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BACKGROUND: Neonatal hypothermia is a major cause of mortality. This study determined the prevalence and factors associated with neonatal hypothermia in two regional referral hospitals in Dar es Salaam, Tanzania. METHODS: Cross-sectional study was carried out between March and May 2021 at the Mwananyamala and Temeke Regional Referral Hospitals. Simple random and stratified sampling procedures were used to select study sites and proportionate population samples from each hospital respectively. Body temperature was measured within 90 minutes post birth; knowledge of the WHO guidelines on thermal protection of new-borns was collected from the mothers and health care providers using questionnaires. Logistic regression was used to assess associations between variables. SPSS version 25 was used to analyse the data and p < 0.05 was considered significant. RESULTS: Total of 296 mother-new-born pairs and 41 health care providers were enrolled in the study. 26 mothers did not consent for the study. 25.6% of the 270 studied neonates were hypothermic. Lack of skin-to-skin contact with the mother; early neonatal weighing and bathing increased likelihood of neonatal hypothermia. Knowledge of neonatal thermal protection among mothers and care-providers was inadequate. CONCLUSIONS: The prevalence of neonatal hypothermia among neonates in the referral hospitals is high. The findings suggest knowledge gaps of the WHO recommended guidelines on neonatal hypothermia are associated with neonatal hypothermia. Efforts to increase awareness of the WHO recommended thermal protection guidelines are needed.

Zinc supplementation has been consistently shown to reduce the incidence of childhood pneumonia, but its effect on the course of pneumonia when administered as an adjunct to antibiotic therapy is still unclear. Three trials published to date have shown mixed results, and a recent trial from India raises the possibility that zinc may be detrimental in some circumstances. Study sites and designs differ, particularly in the timing of zinc treatment and in determining recovery from pneumonia, which can explain the differences in study findings. Serum zinc concentrations are unreliable indicators of zinc status, particularly during acute infectious illnesses. Subgroup analyses, especially using serum zinc levels, must be cautioned against. Future studies are needed that are large enough to be sufficiently powered to accommodate larger treatment failure rates, an issue that ongoing trials will hopefully address.

The objective was to examine whether maternal HIV disease stage during pregnancy and child malnutrition are associated with child mortality. The design used was a prospective cohort study in Tanzania. Indicators of disease stage were assessed for 939 HIV-infected women during pregnancy and at delivery and childrens anthropometric status was obtained at scheduled monthly clinic visits after delivery. Children were followed up for survival status until 24 months after birth. Advanced maternal HIV disease during pregnancy (CD4 count less than 350 vs. greater than of equal to 350 cells/mm3) was associated with increased risk of child mortality through 24 months of age (hazard ratio [HR] = 1.74 95% confidence interval [CI]: 1.32 to 2.30). CD4 count less than 350 cells/ mm3 was also associated with an increased risk of death among children who remained HIV-negative during follow-up (HR = 2.00 95% CI: 1.36 to 2.94). Low maternal hemoglobin concentration and child undernutrition were related to an increased risk of mortality in this cohort of children. Low maternal CD4 cell count during pregnancy is related to increased risk of mortality in children born to HIV-infected women. Care and treatment for HIV disease including highly active antiretroviral therapy to pregnant women could improve child survival. Prevention and treatment of undernutrition in children remain critical interventions in settings with high HIV prevalence. (authors)

Vitamin deficiencies are frequent in children suffering from malaria. The effects of maternal multivitamin supplementation on the risk of malaria in children are unknown. We examined the impact of providing multivitamins or vitamin A/beta-carotene supplements during pregnancy and lactation to HIV-infected women on their children's risk of malaria up to 2 years of age, in a randomized, placebo-controlled trial. Tanzanian women (N = 829) received one of four daily oral regimens during pregnancy and after delivery: 1) vitamins B, C, and E (multivitamins); 2) vitamin A and beta-carotene (VA/BC); 3) multivitamins including VA/BC; or 4) placebo. After 6 months of age, all children received 6-monthly oral vitamin A supplements irrespective of treatment arm. The incidence of childhood malaria was assessed through three-monthly blood smears and at monthly and interim clinic visits from birth to 24 months of age. Compared with placebo, multivitamins excluding VA/BC reduced the incidence of clinical malaria by 71% (95% CI = 11-91%; P = 0.02), whereas VA/BC alone resulted in a nonsignificant 63% reduction (95% CI = -4% to 87%; P = 0.06). Multivitamins including VA/BC significantly reduced the incidence of high parasitemia by 43% (95% CI = 2-67%; P = 0.04). The effects did not vary according to the children's HIV status. Supplementation of pregnant and lactating HIV-infected women with vitamins B, C, and E might be a useful, inexpensive intervention to decrease the burden of malaria in children born to HIV-infected women in sub-Saharan Africa.

Aim: To compare growth patterns between human immunodeficiency virus (HIV)-infected and -uninfected preschool children. To examine the associations between diarrheal and respiratory infections sociodemographic factors and growth. Methods: A longitudinal study was conducted among 524 children who were 6-60 mo of age at recruitment. Information on sociodemographic characteristics was collected at baseline from the caregiver. Hemoglobin malaria infection and HIV status of the children were assessed from a blood sample. Monthly height (length if

Background The aims of this study were to examine the impact of child HIV infection on mortality and to identify nutritional and sociodemographic factors that increase the risk of child mortality independent of human immunodeficiency virus (HIV) infection. Methods We conducted a prospective study in Dar es Salaam, Tanzania, among 687 children 6‐60 months of age who were admitted to hospital with pneumonia. After discharge, children were followed up every 2 weeks during the first year and every 4 months thereafter. Sociodemographic characteristics were determined at baseline, and HIV status, haemoglobin, and malaria infection were assessed from a blood sample. During the first year of follow-up, we measured height, weight, and mid-upper arm circumference (MUAC) monthly. We estimated the risk of mortality according to HIV status and socio-economic characteristics using Cox proportional hazards models. Nutritional status variables (wasting and stunting) were examined as time-varying risk factors. Results Mean age at enrolment was 18 months. A total of 90 children died during an average 24.7 months of follow-up. HIV infection was associated with an adjusted 4-fold higher risk of mortality [relative risk (RR) = 3.92, 95% confidence interval (CI) 2.34‐6.55, P � 0.0001]. Other risk factors included child’s age � 24 months, stunting, low MUAC, anaemia, and lack of water supply in the household. In models with time-varying covariates, stunting and wasting during the previous month were both significant and independently related to increased risk of death. HIV infection appeared to be a stronger predictor of mortality among children who were wasted than among those who were not (P for interaction = 0.05). Conclusions HIV infection is a strong predictor of death among children who have been hospitalized with pneumonia. Preventable conditions including inadequate water supply, child undernutrition, and anaemia contribute significantly to infant and child mortality independent of HIV infection.

Summary Objectives To ascertain whether malaria parasitaemia in children is associated with HIV status. To examine the effect of vitamin A supplementation on malaria parasitaemia in children. Methods We studied the cross-sectional associations between HIV status and malaria parasitaemia among 546 children 6–60 months of age who participated in a double-blind, randomized clinical trial of vitamin A supplementation. Prevalence ratios and 95% confidence intervals (CI) were estimated for the presence of malaria parasites at baseline by HIV status in uni- and multivariate models that adjusted for sociodemographic and environmental variables. Among children with malaria, correlates of high parasite loads were identified. Next, we examined the effect of vitamin A supplementation on the risk of malaria parasitaemia and high parasite density at 4–8 months of the first dose in a subset of children. Results The prevalence of malaria parasitaemia was 11.4% among HIV-infected children, compared with 27.6% among uninfected. After adjusting for season, anaemia, use of bednets, maternal education and indicators of socioeconomic status, we found some evidence for lower prevalence of parasitaemia among HIV positive compared with HIV-negative children (prevalence ratio = 0.56; 95% CI = 0.29, 1.09; P = 0.09). Other important correlates of malaria parasitaemia at baseline included low level of maternal education, poor quality of water supply, and the presence of animals at home. Vitamin A supplementation did not have a significant effect on malaria parasitaemia at 4–8 months of follow-up, overall or within levels of potential effect modifiers. Conclusion HIV infection appears to be negatively correlated with malaria parasitaemia in this group of children. Investing in women's education is likely to decrease the prevalence of malaria parasitaemia in children. Vitamin A supplementation does not seem to have an effect on malaria parasitaemia in this population; possible benefits against clinical episodes and severe malaria deserve further examination.

Background: Monitoring mortality and morbidity attributable to malaria is paramount to achieve elimination of malaria. Diagnosis of malaria is challenging and PCR is a reliable method for identifying malaria with high sensitivity. However, blood specimen collection and transport can be challenging and obtaining dried blood spots (DBS) on filter paper by finger-prick may have advantages over collecting whole blood by venepuncture. Methods: DBS and whole blood were collected from febrile children admitted at the general paediatric wards at a referral hospital in Dar es Salaam, Tanzania. DNA extracted from whole blood and from DBS was tested with a genus-specific PCR targeting the mitochondrial Plasmodium genome. Positive samples by PCR of DNA from whole blood were tested with species-specific PCR targeting the 18S rRNA locus, or sequencing if species-specific PCR was negative. Rapid diagnostic test (RDT) and thin blood smear microscopy was carried out on all patients where remnant whole blood and a blood slide, respectively, were available. Results: Positivity of PCR was 24.5 (78/319) and 11.2% (52/442) by whole blood and DBS, respectively. All samples positive on DBS were also positive on Plasmodium falciparum species-specific PCR. All RDT positive cases were also positive by DBS PCR. All but three cases with positive blood slides were also positive by DBS. Conclusions: In this study, PCR for malaria mitochondrial DNA extracted from whole blood was more sensitive than from DBS. However, DBS are a practical alternative to whole blood and detected approximately the same number of cases as RDTs and, therefore, remain relevant for research purposes. publishedVersion

Objective: To determine the effect of vitamin A supplementation on the risk of diarrhea and of acute respiratory infection. Design: Double-blind, randomized, placebo-controlled trial. Setting: Dar-es-Salaam, Tanzania. Subjects: Six hundred eighty-seven children, 6 to 60 months old, hospitalized with pneumonia, who received vitamin A or placebo at baseline and at 4 and 8 months after discharge from hospital. Main outcome variables: Incidence and duration of episodes of diarrhea and respiratory tract infections during the year after discharge from the hospital. Results: Relative to those receiving placebo, children receiving vitamin A had a significantly smaller risk of severe watery diarrhea (multivariate odds ratio = 0.56, 95% CI = 0.32-0.99, P =.04) but a higher risk of cough and rapid respiratory rate (multivariate odds ratio = 1.67, 95% CI = 1.17-2.36, P =.004). Vitamin A supplementation was also associated with increased risk of acute diarrhea among normally nourished children or children with stunted growth but was relatively protective among children with wasting disease (P value for interaction =.01). The apparently increased risk of respiratory tract infection was limited to children who were seronegative for human immunodeficiency virus (HIV) (P value for interaction =.07). Conclusions: Vitamin A supplements provide a low-cost intervention against morbidity in HIV-infected and undernourished children. Supplements may also have serious non-lethal adverse outcomes in well-nourished individuals. Whether these apparent detrimental effects of vitamin A are transient or long-term needs to be examined. (J Pediatr 2000;137:660-7)

Zinc supplementation prevents incident pneumonia in children; however, the effect for pneumonia treatment remains unclear.A randomized, double-blind, placebo-controlled trial of zinc supplements (daily 25 mg) adjunct to antibiotic treatment of radiology-confirmed acute pneumonia was conducted among hospitalized children (6-36 months) in Dar es Salaam, Tanzania.The trial was stopped early due to low enrollment, primarily owing to exclusion of children outside the age range and3 days of prior illness. Among children enrolled (n = 94), zinc supplementation indicated no beneficial effect on the duration of hospitalization (IRR: 0.69; 95% CI 0.45-1.06; p = 0.09) or the proportion of children who were hospitalized for3 days (RR: 0.85; 95% CI: 0.57-1.25; p = 0.40) or5 days (RR: 1.01; 95% CI: 0.83-1.23; p = 0.92) (IRRs and RRs1.0 favor zinc).Although underpowered, this randomized trial provided no evidence for a beneficial effect of zinc supplementation adjunct to antibiotics for hospitalized children.

Background: Asymptomatic malaria parasitaemia has been reported in areas with high malaria transmission. It may serve as a reservoir for continued transmission, and furthermore complicates diagnostics, as not all individuals with a positive malaria test are necessarily ill due to malaria, although they may present with malaria-like symptoms. Asymptomatic malaria increases with age as immunity to malaria gradually develops. As mortality and morbidity of malaria is higher among younger children it is important to know the prevalence of asymptomatic malaria parasitaemia in this population in order to interpret laboratory results for malaria correctly. Methods: A total of 108 children that had neither been treated for malaria nor had a fever the previous four weeks were recruited consecutively at a maternal and child health clinic (MCHC) in Dar es Salaam, Tanzania. A rapid diagnostic test (RDT) for malaria and dried blood spot (DBS) on filter paper were taken from each child. Social and clinical data were recorded. DNA was extracted from the DBS of study participants by a method using InstaGene™ matrix. PCR targeting the Plasmodium mitochondrial genome was performed on all samples. Results: Median age was 4.6 months (range 0.5-38). All the RDTs were negative. PCR was negative for all study subjects. Conclusion: The study suggests that asymptomatic malaria may not be present in apparently healthy children up to the age of three years in Dar es Salaam, Tanzania. However, because of the small sample size and low median age of the study population, the findings cannot be generalized. Larger studies, including higher age groups, need to be done to clarify whether asymptomatic malaria parasitaemia is present in the general population in the Dar es Salaam area. publishedVersion

Background: Malaria is a major cause of paediatric morbidity and mortality. As no clinical features clearly differentiate malaria from other febrile illnesses, and malaria diagnosis is challenged by often lacking laboratory equipment and expertise, overdiagnosis and overtreatment is common. Methods: Children admitted with fever at the general paediatric wards at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania from January to June 2009 were recruited consecutively and prospectively. Demographic and clinical features were registered. Routine thick blood smear microscopy at MNH was compared to results of subsequent thin blood smear microscopy, and rapid diagnostics tests (RDTs). Genus-specific PCR of Plasmodium mitochondrial DNA was performed on DNA extracted from whole blood and species-specific PCR was done on positive samples. Results: Among 304 included children, 62.6% had received anti-malarials during the last four weeks prior to admission and 65.1% during the hospital stay. Routine thick blood smears, research blood smears, PCR and RDT detected malaria in 13.2%, 6.6%, 25.0% and 13.5%, respectively. Positive routine microscopy was confirmed in only 43% (17/40), 45% (18/40) and 53% (21/40), by research microscopy, RDTs and PCR, respectively. Eighteen percent (56/304) had positive PCR but negative research microscopy. Reported low parasitaemia on routine microscopy was associated with negative research blood slide and PCR. RDT-positive cases were associated with signs of severe malaria. Palmar pallor, low haemoglobin and low platelet count were significantly associated with positive PCR, research microscopy and RDT. Conclusions: The true morbidity attributable to malaria in the study population remains uncertain due to the discrepancies in results among the diagnostic methods. The current routine microscopy appears to result in overdiagnosis of malaria and, consequently, overuse of anti-malarials. Conversely, children with a false positive malaria diagnosis may die because they do not receive treatment for the true cause of their illness. RDTs appear to have the potential to improve routine diagnostics, but the clinical implication of the many RDT-negative, PCR-positive samples needs to be elucidated. publishedVersion

Background Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately. Methods 255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin. Results There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n = 22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI = 0.12, 1.10; p = 0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p < 0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n = 48; 2 cm, compared to 1 cm in the placebo group; 95% CI = 0.20, 1.70; p = 0.01; p for interaction by age group = 0.01). Conclusions Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. Clinicaltrials.gov Identifier NCT00145184

To understand patient and clinician attitudes toward Streptococcus pharyngitis and rheumatic heart disease prevention in Tanzania, data from 3 sources were obtained: a survey of 119 clinicians, outpatient rapid test screening, and interviews with 17 rheumatic heart disease patients. Patients do not seek care for sore throat. Clinicians stated that identifying and treating Streptococcus pharyngitis is not prioritized.

Extended-spectrum beta-lactamases (ESBLs) were present in high proportions of Escherichia coli (25% [9 of 36]) and Klebsiella pneumoniae isolates (17% [9 of 52]) causing pediatric septicemia at a tertiary hospital in Tanzania. Patients with septicemia due to ESBL-producing organisms had a significantly higher fatality rate than those with non-ESBL isolates (71% versus 39%, P = 0.039). This is the first report of the CTX-M-15 genotype of ESBLs on the African continent and the first observation of SHV-12 genotype in an isolate of Salmonella enterica serotype Newport.

Objectives. To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children. Design. Randomized, double blind, placebo-controlled trial. Methods. Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children

Objective. Evidence from animal experiments and observational studies in humans suggests that vitamin A plays a fundamental role in physical growth. However, results from vitamin A supplementation trials in children are inconsistent; whereas some did not find an overall effect on growth, others found benefits only among specific groups, including children with low concentrations of serum retinol or short duration of breastfeeding. The apparent lack of an overall effect of vitamin A on growth could be attributed to context-specific distribution of conditions that affect both growth and the response to supplementation, eg, baseline vitamin A status, deficiency of other nutrients (fat, zinc), and the presence of infectious diseases. Human immunodeficiency virus (HIV) infection, malaria, and diarrheal disease adversely affect growth and are associated with increased prevalence of vitamin A deficiency. We hypothesize that vitamin A supplementation could ameliorate the adverse effect of these infections on child growth. Methods. We conducted a randomized, clinical trial among 687 Tanzanian children who were 6 to 60 months of age and admitted to the hospital with pneumonia. Children were assigned to oral doses of 200 000 IU vitamin A (half that dose if Results. A total of 554 children had at least 2 follow-up measurements of height or weight and constituted the study base. Baseline characteristics did not differ significantly by treatment arm. Seventy-three percent of the children were Conclusions. Vitamin A supplementation improves linear and ponderal growth in infants who are infected with HIV and malaria, respectively, and decreases the risk of stunting associated with persistent diarrhea. Supplementation could constitute a low-cost, effective intervention to decrease the burden of growth retardation in settings where infectious diseases are highly prevalent.