Malawian Children Research Articles

Respiratory and diarrhoeal pathogens in Malawian children hospitalised with diarrhoea and association with short-term growth: A prospective cohort study

Background: Pneumonia and diarrhoea are the leading causes of childhood mortality and morbidity worldwide. The gut-lung axis is associated with disease, and these common infections, especially the parasite Cryptosporidium, are associated with malnutrition. We sought to evaluate the association of respiratory and gastrointestinal (GI) pathogens with short-term growth among children hospitalised with diarrhoeal disease. Methods: In this sub-study, we followed 27 children (two-24 months) who tested positive for Cryptosporidium spp. for eight weeks with two weekly sampling of the respiratory and GI tract. Respiratory and stool pathogens were detected using quantitative molecular methods. Nutritional outcomes were assessed as length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z-scores. Changes over the study period were compared using repeated analysis of variance and mixed effects model analysis. Results: In this period,104 sputum and stool samples were collected. All stool samples had at least one pathogen detected, with an average of 5.1 (SD 2.1) stool pathogens, compared to 84% of the sputum samples with an average 3.5 (SD 1.8). Diarrhoeagenic E. coli were the most common stool pathogens (89%), followed by Cryptosporidium (57.6%) and Adenovirus pan (41%). In sputum, Streptococcus pneumoniae was the most prevalent pathogen (84%), followed by hinovirus (56%) and Moraxella catarrhalis (50%). There was a significant change in WAZ over the follow-up period. Children who had ≥3 GI pathogens had significantly a lower LAZ mean score at enrolment (-1.8 [SD 1.4]) and across the follow-up period. No relationship between respiratory pathogens and short-term growth was observed. Out of 49 sputum samples that had ≥3 pathogens, 42 (85%) concurrent stool samples had ≥3 GI pathogens. Conclusions: Among young children hospitalised with diarrhoea, multiple GI and respiratory pathogens were prevalent over an eight-week follow-up period. The presence of more GI, but not respiratory, pathogens was significantly associated with reduced short-term growth.

Beyond early initiation: A qualitative study on the challenges of hospital-based postpartum breastfeeding support.

Improving breastfeeding practices is key to reducing child mortality globally. Sub-optimal exclusive breastfeeding rates may be associated with inadequate hospital-based postpartum breastfeeding support, particularly in resource-limited health settings such as Malawi. While almost all children in Malawi are breastfed, it is a concern that exclusive breastfeeding rates in Malawi are declining. The objective of this study is to understand postpartum breastfeeding support after delivery at Malawian hospitals from the perspectives of health workers and caregivers. We conducted a secondary analysis of a descriptive qualitative study on health worker and caregiver experiences of breastfeeding support at health facilities in southern Malawi as part of the Innovating for Maternal and Child Health in Africa Initiative. In-depth interviews following a semi-structured topic guide were conducted at three secondary-level district hospitals and one tertiary-level central hospital. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). We interviewed a total of 61 participants, including 30 caregivers and 31 health care workers. Participants shared the following themes: 1) a focus on early initiation of breastfeeding, 2) inadequate follow-up on breastfeeding practice, and 3) feasibility challenges and local solutions. There was an emphasis on early initiation of breastfeeding, which was challenged by maternal exhaustion after delivery. Study participants reported poor follow-up on breastfeeding practice after initial counselling and reacting to adverse outcomes in lieu of adequate monitoring, with a reliance on caregivers to follow-up on challenges. There was poor support for facility-based breastfeeding after initial counselling post-delivery, which revealed an overall neglect in hospital postpartum care for those considered to be in good health after initial assessment. We recommend the development of indicators to track continued facility-based breastfeeding, identify vulnerable infants at-risk of feeding problems, and strengthening care in postnatal wards, which is currently as neglected component of maternity care.

Implication of asymptomatic and clinical Plasmodium falciparum infections on biomarkers of iron status among school-aged children in Malawi

BackgroundIron status is considered as a continuum from an iron deficiency with anaemia, without anaemia, varying amounts of stored iron to iron overload. The burden of Plasmodium falciparum infections is typically high among school-aged children (SAC). Nonetheless, SAC are often less likely to be covered by malaria interventions, making them a group with an untreated reservoir of parasite transmission. This study aimed to assess the effects of asymptomatic and clinical malaria infections on biochemical markers of iron status among SAC in Malawi.MethodsData from the 2015–2016 Malawi Micronutrient Survey (MNS) was used and multivariable logistic regression models using a generalized estimating equation to account for the complex cluster survey design were constructed. Blood samples of 684 children aged 5 to 14 years old were evaluated for clinical and asymptomatic malaria infections. Furthermore, blood samples were used to estimate haemoglobin (Hb), serum ferritin (SF) and, soluble transferrin receptors (sTfR) concentrations.ResultsOf the 684 SAC analysed, approximately 42% had asymptomatic malaria, while 41.0% had clinical malaria. Anaemia (low Hb levels), iron deficiency (low SF concentration), and functional iron deficiency (high sTfR levels) were found in 20%, 5%, and 30% of the children, respectively. School-aged children with asymptomatic malaria had increased odds of being anaemic (adjusted odds ratio [aOR]: 3.71, 95% confidence interval [CI]: 2.29–5.99) and increased levels of sTfR (aOR: 3.00, 95% CI 2.01–4.47). Similarly, SAC with clinical malaria had increased odds of being anaemic (aOR: 3.54, 95% CI 2.19–5.72) and increased levels of sTfR (aOR: 3.02, 95% CI 2.02–4.52).ConclusionsBoth asymptomatic and clinical malaria were independent risk factors for anaemia and functional iron deficiency (FID). The notion that asymptomatic and clinical malaria were associated with both anaemia and FID underscores the need for public health programmers to consider adding mass screening and treatment for malaria to existing school-based health programmes.

Association between asymptomatic infections and linear growth in 18-24-month-old Malawian children.

Inadequate diet and frequent symptomatic infections are considered major causes of growth stunting in low-income countries, but interventions targeting these risk factors have achieved limited success. Asymptomatic infections can restrict growth, but little is known about their role in global stunting prevalence. We investigated factors related to length-for-age Z-score (LAZ) at 24 months by constructing an interconnected network of various infections, biomarkers of inflammation (as assessed by alpha-1-acid glycoprotein [AGP]), and growth (insulin-like growth factor 1[IGF-1] and collagen X biomarker [CXM]) at 18 months, as well as other children, maternal, and household level factors. Among 604 children, there was a continuous decline in mean LAZ and increased mean length deficit from birth to 24 months. At 18 monthsof age, the percentage of asymptomatic children who carried each pathogen was: 84.5% enterovirus, 15.5% parechovirus, 7.7% norovirus, 4.6% rhinovirus, 0.6% rotavirus, 69.6% Campylobacter, 53.8% Giardia lamblia, 11.9% malaria parasites, 10.2% Shigella, and 2.7% Cryptosporidium. The mean plasma IGF-1 concentration was 12.5 ng/ml and 68% of the children had systemic inflammation (plasma AGP concentration >1 g/L). Shigella infection was associated with lower LAZ at 24 months through both direct and indirect pathways, whereas enterovirus, norovirus, Campylobacter, Cryptosporidium, and malaria infections were associated with lower LAZ at 24 months indirectly, predominantly through increased systemic inflammation and reduced plasma IGF-1 and CXM concentration at 18 months.

Acute Malaria in Malawian Children and Adults is Characterized by Thrombocytopenia That Normalizes in Convalescence.

BackgroundPlasmodium falciparum malaria has been linked with significant perturbations of the peripheral cell-mediated immune system during acute phase. Some of these changes include lower than normal platelet counts. Although the exact mechanisms that drive thrombocytopenia in P. falciparum malaria are not fully known, a number of hypotheses have been proposed. We conducted two sets of studies with one aimed at determining platelet counts in Malawian children, and the other in adults during acute P. falciparum malaria and a month post treatment.Materials and MethodsWe recruited a total of 113 HIV-uninfected children with acute malaria [n=54 with uncomplicated malaria (UCM), n=30 with severe malarial anemia (SMA), n=29 presenting with cerebral malaria (CM)]. We also recruited 42 HIV-uninfected healthy controls. Out of the 113 participants with malaria, 73 (65%) [n=34 (63%) UCM, n=21 (70%) SMA and n=18 (62%) CM] were successfully followed-up one month after treatment. A 5mL peripheral blood sample was collected for platelet count using HMX Haematological Analyzer analysis both at baseline (acute malaria) and at follow-up a month later. Platelet counts were also determined in blood samples of 106 HIV-uninfected adults, 47 of whom presented with UCM and 29 with severe malaria (SM) and these counts were compared to those of 30 healthy controls. Of the malaria cases, platelet counts for 44 UCM and 21 SM were determined again during follow-up a month after treatment.ResultsIn both children and adults, platelet counts were significantly lower during acute disease compared to the levels in the healthy controls with the lowest levels observed in CM (children) or SM (adults). These lower than normal levels increased close to normal levels a month post treatment.ConclusionP. falciparum malaria in Malawian children and adults was characterized by profound thrombocytopenia which recovered during convalescence.

Lack of Associations between Environmental Exposures and Environmental Enteric Dysfunction among 18-Month-Old Children in Rural Malawi.

Environmental enteric dysfunction (EED) is common and contributes to linear growth faltering (stunting) and mortality among children in low-resource settings. A few studies on the environmental causes of EED have been conducted but the exact exposures that cause or predispose children to EED are context-specific and not clear. This study aimed to assess associations between selected environmental exposures and EED markers among 620 18-month-old children. This was a secondary analysis of data from Malawian children who participated in a randomized controlled trial (iLiNS-DYAD, registered at clinicaltrials.gov as NCT01239693) from birth to 18 months of age. Data on environmental exposures, including drinking water source, sanitation, exposure to animals, housing materials, season, residential area, and food insecurity were collected at enrolment. Biomarkers of EED included concentrations of calprotectin, regenerating 1B protein (REG1B), and alpha-1-antitrypsin from stool samples to assess intestinal inflammation, repair, and permeability, respectively. We performed bivariate and multivariable analyses to assess associations between environmental exposures and EED biomarkers. Adjusting for possible confounders, we did not find associations between the selected environmental exposures and the three biomarkers. These results do not provide support for our hypothesis that the studied adverse environmental exposures are associated with increased concentrations of children’s EED markers in rural Malawi.

Safety and immunogenicity of a typhoid conjugate vaccine among children aged 9 months to 12 years in Malawi: a nested substudy of a double-blind, randomised controlled trial

SummaryBackgroundTyphoid fever is a substantial public health problem in Africa, yet there are few clinical trials of typhoid conjugate vaccine (TCV). We assessed immunogenicity and safety of Typbar TCV in Malawi.MethodsThis substudy was nested within a phase 3, double-blind, parallel design, randomised controlled trial of TCV in children from Ndirande Health Centre in Ndirande township, Blantyre, Malawi. To be eligible, participants had to be aged between 9 months and 12 years with no known immunosuppression or chronic health conditions, including HIV or severe malnutrition; eligible participants were enrolled into three strata of approximately 200 children (9–11 months, 1–5 years, and 6–12 years), randomly assigned (1:1) to receive TCV or control (meningococcal serogroup A conjugate vaccine [MCV-A]) intramuscularly. Serum was collected before vaccination and at 28 days and 730–1035 days after vaccination to measure anti-Vi antibodies by ELISA. Because of COVID-19, day 730 visits were extended up to 1035 days. This nested substudy evaluated reactogenicity, safety, and immunogenicity by age stratum. Safety outcomes, analysed in the intention-to-treat population, included solicited adverse events within 7 days of vaccination (assessed on 3 separate days) and unsolicited adverse events within 28 days of vaccination. This trial is registered with ClinicalTrials.gov, NCT03299426.FindingsBetween Feb 22 and Sept 6, 2018, 664 participants were screened, and 631 participants were enrolled and randomly assigned (320 to the TCV group and 311 to the MCV-A group). 305 participants in the TCV group and 297 participants in the MCV-A group were vaccinated. Among TCV recipients, anti-Vi IgG geometric mean titres increased more than 500 times from 4·2 ELISA units (EU)/mL (95% CI 4·0–4·4) at baseline to 2383·7 EU/mL (2087·2–2722·3) at day 28, then decreased to 48·0 EU/mL (39·9–57·8) at day 730–1035, remaining more than 11 times higher than baseline. Among MCV-A recipients, anti-Vi IgG titres remained unchanged: 4·3 EU/mL (4·0–4·5) at baseline, 4·4 EU/mL (4·0–4·7) on day 28, and 4·6 EU/mL (4·2–5·0) on day 730–1035. TCV and MCV-A recipients had similar solicited local (eight [3%] of 304, 95% CI 1·3–5·1 and three [1%] of 293, 0·4–3·0) and systemic (27 [9%] of 304, 6·2–12·6 and 27 [9%] of 293, 6·4–13·1) reactogenicity. Related unsolicited adverse events occurred similarly in TCV and MCV-A recipients in eight (3%) of 304 (1·3–5·1) and eight (3%) of 293 (1·4–5·3).InterpretationThis study provides evidence of TCV safety, tolerability, and immunogenicity up to 730–1035 days in Malawian children aged 9 months to 12 years.FundingBill & Melinda Gates Foundation.

Characterization of Lymphocyte Subsets in Lymph Node and Spleen Sections in Fatal Pediatric Malaria.

Secondary lymphoid tissues play a major role in the human immune response to P. falciparum infection. Previous studies have shown that acute falciparum malaria is associated with marked perturbations of the cellular immune system characterized by lowered frequency and absolute number of circulating T cell subsets. A temporary relocation of T cells, possibly by infiltration to secondary lymphoid tissue, or their permanent loss through apoptosis, are two proposed explanations for this observation. We conducted the present study to determine the phenotype of lymphocyte subsets that accumulate in the lymph node and spleen during acute stages of falciparum malaria infection in Malawian children, and to test the hypothesis that lymphocytes are relocated to lymphoid tissues during acute infection. We stained tissue sections from children who had died of the two common clinical forms of severe malaria in Malawi, namely severe malarial anemia (SMA, n = 1) and cerebral malaria (CM, n = 3), and used tissue sections from pediatric patients who had died of non-malaria sepsis (n = 2) as controls. Both lymph node and spleen tissue (red pulp) sections from CM patients had higher percentages of T cells (CD4+ and CD8+) compared to the SMA patient. In the latter, we observed a higher percentage of CD20+ B cells in the lymph nodes compared to CM patients, whereas the opposite was observed in the spleen. Both lymph node and spleen sections from CM patients had increased percentages of CD69+ and CD45RO+ cells compared to tissue sections from the SMA patient. These results support the hypothesis that the relocation of lymphocytes to spleen and lymph node may contribute to the pan-lymphopenia observed in acute CM.

The potential of spot urine as a biomarker for zinc assessment in Malawian children and adults.

Population-level assessment of zinc deficiency remains a challenge due to the lack of suitable biomarkers. Spot urinary zinc concentration (UZC) has the potential to provide information on population zinc status in large-scale surveys, but there is no established cut-off point indicating deficiency. A strong correlation between this biomarker and an established biomarker such as serum zinc concentration (SZC) in paired samples (i.e., from the same individual), could identify the thresholds indicating zinc deficiency. This study, therefore, aimed to regress spot UZC from school-aged children and women from the Malawi micronutrient survey with paired SZC data using a linear mixed-effects model. The nested variance components indicated no linear relationship between the UZC and SZC data, irrespective of adjustments for inflammation and hydration. Thresholds of urinary zinc excretion that have been suggested by expert panels were applied to the spot UZC data, as a post-hoc analysis. The zinc deficiency prevalence estimates derived from these suggested thresholds were not similar to the estimates from the SZC data, and further research is required to understand whether spot UZC can still provide useful information in population zinc assessment.

Association between intestinal bacterial carriage, biomarkers of environmental enteric dysfunction, and stunting in rural Malawian children

Background. Available data from murine studies suggest that intestinal bacteria may have a role in modulating growth phenotypes in the host. We investigated the prevalence of four gut bacteria known in murine models to impair growth (Bifidobacterium longum, Faecalibacterium prausnitzii, Dorea formicigenerans, and Akkermansia muciniphila), the level of fecal biomarkers of environmental enteric dysfunction (EED) and stunting in rural Malawian children. Methods. DNA and protein were extracted from fecal samples of rural Malawian children (aged 1-59 months) at a baseline cross-sectional survey in the Mangochi district of Malawi conducted within the framework of the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial. Intestinal carriage of bacteria was measured by PCR. Neopterin (NEO), myeloperoxidase (MPO), and alpha-1 antitrypsin (AAT), biomarkers of EED, were measured by an enzyme-linked immunosorbent assay (ELISA) test. Height-for-age Z (HAZ) score <-2 defined stunting. Tests of proportions and regression models were used to explore the relationship between bacterial carriage, EED, and stunting. Results. Fecal samples from 613 children were available for laboratory analyses. F. prausnitzii and D. formicigenerans were prevalent in over 70% of children while B. longum was the least prevalent. B. longum carriage in younger children was associated with elevated EED biomarkers. Two thirds of children had elevated NEO, 33% had elevated MPO, and 16% had elevated AAT. Stunting was found in 38%. No significant associations were found between EED biomarkers or intestinal bacteria carriage and stunting. Conclusion. Intestinal carriage of these four bacteria was not associated with stunting in Malawian children. Carriage was also not associated with EED, nor EED biomarker levels associated with stunting. Further factors acting in concert are necessary to impact EED, perturb growth, and alter gut bacterial carriage.

Trends and patterns of stunted only and stunted-underweight children in Malawi: A confirmation for child nutrition practitioners to continue focusing on stunting

AimTo analyse the trends and patterns of stunted only and stunted-underweight children in Malawi between the 2000 and 2015. MethodsThe study used the 2000 and 2015 Malawi Demographic and Health Survey data and employed bivariate and multivariate statistical analysis techniques to explore the difference in the levels of stunted only and stunted-underweight children and key socio-economic factors between 2000 and 2015 and identify key attributes of being stunted only and being stunted-underweight. ResultsThe percentage of stunted only was 37.2% in 2000 and 26.8% in 2015 and the stunted-underweight percentage was 14.5% in 2000 and 8.8% in 2015. Out of the 6.9% children classified as wasted, 2.4% were also underweight and stunted, 2.4% were underweight and 2.1% did not have any other forms of undernutrition. The analysis did not identify any children that were both stunted and wasted. Only 0.7% in 2000 and 0.4% in 2015 were underweight and free of any other forms of undernutrition. There were improvements in mother education level and mother weight during this time-period which may explain the improvements in child nutritional status. ConclusionThe most common form of undernutrition is stunting and nearly all children that are underweight are also stunted. Child nutrition practitioners and health professionals should consider focusing on tackling child stunting.

The Effects of 1 Egg per Day on Iron and Anemia Status among Young Malawian Children: A Secondary Analysis of a Randomized Controlled Trial

ABSTRACTBackgroundYoung children with diets lacking diversity with low consumption of animal source foods are at risk of iron deficiency anemia (IDA).ObjectivesOur objectives were to determine the impact of supplementing diets with 1 egg/d on 1) plasma ferritin, soluble transferrin receptor (sTfR), body iron index (BII), and hemoglobin concentrations and 2) the prevalence of iron deficiency (ID), anemia, and IDA.MethodsMalawian 6–9-mo-old infants in the Mazira trial (clinicaltrials.gov; NCT03385252) were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329). In this secondary analysis, hemoglobin, plasma ferritin, sTfR, C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) were measured at enrollment and 6-mo follow-up. Iron biomarkers were corrected for inflammation. Ferritin, sTfR, BII, and hemoglobin were compared between groups using linear regression. Prevalence ratios (PRs) for anemia (hemoglobin <11 g/dL) and ID (ferritin <12 µg/L, sTfR >8.3 mg/L, or BII <0 mg/kg) between groups were compared using log binomial or modified Poisson regression.ResultsA total of 585 children were included in this analysis (Egg: n = 286; Control: n = 299). At enrollment, the total prevalence of anemia was 61% and did not differ between groups. At 6-mo follow-up, groups did not differ in geometric mean concentration of hemoglobin [mean (95% CI); Egg: 10.9 (10.7, 11.1) g/dL; Control: 11.1 (10.9, 11.2) g/dL] and inflammation-adjusted ferritin [Egg: 6.52 (5.98, 7.10) µg/L; Control: 6.82 (6.27, 7.42) µg/L], sTfR [Egg: 11.34 (10.92, 11.78) mg/L; Control: 11.46 (11.04, 11.89) mg/L] or BII [Egg: 0.07 (0.06, 0.09) mg/kg; Control: 0.07 (0.05, 0.08) mg/kg]. There were also no group differences in anemia [Egg: 46%; Control 40%; PR: 1.15 (95% CI: 0.96, 1.38)], ID [PR: 0.99 (0.94, 1.05)], or IDA [PR: 1.12 (0.92, 1.36)].ConclusionsProviding eggs daily for 6 mo did not affect iron status or anemia prevalence in this context. Other interventions are needed to address the high prevalence of ID and anemia among young Malawian children. This trial is registered at http://www.clinicaltrials.gov as NCT03385252.

Frequency of Small Fish Consumption Is Associated With Improved Iron and Hemoglobin in Young Malawian Children

ObjectivesOur objective was to assess whether fish and meat consumption over 6mo was associated with plasma ferritin, soluble transferrin receptor (sTfR), hemoglobin (Hb), iron deficiency (ID), and anemia in a population of young Malawian children with a high (>50%) prevalence of iron deficiency anemia.MethodsThis secondary data analysis includes 585 Malawian infants, age 6–9mo, from a 6mo egg feeding trial. At enrollment and 6mo follow-up, 24hr dietary recalls and blood draws were conducted. Days with any small fish, large fish, or meat consumption were reported weekly in 7-day food frequency questionnaires. The % of days with flesh food consumption were totaled for each child. Plasma ferritin, sTfR, and Hb were assessed for associations with the % of days with small fish, large fish, and meat intake using linear regression. Prevalence ratios (PR) of ID (ferritin < 12µg/L or sTfR > 8.3 mg/L) and anemia (Hb< 11g/dL) were compared for each flesh food category using log binomial or modified Poisson regression.ResultsThe % of children with observed intake of small fish (4%), large fish (1%), and meat (2%) from 24-hr recalls at enrollment increased to 40%, 12%, and 9%, respectively, at the 6mo follow-up. Over 6mo, children averaged consumption of small fish, large fish, and meat on 25%, 8%, and 6% of days, respectively. More frequent intake of small fish was associated with higher Hb [geometric mean ratio (95% CI) per 10 percentage point difference: 1.01 g/dL (1.00, 1.01)] and lower sTfR [0.98 mg/L (0.96, 1.00)] but was not associated with ferritin concentration [1.03 µg/L (0.99, 1.07)]; nor was it associated with the prevalence of ID [PR (95% CI): 0.99 (0.97, 1.01)] or anemia [0.94 (0.88, 1.01)]. More frequent consumption of large fish was associated with a higher prevalence of anemia [1.09 per 10 percentage point difference in frequency, (1.00, 1.18)] but was not associated with ID [0.96 (0.92, 1.00)]. Meat consumption was predominantly chicken and not associated with iron or anemia indices.ConclusionsSmall fish are a primary contributor to total flesh food intake of young Malawian children and may provide modest improvements to iron status and hemoglobin. Meat and large fish were infrequently consumed and not associated with ID.Funding SourcesBill & Melinda Gates Foundation.

Examining Challenges that Affect the Implementation of the National Reading Programme by Teachers: A Case of Selected Schools in Malawi

The Ministry of Education, Science and Technology (MoEST) in Malawi introduced the National Reading Programme (NRP) in 2015 to improve early grade learners’ literacy skills. However, results from the 2017 and 2018 national reading assessment for Standard 2, Standard 4, and the NRP monitoring strategy revealed that the state of reading achievement was still below average. This study therefore examined challenges that affect the implementation of NRP by teachers. The study was qualitative in nature and was guided by the Social Constructivist Theory. Data was collected through semi-structured interviews with sixteen teachers, four head teachers, two Primary Education Advisors (PEAs) and one NRP Officer. Documentary analysis and classroom observations were done to triangulate data collected through interviews.The study revealed that improvements in aspects of education systems including proper training and distribution of teachers, improved school infrastructure and community involvement, etc., are certainly necessary to achieve universal literacy. The study also suggested that it is only through everyone’s hard work and commitment that would ensure the realisation of the important goal of having all Malawian children be able to read and write.The study is important because it provides a set of principles of learning about ideas and practices that promote learners’ academic achievement in reading and writing. Another anticipated value of the study is that it aggregates previous relevant studies on the problems surrounding language curriculum implementation and synthesises the findings of previous studies.

Prevalence of Cardiac Dysfunction in Malawian Children With Severe Febrile Illness.

To investigate the prevalence of left ventricular systolic dysfunction (LVSD) in Malawian children with severe febrile illness and to explore associations between LVSD and mortality and lactate levels. Prospective observational study. Pediatric ward of a tertiary government referral hospital in Malawi. Children between 60 days and 10 years old with severe febrile illness (fever with at least one sign of impaired perfusion plus altered mentation or respiratory distress) were enrolled at admission from October 2017 to February 2018. Focused cardiac ultrasound (FoCUS) was performed, and serum lactate was measured for each child at enrollment, with repeat FoCUS the following day. LV systolic function was later categorized as normal, reduced, severely reduced, or hyperdynamic by two pediatric cardiologists blinded to clinical course and outcomes. Fifty-four children were enrolled. LVSD was present in 14 children (25.9%; 95% CI, 15.4-40.3%), of whom three had severely reduced function. Thirty patients (60%) had a lactate greater than 2.5 mmol/L, of which 20 (40%) were markedly elevated (>5 mmol/L). Ten children died during admission (18.5%). Of children who survived, 22.7% had decreased LV systolic function versus 40% of those who died. Dysfunction was not associated with mortality or elevated lactate. Cardiac dysfunction may be present in one in four Malawian children with severe febrile illness, and mortality in these patients is especially high. Larger studies are needed to further clarify the role cardiac dysfunction plays in mortality and integrate practical bedside assessments for decision support around individualized resuscitation strategies.

Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status.

ObjectiveTo investigate survival in children referred from primary care in Malawi, with a focus on hypoglycaemia and hypoxaemia progression.MethodsThe study involved a prospective cohort of children aged 12 years or under referred from primary health-care facilities in Mchinji district, Malawi in 2019 and 2020. Peripheral blood oxygen saturation (SpO2) and blood glucose were measured at recruitment and on arrival at a subsequent health-care facility (i.e. four hospitals and 14 primary health-care facilities). Children were followed up 2 weeks after discharge or their last clinical visit. The primary study outcome was the case fatality ratio at 2 weeks. Associations between SpO2 and blood glucose levels and death were evaluated using Cox proportional hazards models and the treatment effect of hospitalization was assessed using propensity score matching.FindingsOf 826 children recruited, 784 (94.9%) completed follow-up. At presentation, hypoxaemia was moderate (SpO2: 90–93%) in 13.1% (108/826) and severe (SpO2: < 90%) in 8.6% (71/826) and hypoglycaemia was moderate (blood glucose: 2.5–4.0 mmol/L) in 9.0% (74/826) and severe (blood glucose: < 2.5 mmol/L) in 2.3% (19/826). The case fatality ratio was 3.7% (29/784) overall but 26.3% (5/19) in severely hypoglycaemic children and 12.7% (9/71) in severely hypoxaemic children. Neither moderate hypoglycaemia nor moderate hypoxaemia was associated with mortality.ConclusionPresumptive pre-referral glucose treatment and better management of hypoglycaemia could reduce the high case fatality ratio observed in children with severe hypoglycaemia. The morbidity and mortality burden of severe hypoxaemia was high; ways of improving hypoxaemia identification and management are needed.

Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: a randomized, triple-blinded, controlled clinical trial

ABSTRACTBackgroundThere is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for the treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery.ObjectivesWe tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high-oleic (HO) peanuts without added DHA (HO-RUTF) or with added DHA (DHA-HO-RUTF), improves cognition when compared with standard RUTF (S-RUTF).MethodsA triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF: DHA-HO-RUTF, HO-RUTF, and S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global z-score and a modified Willatts problem-solving assessment (PSA) intention score for 3 standardized problems, measured 6 mo and immediately after completing RUTF therapy, respectively. MDAT domain z-scores, plasma fatty acid content, anthropometry, and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF.ResultsAmong the 2565 SAM children enrolled, mean global MDAT z-scores were –0.69 ± 1.19 and –0.88 ± 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI: 0.01, 0.38). Children receiving DHA-HO-RUTF had higher gross motor and social domain z-scores than those receiving S-RUTF. The PSA problem 3 scores did not differ by dietary group (OR: 0.92, 95% CI: 0.67, 1.26 for DHA-HO-RUTF). After 4 wk of treatment, plasma phospholipid EPA and α-linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared with S-RUTF (for all 4 comparisons P values < 0.001), but only plasma DHA was greater in DHA-HO-RUTF than S-RUTF (P < 0.001).ConclusionsTreatment of uncomplicated SAM with DHA-HO-RUTF resulted in an improved MDAT score, conferring a cognitive benefit 6 mo after completing diet therapy. This treatment should be explored in operational settings. This trial was registered at clinicaltrials.gov as NCT03094247.

Identifying modifiable risk factors for mortality in children aged 1–59 months admitted with WHO-defined severe pneumonia: a single-centre observational cohort study from rural Malawi

ObjectiveAlthough HIV infection, severe malnutrition and hypoxaemia are associated with high mortality in children with WHO-defined severe pneumonia in sub-Saharan Africa, many do not have these conditions and yet mortality...

Iron Bioavailability from Infant Cereals Containing Whole Grains and Pulses: A Stable Isotope Study in Malawian Children

BackgroundCompared with infant cereals based on refined grains, an infant cereal containing whole grains (WGs) and pulses with adequate amounts of ascorbic acid to protect against absorption inhibitors could be a healthier source of well-absorbed iron. However, iron absorption from such cereals is uncertain. ObjectiveWe measured iron bioavailability from ferrous fumarate (Fefum) added to commercial infant cereals containing 1) refined wheat flour (reference meal), 2) WG wheat and lentil flour (WG-wheat-lentil), 3) WG wheat and chickpea flour (WG-wheat-chickpeas), and 4) WG oat flour (WG-oat) and from ferrous bisglycinate (FeBG) added to the same oat-based cereal (WG-oat-FeBG). MethodsIn a prospective, single-blinded randomized crossover study, 6- to 14-mo-old Malawian children (n = 30) consumed 25-g servings of all 5 test meals containing 2.25 mg stable isotope-labeled iron and 13.5 mg ascorbic acid. Fractional iron absorption (FIA) was assessed by erythrocyte incorporation of isotopes after 14 d. Comparisons were made using linear mixed models. ResultsSeventy percent of the children were anemic and 67% were iron deficient. Geometric mean FIA percentages (–SD, +SD) from the cereals were as follows: 1) refined wheat, 12.1 (4.8, 30.6); 2) WG-wheat-lentil, 15.8 (6.6, 37.6); 3) WG-wheat-chickpeas, 12.8 (5.5, 29.8); and 4) WG-oat, 9.2 (3.9, 21.5) and 7.4 (2.9, 18.9) from WG-oat-FeBG. Meal predicted FIA (P ≤ 0.001), whereas in pairwise comparisons, only WG-oat-FeBG was significantly different compared with the refined wheat meal (P = 0.02). In addition, FIAs from WG-wheat-lentil and WG-wheat-chickpeas were significantly higher than from WG-oat (P = 0.002 and P = 0.04, respectively) and WG-oat-FeBG (P < 0.001 and P = 0.004, respectively). ConclusionIn Malawian children, when given with ascorbic acid at a molar ratio of 2:1, iron bioavailability from Fefum-fortified infant cereals containing WG wheat and pulses is ≈13−15%, whereas that from FeBG- and Fefum-fortified infant cereals based on WG oats is ≈7−9%.

Delayed presentation to hospital care is associated with sequelae but not mortality in children with cerebral malaria in Malawi

BackgroundCerebral malaria is still a major cause of death in children in sub-Saharan Africa. Among survivors, debilitating neurological sequelae can leave children with permanent cognitive impairments and societal stigma, resulting in taxing repercussions for their families. This study investigated the effect of delay in presentation to medical care on outcome in children with cerebral malaria in Malawi.MethodsThis retrospective study included participants enrolled in a longstanding study of cerebral malaria between 2001 and 2021 and considered coma duration prior to arrival at hospital (with or without anti-malarial treatment), HIV status, blood lactate levels at admission and age as factors that could affect clinical outcome. Outcomes were categorized as full recovery, sequelae at the time of discharge, or death. A multinomial regression was fit and run controlling for coma duration, HIV status, lactate levels and age, to determine the association between each explanatory variable and outcome.ResultsA total of 1663 children with cerebral malaria, aged 6 months to 14 years were included. Longer coma duration (in hours) was associated with greater odds of developing sequelae (OR = 1.023, 95% CI 1.007–1.039, p = 0.006) but not death (OR = 1.00, 95% CI 0.986–1.015, p = 0.961). Younger age (in months) was also correlated with higher rates of sequelae, (OR = 0.990, 95% CI 0.983–0.997, p = 0.004) but not with increased mortality (OR = 0.998, 95% CI 0.993–1.003, p = 0.335). Blood lactate levels on admission were correlated with mortality (OR = 1.125, 95% CI 1.090–1.161, p < 0.001) but not associated with increased rates of sequelae (OR = 1.016, 95% CI 0.973–1.060, p = 0.475). Positive HIV status and treatment with an anti-malarial (artemisinin or non-artemisinin-based) prior to arrival at the hospital were not significantly associated with either adverse outcome.ConclusionsIn Malawian children with cerebral malaria, higher rates of sequelae were significantly associated with extended coma duration prior to admission and younger age. Mortality rates were correlated with increased lactate levels on admission. The differential effects of variables on clinical outcomes suggest that there may be different pathogenic pathways leading to sequelae and death. Actions taken by parents and health care professionals are critical in defining when patients arrive at hospital and determining their ultimate outcome.