Genetic subtypes of HIV type 1 in Republic of Congo.

To assess the molecular epidemiology of HIV-1 in Republic of Congo (Congo), we investigated 29 HIV-1s obtained from 82 Congolese AIDS and ARC patients in 1996 and 1997. Part of the env region including the V3 loop was phylogenetically analyzed. The genotypes observed were varied: of 29 specimens, 12 (41 %) were subtype A, 1 (3%) was subtype D, 6 (21%) were subtype G, 6 (21%) were subtype H, 2 (7%) were subtype J, and 2 (7%) could not be classified as any known subtypes (U, unclassified). The heterogeneous profile of HIV-1 infection was different from the profiles of neighboring Central African countries. These data show that subtypes G and H as well as subtype A were circulating with high prevalence. The fact that new genetic subtypes (J and U) are circulating indicates a need for a greater surveillance for these subtypes both in Congo as well as in other parts of the world.

Natural infection of chimpanzees with new lentiviruses related to HIV-1/SIVcpz.

To determine newly identified lentiviruses, termed simian immunodeficiency virus (SIV)cpz97CG4 and SIVcpz97CG6, from two wild-captured juvenile brother chimpanzees in the Republic of Congo, subgenomic pol (integrase, 288 bp), 5'tat/rev-env Cl (including vpu, 354 bp) and env (C2-C4, 544 bp) gene fragments were amplified and sequenced. The analysis revealed significantly discordant phylogenetic positions of SIVcpz97CG in each genomic region. In the trees derived from partial env sequences (V3), both SIVcpz strains clustered in human immunodeficiency virus type 1 (HIV-1) subtype A. However, in the trees derived from partial pol (integrase) and 5'tat/rev-env C1 (including vpu) sequences, they clustered independently from any of the known HIV-1 subtypes. Especially, in the 5'tat/rev-vpu tree, they branched before the root of HIV-1 group M. These findings suggest that these Congolese SIVcpz genomes are mosaic, probably due to a recombinational event in the recent past, and it provides evidence for a rather recently occurring cross-species transmission between humans and chimpanzees.

Contribution of AIDS to the general mortality in Central Africa: evidence from a morgue-based study in Brazzaville, Congo.

OBJECTIVE: To accurately measure AIDS-related mortality relative to other causes and its impact on life expectancy in Brazzaville, Congo. DESIGN: Investigation of all deaths during a 1-month period in Brazzaville. METHODS: From 10 July to 9 August 1996, all bodies handled by Brazzaville's three morgues were examined by a physician. Relatives were interviewed on the circumstances of death, while additional clinical data were gathered from hospital files. Blood samples were systematically drawn from the bodies in two of the three morgues and tested for HIV antibodies. RESULTS: Amongst the 756 bodies examined at the three morgues, 149 (19.7%) AIDS cases were identified. HIV-1 prevalence was 26.2% (38 out of 145) amongst the subjects in the two morgues where HIV serology was systematically performed. AIDS was the leading cause of death in adults (age > or = 15 years), with 25.1% (122 out of 487) of the adults diagnosed with AIDS. The proportion of adult female AIDS cases was significantly higher than the proportion of male cases (30.2 versus 21.0%; P < 0.05). Moreover, female AIDS cases were significantly younger than male cases (median age, 32 versus 42 years; P < 0.00001). Overall AIDS mortality rate amongst adults was 2.8 per 1000 for men and 3.2 per 1000 for women. The impact of AIDS on life expectancy at birth is 4.3 years for women and 3.3 years for men. CONCLUSION: Our study provides a direct measure of AIDS contribution to mortality relative to other causes, using a rapid, low cost, reliable and replicable method. Clearly, the impact of AIDS is strongest on female life expectancy.

PIP: As of December 1997, UNAIDS estimated that 20.8 million people were infected with HIV in sub-Saharan Africa. Brazzaville, Congo, has an estimated population of 850,000, according to the 1996 national census, and an estimated HIV-1 prevalence rate of approximately 5% in the general reproductive-age population. Findings are presented from a study conducted to accurately measure AIDS-related mortality relative to other causes and its impact upon life expectancy in Brazzaville, Congo. From July 10 to August 9, 1996, all bodies handled by Brazzaville's 3 morgues were examined by a physician. Relatives were interviewed on the circumstances of death and additional clinical data were collected from hospital files. Blood samples were systematically drawn from the bodies in 2 of the 3 morgues and tested for HIV antibodies. 149 of the 756 bodies (19.7%) examined at the morgues had AIDS. 38 of the 145 (26.2%) subjects in the 2 morgues in which HIV serology was systematically performed were infected with HIV-1. AIDS was the leading cause of death among people aged 15 years and older, with 122 of the 487 (25.1%) adults diagnosed with AIDS. 30.2% of the adult female deaths were due to AIDS, compared to only 21.0% of the male cases. The median age of female AIDS cases was 32 years, compared to 42 years for male cases, a highly significant difference. The overall AIDS mortality rate among adults was 2.8/1000 for men and 3.2/1000 for women. The impact of AIDS upon life expectancy at birth is 4.3 years for women and 3.3 years for men.

Direct estimation of maternal mortality in Africa.

PIP: Direct estimation of maternal mortality is facilitated in Brazzaville, Congo, by a law requiring that all bodies be delivered to a mortuary before burial. The authors investigated all bodies handled by the city's 3 mortuaries in a 4-week period in 1996. 15 maternal deaths were identified among the 138 female adult bodies. Based on the number of live births (27,888) in a 12-month period in 1995-96 and on the age distribution of the mothers, a maternal mortality rate of 645/100,000 was calculated. The lifetime risk for maternal mortality was estimated as 1 in 25 women. This rate is unexpectedly high since 90% of women in Brazzaville have access to prenatal care and most births occur in maternity hospitals. The excess maternal mortality is attributable, in part, to the high number of abortion-related deaths in young women. In this series, 6 deaths were due to abortion-related septicemia or hemorrhage. Maternal mortality is unlikely to decrease in African cities until more safe reproductive choices are available.^ieng

African origin of GB virus C/hepatitis G virus.

Ninety-four GB virus C/hepatitis G virus (GBV-C/ HGV) RNA-positive serum samples were obtained from all over the world. We found that all 15 GBV-C/HGV isolates from the Pygmies and the Bantu in the Central African region had a 12-amino acid indel (i.e. insertion or deletion) in the non-structural protein (NS) 5A region. Phylogenetic analyses of the NS5A region, using GBV-A as an outgroup, showed that these 15 isolates had diverged from the common ancestor much earlier than the remaining isolates, indicating an African origin of GBV-C/HGV.

Mother-to-child transmission of HIV-1 in Congo, central Africa. Congolese Research Group on Mother-to-Child Transmission of HIV.

OBJECTIVE: To assess the risk of mother-to-child transmission of HIV-1 in a central African population and to study maternal factors associated with perinatal transmission. DESIGN: Prospective cohort study of infants born to HIV-1-positive women and controls born to HIV-1-negative women enrolled sequentially in two prenatal clinics and one maternity hospital in Brazzaville, Congo. SUBJECTS AND METHODS: A total of 118 exposed and 208 control infants were followed from birth for at least 2 years. Assessment of infection in children and computation of transmission rate were made according to the European Economic Community/World Health Organization Ghent guidelines (1992). RESULTS: The transmission rate was 40.4% [95% confidence interval (CI), 30.7-50.1]. Maternal age, parity, history of adverse pregnancy outcome or history of decreased children were not associated with transmission. However, independently, women whose relationship with their infant's father was less than 1 year, or women who had symptoms of HIV-1 during pregnancy had an increased risk of transmission [adjusted odds ratios, 11.1 (95% CI, 2.4-50.2) and 10.3 (95% CI, 2.9-37.1), respectively]. CONCLUSION: The transmission rate observed in Congo is in the upper range of the rates reported in Africa. The uneven distribution of cofactors for perinatal transmission, such as the presence of symptoms of HIV disease during pregnancy, may explain some of the variation observed across studies.

Maternal antibody response at delivery and perinatal transmission of human immunodeficiency virus type 1 in African women.

Prospective cohort studies indicate that 13-45% of human immunodeficiency virus type 1 (HIV-1)-infected pregnant women transmit the virus to their infants. Although factors that influence perinatal transmission are not well understood, drug and immunotherapy trials to interrupt transmission are underway. The identification of women most at risk is essential for prevention, counselling, and medical intervention. We assessed 70 HIV-1-infected pregnant women enrolled in a prospective study of perinatal transmission in Brazzaville, Congo. The relations between maternal health status, antibody levels to selected HIV-1 structural antigens at delivery, and infant outcome were explored. Independent of clinical stage, higher maternal antibody titres to peptides corresponding to the V3 region of gp120 and the immunodominant domain of gp41 were correlated with a higher risk of perinatal transmission. In a logistic regression model, the predicted risk of transmission for symptom-free women whose antibody titres to V3 and gp41 were lowest was 0.02, whereas it was 0.88 for symptomatic women whose antibody titres to V3 and TMSP18 were highest. These associations may give new insight into the mechanisms of perinatal transmission and they may also provide a powerful means of identifying women who would most benefit from intervention trials to halt perinatal transmission.

High variability of the gag/pol transframe region among HIV-1 isolates.

The overlapping region of gag and pol genes of human immunodeficiency virus type 1 (HIV-1) also called transframe region, contains the frameshift locus from gag to pol. This region encodes both the protein p6, the function of which remains unclear, and a putative transframe protein covently linked to the N-terminus of the viral protease within Gag/Pol protein precursor. We have investigated the variability of the transframe region among nine HIV-1 isolates obtained from Congolese AIDS patients. Nucleotide sequences were determined using the polymerase chain reaction and the direct sequencing of amplified products. The sequences of Congolese isolates markedly differed from one another and from other reference HIV-1 strains by both insertion-deletion events and numerous base substitutions. Several putative cleavage sites of precursor polypeptides were modified. When compared to consensus ones the amino acid sequences of p6 protein were very different among divergent HIV-1 isolates, except for a limited group of 10 conserved amino acids.

Cryptococcal meningitis associated with acquired immunodeficiency syndrome (AIDS) in African patients: treatment with fluconazole.

Cryptococcal meningitis associated with acquired immunodeficiency syndrome (AIDS) is particularly common in tropical Africa. This could be explained by the dramatic increase in the number of human immunodeficiency virus (HIV) infections and the high prevalence of Cryptococcus neoformans var. neoformans in the domestic and general environment of HIV-positive and AIDS patients Meningoencephalitis is the usual and dominant clinical feature of cryptococcal infection in AIDS patients and 'slim disease', tuberculosis and candidiasis are the most common opportunistic infections associated with cryptococcal meningitis. In a group of 64 African patients with AIDS and cryptococcosis treatment with a daily dose of 400 mg fluconazole (FCA) during the acute phase showed a clinical cure in 63% of the evaluable patients. Mycological response to treatment with negative culture was found in 76% of our patients (at day 60-90). The overall tolerance of FCA was excellent. This treatment was also used successfully for relapse of cryptococcal meningitis.

Genetic variability affects the detection of HIV by polymerase chain reaction.

Nine isolates of HIV-1 obtained from Congolese AIDS patients were amplified by the polymerase chain reaction (PCR) using primer pairs and oligomer probes derived from the HIV-1 LAV-BRU (BRU) sequence. When compared to BRU, two isolates exhibited a significant decrease of PCR efficiency with a given primer pair. Moreover, the DNA amplified from two other isolates did not hybridize with the corresponding probe despite efficient PCR. Base substitutions were detected in the regions of proviral genomes involved in oligonucleotide annealing and were assumed to be responsible for the failure of both amplification and probing. Our data confirm that the genetic variability of HIV-1 may reduce the efficiency of PCR as a diagnostic procedure, especially in the case of African isolates.

[Pneumocystis carinii pneumonia in patients with AIDS in the Congo]. / Pneumocystoses observées au Congo chez les malades atteints de SIDA.

Forty-five bronchoalveolar lavages (BAL) were performed in Brazzaville in AIDS patients who did not expectorate acid- and alcohol-resistant bacilli (AARB). All patients presented with respiratory symptoms (cough, dyspnoea or chest pain), and all but 6 of them had abnormal radiography of the chest. Four cases of pneumocystosis were diagnosed (9%); 3 of these patients had interstitial pneumonia and dyspnoea. No AARB was found at microscopic examination of BAL which showed Pneumocyctis carinii; no culture on Löwehstein's medium could be made. The authors consider that the low prevalence of pneumocystosis in Africa, compared with industrial countries, is due to a smaller dissemination of the parasite in Africa rather than to immunodepression which is known to be more pronounced in AIDS patients from industrial countries.

Polymerase chain reaction for studies of mother to child transmission of HIV1 in Africa.

The feasibility and implications of the use of the polymerase chain reaction (PCR) assay in studies of HIV1 mother to child transmission in Africa were investigated. Uncultured leukocyte blood cells (PBL) obtained in Brazzaville (Congo) from newborns and infants (mean age = 27 weeks) of infected mothers were tested. HIV1 DNA sequences were identified in the PBL of six of eight newborns and 14 of 23 babies born to HIV1-positive mothers. In addition two of four babies, who at birth had been seropositive and subsequently were seronegative, were HIV1 DNA positive by PCR. This study demonstrates directly, therefore, a high rate of HIV1 transmission in Africa; it also indicates that PCR should be used for such epidemiological studies.

[Campaign strategy against AIDS in Africa: Congolese procedures and experience]. / Strategie de lutte contre le SIDA en Afrique: démarche et expériencecongolaises.

Compared with US and European countries, AIDS prevention in Africa has two specificities: there are no peculiar risk groups and the HIV is transmitted mainly through heterosexual relations. In Congo, the prevention strategy aims at the followings: information and in-service training for health workers; medical and psychological care for contaminated persons; and information to the general public. As AIDS spreads much more in urban areas (3.8%) than in rural areas (less than 1%), the first decision has been to organise a systematic screening of blood donors in Brazzaville, together with a face-to-face counselling for everyone and particularly to HIV positives. The public information is based on public sessions with half-an-hour information and a two-hour discussion. As condoms are not yet psychologically and economically accessible to the African people, the prevention campaigns have to give a panel of possible solutions, including abstinence, decrease in the number of partners, fidelity,.... The approaches are multimedia including theater, songs, posters, TV and radio.

[Carriers of HBs antigen, anti-HIV antibodies and their association with blood donors in Brazzaville]. / Portage de l'antigéne HBs, d'anticorps anti-VIH et de leur association chez les donneurs de sang a Brazzaville.

Serum samples taken from 6,624 blood donors since 1984 to 1987, were tested for Hepatitis B virus surface antigen (HBs Ag) using a microhemagglutination assay and for anti-HIV antibodies by ELISA test. The mean carrier state of HBs Ag was 10.68% and that of anti-HIV antibodies was 6.99%. The association of HBs Ag and anti-HIV antibodies was discovered in 4.84% donors but without correlation for the period of the study.

[Opportunistic parasitic diseases and mycoses in AIDS. Their frequencies in Brazzaville (Congo)]. / Parasitoses et mycoses opportunistes au cours du SIDA. Leurs fréquences à Brazzaville (Congo).

To determine the frequency of opportunistic parasitic and mycotic diseases in adult AIDS patients in the Congo, a study was conducted at l'Hôpital Universitaire de Brazzaville in 1986 and 1987. Diagnosis of AIDS was made using the WHO clinical definition for Africa (Bangui, 1985) and HIV seropositivity Pasteur Elisa test. Oral pharyngeal candidiasis occurred in 36% of cases. Intestinal parasitic profile found in 118 patients, 2/3 of whom were associated with chronic diarrhoea showed clearly relative frequency of isosporiasis (Isospora belli): 9.3% and rarity of crystosporidiosis: 4.2%. 12 meningitic cryptococcosis cases out of 139 patients was confirmed (8.6%); for cerebral toxoplasmosis, it was by comparing the serum toxoplasmosis antibody and cerebrospinal fluid rates on 75 patients that an estimation of 20% was reached. Pneumocytis carinii pneumonia seems to be rare, lower than 10%. No case of disseminated histoplasmosis and malignant strongyloidiasis was observed.

PIP: Studies conducted with locally available means at the University Hospital in Brazzaville have provided data on opportunistic parasitic and mycotic disease in AIDS patients in the Congo. The diagnosis of AIDS was based on the World Health Organization clinical definition for Africa and on positive ELISA tests. Patients were prospectively studied in 1986-87. 12 cases of meningitic cryptococcosis were found in 139 patients studied, for a rate of almost 9% of AIDS cases. Prior to the AIDS epidemic only 2 cases were published in the Congo. 35.6% of 146 cases studied showed oral pharyngeal candidiasis on clinical examination. The frequency of esophageal and bronchopulmonary candidiasis could not be estimated with the means available. 118 AIDS patients had intestinal parasites, of whom 2/3 had chronic diarrhea. 9.3% were caused by Isospora belli and 4.2% by Cryptosporidiosis. Other intestinal flora were apparently affected by routinely administered antiparasite treatments. An estimate of 20% for cerebral toxoplasmosis was obtained by comparing serum toxoplasmosis antibody and cerebrospinal fluid rates for 75 patients. The rate of pneumocystis carinii pneumonia appears on indirect evidence to be under 10%. No cases of disseminated histoplasmosis or malignant strongyloidiasis were observed. The biggest differences between the patterns of opportunistic infection in industrialized countries and especially the US and in the Congo appear to be the lesser frequency in the Congo of pneumocystosis and the greater frequency of Isosporosis and cerebral toxoplasmosis.