Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.

Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

Effect of dietary intervention on the prevalence of asymptomatic malaria among 6-18-month-old children in rural Malawi.

BACKGROUND: The complex interaction between malaria and undernutrition leads to increased mortality and morbidity rate among young children in malaria-endemic regions. Results from previous interventions suggest that improving nutritional status of young children may reduce the burden of malaria. This study tested a hypothesis that provision of lipid-based nutrient supplements (LNS) or corn-soy blend (CSB) supplementation to 6-18-month-old children in Malawi would reduce the prevalence of asymptomatic malaria among them. METHODS: A total of 840 6-month-old children were enrolled in a randomized trial. The participants received 12-month supplementation with three different daily dietary supplementations: CSB, soy-LNS, or milk-LNS, and one control group without supplementation. The prevalence rate of asymptomatic Plasmodium falciparum was determined by real-time PCR from the participant's dried blood spots (DBS) collected at the baseline and every 3 months. The global null hypothesis was tested using modified Poisson regression to estimate the prevalence ratio (PR) between the control group and three intervention groups at all ages combined. All the models were adjusted for malaria at baseline, season of DBS sample collection, site of enrolment, and household asset Z-score. RESULTS: All children combined, the prevalence of P. falciparum was 14.1% at enrollment, 8.7% at 9 months, 11.2% at 12 months, 13.0% at 15 months and 22.4% at 18 months of age. Among all samples that were taken after enrolment, the prevalence was 12.1% in control group, 12.2% in milk-LNS, 14.0% in soy-LNS, and 17.2% in CSB group. Compared to children in the control group the prevalence ratio of positive malaria tests was 1.19 (95% CI 0.81-1.74; P = 0.372) in the milk-LNS group, 1.32 (95% CI 0.88-1.96; P = 0.177) in the soy-LNS group and 1.72 (95% CI 1.19-2.49; P = 0.004) in the CSB group. CONCLUSION: The study findings do not support a hypothesis that LNS or CSB supplementation would reduce the prevalence of asymptomatic malaria among Malawian children. In contrast, there was a signal of a possible increase in malaria prevalence among children supplemented with CSB.

Barriers to accessing malaria treatment amongst school-age children in rural Malawi.

BACKGROUND: Over the last two decades, many countries have moved from malaria control toward malaria elimination. However, some sub-Saharan African countries, like Malawi, have recently seen a reversal in malaria control progress with reported increases in confirmed malaria cases. This may be the result of inadequate access to effective malaria control interventions by key population groups that perpetuate transmission. This study aimed to assess the barriers to accessing malaria treatment among school-aged children (SAC) in Malawi. METHODS: A qualitative study was conducted between September and October 2020, where data were gathered in rural Malawi using free-listing interviews, key-informant interviews, semi-structured interviews and focus group discussions. Purposively sampled participants included SAC, parents of SAC, health workers and key stakeholders at community and district levels. Interviews were digitally recorded and transcribed verbatim. Data were organized using NVivo 12 software and analysed using the thematic method. RESULTS: The study recruited 252 participants, with 156 being SAC, equally divided between boys and girls. Health system barriers to malaria treatment included long waiting hours and queues at clinics, frequent stock-outs of medical supplies, and travel time to the facility. Provider barriers included negative attitude and limited service hours. Individual and cultural barriers included fear of malaria tests and beliefs associating witchcraft as the best treatment for malaria. In addition, COVID-19-related barriers included the inability to follow preventive measures, a shift in focus from malaria to COVID-19, and fear of contracting COVID-19 and/or being tested for COVID-19 at the facility. CONCLUSIONS: This study shows most of the barriers to accessing malaria treatment among SAC are similar to those experienced by other population groups. Furthermore, COVID-19 adversely affected SAC's access to treatment. Interventions that support SAC access to prompt diagnosis and treatment are urgently needed to improve the effective control of malaria.

Genotyping of Anopheles mosquito blood meals reveals nonrandom human host selection: implications for human-to-mosquito Plasmodium falciparum transmission.

BACKGROUND: Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to human-to-mosquito transmission than others. Infection prevalence peaks in school-age children, but it is not known how often they are fed upon. Genotypic profiling of human blood permits identification of individual humans who were bitten. The present investigation used this method to estimate which human demographic groups were most responsible for transmitting malaria parasites to Anopheles mosquitoes. It was hypothesized that school-age children contribute more than other demographic groups to human-to-mosquito malaria transmission. METHODS: In a region of moderate-to-high malaria incidence in southeastern Malawi, randomly selected households were surveyed to collect human demographic information and blood samples. Blood-fed, female Anopheles mosquitoes were sampled indoors from the same houses. Genomic DNA from human blood samples and mosquito blood meals of human origin was genotyped using 24 microsatellite loci. The resultant genotypes were matched to identify which individual humans were sources of blood meals. In addition, Plasmodium falciparum DNA in mosquito abdomens was detected with polymerase chain reaction. The combined results were used to identify which humans were most frequently bitten, and the P. falciparum infection prevalence in mosquitoes that resulted from these blood meals. RESULTS: Anopheles females selected human hosts non-randomly and fed on more than one human in 9% of the blood meals. Few humans contributed most of the blood meals to the Anopheles vector population. Children ≤ 5 years old were under-represented in mosquito blood meals while older males (31-75 years old) were over-represented. However, the largest number of malaria-infected blood meals was from school age children (6-15 years old). CONCLUSIONS: The results support the hypothesis that humans aged 6-15 years are the most important demographic group contributing to the transmission of P. falciparum to the Anopheles mosquito vectors. This conclusion suggests that malaria control and prevention programmes should enhance efforts targeting school-age children and males.

Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.

OBJECTIVE: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). DESIGN: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. SETTING: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

Levels of knowledge regarding malaria causes, symptoms, and prevention measures among Malawian women of reproductive age.

BACKGROUND: Malawi is a malaria-endemic country and approximately 6 million cases are reported annually. Improving knowledge of malaria causes and symptoms, and the overall perception towards malaria and its preventive measures is vital for malaria control. The current study investigated the levels of knowledge of the causes, symptoms and prevention of malaria among Malawian women. METHODS: Data from the 2017 wave of the Malawi Malaria Indicator Survey (MMIS) were analysed. In total, 3422 women of reproductive age (15-49 years) were sampled and analysed. The levels of women's knowledge about: (1) causes of malaria; (2) symptoms of malaria; and, (3) preventive measures were assessed. The tertiles of the composite score were used as the cut-offs to categorize the levels of knowledge as 'low', 'medium' and 'high'. Multinomial logistic regression models were constructed to assess the independent factors while taking into account the complex survey design. RESULTS: Approximately 50% of all respondents had high levels of knowledge of causes, symptoms and preventive measures. The high level of knowledge was 45% for rural women and 55% for urban dwellers. After adjusting for the a wide range of factors, women of age group 15-19 years adjusted odds ratio ((aOR): 2.58; 95% Confidence Interval (CI) 1.69-3.92), women with no formal education (aOR: 3.73; 95% CI 2.20-6.33), women whose household had no television (aOR: 1.50; 95% CI 1.02-2.22), women who had not seen/heard malaria message (aOR: 1.53; 95% CI 1.20-1.95), women of Yao tribe (aOR: 1.95; 95% CI 1.10-3.46), and women from rural areas had low levels of knowledge about the causes of malaria, symptoms of malaria and preventive measures. Additionally, the results also showed that women aged 15-19 years (beta [ß] = - 0.73, standard error [SE] = 0.12); P < .0001, women with no formal education (ß = - 1.17, SE = 0.15); P < .0001, women whose household had no radio (ß = - 0.15, SE = 0.0816); P = 0.0715 and women who had not seen or heard malaria message (ß = - 0.41, SE = 0.07); P < .0001 were likely to have a lower knowledge score. CONCLUSIONS: The levels of malaria knowledge were reported to be unsatisfactory among adult women, underscoring the need to scale up efforts on malaria education. Beside insecticide-treated bed nets (ITNs) and prompt diagnosis, malaria can be best managed in Malawi by increasing knowledge of malaria causes, and symptoms especially for younger women, women with no formal education, women whose households have no media, women from Yao tribes, and rural dwellers.

Presence of Giardia lamblia in stools of six- to 18-month old asymptomatic Malawians is associated with children's growth failure.

AIM: Despite high pathogen burden and malnutrition in low-income settings, knowledge on relationship between asymptomatic viral or parasitic infections, nutrition and growth is insufficient. We studied these relationships in a cohort of six-month-old Malawian infants. METHODS: As part of a nutrient supplementation trial for 12 months, we documented disease symptoms of 840 participant daily and anthropometric measurements every three months. Stool specimens were collected every six months and analysed for Giardia lamblia, Cryptosporidium species and enterovirus, rotavirus, norovirus, parechovirus and rhinovirus using polymerase chain reaction (PCR). The prevalence of the microbes was compared to the children's linear growth and the dietary. RESULTS: The prevalence of the microbes was similar in every intervention group. All age groups combined, children negative for G. lamblia had a mean standard deviation (SD) of -0.01 (0.49) change in length-for-age Z-score (LAZ), compared to -0.12 (0.045) among G. lamblia positive children (difference -0.10, 95% CI -0.21 to -0.00, p = 0.047). The LAZ change difference was also statistically significant (p = 0.042) at age of 18-21 months but not at the other time points. CONCLUSION: Asymptomatic G. lamblia infection was mainly associated with growth reduction in certain three-month periods. The result refers to the chronic nature of G. lamblia infection.

The association of malaria morbidity with linear growth, hemoglobin, iron status, and development in young Malawian children: a prospective cohort study.

BACKGROUND: Although poor complementary feeding is associated with poor child growth, nutrition interventions only have modest impact on child growth, due to high burden of infections. We aimed to assess the association of malaria with linear growth, hemoglobin, iron status, and development in children aged 6-18 months in a setting of high malaria and undernutrition prevalence. METHODS: Prospective cohort study, conducted in Mangochi district, Malawi. We enrolled six-months-old infants and collected weekly data for 'presumed' malaria, diarrhea, and acute respiratory infections (ARI) until age 18 months. Change in length-for-age z-scores (LAZ), stunting, hemoglobin, iron status, and development were assessed at age 18 months. We used ordinary least squares regression for continuous outcomes and modified Poisson regression for categorical outcomes. RESULTS: Of the 2723 children enrolled, 2016 (74.0%) had complete measurements. The mean (standard deviation) incidences of 'presumed' malaria, diarrhea, and ARI, respectively were: 1.4 (2.0), 4.6 (10.1), and 8.3 (5.0) episodes/child year. Prevalence of stunting increased from 27.4 to 41.5% from 6 to 18 months. 'Presumed' malaria incidence was associated with higher risk of stunting (risk ratio [RR] = 1.04, 95% confidence interval [CI] = 1.01 to 1.07, p = 0.023), anemia (RR = 1.02, 95%CI = 1.00 to 1.04, p = 0.014) and better socio-emotional scores (B = - 0.21, 95%CI = - 0.39 to - 0.03, p = 0.041), but not with change in LAZ, haemoglobin, iron status or other developmental outcomes. Diarrhea incidence was associated with change in LAZ (B = - 0.02; 95% CI = - 0.03 to - 0.01; p = 0.009), stunting (RR = 1.02; 95% CI = 1.01 to 1.03; p = 0.005), and slower motor development. ARI incidence was not associated with any outcome except for poorer socio-emotional scores. CONCLUSION: In this population of young children living in a malaria-endemic setting, with active surveillance and treatment, 'presumed' malaria is not associated with change in LAZ, hemoglobin, or iron status, but could be associated with stunting and anemia. Diarrhea was more consistently associated with growth than was malaria or ARI. The findings may be different in contexts where active malaria surveillance and treatment is not provided. TRIAL REGISTRATION: NCT00945698 (July 24, 2009) and NCT01239693 (November 11, 2010).

Lipid-based Nutrient Supplements Do Not Affect Gut Bifidobacterium Microbiota in Malawian Infants: A Randomized Trial.

OBJECTIVES: The aim of the study was to assess the effect of nutritional supplementation with lipid-based nutrient supplements (LNS) and corn-soy blend flour on Bifidobacterium and Staphylococcus aureus gut microbiota composition in Malawian infants. In addition, the microbiota changes over time were characterized in the study infants. METHODS: Healthy 6-month-old Malawian infants were randomly assigned to 1 of 4 intervention schemes for a 6-month period. Infants in the control group were not provided with any supplementary food. Infants in other 3 groups received either micronutrient-fortified corn-soy blend, micronutrient-fortified LNS with milk protein base, or micronutrient-fortified LNS with soy protein base between 6 and 12 months of age. Fecal bifidobacteria and S aureus gut microbiota at 6 and 12 months of age were analyzed by quantitative real-time polymerase chain reaction method. RESULTS: There was no difference in change in bacterial prevalence or counts between the intervention groups during the 6-month study period. When looking at the total study population, higher counts of total bacteria (P = 0.028), Bifidobacterium genus (P = 0.027), B catenulatum (P = 0.031), and lower counts of B infantis (P < 0.001), B lactis (P < 0.001), B longum (P < 0.001), and S aureus (P < 0.001) were detected in the children's stools at 12 months rather than at 6 months of age. CONCLUSIONS: The dietary supplementation did not have an effect on the Bifidobacterium and S aureus microbiota composition of the study infants. The fecal bifidobacterial diversity of the infants, however, changed toward a more adult-like microbiota profile within the observed time.

Gut microbiota in Malawian infants in a nutritional supplementation trial.

OBJECTIVES: To examine whether two forms of lipid-based nutrient supplements (LNS) or a micronutrient-fortified corn-soya blend were associated with development of the gut microbiota in Malawian infants, to assess the microbiota profiles at the age of 6 and 18 months and to follow the changes during the 12-month period. METHODS: This was a substudy of a 4-arm randomised controlled trial conducted in rural Malawi. Infants at the age of 6 months were randomised to receive no supplement during the primary follow-up period (control), 54 g/day of micronutrient-fortified LNS with milk protein base (milk LNS), 54 g/day of micronutrient-fortified LNS with soya protein base (soya LNS), or 71 g/day of micronutrient-fortified corn-soya blend for 12 months. Stool samples were collected at baseline (6 months) and end of trial (18 months). The 16S rRNA gene was amplified and subjected to multiplex sequencing. RESULTS: A total of 213 infants had paired microbiota data at 6 and 18 months of age. The Dirichlet-multinomial test showed no significant difference in microbiota profile between the four intervention groups at either age (each P > 0.10). Bifidobacterium longum was most abundant at both ages. Lactobacillus ruminis, Shigella and Salmonella were present. The abundance of Prevotella and Faecalibacterium increased with age (each P < 0.001), while Bifidobacteriaceae and Enterobacteriaceae exhibited significant decrease (each P < 0.001). CONCLUSIONS: Nutritional supplementation by LNS or corn-soya blend for twelve months did not affect the gut microbiota profile in the rural Malawian context.

Distinctive Intestinal Lactobacillus Communities in 6-Month-Old Infants From Rural Malawi and Southwestern Finland.

OBJECTIVE: Our aim was to compare the composition and diversity of Lactobacillus microbiota in infants living in Malawi and Southwestern Finland. METHODS: The composition and diversity of the Lactobacillus group was analyzed in the feces of healthy 6-month-old infants living in rural Malawi (n = 44) and Southwestern Finland (n = 31), using the quantitative polymerase chain reaction method and PCR-denaturing gradient gel electrophoresis fingerprinting. RESULTS: Malawian infants had higher counts of lactobacilli than their Finnish counterparts (7.45 log cells/g vs 6.86 log cells/g, P < 0.001, respectively) and the Lactobacillus community was richer and more diverse in the Malawian infants. Leuconostoc citreum and Weissella confusa were the predominant species in both study groups, but Malawian infants were more often colonized by these species (100% vs 74.2%, P < 0.001; 95.5% vs 41.9%, P < 0.001, respectively). Moreover, Lactobacillus ruminis, Lactobacillus gasseri, Lactobacillus acidophilus, and Lactobacillus mucosae were detected more often in the Malawian infants (59.1% vs 0.0%, P < 0.001; 38.6% vs 9.7%, P = 0.004; 29.5% vs 0.0%, P < 0.001; 22.7% vs 3.2%, P = 0.017, respectively). Lactobacillus casei group species, however, were only detected in the Finnish infants. CONCLUSIONS: Malawian infants have a more abundant Lactobacillus microbiota with a distinct composition compared with Finnish infants. The environment, including diet and hygiene, may be among the factors influencing these differences.

Effect of complementary feeding with lipid-based nutrient supplements and corn-soy blend on the incidence of stunting and linear growth among 6- to 18-month-old infants and children in rural Malawi.

Low nutritional value of complementary foods is associated with high incidence of childhood growth stunting in low-income countries. This study was done to test a hypothesis that dietary complementation with lipid-based nutrient supplements (LNS) promotes linear growth and reduces the incidence of severe stunting among at-risk infants. A total of 840 6-month-old healthy infants in rural Malawi were enrolled to a randomised assessor-blinded trial. The participants received 12-month supplementation with nothing, milk-LNS, soy-LNS, or corn-soy blend (CSB). Supplements provided micronutrients and approximately 280 kcal energy per day. Outcomes were incidence of severe and very severe stunting [length-for-age z-score, (LAZ) < -3.00 and <-3.50, respectively], and change in LAZ. The incidence of severe stunting was 11.8%, 8.2%, 9.1% and 15.5% (P = 0.098) and that of very severe stunting 7.4%, 2.9%, 8.0% and 6.4% (P = 0.138) in control, milk-LNS, soy-LNS and CSB groups, respectively. Between 9 and 12 months of age, the mean change in LAZ was -0.15, -0.02, -0.12 and -0.18 (P = 0.045) for control, milk-LNS, soy-LNS and CSB groups, respectively. There was no significant between-group difference in linear growth during other age-intervals. Although participants who received milk-LNS had the lowest incidence of severe and very severe stunting, the differences between the groups were smaller than expected. Thus, the results do not provide conclusive evidence on a causal association between the LNS supplementation and the lower incidence of stunting. Exploratory analyses suggest that provision of milk-LNS, but not soy-LNS promotes linear growth among at-risk infants mainly between 9 and 12 months of age.

Lipid-based nutrient supplements do not affect the risk of malaria or respiratory morbidity in 6- to 18-month-old Malawian children in a randomized controlled trial.

BACKGROUND: There is evidence to support the use of lipid-based nutrient supplements (LNSs) to promote child growth and development in low-income countries, but there is also a concern regarding the safety of using iron-fortified products in malaria-endemic areas. OBJECTIVE: The objective of this study was to test the hypothesis that 6- to 18-mo-old rural Malawian children receiving iron-containing (6 mg/d) LNSs would not have excess morbidity compared with infants receiving no supplementation. METHODS: A randomized controlled trial allocated 840 children to receive daily supplementation with 54 g/d LNS with milk protein base (milk-LNS), 54 g/d LNS with soy protein base (soy-LNS), 71 g/d corn-soy blend (CSB), or no supplementation from 6 to 18 mo of age. Morbidity was compared using a non-inferiority margin set at 20% excess morbidity in supplemented groups compared with the nonsupplemented group. RESULTS: Baseline characteristics were similar across groups. The proportion of days with febrile illness between 6 and 18 mo was 4.9%, and there were no differences between the groups: 4.9% (95% CI: 4.3, 5.5%), 4.5% (95% CI: 3.9, 5.1%), 4.7% (95% CI: 4.1, 5.3%), and 5.5% (95% CI: 4.7-6.3%) in the milk-LNS, soy-LNS, CSB, and control groups, respectively. The proportion of days with respiratory problems and diarrhea between 6 and 18 mo also did not differ between groups. Compared with controls, the incident rate ratio (95% CI) for clinical malaria was 0.80 (0.59, 1.09), 0.77 (0.56, 1.06), and 0.79 (0.58, 1.08) in milk-LNS, soy-LNS, and CSB, respectively, with 95% CIs confirming non-inferiority. The incidence of febrile episodes, diarrhea, respiratory problems or admission to hospital, prevalence of malaria parasitemia throughout the follow-up, and mean change in hemoglobin concentration from baseline were also similar between the groups. CONCLUSIONS: Daily supplementation with 54 g of milk-based or soy protein-based LNS or 71 g of CSB did not result in increases in malaria or respiratory morbidity in children in a malaria-endemic setting. However, we could not conclude whether LNSs did or did not increase diarrheal morbidity. This trial was registered at clinicaltrials.gov as NCT00524446.

Presence of human enteric viruses in the stools of healthy Malawian 6-month-old infants.

The acquisition of intestinal microbiota is essential for infants who are also in close contact with intestinal viruses. We assayed the presence of human enteric viruses in the faeces of 44 healthy breast-fed 6-month-old infants from rural Malawi. Half of the infants tested harboured enteroviruses, although the infants had no gastric symptoms, suggesting a viral community mainly composed of human asymptomatic enteroviruses.

Providing lipid-based nutrient supplements does not affect developmental milestones among Malawian children.

AIM: To assess whether using lipid-based nutrient supplements (LNS) to complement the diets of infants and young children affected when they achieved selected developmental milestones. METHODS: In rural Malawi, 840 6-month-old healthy infants were enrolled to a randomised trial. Control participants received no supplements, others were provided with milk-containing LNS, soy-containing LNS or corn-soy blend (CSB) for 12 months. Outcomes were the age at which they achieved key milestone: motor (walking with assistance, standing and walking alone, running), social (drinking from a cup and eating by themselves) and language (saying single comprehensible words and waving goodbye). RESULTS: The mean age at which the subjects walked with assistance was 42.5, 42.3, 42.7 and 43.2 weeks in the control, milk-LNS, soy-LNS and CSB groups, respectively (p = 0.748). There were also no significant differences in the mean age at standing alone (45.0, 44.9, 45.1 and 46.3 weeks), walking alone (54.6, 55.1, 55.3, 56.5 weeks), running (64.6, 63.7, 64.8, 65.9 weeks) or any other social or language milestones (each p > 0.10). CONCLUSION: The findings do not support a hypothesis that providing tested formulations and doses of micronutrient-fortified LNS or CSB would have an impact on when young children in rural Malawi achieved selected developmental milestones.

The Impact of Antenatal Azithromycin and Monthly Sulfadoxine-Pyrimethamine on Maternal Malaria during Pregnancy and Fetal Growth: A Randomized Controlled Trial.

Maternal malaria and infections during pregnancy are risk factors for fetal growth restriction. We assessed the impact of preventive treatment in pregnancy on maternal malaria and fetal growth. Between 2003 and 2006, we enrolled 1,320 pregnant Malawian women, 14-26 gestation weeks, in a randomized trial and treated them with two doses of sulfadoxine-pyrimethamine (SP, control) at enrollment and between 28-34 gestation weeks; with monthly SP from enrollment until 37 gestation weeks; or with monthly SP and azithromycin twice, at enrollment and between 28 and 34 gestation weeks (AZI-SP). Participants were seen at 4-week intervals until 36 completed gestation weeks and weekly thereafter. At each visit, we collected dried blood spots for real-time polymerase chain reaction diagnosing of malaria parasitemia and, in a random subgroup of 341 women, we measured fetal biparietal diameter and femur length with ultrasound. For the monthly SP versus the control group, the odds ratios (OR) (95% CI) of malaria parasitemia during the second, third, and both trimesters combined were 0.79 (0.46-1.37), 0.58 (0.37-0.92), and 0.64 (0.42-0.98), respectively. The corresponding ORs for the AZI-SP versus control group were 0.47 (0.26-0.84), 0.51 (0.32-0.81), and 0.50 (0.32-0.76), respectively. Differences between the AZI-SP and the monthly SP groups were not statistically significant. The interventions did not affect fetal biparietal diameter and femur length growth velocity. The results suggest that preventive maternal treatment with monthly SP reduced malaria parasitemia during pregnancy in Malawi and that the addition of azithromycin did not provide much additional antimalarial effect.

Low length-for-age Z-score within 1 month after birth predicts hyperdynamic circulation at the age of 21 years in rural Malawi.

Low birth weight predisposes to the development of hypertension in middle- and high-income countries. We examined the relation of early life length-for-age score (Z-score) on cardiovascular function in young adults in Malawi, a low-income country. Capture of supine, seated, and standing brachial pulse waveforms (Mobil-O-Graph) were performed in 223 females and 152 males (mean age 21 years), and analyzed according to the length-for-age Z-score tertiles during the first month of life. Plasma LDL cholesterol in young adulthood was slightly lower in the lowest versus highest tertile. Otherwise, blood hemoglobin and plasma chemistry were similar in all tertiles. Irrespective of posture, blood pressure, forward and backward wave amplitudes, and pulse wave velocity were corresponding in all tertiles. In the three postures, the lowest tertile presented with 4.5% lower systemic vascular resistance than the highest tertile (p = 0.005), and 4.4% and 5.5% higher cardiac output than the middle and highest tertiles, respectively (p < 0.01). Left cardiac work was 6.8% and 6.9% higher in the lowest tertile than in the middle and highest tertiles, respectively (p < 0.01). To conclude, in a low-income environment, low length-for-age Z-score after birth predicted hyperdynamic circulation at 21 years of age without changes in blood pressure and metabolic variables.

Body composition among Malawian young adolescents: Cross-validating predictive equations for bioelectric impedance analysis using deuterium dilution method.

BACKGROUND: Body composition can be measured by several methods, each with specific benefits and disadvantages. Bioelectric impedance offers a favorable balance between accuracy, cost and ease of measurement in a range of settings. In this method, bioelectric measurements are converted to body composition measurements by prediction equations specific to age, population and bioimpedance device. Few prediction equations exist for populations in low-resource settings. We formed a prediction equation for total body water in Malawian adolescents using deuterium dilution as reference. METHODS: We studied 86 boys and 92 girls participating in the 11-14-year follow-up of the Lungwena Antenatal Intervention Study, a randomized trial of presumptive infection treatment among pregnant women. We measured body composition by Seca m515 bioimpedance analyser. Participants ingested a weight-standardized dose of deuterium oxide, after which we collected saliva at baseline, at 3 and 4 h post-ingestion, measured deuterium concentration using Fourier-transform infrared spectroscopy and calculated total body water. We formed predictive equations for total body water using anthropometrics plus resistance and reactance at a range of frequencies, applying multiple regression and repeated cross-validation in model building and in prediction error estimation. RESULTS: The best predictive model for percentage total body water (TBW %) was 100*(1.11373 + 0.0037049*height (cm)2/resistance(Ω) at 50 kHz- 0.25778*height(m)- 0.01812*BMI(kg/m2)- 0.02614*female sex). Calculation of absolute TBW (kg) by multiplying TBW (%) with body weight had better predictive power than a model directly constructed to predict absolute total body water (kg). This model explained 96.4% of variance in TBW (kg) and had a mean prediction error of 0.691 kg. Mean bias was 0.01 kg (95% limits of agreement -1.34, 1.36) for boys and -0.01 kg (1.41, 1.38) for girls. CONCLUSIONS: Our equation provides an accurate, cost-effective and participant-friendly body composition prediction method among adolescents in clinic-based field studies in rural Africa, where electricity is available.

Distinct gut microbiota in southeastern African and northern European infants.

BACKGROUND AND OBJECTIVE: The intestinal microbiota composition in infants reflects the early environment. Our objective was to compare the gut microbiota in 6-month-old infants living in rural Malawi with children of the same age living in urban Finland, both being breast-fed and having an age-appropriate diet typical for each area. METHODS: Malawian 6-month-old infants (n=44) were compared with Finnish infants (n=31) of the same age. In both cohorts, infant stool samples were available for microbiota characterization by flow cytometry-fluorescent in situ hybridization and quantitative polymerase chain reaction methods. RESULTS: Bifidobacteria were dominant at 6 months of age in all of the infants, although in greater proportions in Malawian (70.8%) than in Finnish infants (46.8%; P<0.001). Additional distinctions in bacterial group composition comprised Bacteroides-Prevotella (17.2% vs 4.7%; P<0.001) and Clostridium histolyticum (4.4% vs 2.8%; P=0.01), respectively. The species Bifidobacterium adolescentis, Clostridium perfringens, and Staphylococcus aureus were absent in Malawian but detected in Finnish infants. CONCLUSIONS: The gut microbiota of 6-month-old infants in a low-income country differs significantly from that in a high-income country. This may have an effect on both the energy harvest from the diet typifying malnutrition and diarrheal diseases in low-income countries and Western lifestyle diseases in high-income countries.