Research Articles (Infectious Diseases)
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- ItemTelomere length and outcome of treatment for pulmonary tuberculosis in a gold mining community(Nature, 2021-02) Katoto, Patrick D. M. C.; Kayembe‑Kitenge, Tony; Pollitt, Krystal J. Godri; Martens, Dries S.; Ghosh, Manosij; Nachega, Jean B.; Nemery, Benoit; Nawrot, Tim S.Telomere length (TL) is a marker of ageing and mitochondrial DNA (mtDNA) is an early marker of inflammation caused by oxidative stress. We determined TL and mtDNA content among active pulmonary tuberculosis (PTB) patients to assess if these cellular biomarkers differed between artisanal miners and non-miners, and to assess if they were predictive of treatment outcome. We conducted a prospective cohort study from August 2018 to May 2019 involving newly diagnosed PTB patients at three outpatient TB clinics in a rural Democratic Republic of Congo. We measured relative TL and mtDNA content in peripheral blood leukocytes (at inclusion) via qPCR and assessed their association with PTB treatment outcome. We included 129 patients (85 miners and 44 non-miners) with PTB (median age 40 years; range 5–71 years, 22% HIV-coinfected). For each increase in year and HIV-coinfection, TL shortened by − 0.85% (− 0.19 to − 0.52) (p ≤ 0.0001) and − 14% (− 28.22 to − 1.79) (p = 0.02) respectively. Independent of these covariates, patients with longer TL were more likely to have successful TB treatment [adjusted hazard ratio; 95% CI 1.27 for a doubling of leucocyte telomere length at baseline; 1.05–1.44] than patients with a shorter TL. Blood mtDNA content was not predictive for PTB outcome. For a given chronological age, PTB patients with longer telomeres at time of diagnosis were more likely to have successful PTB treatment outcome.
- ItemRegression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries(Pergamon Press, 2021-12) Zaniewski, Elizabeth; Brazier, Ellen; Ostinelli, Cam Ha Dao; Wood, Robin; Osler, Meg; Technau, Karl-Günter; Van Oosterhout, Joep J; Maxwell, Nicola; Van Dijk, Janneke; Prozesky, Hans; Fox, Matthew P; Bor, Jacob; Nash, Denis; Egger, MatthiasObjective: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. Study Design and Setting: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016–2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. Results: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (−21.4 percentage points (pp), 95% CI: −26.8, −16.0) and in Mozambique (−8.8pp, 95% CI: −14.9, −2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). Conclusion: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.
- ItemComparison of antiretroviral therapy adherence among HIV-infected older adults with younger adults in Africa : systematic review and meta-analysis(Springer, 2019) Soomro, Najeebullah; Fitzgerald, Grace; Seeley, Janet; Schatz, Enid; Nachega, Jean B.; Negin, JoelENGLISH ABSTRACT: As access to antiretroviral treatment in low- and middle-income countries improves, the number of older adults (aged ≥ 50 years) living with HIV is increasing. This study compares the adherence to antiretroviral treatment among older adults to that of younger adults living in Africa. We searched PubMed, Medline, Cochrane CENTRAL, CINAHL, Google Scholar and EMBASE for keywords (HIV, ART, compliance, adherence, age, Africa) on publications from 1st Jan 2000 to 1st March 2016. Eligible studies were pooled for meta-analysis using a random-effects model, with the odds ratio as the primary outcome. Twenty studies were included, among them were five randomised trials and five cohort studies. Overall, we pooled data for 148,819 individuals in two groups (older and younger adults) and found no significant difference in adherence between them [odds ratio (OR) 1.01; 95% CI 0.94–1.09]. Subgroup analyses of studies using medication possession ratio and clinician counts to measure adherence revealed higher proportions of older adults were adherent to medication regimens compared with younger adults (OR 1.06; 95% CI 1.02–1.11). Antiretroviral treatment adherence levels among older and younger adults in Africa are comparable. Further research is required to identify specific barriers to adherence in the aging HIV affected population in Africa which will help in development of interventions to improve their clinical outcomes and quality of life.
- 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.
- ItemManaging and preventing vascular catheter infections : a position paper of the international society for infectious diseases(Elsevier, 2019) Lutwick, Larry; Saif Al-Maani, Amal; Mehtar, Shaheen; Memish, Ziad; Rosenthal, Victor Daniel; Dramowski, Angela; Lui, Grace; Osman, Tamer; Bulabula, Andre; Bearman, GonzaloENGLISH ABSTRACT: A panel of experts was convened by the International Society for Infectious Diseases (ISID) to overview recommendations on managing and preventing vascular catheter infections, specifically for the prevention and management of central line-associated bloodstream infections. These recommendations are intended to provide insight for healthcare professionals regarding the prevention of infection in the placement and maintenance of the catheter and diagnosis as well as treatment of catheter infection. Aspects of this area in pediatrics and in limited-resource situations and a discussion regarding the selection of empiric or targeted antimicrobial therapy are particular strengths of this position paper.