Utilization patterns, outcomes and costs of a simplified acute malnutrition treatment programme in Burkina Faso.

Access to treatment for acute malnutrition remains a challenge, in part due to the fragmentation of treatment programmes based on case severity. This paper evaluates utilization patterns, outcomes and associated costs for treating acute malnutrition cases among a cohort of children in Burkina Faso. This study is a secondary analysis of a proof-of-concept trial, called Optimizing treatment for acute Malnutrition (OptiMA), conducted in Burkina Faso in 2016. A total of 4958 eligible children whose mid-upper arm circumference (MUAC) was less than 125 mm or with oedema were followed weekly and given ready-to-use therapeutic foods (RUTF). We evaluated the service utilization and outcomes among patients and estimated resource use and variable cost per patient, and examined factors driving variation in resource use. Children with lower initial MUAC level grew faster but required more time to recover than those with higher initial MUAC level. They also had higher rates of death, default and nonresponse. The simplified OptiMA approach for treating acute malnutrition achieved high rates of recovery overall (84%), especially among less severe cases, with modest quantities of RUTF. The average overall variable cost per child admitted was US$38.0 (SD: 20.5) half of which was accounted for by the cost of RUTF. Cost per recovered case was correlated with case severity, ranging from US$35.1 to US$132.8. If simplified integrated programmes using severity-based RUTF dosing can increase access to treatment at earlier, less severe stages of acute malnutrition, they can help avoid more serious and costlier cases.

Evaluation of an unconditional cash transfer program targeting children's first-1,000-days linear growth in rural Togo: A cluster-randomized controlled trial.

BACKGROUND: In 2014, the government of Togo implemented a pilot unconditional cash transfer (UCT) program in rural villages that aimed at improving children's nutrition, health, and protection. It combined monthly UCTs (approximately US$8.40 /month) with a package of community activities (including behavior change communication [BCC] sessions, home visits, and integrated community case management of childhood illnesses and acute malnutrition [ICCM-Nut]) delivered to mother-child pairs during the first "1,000 days" of life. We primarily investigated program impact at population level on children's height-for-age z-scores (HAZs) and secondarily on stunting (HAZ < -2) and intermediary outcomes including household's food insecurity, mother-child pairs' diet and health, delivery in a health facility and low birth weight (LBW), women's knowledge, and physical intimate partner violence (IPV). METHODS AND FINDINGS: We implemented a parallel-cluster-randomized controlled trial, in which 162 villages were randomized into either an intervention arm (UCTs + package of community activities, n = 82) or a control arm (package of community activities only, n = 80). Two different representative samples of children aged 6-29 months and their mothers were surveyed in each arm, one before the intervention in 2014 (control: n = 1,301, intervention: n = 1,357), the other 2 years afterwards in 2016 (control: n = 996, intervention: n = 1,035). Difference-in-differences (DD) estimates of impact were calculated, adjusting for clustering. Children's average age was 17.4 (± 0.24 SE) months in the control arm and 17.6 (± 0.19 SE) months in the intervention arm at baseline. UCTs had a protective effect on HAZ (DD = +0.25 z-scores, 95% confidence interval [CI]: 0.01-0.50, p = 0.039), which deteriorated in the control arm while remaining stable in the intervention arm, but had no impact on stunting (DD = -6.2 percentage points [pp], relative odds ratio [ROR]: 0.74, 95% CI: 0.51-1.06, p = 0.097). UCTs positively impacted both mothers' and children's (18-23 months) consumption of animal source foods (ASFs) (respectively, DD = +4.5 pp, ROR: 2.24, 95% CI: 1.09-4.61, p = 0.029 and DD = +9.1 pp, ROR: 2.65, 95% CI: 1.01-6.98, p = 0.048) and household food insecurity (DD = -10.7 pp, ROR: 0.63, 95% CI: 0.43-0.91, p = 0.016). UCTs did not impact on reported child morbidity 2 week's prior to report (DD = -3.5 pp, ROR: 0.80, 95% CI: 0.56-1.14, p = 0.214) but reduced the financial barrier to seeking healthcare for sick children (DD = -26.4 pp, ROR: 0.23, 95% CI: 0.08-0.66, p = 0.006). Women who received cash had higher odds of delivering in a health facility (DD = +10.6 pp, ROR: 1.53, 95% CI: 1.10-2.13, p = 0.012) and lower odds of giving birth to babies with birth weights (BWs) <2,500 g (DD = -11.8, ROR: 0.29, 95% CI: 0.10-0.82, p = 0.020). Positive effects were also found on women's knowledge (DD = +14.8, ROR: 1.86, 95% CI: 1.32-2.62, p < 0.001) and physical IPV (DD = -7.9 pp, ROR: 0.60, 95% CI: 0.36-0.99, p = 0.048). Study limitations included the short evaluation period (24 months) and the low coverage of UCTs, which might have reduced the program's impact. CONCLUSIONS: UCTs targeting the first "1,000 days" had a protective effect on child's linear growth in rural areas of Togo. Their simultaneous positive effects on various immediate, underlying, and basic causes of malnutrition certainly contributed to this ultimate impact. The positive impacts observed on pregnancy- and birth-related outcomes call for further attention to the conception period in nutrition-sensitive programs. TRIAL REGISTRATION: ISRCTN Registry ISRCTN83330970.

PMTCT care cascade and factors associated with attrition in the first four years after Option B+ implementation in Mozambique.

OBJECTIVE: To evaluate the effectiveness of the prevention of mother-to-child transmission (PMTCT) Option B+ programme in two provinces with high human immunodeficiency virus (HIV) burden in Mozambique over the first four years of programme implementation. METHODS: We assessed the PMTCT cascade in antenatal care (ANC) from July 2013 to December 2017 using facility-level data and performed a retrospective cohort analysis with patient-level data. We compared the 12-month antiretroviral therapy (ART) retention rates between women with HIV infection who initiated ART under Option B+ ('B+ pregnant') and those who initiated ART for their own health ('own health'). RESULTS: A total of 916 280 pregnant women enrolled in ANC. The proportion of women with a documented HIV status increased from 93% in 2013 to 96% in 2017. The proportion of those tested HIV-positive decreased from 8% to 6% while that of those HIV-positive on ART increased from 42% to 95%. Of the 44 377 HIV-positive women included in the analysis, 35% were lost to care. 'B+ pregnant' women initiating ART in 2015 were less likely to have no follow-up (NFU) compared with 'own health' women starting ART during the same period (adjusted odds ratio: 0.77, 95% confidence interval [CI]: 0.64-0.94, P = 0.01). There was no statistical difference between the two groups during the other years in which ART was initiated. Of those returning for care after their first visit (N = 39 801), the 'B+ pregnant' women showed a higher risk of non-retention than the other group (adjusted hazard ratio: 1.14, 95% CI: 1.03-1.25) when ART was initiated in 2013. The risk decreased during the subsequent years, with no difference observed between the groups. CONCLUSION: PMTCT Option B+ programme scale-up has yielded positive results, including the maintenance of high HIV testing and ART initiation rates in ANC. Challenges still remain, however, in improving immediate engagement in care and long-term retention. Seeking alternative service delivery models to support existing health systems and prevent defaulters is required to achieve the UNAIDS 95-95-95 targets for PMTCT in Mozambique.

OBJECTIF: Evaluer l'efficacité du programme de la prévention de la transmission mère-enfant (PTME) Option B+ dans deux provinces avec une charge élevée du virus de l' immunodéficience humaine (VIH) au Mozambique, au cours des quatre premières années de la mise en œuvre du programme. MÉTHODES: Nous avons évalué la cascade PTME dans les soins des cliniques prénatales (SCP) de juillet 2013 à décembre 2017 à l'aide de données à l'échelle de l'établissement et avons effectué une analyse de cohorte rétrospective avec des données à l'échelle du patient. Nous avons comparé les taux de rétention à 12 mois de la thérapie antirétrovirale (ART) entre les femmes infectées par le VIH qui ont commencé l'ART dans le cadre de l'option B+ (''enceintes B+'') et celles qui ont commencé l'ART pour leur propre santé (''propre santé''). RÉSULTATS: Au total, 916.280 femmes enceintes ont été inscrites dans les SCP. La proportion de femmes avec un statut VIH documenté est passée de 93% en 2013 à 96% en 2017. La proportion de celles testées positives pour le VIH est passée de 8% à 6% tandis que celle des femmes positives au VIH sous ART est passée de 42% à 95%. Sur les 44.377 femmes séropositives incluses dans l'analyse, 35% ont été perdues au cours des soins. Les femmes ''enceintes B+'' qui ont commencé l'ART en 2015 étaient moins susceptibles de ne pas avoir de suivi (NFU) que les femmes ''propre santé'' ayant commencé l'ART au cours de la même période (rapport de cotes ajusté: 0,77 ; intervalle de confiance à 95% [IC]: 0,64-0,94 ; P = 0,01). Il n'y avait aucune différence statistique entre les deux groupes durant les autres années au cours desquelles l'ART a été initiée. Parmi celles retournant pour des soins après leur première visite (N = 39.801), les femmes ''enceintes B+'' présentaient un risque plus élevé de non-rétention que l'autre groupe (rapport de risque ajusté: 1,14 ; IC95%: 1,03-1,25) lorsque l'ART a été initiée en 2013. Le risque diminuait au cours des années suivantes, sans différence observée entre les groupes. CONCLUSION: Le déploiement du programme PTME Option B+ a donné des résultats positifs, notamment le maintien de taux élevés de dépistage du VIH et d'initiation de l'ART dans les SCP. Il reste cependant des défis à relever pour améliorer l'engagement immédiat dans les soins et la rétention à long terme. La recherche de modèles de prestation de services alternatifs pour soutenir les systèmes de santé existants et prévenir les défaillances est nécessaire pour atteindre les objectifs de l'ONUSIDA 95-95-95 pour la PTME au Mozambique.

New approach to simplifying and optimising acute malnutrition treatment in children aged 6-59 months: the OptiMA single-arm proof-of-concept trial in Burkina Faso.

The Optimising treatment for acute MAlnutrition (OptiMA) strategy trains mothers to use mid upper arm circumference (MUAC) bracelets for screening and targets treatment to children with MUAC < 125 mm or oedema with one therapeutic food at a gradually reduced dose. This study seeks to determine whether OptiMA conforms to SPHERE standards (recovery rate > 75 %). A single-arm proof-of-concept trial was conducted in 2017 in Yako district, Burkina Faso including children aged 6-59 months in outpatient health centres with MUAC < 125 mm or oedema. Outcomes were stratified by MUAC category at admission. Multivariate survival analysis was carried out to identify variables predictive of recovery. Among 4958 children included, 824 (16·6 %) were admitted with MUAC < 115 mm or oedema, 1070 (21·6 %) with MUAC 115-119 mm and 3064 (61·8 %) with MUAC 120-124 mm. The new dosage was correctly implemented at all visits for 75·9 % of children. Global recovery was 86·3 (95 % CI 85·4, 87·2) % and 70·5 (95 % CI 67·5, 73·5) % for children admitted with MUAC < 115 mm or oedema. Average therapeutic food consumption was 60·8 sachets per child treated. Recovery was positively associated with mothers trained to use MUAC prior to child's admission (adjusted hazard ratio 1·09; 95 % CI 1·01, 1·19). OptiMA was successfully implemented at the scale of an entire district under 'real-life' conditions. Programme outcomes exceeded SPHERE standards, but further study is needed to determine if increasing therapeutic food dosages for the most severely malnourished will improve recovery.

Measuring retention in care for HIV-positive pregnant women in Prevention of Mother-to-Child Transmission of HIV (PMTCT) option B+ programs: the Mozambique experience.

BACKGROUND: Failure to retain HIV-positive pregnant women on antiretroviral therapy (ART) leads to increased mortality for the mother and her child. This study evaluated different retention measures for women's engagement along the continuum of care for prevention of mother-to-child transmission (PMTCT) option B+ services in Mozambique. METHODS: We compared 'point' retention (patient's presence in care 12-month post-ART initiation or any time thereafter) with the following definitions: alive and in care 12 month post-ART initiation (Ministry of Health; MOH); attendance at a health facility up to 15-month post-ART initiation (World Health Organization; WHO); alive and in treatment at 1-, 2-, 3-, 6-, 9-, and 12-month post-ART initiation (Inter-Agency Task Team; IATT); and alive and in care 12-month post-ART initiation with ≥75% appointment adherence during follow-up (i.e. 'appointment adherence' retention) or with ≥75% of appointments met on time during follow-up (i.e. 'on-time adherence' retention). Kaplan-Meier survival curves were produced to assess variability in retention rates. We used 'on-time adherence' retention as our reference to estimate sensitivity, specificity, and proportion of misclassified patients. RESULTS: Considering the 'point' retention definition, 16,840 HIV-positive pregnant women enrolled in option B+ PMTCT services were identified as 'retained in care' 12-month post-ART initiation. Of these, 60.3% (95% CI 59.6-61.1), 84.8% (95% CI 84.2-85.3), and 16.4% (95% CI 15.8-17.0) were classified as 'retained in care' using MOH, WHO, and IATT definitions, respectively, and 1.2% (95% CI 1.0-1.4) were classified as 'retained in care' using the '≥75% on-time adherence' definition. All definitions provided specificity rates of ≥98%. The sensitivity rates were 3.0% with 78% of patients misclassified according to the WHO definition and 4.3% with 54% of patients misclassified according to the MOH definition. The 'point' retention definition misclassified 97.6% of patients. Using IATT and 'appointment adherence' retention definitions, sensitivity rates (9.0 and 11.7%, respectively) were also low; however, the proportion of misclassified patients was smaller (15.9 and 18.3%, respectively). CONCLUSION: More stringent definitions indicated lower retention rates for PMTCT programs. Policy makers and program managers should include attendance at follow-up visits when measuring retention in care to better guide planning, scale-up, and monitoring of interventions.

Decision-making preferences and risk factors regarding early adolescent pregnancy in Ghana: stakeholders' and adolescents' perspectives from a vignette-based qualitative study.

BACKGROUND: Worldwide, over half of the adolescent pregnancies recorded are unintended. The decision to continue the pregnancy to term or to opt for an abortion is a constant dilemma that is directly or indirectly influenced by stakeholders and also by the wider social environment. This study aimed at understanding the perceived decision-making preferences and determinants of early adolescent pregnancy in the Jamestown area of Accra in Ghana. METHODS: A vignette-based qualitative study design was used. Eight focus group discussions were carried among various purposively selected groups of participants: parents, teachers, adolescent students who had not been pregnant before, and adolescents who had had at least one pregnancy in the past. The vignette was a hypothetical case of a 15-year-old high school student who had not experienced her menses for the past 6 weeks. The data were analyzed using a thematic analysis approach. RESULTS: Lack of parent-daughter communication, the taboo on discussing sex-related issues in households and weak financial autonomy were considered to be the main contributing factors to the high early adolescent pregnancy rates in the community. Partner readiness to assume responsibility for the girl and the baby was a key consideration in either continuing the pregnancy to term or opting for an abortion. The father was overwhelmingly considered to be the one to take the final decision regarding the pregnancy outcome. Irrespective of the fact that the respondents were very religious, opting for an abortion was considered acceptable under special circumstances, especially if the pregnant adolescent was doing well in school. CONCLUSION: Inadequate and inappropriate communication practices around sexuality issues, as well as weak financial autonomy are the major predictors of early adolescent pregnancy in this community. The father is perceived to be the main decision maker regarding a young adolescent's pregnancy outcome. Policy-makers should carefully evaluate the implications of this overwhelming perceived desire for the father to be the final decision-maker regarding adolescent pregnancy outcomes in this community.

Attitudes towards abortion and decision-making capacity of pregnant adolescents: perspectives of medicine, midwifery and law students in Accra, Ghana.

Objectives: Because medical, midwifery and law students in Ghana constitute the next generation of health care and legal practitioners, this study aimed to evaluate their attitudes towards abortion and their perceptions of the decision-making capacity of pregnant adolescents.Methods: We conducted a cross-sectional survey among 340 medical, midwifery and law students. A pretested and validated questionnaire was used to collect relevant data on respondents' sociodemographic characteristics, attitudes towards abortion and the perceived capacity and rationality of pregnant adolescents' decisions. The χ2 test of independency and Fischer's exact test were used where appropriate.Results: We retained 331 completed questionnaires for analysis. Respondents' mean age was 21.0 ± 2.9 years and the majority (95.5%) were of the Christian faith. Women made up 77.9% (n = 258) of the sample. Most students (70.1%) were strongly in favour of abortion if it was for health reasons. More than three-quarters (78.0%) of the students strongly disagreed on the use of abortion for the purposes of sex selection. Most respondents (89.0%) were not in favour of legislation to make abortion available on request for pregnant adolescents, with medical students expressing a more negative attitude compared with law and midwifery students (p < 0.001). Over half of the midwifery students (52.6%) believed that adolescents should have full decision-making capacity regarding their pregnancy outcome, compared with law and medical students (p < 0.001).Conclusion: Tensions between adolescent reproductive autonomy, the accepted culture of third party involvement (parents and partners), and the current abortion law may require keen reflection if an improvement in access to safe abortion services is envisioned.

Dissimilarities across age groups in the associations between complementary feeding practices and child growth: Evidence from rural Togo.

Adequate complementary feeding (CF) practices are essential for achieving optimal growth but challenging to measure comprehensively. This paper describes CF practices in 2,034 children aged 6-23 months and investigates their relationships with length-for-age z-score (LAZ) and stunting, using cross-sectional data collected from May to July 2014 in rural Northern Togo. The World Health Organization infant and young child feeding indicators were computed, along with ancillary indicators on feeding style and timing of introduction of complementary foods. The associations between those indicators and children's LAZ and stunting were assessed using linear and logistic regressions after stratification by age group and adjustment for children, maternal, and household characteristics. CF practices were suboptimal, and their associations with child's growth varied across indicators and age groups. In children aged 6-11 months, reaching the minimum dietary diversity and the minimum acceptable diet was associated with higher LAZ (p < .05). In 18- to 23-month-old children, only the consumption of iron-rich food was associated with both LAZ (p = .02) and stunting (p = .05). The late introduction of family foods was associated with higher odds of being stunted and lower LAZ in children aged 12-17 months (p < .001). The untimely introduction of porridge was associated with higher odds of stunting in children aged 9-23 months (p < .05). Unexpectedly, helping the child to eat was negatively associated with linear growth in all age groups. These findings nurture the ongoing process of review of the World Health Organization infant and young child feeding indicators showing that, in their current version, they hardly capture the links between CF and child's growth at different ages.

Contribution of Maternal Antiretroviral Therapy and Breastfeeding to 24-Month Survival in Human Immunodeficiency Virus-Exposed Uninfected Children: An Individual Pooled Analysis of African and Asian Studies.

Background: Human immunodeficiency virus (HIV)-infected pregnant women increasingly receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggest HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but most evidence relates to the pre-ART era, breastfeeding of limited duration, and considerable maternal mortality. Maternal ART and prolonged breastfeeding while on ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19 219 HEU children from 21 PMTCT trials/cohorts undertaken from 1995 to 2015 in Africa and Asia were pooled to estimate the association between 24-month mortality and maternal/infant factors, using random-effects Cox proportional hazards models. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" were used to estimate the relative contribution of risk factors to overall mortality. Results: Cumulative incidence of death was 5.5% (95% confidence interval, 5.1-5.9) by age 24 months. Low birth weight (LBW <2500 g, adjusted hazard ratio (aHR, 2.9), no breastfeeding (aHR, 2.5), and maternal death (aHR, 11.1) were significantly associated with increased mortality. Maternal ART (aHR, 0.5) was significantly associated with lower mortality. At the population level, LBW accounted for 16.2% of 24-month mortality, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; combined, these factors explained 63.6% of deaths by age 24 months. Conclusions: Survival of HEU children could be substantially improved if public health practices provided all HIV-infected mothers with ART and supported optimal infant feeding and care for LBW neonates.

Mortality risk and associated factors in HIV-exposed, uninfected children.

OBJECTIVE: With increasing maternal antiretroviral treatment (ART), the number of children newly infected with HIV has declined. However, the possible increased mortality in the large number of HIV-exposed, uninfected (HEU) children may be of concern. We quantified mortality risks among HEU children and reviewed associated factors. METHODS: Systematic search of electronic databases (PubMed, Scopus). We included all studies reporting mortality of HEU children to age 60 months and associated factors. Relative risk of mortality between HEU and HIV-unexposed, uninfected (HUU) children was extracted where relevant. Inverse variance methods were used to adjust for study size. Random-effects models were fitted to obtain pooled estimates. RESULTS: A total of 14 studies were included in the meta-analysis and 13 in the review of associated factors. The pooled cumulative mortality in HEU children was 5.5% (95% CI: 4.0-7.2; I(2) = 94%) at 12 months (11 studies) and 11.0% (95% CI: 7.6-15.0; I(2) = 93%) at 24 months (four studies). The pooled risk ratios for the mortality in HEU children compared to HUU children in the same setting were 1.9 (95% CI: 0.9-3.8; I(2) = 93%) at 12 months (four studies) and 2.4 (95% CI: 1.1-5.1; I(2) = 93%) at 24 months (three studies). CONCLUSION: Compared to HUU children, mortality risk in HEU children was about double at both age points, although the association was not statistically significant at 12 months. Interpretation of the pooled estimates is confounded by considerable heterogeneity between studies. Further research is needed to characterise the impact of maternal death and breastfeeding on the survival of HEU infants in the context of maternal ART, where current evidence is limited.

[HIV seroprevalence among drug users in Togo]. / Séroprévalence du VIH chez les usagers de drogues au Togo.

CONTEXT: In the context of implementing a serological and behavioural surveillance system among drugs users, this study estimated the prevalence of HIV infection and related risk behaviours among drug users (DUs) in Togo. METHOD: A cross-sectional study was conducted among DUs in Togo from November 2011 to January 2012. This study involved all DUs regardless of the type of drug and the mode of consumption, over the age of 18 years, who had lived in Togo for at least 3 months. Behavioural data were collected by face-to-face interviews and serum was obtained for HIV antibody testing. HIV prevalence was estimated together with its 95% confidence interval (CI). Univariate and then multivariate analyses were performed to study the factors associated with HIV prevalence. RESULTS: A total of 387 DUs participated in the survey and 235 (60.7%) of them were enrolled in Lomé, the country's capital. The median age of DUs was 32 years with an interquartile range of [25-39 years] and 10 (2.6%) were women. The mode of drug consumption was: smoking or inhaling drugs in 92.8% of cases and 2.8% of DUs used drugs by injection. HIV testing was accepted in 98.4% of cases. The estimated HIV prevalence among drugs users was 5.5%, (95% CI, 3.2-7.8%). CONCLUSION: This study, the first to be conducted among DUs in Togo, found an HIV prevalence of 5.5%, which is higher than the HIV prevalence in the general population (3.2% in 2010). Specific care of DUs is essential in order to reduce HIV prevalence in Togo.

Treatment outcomes and associated factors for hospitalization of children treated for acute malnutrition under the OptiMA simplified protocol: a prospective observational cohort in rural Niger.

Introduction: Globally, access to treatment for severe and moderate acute malnutrition is very low, in part because different protocols and products are used in separate programs. New approaches, defining acute malnutrition (AM) as mid-upper arm circumference (MUAC) < 125 mm or oedema, are being investigated to compare effectiveness to current programs. Optimizing Malnutrition treatment (OptiMA) is one such strategy that treats AM with one product - ready-to-use therapeutic food, or RUTF - at reduced dosage as the child improves. Methods: This study aimed to determine whether OptiMA achieved effectiveness benchmarks established in the Nigerien National Nutrition protocol. A prospective cohort study of children in the rural Mirriah district evaluated outcomes among children 6-59 months with uncomplicated AM treated under OptiMA. In a parallel, unconnected program in one of the two trial sites, all non-malnourished children 6-23 months of age were provided small quantity lipid-based nutritional supplements (SQ-LNS). A multivariate logistic regression identified factors associated with hospitalization. Results: From July-December 2019, 1,105 children were included for analysis. Prior to treatment, 39.3% of children received SQ-LNS. Recovery, non-response, and mortality rates were 82.3%, 12.6%, and 0.7%, respectively, and the hospitalization rate was 15.1%. Children who received SQ-LNS before an episode of AM were 43% less likely to be hospitalized (ORa=0.57; 0.39-0.85, p = 0.004). Discussion: OptiMA had acceptable recovery compared to the Nigerien reference but non-response was high. Children who received SQ-LNS before treatment under OptiMA were less likely to be hospitalized, showing potential health benefits of combining simplified treatment protocols with food-based prevention in an area with a high burden of malnutrition such as rural Niger.

Optimising the dosage of ready-to-use therapeutic food in children with uncomplicated severe acute malnutrition in the Democratic Republic of the Congo: a non-inferiority, randomised controlled trial.

Background: Current standard management of severe acute malnutrition uses ready-to-use therapeutic food (RUTF) at a single weight-based calculation resulting in an increasing amount of RUTF provided to the family as the child's weight increases during recovery. Using RUTF at a gradually reduced dosage as the child recovers could reduce costs while achieving similar growth response. Methods: We conducted an open-label, non-inferiority, randomised controlled trial in the Democratic Republic of the Congo. Children aged 6-59 months with a mid-upper-arm circumference (MUAC) of less than 115 mm or a weight-for-height z-score (WHZ) of less than -3 or bipedal oedema and without medical complication were randomly assigned (1:1 ratio) using a specially developed software and random blocks (size was kept confidential), to either the current standard treatment (increasing the RUTF amount with increasing weight) or the OptiMA strategy (decreasing the RUTF dose with increasing weight and MUAC). The main endpoint was proportion of children who achieved recovery over the 6 months follow up period, as defined as meeting the following criteria for two consecutive weeks after a minimum of 4 weeks' treatment: axillary temperature less than 37.5 °C, no bipedal oedema, and anthropometric improvement (either MUAC 125 mm or greater or WHZ -1.5 or higher). We performed analyses on the intention-to-treat (ITT) (all children) and per-protocol populations (participants who had a minimum prescription of 4 weeks' RUTF, received at least 90% of the total amount of RUTF they were supposed to receive as per the protocol, and had a maximum interval of 6 weeks between any two visits in the 6-month follow-up). The non-inferiority margin was 10%. This trial is registered at ClinicalTrials.gov, and is now closed NCT03751475. Findings: Between July 22, 2019, and January 20, 2020, 491 children were randomly assigned, of whom 482 were analysed (240 in the standard group and 242 in the OptiMA group). In the ITT analysis, 234 (98%) children in the standard group and 231 (96%) children in OptiMA recovered (difference 2.0%, 95% CI -2.0% to 6.4%). In the PP analysis, 234 (98%) children in the standard group and 228 (97%) in OptiMA recovered (difference 1.3%, 95% CI -2.3% to 5.1%). Sensitivity analyses applying the same anthropometric recovery criteria to each group also showed non-inferiority of the OptiMA strategy in ITT and PP analysis. Interpretation: This non-inferiority trial treating uncomplicated children with MUAC of less than 115 mm or a WHZ of less than -3 or bipedal oedema with decreasing RUTF dose as MUAC and weight increase demonstrated non-inferiority compared to the standard protocol in a highly food-insecure context in the Democratic Republic of the Congo. These findings add evidence on the safety of RUTF dose reduction with significant RUTF cost savings. Funding: Innocent Foundation and European Civil Protection and Humanitarian Aid Operations. Translation: For the French translation of the abstract see Supplementary Materials section.

Estimates of peripartum and postnatal mother-to-child transmission probabilities of HIV for use in Spectrum and other population-based models.

BACKGROUND: The Global Plan Towards the Elimination of New HIV Infections among Children and Keeping Their Mothers Alive aims to reduce by 2015 the number of new infections in children, in 22 priority countries, by at least 90% from 2009 levels. Mathematical models, such as Spectrum, are used to estimate national and global trends of the number of infants infected through mother-to-child transmission (MTCT). However, other modelling exercises have also examined MTCT under different settings. MTCT probabilities applied in models to populations that are assumed to receive antiretroviral interventions need to reflect the most current risk estimates. METHODS: The UNAIDS Reference Group on Estimates, Modelling and Projections held a consultation to review data on MTCT probabilities. Published literature, recent conferences and data from personal communications with principle investigators were reviewed. Based on available data, peripartum and postnatal transmission probabilities were estimated for different antiretroviral drug regimens and maternal CD4 levels including for women with incident infection. RESULTS: Incident infections occurring during pregnancy are estimated to be associated with a 30% probability of MTCT; incident infections during breast feeding lead to a 28% probability of postnatal MTCT. The 2010 WHO recommended regimens (Options A or B) are estimated to be associated with a 2% peripartum transmission probability and 0.2% transmission probability per month of breast feeding. Peripartum and postnatal transmission probabilities were lowest for women who were taking antiretroviral therapy before the pregnancy namely 0.5% peripartum and 0.16% per month of breast feeding, respectively. DISCUSSION: These updated probabilities of HIV transmission (applied to Spectrum in April 2011) will be used to estimate new child HIV infections and track progress towards the 2015 targets of the Global Plan.

Simplifying and optimising the management of uncomplicated acute malnutrition in children aged 6-59 months in the Democratic Republic of the Congo (OptiMA-DRC): a non-inferiority, randomised controlled trial.

BACKGROUND: Global access to acute malnutrition treatment is low. Different programmes using different nutritional products manage cases of severe acute malnutrition and moderate acute malnutrition separately. We aimed to assess whether integrating severe acute malnutrition and moderate acute malnutrition treatment into one programme, using a single nutritional product and reducing the dose as the child improves, could achieve similar or higher individual efficacy, increase coverage, and minimise costs compared with the current programmes. METHODS: We conducted an open-label, non-inferiority, randomised controlled trial in the Democratic Republic of the Congo. Acutely malnourished children aged 6-59 months with a mid-upper-arm circumference (MUAC) of less than 125 mm or oedema were randomly assigned (1:1), using specially developed software and random blocks (size was kept confidential), to either the current standard strategy (one programme for severe acute malnutrition using ready-to-use therapeutic food [RUTF] at an increasing dose as weight increased, another for moderate acute malnutrition using a fixed dose of ready-to-use supplementary food [RUSF]) or the OptiMA strategy (a single programme for both severe acute malnutrition and moderate acute malnutrition using RUTF at a decreasing dose as MUAC and weight increased). The primary endpoint was a favourable outcome at 6 months, defined as being alive, not acutely malnourished as per the definition applied at inclusion, and with no further episodes of acute malnutrition throughout the 6-month observation period; the endpoint was analysed in the intention-to-treat (all children) and per-protocol populations (participants who had a minimum prescription of 4 weeks' RUTF, received at least 90% of the total amount of RUTF they were supposed to receive as per the protocol, or were prescribed RUSF rations for a minimum of 4 weeks [ie, minimum of 28 RUSF sachets], and had a maximum interval of 6 weeks between any two visits in the 6-month follow-up). The non-inferiority analysis (margin 10%) was to be followed by a superiority analysis (margin 0%) if non-inferiority was concluded. This trial is registered at ClinicalTrials.gov, NCT03751475, and is now closed. FINDINGS: Between July 22 and Dec 6, 2019, 912 children were randomly assigned; after 16 were excluded, 896 were analysed (446 in the standard group and 450 in the OptiMA group). In the intention-to-treat analysis, 282 (63%) of 446 children in the standard group and 325 (72%) of 450 children in the OptiMA group had a favourable outcome (difference -9·0%, 95% CI -15·9 to -2·0). In the per protocol analysis, 161 (61%) of 264 children in the standard group and 291 (74%) of 392 children in the OptiMA group had a favourable outcome (-13·2%, -21·6 to -4·9). INTERPRETATION: In this non-inferiority trial treating children with MUAC of less than 125 mm or oedema, decreasing RUTF dose according to MUAC and weight increase proved to be a superior strategy to the standard protocol in the Democratic Republic of the Congo. These results demonstrate the safety and benefits of an approach that could substantially increase access to treatment for millions of children with acute malnutrition in sub-Saharan Africa. FUNDING: Innocent Foundation and European Civil Protection and Humanitarian Aid Operations. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Simplifying and optimising management of acute malnutrition in children aged 6 to 59 months: study protocol for a 3 arms community-based individually randomised controlled trial in decentralised Niger.

BACKGROUND: Simplified approaches of acute malnutrition (AM) treatment have been conducted over the past 5 years intending to unify processes and increase coverage among children aged 6 to 59 months without medical complication. The Optimsing treatment for Acute Malnutrition (OptiMA) and the Combined Protocol for Acute Malnutrition Study (ComPAS) are mid-upper arm circumference (MUAC)-based approaches treating children with MUAC < 125 mm or oedema with one sole product-ready-to-use therapeutic food-at a gradually tapered doses. This trial aims to compare the OptiMA and ComPAS strategies to the standard nutritional protocol of Niger assessed by a favourable outcome in the treatment of uncomplicated AM at 6 months post-randomisation and in terms of recovery rate after treatment of uncomplicated SAM (WHZ < - 3 or MUAC < 115mm or oedema) and among the most vulnerable children (MUAC < 115mm or oedema). METHODS: A non-inferiority individually randomised controlled clinical trial was conducted at the primary health centres level and in the community in the Zinder region in Niger in March 2021. Participants are children aged 6-59 months attending outpatient health centres with MUAC < 125mm or oedema without medical complications. All participants are followed for 6 months. Simplified strategies propose a gradual reduction of RUTF according to MUAC and weight in OptiMA and MUAC only in ComPAS. Favourable outcome is compositely defined at 6 months post-inclusion as being alive, not acutely malnourished by the definition applied at inclusion and without any additional episode of AM throughout the 6-month observation period. Recovery is defined throughout the 6 months post-randomisation by a minimum of 4-week duration of treatment, an axillary temperature < 37.5°C, an absence of bipedal oedema and a MUAC ≥ 125 mm for two consecutive weeks. The sample size calculation required 567 children per arm for the main objective, 295 and 384 children per arm for the secondary objectives among SAM and MUAC < 115 mm children, respectively. Per-protocol and intention-to-treat analyses will be conducted for each outcome. DISCUSSION: This trial is intending to generate much-needed evidence on various simplified and optimised AM treatment approaches and to participate in reaching a consensus on such nutrition protocols. TRIAL REGISTRATION: ClinicalTrials.gov NCT04698070 . Registered on January 6, 2021.

Incidence of relapse following a new approach to simplifying and optimising acute malnutrition treatment in children aged 6-59 months: a prospective cohort in rural Northern Burkina Faso.

The present study aimed to determine the 3-month incidence of relapse and associated factors among children who recovered under the Optimising treatment for acute MAlnutrition (OptiMA) strategy, a MUAC-based protocol. A prospective cohort of children successfully treated for acute malnutrition was monitored between April 2017 and February 2018. Children were seen at home by community health workers (CHWs) every 2 weeks for 3 months. Relapse was defined as a child who had met OptiMA recovery criteria (MUAC ≥ 125 mm for two consecutive weeks) but subsequently had a MUAC < 125 mm at any home visit. Cumulative incidence and incidence rates per 100 child-months were estimated. Multivariable survival analysis was conducted using a shared frailty model with a random effect on health facilities to identify associated factors. Of the 640 children included, the overall 3-month cumulative incidence of relapse was 6⋅8 % (95 % CI 5⋅2, 8⋅8). Globally, the incidence rate of relapse was 2⋅5 (95 % CI 1⋅9, 3⋅3) per 100 child-months and 3⋅7 (95 % CI 1⋅9, 6⋅8) per 100 child-months among children admitted with a MUAC < 115 mm. Most (88⋅6 %) relapses were detected early when MUAC was between 120 and 124 mm. Relapse was positively associated with hospitalisation, with an adjusted hazard ratio (aHR) of 2⋅06 (95 % CI 1⋅01, 4⋅26) for children who had an inpatient stay at any point during treatment compared with children who did not. The incidence of relapse following recovery under OptiMA was relatively low in this context, but the lack of a standard relapse definition does not allow for comparison across settings Closer follow-up with caretakers whose children are admitted with MUAC < 115 mm or required hospitalisation during treatment should be considered in managing groups at high risk of relapse. Training caretakers to screen their children for relapse at home using MUAC could be more effective at detecting early relapse, and less costly, than home visits by CHWs.

Ten-year attrition and antiretroviral therapy response among HIV-positive adults: a sex-based cohort analysis from eight West African countries.

INTRODUCTION: Sex differences have already been reported in sub-Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow-up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults. METHODS: We used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no-follow-up and 10-year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively. RESULTS: A total of 71,283 patients (65.8% women) contributed to 310,007 person-years of follow-up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10-year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow-up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10-year attrition throughout the 10-year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/µL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/µL in their sixth year of follow-up, whereas men failed to reach it even at the end of the 10-year follow-up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%). CONCLUSIONS: In West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex-adapted are needed for patients in care to monitor attrition, detect early high-risk groups so that they can stay in care with a durably controlled infection.

Quality of life assessment in HIV clinical research in resource-limited settings: better late than never.

Comprehensive and sustained optimal care for patients infected with HIV can now be achieved in resource-constrained settings, thanks to the sustainability of programs providing antiretroviral therapy (ART). But the primary goals of HIV virological suppression and improved survival need to be accompanied by a substantial improvement in patient's experience with HIV care and treatment. An assessment of both patients' quality of life and perceived toxicity and symptoms should now be systematically integrated into HIV clinical research in resource-constrained countries. This will allow treatment strategies aimed at optimizing the durability of response to ART in these settings to be properly evaluated and compared.