Effect of milk protein and whey permeate in large quantity lipid-based nutrient supplement on linear growth and body composition among stunted children: A randomized 2 × 2 factorial trial in Uganda.

BACKGROUND: Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children. METHODS AND FINDINGS: We performed a randomized, double-blind, 2 × 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) -3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p < 0.001) kg/m2 increase in fat mass index (FMI), but 0.06 (95% CI [-0.002; 0.12]; p = 0.057) kg/m2 decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [-0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [-0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were -0.08 (95% CI [-0.21, 0.05]; p = 220) cm and -0.2 (95% CI [-0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m2, 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m2, 95% CI [-0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration. CONCLUSIONS: Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered. TRIAL REGISTRATION: ISRCTN13093195.

Nutritional status of young children born with low birthweight in a low resource setting: an observational study.

OBJECTIVE: Every year, an estimated 20 million babies are born with low birthweight and this number is increasing globally. Survivors are at risk of lifelong morbidities like undernutrition. We assessed the growth and nutritional status for children born with low birthweight at Mulago Hospital, Uganda. METHODS: We conducted a cross sectional study to describe the nutritional status of children aged between 22 and 38 months and born weighing ≤ 2000 g. Anthropometric measurements; weight for height, height for age and weight for age z-scores were generated based on the World Health Organization standards to define wasting, stunting and underweight respectively. Data was collected using a structured questionnaire and analysis was done using STATA version 14. RESULTS: Of the 251 children, 129 (51.4%) were male, mean age was 29.7 months SD 4.5) and maternal mean age was 29.9 (SD 5.3). A total of 101(40.2%) had normal nutritional status. The prevalence of wasting, underweight and stunting were: 8 (3.2%), 36 (14.4%) and 106 (42.2%) respectively. CONCLUSION: Six of ten children born with low birthweight were at risk of undernutrition in early childhood: underweight and stunting were higher than the national prevalence. Targeted interventions are needed for children with very low birth weight.

Thymus size and its correlates among children admitted with severe acute malnutrition: a cross-sectional study in Uganda.

BACKGROUND: Malnutrition continues to be a major cause of mortality and morbidity among children in resource limited settings. Children with severe acute malnutrition (SAM) experience severe thymus atrophy, possibly reflecting poor immune function. This immune dysfunction is responsible for the severe infections they experience which lead to mortality. Since their immune dysfunction is not fully understood and there has been a lapse in research in this field, more research is needed. Knowing the correlates of thymus size may help clinicians identify those with more severe atrophy who might have more severe immune impairment. We aimed to describe thymus size and its correlates at admission among children hospitalized with SAM. METHODS: This cross-sectional study involved children 6-59 months admitted with complicated SAM in Mulago National Referral Hospital. Well-nourished children from same communities were used as a community reference group for thymus size. At admission, thymus size was measured by ultrasound scan. Demographic, clinical and laboratory variables were identified at admission. A linear regression model was used to determine correlates of thymus size among children with SAM. RESULTS: Among 388 children with SAM, the mean age was 17±8.5 months and 58% were boys. The mean thymus size was 3.14 (95% CI 2.9; 3.4) cm2 lower than that of the 27 healthy community reference children (1.06 vs 4.2 cm2, p<0.001) when controlled for age. Thymus size positively correlated with current breastfeeding (0.14, 95% CI 0.01, 0.26), anthropometric measurements at admission (weight, length, mid-upper-arm circumference, weight-for-height Z scores and length-for-age Z scores) and suspected tuberculosis (0.12, 95% CI 0.01; 0.22). Thymus size negatively correlated with > 2 weeks duration of sickness (-0.10; 95% CI -0.19; -0.01). CONCLUSION: The thymus is indeed a barometer for nutrition since all anthropometric measurements and breastfeeding were associated with bigger thymus. The immune benefits of breastfeeding among children with SAM is underscored. Children with longer duration of illness had a smaller thymus gland indicating that infections have a role in the cause or consequence of thymus atrophy.

Cryptococcal meningitis and immune reconstitution inflammatory syndrome in a pediatric patient with HIV after switching to second line antiretroviral therapy: a case report.

BACKGROUND: Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published. CASE PRESENTATION: A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free. CONCLUSIONS: We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.

Diarrhea, Dehydration, and the Associated Mortality in Children with Complicated Severe Acute Malnutrition: A Prospective Cohort Study in Uganda.

OBJECTIVE: To assess predictors of diarrhea and dehydration and to investigate the role of diarrhea in mortality among children with complicated severe acute malnutrition. STUDY DESIGN: A prospective cohort study, nested in a probiotic trial, was conducted in children with complicated severe acute malnutrition. Children were treated according to World Health Organization and national guidelines, and diarrhea and dehydration were assessed daily. Multiple linear and log-linear Poisson regression models were used to identify predictors of days with diarrhea and dehydration, respectively, and multiple logistic regression was used to assess their role in mortality. RESULTS: Among 400 children enrolled, the median (IQR) age was 15.0 months (11.2-19.2 months), 58% were boys, and 61% had caregiver-reported diarrhea at admission. During hospitalization, the median (range) number of days with diarrhea was 5 (0-31), the median duration of hospitalization was 17 days (1-69 days), and 39 (10%) died. Of 592 diarrhea episodes monitored, 237 were admission episodes and 355 were hospital acquired. During hospitalization, young age was associated with days with diarrhea, and young age and HIV infection were associated with dehydration. Both days with diarrhea and dehydration predicted duration of hospitalization as well as mortality. The odds of mortality increased by a factor of 1.4 (95% CI, 1.2-1.6) per day of diarrhea and 3.5 (95% CI, 2.2-6.0) per unit increase in dehydration score. CONCLUSIONS: Diarrhea is a strong predictor of mortality among children with complicated severe acute malnutrition. Improved management of diarrhea and prevention of hospital-acquired diarrhea may be critical to decreasing mortality.

Predictors of mortality among hospitalized children with severe acute malnutrition: a prospective study from Uganda.

BACKGROUND: We determined the predictors of mortality among children admitted with severe acute malnutrition (SAM). METHODS: This was a prospective study nested in a randomized trial among 6-59-month-old children admitted with SAM. Socio-demographic and medical history data were collected using questionnaires and clinical examination, anthropometry and laboratory tests were performed. They were monitored daily until discharge or death during hospitalization while receiving care according to national guidelines. Predictors of death were assessed using Cox regression. RESULTS: Of 400 children, 9.8% (n = 39) died during hospitalization. Predictors of mortality included diarrhoea at admission [hazard ratio [HR] 2.19, 95% confidence interval (CI): 1.06; 4.51], lack of appetite [HR 4.50, 95% CI: 1.76; 11.50], suspected sepsis [HR 2.23, 95% CI: 1.18; 4.24] and skin ulcers [HR 4.23, 95% CI: 1.26; 4.17]. Chest indrawing [HR 5.0, 95% CI: 1.53; 16.3], oxygen saturation below 94% [HR 3.92, 95% CI: 1.42; 10.83] and confirmed HIV infection [HR 3.62, 95% CI: 1.69; 7.77] also predicted higher mortality. CONCLUSION: Infections were major contributors to mortality. This underscores the need for improved prevention and management of these infections among children with severe malnutrition.

Utilization of "prevention of mother-to-child transmission" of HIV services by adolescent and young mothers in Mulago Hospital, Uganda.

BACKGROUND: Prevention of mother to child transmission (PMTCT) has lowered the incidence of paediatric HIV globally. The risk of mother-to-child transmission of HIV (MTCT) remains high in Africa, where there is a high prevalence of pregnancy and poor health-seeking behaviour among young girls and women. METHODS: In this cross-sectional, mixed-methods study, we evaluated the utilization of PMTCT services and associated factors among adolescent and young postpartum mothers aged 15 to 24 years at a public urban referral hospital in Uganda. Both HIV-positive and HIV-negative participants were recruited. Utilization of PMTCT services was defined as use of the PMTCT cascade of services including ever testing for HIV, receiving HIV test results; If tested negative, subsequent retesting up to 14 weeks; If tested positive, Antiretroviral drugs (ARVs) for the mother, ARVs and septrin prophylaxis for infant, safe delivery, safer infant feeding, early infant diagnosis within 6 weeks, and linkage to treatment and care. Optimal utilization of PMTCT was defined as being up to date with utilization of PMTCT services for reported HIV status at the time of being interviewed. The overall proportion of participants who optimally utilized PMTCT services was determined using descriptive statistics. Qualitative data was analyzed manually using the content thematic approach. RESULTS: Of the 418 participants, 65 (15.5%) were HIV positive. Overall, only 126 of 418 participants (30.1%) had optimally utilized PMTCT services. However, utilization of PMTCT services was better among HIV positive mothers, with 83% (54/65) having utilized the services optimally, compared to only 20% (72/353) of the HIV negative mothers (OR 18.2 (95% CI; 9.0-36.7)). The benefits of knowing ones HIV status, health of the unborn child, and counseling and support from health workers and peers, were the major factors motivating adolescent and young mothers to utilize PMTCT services, while stigma, financial constraints, non-disclosure, and lack of partner and family support were key demotivating factors. CONCLUSION: Utilization of PMTCT services by these adolescent and young mothers was suboptimal. Special consideration should be given to adolescents and young women in the design of elimination of mother to child transmission (EMTCT) programs, to improve the utilization of PMTCT services.

Effect of Probiotics on Diarrhea in Children With Severe Acute Malnutrition: A Randomized Controlled Study in Uganda.

OBJECTIVES: The aim of the study was to assess the effect of probiotics on diarrhea during in- and outpatient treatment of children with severe acute malnutrition (SAM). METHODS: A randomized, double-blind, placebo-controlled study was conducted involving 400 children admitted with SAM. Patients received 1 daily dose of a blend of Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus (10 billion colony-forming units, 50:50) or placebo during hospitalization followed by an 8- to 12-week outpatient treatment period, depending on patients' recovery rate. All outcomes were reported for in- and outpatient treatment separately. The primary outcome was number of days with diarrhea during hospitalization. Secondary outcomes included other diarrhea outcomes, pneumonia, weight gain, and recovery. RESULTS: There was no difference in number of days with diarrhea between the probiotic (n = 200) and placebo (n = 200) groups during inpatient treatment (adjusted difference +0.2 days, 95% confidence interval -0.8 to 1.2, P = 0.69); however, during outpatient treatment, probiotics reduced days with diarrhea (adjusted difference -2.2 days 95% confidence interval -3.5 to -0.3, P = 0.025). There were no effects of probiotics on diarrhea incidence and severity or pneumonia, weight gain or recovery during in- or outpatient treatment. Twenty-six patients died in the probiotic versus 20 in the placebo group (P = 0.38). CONCLUSIONS: Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus had no effect on diarrhea in children with SAM during hospitalization, but reduced the number of days with diarrhea in outpatient treatment by 26%. Probiotics may have a role in follow-up of hospitalized children with SAM or in community-based treatment of malnourished children, but further studies are needed to confirm this.

Validation of a Simple Stool Diary Used by Caregivers to Document Diarrhea Among Young Children in a Low-Income Country.

OBJECTIVES: The aim of the study was the development and validation of a simple stool diary for caretakers collecting data on stool frequency and consistency among young children in a low-income country. METHODS: Focus group studies evaluated how diarrhea was understood by caregivers (content validity). The sensitivity, reliability, and correlations between dehydration and diary scores (construct validity) were tested in a clinical trial. RESULTS: Caregivers recognized and understood the concept and severity of diarrhea. Stool frequency and liquid consistency decreased in children admitted with diarrhea (P < 0.0001 for both), confirming good sensitivity of the diary. High reliability was obtained after a few days of training. The caregiver intracorrelation coefficients were 0.66 (0.55-0.77) and 0.75 (0.66-0.84) after 2 and 7 days of training, respectively, and subjective staff evaluation of caregiver scores showed that ≤6% of caregivers had low scoring abilities after 3 days. The degree of dehydration (4-point score) was correlated with both increasing stool frequency and liquid stool consistency (+0.2 points [0.07-0.3], P = 0.0018 for 6 or more diarrheal stools, compared to 3 or more diarrheal stools per day, and +0.5 points (0.3-0.6), P < 0.0001 for diarrheal episodes with 3 or more watery stools/day compared with episodes with 3 or more "watery + abnormally loose + loose" stools per day). CONCLUSIONS: The diary showed high validity, good reliability, and high sensitivity. After 3 days of training, caregivers with mainly no or limited education could report stool consistency with good reliability. Stool consistency, which correlated strongly with dehydration, may be considered an important marker of diarrhea severity in future research.

Transition from F-75 to ready-to-use therapeutic food in children with severe acute malnutrition, an observational study in Uganda.

BACKGROUND: World Health Organization now recommends the transition from F-75 to ready-to-use therapeutic foods (RUTF) in the management of severe acute malnutrition (SAM). We described the transition from F-75 to RUTF and identified correlates of failed transition. METHODS: We conducted an observational study among children aged 6-59 months treated for SAM at Mulago hospital, Kampala, Uganda. Therapeutic feeding during transition phase was provided by first offering half of the energy requirements from RUTF and the other half from F-75 and then increasing gradually to RUTF as only energy source. The child was considered to have successfully transitioned to RUTF if child was able to gradually consume up to 135 kcal/kg/day of RUTF in the transition phase on first attempt. Failed transition to RUTF included children who failed the acceptance test or those who had progressively reduced RUTF intake during the subsequent days. Failure also included those who developed profuse diarrhoea or vomiting when RUTF was ingested. RESULTS: Among 341 of 400 children that reached the transition period, 65% successfully transitioned from F-75 to RUTF on first attempt while 35% failed. The median (IQR) duration of the transition period was 4 (3-8) days. The age of the child, mid-upper arm circumference, weight-for-height z-score and weight at transition negatively predicted failure. Each month increase in age reflected a 4% lower likelihood of failure (OR 0.96 (95% CI 0.93; 0.99). Children with HIV (OR 2.73, 95% CI 1.27; 5.85) and those rated as severely ill by caregiver (OR 1.16, 95% CI: 1.02; 1.32) were more likely to fail. At the beginning of the rehabilitation phase, the majority (95%) of the children eventually accepted RUTF while only 5% completed rehabilitation in hospital on F-100. CONCLUSION: Transition from F-75 to RUTF for hospitalized children with SAM by gradual increase of RUTF was possible on first attempt in 65% of cases. Younger children, severely wasted, HIV infected and those with severe illness as rated by the caregiver were more likely to fail to transit from F-75 to RUTF on first attempt.

Adherence to antiretroviral therapy and retention in care for adolescents living with HIV from 10 districts in Uganda.

BACKGROUND: Adolescents have gained increased attention because they are the only age group where HIV related mortality is going up. We set out to describe the level and factors associated with adherence to antiretroviral therapy (ART) as well as the 1 year retention in care among adolescents in 10 representative districts in Uganda. In addition, we explored the barriers and facilitators of adherence to ART among adolescents. METHODS: The study involved 30 health facilities from 10 representative districts in Uganda. We employed both qualitative and quantitative data collection methods in convergent design. The former involved Focus group discussions with adolescents living with HIV, Key informant interviews with various stakeholders and in depth interviews with adolescents. The quantitative involved using retrospective records review to extract the last recorded adherence level from all adolescents who were active in HIV care. Factors associated with adherence were extracted from the ART cards. For the 1 year retention in care, we searched the hospital records of all adolescents in the 30 facilities who had started ART 1 year before the study to find out how many were still in care. RESULTS: Out of 1824 adolescents who were active on ART, 90.4 % (N = 1588) had ≥95 % adherence recorded on their ART cards at their last clinic visit. Only location in rural health facilities was independently associated with poor adherence to ART (P = 0.008, OR 2.64 [1.28 5.43]). Of the 156 adolescents who started ART, 90 % (N = 141) were still active in care 1 year later. Stigma, discrimination and disclosure issues were the most outstanding of all barriers to adherence. Other barriers included poverty, fatigue, side effects, pill burden, depression among others. Facilitators of adherence mainly included peer support groups, counseling, supportive health care workers, short waiting time and provision of food and transport. CONCLUSION: Adherence to ART was good among adolescents. Being in rural areas was associated with poor adherence to ART and 1 year retention in care was very good among adolescents who were newly started on ART. Stigma and disclosure issues continue to be the main barriers to adherence among adolescents.

Early perinatal outcomes of babies born to adolescent mothers at two maternity hospitals in Mogadishu, Somalia.

Background: Adolescent motherhood remains a major problem in developing countries. We set out to describe the perinatal outcomes of infants born to adolescent mothers and to determine factors associated with birth asphyxia among these infants in Mogadishu, Somalia. Methods: This cross-sectional study involved adolescent mothers who presented in labor. Sociodemographic and medical data was collected and mother-infant pairs were followed up at 24hrs. Poor perinatal outcomes were: low birth weight, birth asphyxia, death or hospitalization after 24 hours. Data was entered into Epi data 3.1 and analysed using STATA version 12.0. Results: Of the 270 adolescents, mean age was 17.7 years (±1.19), 89% were married, 94% were unemployed and 54% had not received formal education. Of the 270 babies born, 70 (25.9%) had poor perinatal outcomes which included; 35 (12.9%) died; of whom 30 (11.1%) were stillbirths. Thirty-two infants (13.3%) had birth asphyxia and 18 (6.7%) had low birth weight. Prolonged labor (p-value=<0.001) and preterm birth (p-value=0.023) were significantly associated with birth asphyxia while living in Mogadishu was protective (p- value=0.018). Conclusions: About one in four adolescent mother's babies had poor perinatal outcomes. Prolonged labor and preterm delivery and were associated with birth asphyxia while residing closer to the facilities was protective.

Nutritional Recovery of Children With HIV and Severe Acute Malnutrition Attending an Outpatient Therapeutic Care Program.

BACKGROUND: Despite significant morbidity and mortality from HIV and severe acute malnutrition (SAM) among children in sub-Saharan Africa, research is lacking in these children. We describe the proportion of children living with HIV with SAM achieving recovery, the factors associated with recovery, and time to recovery in an outpatient therapeutic care program. SETTING AND METHODS: This is a retrospective observational study of children with SAM and HIV on antiretroviral therapy (6 months-15 years), enrolled in outpatient therapeutic care from 2015 to 2017 at a pediatric HIV clinic in Kampala, Uganda. SAM diagnosis and recovery by 120 days after enrollment were determined per World Health Organization guidelines. Cox-proportional hazards models were used to determine predictors of recovery. RESULTS: Data from 166 patients were analyzed (mean age 5.4 years, SD 4.7). Outcomes showed 36.1% recovered, 15.6% were lost to follow-up, 2.4% died, and 45.8% failed. Average time to recovery was 59.9 days (SD 27.8). Patients 5 years or older were less likely to recover (crude hazard ratio [CHR] = 0.33, 95% CI: 0.18 to 0.58). In multivariate analysis, febrile patients were less likely to recover (adjusted hazard ratio = 0.53, 95% CI: 0.12 to 0.65). Patients with CD4 count of 200 or less at enrollment were less likely to recover (CHR = 0.46, 95% CI: 0.22 to 0.96). CONCLUSIONS: Despite treatment with antiretroviral therapy for children living with HIV, we observed poor rates of recovery from SAM, below the international target of >75%. Moreover, patients 5 years and older, fever, or low CD4 at diagnosis of SAM may require more intense therapy or closer monitoring than their counterparts.

Correlates of Iron, Cobalamin, Folate, and Vitamin A Status among Stunted Children: A Cross-Sectional Study in Uganda.

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12-59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148-221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24-59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection.

As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies.

Prevalence and factors associated with anaemia in children aged 6-24 months living a high malaria transmission setting in Burundi.

BACKGROUND: In very young children, anaemia has been linked to increased morbidity, mortality and poor cognitive development. Although Burundi has a high burden of anaemia, which may be worsened by the high burden of malaria, little is known about the extent of the problem in very young children who are most at risk of severe disease. We estimated the prevalence, and assessed the factors associated with anaemia in children aged 6-24 months using baseline data collected as part of an on-going study evaluating the effect of Micronutrient supplementation on anaemia and cognition among children in high malaria transmission settings in Burundi. METHODS: Between February and March 2020, surveys were conducted in 498 households within the catchment area of Mukenke Health Center. One child aged 6-24 months was selected per household to participate in the survey. Following written informed consent, we administered a questionnaire to the child's primary caregiver to capture information on child's demographics, nutritional status, food intake, health (status, and morbidity and treatment-seeking practices), as well as the household markers of wealth. A physical exam was conducted, and a blood sample was collected to: 1) assess for presence of plasmodium infection using a rapid diagnosis test; 2) estimate the haemoglobin levels using a portable haemocue machine. A stool sample was also collected to examine for the presence of helminth infections. RESULTS: The prevalence of anaemia was 74.3% (95% confidence interval [CI] 61.5%-84.0%), with most of the anaemic study participants classified as having moderate anaemia (59.2%). A total of 62 (12.5%) participants had positive malaria rapid diagnosis tests. Factors significantly associated with higher odds of developing anaemia included not receiving deworming medication (adjusted Odd ratio [aOR] = 3.54, 95% CI 1.79-6.99, p<0.001), the child's home location (Mukenke II: aOR = 2.22, 95% CI 1.89-2.62, p<0.001; Mukenke: aOR = 2.76, 95% CI 2.46-3.10, p<0.001 and Budahunga: aOR = 3.12, 95% CI 2. 94-3.31, p<0.001) and the child's age group (Children aged 6-11 months: aOR = 2.27, 95% CI 1.32-3.91, p<0.001). Education level was inversely associated with less odds of anaemia: child's primary care giver with a secondary (aOR = 0.67; 95% CI: 0.47-0.95, p = 0,024) and tertiary education level (aOR = 0.48; 95% CI: 0.38-0.61, p<0.001). CONCLUSION: Anaemia is highly prevalent among young children in high malaria transmission setting. Anaemia is more prevalent among children who not dewormed and those with malaria. To prevent the long-term adverse outcomes of the anaemia in children, policy makers should focus on improving uptake of the deworming and malaria prevention programs, promote preventive interventions and improve the education of women especially in families with very young children.

Ultrasound findings in Plasmodium falciparum malaria: a pilot study.

OBJECTIVE: To investigate whether hand-carried ultrasound technology may be valuable in the assessment of children with acute malaria. Every year, approximately 800,000 children under the age of 5 yrs die of complications of Plasmodium falciparum malaria infection. The advent of hand-carried ultrasound technology has made diagnostic ultrasonography possible in underresourced settings. DESIGN: We performed a pilot observational study collecting clinical data and performing ultrasound examinations on children diagnosed with P. falciparum malaria infection. The targeted ultrasound examination included measurement of optic nerve sheath diameter, color transcranial Doppler insonation of the cerebral vasculature, cardiac ultrasound, and abdominal ultrasound. SETTING: Pediatric acute care unit of Mulago Hospital in Kampala, Uganda. PATIENTS: Thirty-three hospitalized children between the ages of 6 months and 12 yrs with documented acute P. falciparum infection. INTERVENTION: Targeted bedside ultrasound examination. MEASUREMENTS AND MAIN RESULTS: Increased optic nerve sheath diameter was observed in one third of all patients with malaria and in 100% of the patients diagnosed with cerebral malaria. Although higher-than-normal cerebral blood flow velocities were demonstrated in three (25%) of 12 patients with severe anemia, most patients demonstrated a normal cerebral blood flow velocity, suggesting a blunted response to anemia. We did not find evidence of pulmonary hypertension by cardiac ultrasound, and cardiac function did not seem depressed, even among patients with severe anemia and lactic acidosis. Finally, spleen size as determined by palpation significantly overestimated the true incidence of splenomegaly as measured by ultrasound (48% and 24%, respectively). CONCLUSIONS: A targeted ultrasound examination focusing on optic nerve sheath diameter, color transcranial Doppler, cardiac ultrasound, and spleen size may prove useful for patient classification, risk stratification, research studies, and treatment monitoring in pediatric malaria. More studies should be done.

Weight-for-Height Z-score Gain during Inpatient Treatment and Subsequent Linear Growth during Outpatient Treatment of Young Children with Severe Acute Malnutrition: A Prospective Study from Uganda.

BACKGROUND: Linear catch-up growth after treatment of severe acute malnutrition (SAM) is low, and little is known about the association between ponderal and subsequent linear growth. OBJECTIVE: The study assessed the association of weight-for-height z-score (WHZ) gain with subsequent linear growth during SAM treatment and examined its modifiers. METHODS: This was a prospective study, nested in a trial (ISRCTN16454889), among 6-59-mo-old children treated for SAM in Uganda. Weight, total length (TL), and knee-heel length (KHL) were measured at admission, weekly during inpatient therapeutic care (ITC), at discharge, and fortnightly during outpatient therapeutic care (OTC) for 8 wk. Linear regression was used to assess the association between WHZ gain during ITC and linear growth during OTC. RESULTS: Of 400 children, 327 were discharged to OTC and 290 were followed up for 8 wk. Mean WHZ gains were 0.45 in ITC and 1.24 in OTC, whereas mean height-for-age z-score (HAZ) declined by 0.41 during ITC and increased by 0.14 during OTC. WHZ gain during ITC was positively associated with HAZ, TL, and KHL gains during OTC [regression coefficients (ß) (95% CI): 0.12 (0.09, 0.15) z-score; 3.1 (2.4, 3.8) mm and 0.5 (0.1, 0.7) mm, respectively]. The regression coefficients were highest for the middle tertile of WHZ gain with respect to HAZ and TL. Admission diarrhea and low plasma citrulline reduced the association between WHZ gain during ITC and HAZ and TL gain during OTC (P < 0.001). In contrast, pneumonia (P = 0.051) and elevated plasma C-reactive protein (P < 0.001) increased the association with TL gain, but reduced the association with KHL gain (P < 0.001). CONCLUSIONS: Among children admitted with SAM, considerable WHZ gain during ITC was followed by very modest linear catch-up growth during OTC, with no indication of a WHZ gain threshold, above which linear growth was higher. To optimize linear growth in these children, early treatment of infections and conditions affecting the gut may be necessary.

Weight and mid-upper arm circumference gain velocities during treatment of young children with severe acute malnutrition, a prospective study in Uganda.

BACKGROUND: Weight gain is routinely monitored to assess hydration and growth during treatment of children with complicated severe acute malnutrition (SAM). However, changes in weight and mid-upper arm circumference (MUAC) gain velocities over time are scarcely described. We assessed weight and MUAC gain velocities in 6-59 mo-old children with complicated SAM by treatment phase and edema status. METHODS: This was a prospective study, nested in a randomized/probiotic trial ( ISRCTN16454889 ). Weight and MUAC gain velocities were assessed by treatment phase and edema at admission using linear mixed-effects models. RESULTS: Among 400 children enrolled, the median (IQR) age was 15.0 (11.2;19.2) months, 58% were males, and 65% presented with edema. During inpatient therapeutic care (ITC), children with edema vs no edema at admission had negative weight gain velocity in the stabilization phase [differences at day 3 and 4 were - 11.26 (95% CI: - 20.73; - 1.79) g/kg/d and - 13.09 (95% CI: - 23.15; - 3.02) g/kg/d, respectively]. This gradually changed into positive weight gain velocity in transition and eventually peaked at 12 g/kg/d early in the rehabilitation phase, with no difference by edema status (P > 0.9). During outpatient therapeutic care (OTC), overall, weight gain velocity showed a decreasing trend over time (from 5 to 2 g/kg/d), [difference between edema and non-edema groups at week 2 was 2.1 (95% CI: 1.0;3.2) g/kg/d]. MUAC gain velocity results mirrored those of weight gain velocity [differences were - 2.30 (95% CI: - 3.6; - 0.97) mm/week at week 1 in ITC and 0.65 (95% CI: - 0.07;1.37) mm/week at week 2 in OTC]. CONCLUSIONS: Weight and MUAC gain velocities among Ugandan children with complicated SAM showed an increasing trend during transition and early in the rehabilitation phase, and a decreasing trend thereafter, but, overall, catch-up growth was prolonged. Further research to establish specific cut-offs to assess weight and MUAC gain velocities during different periods of rehabilitation is needed.

Restitution of gut microbiota in Ugandan children administered with probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) during treatment for severe acute malnutrition.

Severe acute malnutrition (SAM) is a major challenge in low-income countries and gut microbiota (GM) dysbiosis may play a role in its etiology. Here, we determined the GM evolution during rehabilitation from SAM and the impact of probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) supplementation. The GM (16S rRNA gene amplicon sequencing) of children admitted to hospital with SAM showed distinct composition over admission (e.g. Klebsiella spp., and Enterobacteriaceae spp.), discharge (e.g. Clostridiaceae spp., Veilonella dispar) and follow-up (e.g. Lactobacillus ruminis, Blautia spp., Faecalibacterium prausnitzii), reaching similar ß- and α-diversity as healthy individuals. Children with diarrhea had reduced distribution of Bacteroidaceae, Lachnospiraceae, increased Enterobacteriaceae and Moraxellaceae, and lower α-diversity. Children suffering from edematous SAM had diminished proportion of Prevotellaceae, Lachnospiraceae, Ruminoccaceae and a higher α-diversity when compared to non-edematous SAM. Supplementation of probiotics did not influence ß-diversity upon discharge or follow-up, but it increased (p < .05) the number of observed species [SE: > 4.5]. Children where the probiotic species were detected had lower cumulative incidence (p < .001) of diarrhea during the follow-up period compared to children receiving placebo and children receiving probiotics, but where the probiotics were not detected. The GM of children with non-edematous and edematous SAM differ in composition, which might have implications for future GM targeted treatments. Probiotics treatment reduced the cumulative incidence of diarrhea during the outpatient phase, with the strongest effect in children where the administered probiotics could be detected in the GM.