Peter L. Perine

Perinatal transmission of HIV-I in Zambia.

OBJECTIVE--To determine the occurrence of vertical transmission of HIV-I from women positive for the virus and the prognosis for their babies. DESIGN--Women presenting in labour were tested for HIV-I. Their newborn babies were also tested. Women positive for the virus were followed up with their babies for two years. SETTING--Teaching hospital in Lusaka, Zambia. SUBJECTS--1954 Women, of whom 227 were seropositive. Of 205 babies, 192 were positive for HIV-I. After birth 109 seropositive mothers and their babies and 40 seronegative mothers and their babies were available for follow up. MAIN OUTCOME MEASURES--Serological examination of mothers and their babies by western blotting. Birth weight and subsequent survival of babies. Women and babies were tested over two years for signs of seroconversion and symptoms of infection with HIV, AIDS related complex, and AIDS. RESULTS--Of the 109 babies born to seropositive mothers and available for follow up, 18 died before 8 months, 14 with clinical AIDS. Of the 91 remaining, 23 were seropositive at 8 months. By 24 months 23 of 86 surviving babies were seropositive, and a further five infected babies had died, four were terminally ill, 17 had AIDS related complex, and two had no symptoms. The overall rate of perinatal transmission was 42 out of 109 (39%). The overall mortality of infected children at 2 years was 19 out of 42 (44%). Before the age of 1 year infected children had pneumonia and recurrent coughs, thereafter symptoms included failure to thrive, recurrent diarrhoea and fever, pneumonia, candidiasis, and lymphodenopathy. All babies had received live attenuated vaccines before 8 months with no adverse affects. CONCLUSIONS--Vertical transmission from infected mothers to their babies is high in Zambia and prognosis is poor for the babies. Perinatal transmission and paediatric AIDS must be reduced, possibly by screening young women and counselling those positive for HIV-I against future pregnancy.

Apparent vertical transmission of human immunodeficiency virus type 1 by breast-feeding in Zambia

n To evaluate the epidemiologic significance of breastfeeding to the transmission of human immunodeficiency virus (HIV) in a country with a high prevalence of HIV infection, the 1720 seronegative women who delivered at the University Teaching Hospital in Lusaka, Zambia, in a 3- month period in 1987 were enrolled in a longitudinal study. Only 634 (37%) of these women returned for testing at the 1-year follow-up point. Of these, 19 (3%) had become seropositive. The infection was asymptomatic in all 19 women at the time of the 1-year follow-up; however, 5 of these women soon developed generalized persistent adenopathy and 3 had spontaneous abortions during the year in which seroconversion occurred. 30 of the spouses of the women in the study sample were HIV-positive; the relative risk of seroconversion was 3.84 in women with HIV-infected spouses compared to those with HIV-negative spouses. Other significant risk factors for HIV seroconversion included: history of genital ulceration after delivery (relative risk, 15.51), use of a cloth to remove vaginal secretions during intercourse (dry sex) (relative risk, 37.95), and blood transfusion (relative risk, 10.89). 3 infants born to these 19 women also seroconverted; 2 years after seroconversion, only 1 of the 3 infected children was symptomatic (persistent, generalized lymphadenopathy). Other sources of HIV infection 9e.g., scarification, blood transfusions, use of contaminated needles during immunization) aside from breastfeeding were not recorded in these 3 infants. Although there is a high prevalence of HIV infection in Zambia, the health benefits of breastfeeding (in terms of the prevention of mortality from diarrheal disease) still outweigh the small risk of HIV transmission.n

Genetic analysis of HIV-1 isolates from Zambia and an expanded phylogenetic tree for HIV-1

Geographic variation in the HIV-1 virus is extensive but incompletely documented. We herein report the first genetic characterization of HIV-1 isolates from Zambia. The genomic region encoding the GAG polyprotein has been compared among 22 Zambian isolates and 14 North American isolates using a combination of polymerase chain reaction (PCR) and DNA sequencing methods. The Zambian isolates were similar to one another but distinct from other HIV-1 isolates. They exhibited a characteristic PCR fingerprint wherein certain primer combinations were unable to amplify because of mispairing. The sequence of the complete gag gene of three isolates from Zambia has been determined, and phylogenetic tree analysis placed them in a branch distinct from other African isolates and North American isolates. The PCR procedure used here may be widely applicable for genetic characterization of HIV-1.

IgG subclass responses to human immunodeficiency virus-1 antigens: Lack of IgG2 response to gp41 correlates with clinical manifestation of disease

To analyze differential antibody responsiveness of potential pathogenetic significance, sera from 66 patients with human immunodeficiency virus-1 (HIV-1) infections at various Walter Reed (WR) stages of the disease were analyzed to determine the subclass distribution of HIV antibodies. Although all IgG subclasses were involved in the HIV antibody response, the frequency was highest for IgG1 and the lowest for IgG4. When IgG subclass responses to different HIV antigens were compared qualitatively, IgG1 was the major subclass reactive with env, pol, and gag antigens; IgG2 and IgG3 were almost equally represented in response to gag gene products; and IgG4 showed minimal reactivity to p24 antigen in all HIV-infected patients regardless of their clinical presentation. In contrast, significantly lower levels of IgG2 anti-gp41 were observed in patients at WR 5 and 6 (5%) when compared to those at stage WR 1 and 2 (88%). The IgG2 response to a recombinant gp 120/41 antigen, however, remained unchanged, suggesting that the lack of IgG2 response may be associated with lack of responsiveness to the carbohydrate epitope on gp41. Indeed, parallel measurements of IgG antibody responses to group A carbohydrate were also lower in patients at WR 5 and 6 stages, without affecting antibody responses to polyribosyl ribitol phosphate and phosphocholine. As antibody responses to group A carbohydrate with its N-acetyl D-glucosamine (GlcNAc) determinant were lower at the WR 5 and 6 stage of HIV disease, GlcNAc may be one of the antigenic determinants on gp41 that plays a critical role in some of the pathologic events of HIV infection.

Persistence of antibody to hepatitis B surface antigen after low-dose, intradermal hepatitis B immunization and response to a booster dose

To determine the duration of antibody after low-dose, intradermal (i.d.), plasma-derived hepatitis B vaccination and the response to a booster dose, we studied two classes of medical students who were immunized with 2 micrograms doses i.d. In one class, 73/88 (85%) who had been immunized by skilled personnel at 0, 1 and 6 months, had protective concentrations (greater than or equal to 10 mIU ml-1) of anti-HBs at 20 months after the first dose. Twelve (92%) out of 13 students who received only two doses at 0 and 1 months also had protective concentrations at month 20. At month 27, 11/16 (69%) with antibody less than or equal to 10 mIU ml-1 responded to a fourth dose of 2 micrograms i.d. with protective concentrations of anti-HBs. In the second class, after three doses of vaccine at 0, 1, and 6 months, protective concentrations of anti-HBs were present in 90/93 (97%) at 14 months and in 71/80 (89%) at 25 months. In those who received only two doses, protective concentrations were found in 24/31 (74%) at 14 months and 9/16 (56%) at 25 months. After a booster dose of 2 micrograms i.d. at month 25, anti-HBs concentrations rose from a geometric mean of 78 to 1198 mIU ml-1 in 60 subjects previously immunized with three doses and from 18 to 1054 mIU ml-1 in 16 students previously immunized with only two doses. Overall, 73/76 (96%) of students in the second group had protective concentrations of antibody after the booster dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-Term Preservation of Whole Blood Samples for Flow Cytometry Analysis in Normal and HIV-Infected Individuals from Africa:

A whole blood method requiring less than 4 ml of heparinized blood was developed to assess the practicality of preparing whole blood samples that could be easily stored, transported and readily used to determine the lymphocyte phenotypes and proliferation responses of individuals from remote areas who are infected with the human immunodeficiency virus. Minor modifications in standard whole blood procedure for lymphocyte phenotyping have significantly increased the stability of light scatter and fluorescence intensity of the cells for subsequent flow cytometry (FC) analysis. These changes include removal of lysis solution prior to fixation, fixation of monoclonal antibody-stained cells in 1% paraformaldehyde for 30 minutes and storage of fixed samples in medium containing 1% bovine serum albumin. Lymphocyte subsets and their functional subsets could reliably be determined on samples stored for up to 4 weeks. Further, blood samples could be kept at room temperature for up to 96 hours or at ambient temperature during transportation from Africa before staining for FC without affecting their quantitation. While samples could be processed for FC analysis under field-laboratory conditions, proliferation assays could only be performed on samples that were transported within 48 hours of their collection. The whole blood method saves time and expense and decreases the volumes of blood required to perform phenotypic analysis and functional assays on specimens collected in remote areas.

Hepatitis B vaccine booster dose: Low-dose recombinant hepatitis B vaccines as a booster dose

BACKGROUNDnThe timing and best regimen for a booster dose of hepatitis B vaccine have not been determined.nnnMETHODSnTwo studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine.nnnRESULTSnIn the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations).nnnCONCLUSIONnA 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Designing appropriate intervention strategies for HIV/AIDS in southern Africa

Zambias estimated 190 population was 8.1 million of whom 43% resided in cities. 1000 health care facilities are spread throughout 9 provinces and comprise village and district health clinics as well as provincial hospitals and the University Teaching Hospital (UTH) in Lusaka. A national sexually transmitted disease (STD) control program was launched in 1980 by the Ministry of Health to initially assess the extent of diseases on the basis of sample surveys and ultimately make preventive and curative interventions. The 1987 annual incidence of STDs in the adult population was 18/1000 with the male: female ration of 1.7:1. Genital ulcers due to syphilis or chancroid comprised more than 50% of new STD cases with the remainder resulting from gonorrhea chlamydia or trichomonias vaginalis. HIV seroprevalence surveys among antenatal women delivering on labor wards at the UTH show an increase from 8.6% to 22% over the period 1985-90; the level of male HIV seroprevalence increase is probably the same or greater. Risk factors among sexually active male adults are blood transfusions travel outside of Zambia and positive serological tests for syphilis; while blood transfusion and history of venereal disease are risk factors for female adults. Adults having had more than 50 sex partners are at highest risk for HIV infection; circumcised men have a significantly lower prevalence of HIV compared to uncircumcised men; and the female practice of removing vaginal secretions with a cloth to increase penile-vaginal friction increases the risk of transmission. Studies indicate however that condoms used alone or with spermicides are not effective in preventing the sexual transmission of HIV except in highly motivated couples. The cost and availability of condoms limit their use while the importance of their need is poorly recognized by health agencies. It is estimated from blood tests and interviews that 2.6 million Zambians between ages 15-34 years are at risk of HIV infection. Constrained by the lack of available resources to provide condoms on mass scale Ministry of Health programs reach out to diagnose and treat STD patients and partners and provide them with condoms. Primary and secondary syphilis and chancroid are the 2 most important STDs which may increase the risk of HIV transmission. Both can usually be cured with single doses of antibiotics.