Lepage P

Infective and anti-infective properties of breastmilk from HIV-1-infected women.

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.

Four years of natural history of HIV-1 infection in African women: a prospective cohort study in Kigali (Rwanda) 1988-1993.

Clinical features and mortality due to human immunodeficiency virus type-1 (HIV-1) infection in women are described as part of a prospective 4-year cohort study on perinatal transmission of HIV in Kigali, Rwanda. Two hundred fifteen HIV-seropositive (HIV+) and 216 HIV-seronegative (HIV-) pregnant women were enrolled at delivery between November 1988 and June 1989. Clinical information collected during systematic quarterly examinations was compared. HIV antibody tests were performed at delivery and CD4/CD8 lymphocyte counts at 15 days postpartum. HIV--women who seroconverted during the follow-up period were excluded from the analysis of the comparison group starting at the date of seroconversion. At enrollment, all HIV+ women were asymptomatic for acquired immune deficiency syndrome (AIDS). Incidence of tuberculosis was 2.9 per 100 women-years (WY) after 4 years of follow-up in HIV+ women versus 0.2 per 100 WY among HIV- women (relative risk, 18.2; 95% confidence interval 2.4-137.0). Among HIV+ women, the incidence of AIDS (World Health Organization clinical AIDS definition) was 3.5 per 100 WY. The mortality rate was 4.4 per 100 WY among HIV+ women versus 0.5 per 100 WY among HIV- women. Clinical AIDS was present in only half of the fatalities. Tuberculosis was a major cause of morbidity and mortality in these HIV+ African women. An early diagnosis and an appropriate treatment or prevention of tuberculosis should improve the quality of life of HIV-infected patients in Africa.

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.

Seroincidence of HIV-1 infection in african women of reproductive age: a prospective cohort study in Kigali, Rwanda, 1988-1992

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.

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from Rwanda, 1984–1990

A total of 383 clinical isolates of Streptococcus pneumoniae, obtained from an equal number of patients in Kigali, Rwanda, was tested for resistance to penicillin G with a 1 microgram oxacillin disc. Of these isolates, 99 (25.8%) showed reduced zones of inhibition. By means of an agar dilution method, 21% all isolates were confirmed as relatively resistant (MIC > or = 0.12- < or = 1.0 mg/l) strains of Streptococcus pneumoniae (RRSP). A high degree of resistance to penicillin G (MIC > or = 2 mg/l) was not observed. Resistance to chloramphenicol (MIC > or = 8 mg/l) was found in 31% RRSP and in 6% penicillin susceptible strains (PSSP). Doxycycline resistance was common in both RRSP and PSSP strains. All isolates remained fully susceptible to erythromycin. Children more often harboured a strain giving a reduced inhibition zone than did adults (74/230 versus 25/153; P = 0.0005). A total of 32 serotypes or serogroups were identified, seven of them relating to 64.8% all isolates typed. Of all the isolates 84% belonged to a serotype represented in the 23-valent vaccine or to a cross-reacting serotype. Serotype 25, not included in the vaccine, accounted for 10.7% typed isolates from adults but only for 2.0% typed isolates from children. Results of susceptibility testing and clinical experience suggest that penicillin G, ampicillin and chloramphenicol should not be used alone as empirical treatment for pneumococcal meningitis in patients in Rwanda.

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.

Estimating the incubation period of paediatric AIDS in Rwanda.

ObjectiveTo estimate the distribution of the incubation period of paediatric AIDS in Rwanda. DesignData were collected between February 1984 and December 1990 at the Centre Hospitalier de Kigali (CHK), the capital city of Rwanda, Central Africa. PatientsWe 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%. MethodsWe 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. ResultsWe 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. ConclusionsOur 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.

ARE MEDICAL INJECTIONS A RISK FACTOR FOR HIV INFECTION IN CHILDREN

In 1984-86 the authors diagnosed 107 cases of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) in 107 children at Rwandas Centre Hospitalier de Kigali. Of the 76 children who were available for medical examination serologic study and interview only 18 (24%) had seronegative mothers. This finding suggests that the role of blood transfusion and medical injection in the transmission of human immunodeficiency virus (HIV) to children may not be as significant as is generally believed. A history of blood transfusion was found in 7 of the 18 children with HIV seronegative mothers but in only 3 of the 58 children whose mothers were seropositive. However there was no difference between the 2 groups in terms of the number of medical injections per month of life. The absence of a history of transfusion in 11 of the 18 children with seronegative mothers prompted a re-evaluation of the serological status of these women by indirect immunofluorescence and HIV env/core recombinant confirmation enzyme immunoassay. 2 of the 8 mothers of children without a transfusion history and 1 of 4 mothers of children with previous transfusion were found to have strong positive results with both core and env antigen by enzyme immunoassay. Thus it is recommended that seronegativity in mothers should be confirmed before parenteral exposure to HIV is implicated in HIV seropositive children.

Nosocomial transmission of HIV in Africa: what tribute is paid to contaminated blood transfusions and medical injections?

We reviewed the published data on the possible impact of medical injections and blood transfusions on the spread of human immunodeficiency virus (HIV) in Africa. We also compared these results to our experience in Rwanda, central Africa. The importance of medical injections in the epidemic of HIV infection seems to differ from one area to another. The excess of injections experienced by HIV seropositive subjects in Zaire could be secondary to the parenteral treatment of early HIV-related illness or to the treatment of sexually transmitted diseases, rather than being the cause of HIV infection, as suggested by Rwandese studies. In contrast, blood transfusions have been shown to represent an important source of nosocomial HIV infection in many African countries. Effective and relatively inexpensive measures to diminish the iatrogenic spread of HIV infection in developing countries are summarized.

Maternal humoral factors associated with perinatal human immunodeficiency virus type-1 transmission in a cohort from Kigali, Rwanda, 1988-1994

OBJECTIVESnto study different parameters of humoral immunity responses in the serum of 39 human immunodeficiency virus type-1 infected pregnant women from Kigali, (Rwanda) in correlation with perinatal transmission.nnnMETHODSnthis study was done between 1988 and 1994. Thirty nine HIV-1 infected women, 18 transmitting (T) and 21 non-transmitting (NT) mothers, have been chosen based on the quantity of sera available for analysis. Maternal data were collected at the time of delivery or during the preceding month. Quantification of viral load was performed by the signal amplification bDNA assay. Specific reactivity of antibody was tested against recombinant p24 protein and five different synthetic peptides from gp120 and gp41 based on HIV LAI-strain sequences. Neutralization assays were performed against laboratory (RII strain of the HIV-1 C subtype) and primary strains (two NSI and one SI of the HIV-1 A subtype). Antibody Dependent Cellular Cytotoxicity assay was performed with CEM.NK(R) cells against a laboratory HIV-1 strain.nnnRESULTSnabsence of correlation regarding maternal viral load, or viral subtype and vertical transmission was observed. By contrast, the CD4/CD8 ratio was significantly higher in non-transmitting mothers compared to transmitting mothers. Moreover, high anti-p24 antibody avidity was correlated with a lower risk of perinatal transmission. Furthermore, transmission risk appeared significantly higher with reactivity of serum samples to linear epitopes of gp41 (amino acids 566-582, 578-594), whereas risk appeared lower with reactivity to the immunodominant domain of gp41 (amino acids 597-609). No significant difference was observed in titres of antibody neutralizing primary isolates (two NSI (non syncitium inducer) and one SI (syncitium inducer) of the HIV-1 A subtype) and laboratory strain (RII strain, of the HIV-1 C subtype) between transmitting and non-transmitting mothers sera. In addition, titres of Antibody Dependent Cellular Cytotoxicity were similar in transmitting versus non-transmitting mothers. However, high Antibody Dependent Cellular Cytotoxicity titres were correlated with a good clinical status of children.nnnCONCLUSIONSnthree parameters such as high CD4/CD8 ratio, high anti-p24 antibody avidity and high reactivity against the immunodominant epitope of gp41 have been shown to be correlated with no perinatal transmission. High Antibody Dependent Cellular Cytotoxicity titres appeared to be linked to a good clinical status of children after birth. One parameter, reactivity against two linear epitopes of gp41, appeared to be correlated with vertical transmission.