Effect of HIV-1 infection on pregnancy outcome in women in Kigali, Rwanda, 1992-1994. Pregnancy and HIV Study Group.

OBJECTIVE: To study the effect of HIV-1 infection on pregnancy outcome in women provided with antenatal services including malaria and sexually transmitted disease (STD) treatment in Kigali, Rwanda. SUBJECTS AND METHODS: Pregnant women attending the antenatal clinic ward of the Centre Hospitalier de Kigali in their last 3 months of pregnancy were tested for HIV antibody after consent had been obtained. All HIV-1-infected women were included and compared with HIV-negative women of same age and parity. Until delivery, each woman enrolled had a monthly follow-up including malaria and STD aetiological diagnosis and treatment. At the time of delivery, obstetrical and neonatal characteristics were recorded. Mothers and their children were followed until 6 weeks postpartum. RESULTS: By mid-August 1993, 384 HIV-positive and 381 HIV-negative women had been enrolled and by the end of November 1993, 729 women (95.3%; 364 HIV-positive and 365 HIV-negative) had delivered 725 livebirths, including eight and six twins, respectively; 10 stillbirths were recorded amongst HIV-positive women and eight amongst HIV-negative women (P=0.60). Excluding twins, premature birth (< 37 completed weeks of gestation) was observed in 22.7% of infants born to HIV-positive women versus 14.1% of those born to HIV-negative women; low birth weight (< 2500 g) was observed in 25.5% of infants born to HIV-positive women versus 14.8% of those born to HIV-negative women. Low birth weight was significantly more frequent in full-term infants born to HIV-positive mothers than to HIV-negative mothers. No significant difference in low birth weight rate was observed in preterm infants. Death occurred in 5.1% of children during the perinatal period without statistically significant difference between the two groups. HIV-positive women were more likely to have a postpartum haemorrhage. CONCLUSION: In the context of high HIV prevalence, maternal HIV infection is associated with adverse obstetrical and neonatal outcomes even when treating STD and malaria.

Growth of human immunodeficiency type 1-infected and uninfected children: a prospective cohort study in Kigali, Rwanda, 1988 to 1993.

OBJECTIVE: To compare the anthropometric characteristics of children with and without HIV-1 infection. METHODS: In a prospective cohort study of 218 children born to HIV-1 seropositive mothers and 218 children born to HIV-1 seronegative mothers in Kigali, Rwanda, 3 groups were compared: infected children (n = 46); uninfected children born to seropositive mothers (n = 140); and uninfected children born to seronegative mothers (n = 207). Weight, height and head circumference were measured at birth, every 3 months during the first year of life and every 6 months thereafter. The weight-for-age, height-for-age, weight-for-height and head circumference-for-age mean z scores were calculated. RESULTS: The weight-for-age, height-for-age and head circumference-for-age mean z scores were lower among HIV-infected children than among uninfected ones at each time period. The reduction in the weight-for-age mean z score was the greatest between 12 and 36 months. The reduction in the height-for-age mean z score of HIV-infected children was persistently below 2 SD after 9 months of age. On the other hand the weight-for-height mean z score was not consistently lower in HIV-infected children when compared with uninfected ones. The anthropometric characteristics of uninfected children born to seropositive mothers were similar to those of children born to seronegative mothers. CONCLUSIONS: In this study HIV-infected children were more frequently stunted (low height-for-age) than uninfected ones. Wasting (low weight-for-height) was not common among HIV-infected children.

[Septic meningitis in children in Rwanda from 1983 to 1990. Retrospective study at the Kigali Hospital Center]. / Les méningites septiques de l'enfant au Rwanda de 1983 à 1990. Etude rétrospective au Centre Hospitalier de Kigali.

To assess septic meningitis in pediatric units in terms of the bacteriologic distribution, mortality, and groups at risk, we conducted a retrospective study in the pediatric department of the Kigali Hospital Center (Rwanda). Based on bacteriologic study of 1215 cerebrospinal fluid samples, there were 321 cases of septic meningitis due to identifiable germs and 68 involving cloudy fluid with no detectable germs, i.e. 1.5% of admissions to the Pediatric Unit of the Kigali Hospital Center. The most common organisms were pneumococcus (36.5%), Haemophilus influenzae (31%), salmonella (13%), and meningococcus (11.5%). Most of the children (75%) presenting septic meningitis were under the age of 5 years. Overall mortality was 38% with rates of 52% and 39% for cases involving pneumococcus and salmonella respectively. The predominant clinical symptoms of pneumococcus meningitis were coma (p:0.000055) and respiratory compromise (p:0.02). In contrast Haemophilus influenzae meningitis was associated with a lower incidence of coma (p:0.05) and malnutrition (p:0.017). Salmonella meningitis was characterized by a higher incidence of fever over 38.9 degrees C (p:0.025) and malnutrition (p:0.01). In patients with meningococcus meningitis, the incidence of convulsions appeared to be higher, at the threshold of statistical significance (p:0.052), whereas coma (p:0062) and respiratory distress (p:0.0024) were uncommon. Independently of etiology, no clinical symptom was associated with a statistically higher risk for death.

An assessment of the timing of mother-to-child transmission of human immunodeficiency virus type 1 by means of polymerase chain reaction.

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.

Biological markers associated with prolonged survival in African children maternally infected by the human immunodeficiency virus type 1.

Sixteen children over the age of 5 years (Group 1) have been identified out of 537 children infected by human immunodeficiency virus and born to HIV-infected mothers, in Kigali, Rwanda. They were followed up for 2 years and compared with 16 younger AIDS patients (Group 2) and with 16 age- and gender-matched HIV-1 seronegative children (Group 3). Fourteen Group 1 subjects had anti-HIV-1 IgM which persisted during the entire study period, in 11 cases directed to HIV-1 envelope proteins. In vitro, immortalization of B lymphocytes by the Epstein-Barr virus confirmed a high production of IgM to envelope proteins. All these patients had anti-p 17 IgG which was not observed in 7 patients from Group 2. All 16 children mounted significant titers of neutralizing antibodies to HTLV-IIIB, and, in 8 patients tested, against two other HIV-1 strains, RII and MN. HIV-1-specific major histocompatibility complex (MHC)-restricted cytotoxic T cells were demonstrated in 3 of 5 of the subgroup who were tested. Prolonged survival over 5 years in children with maternally acquired HIV-1 infection is associated with a high titer of neutralizing antibodies, a persistent production of IGM to HIV-1 envelope proteins and of IgG to p 17.

Postnatal transmission of human immunodeficiency virus type 1 from mother to infant. A prospective cohort study in Kigali, Rwanda.

BACKGROUND: Although transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant has been well documented during pregnancy and delivery, little is known about the possible transmission of HIV-1 during the postnatal period. METHODS: We conducted a prospective cohort study in Kigali, Rwanda, of 212 mother-infant pairs who were seronegative for HIV-1 at delivery. All the infants were breast-fed. The subjects were followed at three-month intervals, with Western blot assays for antibodies to HIV-1 and testing of mononuclear cells by a double polymerase chain reaction (PCR) using three sets of primers. To evaluate potential risk factors, each mother who seroconverted was matched with three seronegative control women. RESULTS: After a mean follow-up of 16.6 months, 16 of the 212 mothers became seropositive for HIV-1. Of their 16 infants, 9 became seropositive. One infant was excluded from the analysis because of a positive test by PCR on the blood sample obtained at birth. Postnatal seroconversion to HIV-1 occurred in four of the five infants born to the mothers who seroconverted during the first 3 months post partum, and in four infants of the 10 mothers who seroconverted between month 4 and month 21. In all cases, the infant seroconverted during the same three-month period as the mother. The main risk factor for maternal seroconversion was being single. CONCLUSIONS: HIV-1 infection can be transmitted from mothers to infants during the postnatal period. Colostrum and breast milk may be efficient routes for the transmission of HIV-1 from recently infected mothers to their infants.

Perinatal transmission of HIV-1: lack of impact of maternal HIV infection on characteristics of livebirths and on neonatal mortality in Kigali, Rwanda.

We present the baseline results of a prospective cohort study on the perinatal transmission of HIV-1 in Kigali, Rwanda. HIV-1-antibody testing was offered to all women of urban origin delivering a live newborn at the maternity ward of the Centre Hospitalier de Kigali from November 1988 to June 1989; 218 newborns of 215 HIV-positive mothers were matched to 218 newborns of 216 HIV-negative mothers. The matching criteria were maternal age and parity. No differences in socioeconomic characteristics were observed between HIV-positive and HIV-negative women. HIV-positive mothers more frequently reported a history of at least one death of a previously born child (P less than 0.01) and a history of abortion (P less than 0.001). Most of the HIV-positive women were asymptomatic, but 72.4% of them had a CD4; CD8 ratio less than 1 versus 10.1% in the HIV-negative group (P less than 0.001). The frequency of signs and symptoms was not statistically different in the two groups, except for a history of herpes zoster or chronic cough, which was more frequent among HIV-positive women. The rates of prematurity, low birth weight, congenital malformations and neonatal mortality were comparable in the two groups. However, infants of HIV-positive mothers had a mean birth weight 130 g lower than the infants of HIV-negative mothers (P less than 0.01). The impact of maternal HIV-1 infection on the infant seems limited during the neonatal period.

Evaluation and simplification of the World Health Organization clinical case definition for paediatric AIDS.

The World Health Organization (WHO) clinical case definition for paediatric AIDS was tested during a 1-month period on 221 consecutive hospitalized children in Kigali, Rwanda. Relevant clinical features not included in the WHO case definition were also evaluated. Thirty-four out of the 221 children (15.4%) were HIV seropositive. Although the specificity of the WHO case definition was high (92%), the sensitivity and the positive predictive value (PPV) were low (41 and 48%, respectively). The following individual signs had a PPV at least equal to the complete WHO case definition: chronic diarrhoea (47%), respiratory distress secondary to lower respiratory tract infection (50%), oral candidiasis (53%), parotitis (67%), generalized lymphadenopathy (88%), and herpes zoster infection (100%). When logistic regression analysis was done on the nine variables included in the WHO case definition, confirmed maternal infection was the best predictive variable for HIV seropositivity in children (P less than 10(-5). We further excluded the serological status of the mother from the analysis and performed a stepwise logistic regression analysis on the 18 clinical signs and symptoms for which information had been collected. Those signs and symptoms contributing the most to the regression were: respiratory distress, chronic diarrhoea and generalized lymphadenopathy. Based on these findings, we propose a simplified clinical case definition for paediatric AIDS in Africa with better sensitivity, specificity and PPV than the WHO case definition. Further work is needed using this approach to develop case definitions useful for epidemiological surveillance and for case management.

PIP: The World Health Organization (WHO) clinical case definition for pediatric acquired immunodeficiency syndrome (AIDS) was evaluated over a 1-month period in 221 consecutive hospitalized children in Kigali, Rwanda. The median age of the children studied was 18 months (range, 1 month-14 years); 55% were boys. 34 (15%) of these 221 children were seropositive for the human immunodeficiency virus (HIV). Although the specificity of the WHO case definition was high (92%), its sensitivity was only 41% and the positive predictive value was 48%. The following individual signs had a positive predictive value at least equal to the complete WHO case definition: chronic diarrhea (47%), respiratory distress secondary to lower respiratory tract infection (50%), oral candidiasis (53%), parotitis (67%), generalized lymphadenopathy (88%), and herpes zoster infection (100%). Logistic regression analysis on the 9 variables included in the WHO case definition indicated that confirmed maternal HIV infection was the best predictive variable for HIV seropositivity in children. When maternal serological status (rarely available in Rwanda) was excluded from the analysis and a stepwise logistic regression analysis was performed on the 18 clinical signs and symptoms for which data had been collected, respiratory distress, chronic diarrhea, and generalized lymphadenopathy emerged as the signs contributing the most. On the basis of these findings, a simplified clinical case definition of pediatric AIDS is proposed for settings where resources are limited and HIV seroprevalence is high. According to this definition, pediatric AIDS should be suspected in a child presenting with 1 or both of the following clinical signs: respiratory distress secondary to lower respiratory tract infection and/or generalized lymphadenopathy. However, it is necessary to test this definition on a larger scale in Central Africa and in other parts of the world with different rates of HIV seroprevalence.