Clinical predictors of HIV infection in hospitalized children aged 2-18 months in Harare, Zimbabwe.

BACKGROUND: In Africa without antiretroviral treatment more than half of the HIV infected children die by 2 years. The recommended HIV virological testing for early infant diagnosis is not widely available in developing countries therefore a presumptive diagnosis is made in infants presenting with symptoms suggestive of HIV disease. OBJECTIVES: To identify presenting signs and symptoms predictive of HIV infection in hospitalized children aged between 2- 18 months at Harare Hospital, Zimbabwe. METHODS: In a cross sectional study the baseline clinical information was collected and HIV infection confirmed using DNA PCR. Multiple logistic regression analysis was used to identify significant predictors of symptomatic HIV infection. Diagnostic parameters (sensitivity, specificity) and their 95% confidence intervals were calculated. RESULTS: 355 children with an overall median age of 6 months (IQR: 3, 10.5 months) of whom 203 (57.2%) were HIV DNA PCR positive. Clinical signs independently predictive of HIV infection were cyanosis, generalized lymphadenopathy, oral thrush, weight for age z-score <-2 and splenomegaly. The sensitivity of these signs ranged from 43-49% with a higher specificity (ranging from 72.3-89.5%). CONCLUSION: Clinical identification using individual signs for probable HIV infection in hospitalized children below 18 months would provide an opportunity for early diagnosis, treatment.

A pilot study to assess the immunologic and virologic efficacy of generic nevirapine, zidovudine and lamivudine in the treatment of HIV-1 infected women with pre-exposure to single dose nevirapine or short course zidovudine and their spouses in Chitungwiza, Zimbabwe.

OBJECTIVE: A pilot study to assess effectiveness of generic Nevirapine (NVP)+Zidovudine (AZT)+Lamivudine (3TC) as potent antiretroviral therapy (ART) in women exposed to either SD NVP or short course (SC) AZT through participation in prevention of mother-to-child transmission of HIV-1 (pMTCT) interventions, and their spouses. DESIGN: A pilot study of antiretroviral treatment of adults with AIDS. SETTING: Primary health care clinics; Seke North and St Mary's in Chitungwiza, Zimbabwe. SUBJECTS: Women with pre-exposure to SD NVP or SC AZT and their spouses with CD4 count < 200 cells/ INTERVENTIONS: Generic AZT/3TC twice daily plus NVP daily for the first 14 days and then twice a day thereafter, administered to the cohort. MAIN OUTCOME MEASURES: The baseline median CD4 count for women and men was 128.5 and 119.0 cells/ microL respectively. The geomean virus load was similar for the women and men. At weeks 16, 24 and 48, 82.8%, 85.1% and 73.8% had < 400 copies/ml of HIV RNA respectively. Only at 16 weeks, was the proportion of women (75.9%) with undetectable virus significantly lower than that for men (93.9%), p = 0.031. Median CD4 count for both men and women increased significantly, p < 0.001. There were no significant differences in virologic responses between the women with pre-exposure to SD NVP and SC AZT. The mean adherence for women and men was similar, > 98%. CONCLUSION: Women showed a significantly reduced response top ART relative to men only at 16. However, prior exposure to SD NVP for PMTCT was no more likely to negatively influence responses to ART than use of SC AZT.

Prenatal transmission of subtype C HIV-1 in Zimbabwe: HIV-1 RNA and DNA in maternal and cord blood.

Maternal and cord samples from HIV-seropositive women and their infants in Zimbabwe, where subtype C is the predominant strain of HIV, were analyzed to determine the frequency of detection of HIV RNA and DNA. HIV RNA was detected in 90% of maternal and in 38% of cord plasma at levels at least 25% of maternal plasma. Heteroduplex mobility assays and sequencing of virus envelope (C2-V5) demonstrated closely related, but unique, subtype C viruses in maternal and cord RNA, and a significantly greater frequency of cord viremia among women with homogenous, compared with heterogeneous viral envelope RNA. Quantification of RNA, measures of envelope viral diversity, and phylogenetic analysis of maternal and cord plasma RNA provide evidence for the frequent exposure and potential transmission of HIV from mother to infant before birth.

An evaluation of dipstick-dot immunoassay in the detection of antibodies to HIV-1 and 2 in Zimbabwe.

There is a need, in many developing countries, for simple and inexpensive HIV serology tests for use at the district level of health care. The Programme for Appropriate Technology in Health has developed a simple dipstick ELISA to detect antibodies to HIV-1 and 2, at a cost considerably lower than current ELISAs, which requires no specialized washing or reading equipment. In order to evaluate this dipstick under local conditions we used a panel of 546 sera selected from frozen stocks maintained by the Zimbabwe AIDS Prevention Project in Harare, Zimbabwe. Prior to storage, the sera had been tested by Abbott recombinant peptide HIV-1 and 2 ELISA and Enzygnost synthetic peptide HIV-1 and 2 ELISA. The panel included sera that were positive by both (including symptomatics and asymptomatics), negative by both, and sera showing discrepant test results. The panel was not representative of a "normal' batch of sera in Zimbabwe, and in particular included an abnormally high number of sera showing discrepant results. Thawed sera were retested using the Abbott recombinant peptide HIV-1 and 2 ELISA and concurrently with the synthetic peptide ICL-Dipstick ELISA. Both the sensitivity and specificity of the ICL Dipstick exceeded 99% when using sera that were positive or negative in all 3 plate ELISAs as the gold standard. When using sera that gave discrepant results between the two pre-storage ELISAs, most results with the ICL Dipstick concurred with findings from other test systems, including Western blot and p24 antigen detection. Considering the accuracy, low cost and case of operation of the ICL Dipstick ELISA, this test can be recommended for use for the rapid detection of antibodies to HIV at district level in developing countries.

Hepatitis C virus and HIV antibodies in patients with hepatocellular carcinoma in Zimbabwe: a pilot study.

To determine the role of hepatitis C virus (HCV) infection in the aetiology of hepatocellular carcinoma (HCC) in Zimbabwe, HCV antibodies (anti-HCV) were determined in sera from 63 HCC patients using a second generation enzyme immunoassay. Anti-HCV was found in 15 patients (23.8%), 12 of whom (80%) were males. The mean ages of anti-HCV positive and anti-HCV negative patients were 62.1 (SD = 10.6) and 44.3 (SD = 15.2) years, respectively (P < 0.001). HIV antibodies were found in 17/59 patients (28.8%), 12 of whom (70.6%) were males. The mean ages of HIV positive and HIV negative patients were 39.4 (SD = 15.2) and 51.0 (SD = 15.2) years (P = 0.011). Hepatitis B surface antigen (HBsAg) was detected in 26/61 patients (42.6%) with mean ages of HBsAg positive vs negative patients of 41.5 (SD = 15.4) years for HIV positive and 53.1 (SD = 15.1) years for HIV negative subjects (P = 0.005). Younger HCC patients had high prevalences of HBsAg and anti-HIV and a low prevalence of anti-HCV; while older patients had a high prevalence of anti-HCV and low prevalences of HBsAg and anti-HIV. This study suggested that HCV infection is probably an important aetiological agent of HCC in Zimbabwe; however, the role of HIV infection as a cause of HCC either singly or as a co-factor with hepatitis B virus infection remains speculative and warrants further study.

PIP: Several studies have reported a high prevalence of hepatitis C virus (HCV) antibodies (anti-HCV) in patients with hepatocellular carcinoma (HCC). In addition, HIV infection may be a causative factor for HCC. To determine the role of HCV infection in the etiology of HCC in Zimbabwe, the presence of anti-HCV was assessed in sera from 63 HCC patients using a second-generation enzyme immunoassay. Anti-HCV was isolated in 15 patients (23.8%), of whom 12 were male. The mean ages of anti-HCV-positive and anti-HCV-negative patients were 62.1 and 44.3 years, respectively. HIV antibodies were found in 17 (28.8%) of 59 patients, of whom 12 were male. The mean ages of HIV-positive and HIV-negative patients were 39.4 and 51.0 years, respectively. Hepatitis B surface antigen (HBsAg) was detected in 26 of 61 patients (42.6%), with the mean ages of HBsAg-positive versus HBsAg-negative patients of 41.5 years for HIV-positive and 53.1 years for HIV-negative subjects. Younger HCC patients had high prevalences of HBsAg and anti-HIV, and a low prevalence of anti-HCV, while older patients had a high prevalence of anti-HCV and low prevalences of HBsAg and anti-HIV. These findings suggest that HCV infection is probably an important etiological agent of HCC in Zimbabwe.

Rapid and simple hepatitis assays: encouraging results from a blood donor population in Zimbabwe.

A rapid assay to detect antibodies to hepatitis C virus (HCV) in serum and two rapid/simple assays to detect hepatitis B surface antigen (HBsAg) in whole blood/serum were evaluated for their accuracy and suitability at the National Blood Transfusion Service, Harare, Zimbabwe. For this purpose, a total of 206 sera (196 routinely collected and 10 frozen) were tested using the HCV-SPOT (Genelabs Diagnostics), the SimpliRED HBsAg test (AGEN), and the Dipstick-HBsAg (PATH/Immuno-Chemical Laboratories). The results were compared with those obtained using a routine HBsAg enzyme immunoassay (EIA) (Auszyme, Abbott) and an HCV IgG second-generation EIA (Abbott). An HCV IgM test (Abbott) was used for samples that produced discordant results, and all HCV-reactive samples were confirmed using the INNO-LIA HCV Ab III synthetic peptide assay (Innogenetics). Overall, the concordance between the HCV-SPOT and the HCV EIA was 97.6% (201/206). For the 193 sera that were true HCV negatives, the number of false positives was six with the HCV-SPOT test, while the HCV EIA produced three (specificity = 97.0% and 98.5%, resp.). Of these false positives, two were so in both tests. None of the false positives contained IgM antibodies to HCV, and there were no false negatives in the two HCV tests. The concordance between the two rapid HBsAg tests and the HBsAg EIA was 99.5% (205/206). All the rapid/simple tests were easy to perform and interpret, required no (or minimal) laboratory equipment, and could be taught easily to local laboratory personnel. The cost of these tests is equivalent to or less than that of routine EIA methods.

Schistosomiasis and hepatitis B infection in pregnancy: implications for vaccination against hepatitis B.

A study to investigate the prevalence of schistosomiasis and hepatitis B viral (HBV) infection, among pregnant women was carried out at Howard Hospital in Chiweshe District, Zimbabwe. Urine and stool specimens, for the determination of Schistosoma haematobium and Schistosoma mansoni respectively, were collected from 299 pregnant women attending an antenatal clinic. In addition, five ml of blood was collected from each of the women for the determination of hepatitis B serum markers, HBsAg and anti-HB antibodies. S. haematobium and S. mansoni infection prevalence was 50 pc among the pregnant women. About 13 pc of them had both infections. Frequency of stillbirth or infant mortality was 16 pc among expectant mothers who previously had schistosoma infection compared to 8 pc among those who had no history of schistosomal infection. Only 2 pc of the pregnant women tested positive for the two hepatitis B markers. However, further hepatitis B prevalence B studies still have to be carried out with a larger cohort of pregnant women in schistosomiasis endemic areas. At the same time the seroconversion rates of children born from mothers living in schistosomiasis endemic areas would need to be compared with those of non-endemic areas before any changes in the recommended vaccination schedule are made.