Andrew Seal

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).

Adverse Pregnancy Outcomes in an Area Where Multidrug-Resistant Plasmodium vivax and Plasmodium falciparum Infections Are Endemic

BACKGROUND Plasmodium falciparum infection exerts a considerable burden on pregnant women, but less is known about the adverse consequences of Plasmodium vivax infection. METHODS In Papua, Indonesia, where multiple drug resistance to both species has emerged, we conducted a cross-sectional hospital-based study to quantify the risks and consequences of maternal malaria. RESULTS From April 2004 through December 2006, 3046 pregnant women were enrolled in the study. The prevalence of parasitemia at delivery was 16.8% (432 of 2570 women had infections), with 152 (35.2%) of these 432 infections being associated with fever. The majority of infections were attributable to P. falciparum (250 [57.9%]); 146 (33.8%) of the infections were attributable to P. vivax, and 36 (8.3%) were coinfections with both species. At delivery, P. falciparum infection was associated with severe anemia (hemoglobin concentration, <7 g/dL; odds ratio [OR], 2.8; 95% confidence interval [95% CI], 2.0-4.0) and a 192 g (95% CI, 119-265) reduction in mean birth weight (P<.001). P. vivax infection was associated with an increased risk of moderate anemia (hemoglobin concentration, 7-11 g/dL; OR, 1.8; 95% CI, 1.2-2.9; P=.01) and a 108 g (95% CI, 17.5-199) reduction in mean birth weight (P<.019). Parasitemia was associated with preterm delivery (OR, 1.5; 95% CI, 1.1-2.0; P=.02) and stillbirth (OR, 2.3; 95% CI, 1.3-4.1; P=.007) but was not associated with these outcomes after controlling for the presence of fever and severe anemia, suggesting that malaria increases the risk of preterm delivery and stillbirth through fever and contribution to severe anemia rather than through parasitemia per se. CONCLUSIONS These observations highlight the need for novel, safe, and effective treatment and prevention strategies against both multidrug-resistant P. falciparum and multidrug-resistant P. vivax infections in pregnant women in areas of mixed endemicity.

Operational implications of using 2006 World Health Organization growth standards in nutrition programmes: secondary data analysis

Objective To assess the implications of adopting the World Health Organization 2006 growth standards in combination with current diagnostic criteria in emergency and non-emergency child feeding programmes. Design Secondary analysis of data from three standardised nutrition surveys (n=2555) for prevalence of acute malnutrition, using weight for height z score (<−2 and <−3) and percentage of the median (<80% and <70%) cut-offs for moderate and severe acute malnutrition from the National Center for Health Statistics/WHO growth reference (NCHS reference) and the new WHO 2006 growth standards (WHO standards). Setting Refugee camps in Algeria, Kenya, and Bangladesh. Population Children aged 6-59 months. Results Important differences exist in the weight for height cut-offs used for defining acute malnutrition obtained from the WHO standards and NCHS reference data. These vary according to a childs height and according to whether z score or percentage of the median cut-offs are used. If applied and used according to current practice in nutrition programmes, the WHO standards will result in a higher measured prevalence of severe acute malnutrition during surveys but, paradoxically, a decrease in the admission of children to emergency feeding programmes and earlier discharge of recovering patients. The expected impact on case fatality rates of applying the new standards in conjunction with current diagnostic criteria is unknown. Conclusions A full assessment of the appropriate use of the new WHO standards in the diagnosis of acute malnutrition is urgently needed. This should be completed before the standards are adopted by organisations that run nutrition programmes targeting acute malnutrition.

Adolescent nutrition in a rural community in Bangladesh.

The objective of this study was to assess the nutritional status of adolescent boys and girls in a rural community in Bangladesh. Between December 1996 and January 1997, a cross-sectional survey was carried out in 803 households, each containing at least one adolescent, sampled consecutively from four purposely-selected villages in Rupganj Thana, Narayanganj district. Initially, the guardians of 1483 healthy and unmarried 10–17 year old adolescents (51% boys and 49% giris) were interviewed about family structure and socio-economic status. Out of these children, 906 (47% boys and 53% girls) from 597 households were weighed, had their height and MUAC measured and were clinically examined. Blood was then collected from 861 adolescents for haemoglobin estimation. The median monthly income per person in these 597 families was approximately Taka 554 (US

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

12). Twenty seven per cent of the household heads were labourers, 21% were solvent farmers, 14% ran small scale businesses and 6% were unemployed. Sixty seven per cent of adolescents were thin (defined as BMI < 5th centile of WHO recommended reference) with 75% boys and 59% girls being affected. The percentage of thin adolescents fell from 95% at age 10 years to 12 % at age 17 years. The prevalence of stunting (height for age < 3rd centile NCHS/WHO) was 48% for both boys and girls and rose from 34% at age 10 to 65% at age 17. On clinical examination angular stomatitis was present in 46%, 27% nad glossitis, 38% had pallor, 11% ha’d dental caries, 3.2% had an conspicuously enlarged thyroid and 2.1% had eye changes of vitamin A deficiency. According to INACG (International Nutritional Anaemia Consultative Group, 1985) cut-off values, 94% of the boys and 98% of the girls were anaemic. We conclude that rural Bangladesh adolescents suffer from high rates of malnutrition and almost universal anaemia. Nutritional interventions to target this population are urgently required.

Nutritional status and age at menarche in a rural area of Bangladesh.

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.

Prevalence of wasting among under 6-month-old infants in developing countries and implications of new case definitions using WHO growth standards: a secondary data analysis

The age at menarche and its association with nutritional status in a rural area of Bangladesh was determined. A cross-sectional study was conducted in four villages of Rupganj Thana of Narayanganj district. Data was collected through October to December 1996 using a pre-tested structured questionnaire interview schedule, and nutritional status was measured by weight, height, body mass index (BMI) and physical examination. Data were obtained on 436 adolescent girls aged 10-17 years. Among them, 165 (37.8%) girls had commenced menarche. The mean age at menarche as determined by retrospective recall was 13 years SD 0.89 (n = 165). The median age at menarche determined by the status quo method was 13.0. Among the adolescents 60.1% were thin (BMI < 5th centile WHO recommended reference) and 48.2% were stunted (< 3rd centile NCHS/WHO). The mean weight and BMI were significantly higher among the menstruating girls of 13, 14 and 15 years (p < 0.01) than non-menstruating girls. The mean height was found to be significantly higher at 11-14 years among the menstruating girls (p < 0.05). A lower prevalence of angular stomatitis was found among the menstruating adolescent girls compared with the non-menstruating girls, 36.4% versus 46.5%, although this was statistically non-significant (odds ratio = 0.66, 95% CI 0.43-1.00). For glossitis, no significant difference was found. Among the menstruating girls 12.1% were suffering from menorrhagia and 31.5% from dysmenorrhoea. We conclude that the age of menarche among this rural Bangladeshi community is not as delayed as expected. Not surprisingly, menarche is associated with better nutritional status. The surveyed population had extremely high rates of undernutrition which suggests that adolescents in this and similar situations require specific intervention programmes to improve their nutritional status.The age at menarche and its association with nutritional status in a rural area of Bangladesh was determined. A cross-sectional study was conducted in four villages of Rupganj Thana of Narayanganj district. Data was collected through October to December 1996 using a pre-tested structured questionnaire interview schedule, and nutritional status was measured by weight, height, body mass index (BMI) and physical examination. Data were obtained on 436 adolescent girls aged 10-17 years. Among them, 165 (37.8%) girls had commenced menarche. The mean age at menarche as determined by retrospective recall was 13 years SD 0.89 (n=165). The median age at menarche determined by the status quo method was 13.0. Among the adolescents 60.1% were thin (BMI< 5th centile WHO recommended reference) and 48.2% were stunted (< 3rd centile NCHS/WHO). The mean weight and BMI were significantly higher among the menstruating girls of 13, 14 and 15 years (p < 0.01) than non-menstruating girls. The mean height was found to be significantly higher at 11-14 years among the menstruating girls (p < 0.05). A lower prevalence of angular stomatitis was found among the menstruating adolescent girls compared with the non-menstruating girls, 36.4% versus 46.5%, although this was statistically non-significant (odds ratio=0.66, 95% CI 0.43-1.00). For glossitis, no significant difference was found. Among the menstruating girls 12.1% were suffering from menorrhagia and 31.5% from dysmenorrhoea. We conclude that the age of menarche among this rural Bangladeshi community is not as delayed as expected. Not surprisingly, menarche is associated with better nutritional status. The surveyed population had extremely high rates of undernutrition which suggests that adolescents in this and similar situations require specific intervention programmes to improve their nutritional status.

Excess dietary iodine intake in long-term African refugees.

Objectives To determine wasting prevalence among infants aged under 6 months and describe the effects of new case definitions based on WHO growth standards. Design Secondary data analysis of demographic and health survey datasets. Setting 21 developing countries. Population 15 534 infants under 6 months and 147 694 children aged 6 to under 60 months (median 5072 individuals/country, range 1710–45 398). Wasting was defined as weight-for-height z-score <−2, moderate wasting as −3 to <−2 z-scores, severe wasting as z-score <−3. Results Using National Center for Health Statistics (NCHS) growth references, the nationwide prevalence of wasting in infant under-6-month ranges from 1.1% to 15% (median 3.7%, IQR 1.8–6.5%; ∼3 million wasted infants <6 months worldwide). Prevalence is more than doubled using WHO standards: 2.0–34% (median 15%, IQR 6.2–17%; ∼8.5 million wasted infants <6 months worldwide). Prevalence differences using WHO standards are more marked for infants under 6 months than children, with the greatest increase being for severe wasting (indicated by a regression line slope of 3.5 for infants <6 months vs 1.7 for children). Moderate infant-6-month wasting is also greater using WHO, whereas moderate child wasting is 0.9 times the NCHS prevalence. Conclusions Whether defined by NCHS references or WHO standards, wasting among infants under 6 months is prevalent in many of the developing countries examined in this study. Use of WHO standards to define wasting results in a greater disease burden, particularly for severe wasting. Policy makers, programme managers and clinicians in child health and nutrition programmes should consider resource and risk/benefit implications of changing case definitions.

The effect of body shape on weight-for-height and mid-upper arm circumference based case definitions of acute malnutrition in Ethiopian children.

OBJECTIVE To assess the iodine status of long-term refugees dependent on international food aid and humanitarian assistance. DESIGN A series of cross-sectional two-stage cluster or systematic random sample surveys which assessed urinary iodine excretion and the prevalence of visible goitre. Salt samples were also collected and tested for iodine content by titration. SETTING Six refugee camps in East, North and Southern Africa. SUBJECTS Male and female adolescents aged 10-19 years. MAIN RESULTS The median urinary iodine concentration (UIC) ranged from 254 to 1200 microg l(-1) and in five of the camps exceeded the recommended maximum limit of 300 microg l(-1), indicating excessive iodine intake. Visible goitre was assessed in four surveys where it ranged from 0.0 to 7.1%. The camp with the highest UIC also had the highest prevalence of visible goitre. The iodine concentrations in 11 salt samples from three camps were measured by titration and six of these exceeded the production-level concentration of 20 to 40 ppm recommended by the World Health Organization (WHO), but were all less than 100 ppm. CONCLUSIONS Excessive consumption of iodine is occurring in most of the surveyed populations. Urgent revision of the level of salt iodisation is required to meet current WHO recommendations. However, the full cause of excessive iodine excretion remains unknown and further investigation is required urgently to identify the cause, assess any health impact and identify remedial action.

Chronic disease outcomes after severe acute malnutrition in Malawian children (ChroSAM): a cohort study

Background: Nutritional anthropometry surveys from Somalia and Ethiopia have reported that standard weight-for-height z-score (WHZ) and mid-upper arm circumference (MUAC) case definitions return different estimates of the prevalence of acute malnutrition in pastoralist livelihood zones but similar estimates of the prevalence of acute malnutrition in the agrarian livelihood zones. A study undertaken in Somalia to investigate this finding reported that children from pastoralist livelihood zones tended to have longer limbs and lower SSRs than children from agrarian livelihood zones. Aim: The present study investigated the relationship between weight-for-height and body shape and the relationship between MUAC and body shape in different populations of Ethiopian children. Subjects and methods: Six cross-sectional nutritional anthropometry surveys were undertaken. The combined survey datasets form the study sample. Data sources were grouped according to the livelihood zone from which data originated (either settled agrarian or semi-nomadic pastoralist). Case definitions of acute malnutrition using WHZ calculated using the NCHS and WHO reference populations and MUAC uncorrected for age or height were used. The SSR was used as an index of body shape. The association between body shape and the different case definitions of acute malnutrition were investigated using standard statistical techniques. Results: Weight-for-height and MUAC case definitions yielded similar estimates of the prevalence of acute malnutrition in agrarian children but different estimates of the prevalence of acute malnutrition in pastoralist children. These populations also exhibit different SSRs. The SSR is an important predictor of weight-for-height. The SSR is a poor predictor of MUAC. Conclusion: WHZ and WHZ case status in children are associated with body shape and may overestimate the prevalence of acute malnutrition in some populations. Consideration should be given as to whether WHZ should be replaced by MUAC for the purposes of estimating the prevalence of acute malnutrition.