Cervical cytomegalovirus reactivation, cytokines and spontaneous preterm birth in Kenyan women.

Genital cytomegalovirus (CMV) reactivation is common during the third trimester of pregnancy. We hypothesized that cervical CMV shedding may increase risk of spontaneous preterm birth (sPTB) through the release of inflammatory cytokines in the cervix. We conducted a nested case-control analysis to determine the relationship between CMV shedding and sPTB using data and samples from a prospective cohort study in western Kenya. Women who delivered between 28 + 0 and 33 + 6 weeks gestation were matched by gestational age at sample collection to controls who delivered ≥ 37 + 0 weeks. Levels of CMV DNA and interleukin (IL)-1 beta (ß), IL-6, IL-8 and tumor necrosis factor (TNF)-α were measured in cervical swabs. We used conditional logistic regression to assess relationships between CMV shedding, cervical cytokine levels and sPTB. Among 86 cases and 86 matched controls, cervical CMV levels were not significantly associated with sPTB [odds ratio (OR) = 1·23, 95% confidence interval (CI) = 0·59-2·56], but were significantly associated with higher levels of cervical IL-6 (ß = 0·15, 95% CI = 0·02-0·29) and TNF-α (ß = 0·14, 95% CI = 0·01-0·27). In univariate analysis, higher odds of sPTB was associated with higher cervical IL-6 levels (OR = 1·54, 95% CI = 1·00-2·38), but not with other cervical cytokines. In this cohort of Kenyan women, we did not find a significant association between cervical CMV shedding and sPTB before 34 weeks.

Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease.

BACKGROUND: Associations between vitamin D status and childhood asthma are increasingly reported, but direct causation and mechanisms underlying an effect remain unknown. We investigated the effect of early-life vitamin D deficiency on the development of murine neonatal allergic airways disease (AAD). METHODS: In utero and early-life vitamin D deficiency was achieved using a vitamin D-deficient diet for female mice during the third trimester of pregnancy and lactation. Offspring were weaned onto a vitamin D-deficient or vitamin D-replete diet, and exposure to intranasal house dust mite (HDM) or saline was commenced from day 3 of life for up to 6 weeks, when airway hyper-responsiveness (AHR), airway inflammation and remodelling were assessed. RESULTS: Neonatal mice that had in utero and early-life vitamin D deficiency had significantly increased pulmonary CD3(+) CD4(+) T1ST2(+) cells and reduced CD4(+) IL-10(+) cells. This effect was enhanced following HDM exposure. AHR in HDM-exposed mice was unaffected by vitamin D status. Introduction of vitamin D into the diet at weaning resulted in a significant reduction in serum IgE levels, reduced pulmonary eosinophilia and peri-bronchiolar collagen deposition. CONCLUSION: Peri-natal vitamin D deficiency alone has immunomodulatory effects including Th2 skewing and reduced IL-10-secreting T regulatory cells, exaggerated with additional allergen exposure. Vitamin D deficiency in early life does not affect AHR, but contributes to disease severity with worse eosinophilic inflammation and airway remodelling. Importantly, supplementation with vitamin D improves both of these pathological abnormalities.

A prospective study of risk factors for herpes simplex virus type 2 acquisition among high-risk HIV-1 seronegative women in Kenya.

OBJECTIVES: Several studies have demonstrated an association between herpes simplex virus type 2 (HSV-2) and HIV-1, but available data on risk factors for HSV-2 acquisition are limited. The objective of this analysis was to determine the incidence and risk factors for HSV-2 acquisition among HIV-1-seronegative female sex workers in Kenya. METHODS: Between February 1993 and December 2006, HIV-1-seronegative women attending a municipal sexually transmitted infection (STI) clinic were invited to enroll in a prospective cohort study. Screening for HIV-1 and STIs were done at monthly follow-up visits. Archived blood samples were tested for HSV-2. RESULTS: Of 1527 HIV-1-seronegative women enrolled, 302 (20%) were HSV-2 seronegative at baseline of whom 297 had at least one follow-up visit. HSV-2 incidence was high (23 cases/100 person-years; 115 cases). In multivariate analysis, HSV-2 was significantly associated with more recent entry into sex work, workplace and higher number of sex partners per week. Condom use was protective, although this was statistically significant only for the intermediate strata (25-75% condom use; HR 0.43; p = 0.05). There were statistical trends for bacterial vaginosis to increase HSV-2 risk (HR 1.56; p = 0.07) and for oral contraceptive use to decrease risk (HR 0.50; p = 0.08). The 23% annual HSV-2 incidence in this study is among the highest reported anywhere in the world. CONCLUSIONS: Women were at increased risk if they had recently entered sex work, had a higher number of sex partners or worked in bars. HSV-2 risk reduction interventions are urgently needed among high-risk African women.

Prospective study of correlates of vaginal Lactobacillus colonisation among high-risk HIV-1 seronegative women.

OBJECTIVE: Vaginal colonisation with Lactobacillus species is characteristic of normal vaginal ecology. The absence of vaginal lactobacilli, particularly hydrogen peroxide (H(2)O(2))-producing isolates, has been associated with symptomatic bacterial vaginosis (BV) and increased risk for HIV-1 acquisition. Identification of factors associated with vaginal Lactobacillus colonisation may suggest interventions to improve vaginal health. METHODS: We conducted a prospective cohort study of correlates of vaginal Lactobacillus colonisation among Kenyan HIV-1 seronegative female sex workers. At monthly follow-up visits, vaginal Lactobacillus cultures were obtained. Generalised estimating equations were used to examine demographic, behavioural and medical correlates of Lactobacillus isolation, including isolation of H(2)O(2)-producing strains. RESULTS: Lactobacillus cultures were obtained from 1020 women who completed a total of 8896 follow-up visits. Vaginal washing, typically with water alone or with soap and water, was associated with an approximately 40% decreased likelihood of Lactobacillus isolation, including isolation of H(2)O(2)-producing strains. Recent antibiotic use, excluding metronidazole and treatments for vaginal candidiasis, reduced Lactobacillus isolation by approximately 30%. H(2)O(2)-producing lactobacilli were significantly less common among women with Trichomonas vaginalis infection and those who were seropositive for herpes simplex virus type 2. In contrast, H(2)O(2)-producing lactobacilli were significantly more common among women with concurrent vaginal candidiasis. CONCLUSIONS: Modifiable biological and behavioural factors are associated with Lactobacillus colonisation in African women. Our results suggest intervention strategies to improve vaginal health in women at high risk for HIV-1.

Vaginal lavage with chlorhexidine during labour to reduce mother-to-child HIV transmission: clinical trial in Mombasa, Kenya.

OBJECTIVES: To evaluate the effect of vaginal lavage with diluted chlorhexidine on mother-to child transmission of HIV (MTCT) in a breastfeeding population. METHODS: This prospective clinical trial was conducted in a governmental hospital in Mombasa, Kenya. On alternating weeks, women were allocated to non-intervention or to intervention consisting of vaginal lavage with 120 ml 0.2% chlorhexidine, later increased to 0.4%, repeated every 3 h from admission to delivery. Infants were tested for HIV by DNA polymerase chain reaction within 48 h and at 6 and 14 weeks of life. RESULTS: Enrolment and follow-up data were available for 297 and 309 HIV-positive women, respectively, in the non-lavage and the lavage groups. There was no evidence of a difference in intrapartum MTCT (17.2 versus 15.9%, OR 0.9, 95% CI 0.6-1.4) between the groups. Lavage solely before rupture of the membranes tended towards lower MTCT with chlorhexidine 0.2% (OR 0.6, 95% CI 0.3-1.1), and even more with chlorhexidine 0.4% (OR 0.1, 95% CI 0.0-0.9). CONCLUSION: The need remains for interventions reducing MTCT without HIV testing, often unavailable in countries with a high prevalence of HIV. Vaginal lavage with diluted chlorhexidine during delivery did not show a global effect on MTCT in our study. However, the data suggest that lavage before the membranes are ruptured might be associated with a reduction of MTCT, especially with higher concentrations of chlorhexidine.

Correlation between maternal and infant HIV infection and low birth weight: a study in Mombasa, Kenya.

This article aimed to examine the association between maternal and infant HIV infection and low birth weight (LBW <2500 grams). Data from 8563 singleton liveborns in Mombasa, Kenya, were analysed. Maternal HIV infection was found in 14.1% of the women and 9.6% of neonates had a birth weight of <2500 grams. In multivariate analysis, maternal HIV infection was independently associated with LBW (RR=1.46, 95% CI=1.20-1.79, P =0.0002). Maternal age, primiparity, sex of the baby, religion, syphilis infection, anaemia and previous history of stillbirth were also independently associated with LBW (RR: 1.32, 2.19, 1.44, 1.56, 1.61, 1.31 and 1.69, respectively). The rate of intra-uterine HIV transmission was 5.1% and 20.1% of the exposed infants were infected during the intrapartum period. Intrapartum infected infants had a relative risk of LBW of 1.95 (95% CI=1.18-2.87, P <0.01) compared to uninfected children, whereas the birth weight of infants infected in utero was not different from uninfected infants (RR=1.18, 95% CI=0.56-2.60, P=0.630). HIV infected mothers are more likely to have small babies, even after controlling for possible confounding factors. Low birth weight babies were more at risk for peripartum HIV transmission, but further research is needed to study mechanisms of transmission in relation to birth weight.

Exposure to HIV-1 during delivery and mother-to-child transmission.

BACKGROUND: The correlation between the presence of HIV-1 in maternal cervicovaginal secretions and in the infant's oro-pharyngal secretions at birth, and mother-to-child HIV transmission (MTCT) were examined to obtain a better understanding of its mechanism. METHODS: Women without medical and obstetrical complications, living within a reasonable distance of the government hospital in Mombasa, Kenya, were recruited after informed consent. Maternal and infant characteristics were collected. Polymerase chain reaction was used to detect HIV-1 in cervico-vaginal and oro-pharyngal secretions. Infants were tested for HIV-1 by polymerase chain reaction within 48 h and at 6 weeks after delivery. RESULTS: Between April 1998 and April 1999, 228 woman-infant pairs were included in the study. HIV-1 DNA in cervico-vaginal secretions was independently associated with HIV-1 maternal viral load and with infant birth-weight, whereas HIV-1 RNA was associated with maternal viral load and maternal age. HIV-1 DNA in the oropharyngal secretions was also independently associated with maternal viral load. MTCT rate at the age of 6 weeks was 23.6%. Intrapartum and early postpartum HIV transmission was independently associated with maternal viral load [adjusted odds ratio (OR), 1.6; 95% confidence interval (CI),1.0-2.7], detection of HIV-1 RNA in cervico-vaginal secretions (adjusted OR, 3.2; 95% CI, 1.5-7.3) and of HIV-1 DNA in oro-pharyngeal secretions (adjusted OR, 3.2; 95% CI, 1.1-9.0). DISCUSSION: As far as is known, this is the first study showing that infant exposure to HIV-1 in the birth canal and the presence of HIV-infected cells in the infant's oropharyngeal cavity are independently associated with intrapartum and early postpartum MTCT. It supports the hypothesis that MTCT could occur through the oral route.

Hospitalisation for adverse events related to drug therapy: incidence, avoidability and costs.

OBJECTIVES: To determine the incidence of hospital admissions for adverse events related to drug therapy, and to assess whether these drug-related admissions (DRAs) could have been reasonably prevented. SETTING: A tertiary teaching hospital. DESIGN AND PATIENTS: Prospective assessment of all admissions through the emergency department and resulting in a stay of more than 24 hours during 30 consecutive days in November and December 1994 to determine if the admission was related to drug therapy. Cases of intentional overdose were excluded. MAIN OUTCOME MEASURES: The number, type, causality and avoidability of drug-related admissions. RESULTS: Of 965 admissions, 55 (5.7%) were assessed as being drug-related. Drug-related admissions (DRAs) were designated possibly (38%), probably (46%) or definitely (16%) drug-related; caused by prescribing factors (26%), patient noncompliance (27%) and adverse drug reactions (47%); and classified as definitely (5.5%), possibly (60.0%) and not (34.5%) avoidable. The estimated annual cost to the hospital for all DRAs was $3,496,956 and for unavoidable DRAs was $1,629,494. CONCLUSION: The DRA rate we found lies around the middle of the range of other published rates. Few DRAs were judged definitely avoidable and over one-third were unavoidable. Nevertheless, the largest proportion were judged possibly avoidable. As the drugs identified in this study are clearly needed in the community, efforts to reduce DRAs must concentrate on education, counselling and monitoring of drug therapy.