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.

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.

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.

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.

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.

Zika virus outbreak in New Caledonia and Guillain-Barré syndrome: a case-control study.

Zika virus (ZIKV) infection has been associated with neurologic disorders including Guillain-Barré syndrome (GBS). In New Caledonia during the ZIKV outbreak (2014-2015), case-control and retrospective studies have been performed to assess the link between ZIKV and GBS. Among the 15 cases included, 33% had evidence of a recent ZIKV infection compared to only 3.3% in the 30 controls involved. All patients were Melanesian, had facial diplegia and similar neurophysiological pattern consistent with acute inflammatory demyelinating polyneuropathy, and recovered well. Furthermore, during the peak of ZIKV transmission, we observed a number of GBS cases higher than the calculated upper limit, emphasizing the fact that ZIKV is now a major trigger of GBS.

Filariasis serosurvey, New Caledonia, South Pacific, 2013.

BACKGROUND: Lymphatic filariasis (LF) is a major public health problem in the Pacific. As the global prevalence of infection was not known in New Caledonia (NC), a serosurvey study was conducted by determining the prevalence of circulating filarial antigens, as recommended by the World Health Organization. FINDINGS: A cross sectional study on a 2 degree stratified sample was carried out from June to November 2013. Inclusion criteria were: individuals aged 2 to 80 y/o, who had been hospitalized or sought medical care for a non-infectious cause and who had been living in NC for more than 6 months. LF antigenic detection was performed using the immunocromatographic BinaxNOW filariasis card test (ICT). Among the 1,035 individuals tested, 7 were antigenic. The overall LF antigenic prevalence was 0.62% (CI 95% [0.60-0.63]). All patients were unrelated to each other; none of them presented clinical symptoms of LF. Four of the 7 ICT positive patients reported having travelled to LF endemic areas, 2 patients had never traveled outside NC and the last one had only traveled in non-endemic areas. For the 7 ICT positive patients, the research of microfilariae in blood smears and filarial DNA by PCR was negative. CONCLUSION: The prevalence of filarial antigenemia in NC is less than 1%, the threshold that defines the filarial endemic areas for WHO. Nevertheless, as two patients who had never travelled outside NC and one who had only travelled to non-endemic areas were antigenic, we cannot conclude that NC is totally free of LF.

Relationships Between Clinico-Epidemiological Patterns of Invasive Meningococcal Infections and Complement Deficiencies in French South Pacific Islands (New Caledonia).

PURPOSE: Invasive Meningococcal Disease (IMD) is three fold more common in New Caledonia (NC) than in metropolitan France and many IMD cases (35.7%) are due to Y and W135 serogroups. The purpose of our study was to identify IMD risk factors in NC. METHODS: A retrospective study of all IMD cases that occurred in NC between 2005 and 2011 was conducted. Socio-environmental, clinical and biological data were collected. A search for immune deficiency was proposed to all cases. IMD presentation and outcome were compared according to meningoccal serogroups and the complement deficiency status (C-deficiency). RESULTS: Sixty-six sporadic IMD cases (29 B serogroup, 20 Y or W135, 6 C, 1 A, 10 unknown) occurred in 64 patients often <24 years-old and of Melanesian origin. Five patients died (7.8%). No socio-environmental risk factors were identified. No asplenia, HIV infection or immunoglobulin deficiencies were found. Two patients had diabetes and 28 of 53 (52.8%) patients had C-deficiency including 20 (71.4%) cases of late complement component deficiency. Patients with C-deficiency were mainly Melanesian (92.8%) originating from the Loyalty Islands (62.1%). They were mostly infected with Y/W135 (42.9%) or B serogroups (32.1%). They often developed later and more severe disease than patients without C-deficiency (need for intensive cares in 60% versus 28.0% of cases, p = 0.01). CONCLUSIONS: A high prevalence of C-deficiency in the Melanesian population may explain epidemiological and clinical features of IMD in NC. Our results imply an adaptation of meningococcal vaccine strategies in NC.