Biomedical subjects
Publications and source records attributed to F Dabis.
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OBJECTIVE: To estimate the seroincidence of HIV-1 infection among women of reproductive age in Kigali, Rwanda. DESIGN: Fixed prospective cohort followed for 36 months between November 1988 and June 1992, as part of an ongoing study of mother-to-child transmission of HIV-1. SETTING: Centre Hospitalier, Kigali, Rwanda. SUBJECTS: A total of 216 HIV-seronegative women were enrolled at delivery between November 1988 and June 1989. METHODS: A blood sample was obtained at delivery to test for HIV antibodies (by enzyme-linked immunosorbent assay and Western blot). Serum was tested every 3 months during follow-up. Incidence density rates of HIV seroconversion were estimated. RESULTS: The follow-up rate after 3 years was 89%, assessed by the maximum person-years method. The seroincidence density rate was 3.5 per 100 women-years (95% confidence interval, 1.9-5.0). It decreased linearly from 7.6 during the first 6-months postpartum to 2.5 per 100 women-years during the last 6 months of the third year of follow-up. Maternal age did not affect HIV incidence rates. We examined the role of the cohort, counselling, and the first 6-month postpartum effects on this estimate. CONCLUSION: This fixed cohort provided an overall estimation of the HIV infection incidence rate and its dynamics. These figures could be used for programming future HIV preventive vaccine efficacy trials in Rwanda.
To approximate the contributions of in utero, intrapartum, and postnatal transmission of human immunodeficiency virus type-1 (HIV-1) and to evaluate polymerase chain reaction (PCR) as a diagnostic tool for pediatric HIV infection, blood was collected at birth (cord blood), and at 3, 6-12, and 13-24 months in 218 children born to HIV-1-seropositive mothers in Kigali, Rwanda. Proviral DNA was detected by a double PCR using two sets of three primers (gag, pol, and env). Pediatric HIV-1 infection was defined according to serological and clinical criteria. The probability of having a positive PCR at a given time was calculated by a nonparametric method. Among children with unequivocal evidence of infection (n = 47), it was 30.5% on cord blood and 80.6% at 3 months. Thus, in children born to HIV-1-infected mothers, the estimated rate of transmission in the late postnatal period is 4.9%, and the rate of transmission in the intrapartum plus postnatal periods is 17.6%. Among 117 HIV-1-uninfected children born to HIV-1-infected mothers, six (5%) had a false-positive PCR on cord blood. These results should be taken into account in designing intervention trials aimed at reducing mother-to-child transmission of HIV-1.
Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly by cell-to-cell contact. We postulated that transmission of HIV-1 through breastmilk could be favoured by the presence of infected cells, by deficiency of anti-infective substances in breastmilk, or both factors. 215 HIV-1-infected women were enrolled at delivery in Kigali, Rwanda; milk samples were collected 15 days, 6 months, and 18 months post partum. HIV-1 IgG, secretory IgA, and IgM were assayed by western blot, for the latter two after removal of IgG with protein G. In the 15-day and 6-month samples, we sought viral genome in milk cells by a double polymerase chain reaction with three sets of primers (gag, pol, and env). HIV-1 infection in the offspring was defined according to serological and clinical criteria. At 15 days, 6 months, and 18 months post partum, HIV-1 specific IgG was detected in 95%, 98%, and 97% of breastmilk samples, IgA in 23%, 28%, and 41%, and IgM in 66%, 78%, and 41%. In children who survived longer than 18 months, the probability of infection was associated with lack of persistence of IgM and IgA in their mothers' milk (adjusted chi 2 for trend, p = 0.01 for IgM and p = 0.05 for IgA). The presence of HIV-1-infected cells in the milk 15 days post partum was strongly predictive of HIV-1 infection in the child, by both univariate (p < 0.05) and multivariate analysis (p = 0.01). The combination of HIV-1-infected cells in breastmilk and a defective IgM response was the strongest predictor of infection. HIV-1 infection in breastfed children born to infected mothers is associated with the presence of integrated viral DNA in the mothers' milk cells. IgM and IgA anti-HIV-1 in breastmilk may protect against postnatal transmission of the virus.
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PURPOSE: In the last 8 years, numerous cohort studies have been conducted to estimate the rate of mother-to-child transmission (MTCT) of HIV. Many of these have faced problems in data collection and analysis, making it difficult to compare transmission rates between studies. This workshop on methodological aspects of the study of MTCT of HIV-1 was held in Ghent (Belgium) in February 1992. STUDY SELECTION AND DATA EXTRACTION: Fourteen teams of investigators participated, representing studies from Central (five) and Eastern Africa (three), Europe (two), Haiti (one) and the United States (three). A critical evaluation of the projects was carried out, under four headings: (1) enrollment and follow-up procedures, (2) diagnostic criteria and case definitions, (3) measurement and comparison of MTCT rates and (4) determinants of transmission. RESULTS OF DATA ANALYSIS: Reported transmission rates ranged from 13 to 32% in industrialized countries and from 25 to 48% in developing countries. However, no direct comparisons could be made because methods of calculation differed from study to study. Based on this review, a common methodology was developed. Agreement was reached on definitions of HIV-related signs/symptoms, paediatric AIDS and HIV-related deaths. A classification system of children born to HIV-1-infected mothers according to their probable HIV infection status during the first 15 months of life, allowed the elaboration of a direct method of computation of the transmission rate and of an indirect method for studies with a comparison group of children born to HIV-seronegative mothers. This standardized approach was subsequently applied to selected data sets. CONCLUSIONS: The methodology can now be applied to all studies with sufficient follow-up and comparisons made between transmission rates. This step is essential for assessing determinants of transmission and for the development of a common approach for the evaluation of interventions aimed at reducing or interrupting MTCT of HIV.
OBJECTIVE: The results of developmental testing of 218 children born to human immunodeficiency virus (HIV)-seropositive mothers and infected or uninfected themselves were compared with those of 218 children born to HIV-seronegative mothers in an ongoing cohort study in Kigali, Rwanda. METHODS: When the children were 6, 12, 18, and 24 months of age, a specific neurodevelopmental examination was performed blindly by study physicians assessing gross motor development, fine motor development, language acquisition, and social contacts. RESULTS: Only one acute severe HIV-related encephalopathy was identified among the 50 infected children. The proportion of abnormal neurologic examinations in HIV-infected children varied from 15% to 40% according to age and was always higher than in HIV-uninfected children born to HIV-seropositive and seronegative mothers (< or = 5% or less of abnormal examinations at each time period). After excluding those children with clinical acquired immunodeficiency syndrome (AIDS) from the analysis, the proportion of abnormal examinations in infected children was 12.5% at 6 months, 16% at 12 months, 20% at 18 months, and 9% at 24 months of age and was still more frequent than in HIV-uninfected children. The developmental delay was principally due to significantly lower gross motor scores. CONCLUSIONS: HIV-1-infected children are more frequently developmentally delayed than uninfected children during the first 2 years of life in this African population. This developmental delay is related to the AIDS stage of pediatric HIV infection.
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OBJECTIVE: To compare the reactogenicity and immunogenicity of high-dose Edmonston-Zagreb (EZ) measles vaccine in children with and without human immunodeficiency virus, type 1 (HIV-1), infection. DESIGN: Prospective cohort study. SETTING: General pediatric clinic and home visits in Kigali, the capital of Rwanda. PARTICIPANTS: Infants born to HIV-1-seropositive and -seronegative mothers were vaccinated with a 10(5.0) 50% tissue culture infective dose of EZ measles vaccine at 6 months of age. Control visits were made 10 and 14 days later to monitor local and general reactions. Measles serum antibodies were measured by an enzyme-linked immunosorbent assay technique at birth and at 6 and 9 months of age. Three groups were compared: infected children (n = 43), uninfected children born to seropositive mothers (n = 135), and uninfected children born to seronegative mothers (n = 194). RESULTS: Three hundred twenty-three children (86.8%) were available for the reactogenicity study. No statistically significant difference between the three groups was found in the occurrence of minor adverse reactions. No severe adverse reaction was observed. One hundred ninety children (51.1%) were available for the immunogenicity study. The percentage of infants negative for measles antibody at 6 months was significantly higher (P = .021) in HIV-infected children (85%) and in uninfected children born to seropositive mothers (90%) than in uninfected children born to seronegative mothers (75%). The overall seroconversion rate at 9 months was 90% (95% confidence interval, 85.7% to 94.3%), without any statistically significant difference between the three groups. CONCLUSION: High-dose EZ vaccine administered at 6 months of age is safe and highly immunogenic in both HIV-infected and uninfected children.
A hospital-based surveillance system of infection by the human immunodeficiency virus (HIV) has been implemented in nine wards of the Bordeaux University Hospital by the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine (GECSA). The aim was to systematically collect clinical, biological and epidemiological data on HIV-infected patients who were followed by physicians from the participating hospitals. The analysis of the data at enrollment was performed on the 1,242 patients whose infection was diagnosed between January 1983 and December 1989. The male to female ratio was 2.5:1 and the proportion of women has increased over time. For men, 39.8% were homosexual or bisexual, 36.9% were intravenous drug users (IVDU's) and 2.6% had both risk behaviours. For women, the most frequently reported high-risk behaviour was IVDU (50.3%), followed by heterosexual contacts with an HIV-infected or at-risk person (HET) (28.6%). The distribution of risk behaviour has changed over time, with an increase in the proportion of HET and a decrease in the proportion of IVDU's for both sexes. The proportion of patients included that fulfilled the definition for AIDS was 18.9%. Based on this system, the incidence rate of diagnosis of HIV infection in the Aquitaine region, regardless of the clinical stage of the infection was estimated to be at least 63.4 per million inhabitants and per year in 1988-1989. The GECSA surveillance system points out some of the specificities of the progression of the HIV epidemic in the Aquitaine region.(ABSTRACT TRUNCATED AT 250 WORDS)
This article reviews the virological and epidemiological data available on transmission of the human immunodeficiency virus type 1 (HIV-1) by breast milk. Colostrum and breast milk are considered major modes of transmission for many animal retroviruses as well as human T-cell leukemia virus, mainly as the consequence of ingestion of infected cells. Several cases that strongly suggest transmission of HIV-1 through breast-feeding have now been reported. In addition, recent evidence suggests that postpartum HIV-1 seroconversion of a mother may be associated with a high risk of postnatal transmission to offspring via breast milk. Preventive measures such as pasteurization of breast milk have not been fully examined. While the World Health Organization continues to promote breast-feeding in areas where no safe alternative exists, the Centers for Disease Control recommends that American women who are infected by HIV-1 not practice breast-feeding if a safe alternative is available. Large-scale, carefully controlled, prospective studies of the risk of HIV-1 infection associated with breast-feeding are of the utmost priority. Feasible and ethically acceptable feeding alternatives should be developed for countries where formula feeding has a strong negative effect on child morbidity and mortality.
OBJECTIVE: To estimate the distribution of the incubation period of paediatric AIDS in Rwanda. DESIGN: Data were collected between February 1984 and December 1990 at the Centre Hospitalier de Kigali (CHK), the capital city of Rwanda, Central Africa. PATIENTS: We used a sample of 685 AIDS cases registered consecutively in the Department of Paediatrics of the CHK, in which the proportion of perinatally acquired HIV-1 infection was estimated to be 98.6%. METHODS: We performed both non-parametric and parametric analyses. The methods of estimation were adapted to truncated data, using essentially the same methods as Auger et al. in their analysis of data from the New York City and the New York State AIDS case registries in 1988. RESULTS: We found that a double Weibull model fitted the data very well and that the risk of developing AIDS was high for subjects under 18 months of age, but lower for older subjects. CONCLUSIONS: Our results were qualitatively similar to those of Auger et al.. There were quantitative differences between the two studies, but it was not possible to compare median survival periods. Parameters such as median or mean survival times cannot be validly estimated using only data from registers because these data exclude infected subjects who have not yet developed AIDS.
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