Christopher Ndugwa

Detection of Kaposi Sarcoma—Associated Herpesvirus DNA in Saliva and Buffy-Coat Samples from Children with Sickle Cell Disease in Uganda

Among 233 children, Kaposi sarcoma-associated herpesvirus (KSHV) DNA was detected in 43% of children seropositive for both K8.1 and orf73, in 29% of children seropositive for K8.1 only, in 14% of children seropositive for orf73 only, and in 7% of children seronegative for both K8.1 and orf73; among 228 mothers, KSHV DNA was detected in 27%, 25%, 4%, and 1%, respectively. KSHV DNA was detected more frequently and at higher levels in saliva than in buffy-coat samples and in children than in mothers. In both children and mothers, detection in saliva was associated with detection in peripheral blood. Detection was associated with K8.1 seropositivity, younger age, and high household density, indicating the importance of in-household person-to-person transmission, likely via saliva.

Placental membrane inflammation and risks of maternal-to-child transmission of HIV-1 in Uganda.

UNLABELLED Prospective follow-up of 172 HIV-infected pregnant women and their infants was conducted at Mulago Hospital, Kampala, Uganda during 1990 to 1992. Information was collected on maternal immune status (CD4 counts or clinical AIDS), and concurrent infections with sexually transmitted diseases. Infants were observed on a follow-up basis to determine HIV infection, using polymerase chain reaction (PCR) under 15 months of age and enzyme immunoassay/Western blot for those older than 15 months. Placental membrane inflammation (chorioamnionitis and funisitis), and placental villous inflammation (villitis, intervillitis, and deciduitis) were diagnosed by histopathology. Mother-to-child HIV transmission rates were assessed, and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of transmission were estimated using women with no placental pathology or evidence of immune suppression as a reference group. RESULTS The overall mother-to-child HIV transmission rate was 23.3%. Women with no placental membrane inflammation or immune suppression had a transmission rate of 11.3%; compared with 25.5% in women with placental inflammation and no immunosuppression (adjusted OR, 2.87; 95% CI, 1.04-7.90), and 37.0% in immunosuppressed women (OR, 3.07; 95% CI, 1.42-6.67). We estimate that 34% of HIV transmission could be prevented by treatment of placental membrane inflammation in nonimmunocompromised women. Transmission rates were 40.9% with genital ulcer disease (OR, 3.57; 95% CI, 1.28-9.66). Placental villous inflammation and artificial rupture of membranes did not increase transmission rates and cesarean section was associated with a nonsignificant reduction of risk (OR, 0.70; 95% CI 0.24-2.06). CONCLUSION Placental membrane inflammation increases the rate of mother-to-child HIV transmission.

Water, Socioeconomic Factors, and Human Herpesvirus 8 Infection in Ugandan Children and Their Mothers

Background:Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its distribution is uneven. Transmission occurs during childhood within families by unclear routes. Methods:We evaluated 600 Ugandan children with sickle cell disease and their mothers for factors associated with HHV-8 seropositivity in a cross-sectional study. HHV-8 serostatus was determined using an HHV-8 K8.1 glycoprotein enzyme immunoassay. Odds ratios for seropositivity were estimated using logistic regression, and factor analysis was used to identify clustering among socioeconomic variables. Results:One hundred seventeen (21%) of 561 children and 166 (34%) of 485 mothers with definite HHV-8 serostatus were seropositive. For children, seropositivity was associated with age, mothers HHV-8 serostatus (especially for children aged 6 years or younger), lower maternal education level, mothers income, and low-status fathers occupation (P < 0.05 for all). Using communal standpipe or using surface water sources were both associated with seropositivity (OR 2.70, 95% CI 0.80-9.06 and 4.02, 95% CI 1.18-13.7, respectively) as compared to using private tap water. These associations remained, albeit attenuated, after adjusting for maternal education and childs age (P = 0.08). In factor analysis, low scores on environmental and family factors, which captured household and parental characteristics, respectively, were positively associated with seropositivity (Ptrend < 0.05 for both). For mothers, HHV-8 seropositivity was significantly associated with water source and maternal income. Conclusions:HHV-8 infection in Ugandan children was associated with lower socioeconomic status and using surface water. Households with limited access to water may have less hygienic practices that increase risk for HHV-8 infection.

High Levels of Epstein-Barr Virus DNA in Saliva and Peripheral Blood from Ugandan Mother-Child Pairs

In Africa, Epstein-Barr virus (EBV) is associated with Burkitt lymphoma. We measured levels of EBV DNA in saliva and buffy coats from 233 asymptomatic Ugandan children with sickle cell disease and their mothers by quantitative real-time polymerase chain reaction. EBV DNA was detected in saliva from 90% of the children (median [interquartile range [IQR]] level, 5.2 [4.2-6.0] log(10) copies/mL of saliva) and 79% of the mothers (median [IQR] level, 4.8 [3.7-5.6] log(10) copies/mL of saliva) (P < .001). EBV DNA was detected in buffy coats from 86% of the children (median [IQR] level, 2.5 [2.2-2.9] log(10) copies/1 x 10(6) peripheral white blood cells [PWBCs]) and 72% of the mothers (median [IQR] level, 2.7 [2.4-3.1] log(10) copies/1 x 10(6) PWBCs) (P = .24). Detection of EBV DNA in saliva was positively correlated with detection in buffy coats. EBV DNA was detected more frequently in saliva and buffy coats than was human herpesvirus 8 DNA. Our results indicate that EBV infection persists, with virus readily detectable in saliva and buffy coats from persons without apparent symptoms in Africa.

Molecular Evidence for Mother-to-Child Transmission of Kaposi Sarcoma–Associated Herpesvirus in Uganda and K1 Gene Evolution within the Host

BACKGROUND Epidemiological studies of Kaposi sarcoma (KS)-related herpesvirus (KSHV) indicate that having a KSHV-seropositive mother is a risk factor for KSHV infection in children. METHODS We determined the KSHV K1 sequences in concordantly polymerase chain reaction-positive Ugandan mother-child pairs, to ascertain whether they shared the same viral strain. We also examined sequences amplified from saliva and buffy coat samples from the same subjects, to investigate potential intrasubject sequence differences. RESULTS We obtained K1 sequences from 6 of 10 mother-child pairs. In 1 pair, the subtypes differed between mother and child. The mother and child in 2 other pairs shared the same subtype, but the sequences differed. The mother and child in 2 pairs shared KSHV strains with exact (100%) nucleotide homology. The last pair showed evidence of viral strain concordance between mother and child but also showed evidence of evolution of the viral sequence within the child. Of 26 study subjects, 19 showed no evidence of intrasubject K1 sequence variability, but, in 7 subjects, all of whom were children, amino acid variation of 1%-4% was observed. CONCLUSIONS Our findings are consistent with KSHV transmission from maternal and nonmaternal sources in KS-endemic regions. Our results also provide evidence for ongoing evolution of the K1 gene in KSHV-infected children.

NEURODEVELOPMENTAL OUTCOMES OF UGANDAN INFANTS WITH HIV INFECTION : AN APPLICATION OF GROWTH CURVE ANALYSIS

Neurodevelopmental outcomes of human immunodeficiency virus Type 1 (HIV-1)-infected infants of non-drug-using mothers were assessed in a controlled, prospective study from birth to 24 months with 3 groups: 61 infants of HIV-infected mothers, 234 uninfected infants of HIV-infected mothers (seroreverters), and 115 uninfected infants of uninfected mothers. Compared with seroreverters and uninfected infants, HIV-infected infants demonstrated lower mental and motor development on the Bayley Scales and greater deceleration in their rate of motor development. HIV-infected infants with abnormal neurologic exams had lower motor and mental test scores and lower rates of motor Bayley Scales scores than their HIV-infected counterparts with normal neurologic exams. Contrary to prediction, no group differences in mean performance or growth rates were found on visual information processing on the Fagan Test of Infant Intelligence.

Epidemiologic and clinical features of HIV-infected and HIV-uninfected ugandan children younger than 18 months

Methods: Groups of HIV‐infected and HIV‐uninfected infants younger than 18 months (mainly younger than 6 months) were compared to identify clinical features that could differentiate the two groups. The HIV‐infected group also was compared with HIV‐infected children older than 18 months. Recruitment was as follows for the group younger than 18 months: 708 children admitted with sepsis and clinical features suggestive of HIV infection were screened for HIV1 and HIV2 by HIV enzyme‐linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) was undertaken on all ELISA‐seropositive blood samples (270). HIV infection was confirmed in 136 (19.2%), 438 (61.9%) were HIV‐seronegative, 27 (3.8%) were HIV seroreverters, 36 (5.1%) were HIV‐seropositive but PCR negative (uninfected), and 71 (10.0%) were indeterminate. One hundred thirty‐six HIV‐infected children were compared with 501 uninfected children. Confirmed HIV‐infected children older than 18 months attending the pediatric HIV clinic were compared with the 136 HIV‐infected children younger than 18 months. Results: Under 18 months, the median age of HIV‐infected children (n = 136) was 4.0 months (range, 3 d‐18 mo) and the median age of the uninfected children (n = 501) was 1.0 month (range, 3 d‐18 mo). HIV‐infected children were more likely to have had injections, chloroquine, and nystatin, and to have attended a health center or hospital (p < .001). In the HIV‐infected group, the Z score for weight‐for‐age was ‐1.75, length‐for‐age ‐0.78, and weight‐for‐length 1.86, significantly lower scores than those of the uninfected group, which were ‐0.60, ‐0.23, and 3.05, respectively (p < .05). The mean head circumference was below the third percentile in 40% of HIV‐infected compared with 22% of uninfected children (p < .001). Overall, 56 (8%) children had marasmus, 6 (0.8%) kwashiorkor, and 3 (0.4%) marasmic kwashiorkor. Sixteen percent of the HIV‐infected and 7% of uninfected children had marasmus (p < .05). The 1989 revised World Health Organization clinical criteria for diagnosis of AIDS had sensitivity, specificity, and positive predictive values of 28%, 98%, and 93%, respectively. Older than 18 months (n = 109), the median age was 24 months (range, 18‐60 mo). The following were significantly more common in HIV‐infected children older than 18 months than in those younger than 18 months: bacille Calmette‐Guérin vaccination scar, parotid enlargement, nonspecific generalized dermatitis, and chronic diarrhea (p < .001). Oral candidiasis was more common in the group younger than 18 months (p < .001). In infants examined in the hospital for infective conditions, oropharyngeal candidiasis, ear discharge, dermatologic disorders, generalized lymphadenopathy, lobar consolidation, hepatosplenomegaly, and failure to thrive, especially marasmus, were important indicators of HIV infection.

Identification of diverse HIV type 1 subtypes and dual HIV type 1 infection in pregnant Ugandan women.

Vertical (mother-to-child) transmission accounts for the majority of pediatric HIV-1 infections. Many factors are involved in vertical transmission, however it is not clear which factors are most important for determining whether a mother will transmit HIV-1 to her infant. It has been suggested that HIV-1 subtype may influence vertical transmission and that subtype D viruses may be less likely to be transmitted in this setting. We analyzed HIV-1 gp120 V3 region sequences from the plasma of 20 pregnant Ugandan women of known transmission status who did not receive antiretroviral prophylaxis. V3 regions were cloned, sequenced, and subtyped by phylogenetic analysis. Among 11 women who transmitted HIV-1 to their infants, we detected subtypes A, C, D, and G. Two of the transmitters had dual infection with subtypes A and D. In addition, a third was infected with two distinct strains of subtype G viruses. HIV-1 subtype A and D viruses were found in 9 women who did not transmit the virus to their infants. This study reveals that pregnant Ugandan women harbor diverse HIV-1 subtypes, including women who transmit HIV-1 to their infants. Transmission of HIV-1 with subtype D V3 regions was confirmed in 4 of the 11 transmitters, including 2 who had dual infection with subtype A and D HIV-1.

Beta 2-microglobulin, HIV-1 p24 antibody and acid-dissociated HIV-1 p24 antigen levels: predictive markers for vertical transmission of HIV-1 in pregnant Ugandan women.

ObjectivesTo evaluate the clinical utility of plasma β2-microglobulin (β2M) levels, acid-dissociated HIV-1 p24 antigen, and HIV-1 p24-antibody titers in predicting HIV-1 vertical transmission in 227 HIV-1-infected Ugandan pregnant women. DesignPlasma β2M levels, acid-dissociated HIV-1 p24-antigen positivity, and HIV-1 p24-antibody titers were determined using commercial enzyme immunoassays (EIA) in a Ugandan cohort of 52 HIV-1-seropositive transmitting mothers, 175 HIV-1-seropositive non-transmitting mothers, and 52 seronegative mothers within 6 weeks prior to delivery. ResultsTransmitter mothers had significantly higher plasma concentrations of β2M (1.80

Relation of Vitamin A and Carotenoid Status to Growth Failure and Mortality Among Ugandan Infants With Human Immunodeficiency Virus

pM 1.13 mg/l) than non-transmitter seropositive mothers (1.32