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Hepatitis B Virus Infection in Human Immunodeficiency Virus Infected Southern African Adults: Occult or Overt – That Is the Question
Trevor G. Bell, Euphodia Makondo, Neil A. Martinson, Anna Kramvis
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045750
Abstract: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share transmission routes and are endemic in sub-Saharan Africa. The objective of the present study was to use the Taormina definition of occult HBV infection, together with stringent amplification conditions, to determine the prevalence and characteristics of HBV infection in antiretroviral treatment (ART)-na?ve HIV+ve adults in a rural cohort in South Africa. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA) tests. HBV DNA-positivity was determined by polymerase chain reaction (PCR) of at least two of three different regions of the HBV genome. HBV viral loads were determined by real-time PCR. Liver fibrosis was determined using the aspartate aminotransferase-to-platelet ratio index. Of the 298 participants, 231 (77.5%) showed at least one HBV marker, with 53.7% HBV DNA?ve (resolved) and 23.8% HBV DNA+ve (current) [8.7% HBsAg+ve: 15.1% HBsAg?ve]. Only the total number of sexual partners distinguished HBV DNA+ve and HBV DNA?ve participants, implicating sexual transmission of HBV and/or HIV. It is plausible that sexual transmission of HBV and/or HIV may result in a new HBV infection, superinfection and re-activation as a consequence of immunesuppression. Three HBsAg?ve HBV DNA+ve participants had HBV viral loads <200 IU/ml and were therefore true occult HBV infections. The majority of HBsAg?ve HBV DNA+ve participants did not differ from HBsAg+ve HBV DNA+ve (overt) participants in terms of HBV viral loads, ALT levels or frequency of liver fibrosis. Close to a quarter of HIV+ve participants were HBV DNA+ve, of which the majority were HBsAg?ve and were only detected using nucleic acid testing. Detection of HBsAg?ve HBV DNA+ve subjects is advisable considering they were clinically indistinguishable from HBsAg+ve HBV DNA+ve individuals and should not be overlooked, especially if lamivudine is included in the ART.
Prevention of mother-to-child Transmission: A report-back from the XV International AIDS Conference, Bangkok, 11 - 16 July 2004
Neil Martinson, Lynn Morris, Glenda Gray, James McIntyre
Southern African Journal of HIV Medicine , 2004,
Abstract: The XV International AIDS Conference was held in Bangkok from 11 to 16 July 2004. The theme of the conference was ‘Access for all\'. It was an enormous gathering; 10 000 abstracts were accepted for presentation, of which approximately 400 were oral. There were 19 500 attendees from all over the globe with a high representation from Asian countries. South Africa was well represented by a large contingent including politicians, researchers, activists and government officials. The abstracts and presentations which may have an impact on policy and research directions have been reviewed and are summarised. Southern African Journal of HIV Medicine Vol. 5 (3) 2004: 17-21
Cotrimoxazole Prophylaxis and Tuberculosis Risk among People Living with HIV
Christopher J. Hoffmann, Richard E. Chaisson, Neil A. Martinson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0083750
Abstract: Objectives Many randomized and cohort studies have reported a survival benefit with cotrimoxazole prophylaxis without detecting a difference in tuberculosis (TB) incidence by cotrimoxazole status. However, several in vitro studies have reported that cotrimoxazole possesses anti-TB activity. We sought to compare TB incidence and TB diagnostic yield by cotrimoxazole use among participants in a well characterized cohort of HIV-infected adults living in a high TB prevalence region. Methods We analyzed prospective data from a long-term longitudinal cohort of adults receiving HIV care and TB investigations in Soweto, South Africa. Using longitudinal analysis, we compared total and laboratory confirmed TB incidence by cotrimoxazole status as well as all-cause mortality. In addition, we compared TB culture results by cotrimoxazole status. Results In a multivariable analysis, adjusted for sex, body mass index, WHO clinical stage, time-updated CD4 count, and antiretroviral therapy status, we observed an association between cotrimoxazole and an increase in TB incidence (hazard ratio 1.7, 95% CI: 1.2, 2.2). However, when restricted to laboratory-confirmed TB, there was no association between cotrimoxazole and TB incidence (hazard ratio: 0.97, 95% CI: 0.39, 2.4). In TB cases, we found no difference in the proportion of positive sputum cultures or days to culture positivity by cotrimoxazole status. Cotrimoxazole was associated with a reduction in mortality. Conclusions In this cohort with a mortality benefit from cotrimoxazole, we found an increased risk of all TB among individuals using cotrimoxazole, likely a result of residual confounding, but no association between use of cotrimoxazole and laboratory-confirmed TB. Cotrimoxazole did not compromise TB diagnosis.
A Review of the Study Designs and Statistical Methods Used in the Determination of Predictors of All-Cause Mortality in HIV-Infected Cohorts: 2002–2011
Kennedy N. Otwombe, Max Petzold, Neil Martinson, Tobias Chirwa
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087356
Abstract: Background Research in the predictors of all-cause mortality in HIV-infected people has widely been reported in literature. Making an informed decision requires understanding the methods used. Objectives We present a review on study designs, statistical methods and their appropriateness in original articles reporting on predictors of all-cause mortality in HIV-infected people between January 2002 and December 2011. Statistical methods were compared between 2002–2006 and 2007–2011. Time-to-event analysis techniques were considered appropriate. Data Sources Pubmed/Medline. Study Eligibility Criteria Original English-language articles were abstracted. Letters to the editor, editorials, reviews, systematic reviews, meta-analysis, case reports and any other ineligible articles were excluded. Results A total of 189 studies were identified (n = 91 in 2002–2006 and n = 98 in 2007–2011) out of which 130 (69%) were prospective and 56 (30%) were retrospective. One hundred and eighty-two (96%) studies described their sample using descriptive statistics while 32 (17%) made comparisons using t-tests. Kaplan-Meier methods for time-to-event analysis were commonly used in the earlier period (n = 69, 76% vs. n = 53, 54%, p = 0.002). Predictors of mortality in the two periods were commonly determined using Cox regression analysis (n = 67, 75% vs. n = 63, 64%, p = 0.12). Only 7 (4%) used advanced survival analysis methods of Cox regression analysis with frailty in which 6 (3%) were used in the later period. Thirty-two (17%) used logistic regression while 8 (4%) used other methods. There were significantly more articles from the first period using appropriate methods compared to the second (n = 80, 88% vs. n = 69, 70%, p-value = 0.003). Conclusion Descriptive statistics and survival analysis techniques remain the most common methods of analysis in publications on predictors of all-cause mortality in HIV-infected cohorts while prospective research designs are favoured. Sophisticated techniques of time-dependent Cox regression and Cox regression with frailty are scarce. This motivates for more training in the use of advanced time-to-event methods.
Linking the global positioning system (GPS) to a personal digital assistant (PDA) to support tuberculosis control in South Africa: a pilot study
Barry Dwolatzky, Estelle Trengove, Helen Struthers, James A McIntyre, Neil A Martinson
International Journal of Health Geographics , 2006, DOI: 10.1186/1476-072x-5-34
Abstract: The study took place in two communities in Greater Johannesburg, South Africa: Wheillers Farm, a relatively sparsely populated informal settlement, and a portion of Alexandra, an urban township with densely populated informal settlements. Ten participants in each community were asked to locate their homes on aerial photographs. Nine from Wheillers Farm and six from Alexandra were able to identify their homes. The total time taken by a research assistant, unfamiliar with the area, to locate 10 homes in each community using the given addresses was compared with the total time taken by a community volunteer with half an hour of training to locate the same homes using the device. Time taken to locate the ten households was reduced by 20% and 50% in each community respectively using the PDA/GPS device.In this pilot study we show that it is feasible to use a simple PDA/GPS device to locate the homes of patients. We found that in densely populated informal settlements, GPS technology is more accurate than aerial photos in identifying homes and more efficient than addresses provided by participants. Research assessing issues of, confidentiality and cost effectiveness would have to be undertaken before implementing PDA/GPS – based technology for this application. However, this PDA/GPS device could be used to reduce part of the burden on TB control programs."Globally there were 4.4 million new cases of tuberculosis in 2003 [1] of which a quarter were in Africa where the HIV epidemic has resulted in rapid increases in TB caseloads. HIV infection is the greatest risk factor for TB disease and current TB control strategies appear insufficient to halt the swift rise in new cases of TB consequent to HIV [2,3]. Curative therapy for TB is complex and lasts for six to eight months. Lack of knowledge of the disease, rapid subjective responses to TB treatment, travel barriers, stigma, adverse effects of medication and poor user experiences with an overburdened TB control programme (TBC
Longitudinal Analysis of QuantiFERON-TB Gold In-Tube in Children with Adult Household Tuberculosis Contact in South Africa: A Prospective Cohort Study
Maunank Shah, Tafadzwa S. Kasambira, Peter V. Adrian, Shabir A. Madhi, Neil A. Martinson, Susan E. Dorman
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026787
Abstract: Background QuantiFERON-TB Gold In Tube (QFT-GIT) is a tool for detecting M. tuberculosis infection. However, interpretation and utility of serial QFT-GIT testing of pediatric tuberculosis (TB) contacts is not well understood. We compared TB prevalence between baseline and 6 months follow-up using QFT-GIT and tuberculin skin testing (TST) in children who were household contacts of adults with pulmonary TB in South Africa, and explored factors associated with QFT-GIT conversions and reversions. Method Prospective study with six month longitudinal follow-up. Results Among 270 enrolled pediatric contacts, 196 (73%) underwent 6-month follow-up testing. The 6-month prevalence estimate of MTB infection in pediatric contacts increased significantly from a baseline of 29% (79/270, 95%CI [24–35]) to 38% (103/270, 95% CI [32–44], p<0.001) using QFT-GIT; prevalence increased from a baseline of 28% (71/254, 95%CI [23–34]) to 33% (88/263, 95%CI [21–32], p = 0.002) using TST. Prevalence estimates were influenced by thresholds for positivity for TST, but not for QFT-GIT. Among 134 children with a negative or indeterminate baseline QFT-GIT, 24 (18%) converted to positive at follow-up; conversion rates did not differ significantly when using more stringent thresholds to define QFT-GIT conversion. Older age >10 years (AOR 8.9 95%CI [1.1–72]) and baseline TST positivity ≥5 mm (AOR 5.2 95%CI [1.2–23]) were associated with QFT-GIT conversion. Among 62 children with a positive baseline QFT-GIT, 9 (15%) reverted to negative; female gender (AOR 18.5 95%CI [1.1–321]; p = 0.04] was associated with reversion, while children with baseline positive TST were less likely to have QFT-GIT reversion (AOR 0.01 95%CI [0.001–0.24]). Conclusion Among pediatric contacts of adult household TB cases in South Africa, prevalence estimates of TB infection increased significantly from baseline to 6 months. Conversions and reversions occurred among pediatric TB contacts using QFT-GIT, but QFT-GIT conversion rates were less influenced by thresholds used for conversions than were TST conversion rates.
Predictors of persistent cytologic abnormalities after treatment of cervical intraepithelial neoplasia in Soweto, South Africa: a cohort study in a HIV high prevalence population
Yasmin Adam, Cyril J van Gelderen, Guy de Bruyn, James A McIntyre, Diane A Turton, Neil A Martinson
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-211
Abstract: Women with high grade squamous intraepithelial lesions or worse (HSIL), less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap) smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regressionThe median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear.We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer.Cervical cancer is the second leading cancer in women after breast malignancy in South Africa (SA)[1]. The life-time risk of developing invasive cervical cancer (ICC) is 1 in 31 for South African women. The crude rates for ICC were 26.1 per 100 000 in 1999, with a corresponding age-standardized incidence rate of 28.7 per 100 000 and the risk increased with age, peaking at 136.4 per 100 000 in women between the ages of 65 and 69[2]. W
Circumcision for prevention against HIV: marked seasonal variation in demand and potential public sector readiness in Soweto, South Africa
Guy de Bruyn, Martin D Smith, Glenda E Gray, James A McIntyre, Russell Wesson, Gary Passos, Neil A Martinson
Implementation Science , 2007, DOI: 10.1186/1748-5908-2-2
Abstract: A recently completed randomized controlled trial of male circumcision (MC) for the prevention of HIV acquisition demonstrated that MC reduces the risk of HIV infection [1], confirming similar findings from many prior observational studies [2]. At the efficacy and cost of the procedure reported in the trial, MC may be cost-saving as a public health intervention [3]. These findings add to the options for personal prevention of HIV acquisition, and support the addition of MC as a component of prevention programs in countries with a high prevalence of HIV. In the absence of UNAIDS endorsement to back policy and program development [4], implementation issues need to be debated.However, to have an impact, a large proportion of the male population would have to be circumcised. Indeed, this conclusion is supported by epidemic modeling for the population of Soweto [5], and at a country level in South Africa [6]. The current live male birth cohort in Soweto numbers approximately 15,000 per year (J. McIntyre, personal communication). The prevalence of MC is estimated to be between 20% and 35%, based on surveys in communities within 100 km of Soweto [7,8]. Population coverage of 60% of males within a birth cohort, without expanding to other uncircumcised men, would require at least 8,000 procedures per year. Additionally, MC appears to be acceptable to the majority of uncircumcised men in this area, if found to be beneficial in the prevention of HIV/STI's [7,8]. Partner preferences are commonly cited as a reason for adult men undergoing the procedure, because women find it acceptable as well.Furthermore, South African investigators will soon initiate clinical research studies in HIV prevention, such as large HIV vaccine efficacy studies involving several thousand male participants. One of these trial sites is in Soweto. The ethical justification for the adoption of such measures as part of the standard of prevention for trial participants is still being debated, but clinical tr
High Prevalence of Pulmonary Tuberculosis but Low Sensitivity of Symptom Screening among HIV-Infected Pregnant Women in South Africa
Christopher J. Hoffmann, Ebrahim Variava, Modiehi Rakgokong, Katlego Masonoke, Martin van der Watt, Richard E. Chaisson, Neil A. Martinson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062211
Abstract: Symptom screening is a recommended component of intensified case-finding (ICF) for pulmonary tuberculosis (TB) among HIV-infected individuals. Symptomatic individuals are further investigated to either exclude or diagnose pulmonary TB, thus reducing the number of individuals requiring costly laboratory investigation. Those with laboratory evaluations negative for pulmonary TB or who lack symptoms may be eligible for antiretroviral therapy (ART) and/or TB isoniazid preventive therapy (IPT). A four-part symptom screen has been recommended by the World Health Organization (WHO) for identifying TB suspects and those unlikely to have TB. A meta-analysis of studies among HIV-infected individuals calculated a sensitivity of 90.1% for the four-part symptoms screen - of any of cough, fever, night sweats, or weight loss - among patients in clinical care, making it an effective tool for identifying most patients with TB. An important population for intensified case-finding not included in that meta-analysis was HIV-infected pregnant women. We undertook a cross-sectional survey among HIV-infected pregnant women receiving prenatal care at community clinics in South Africa. We obtained a four-symptom review and sputum smear microscopy and mycobacterial culture on all participants. Among 1415 women, 226 (16%) had a positive symptom screen, and 35 (2.5%) were newly diagnosed with culture-positive TB. Twelve were on TB treatment at the time of screening, yielding 47 (3.3%) women with prevalent TB. Symptom screening among women without known TB had a sensitivity of 28% and specificity of 84%. The poor performance of symptom screening to identify women with TB suggests that other approaches may be needed for intensified case-finding to be effective for this population.
Incidence of TB and HIV in Prospectively Followed Household Contacts of TB Index Patients in South Africa
Cari van Schalkwyk, Ebrahim Variava, Adrienne E. Shapiro, Modiehi Rakgokong, Katlego Masonoke, Limakatso Lebina, Alex Welte, Neil Martinson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095372
Abstract: Objective To report the incidence rates of TB and HIV in household contacts of index patients diagnosed with TB. Design A prospective cohort study in the Matlosana sub-district of North West Province, South Africa. Methods Contacts of index TB patients received TB and HIV testing after counseling at their first household visit and were then followed up a year later, in 2010. TB or HIV diagnoses that occurred during the period were determined. Results For 2,377 household contacts, the overall observed TB incidence rate was 1.3 per 100 person years (95% CI 0.9–1.9/100py) and TB incidence for individuals who were HIV-infected and HIV seronegative at baseline was 5.4/100py (95% CI 2.9–9.0/100py) and 0.7/100py (95% CI 0.3–1.4/100py), respectively. The overall HIV incidence rate was 2.2/100py (95% CI 1.3–8.4/100py). Conclusions In the year following a household case finding visit when household contacts were tested for TB and HIV, the incidence rate of both active TB and HIV infection was found to be extremely high. Clearly, implementing proven strategies to prevent HIV acquisition and preventing TB transmission and progression to disease remains a priority in settings such as South Africa.
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