A prospective study of vertical transmission of HIV-2 in Bissau, Guinea-Bissau.

OBJECTIVES: To determine the vertical transmission rate of HIV-2 and clinical findings associated with vertically transmitted HIV-2 infection. DESIGN: A prospective study of HIV-2 transmission in children of HIV-2-seropositive mothers, and a comparison of clinical findings between children of seropositive and seronegative mothers. SETTING: Recruitment of women delivering at the national hospital in Bissau, Guinea-Bissau. Follow-up by home visits. SUBJECTS AND METHODS: Eighty-six newborns of 82 HIV-2-seropositive mothers and a control group of 102 newborns of HIV-seronegative mothers were followed-up clinically and by HIV serology until the children reached the age of 20 months. RESULTS: Of the 86 children of seropositive mothers, 51 had a complete follow-up, 22 died and 13 were lost due to change of residence. Of the 102 children of seronegative mothers, 63 had a complete follow-up, 13 died and 26 were lost due to change of residence. None of 51 children of seropositive mothers had serological evidence of HIV-2 infection at the end of the follow-up period. There was no significant difference in the frequency of clinical symptoms between the children in the study group and the children in the control group. The mortality during the first year of life was not significantly different between the children of seropositive and seronegative mothers (13 out of 80 and 11 out of 94, respectively, P > 0.05, excluding children lost to follow-up). Only three of the dead children of seropositive mothers and one of the dead children of seronegative mothers had any symptoms that might be related to HIV-2 infection (diarrhoea > 1 month). CONCLUSION: Vertical transmission of HIV-2 appears to be rare.

PIP: Between May 1987 and December 1988 in Guinea-Bissau, health workers followed 86 HIV-2 seropositive mothers and their infants delivered at the National Hospital Simao-Mendes in Bissau for 20 months to learn the HIV-2 vertical transmission rate and to compare their clinical findings with those of 102 infants of HIV-2 seronegative women. The ELISA and Western Blot analysis used antigen-purified virions of the SBL-6669 strain of HIV-2 grown on U937:2 cells. During the enrollment period, hospital workers tested 3246 women; tests confirmed that 211 (6.5%) and 3 (0.1%) were HIV-2 seropositive, respectively. 1 HIV-2 seronegative mother seroconverted during the study, but none of the infants of HIV-2 seronegative mothers seroconverted. Infant mortality of cases did not differ significantly from that of controls (16.2% vs. 11.7%). After 1 year of age, however, children of HIV-2 seropositive mothers were significantly more likely to die than the controls (15% vs. 3%; p .05). When the researchers added the children lost to follow up, there no longer was a significant difference in mortality after 1 year (23.9% vs. 24.1%). Just 3 of the deceased infants of the HIV-2 seropositive mothers and 1 of the deceased infants of seronegative mothers suffered from symptoms from symptoms that may have been related to HIV-2 infection. 1 of these deceased infants was HIV-2 seropositive at 12 months. These symptoms included prolonged fever, vomiting, diarrhea, and respiratory symptoms. Children in the study group did not experience more frequent clinical symptoms of HIV-2 infection than did the controls during the 3rd and 4th home visits. At the last visit (i.e., 4th visit; when the children were older than 17 months), none of the children of the HIV-2 seropositive mothers tested positive for HIV- 2. Vertical transmission of HIV-2 infection may be rare.

HIV-2 infection in hospitalized patients in Bissau, Guinea-Bissau.

During 11 months in 1989-1990, 1009 consecutive hospitalized adult patients admitted to the medical wards of the National Hospital in Bissau were interviewed, examined clinically, and tested for antibodies to HIV-1 and HIV-2. The prevalence of HIV-2 infection was 20.4% (206 out of 1009) and of HIV-2-associated AIDS 4.4% (44 out of 1009). HIV-2 infection was more frequent in women (25%, 110 out of 440) than in men (16.9%, 96 out of 569). HIV-1 infection was diagnosed in one patient only, and one patient (with AIDS) had reactivity to both HIV-1 and HIV-2. Among HIV-2-seropositive patients, AIDS was demonstrated in 21.3% and AIDS-related symptoms (not fulfilling the AIDS criteria) in 19.4%. The frequency of AIDS-associated symptoms was significantly higher in HIV-2-seropositive patients than in seronegative patients. The clinical profile of the HIV-2-associated AIDS cases was very similar to that described in HIV-1-associated AIDS cases in Africa. Seven out of 51 patients fulfilling the clinical criteria for AIDS were HIV-seronegative. The World Health Organization (WHO) clinical case definition for AIDS in Africa had a specificity of 99% and a positive predictive value of 86%. Tuberculosis was more common in HIV-2-seropositive patients (6.3%) than in HIV-2-seronegative patients (2.2%). A history of blood transfusion was a significant risk factor for HIV-2 infection. HIV-2 infection and AIDS are public health problems in Guinea-Bissau.

HIV-2-associated AIDS and HIV-2 seroprevalence in Bissau, Guinea-Bissau.

During a 6-month period in 1987, we examined patients clinically suspected of the acquired immune deficiency syndrome (AIDS) at the national hospital in Bissau, the capital of Guinea-Bissau, and found 20 cases that fulfilled the criteria for AIDS. The two most prevalent major symptoms were weight loss and diarrhea, and the most common minor symptoms generalized lymphadenopathy and generalized dermatitis. Six of 20 patients died within a couple of months. Nineteen of 20 patients were tested for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) antibodies and were shown to be HIV-2 seropositive. During the same time period, a seroprevalence study of HIV-2 and HIV-1 was carried out, including 2,122 patients or healthy persons in Bissau. Antibodies to HIV-2 were demonstrated by enzyme-linked immunosorbent assay and verified by Western blot analysis in 8.6% (46/535) of prenatal women, in 7.9% (9/114) of women attending a family-planning clinic, in 4.4% (19/427) of applicants for scholarships, in 17.6% (16/91) of blood donors tested during the first 2 months and 5.3% (10/189) of blood donors tested during the following months, in 5.7% (2/35) of police officers, in 36.7% (11/30) of female prostitutes, in 15.8% (97/614) of outpatients suspected of having tuberculosis, and in 55.2% (48/87) of patients clinically suspected of AIDS or AIDS-related disease. One of 2,001 subjects tested had antibodies specific for HIV-1. Another subject had an antibody pattern compatible with both HIV-1 and HIV-2 infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved detection of HIV-2 DNA in clinical samples using a nested primer-based polymerase chain reaction.

A two-step polymerase chain reaction (PCR), with four double (nested) primer pairs, used for the detection of HIV-2 in clinical samples is described. With these four nested primer pairs we could detect HIV-2 DNA in 17 of 17 virus isolates and in blood mononuclear cell samples from 31 of 37 (83.7%) seropositive individuals after ethidium bromide staining of the amplified DNA. The nested primer PCR was also compared with a single primer pair-based PCR followed by hybridization. The sensitivities of the two methods were almost equal, but the nested primer PCR offered obvious technical advantages.

Cross-neutralizing antibodies against HIV-1 (HTLV-IIIB and HTLV-IIIRF) and HIV-2 (SBL-6669 and a new isolate SBL-K135).

A total of 57 HIV-1 antibody-positive sera and 43 HIV-2 antibody-positive sera were all tested for neutralizing capacity against two HIV-1 isolates (HTLV-IIIB and HTLV-IIIRF) and two HIV-2 isolates (SBL-6669 and SBL-K135). SBL-K135 is a new HIV-2 isolate obtained from a patient with clinical AIDS from Guinea-Bissau. Among the HIV-1--positive sera, 84% neutralized any of the HIV-1 isolates, 67% neutralized both HIV-1 isolates, and 35% neutralized any of the HIV-2 isolates. Among the HIV-2--positive sera, 91% neutralized any of the HIV-2 isolates, 67% neutralized both HIV-2 isolates, and 37% neutralized any of the HIV-1 isolates. Thus, neutralizing antibodies in HIV-1-- and HIV-2--positive sera can be cross-reacting, type-specific, or strain-specific. The cross-neutralizing titers were lower than the neutralizing titers against the type-specific viral isolates. The presence of cross-neutralizing antibodies was related to the presence of neutralizing antibodies against both type-specific isolates.

Clinical and immunological follow-up of previously hospitalized HIV-2 seropositive patients in Bissau, Guinea-Bissau.

A follow-up study was done in Bissau on 113 HIV-2 seropositive patients and 97 HIV-2 seronegative patients 3-15 months after hospitalization. Follow-up totalled 63.5 person years for seropositive patients and 62 for seronegative patients. The mortality during the follow-up period was 43.3% among the seropositive patients (rate 72/100 person years; p.y.) and 25.8% among the seronegative patients (40/100 p. y.). Among 25 HIV-2 associated AIDS cases the mortality was 80% (rate 117/100 p. y.). The median survival time for the AIDS patients was 8 months. Among 48 HIV-2 seropositive patients who lacked signs or symptoms included in the WHO case definition for AIDS at the time of hospitalization 6 patients (12.5%) developed AIDS related symptoms (ARS) during altogether 31.5 person years of follow-up (rate 19/100 p. y.). Tuberculin anergy was demonstrated in 83.3% (15/18) of HIV-2 seropositive patients with AIDS or ARS, in 14.3% (6/42) of seropositive patients without HIV-related symptoms and in 6.9% (5/72) of seronegative patients. A low CD4 T-lymphocyte count in combination with a low CD4/CD8 T-cell ratio was found significantly more often in HIV-2 seropositive patients with AIDS or ARS (62.5%, 10/16) than in HIV-2 seropositive patients without HIV associated symptoms (6.9%, 2/29) or in seronegative patients (2.7%, 1/37). Thus the mortality among recently hospitalized HIV-2 seropositive patients was high and a high proportion of seropositive patients with HIV-related symptoms had evidence of immunodeficiency.

Low doses of quinine during a short time period are effective for clearance of Plasmodium falciparum in asymptomatic children in Guinea Bissau.

Asymptomatic children in Guinea Bissau were given 5 mg quinine per kg body weight two times daily for 5 days (n = 18) or 3 days (n = 20) for treatment of Plasmodium falciparum. Parasites disappeared within four days after initiation of treatment and remained absent during the first week afterwards. Six children reported adverse reactions, mainly mild tinnitus which disappeared after termination of treatment. Reduced doses of quinine for shorter treatment periods was effective in this study. Further studies in symptomatic patients are needed to elucidate whether this low-dose regimen could be an alternative to chloro-quine in the treatment of P. falciparum in Africa.

Envelope cross-reactivity between human immunodeficiency virus types 1 and 2 detected by different serological methods: correlation between cross-neutralization and reactivity against the main neutralizing site.

A total of 70 human immunodeficiency virus type 1 (HIV-1) and 42 HIV-2 antibody-positive serum samples, collected from groups of individuals in which only one type of HIV prevails, were tested for cross-reactivity against HIV-2 and HIV-1 proteins by Western blot (WB) (immunoblot), radioimmunoprecipitation assay (RIPA), neutralization analysis, and enzyme-linked immunosorbent assay with as antigen synthetic peptides representing selected parts of the envelope (env) glycoproteins. Cross-reactions against the env glycoproteins were observed by WB in 10% (7 of 70) and by RIPA in 40% (28 of 70) of the HIV-1 antibody-positive serum samples and by WB in 29% (12 of 42) and by RIPA in 48% (20 of 42) of the HIV-2 antibody-positive serum samples. Testing by enzyme-linked immunosorbent assay against a 36-amino-acid peptide (Cys-301-Cys-336) of the external glycoprotein of strain HTLV-IIIB of HIV-1 (HIV-1HTLV-IIIB) (known to represent a dominating, linear neutralizing site) showed type-specific reactions in 67% (38 of 57) of HIV-1 antibody-positive serum samples. Type-specific reactions against a homologous 35-amino-acid peptide of strain SBL-6669 of HIV-2 (HIV-2SBL-6669) were found in 75% (30 of 40) of HIV-2 antibody-positive serum samples, and these reactions were correlated to neutralization against HIV-2SBL-6669. Cross-reactions against these peptides were seen in 23% (13 of 57) and 33% (13 of 40) of the HIV-1 and HIV-2 antibody-positive serum samples, respectively. These cross-reactions were correlated to cross-neutralization against HIV-1HTLV-IIIB and HIV-2SBL-6669. Cross-neutralization against one heterotypic virus strain was demonstrated in 16% (9 of 57) of HIV-1 antibody-positive serum samples and in 22% (5 of 22) of HIV-2 antibody-positive serum samples, but no correlation was found between cross-neutralization and env cross-reactivity in WB or RIPA.