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Browsing by Author "Reid SE"

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    A model of tuberculosis screening for pregnant women in resource-limited settings using Xpert MTB/RIF.
    (2012) Turnbull ER; Kancheya NG; Harris JB; Topp SM; Henostroza G; Reid SE; Tuberculosis Department, Centre for Infectious Disease Research in Zambia, 5977 Benakale Road, P.O. Box 34681, Northmead, Lusaka, Zambia; Schools of Medicine and Public Health, University of Alabama at Birmingham, AL 35233, USA. eleanor.turnbull@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Timely diagnosis and treatment of maternal tuberculosis (TB) is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO) recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay for Mycobacterium tuberculosis that simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.
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    Accuracy of giant African pouched rats for diagnosing tuberculosis: comparison with culture and Xpert
    (2017-Nov-01) Mulder C; Mgode GF; Ellis H; Valverde E; Beyene N; Cox C; Reid SE; Van't Hoog AH; Edwards TL; Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling, Sokoine University of Agriculture, Morogoro, Tanzania, Department of Global Health, Academic Medical Centre, Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, The Netherlands.; Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling, Sokoine University of Agriculture, Morogoro, Tanzania, Vanderbilt University Medical School, Nashville, Tennessee.; Department of Global Health, Academic Medical Centre, Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, The Netherlands.; Waikato University, Hamilton, New Zealand.; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA, Tuberculosis Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling, Sokoine University of Agriculture, Morogoro, Tanzania.; Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling, Sokoine University of Agriculture, Morogoro, Tanzania, Waikato University, Hamilton, New Zealand.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    SETTING: Enhanced tuberculosis (TB) case finding using detection rats in Tanzania. OBJECTIVES: To assess the diagnostic accuracy of detection rats compared with culture and Xpert® MTB/RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients. DESIGN: A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert. RESULTS: Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI 76.0-86.5) when compared with Xpert, which was statistically significantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light-emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone. CONCLUSION: Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear-negative TB patients if more advanced diagnostics are not available.
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    An evaluation of the performance and acceptability of three LED fluorescent microscopes in Zambia: lessons learnt for scale-up.
    (2011) Turnbull ER; Kaunda K; Harris JB; Kapata N; Muvwimi MW; Kruuner A; Henostroza G; Reid SE; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. eleanor.turnbull@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    The World Health Organization recommends the roll-out of light-emitting diode (LED) fluorescent microscopes (FM) as an alternative to light microscopes in resource-limited settings. We evaluated the acceptability and performance of three LED FMs after a short orientation among laboratory technicians from government health centers in Zambia. Sixteen technicians with varied light microscopy experience were oriented to FMs and divided into groups; each group read a different set of 40 slides on each LED FM (Primo Star iLED™, Lumin™, FluoLED™) and on a reference mercury-vapor FM (Olympus BX41TF). Slide reading times were recorded. An experienced FM technician examined each slide on the Olympus BX41TF. Sensitivity and specificity compared to TB culture were calculated. Misclassification compared to the experienced technician and inter-rater reliability between trainees was assessed. Trainees rated microscopes on technical aspects. Primo Star iLED™, FluoLED™ and Olympus BX41TF had comparable sensitivities (67%, 65% and 65% respectively), with the Lumin™ significantly worse (56%; p<0.05). Specificity was low for trainees on all microscopes (75.9%) compared to the experienced technician on Olympus BX41TF (100%). Primo Star iLED™ had significantly less misclassification (21.1% p<0.05) than FluoLED™ (26.5%) and Lumin™ (26.8%) and significantly higher inter-rater reliability (0.611; p<0.05), compared to FluoLED™ (0.523) and Lumin™ (0.492). Slide reading times for LED FMs were slower than the reference, but not significantly different from each other. Primo Star iLED™ rated highest in acceptability measures, followed by FluoLED™ then Lumin™. Primo Star iLED™ was consistently better than FluoLED™ and Lumin™, and performed comparably to the Olympus BX41TF in all analyses, except reading times. The Lumin™ compared least favorably and was thought unacceptable for use. Specificity and inter-rater reliability were low for all microscopes suggesting that a brief orientation was insufficient in this setting. These results provide important data for resource-limited settings to consider as they scale-up LED FMs.
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    Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy.
    (2004-Nov) Reid SE; Reid CA; Vermund SH; Centre for Infectious Disease Research in Zambia, PO Box 34681, Plot 5977 Benakale Road, Northmead, Lusaka, Zambia. stewart@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Declining drug costs and increases in international donor interest are leading to greater availability of antiretroviral treatment programmes for persons living with the human immunodeficiency virus in parts of sub-Saharan Africa. Ensuring adequate adherence to antiretroviral drug therapy is one of the principal challenges facing successful implementation in Africa, where 70% of the world's infected persons live. Tuberculosis and leprosy are two diseases of global importance whose control programmes can provide important lessons for developing antiretroviral drug adherence strategies. This paper examines various approaches used in tuberculosis and leprosy control which could help enhance adherence to antiretroviral therapy in resource-limited settings.
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    Burnout and use of HIV services among health care workers in Lusaka District, Zambia: a cross-sectional study.
    (2009-Jul-13) Kruse GR; Chapula BT; Ikeda S; Nkhoma M; Quiterio N; Pankratz D; Mataka K; Chi BH; Bond V; Reid SE; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia. gkruse@partners.org
    BACKGROUND: Well-documented shortages of health care workers in sub-Saharan Africa are exacerbated by the increased human resource demands of rapidly expanding HIV care and treatment programmes. The successful continuation of existing programmes is threatened by health care worker burnout and HIV-related illness. METHODS: From March to June 2007, we studied occupational burnout and utilization of HIV services among health providers in the Lusaka public health sector. Providers from 13 public clinics were given a 36-item, self-administered questionnaire and invited for focus group discussions and key-informant interviews. RESULTS: Some 483 active clinical staff completed the questionnaire (84% response rate), 50 staff participated in six focus groups, and four individuals gave interviews. Focus group participants described burnout as feeling overworked, stressed and tired. In the survey, 51% reported occupational burnout. Risk factors were having another job (RR 1.4 95% CI 1.2-1.6) and knowing a co-worker who left in the last year (RR 1.6 95% CI 1.3-2.2). Reasons for co-worker attrition included: better pay (40%), feeling overworked or stressed (21%), moving away (16%), death (8%) and illness (5%). When asked about HIV testing, 370 of 456 (81%) reported having tested; 240 (50%) tested in the last year. In contrast, discussion groups perceived low testing rates. Both discussion groups and survey respondents identified confidentiality as the prime reason for not undergoing HIV testing. CONCLUSION: In Lusaka primary care clinics, overwork, illness and death were common reasons for attrition. Programmes to improve access, acceptability and confidentiality of health care services for clinical providers and to reduce workplace stress could substantially affect workforce stability.
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    CD4+ response and subsequent risk of death among patients on antiretroviral therapy in Lusaka, Zambia.
    (2009-Sep-01) Chi BH; Giganti M; Mulenga PL; Limbada M; Reid SE; Mutale W; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    INTRODUCTION: Where virologic monitoring is not routinely available, immunologic criteria are commonly used to determine treatment failure while on antiretroviral therapy (ART). However, few have studied CD4+ response and its relationship to subsequent clinical outcomes in a programmatic setting. METHODS: We analyzed cohort data from Zambia to investigate whether 6- and 12-month CD4+ response after ART initiation was associated with later mortality. We used Cox proportional hazards models that accounted for different strata of baseline CD4 counts and adjusted for age, sex, clinical stage, tuberculosis coinfection, baseline hemoglobin, initial ART regimen, and adherence behavior. RESULTS: We analyzed data from 2 cohorts, from 6 months onward (n = 24,366; median follow-up = 467 days, interquartile range 222-791) and from 12 months onward (n = 17,920; median follow-up = 423 days, interquartile range 191-689). In the post-6-month analysis, hazard for death was significantly higher when absolute CD4+ response was <100 cells per microliter [adjusted hazard ratio (AHR) = 2.25, 95% confidence interval (CI): 1.91 to 2.64], relative response was <10% above baseline (AHR = 2.60, 95% CI: 2.12 to 3.19), and absolute CD4+ count was <100 per microliter (AHR = 2.79, 95% CI: 2.26 to 3.45). In the post-12 month analysis, mortality was associated with rise in absolute CD4+ cell count <200 per microliter (AHR = 2.41, 95% CI: 1.83 to 3.17), relative rise in CD4+ cell count of <10% above baseline (AHR = 3.41, 95% CI: 2.51 to 4.64), and absolute CD4+ count at 12 months <100 per microliter (AHR = 4.11, 95% CI: 2.96 to 5.68). CONCLUSION: Commonly used definitions for immunologic treatment failure are associated with elevated mortality risk among patients on ART.
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    Chest radiograph reading and recording system: evaluation in frontline clinicians in Zambia.
    (2016-Mar-23) Henostroza G; Harris JB; Kancheya N; Nhandu V; Besa S; Musopole R; Krüüner A; Chileshe C; Dunn IJ; Reid SE; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. germanh@uab.edu.; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, USA.; Prisons Health Services, Ministry of Home Affairs, Lusaka, Zambia.; Department of Medicine, Institute of Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Radiology, University of British Columbia, Vancouver, Canada.; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, USA. germanh@uab.edu.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: In Zambia the vast majority of chest radiographs (CXR) are read by clinical officers who have limited training and varied interpretation experience, meaning lower inter-rater reliability and limiting the usefulness of CXR as a diagnostic tool. In 2010-11, the Zambian Prison Service and Ministry of Health established TB and HIV screening programs in six prisons; screening included digital radiography for all participants. Using front-line clinicians we evaluated sensitivity, specificity and inter-rater agreement for digital CXR interpretation using the Chest Radiograph Reading and Recording System (CRRS). METHODS: Digital radiographs were selected from HIV-infected and uninfected inmates who participated in a TB and HIV screening program at two Zambian prisons. Two medical officers (MOs) and two clinical officers (COs) independently interpreted all CXRs. We calculated sensitivity and specificity of CXR interpretations compared to culture as the gold standard and evaluated inter-rater reliability using percent agreement and kappa coefficients. RESULTS: 571 CXRs were included in analyses. Sensitivity of the interpretation "any abnormality" ranged from 50-70 % depending on the reader and the patients' HIV status. In general, MO's had higher specificities than COs. Kappa coefficients for the ratings of "abnormalities consistent with TB" and "any abnormality" showed good agreement between MOs on HIV-uninfected CXRs and moderate agreement on HIV-infected CXRs whereas the COs demonstrated fair agreement in both categories, regardless of HIV status. CONCLUSIONS: Sensitivity, specificity and inter-rater agreement varied substantially between readers with different experience and training, however the medical officers who underwent formal CRRS training had more consistent interpretations.
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    Coordinating the prevention, treatment, and care continuum for HIV-associated tuberculosis in prisons: a health systems strengthening approach.
    (2018-Nov) Herce ME; Muyoyeta M; Topp SM; Henostroza G; Reid SE; Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia.; Division of Infectious Diseases, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
    PURPOSE OF REVIEW: To advance a re-conceptualized prevention, treatment, and care continuum (PTCC) for HIV-associated tuberculosis (TB) in prisons, and to make recommendations for strengthening prison health systems and reducing HIV-associated TB morbidity and mortality throughout the cycle of pretrial detention, incarceration, and release. RECENT FINDINGS: Despite evidence of increased HIV-associated TB burden in prisons compared to the general population, prisoners face entrenched barriers to accessing anti-TB therapy, antiretroviral therapy, and evidence-based HIV and TB prevention. New approaches, suitable for the complexities of healthcare delivery in prisons, have emerged that may address these barriers, and include: novel TB diagnostics, universal test and treat for HIV, medication-assisted treatment for opioid dependence, comprehensive transitional case management, and peer navigation, among others. SUMMARY: Realizing ambitious international HIV and TB targets in prisons will only be possible by first addressing the root causes of the TB/HIV syndemic, which are deeply intertwined with human rights violations and weaknesses in prison health systems, and, second, fundamentally re-organizing HIV and TB services around a coordinated PTCC. Taking these steps can help ensure universal access to comprehensive, good-quality, free and voluntary TB/HIV prevention, treatment, and care, and advance efforts to strengthen health resourcing, staffing, information management, and primary care access within prisons.
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    Derivation of a tuberculosis screening rule for sub-Saharan African prisons.
    (2014-Jul) Harris JB; Siyambango M; Levitan EB; Maggard KR; Hatwiinda S; Foster EM; Chamot E; Kaunda K; Chileshe C; Krüüner A; Henostroza G; Reid SE; Zambia Prisons Service, Ministry of Home Affairs, Lusaka, Zambia.; Department of Health Care Organization and Policy, University of Alabama at Birmingham, Alabama, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Epidemiology, Birmingham, Alabama, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    SETTING: Lusaka Central Prison, Zambia. OBJECTIVE: To derive screening rules for tuberculosis (TB) using data collected during a prison-wide TB and human immunodeficiency virus (HIV) screening program. DESIGN: We derived rules with two methodologies: logistic regression and classification and regression trees (C&RT). We evaluated the performance of the derived rules as well as existing World Health Organization (WHO) screening recommendations in our cohort of inmates, as measured by sensitivity, specificity, and positive and negative predictive values. RESULTS: The C&RT-derived rule recommended diagnostic testing of all inmates who were underweight (defined as body mass index [BMI] < 18.5 kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71% specificity. The logistic regression-derived rule recommended diagnostic testing of inmates who were underweight, HIV-infected or had chest pain; the logistic regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO recommendations had sensitivities that were similar to our logistic regression rule but had poorer specificities, resulting in a greater testing burden. CONCLUSION: Low BMI and HIV infection were the most robust predictors of TB in our inmates; chest pain was additionally retained in one model. BMI and HIV should be further evaluated as the basis for TB screening rules for inmates, with modification as needed to improve the performance of the rules.
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    Does provider-initiated counselling and testing (PITC) strengthen early diagnosis and treatment initiation? Results from an analysis of an urban cohort of HIV-positive patients in Lusaka, Zambia.
    (2012-Sep-24) Topp SM; Li MS; Chipukuma JM; Chiko MM; Matongo E; Bolton-Moore C; Reid SE; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. globalstopp@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    INTRODUCTION: Building on earlier works demonstrating the effectiveness and acceptability of provider-initiated counselling and testing (PITC) services in integrated outpatient departments of urban primary healthcare clinics (PHCs), this study seeks to understand the relative utility of PITC services for identifying clients with early-stage HIV-related disease compared to traditional voluntary testing and counselling (VCT) services. We additionally seek to determine whether there are any significant differences in the clinical and demographic profile of PITC and VCT clients. METHODS: Routinely collected, de-identified data were collated from two cohorts of HIV-positive patients referred for HIV treatment, either from PITC or VCT in seven urban-integrated PHCs. Univariate and multivariate analyses were conducted to compare the two cohorts across demographic and clinical characteristics at enrolment. RESULTS: Forty-five per cent of clients diagnosed via PITC had CD4 < 200, and more than 70% (i.e. two thirds) had CD4 < 350 at enrollment, with significantly lower CD4 counts than that of VCT clients (p < 0.001). PITC clients were more likely to be male (p = 0.0005) and less likely to have secondary or tertiary education (p < 0.0001). Among those who were initiated on antiretroviral therapy (ART), PITC clients had lower odds of initiating treatment within four weeks of enrollment into HIV care (adjusted odds ratio, or AOR: 0.86; 95% confidence interval, or CI: 0.75-0.99; p = 0.035) and significantly lower odds of retention in care at six months (AOR: 0.84; CI: 0.77-0.99; p = 0.004). CONCLUSIONS: In Lusaka, Zambia, large numbers of individuals with late-stage HIV are being incidentally diagnosed in outpatient settings. Our findings suggest that PITC in this setting does not facilitate more timely diagnosis and referral to care but rather act as a "safety net" for individuals who are unwilling or unable to seek testing independently. Further work is needed to document the way provision of clinic-based services can be strengthened and linked to community-based interventions and to address socio-cultural norms and socio-economic status that underpin healthcare-seeking behaviour.
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    Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.
    (2010-May-01) Chi BH; Mwango A; Giganti M; Mulenga LB; Tambatamba-Chapula B; Reid SE; Bolton-Moore C; Chintu N; Mulenga PL; Stringer EM; Sheneberger R; Mwaba P; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale. METHODS: We compared drug substitutions, mortality, and "programmatic failure" among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up. RESULTS: Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF. CONCLUSIONS: TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambia's policy decision.
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    Early lessons from the integration of tuberculosis and HIV services in primary care centers in Lusaka, Zambia.
    (2008-Jul) Harris JB; Hatwiinda SM; Randels KM; Chi BH; Kancheya NG; Jham MA; Samungole KV; Tambatamba BC; Cantrell RA; Levy JW; Kimerling ME; Reid SE; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Jennie.Harris@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Zambia faces overlapping tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics; however, care for co-infected patients often occurs through separate, vertical programs. OBJECTIVE: To establish a program to integrate TB and HIV services in Lusaka primary care centers. METHODS: In collaboration with the Zambian Ministry of Health, TB-HIV integration activities began in December 2005 and were expanded to seven health centers by March 2007. Principal activities included developing staff capacity to manage co-infected patients, implementing HIV testing within TB departments and establishing referral systems between departments. RESULTS: Using a provider-initiated approach, 2053 TB patients were offered HIV testing. Seventy-seven per cent agreed to be tested; 69% of those tested were HIV-infected. Of these, 59% were enrolled in HIV care. The proportion of antiretroviral treatment (ART) program enrollees who were TB-HIV co-infected increased by 38% after program implementation. The median CD4 count among co-infected patients was 161 cells/microl, with 88% eligible for ART. CONCLUSION: Integration of HIV testing and referral services into urban primary care centers identified many co-infected patients and significantly increased the proportion of TB patients among people accessing HIV care. Ongoing challenges include maximizing the number of patients accepting HIV testing and overcoming barriers to enrollment into HIV care.
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    Effectiveness of generic and proprietary first-line anti-retroviral regimens in a primary health care setting in Lusaka, Zambia: a cohort study.
    (2012-Apr) Stringer JS; Mwango AJ; Giganti MJ; Mulenga L; Levy JW; Stringer EM; Mulenga P; Saag MS; Musonda P; Williams FB; Reid SE; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. stringer@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Although generic anti-retroviral drugs are in common use throughout the developing world, studies comparing their clinical effectiveness with that of proprietary formulations are lacking. METHODS: We analysed observational data from a large cohort of adults on anti-retroviral therapy (ART) to assess potential differences between generic and proprietary zidovudine (ZDV) formulations in post-90-day mortality, 'programme failure' (a composite of death, follow-up losses and withdrawals) and other clinical outcomes. We accounted for drug exposure in three ways: an 'initial dispensation' approach that categorized patients according to the first prescription; 'time-varying' approach that attributed an outcome to the formulation taken at the time of event; and 'predominant exposure' approach that considered only those with >75% exposure to either brand or generic ZDV. Proprietary formulations were used as the reference group in all adjusted Cox proportional hazard regressions. RESULTS: Among 14 736 patients eligible for analysis, 7277 (49%) initiated a generic formulation of ZDV and 7459 (51%) initiated a proprietary formulation. When categorized according to initial dispensation, no difference in post-90-day mortality was observed between the two groups [adjusted hazard ratio (AHR): 0.93, 95% confidence interval (CI): 0.77-1.12]. Similar findings were noted when drug formulation was treated as a time-varying exposure (AHR: 1.15, 95% CI: 0.89-1.48) when analysis was limited to those with a predominant exposure to one formulation or the other (AHR: 0.59, 95% CI: 0.24-1.49). Results were consistent across all approaches when programme failure was considered as an outcome. No longitudinal differences were detected between formulations for CD4 response, weight change and haemoglobin concentration. Generic ZDV formulations were associated with slight decreases in single-drug substitution. CONCLUSIONS: In this large programmatic cohort of adults starting ZDV-based first-line therapy, clinical outcomes appeared similar among patients on generic or proprietary formulations. These findings support continued use of generic anti-retroviral drug formulations in resource-constrained settings.
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    Evaluation of a Task-Shifting Strategy Involving Peer Educators in HIV Care and Treatment Clinics in Lusaka, Zambia.
    (2012-Mar-07) Born LJ; Wamulume C; Neroda KA; Quiterio N; Giganti MJ; Morris M; Bolton-Moore C; Baird S; Sinkamba M; Topp SM; Reid SE; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; University of Alabama at Birmingham, Alabama, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA.; Centre for Infectious Disease Research in Zambia , Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; University of Washington, Seattle, Washington, USA.; Harvard Medical School , Boston, Massachusetts, USA.; Lusaka District Health Management Team , Lusaka, Zambia.; Emory University School of Medicine , Atlanta, Georgia, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    Rapid expansion of antiretroviral therapy (ART) and a shortage of health care workers (HCWs) required the implementation of a peer educator (PE) model as part of a task-shifting strategy in Lusaka District clinics. The purpose of this study was to evaluate patient and staff perceptions regarding whether the PE program: a) relieved the workload on professional HCWs; and b) delivered services of acceptable quality. Qualitative and quantitative data were gathered from five primary care clinics delivering ART in Lusaka, Zambia. Closed surveys were conducted with 148 patients receiving ART, 29 PEs, and 53 HCWs. Data was imported into Microsoft Excel to calculate descriptive statistics. Six focus group discussions and eight key informant (KI) interviews were conducted, recorded, transcribed, and coded to extract relevant data. Survey results demonstrated that 50 of 53 (96.1%) HCWs agreed PEs reduced the amount of counseling duties required of HCWs. HCWs felt that PEs performed as well as HCWs in counseling patients (48 of 53; 90.6%) and that having PEs conduct counseling enabled clinical staff to see more patients (44 of 53; 83%). A majority of patients (141 of 148; 95.2%) agreed or strongly agreed that PEs were knowledgeable about ART, and 89 of 144 (61.8%) expressed a high level of confidence with PEs performing counseling and related tasks. Focus group and KI interviews supported these findings. PEs helped ease the work burden of HCWs and provided effective counseling, education talks, and adherence support to patients in HIV care. Consideration should be given to formalizing their role in the public health sector.
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    High prevalence of tuberculosis in newly enrolled HIV patients in Zambia: need for enhanced screening approach.
    (2016-Aug) Henostroza G; Harris JB; Chitambi R; Siyambango M; Turnbull ER; Maggard KR; Krüüner A; Kapata N; Reid SE; Tuberculosis Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Tuberculosis Department, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; National Tuberculosis and Leprosy Control Programme, Ministry of Health of Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    SETTING: Tuberculosis (TB) remains a leading cause of morbidity and mortality in sub-Saharan Africa. In Zambia, smear microscopy and chest radiography (CXR) are the primary TB diagnostic tools, and most cases are not bacteriologically confirmed. OBJECTIVE: We implemented enhanced screening to determine the TB burden among new human immunodeficiency virus (HIV) clinic enrollees. DESIGN: Consecutive adult HIV clinic enrollees were screened, regardless of symptoms. All underwent microscopy (Ziehl-Neelsen/fluorescence microscopy) on three sputum specimens, physical examination, and digital CXR. Sputum, blood and urine specimens were cultured. Xpert(®) MTB/RIF testing was performed retrospectively. RESULTS: From July 2011 to April 2012, 399 patients were enrolled. The median age was 34.4 years; body mass index was 20.8 kg/m(2), CD4 count was 202 cells/μl and 86% were symptomatic. Culture-confirmed TB was diagnosed in 72/399 (18%) patients; an additional 31/399 (8%) were culture-negative but diagnosed clinically. Symptom screening for any cough, fever, weight loss or night sweats had high sensitivity (95%) but low specificity (14%) for detecting culture-confirmed cases. Among culture-confirmed cases, 35/72 (49%) were missed clinically and detected only by culture. Xpert was 64% sensitive and 98% specific. CONCLUSIONS: High TB prevalence was found in Zambians newly enrolled into HIV care. Screening with sensitive diagnostics should be considered with culture when feasible in this population.
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    Integrating active tuberculosis case finding in antenatal services in Zambia.
    (2014-Dec) Kancheya N; Luhanga D; Harris JB; Morse J; Kapata N; Bweupe M; Henostroza G; Reid SE; National TB Program, Ministry of Community Development Mother to Child Health, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Ministry of Health, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    SETTING: Three out-patient antenatal care (ANC) clinics in Lusaka, Zambia. OBJECTIVE: To estimate tuberculosis (TB) prevalence in human immunodeficiency virus (HIV) infected and symptomatic, non-HIV-infected pregnant women and explore the feasibility of routine TB screening in ANC settings. DESIGN: Peer educators administered TB symptom questionnaires to pregnant women attending their first ANC clinic visit. Presumptive TB patients were defined as all HIV-infected women and symptomatic non-HIV-infected women. Sputum samples were tested using smear microscopy and culture to estimate TB prevalence. RESULTS: All 5033 (100%) women invited to participate in the study agreed, and 17% reported one or more TB symptoms. Among 1152 presumed TB patients, 17 (1.5%) had previously undiagnosed culture-confirmed TB; 2 (12%) were smear-positive. Stratified by HIV status, TB prevalence was 10/664 (1.5%, 95%CI 0. 7-2.8) among HIV-infected women and 7/488 (1.4%, 95%CI 0.6-2.9) among symptomatic non-HIV-infected women. In HIV-infected women, the only symptom significantly associated with TB was productive cough; symptom screening was only 50% sensitive. CONCLUSION: There is a sizable burden of TB in pregnant women in Zambia, which may lead to adverse maternal and infant outcomes. TB screening in ANC settings in Zambia is acceptable and feasible. More sensitive diagnostics are needed.
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    Integrating HIV care and treatment into tuberculosis clinics in Lusaka, Zambia: results from a before-after quasi-experimental study.
    (2018-Oct-26) Herce ME; Morse J; Luhanga D; Harris J; Smith HJ; Besa S; Samungole G; Kancheya N; Muyoyeta M; Reid SE; Lusaka District Health Office, Ministry of Health, Government of the Republic of Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. michael.herce@cidrz.org.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia. michael.herce@cidrz.org.
    BACKGROUND: Patients with HIV-associated tuberculosis (TB) often have their TB and HIV managed in separate vertical programs that offer care for each disease with little coordination. Such "siloed" approaches are associated with diagnostic and treatment delays, which contribute to unnecessary morbidity and mortality. To improve TB/HIV care coordination and early ART initiation, we integrated HIV care and treatment into two busy TB clinics in Zambia. We report here the effects of our intervention on outcomes of linkage to HIV care, early ART uptake, and TB treatment success for patients with HIV-associated TB in Lusaka, Zambia. METHODS: We provided integrated HIV treatment and care using a "one-stop shop" model intervention. All new or relapse HIV-positive TB patients were offered immediate HIV program enrolment and ART within 8 weeks of anti-TB therapy (ATT) initiation. We used a quasi-experimental design, review of routine program data, and survival analysis and logistic regression methods to estimate study outcomes before (June 1, 2010-January 31, 2011) and after (August 1, 2011-March 31, 2012) our intervention among 473 patients with HIV-associated TB categorized into pre- (n = 248) and post-intervention (n = 225) cohorts. RESULTS: Patients in the pre- and post-intervention cohorts were mostly male (60.1% and 52.9%, respectively) and young (median age: 33 years). In time-to-event analyses, a significantly higher proportion of patients in the post-intervention cohort linked to HIV care by 4 weeks post-ATT initiation (53.9% vs. 43.4%, p = 0.03), with median time to care linkage being 59 and 25 days in the pre- and post-intervention cohorts, respectively. In Cox proportional hazard modelling, patients receiving the integration intervention started ART by 8 weeks post-ATT at 1.33 times the rate (HR = 1.33, 95% CI: 1.00-1.77) as patients pre-intervention. In logistic regression modelling, patients receiving the intervention were 2.02 times (95% CI: 1.11-3.67) as likely to have a successful TB treatment outcome as patients not receiving the intervention. CONCLUSIONS: Integrating HIV treatment and care services into routine TB clinics using a one-stop shop model increased linkage to HIV care, rates of early ART initiation, and TB treatment success among patients with HIV-associated TB in Lusaka, Zambia.
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    Integrating HIV treatment with primary care outpatient services: opportunities and challenges from a scaled-up model in Zambia.
    (2013-Jul) Topp SM; Chipukuma JM; Chiko MM; Matongo E; Bolton-Moore C; Reid SE; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. globalstopp@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: Integration of HIV treatment with other primary care services has been argued to potentially improve effectiveness, efficiency and equity. However, outside the field of reproductive health, there is limited empirical evidence regarding the scope or depth of integrated HIV programmes or their relative benefits. Moreover, the body of work describing operational models of integrated service-delivery in context remains thin. Between 2008 and 2011, the Lusaka District Health Management Team piloted and scaled-up a model of integrated HIV and general outpatient department (OPD) services in 12 primary health care clinics. This paper examines the effect of the integrated model on the organization of clinic services, and explores service providers' perceptions of the integrated model. METHODS: We used a mixed methods approach incorporating facility surveys and key informant interviews with clinic managers and district officials. On-site facility surveys were carried out in 12 integrated facilities to collect data on the scope of integrated services, and 15 semi-structured interviews were carried out with 12 clinic managers and three district officials to explore strengths and weaknesses of the model. Quantitative and qualitative data were triangulated to inform overall analysis. FINDINGS: Implementation of the integrated model substantially changed the organization of service delivery across a range of clinic systems. Organizational and managerial advantages were identified, including more efficient use of staff time and clinic space, improved teamwork and accountability, and more equitable delivery of care to HIV and non-HIV patients. However, integration did not solve ongoing human resource shortages or inadequate infrastructure, which limited the efficacy of the model and were perceived to undermine service delivery. CONCLUSION: While resource and allocative efficiencies are associated with this model of integration, a more important finding was the model's demonstrated potential for strengthening organizational culture and staff relationships, in turn facilitating more collaborative and motivated service delivery in chronically under-resourced primary healthcare clinics.
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    "It's Not Like Taking Chocolates": Factors Influencing the Feasibility and Sustainability of Universal Test and Treat in Correctional Health Systems in Zambia and South Africa.
    (2019-Jun) Topp SM; Chetty-Makkan CM; Smith HJ; Chimoyi L; Hoffmann CJ; Fielding K; Reid SE; Olivier AJ; Hausler H; Herce ME; Charalambous S; Johns Hopkins University, Baltimore, MD, USA.; TB/HIV Care Association, Cape Town, South Africa.; London School of Hygiene & Tropical Medicine, London, UK.; College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia. globalstopp@gmail.com.; Institute for Global Health & Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, USA.; The Aurum Institute, Johannesburg, South Africa.; Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, School of Medicine, Birmingham, AL, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; School of Public Health, University of Witwatersrand, Johannesburg, South Africa.
    BACKGROUND: Sub-Saharan African correctional facilities concentrate large numbers of people who are living with HIV or at risk for HIV infection. Universal test and treat (UTT) is widely recognized as a promising approach to improve the health of individuals and a population health strategy to reduce new HIV infections. In this study, we explored the feasibility and sustainability of implementing UTT in correctional facilities in Zambia and South Africa. METHODS: Nested within a UTT implementation research study, our qualitative evaluation of feasibility and sustainability used a case-comparison design based on data from 1 Zambian and 3 South African correctional facilities. Primary data from in-depth interviews with incarcerated individuals, correctional managers, health care providers, and policy makers were supplemented by public policy documents, study documentation, and implementation memos in both countries. Thematic analysis was informed by an empirically established conceptual framework for health system analysis. RESULTS: Despite different institutional profiles, we were able to successfully introduce UTT in the South Africa and Zambian correctional facilities participating in the study. A supportive policy backdrop was important to UTT implementation and establishment in both countries. However, sustainability of UTT, defined as relevant government departments' capacity to independently plan, resource, and administer quality UTT, differed. South Africa's correctional facilities had existing systems to deliver and monitor chronic HIV care and treatment, forming a "scaffolding" for sustained UTT despite some human resources shortages and poorly integrated health information systems. Notwithstanding recent improvements, Zambia's correctional health system demonstrated insufficient material and technical capacity to independently deliver quality UTT. In the correctional facilities of both countries, inmate population dynamics and their impact on HIV-related stigma were important factors in UTT service uptake. CONCLUSION: Findings demonstrate the critical role of policy directives, health service delivery systems, adequate resourcing, and population dynamics on the feasibility and likely sustainability of UTT in corrections in Zambia and South Africa.
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    Opt-out provider-initiated HIV testing and counselling in primary care outpatient clinics in Zambia.
    (2011-May-01) Topp SM; Chipukuma JM; Chiko MM; Wamulume CS; Bolton-Moore C; Reid SE; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. stephanie.topp@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    OBJECTIVE: To increase case-finding of infection with human immunodeficiency virus (HIV) in Zambia and their referral to HIV care and treatment by supplementing existing client-initiated voluntary counselling and testing (VCT), the dominant mode of HIV testing in the country. METHODS: Lay counsellors offered provider-initiated HIV testing and counselling (PITC) to all outpatients who attended primary clinics and did not know their HIV serostatus. Data on counselling and testing were collected in registers. Outcomes of interest included HIV testing coverage, the acceptability of testing, the proportion testing HIV-positive (HIV+), the proportion enrolling in HIV care and treatment and the time between testing and enrolment. FINDINGS: After the addition of PITC to VCT, the number tested for HIV infection in the nine clinics was twice the number undergoing VCT alone. Over 30 months, 44,420 patients were counselled under PITC and 31,197 patients, 44% of them men, accepted testing. Of those tested, 21% (6572) were HIV+; 38% of these HIV+ patients (2515) enrolled in HIV care and treatment. The median time between testing and enrolment was 6 days. The acceptability of testing rose over time. CONCLUSION: The introduction of routine PITC using lay counsellors into health-care clinics in Lusaka, Zambia, dramatically increased the uptake and acceptability of HIV testing. Moreover, PITC was incorporated rapidly into primary care outpatient departments. Maximizing the number of patients who proceed to HIV care and treatment remains a challenge and warrants further research.
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