Paluku Bahwere

Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi

BACKGROUND Severe acute malnutrition affects 13 million children worldwide and causes 1-2 million deaths every year. Our aim was to assess the clinical and nutritional efficacy of a probiotic and prebiotic functional food for the treatment of severe acute malnutrition in a HIV-prevalent setting. METHODS We recruited 795 Malawian children (age range 5 to 168 months [median 22, IQR 15 to 32]) from July 12, 2006, to March 7, 2007, into a double-blind, randomised, placebo-controlled efficacy trial. For generalisability, all admissions for severe acute malnutrition treatment were eligible for recruitment. After stabilisation with milk feeds, children were randomly assigned to ready-to-use therapeutic food either with (n=399) or without (n=396) Synbiotic2000 Forte. Average prescribed Synbiotic dose was 10(10) colony-forming units or more of lactic acid bacteria per day for the duration of treatment (median 33 days). Primary outcome was nutritional cure (weight-for-height >80% of National Center for Health Statistics median on two consecutive outpatient visits). Secondary outcomes included death, weight gain, time to cure, and prevalence of clinical symptoms (diarrhoea, fever, and respiratory problems). Analysis was on an intention-to-treat basis. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN19364765. FINDINGS Nutritional cure was similar in both Synbiotic and control groups (53.9% [215 of 399] and 51.3% [203 of 396]; p=0.40). Secondary outcomes were also similar between groups. HIV seropositivity was associated with worse outcomes overall, but did not modify or confound the negative results. Subgroup analyses showed possible trends towards reduced outpatient mortality in the Synbiotic group (p=0.06). INTERPRETATION In Malawi, Synbiotic2000 Forte did not improve severe acute malnutrition outcomes. The observation of reduced outpatient mortality might be caused by bias, confounding, or chance, but is biologically plausible, has potential for public health impact, and should be explored in future studies. FUNDING Department for International Development (DfID).

Community-acquired bacteremia among hospitalized children in rural central Africa.

OBJECTIVE To describe the epidemiology of community-acquired bacteremia in children admitted to a rural hospital in central Africa and to identify useful diagnostic signs or symptoms. METHODS On admission, a blood culture was obtained from all children admitted to Childrens Hospital of Lwiro between 1989 and 1990. Clinical and biologic signs of infection and nutritional status were recorded. RESULTS Among the 779 children included in the study, 15.9% were bacteremic on admission. The rate of bacteremia was the highest among children with jaundice (20/56; 35.7%) and fever (119/487; 24.4%). In contrast, children with severe malnutrition had a lower rate of bacteremia (13.2%) than weight growth retarded or well-nourished children (19.5%) (P = 0.046). Fever was the most useful diagnostic criteria (sensitivity and negative predictive value of 96.0% and 97.8%, respectively) even in severely malnourished children (sensitivity and negative predictive value of 96.4% and 99.1%, respectively). Enterobacteriacea, mostly Salmonella spp, caused 73% of the bacteremia. There was a high rate of resistance to ampicillin and chloramphenicol among the responsible organisms. Only 31 (47.7%) of 65 bacteremic children responded to the combination of ampicillin and gentamicin. The presence of bacteremia on admission did not significantly increase the risk of morality during hospitalization (19.4% compared with 13.5%; P = 0.088). Age less than 12 months and jaundice were independent risk factors for deaths in bacteremic children. CONCLUSIONS Community-acquired bacteremia caused by multiresistant Enterobacteriacea is an important problem of hospitalized well-nourished and malnourished children in central Africa. Fever on admission is a sensitive diagnostic sign, even in malnourished children.

Follow-up of post-discharge growth and mortality after treatment for severe acute malnutrition (FuSAM study): a prospective cohort study.

Background Management of Severe Acute Malnutrition (SAM) plays a vital role in achieving global child survival targets. Effective treatment programmes are available but little is known about longer term outcomes following programme discharge. Methods From July 2006 to March 2007, 1024 children (median age 21.5 months, IQR 15–32) contributed 1187 admission episodes to an inpatient-based SAM treatment centre in Blantyre, Malawi. Long term outcomes, were determined in a longitudinal cohort study, a year or more after initial programme discharge. We found information on 88%(899/1024). Results In total, 42%(427/1024) children died during or after treatment. 25%(105/427) of deaths occurred after normal programme discharge, >90 days after admission. Mortality was greatest among HIV seropositive children: 62%(274/445). Other risk factors included age <12 months; severity of malnutrition at admission; and disability. In survivors, weight-for-height and weight-for-age improved but height-for-age remained low, mean −2.97 z-scores (SD 1.3). Conclusions Although SAM mortality in this setting was unacceptably high, our findings offer important lessons for future programming, policy and research. First is the need for improved programme evaluation: most routine reporting systems would have missed late deaths and underestimated total mortality due to SAM. Second, a more holistic view of SAM is needed: while treatment will always focus on nutritional interventions, it is vital to also identify and manage underlying clinical conditions such as HIV and disability. Finally early identification and treatment of SAM should be emphasised: our results suggest that this could improve longer term as well as short term outcomes. As international policy and programming becomes increasingly focused on stunting and post-malnutrition chronic disease outcomes, SAM should not be forgotten. Proactive prevention and treatment services are essential, not only to reduce mortality in the short term but also because they have potential to impact on longer term morbidity, growth and development of survivors.

Acceptability and effectiveness of chickpea sesame-based ready-to-use therapeutic food in malnourished HIV-positive adults

Objective: A prospective descriptive study to assess acceptability and effectiveness of a locally made ready-to-use therapeutic food (RUTF) in HIV-infected chronically sick adults (CSA) with mid-upper-arm circumference (MUAC) <210 mm or pitting edema. Methods: Sixty-three wasted AIDS adults were prescribed 500 g representing ~2600 kcal/day of locally made RUTF for three months and routine cotrimoxazole. Weight, height, MUAC, Karnofsky score and morbidity were measured at admission and at monthly intervals. The amount of RUTF intake and acceptability were assessed monthly. Results: Ninety-five percent (60/63) of the CSA that were invited to join the study agreed to participate. Mean daily intake in these 60 patients was 300 g/person/day (~1590 Kcal and 40 g of protein). Overall, 73.3% (44/60) gained weight, BMI, and MUAC. The median weight, MUAC and BMI gains after three months were 3.0 kg, 25.4 mm, and 1.1 kg/m2, respectively. The intervention improved the physical activity performance of participants and 78.3% (47/60) regained sufficient strength to walk to the nearest health facility. Mortality at three months was 18.3% (11/60). Conclusion: Locally made RUTF was acceptable to patients and was associated with a rapid weight gain and physical activity performance. The intervention is likely to be more cost effective than nutritional support using usual food-aid commodities.

Uptake of HIV testing and outcomes within a Community-based Therapeutic Care (CTC) programme to treat Severe Acute Malnutrition in Malawi: a descriptive study

BackgroundIn Malawi and other high HIV prevalence countries, studies suggest that more than 30% of all severely malnourished children admitted to inpatient nutrition rehabilitation units are HIV-infected. However, clinical algorithms designed to diagnose paediatric HIV are neither sensitive nor specific in severely malnourished children. The present study was conducted to assess : i) whether HIV testing can be integrated into Community-based Therapeutic Care (CTC); ii) to determine if CTC can improve the identification of HIV infected children; and iii) to assess the impact of CTC programmes on the rehabilitation of HIV-infected children with Severe Acute Malnutrition (SAM).MethodsThis community-based cohort study was conducted in Dowa District, Central Malawi, a rural area 50 km from the capital, Lilongwe. Caregivers and children admitted in the Dowa CTC programme were prospectively (Prospective Cohort = PC) and retrospectively (Retrospective Cohort = RC) admitted into the study and offered HIV testing and counseling. Basic medical care and community nutrition rehabilitation was provided for children with SAM. The outcomes of interest were uptake of HIV testing, and recovery, relapse, and growth rates of HIV-positive and uninfected children in the CTC programme. Students t-test and analysis of variance were used to compare means and Kruskall Wallis tests were used to compare medians. Dichotomous variables were compared using Chi2 analyses and Fishers exact test. Stepwise logistic regression with backward elimination was used to identify predictors of HIV infection (α = 0.05).Results1273 and 735 children were enrolled in the RC and PC. For the RC, the average age (SD) at CTC admission was 30.0 (17.2) months. For the PC, the average age at admission was 26.5 (13.7) months. Overall uptake of HIV testing was 60.7% for parents and 94% for children. HIV prevalence in severely malnourished children was 3%, much lower than anticipated. 59% of HIV-positive and 83% of HIV-negative children achieved discharge Weight-For-Height (WFH) ≥ 80% of the NCHS reference median (p = 0.003). Clinical algorithms for diagnosing HIV in SAM children had poor sensitivity and specificity.ConclusionCTC is a potentially valuable entry point for providing HIV testing and care in the community to HIV infected children with SAM.

Improvements in nutritional management as a determinant of reduced mortality from community-acquired lower respiratory tract infection in hospitalized children from rural central Africa.

Background: In-hospital mortality from lower respiratory tract infections (LTRI) is unacceptably high in developing countries where LTRI are still a leading cause of death. Objective: To identify new approaches to reduce in-hospital mortality of LRTI through the improvement of its management. Methods: The prospectively collected database of children admitted during an 11-year period with LRTI in a pediatric rural hospital in Central Africa was reviewed to determine the predictors of death and to evaluate the impact on mortality of 4 different protocols for the management of malnutrition. Results: During the study period, 859 children were admitted with a nonmeasles severe LRTI. In the 3-year period during which blood cultures were obtained, 29.0% of the children with LRTI were bacteremic, and multiresistant Enterobacteriaceae were recovered in 81.4% of positive blood cultures. Independent predictors of death in children without edema were age <24 months, dehydration and hepatomegaly with adjusted odds ratios (numbers in parentheses, 95% confidence interval) of 3.47 (1.70–7.08), 4.24 (2.11–8.50) and 2.90 (1.43–5.85), respectively. In those with edema, a significantly increased risk of death was noted for girls [4.31 (1.71–10.90)], in children with z-score of weight to height ≤ −3 [5.45 (1.67–17.79)] and when the serum albumin was <16 g/l [2.58 (1.01–6.58)]. The improvement in the management of malnutrition was followed by a reduction of LRTI-related mortality in children with edema from 32.4 to 8.9% (P < 0.001). In children without edema, the LRTI-related mortality decreased from ~12% to 3.5% when their diet was supplemented with micronutrients. Conclusion: This study indicates that the improvement of the management of underlying nutritional deficiencies is crucial for the reduction of the high in-hospital case fatality rate associated with severe nonmeasles LRTI. The empiric antibiotic regimen should be modified to cover for multiresistant Enterobacteriaceae.

Effectiveness of milk whey protein-based ready-to-use therapeutic food in treatment of severe acute malnutrition in Malawian under-5 children: a randomised, double-blind, controlled non-inferiority clinical trial

Abstract The cost of ready‐to‐use therapeutic food (RUTF) used in community‐based management of acute malnutrition has been a major obstacle to the scale up of this important child survival strategy. The current standard recipe for RUTF [peanut‐based RUTF (P‐RUTF )] is made from peanut paste, milk powder, oil, sugar, and minerals and vitamins. Milk powder forms about 30% of the ingredients and may represent over half the cost of the final product. The quality of whey protein concentrates 34% (WPC34) is similar to that of dried skimmed milk (DSM) used in the standard recipe and can be 25–33% cheaper. This blinded, parallel group, randomised, controlled non‐inferiority clinical trial tested the effectiveness in treating severe acute malnutrition (SAM) of a new RUTF formulation WPC‐RUTF in which WPC34 was used to replace DSM. Average weight gain (non‐inferiority margin Δ = −1.2 g kg−1 day−1) and recovery rate (Δ = −10%) were the primary outcomes, and length of stay (LOS) was the secondary outcome (Δ = +14 days). Both per‐protocol (PP) and intention‐to‐treat (ITT) analyses showed that WPC‐RUTF was not inferior to P‐RUTF for recovery rate [difference and its 95% confidence interval (CI) of 0.5% (95% CI –2.7, 3.7) in PP analysis and 0.6% (95% CI –5.2, 6.3) in ITT analysis] for average weight gain [0.2 (−0.5; 0.9) for both analyses] and LOS [−1.6 days (95% CI, −4.6, 1.4 days) in PP analysis and −1.9 days (95% CI, −4.6, 0.8 days) for ITT analysis]. In conclusion, whey protein‐based RUTF is an effective cheaper alternative to the standard milk‐based RUTF for the treatment of SAM.

Randomized controlled trial of the effectiveness of a soybean-maize-sorghum-based ready-to-use complementary food paste on infant growth in South Kivu Democratic Republic of Congo.

BACKGROUND Evidence of the effectiveness of lipid-based ready-to-use complementary foods (RUCF) at improving linear growth among infants aged 6-12 mo is scarce, and further work is warranted. OBJECTIVE The objective was to assess the effectiveness of a fortified soybean-maize-sorghum RUCF paste compared with a fortified corn soy blend (UNIMIX) porridge on the prevalence of underweight and stunting among infants in South Kivu Province, Democratic Republic of Congo. DESIGN Infants were randomly assigned at 6 mo of age to receive either RUCF (n = 691) or UNIMIX (n = 692) for 6 mo. In addition to admission and monthly anthropometric measurements, hemoglobin, triglyceride, and cholesterol were measured at enrollment and at the end of the study. RESULTS No significant differences in the prevalence of stunting (RUCF: 48.6%; UNIMIX: 46.4%; P = 0.31), the prevalence of underweight (RUCF: 20.4%; UNIMIX: 18.2%; P = 0.42), or weight gain (RUCF: 1.2 ± 0.7 kg; UNIMIX: 1.3 ± 0.7 kg; P = 0.08) were found. A small but statistically significant difference in length gain (RUCF: 5.2 ± 2.0; UNIMIX: 5.4 ± 2.0; P = 0.03) was found. No significant differences in the concentrations of hemoglobin, serum triglyceride, and serum cholesterol were found between the 2 groups. CONCLUSION No significant differences were found between the RUCF and UNIMIX in the reduction of the prevalence of stunting and underweight at 12 mo of age among rural Congolese infants. This trial was registered at controlled-trials.com as ISRCTN20267635.

Breast-milk intake of 9–10-mo-old rural infants given a ready-to-use complementary food in South Kivu, Democratic Republic of Congo

BACKGROUND Lipid-based ready-to-use foods are currently used for infant feeding, but their potential effect on breast-milk intake is not well documented. OBJECTIVE The objective was to assess the breast-milk intake of 9-10-mo-old infants given either a ready-to-use complementary food (RUCF) paste or a standard corn-soy blend (UNIMIX) porridge in South Kivu, Democratic Republic of Congo. DESIGN Infants were randomly assigned at 6 mo of age to receive either RUCF (n = 700) or UNIMIX (n = 700) for 6 mo. Breast-milk intake was measured at 9-10 mo in a subsample of 58 infants (29 from each group). Mothers received a dose of ≈30 g deuterium oxide. Predose and postdose saliva samples were collected from both mothers and infants over 2 wk. Breast-milk intake (g/d) was measured from saliva samples by using infrared spectroscopy. RESULTS Mean (±SD) breast-milk intake was not significantly (P = 0.69) different between the 2 groups: RUCF (705 ± 236 g/d) and UNIMIX (678 ± 285 g/d). Mean (±SD) nonmilk oral water intakes were 338.3 ± 251.1 and 336.4 ± 227.2 g/d for RUCF and UNIMIX, respectively (P = 0.98). CONCLUSIONS No differences in breast-milk intake were observed between infants consuming either RUCF or UNIMIX. The deuterium-dose-to-the-mother dilution technique is an affordable technique that we recommend for periodic evaluation of breast-milk intake in resource-poor settings. This trial is registered at controlled-trials.com as ISRCTN20267635.

Comparison of the effectiveness of a milk-free soy-maize-sorghum-based ready-to-use therapeutic food to standard ready-to-use therapeutic food with 25% milk in nutrition management of severely acutely malnourished Zambian children:an equivalence non-blinded cluster randomised controlled trial

Community-based Management of Acute Malnutrition using ready-to-use therapeutic food (RUTF) has revolutionised the treatment of severe acute malnutrition (SAM). However, 25% milk content in standard peanut-based RUTF (P-RUTF) makes it too expensive. The effectiveness of milk-free RUTF has not been reported hitherto. This non-blinded, parallel group, cluster randomised, controlled, equivalence trial that compares the effectiveness of a milk-free soy-maize-sorghum-based RUTF (SMS-RUTF) with P-RUTF in treatment of children with SAM, closes the gap. A statistician randomly assigned health centres (HC) either to the SMS-RUTF (n = 12; 824 enrolled) or P-RUTF (n = 12; 1103 enrolled) arms. All SAM children admitted at the participating HCs were enrolled. All the outcomes were measured at individual level. Recovery rate was the primary outcome. The recovery rates for SMS-RUTF and P-RUTF were 53.3% and 60.8% for the intention-to-treat (ITT) analysis and 77.9% and 81.8% for per protocol (PP) analyses, respectively. The corresponding adjusted risk difference (ARD) and 95% confidence interval, were -7.6% (-14.9, 0.6%) and -3.5% (-9,6., 2.7%) for ITT (P = 0.034) and PP analyses (P = 0.257), respectively. An unanticipated interaction (interaction P < 0.001 for ITT analyses and 0.0683 for PP analyses) between the study arm and age group was observed. The ARDs were -10.0 (-17.7 to -2.3)% for ITT (P = 0.013) and -4.7 (-10.0 to 0.7) for PP (P = 0.083) analyses for the <24 months age group and 2.1 (-10.3,14.6)% for ITT (P = 0.726) and -0.6 (-16.1, 14.5) for PP (P = 0.939) for the ≥24 months age group. In conclusion, the study did not confirm our hypothesis of equivalence between SMS-RUTF and P-RUTF in SAM management.