Ugandan Infants Research Articles

Maternal education is associated with vaccination status of infants less than 6 months in Eastern Uganda: a cohort study

BackgroundDespite provision of free childhood vaccinations, less than half of all Ugandan infants are fully vaccinated. This study compares women with some secondary schooling to those with only primary schooling with regard to their infants' vaccination status.MethodsA community-based prospective cohort study conducted between January 2006 and May 2008 in which 696 pregnant women were followed up to 24 weeks post partum. Information was collected on the mothers' education and vaccination status of the infants.ResultsAt 24 weeks, the following vaccinations had been received: bacille Calmette-Guérin (BCG): 92%; polio-1: 91%; Diphteria-Pertussis-Tetanus-Hepatitis B-Haemophilus Influenza b (DPT-HB-Hib) 3 and polio-3: 63%. About 51% of the infants were fully vaccinated (i.e., had received all the scheduled vaccinations: BCG, polio 0, polio 1, DPT-HB-Hib1, polio 2, DPT-HB-Hib 2, polio 3 and DPT-HB-Hib 3). Only 46% of the infants whose mothers' had 5-7 years of primary education had been fully vaccinated compared to 65% of the infants whose mothers' had some secondary education. Infants whose mothers had some secondary education were less likely to miss the DPT-HB-Hib-2 vaccine (RR: 0.5, 95% CI: 0.3, 0.8), Polio-2 (RR: 0.4, 95%CI: 0.3, 0.7), polio-3 (RR: 0.5, 95%CI: 0.4, 0.7) and DPT-HB-Hib-3 (RR: 0.5, 95%CI: 0.4, 0.7). Other factors showing some association with a reduced risk of missed vaccinations were delivery at a health facility (RR = 0.8; 95%CI: 0.7, 1.0) and use of a mosquito net (RR: 0.8; 95%CI: 0.7, 1.0).ConclusionInfants whose mothers had a secondary education were at least 50% less likely to miss scheduled vaccinations compared to those whose mothers only had primary education. Strategies for childhood vaccinations should specifically target women with low formal education.

Analysis of HIV Tropism in Ugandan Infants

HIV-infected infants may have CXCR4-using (X4-tropic) HIV, CCR5-using (R5-tropic) HIV, or a mixture of R5-tropic and X4-tropic HIV (dual/mixed, DM HIV). The level of infectivity for R5 virus (R5-RLU) varies among HIV infected infants. HIV tropism and R5-RLU were measured in samples from HIV-infected Ugandan infants using a commercial assay. DM HIV was detected in 7/72 (9.7%) infants at the time of HIV diagnosis (birth or 6-8 weeks of age, 4/15 (26.7%) with subtype D, 3/57 (5.3 %) with other subtypes, P=0.013). A transition from R5-tropic to DM HIV was observed in only two (6.7%) of 30 infants over 6-12 months. Six (85.7%) of seven infants with DM HIV died, compared to 21/67 (31.3%) infants with R5-tropic HIV (p=0.09). Higher R5-RLU at 6-8 weeks was not associated with decreased survival. Infants with in utero infection had a higher median R5-RLU than infants who were HIV-uninfected at birth (p=0.025).

Considerations in Using US-Based Laboratory Toxicity Tables to Evaluate Laboratory Toxicities Among Healthy Malawian and Ugandan Infants

To determine normal hematologic and selected blood chemistry values among healthy, full-term, non-HIV-exposed infants in Uganda and Malawi, and to determine the proportion of healthy babies with an apparent laboratory toxicity based on Division of AIDS toxicity tables. This was a cross-sectional laboratory study of infants from birth to 6 months of age. Blood samples were collected from a total of 561 infants and analyzed according to age categories similar to those in the 2004 Division of AIDS toxicity tables. Select chemistry and hematology parameters were determined and values compared with those in the toxicity tables. In the first 56 days of life, there were few graded toxicities except for neutropenia in 2 of 10 (20%) Ugandan and 13 of 45 (29%) Malawian infants at birth. After 7 days, about 20% of the infants in Uganda and Malawi would have been classified as having a neutropenia whereas 47% and 53% of those more than 2 months of age in Uganda and Malawi respectively, would have been reported as having an abnormal hemoglobin. Chemistry findings were not different from US norms. These findings underscore the importance of establishing relevant local laboratory norms for infants.

Cranial ultrasound findings in well newborn Ugandan infants

BackgroundThere has been no study assessing cranial ultrasound (cUS) scans in newborn infants born in equatorial Africa.ObjectiveTo assess the cUS scans of apparently well newborn term Ugandan infants and to...

Vertical transmission of X4-tropic and dual-tropic HIV-1 in five Ugandan mother–infant pairs

We previously reported the existence of CXCR4-using HIV-1 in 6-14 week-old Ugandan infants. Whether these viruses were transmitted from the mother perinatally or evolved after transmission is not known. In the current study, we investigated the origin of the CXCR4-using viruses in these infants by comparing HIV-1 envelope clones from the infants to those from their mothers at or near the time of delivery. Envelope clones were isolated from five Ugandan infant plasma samples that harbored CXCR4-using viruses, collected at the time of HIV diagnosis (four at birth, one at week 6), and from their mothers at delivery. Coreceptor usage and phylogenetic relatedness of HIV-1 populations in mother-infant pairs were analyzed in detail using the Trofile assay and sequence analysis of envelope clones, respectively. X4-tropic clones were identified in two mother-infant pairs and dual-tropic clones were found in three pairs, either alone or in combination with R5-tropic viruses. Dual-tropic clones varied in their ability to infect CXCR4-expressing cells. In each mother-infant pair, X4-tropic or dual-tropic clones shared similar phenotypic profiles and V3 sequence patterns; gp160 sequences of X4-tropic and dual-tropic clones from infants were phylogenetically indistinguishable from those of their mothers. The virus populations were phylogenetically homogenous in three infants and segregated according to coreceptor tropism in the remaining two infants. This study demonstrates that X4-tropic and dual-tropic HIV-1 can be transmitted from mother to infant, before, during or shortly after delivery, and establishes vertical transmission as an important source of CXCR4-using viruses in infants.

Assessing the association between trends in a biomarker and risk of event with an application in pediatric HIV/AIDS

We present a new joint longitudinal and survival model aimed at estimating the association between the risk of an event and the change in and history of a biomarker that is repeatedly measured over time. We use cubic B-splines models for the longitudinal component that lend themselves to straight-forward formulations of the slope and integral of the trajectory of the biomarker. The model is applied to data collected in a long term follow-up study of HIV infected infants in Uganda. Estimation is carried out using MCMC methods. We also explore using the deviance information criteria, the conditional predictive ordinate and ROC curves for model selection and evaluation.

In Utero HIV Infection Is Associated with an Increased Risk of Nevirapine Resistance in Ugandan Infants Who Were Exposed to Perinatal Single Dose Nevirapine

Use of single dose nevirapine (sdNVP) to prevent HIV mother-to-child transmission is associated with the emergence of NVP resistance in many infants who are HIV infected despite prophylaxis. We combined results from four clinical trials to analyze predictors of NVP resistance in sdNVP-exposed Ugandan infants. Samples were tested with the ViroSeq HIV Genotyping System and a sensitive point mutation assay (LigAmp, for detection of K103N, Y181C, and G190A). NVP resistance was detected at 6-8 weeks in 36 (45.0%) of 80 infants using ViroSeq and 33 (45.8%) of 72 infants using LigAmp. NVP resistance was more frequent among infants who were infected in utero than among infants who were diagnosed with HIV infection after birth by 6-8 weeks of age. Detection of NVP resistance at 6-8 weeks was not associated with HIV subtype (A vs. D), pre-NVP maternal viral load or CD4 cell count, infant viral load at 6-8 weeks, or infant sex. NVP resistance was still detected in some infants 6-12 months after sdNVP exposure. In this study, in utero HIV infection was the only factor associated with detection of NVP resistance in infants 6-8 weeks after sdNVP exposure.

Factors associated with caregivers’ perception of children's health and oral health status: a study of 6‐ to 36‐month‐olds in Uganda

The impact of oral diseases on quality of life of children and their families has not been thoroughly investigated. Focusing on Ugandan infants aged 6-36 months and their caregivers, this study examined the degree to which clinical and psychosocial factors were associated with caregivers' overall evaluation of their children's oral health and health status. Eight hundred and sixteen children were examined for dental caries and anthropometric status in 2007. A questionnaire was completed by the caregivers. Poor child oral health was reported by 40.2% and 17.5% of caregivers who reported their children's health as, respectively, poor and good. Having the least family wealth [odds ratio (OR) = 1.9] and reporting distressed family activities (OR = 2.3) were associated with higher odds of reporting poor child oral health, whereas being a rural resident (OR = 0.4) and reporting no symptoms during tooth eruption (OR = 0.3) were associated with lower odds. Perception of poor child oral health (OR = 2.8) and having the least family wealth (OR = 1.7) were associated with higher odds of reporting poor child health status, whereas no stunting was associated with lower odds (OR = 0.5). The results support the growing recognition of oral health as a predictor of health and well-being in early childhood.

Determinants of infant growth in Eastern Uganda: a community-based cross-sectional study.

BackgroundChild under-nutrition is a leading factor underlying child mortality and morbidity in Sub-Saharan Africa. Several studies from Uganda have reported impaired growth, but there have been few if any community-based infant anthropometric studies from Eastern Uganda. The aim of this study was to describe current infant growth patterns using WHO Child Growth Standards and to determine the extent to which these patterns are associated with infant feeding practices, equity dimensions, morbidity and use of primary health care for the infants.MethodsA cross-sectional survey of infant feeding practices, socio-economic characteristics and anthropometric measurements was conducted in Mbale District, Eastern Uganda in 2003; 723 mother-infant (0–11 months) pairs were analysed. Infant anthropometric status was assessed using z-scores for weight-for-length (WLZ), length-for-age (LAZ) and weight-for-age (WAZ). Dependent dichotomous variables were constructed using WLZ < -2 (wasting) and LAZ < -2 (stunting) as cut-off values. A conceptual hierarchical framework was used as the basis for controlling for the explanatory factors in multivariate analysis. Household wealth was assessed using principal components analysis.ResultsThe prevalences of wasting and stunting were 4.2% and 16.7%, respectively. Diarrhoea during the previous 14 days was associated with wasting in the crude analysis, but no factors were significantly associated with wasting in the adjusted analysis. The adjusted analysis for stunting showed associations with age and gender. Stunting was more prevalent among boys than girls, 58.7% versus 41.3%. Having brothers and/or sisters was a protective factor against stunting (OR 0.4, 95% CI 0.2–0.8), but replacement or mixed feeding was not (OR 2.7, 95% CI 1.0–7.1). Lowest household wealth was the most prominent factor associated with stunting with a more than three-fold increase in odds ratio (OR 3.5, 95% CI 1.6–7.8). This pattern was also seen when the mean LAZ was investigated across household wealth categories: the adjusted mean difference between the top and the bottom wealth categories was 0.58 z-scores, p < 0.001. Those who had received pre-lacteal feeds had lower adjusted mean WLZ than those who had not: difference 0.20 z-scores, p = 0.023.ConclusionSub-optimal infant feeding practices after birth, poor household wealth, age, gender and family size were associated with growth among Ugandan infants.

Analysis of Nevirapine (NVP) Resistance in Ugandan Infants Who Were HIV Infected Despite Receiving Single-Dose (SD) NVP versus SD NVP Plus Daily NVP Up to 6 Weeks of Age to Prevent HIV Vertical Transmission

Single-dose nevirapine (SD NVP) at birth plus NVP prophylaxis for the infant up to 6 weeks of age is superior to SD NVP alone for prevention of vertical transmission of human immunodeficiency virus (HIV) through breastfeeding. We analyzed NVP resistance in HIV-infected Ugandan infants who received either SD NVP or extended NVP prophylaxis. We tested plasma HIV by using a genotyping assay (ViroSeq; Celera Diagnostics), a phenotypic resistance assay (PhenoSense; Monogram Biosciences), and sensitive point mutation assay (LigAmp, for K103N, Y181C, and G190A). When infants were 6 weeks old, ViroSeq detected NVP resistance in a higher proportion of infants in the extended NVP arm than in the SD NVP arm (21 of 25 [84%] vs. 12 of 24 [50%]; P = .01). Similar results were obtained with LigAmp and PhenoSense. In both study arms, infants who were HIV infected at birth frequently had NVP resistance detected. In contrast, infants in the extended NVP arm who were HIV infected after birth were more likely to have resistance detected at 6 weeks, compared with infants in the SD NVP arm. The use of extended NVP prophylaxis was also associated with detection of NVP resistance by ViroSeq at 6 months (7 of 7 [100%] infants in the extended NVP arm had resistance detected, compared with 1 of 6 [16.7%] infants in the SD NVP arm; P = .005). The use of extended NVP prophylaxis was associated with increased selection for and persistence of NVP resistance in HIV-infected Ugandan infants.

Analysis of Nevirapine Resistance Mutations in Cloned HIV Type 1 Variants from HIV-Infected Ugandan Infants Using a Single-Step Amplification-Sequencing Method (AmpliSeq)

We analyzed the genetic linkage of nevirapine (NVP) resistance mutations and the genetic complexity of HIV-1 variants in Ugandan infants who were HIV infected despite single dose (SD) prophylaxis. Plasma samples were obtained from six HIV-infected infants who had two or more NVP resistance mutations detected by population sequencing (ViroSeq). ViroSeq PCR products were cloned and transformed, and a single-step amplification-sequencing reaction (AmpliSeq) was used to analyze NVP resistance mutations in cloned HIV-1 variants directly from bacterial colonies. Fifty clones were analyzed for each infant sample. This analysis revealed numerous NVP resistance mutations not detected by population sequencing, genetically linked NVP resistance mutations, and a high degree of genetic complexity at codons that influence NVP susceptibility.

HIV‐1 Tropism and Survival in Vertically Infected Ugandan Infants

Human immunodeficiency virus type 1 (HIV-1) may utilize the CXCR4 coreceptor (X4 virus), the CCR5 coreceptor (R5 virus), or both (dual/mixed [DM] virus). We analyzed HIV-1 coreceptor tropism in Ugandan infants enrolled in the HIVNET (HIV Network for Prevention Trials) 012 trial. Plasma or serum was analyzed using a commercial coreceptor tropism assay. HIV env subtype was determined by phylogenetic methods. Tropism results were obtained for 57 samples from infants collected 6-14 weeks after birth. Fifty-two infants had only R5 virus, and 5 had either X4 or DM virus. The mothers of those 5 infants also had X4 or DM virus. In infants, subtype D infection was associated with high-level infectivity in CCR5-bearing cells and also with the detection of X4 or DM strains. High-level infectivity in CCR5-bearing cells was associated with decreased infant survival, but infection with X4 or DM virus was not. HIV clones from infants with DM viral populations showed different patterns of coreceptor use. V3 loop sequence-based algorithms predicted the tropism of some, but not all, env clones. Complex patterns of HIV tropism were found in HIV-infected newborn infants. Subtype D infection was associated with X4 virus and with high-level replication in CCR5-bearing cells. High-level replication of R5 virus was associated with decreased infant survival.

Resistance after single-dose nevirapine prophylaxis emerges in a high proportion of Malawian newborns

The administration of single-dose nevirapine to women in labor and their infants can prevent HIV-1 mother-to-child transmission. We examined nevirapine resistance in infants who were HIV-1 infected despite single-dose nevirapine prophylaxis, including 18 Ugandan infants (HIVNET 012 trial, nine subtype A and nine subtype D) and 23 Malawian infants (NVAZ trial, all subtype C). Nevirapine resistance was more frequent in infants with subtype C than with subtypes A and D (87 versus 50%, P = 0.016).

An Examination of the Combined Effects of Maternal Characteristics, Environment and Treatment Programs on the Prevalence of Diarrhea Amongst Infants and Children in Uganda

At least two decades of research identifies Diarrhea as among the leading causes of morbidity and mortality among children in developing countries. Some estimate that approximately 20% of all deaths amongst children are directly related to diarrhea. In 1993, the World Health Organization estimated that in some sub-Saharan countries more than 50% of the deaths of children are due to diarrhea. Studies show that the risk of exposure to the causes of diarrhea is strongly related to both environmental characteristics and the socioeconomic characteristics of mothers. Indeed, infant mortality itself continues to be used as an indicator of standard of living and environmental conditions. This is especially true for children below the age of 2 years. Studies indicate that the characteristics of the primary caregivers, the cleanliness of the environment, and the availability of treatment, are all significant factors in the prevalence of diarrhea amongst infants in a population. While these patterns are frequently documented in research, few studies have examined in detail the separate and combined effects of mother's characteristics, environment, and the availability of health care. The present study examines the interrelationship of socioeconomic characteristics of mothers, selected environmental factors, treatment options, and the prevalence of diarrhea in Ugandan infants. The research utilizes data from the Uganda Demographic and Health Survey. This study elaborates the specific conditions and circumstances that account for variation in the health of children and how these relate to the characteristics of the mothers and well as the environment.

Characterization of a subtype D human immunodeficiency virus type 1 isolate that was obtained from an untreated individual and that is highly resistant to nonnucleoside reverse transcriptase inhibitors.

Human immunodeficiency virus type 1 (HIV-1) isolates derived from HIV-infected, treatment-naive Ugandan infants were propagated and tested for sensitivity to antiretroviral (ARV) drugs. Although most subtype A and D isolates displayed inhibition profiles similar to those of subtype B strains, a subtype D isolate identified as D14-UG displayed high-level resistance to nevirapine in peripheral blood mononuclear cell cultures (>2,000-fold) and in MT4 cell cultures ( approximately 800-fold) but weaker resistance to delavirdine ( approximately 13-fold) and efavirenz ( approximately 8-fold) in MT4 cell cultures. To investigate the possible mechanism for this resistance to nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs), the RT coding region in pol was sequenced and compared to the consensus RT sequence of NNRTI-resistant and NNRTI-sensitive subtype A, B, and D HIV-1 isolates. D14-UG did not contain the classic amino acid substitutions conferring NNRTI resistance (e.g., Y181C, K103N, and G190A) but did have some putative sites associated with drug resistance, I135L, T139V, and V245T. Wild-type and mutated protease-RT genes from D14-UG and an NNRTI-sensitive subtype D isolate from Uganda (D13-UG) were cloned into pNL4-3 to produce recombinant viruses and to determine the effects of the mutations on susceptibility to ARV drugs, specifically, NNRTIs. The results showed that I135L and/or V245T mutations can confer high-level resistance to nevirapine and delavirdine as well as low level cross-resistance to efavirenz. Finally, ex vivo fitness analyses suggested that NNRTI-resistant sites 135L and 245T in wild-type isolate D14-UG may reduce RT fitness but do not have an impact on the fitness of the primary HIV-1 isolate.

IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of immunodeficiency virus infection in Ugandan infants.

The value of HIV-1 IgA antibodies for early diagnosis of HIV infection in infants in serum, saliva and urine was investigated at Mulago Hospital, Kampala. Sensitivity and specificity in serum of HIV-infected infants at different ages were: 0 to 1 months, 88 and 95%; 1 to 3 months, 88 and 97%; 4 to 6 months, 80 and 96%. They decreased between 67 and 77% and 80 to 91%, respectively, in older age groups. Sensitivity for saliva was lower (53 to 79%) and urine only 37 to 62%, although specificity was reasonably high (>85%). The high proportion of infants with raised HIV IgA in the first months of life (88%) may represent prenatal infection. Sensitivity of serum and especially salivary and urinary HIV IgA is too low to be of practical value for early diagnosis of HIV infection in infants.

IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of human immunodeficiency virus infection in Ugandan infants

IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of human immunodeficiency virus infection in Ugandan infants

Survival of Ugandan infants with subtype A and D HIV-1 infection (HIVNET 012).

Virologic factors may influence survival of HIV-1-infected infants. We compared survival of Ugandan infants with subtype A and subtype D HIV-1 infection. This study was performed in the context of the Ugandan clinical trial HIVNET 012, which compared the efficacy of single-dose nevirapine (NVP) and short-course zidovudine (AZT) for prevention of HIV-1 mother-to-child transmission. HIV-1 subtypes were determined by phylogenetic analysis of HIV-1 protease and reverse transcriptase sequences from 32 women in the NVP arm and 54 women in the AZT arm of HIVNET 012 whose infants were HIV-1 infected by 6 to 8 weeks of age. We found no association between HIV-1 subtype (A vs. D) and infant survival in this cohort. Further studies are needed to evaluate whether HIV-1 subtype influences clinical outcome in pediatric HIV-1 infection.

Iron Deficiency Anemia Is Highly Prevalent among Human Immunodeficiency Virus–Infected and Uninfected Infants in Uganda

Although anemia is a common finding among human immunodeficiency (HIV)-infected infants in sub-Saharan Africa, the factors contributing to the pathogenesis of anemia have not been well characterized. We sought to characterize the relative contribution of iron deficiency and chronic disease to the anemia among infants. Hemoglobin, ferritin, erythropoietin, tumor necrosis factor-alpha (TNF-alpha), neopterin, CD4(+) lymphocyte count and plasma HIV load were measured in 165 HIV-infected and 39 uninfected 9-mo-old infants seen in an outpatient pediatric clinic in Kampala, Uganda. Among HIV-infected and uninfected infants, the prevalence of anemia (hemoglobin < 110 g/L) was 90.9 and 76.9%, respectively (P = 0.015), and the prevalence of iron deficiency anemia (hemoglobin < 110 g/L and ferritin < 12 microg/L) was 44.3 and 45.4%, respectively (P = 0.92). The relatively higher prevalence of anemia among HIV-infected infants was attributed to the anemia of chronic disease. Among infants with and without iron deficiency, the fitted regression line was log(10) plasma erythropoietin = 2.86 - 0.016.hemoglobin, and log(10) plasma erythropoietin = 4.11 - 0.028.hemoglobin, respectively, with a difference in the slope of the regression lines between log(10) erythropoietin and hemoglobin among infants with and without iron deficiency (P = 0.049). Infants in Uganda have an extremely high prevalence of anemia, and nearly half of the anemia is due to iron deficiency. The erythropoietin response to anemia appears to be upregulated among infants with iron deficiency.

Relation of vitamin A and carotenoid status to growth failure and mortality among ugandan infants with human immunodeficiency virus

Although growth failure is common during pediatric infection with human immunodeficiency virus (HIV) and associated with increased mortality, the relation of specific nutrition factors with growth and mortality has not been well characterized. A longitudinal study was conducted with 194 HIV-infected infants in Kampala, Uganda. Plasma vitamin A, carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin), and vitamin E were measured at age 14 wk, and weight and height were followed up to age 12 mo. Vitamin A and low plasma carotenoid concentrations were predictive of decreased weight and height velocity. Between ages 14 wk and 12 mo, 32% of infants died. Underweight, stunting, and low concentrations of plasma carotenoids were associated with increased risk of death in univariate analyses. Plasma vitamin A concentrations were not associated with risk of death. In a final multivariate model adjusting for weight-for-age, plasma β-carotene was significantly associated with increased mortality (odds ratio: 3.16, 95% confidence interval: 1.38 to 7.21, P < 0.006). These data suggest that low concentrations of plasma carotenoids are associated with increased risk of death during HIV infection among infants in Uganda.