Zambian Children Research Articles

Pediatric Symptom Checklist-17: Factor Structure and Uniform Differential Item Functioning Across Gender and Age in HIV Orphans and Vulnerable Children in Zambia.

This study aimed to investigate the psychometric properties of the Pediatric Symptom Checklist-17 (PSC-17) in a sample of children orphaned or made vulnerable (OVC) by HIV in Zambia. Caregivers of 1,076 OVC (55.1% boys; Mage = 12.91 years) completed the PSC-17. Competing models, including confirmatory factor analysis (CFA), hierarchical CFA, bifactor CFA, exploratory structural equation modeling (ESEM), and bifactor ESEM, were tested to evaluate the optimal factor structure of the PSC-17. Results showed that the bifactor ESEM provided the best approximation of the PSC-17 data with a well-defined general psychosocial problems factor explaining 72% of the reliable variance in the total score and an internalizing factor containing 63% of reliable variance unique from the general factor. The observed overall psychosocial problems score was associated with lower academic achievement and working memory (with small effect sizes), supporting the discriminant validity of score interpretation. Results of multiple indicators multiple causes (MIMIC) analyses revealed that all items functioned equivalently across child gender and age.

The association between food groups and childhood anemia in Zambia, based on the analysis of Zambia Demographic and Health Survey 2018.

High prevalence of anemia among children has been an important public health concern globally. In Zambia, the prevalence of anemia among children aged 6-59 months was 58%. Previous studies have suggested that feeding a variety of food prevents anemia. However, it is not yet determined if out of several food groups available locally, some foods have played crucial roles in anemia among young children. The objective of this study was to find out the food groups that were associated with childhood anemia among Zambian children aged 6-59 months. We have obtained the individual- level data related to health and nutrition of the Zambia Demographic Health Survey (ZDHS) 2018 with permission. Children’s feeding, demographic, and household information were analyzed using logistic regression models. Children who consumed food made from grains (AOR:1.2; 95%CI: 1.01-1.46; p=0.044) and cheese or food made from milk (AOR:2.7; 95%CI: 1.19-6.00; p=0.018) showed relatively higher prevalence of anemia than those who did not. Additionally, malnutrition, mother’s anemia and education, and area of living were also significantly associated with prevalence of anemia. Most common food in Zambia is food made from grain. Grain consists of phytic acids which can prevent iron absorption. This is a potential reason for the highlevel anemia among children. Dephytinization strategies should be considered through further studies.

Validation of the National Institute of Health Toolbox Cognition Battery (NIHTB-CB) in Children and Adolescents with and without HIV Infection in Lusaka, Zambia.

The objective of this study was to validate the NIH Toolbox Cognition Battery (NIHTB-CB) in Zambian children with and without HIV-infection. Children living with HIV and HIV-exposed, uninfected (HEU) children completed traditional neuropsychological and NIHTB-CB tasks. Using pairwise correlation and a linear regression model we measured associations between traditional measure composite scores and parental ratings of children's abilities, and NIHTB-CB scores. A Receiver Operating Characteristic (ROC) curve was developed to identify participants with impairment. 389 children, 8-17 years old participated. NIHTB-CB and traditional measures converged well as a whole and when comparing analogous individual tests across the two batteries. The NIHTB-CB composite score discriminated between the groups and was positively associated with external criteria for cognitive function: parental ratings of intelligence and school performance. Some English vocabulary and/or an unfamiliar cultural context presented challenges. NIHTB-CB was associated with children's everyday cognitive abilities, though future use may require linguistic and cultural adaptation.

Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era.

ObjectiveThis study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new‐onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30‐day mortality and cause of death are also reported.MethodsChildren living with HIV (CLWHIV) with new‐onset seizures were prospectively evaluated at one large urban teaching hospital and two non‐urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed.ResultsFrom April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2‐10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non‐accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty‐two (30%) children died within 30 days of the index seizure.SignificanceDespite widespread ART roll out in Zambia, new‐onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

Epithelial Abnormalities in the Small Intestine of Zambian Children With Stunting.

BackgroundEnvironmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen in vivo in adults and children with EE. We set out to identify epithelial lesions which might explain this phenomenon in Zambian children with stunting non-responsive to nutritional support.MethodsWe performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy.ResultsConfocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes of EE: villus blunting, lamina propria and epithelial inflammation, and depletion of secretory cells (Paneth cells and goblet cells). Epithelial abnormalities included marked variability in epithelial height, disorganised and shortened microvilli, dilated intercellular spaces, pseudostratification, formation of synechiae between epithelium on adjacent villi, crypt destruction, and abundant destructive lesions which may correspond to the microerosions identified on CLE.ConclusionEpithelial abnormalities were almost universal in Zambian children with non-responsive stunting, including epithelial microerosions, cell-cell adhesion anomalies, and defects in secretory cells which may all contribute to impairment of mucosal barrier function and microbial translocation.

Assessing Diet and Nutritional Intake of Rural Children in Zambia Using a Food Frequency Questionnaire

ABSTRACT In this survey, to assess the energy and nutrient intake of rural children in Zambia, a semi-quantitative food frequency questionnaire (FFQ) was developed using the direct weighing method for 126 children, and then a dietary survey with 153 children was conducted using the FFQ. The dietary survey revealed that rural children in Zambia are deficient in energy intake compared to international standards. However, the protein intake met the recommended level; most of it came from vegetables. The carbohydrate intake rate was high, while the fat intake rate was relatively low because of a diet that was highly dependent on maize.

Histo-Blood Group Antigens, Enteropathogen Carriage and Environmental Enteropathy in Stunted Zambian Children.

Stunting, the most common form of childhood undernutrition, is associated with environmental enteropathy (EE). Enteric infections are believed to play a role in the pathophysiology of EE and stunting though the exact mechanism remains undetermined. The FUT2 (secretor) and FUT3 (Lewis) genes have been shown to be associated with some symptomatic enteric infections in both children and adults. These genes are responsible for the presence of histo-blood group antigens (HBGAs) in various secretions and epithelial surfaces.We evaluated whether the secretor and Lewis status influences asymptomatic enteric infections and thus EE severity on duodenal biopsies of stunted children. In this case-control study, we used saliva samples to determine the secretor and Lewis status of stunted children (cases, n = 113) enrolled in a nutritional rehabilitation program and from their well-nourished counterparts (controls, n = 42). Where available, saliva was also collected from the mothers. Baseline stool samples were used to detect asymptomatic enteropathogen carriage. Duodenal biopsies were collected from a subgroup of stunted children (n = 77) who had an upper gastrointestinal endoscopy done as part of the evaluation process for their non-response to nutritional therapy. The proportion of secretors was similar between the cases and the controls (82% vs 81%, P = 0.81). The stunted children had significantly higher rates of carrying multiple enteropathogens, but this was not associated with their secretor status nor that of their mothers. The secretor status was also not associated with mucosal morphometry of duodenal biopsies. This case-control analysis in Zambian children does not support the hypothesis that fucosylation status determines asymptomatic enteropathogen carriage in stunting.

Sexual debut and risk behaviors among orphaned and vulnerable children in Zambia: which protective deficits shape HIV risk?

ABSTRACT Orphaned and vulnerable children (OVC) are not only affected by, but also rendered at-risk of, HIV due to overlapping deficits in protective assets, from school to household financial security. Drawing from a protective deficit framework, this study examines correlates of sexual risk – including multiple sexual partnerships, unprotected sex, and age at sexual debut – among OVC aged 13–17 years in Zambia. In May-October 2016, a two-stage stratified random sampling design was used to recruit OVC and their adult caregivers (N = 2,034) in four provinces. OVC-caregiver dyads completed a structured interview addressing household characteristics, protective assets (i.e. finances, schooling, and nutrition), and general health and wellbeing. Associations of factors derived from the multi-component protective deficits framework were examined using multivariable ordered logistic regression, comparing sexually inexperienced OVC to those with a sexual debut and reporting ≥1 sexual behavior(s). A sub-analysis of older (ages 15–17) OVC identified correlates of early (before age 15) and later (at or after age 15) sexual debut using multinomial logistic regression. Among 735 OVC aged 13–17, 14% reported a sexual debut, among whom 14% and 22% reported 2+ past-year partners and non-condom last sex, respectively. Older age (Adjusted Odds Ratio [aOR] = 2.08, 95% Confidence Interval [CI] 1.32–3.27), male sex (aOR = 1.90, CI 1.22–2.96), not having a birth certificate (aOR = 2.05, CI 1.03–4.09), out-of-school status (aOR = 2.63, CI 1.66–4.16), and non-household labor (aOR = 1.84, CI 1.01–3.38) were significantly associated with higher sexual risk. Male sex was the only factor significantly associated with early sexual debut in multivariable analysis. Sexual risk-reduction strategies require age- and sex-specific differentiation and should be prioritized for OVC in financially distressed households.

Anthropometry, body composition and chronic disease risk factors among Zambian school-aged children who experienced severe malnutrition in early childhood.

There is limited information as to whether people who experience severe acute malnutrition (SAM) as young children are at increased risk of overweight, high body fat and associated chronic diseases in later life. We followed up, when aged 7-12 years, 100 Zambian children who were hospitalised for SAM before age 2 years and eighty-five neighbourhood controls who had never experienced SAM. We conducted detailed anthropometry, body composition assessment by bioelectrical impedance and deuterium dilution (D2O) and measured blood lipids, Hb and HbA1c. Groups were compared by linear regression following multiple imputation for missing variables. Children with prior SAM were slightly smaller than controls, but differences, controlling for age, sex, socio-economic status and HIV exposure or infection, were significant only for hip circumference, suprailiac skinfold and fat-free mass index by D2O. Blood lipids and HbA1c did not differ between groups, but Hb was lower by 7·8 (95 % CI 0·8, 14·7) g/l and systolic blood pressure was 3·4 (95 % CI 0·4, 6·4) mmHg higher among the prior SAM group. Both anaemia and high HbA1c were common among both groups, indicating a population at risk for the double burden of over- and undernutrition and associated infectious and chronic diseases. The prior SAM children may have been at slightly greater risk than the controls; this was of little clinical significance at this young age, but the children should be followed when older and chronic diseases manifest.

Helicobacter pylori infection and hypochlorhydria in Zambian adults and children: A secondary data analysis.

BackgroundHypochlorhydria (gastric pH >4) increases susceptibility to diarrhoea, iron deficiency, and gastric cancer. We sought to clarify the prevalence of this condition and its predisposing factors in Zambia by pooling data from previous studies conducted in hospital and community settings.MethodsGastric pH was measured in participants from five separate studies by collecting gastric aspirate from fasted adults and children under 3 years of age undergoing gastroscopy. Gastric pH was correlated with serological testing for Human Immunodeficiency Virus (HIV) and Helicobacter pylori (H. pylori) infections.ResultsWe studied 597 individuals (487 adults and 110 children). Hypochlorhydria was present in 53% of adults and 31% of children. HIV infection was detected in 41% of adults and 11% of children. H. pylori serology was available for 366 individuals: 93% of adults and 6% of children were seropositive. In univariate analysis, hypochlorhydria was significantly associated with HIV seropositivity (OR 1.7; 95% CI 1.2–2.4; p = 0.004) and H. pylori antibody seropositivity (OR 4.9; 95% CI 2.8–8.6; p<0.0001), and with advancing age in HIV negative individuals (p = 0.0001). In multivariable analysis, only H. pylori was associated with hypochlorhydria (OR 4.0; 95% CI 2.2–7.2; p<0.0001) while excluding possible exposure to proton pump inhibitors.ConclusionsHypochlorhydria is common in our population, with H. pylori being the dominant factor. Only young HIV seronegative individuals had a low prevalence of hypochlorhydria. This may have implications for the risk of other health conditions including gastric cancer.

Neighborhood-Based Socioeconomic Determinants of Cognitive Impairment in Zambian Children With HIV: A Quantitative Geographic Information Systems Approach.

Place-based inequalities, such as exposure to violence and access to nutritious food and clean water, may contribute to human immunodeficiency virus (HIV)-associated cognitive impairment. In this study, we investigated neighborhood effects on cognition in children and adolescents with HIV in Lusaka, Zambia. We conducted a prospective cohort study of 208 children with perinatally acquired HIV (ages 8-17) and 208 HIV-exposed uninfected controls. Participants underwent neuropsychological testing and interviews assessing socioeconomic status. Geographic regions with clusters of participants with HIV and cognitive impairment were identified using quantitative geographic information systems (QGIS) and SaTScan. Associations between location of residence and cognitive function were evaluated in bivariable and multivariable regression models. Mediation analysis was performed to assess direct and indirect effects of location of the residence on cognitive impairment. Residence in Chawama, one of the poorest neighborhoods in Lusaka, was significantly associated with cognitive impairment in participants with HIV (odds ratio 2.9; P = .005) and remained significant in a multivariable regression model controlling for potential confounders. Mediation analysis found that 46% of the cognitive effects of residence in Chawama were explained by higher rates of malnutrition, lower school attendance, and poorer self-reported health. Place-based socioeconomic inequality contributes to cognitive impairment in Zambian children and adolescents with HIV. Neighborhood effects may be mediated by concentrated poverty, malnutrition, limited access to education and health care, and other yet unknown environmental factors that may be potentially modifiable.

The Etiology of Pneumonia in HIV-infected Zambian Children: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

Despite recent declines in new pediatric HIV infections and childhood HIV-related deaths, pneumonia remains the leading cause of death in HIV-infected children under 5. We describe the patient population, etiology and outcomes of childhood pneumonia in Zambian HIV-infected children. As one of the 9 sites for the Pneumonia Etiology Research for Child Health study, we enrolled children 1-59 months of age presenting to University Teaching Hospital in Lusaka, Zambia, with World Health Organization-defined severe and very severe pneumonia. Controls frequency-matched on age group and HIV infection status were enrolled from the Lusaka Pediatric HIV Clinics as well as from the surrounding communities. Clinical assessments, chest radiographs (CXR; cases) and microbiologic samples (nasopharyngeal/oropharyngeal swabs, blood, urine, induced sputum) were obtained under highly standardized procedures. Etiology was estimated using Bayesian methods and accounted for imperfect sensitivity and specificity of measurements. Of the 617 cases and 686 controls enrolled in Zambia over a 24-month period, 103 cases (16.7%) and 85 controls (12.4%) were HIV infected and included in this analysis. Among the HIV-infected cases, 75% were <1 year of age, 35% received prophylactic trimethoprim-sulfamethoxazole, 13.6% received antiretroviral therapy and 36.9% of caregivers reported knowing their children's HIV status at time of enrollment. A total of 35% of cases had very severe pneumonia and 56.3% had infiltrates on CXR. Bacterial pathogens [50.6%, credible interval (CrI): 32.8-67.2], Pneumocystis jirovecii (24.9%, CrI: 15.5-36.2) and Mycobacterium tuberculosis (4.5%, CrI: 1.7-12.1) accounted for over 75% of the etiologic fraction among CXR-positive cases. Streptococcus pneumoniae (19.8%, CrI: 8.6-36.2) was the most common bacterial pathogen, followed by Staphylococcus aureus (12.7%, CrI: 0.0-25.9). Outcomes were poor, with 41 cases (39.8%) dying in hospital. HIV-infected children in Zambia with severe and very severe pneumonia have poor outcomes, with continued limited access to care, and the predominant etiologies are bacterial pathogens, P. jirovecii and M. tuberculosis.

The Etiology of Pneumonia in Zambian Children: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

Childhood pneumonia in developing countries is the foremost cause of morbidity and death. Fresh information on etiology is needed, considering the changing epidemiology of pneumonia in the setting of greater availability of effective vaccines, changing antibiotic use and improved access to care. We report here the Zambia site results of the Pneumonia Etiology Research for Child Health study on the etiology of pneumonia among HIV-uninfected children in Lusaka, Zambia. We conducted a case-control study of HIV-uninfected children age 1-59 months admitted with World Health Organization-defined severe or very severe pneumonia to a large tertiary care hospital in Lusaka. History, physical examination, chest radiographs (CXRs), blood cultures and nasopharyngeal/oropharyngeal swabs were obtained and tested by polymerase chain reaction and routine microbiology for the presence of 30 bacteria and viruses. From age and seasonally matched controls, we tested blood and nasopharyngeal/oropharyngeal samples. We used the Pneumonia Etiology Research for Child Health integrated analysis to determine the individual and population etiologic fraction for individual pathogens as the cause of pneumonia. Among the 514 HIV-uninfected case children, 208 (40.5%) had abnormal CXRs (61 of 514 children were missing CXR), 8 (3.8%) of which had positive blood cultures. The overall mortality was 16.0% (82 deaths). The etiologic fraction was highest for respiratory syncytial virus [26.1%, 95% credible interval (CrI): 17.0-37.7], Mycobacterium tuberculosis (12.8%, 95% CrI: 4.3-25.3) and human metapneumovirus (12.8%, CrI: 6.1-21.8). Childhood pneumonia in Zambia among HIV-uninfected children is most frequently caused by respiratory syncytial virus, M. tuberculosis and human metapneumovirus, and the mortality remains high.

Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations.

BackgroundDispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial.MethodsChildren weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0–36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment.ResultsIn the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4–6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1–45.1), 16.7 (9.2–25.9), 317 (263–399), and 9.5 (7.5–11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0–7.9-, 8–11.9-, and ≥25-kg weight bands, isoniazid in the 4.0–7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults.ConclusionsRecommended weight band–based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization–recommended doses requires further evaluation.

Cryptosporidiosis is predominantly an urban, anthroponotic infectious disease among Zambian children.

Cryptosporidium species are leading causes of diarrhoea in children and immunocompromised individuals. This study aimed to characterise Cryptosporidium species from children in rural and urban settings of Zambia. Stool samples collected from 490 children aged <5 y with diarrhoea were assessed for Cryptosporidium oocysts microscopically. A structured questionnaire was used to collect demographic and socioeconomic characteristics. Positive samples were subjected to PCR and gp60 sequence analysis. The overall prevalence was 10% (50/490, 95% CI 7.8 to 13.2) with a peak in March, the late rainy season. Children who came from households where boiling water was not practised (OR=2.5, 95% CI 1.29 to 5.17; p=0.007) or who had experienced recurrent episodes of diarrhoea (OR=9.31, 95% CI 3.02 to 28.73; p=0.001) were more likely to have Cryptosporidium infection. Genotyping of 16 positive samples (14 from urban and 2 from rural sources) revealed Cryptosporidium hominis (14/16) and Cryptosporidium parvum (2/16). The Cryptosporidium hominis subtypes identified were Ia, Ib and Ie with subtype families IeAIIG3 (1), IbA9G3R2 (2), IaA31R3 (3), IbA9G3 (5), IaA27R3 (1), IaA30R3 (1) and Ia (1). Subtypes IbA9G3 and Ia were identified in children from a rural area. Cryptosporidium parvum subtypes were IIcA5G3R2 (1) and IIcA5G3a (1). All isolates successfully genotyped were C. hominis or anthroponotic C. parvum, suggesting that anthroponotic transmission dominates in Lusaka and the surrounding countryside.

Epidemiology and Seasonality of Endemic Human Coronaviruses in South African and Zambian Children: A Case-Control Pneumonia Study.

Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children hospitalized with clinical pneumonia and among community controls living in countries with a high HIV burden, namely South Africa and Zambia, between August 2011 to October 2013. Nasopharyngeal/oropharyngeal swabs were collected from all cases and controls and tested for endemic HCoV species and 12 other respiratory viruses using a multiplex real-time PCR assay. We found that the likelihood of detecting endemic HCoV species was higher among asymptomatic controls than cases (11% vs. 7.2%; 95% CI: 1.2–2.0). This was however only observed among children > 6 months and was mainly driven by the Betacoronavirus endemic species (HCoV-OC43 and –HKU1). Endemic HCoV species were detected through the year; however, in Zambia, the endemic Betacoronavirus species tended to peak during the winter months (May–August). There was no association between HIV status and endemic HCoV detection.

Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults

Background:Environmental enteropathy (EE) contributes to growth failure in millions of children worldwide, but its relationship to clinical malnutrition has not been elucidated. We used RNA sequencing to compare duodenal biopsies from adults and children with EE, and from children with severe acute malnutrition (SAM), to define key features of these malnutrition-related enteropathies.Methods:RNA was extracted and sequenced from biopsies of children with SAM in hospital (n=27), children with non-responsive stunting in the community (n=30), and adults living in the same community (n=37) using an identical sequencing and analysis pipeline. Two biopsies each were profiled and differentially expressed genes (DEGs) were computed from the comparisons of the three groups. DEG lists from these comparisons were then subjected to analysis with CompBio software to assemble a holistic view of the biological landscape and IPA software to interrogate canonical pathways.Findings:Dysregulation was identified in goblet cell/mucin production and xenobiotic metabolism/detoxification for both cohorts of children, versus adults. Within the SAM cohort, substantially greater induction of immune response and barrier function, including NADPH oxidases was noted, concordant with broadly reduced expression of genes associated with the brush border and intestinal structure/transport/absorption. Interestingly, down regulation of genes associated with the hypothalamic-pituitary-adrenal axis was selectively observed within the cohort of children with stunting.Interpretation:Gene expression profiles in environmental enteropathy and severe acute malnutrition have similarities, but SAM has several distinct transcriptional features. The intestinal capacity to metabolise drugs and toxins in malnourished children requires further study.Funding:Bill & Melinda Gates Foundation (OPP1066118)

Treatment outcomes among children younger than five years living with HIV in rural Zambia, 2008\u20132018: a cohort study

BackgroundHIV testing and treatment guidelines for children in sub-Saharan Africa have evolved over time, such that children are now treated at younger ages. The objective of this study was to describe the treatment experience for immunologic, virologic, and growth outcomes among HIV-infected Zambian children younger than 5 years of age from 2008 to 2018.MethodsParticipants enrolled in a clinical cohort study in Macha, Zambia and initiating antiretroviral treatment before 5 years of age between 2008 and 2015 were included in the analysis and followed up to the end of 2018. Outcomes, including growth, CD4+ T-cell percentage, viral suppression, and mortality, were evaluated among all children using longitudinal and survival analyses. Comparisons by age at treatment initiation (< 1, 1 to < 2, and 2 to < 5 years) were also evaluated.ResultsThree hundred eighty-one children initiating treatment before 5 years of age between 2008 and 2015 were included in the analysis. Growth metrics and CD4+ T-cell percentage improved over time after treatment initiation. However, 20% of children remained underweight and 40% of children remained stunted after the first 36 months of treatment. 85% of children had a viral load < 400 copies/mL after 12 months of treatment. However, children < 1 year at treatment initiation were more likely to have a detectable viral load in the first 12 months of treatment and less likely to achieve viral suppression compared to older children. Mortality was highest in the first 12 months of treatment, among underweight children, and among children initiating treatment in 2008–2010 compared to 2011–2015.ConclusionsMost children initiating antiretroviral treatment from 2008 to 2015 in rural Zambia responded well to treatment. However, many children remained underweight and stunted, and experienced high mortality rates during the first few months of treatment. This supports continued efforts to improve early infant diagnosis, nutritional support, and pediatric drug formulations.

Relative importance of early childhood development domains for schooling progression: Longitudinal Evidence from the Zambia Early Childhood Development Project

While the effects of early childhood development on later educational outcomes have been widely studied in western countries, rigorous evidence from sub-Saharan African countries is limited. This longitudinal study uses Zambian children’s developmental outcomes at age six as predictors of educational enrollment and attainment at age 15. Fine motor, receptive language, and early literacy skills were most strongly associated with on-track enrollment. Fine motor skills were most predictive of enrollment. Cognitive, socio-emotional, and executive functioning skills predicted grade repetition. Overall, the results suggest substantial heterogeneity in the associations between domains of early childhood development and adolescent schooling outcomes in Zambia.

Age-specific differences in the magnitude of malaria-related anemia during low and high malaria seasons in rural Zambian children.

BackgroundMalaria causes anemia by destruction of red blood cells and inhibition of erythropoiesis.ObjectiveWe assessed whether the magnitude of the malaria‐specific effect on anemia differs by age, during low and high malaria seasons.MethodIn rural Zambian children participating in a pro‐vitamin A efficacy trial, we estimated differences in the prevalence of anemia (defined as hemoglobin < 110 g/L for children < 60 months. and < 115 g/L in older children) by malaria status and assessed malaria‐age interactions. Regression models (with anemia as the outcome) were used to model malaria‐age interaction in both the low and high malaria seasons, controlling for potential confounders.ResultsAverage age was 68 months at baseline (n = 820 children). In the low malaria season, anemia prevalence was 29% in malaria‐negative children and 54% in malaria‐positive children (p < 0.001), with no malaria‐age interactions (p = 0.44). In the high malaria season, anemia prevalence was 41% in malaria‐negative children and 54% in malaria‐positive children (p < 0.001), with significant malaria‐age interactions (p = 0.02 for anemia). Age‐stratified prevalence of anemia in malaria positive versus negative children was 67.0% versus 37.1% (in children < 60 months); 57.0% versus 37.2% (in 60–69 months.); 46.8% versus 37.2% (in 70–79 months.); 37.0% versus 37.3% (in 80–89 months) and 28.0% versus 37.4% (in 90+ months).ConclusionsMalarial anemia is most severe in younger children, especially when transmission is intense. Anemia control programs must prioritize this vulnerable group.