Browsing by Author "Fenner, Lukas"
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- ItemHIV viral load as an independent risk factor for tuberculosis in South Africa : collaborative analysis of cohort studies(Wiley Open Access, 2017) Fenner, Lukas; Atkinson, Andrew; Boulle, Andrew; Fox, Matthew P.; Prozesky, Hans; Zurcher, Kathrin; Ballif, Marie; Furrer, Hansjakob; Zwahlen, Marcel; Davies, Mary-Ann; Egger, MatthiasIntroduction: Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART). Methods: We included all HIV-positive adult patients ( 16 years) in care between 2000 and 2014 at three ART programmes in South Africa. Patients with previous TB were excluded. Missing CD4 cell counts and HIV-RNA viral loads at ART start (baseline) and during follow-up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV-RNA levels, and estimated the rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts, and WHO clinical stage in the model. We also used Poisson general additive regression models with time-updated CD4 and HIV-RNA values, adjusting for age and sex. Results: We included 44,260 patients with a median follow-up time of 2.7 years (interquartile range [IQR] 1.0–5.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34 years (IQR 28–41); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells/μL (IQR 79–229) and the median HIV-RNA viral load 58,000 copies/mL (IQR 6,000–240,000). Overall TB incidence was 26.2/1,000 person-years (95% confidence interval [CI] 25.3–27.0). Compared to the lowest viral load category (0–999 copies/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15–1.75, p < 0.001) in the highest group (>10,000 copies/mL). Time-updated analyses for CD4/HIV-RNA confirmed the association of viral load with the risk for TB. Conclusions: Our results indicate that ongoing HIV replication is an important risk factor for TB, regardless of CD4 cell counts, and underline the importance of early ART start and retention on ART.
- ItemImplementation of tuberculosis intensive case finding, isoniazid preventive therapy, and infection control ("Three I's") and HIV-tuberculosis service integration in lower income countries(Public Library of Science, 2016) Charles, M. Katherine; Lindegren, Mary Lou; Wester, C. William; Blevins, Meridith; Sterling, Timothy R.; Dung, Nguyen Thi; Dusingize, Jean Claude; Avit-Edi, Divine; Durier, Nicolas; Castelnuovo, Barbara; Nakigozi, Gertrude; Cortes, Claudia P.; Ballif, Marie; Fenner, Lukas; International epidemiology Databases to Evaluate AIDS (IeDEA) CollaborationSetting: World Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control (“Three I’s”) for TB prevention and control among persons living with HIV. Objective: To assess the implementation of the “Three I’s” of TB-control at HIV treatment sites in lower income countries. Design: Survey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa. Results: ICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03). Conclusions: Implementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.
- ItemMultiple introductions of mycobacterium tuberculosis lineage 2–Beijing into Africa over centuries(Frontiers Media, 2019) Rutaihwa, Liliana K.; Menardo, Fabrizio; Stucki, David; Gygli, Sebastian M.; Ley, Serej D.; Malla, Bijaya; Feldmann, Julia; Borrell, Sonia; Beisel, Christian; Middelkoop, Kerren; Carter, E. Jane; Diero, Lameck; Ballif, Marie; Jugheli, Levan; Reither, Klaus; Fenner, Lukas; Brites, Daniela; Gagneux, SebastienENGLISH ABSTRACT: The Lineage 2–Beijing (L2–Beijing) sub-lineage of Mycobacterium tuberculosis has received much attention due to its high virulence, fast disease progression, and association with antibiotic resistance. Despite several reports of the recent emergence of L2–Beijing in Africa, no study has investigated the evolutionary history of this sub-lineage on the continent. In this study, we used whole genome sequences of 781 L2 clinical strains from 14 geographical regions globally distributed to investigate the origins and onward spread of this lineage in Africa. Our results reveal multiple introductions of L2–Beijing into Africa linked to independent bacterial populations from East- and Southeast Asia. Bayesian analyses further indicate that these introductions occurred during the past 300 years, with most of these events pre-dating the antibiotic era. Hence, the success of L2–Beijing in Africa is most likely due to its hypervirulence and high transmissibility rather than drug resistance.
- ItemSeasonal variations in tuberculosis diagnosis among HIV-positive individuals in Southern Africa : analysis of cohort studies at antiretroviral treatment programmes(BMJ Publishing Group, 2018-01) Ballif, Marie; Zurcher, Kathrin; Reid, Stewart E.; Boulle, Andrew; Fox, Matthew P.; Prozesky, Hans W.; Chimbetete, Cleophas; Zwahlen, Marcel; Egger, Matthias; Fenner, LukasObjectives Seasonal variations in tuberculosis diagnoses have been attributed to seasonal climatic changes and indoor crowding during colder winter months. We investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral therapy (ART) programmes in Southern Africa. Setting Five ART programmes participating in the International Epidemiology Database to Evaluate AIDS in South Africa, Zambia and Zimbabwe. Participants We analysed data of 331 634 HIV-positive adults (>15 years), who initiated ART between January 2004 and December 2014. Primary outcome measure We calculated aggregated averages in monthly counts of PTB diagnoses and ART initiations. To account for time trends, we compared deviations of monthly event counts to yearly averages, and calculated correlation coefficients. We used multivariable regressions to assess associations between deviations of monthly ART initiation and PTB diagnosis counts from yearly averages, adjusted for monthly air temperatures and geographical latitude. As controls, we used Kaposi sarcoma and extrapulmonary tuberculosis (EPTB) diagnoses. Results All programmes showed monthly variations in PTB diagnoses that paralleled fluctuations in ART initiations, with recurrent patterns across 2004–2014. The strongest drops in PTB diagnoses occurred in December, followed by April–May in Zimbabwe and South Africa. This corresponded to holiday seasons, when clinical activities are reduced. We observed little monthly variation in ART initiations and PTB diagnoses in Zambia. Correlation coefficients supported parallel trends in ART initiations and PTB diagnoses (correlation coefficient: 0.28, 95% CI 0.21 to 0.35, P<0.001). Monthly temperatures and latitude did not substantially change regression coefficients between ART initiations and PTB diagnoses. Trends in Kaposi sarcoma and EPTB diagnoses similarly followed changes in ART initiations throughout the year. Conclusions Monthly variations in PTB diagnosis at ART programmes in Southern Africa likely occurred regardless of seasonal variations in temperatures or latitude and reflected fluctuations in clinical activities and changes in health-seeking behaviour throughout the year, rather than climatic factors.