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Publications (9)26.11 Total impact

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    ABSTRACT: 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. To identify presenting signs and symptoms predictive of HIV infection in hospitalized children aged between 2- 18 months at Harare Hospital, Zimbabwe. 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. 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%). Clinical identification using individual signs for probable HIV infection in hospitalized children below 18 months would provide an opportunity for early diagnosis, treatment.
    African health sciences 09/2012; 12(3):259-67.
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    ABSTRACT: The World Health Organization (WHO)'s "3 x 5 program" has spurred efforts to place 3 million people on combination antiretroviral therapy (ART) for treatment of AIDS in resource-limited countries. Paradoxically, the cost of CD4+ T-lymphocyte count essential for decision-making to commence HIV positive adults on ART as well as for monitoring responses to ART remains unaffordable in most resource-limited countries. Thus, low-cost methods for enumerating CD4+ T-lymphocyte are urgently needed. To evaluate Cyflow cytometry (Cyflow SL, Partec, Munster, Germany) for enumeration of absolute CD4+ T-lymphocyte in subtype C HIV-1 seropositive subjects using FACSCount (Becton and Dickinson, Immunocytometry Systems, San Jose, CA, USA) as the "predicate method". A total of 150 HIV-1 seropositive subjects were included in the evaluation exercise. Fifty-eight specimens were collected from pregnant HIV-1 seropositive women (subtype C drug resistance study). Twenty-seven specimens were collected from women and their spouses with AIDS followed in a Duke ART study to assess the immunologic and virologic responses to generic ART, comprising Stavudine, Lamivudine and Nevirapine (Stalanev, Varichem Labs, Harare, Zimbabwe). Sixty-five specimens were collected from AIDS patients enrolled in an ongoing Kaposi Sarcoma (KS) study to investigate impact of ART on KS progression. Enumeration of CD4+ T-lymphocytes using FACSCount is routinely conducted for all the three studies. The Medical Research Council of Zimbabwe and Medicines Control Authority of Zimbabwe approved the studies. Whole blood was collected in EDTA vacutainer tubes and aliquoted into two tubes (200 microL in each). CD4+ T-lymphocyte counts were enumerated using a Cyflow counter, in the Department of Immunology and a FACSCount in the Department of Obstetrics and Gynaecology within 6 hours of phlebotomy following manufacturers' instructions. Using linear regression analysis, there was a very strong correlation (R = 0.991) between the overall CD4+ T-lymphocyte counts obtained by FACSCount and those obtained by Cyflow. When data analysis was stratified by study groups, there was a strong correlation between the FACSCount and Cyflow CD4+ T-lymphocyte counts from subjects in the three independent studies; Subtype C resistance (R2 = 0.987), Duke ART (R2 = 0.980) and KS (R2 = 0.994), Table 1. Using Bland-Altman plots, the overall, absolute CD4+ T lymphocytes obtained by the two methods were in excellent agreement (mean difference 1.21, 95% Confidence Interval {CI): -2.1 to 3.3). For the 0-250 CD4+ T-lymphocytes range, the CD4 counts obtained using FACSCount were also in good agreement with those obtained using Cyflow counter (mean difference = 2.6 cells/microL, 95% CI: -1.1 to 6.3). Similarly, in the 251-500 (mean difference 1.0, cells/microL, 95% CI: -3.7 to 5.6) and the 501-1200 (mean difference = 0.29 cells/microL, 95% CI: -8.1 to 8.7) CD4 T-lymphocytes range, good agreement was observed. The Cyflow counter is as accurate as the FACSCount in enumerating absolute CD4+ T-lymphocytes in the range 1-1200 cells/muL. Cyflow cytometry is relatively affordable, easy to use technology that is useful not only in identifying HIV seropositive individuals who require ART but also for monitoring immunologic responses to ART.
    Journal of Translational Medicine 02/2006; 4:33. · 3.46 Impact Factor
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    ABSTRACT: The gold standard for diagnosis of HIV-1 infection in infants under the age of 2 years is DNA or reverse transcriptase polymerase chain reaction. However, these tests are expensive and therefore not available in resource-limited countries. With the increasing availability of antiretroviral drugs for prevention of mother-to-child transmission of HIV and treatment of AIDS in resource-poor countries, there is an urgent need to develop cheaper, alternative, and cost-effective laboratory methods for early diagnosis of infant HIV-1 infection that will be useful in identifying infected infants who may benefit from early cotrimoxazole prophylaxis or commencement of antiretroviral therapy. We evaluated an alternative method, the enzyme-linked immunosorbent assay-based qualitative ultrasensitive p24 antigen assay for diagnosis of subtype C HIV-1 infection in infants under the age of 2 years using DNA polymerase chain reaction as the reference method. The assay showed a sensitivity of 96.7% (95% CI: 93.0-100) for detection of HIV-1 infection among infants 0-18 months of age with a specificity of 96.1% (95% CI: 91.7-100). These evaluated parameters were not statistically different between infants aged 0-6 and 7-18 months. The ultrasensitive p24 antigen assay is a useful diagnostic test for detection of HIV-1 infection among infants aged 0-18 months.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2005; 39(4):391-4. · 4.65 Impact Factor
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    ABSTRACT: BACKGROUND: Serologic tests for HIV infection in infants less than 18 months do not differentiate exposure and infection since maternally acquired IgG antibodies may be detected in infants. Thus, the gold standard for diagnosis of HIV-1 infection in infants under the age of 2 years is DNA or reverse transcriptase polymerase chain reaction. There is an urgent need to evaluate alternative and cost effective laboratory methods for early diagnosis of infant HIV-1 infection as well as identifying infected infants who may benefit from cotrimoxazole prophylaxis and/or initiation of highly active antiretroviral therapy. METHODS: Whole blood was collected in EDTA from 137 infants aged 0 to 18 months. DNA polymerase chain reaction was used as the reference standard for diagnosis of HIV-1 infection. T-cell subset profiles were determined by flow cytometry. RESULTS: Seventy-six infants were DNA PCR positive while 61 were negative. The median CD4 counts of PCR negative infants were significantly higher than those of the PCR positive infants, p < 0.001. The median CD4/CD8 ratio and the %CD4 of the PCR positive infants were both significantly lower than those of the negative infants, p < 0.001. The CD4/CD8 ratio had a >98% sensitivity for diagnosis of HIV-1 infection and a specificity of >98%. CONCLUSION: The CD4/CD8 ratio appears useful in identifying HIV-infected infants. The development of lower cost and more robust flow cytometric methods that provide both CD4/CD8 ratio and %CD4 may be cost-effective for HIV-1 diagnosis and identification of infants for cotrimoxazole prophylaxis and/or highly active antiretroviral therapy.
    Journal of Translational Medicine 03/2005; 3(1):6. · 3.46 Impact Factor
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    ABSTRACT: HIV-1 mRNA levels (virus load) were quantified for 191 pulmonary tuberculosis (TB) patients and 132 HIV-1 seropositive controls. Human leukocyte antigen (HLA) class I and II genes were typed for 188 patients and 121 HIV-1 seropositive controls. The mean log virus load was higher among cases than HIV-1 seropositive controls (p < 0.0001). Among the controls, mean log virus load was higher among males than females (p = 0.04). There was no association between virus load and homozygosity at HLA class I and II among the controls. In contrast, among the cases, HLA-DRB1 homozygosity was associated with high virus load (p = 0.008), conferring risk for rapid progression to AIDS, thus lending support to the heterozygote advantage hypothesis. The observed decreased virus load in HLA-DRB-1 heterozygotes may be due to a better control of M. tb. infection in the context of HIV-1 disease.
    Human Immunology 11/2002; 63(11):1026-32. · 2.30 Impact Factor
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    ABSTRACT: : 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. (C) 2000 Lippincott Williams & Wilkins, Inc.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2000; 25(5). · 4.65 Impact Factor
  • JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2000; · 4.65 Impact Factor
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    ABSTRACT: 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.
    Tropical Medicine & International Health 02/1997; 2(1):83-8. · 2.94 Impact Factor
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    ABSTRACT: 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. A pilot study of antiretroviral treatment of adults with AIDS. Primary health care clinics; Seke North and St Mary's in Chitungwiza, Zimbabwe. Women with pre-exposure to SD NVP or SC AZT and their spouses with CD4 count < 200 cells/ Generic AZT/3TC twice daily plus NVP daily for the first 14 days and then twice a day thereafter, administered to the cohort. 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%. 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.
    The Central African journal of medicine 52(1-2):1-8.