Maternal immune responses and risk of infant infection with HIV-1 after a short course Zidovudine in a cohort of HIV-1 infected pregnant women in rural Kenya.

OBJECTIVE: To investigate the effects of short-course nucleoside reverse transcriptase inhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infant infection with HIV-1 among rural-based mothers in western Kenya. DESIGN: A prospective cohort study involving HIV-1 seropositive pregnant mothers and their infants. SUBJECTS: One hundred and seven HIV-1 seropositive asymptomatic pregnant women and their infants. METHODS: After informed consent, the women were enrolled at gestation age between 16-24 weeks. For cultural and economic reasons, all mothers were allowed to breast feed their infants. Short-course antepartum regime of AZT was administered to all mothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+ T cell subset assays were performed before 3rd trimester (about 36 weeks gestation) and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samples sequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 months of age. INTERVENTIONS: Antepartum short-course orally administered AZT: 300mg twice-daily starting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mg every three hours during labour until delivery. MAIN OUTCOME MEASURES: Maternal CD4+ T cell counts before and after AZT treatment. Determination of infant HIV-1 infection status. RESULTS: Among 107 women sampled, only 59 received full dose of AZT and thus qualified for present analysis. Of these, 12 infected their children with HIV, while 47 did not. Comparison of CD4+ T cells before and after AZT treatment scored a significant rise in all mothers (P = 0.01). This increase in CD4+ T cells was not significant among mothers who infected their infants with HIV-1 (P = 0.474). However, a significant rise in CD4+ T cells following AZT therapy was observed only in mothers who did not transmit HIV-1 to their infants (P=0.014). CONCLUSION: These data suggest that a rise in the CD4+ T cell counts following short AZT regimen, now widely in use in resource-weak countries, may be evidence of the active suppression of the replication of HIV. However, further studies to examine the multi-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need to be carried out to help fully explain the effect of AZT on immune response and whether the CD4+T cell count can be used as a true test of immunological normalisation during antiretroviral therapy.

Suppression of T-cell proliferative response in Plasmodium falciparum malaria patients--preliminary results.

We report suppression of T-cell proliferative responses to P.falciparum specific antigen and mitogens. T-cells derived from malaria patients were co-cultured with P.falciparum antigen or mitogens and the T-cell activity determined by radioactive thymidine incorporation assay system. We found inhibition of T-cell responses to P.falciparum antigen in 13 out of 24 malaria patients studied. The suppression ranged from 4%-60%. Results of mitogenic responses of T-cells showed a wide variation. Suppression of concanavalin A (Con A) responses ranged from 48%-64% (4 out of 10 patients) while phytohaemagglutinin (PHA) responses varied from 4%-60% (8 out of 10 patients) and those of purified protein derivative (PPD) antigen from 12%-44% (3 out of 6 patients). Together, these preliminary results show a marked impairment in T-cell responses to parasite antigen and mitogens in P. falciparum infected patients.

Immunology of HIV infection and AIDS: a review.

AIDS epidemic has highlighted the crucial importance of cell-mediated protective mechanisms against intracellular pathogens. Attempts are made in this review to focus on the current concepts in HIV infection and host responses, immunopathogenic mechanisms, vaccine approaches and the treatment aspects of AIDS patients.

A prevalence study of HIV antibodies in rural Kenya.

In order to describe the prevalence of HIV antibodies and AIDS in West Kenya, serological tests, including ELISA, and in some cases immunoblotting, were performed on whole blood collected on filter paper from 603 Kenyans. Serum samples from 55 of these persons underwent the same examinations, and 45 were further examined by immunofluorescence and a commercial ELISA. The majority of the Kenyans examined were residents of a province in West Kenya, while the others were students from other parts of Kenya, predominantly rural areas. Male/female ratio was 62/38. Median age was 18 years (range 0-70). Five Danes with previously demonstrated HIV antibodies, and 10 Danish controls were examined for HIV antibodies in filter paper whole blood, and in serum by ELISA and immunoblotting. The tests carried out on the filter paper blood were found to be reliable. Only one of the examined Kenyans had antibodies to HIV by both ELISA and immunoblotting, representing a prevalence of 0.17% (95% confidence limits: 0.00-0.93%). This low prevalence is not in accord with results previously presented from rural districts in Kenya.

T cell-mediated immunity in murine malaria. II. Induction of protective immunity to P. chabaudi by antigen-fed macrophages and antigen-educated lymphocytes.

We previously described assay systems for generating antigen specific proliferating T cells to P. chabaudi antigens. In the present study we examine whether the various sensitization approaches confer immunity against a cloned virulent strain IP-PCI of P. chabaudi. We present data indicating that effective specific protective immunity can be induced through P. chabaudi antigen fed macrophages and antigen educated spleen cells (initiator lymphocytes). The expression of this protective immunity is proposed to depend on (a) antigen presentation and/or accessory function of macrophages and (b) the subsequent activation of T cell functions related to protection. Indeed analysis of different macrophage populations revealed a correlation between the expression of Ia molecules and IL-1 secretion with their capacity to induce antigen specific T cells in vivo and subsequent protective immune mechanisms. Thus these results emphasize the critical functions of accessory cells in determining the outcome of malaria infections.

T-cell mediated immunity in murine malaria. I. Induction of T-cell dependent proliferative responses to Plasmodium chabaudi.

To investigate the mechanisms of cell mediated immunity to malaria, we studied different systems to measure specific activation of T lymphocytes by P. chabaudi antigens. Mice were primed by subcutaneous administration of parasite antigens followed by co-cultivation of lymphocytes taken from the draining lymph nodes in the presence of the priming antigen. A marked proliferative response was observed which was shown to be antigen specific, T-cell mediated and accessory cell dependent. Continuous T-cell lines were propagated in culture by repetitive restimulation in the presence of antigen and accessory cells, followed by expansion in a conditioned medium containing T-cell growth factors. These lines could be induced to proliferate to the priming antigen only in the presence of syngeneic accessory cells thus indicating that H-2 restriction operates in the recognition of plasmodium antigens by T cells. We also induced parasite specific T cells by the use of an in vitro primary 'education' system. Lymphocytes from unprimed mice were sensitized on parasite-fed macrophages and were then injected subcutaneously into each hind foot pad of syngeneic animals. This led to recruitment of antigen-reactive cells which were assayed in vitro by the ability of lymphocytes taken from the draining popliteal lymph nodes to proliferate in response to the sensitizing antigen. In vivo immunization with Plasmodium antigen fed macrophages also signalled antigen specific T cells that recruited reactive T cells in the draining lymph nodes.

Evaluation of five immunodiagnostic techniques in echinococcosis patients.

Double diffusion (DD), indirect haemagglutination (IHA), immunoelectrophoresis (IEP), latex agglutination (LA), and complement fixation (CF) tests were evaluated for sensitivity and specificity in the diagnosis of 141 surgically-proven Turkana echinococcosis patients and 10 controls. The overall sensitivities for the tests were: IHA, 86.7%; LA, 53.3%; CF, 63.3%; DD, 55.0%; IEP, 55.0%. LA and CF tests produced a high number of false positive results; IHA gave a false positive result in 10% of cases; no false positives were obtained with IEP and DD. A combination of the latter three tests would therefore offer the best chance of detecting specific anti-Echinococcus antibodies, with an average sensitivity of 62.7%. The possible reasons for the relatively high incidence of false negative values are discussed.