV, crowding, and housing conditions among Indigenous peoples was too scant to draw firm conclusions. Preventive programmes that are culturally appropriate targeting these determinants appear feasible, although their effectiveness is largely unproven. Interpretation: Indigenous peoples were generally reported to have a higher prevalence of several proximate determinants of tuberculosis than non-Indigenous peoples, with wide variation across Indigenous communities. These findings emphasise the need for community-led, culturally appropriate strategies to address smoking, food insecurity, and diabetes in Indigenous populations as important public health goals in their own right, and also to reduce the burden of tuberculosis. Funding: Canadian Institutes of Health Research