Research Articles (Infectious Diseases)


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    Telomere 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.
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    Regression 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, Matthias
    Objective: 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.
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    COVID-19 travel restrictions and the International Health Regulations – Call for an open debate on easing of travel restrictions
    (Elsevier, 2020-05) Petersen, Eskild; McCloskey, Brian; Hui, David S.; Kock, Richard; Ntoumi, Francine; Memish, Ziad A.; Kapata, Nathan; Azhar, Esam I.; Pollack, Marjorie; Madoff, Larry C.; Hamer, Davidson H.; Nachega, Jean B.; Pshenichnaya, N.; Zumla, Alimuddin
    The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) has made national governments worldwide to mandate several generic infection control measures such as physical distancing, self-isolation, and closure of non-essential shops, restaurants schools, among others. Some models suggest physical distancing would have to persist for 3 months to mitigate the peak effects on health systems and could be required on an intermittent basis for 12 to 18 months ( Flaxman et al., 2020 ). Apart from these control measures travel restrictions during the early phase of the China outbreak were useful to confine it to Wuhan, the major source of the outbreak ( Kraemer et al., 2020 ) although ultimately these measures did not prevent the spread of COVID-19 to other regions of China. The global spread of the SARS-CoV-2 has clearly been associated with regional and international travel which has contributed to the pandemic ( Candido et al., 2020 ). To limit cross-border spread, both regionally and globally, many countries have swiftly adopted sweeping measures, including full lockdowns of shops, companies, shutting down airports, imposing travel restrictions and completely sealing their borders, to contain transmission ( Gostin and Wiley, 2020 ). The grounding of international travel as part of the global response to prevent spread has caused profound disruption of travel and trade and has threatened the survival of many airlines, travel companies, and associated businesses.
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    COVID-19 response in low- and middle-income countries : don’t overlook the role of mobile phone communication
    (Elsevier, 2020-07-26) Verhagen, Lilly M.; de Groot, R.; Lawrence, C. A.; Taljaard, J.; Cotton, M. F.; Rabie, H.
    Estimates of health capacities in the context of the coronavirus disease 2019 (COVID-19) pandemic indicate that most low- and middle-income countries (LMICs) are not operationally ready to manage this health emergency. Motivated by worldwide successes in other infectious disease epidemics and our experience in Sub-Saharan Africa, we support mobile phone communication to improve data collection and reporting, communication between healthcare workers, public health institutions, and patients, and the implementation of disease tracking and subsequent risk-stratified isolation measures. Programmatic action is needed for centrally coordinated reporting and communication systems facilitating mobile phones in crisis management plans for addressing the COVID-19 pandemic in LMICs. We summarize examples of worldwide mobile phone technology initiatives that have enhanced patient care and public health outcomes in previous epidemics and the current COVID-19 pandemic. In addition, we provide an overview of baseline conditions, including transparency about privacy guarantees, necessary for the successful use of mobile phones in assisting in the fight against COVID-19 spread.
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    Xpert mycobacterium tuberculosis/rifampicin-detected rifampicin resistance is a suboptimal surrogate for multidrug-resistant tuberculosis in Eastern Democratic Republic of the Congo : diagnostic and clinical implications
    (Oxford University Press, 2020-06) Bisimwa, Bertin C.; Nachega, Jean B.; Warren, Robin M.; Theron, Grant; Metcalfe, John Z.; Shah, Maunank; Diacon, Andreas H.; Sam-Agudu, Nadia A.; Yotebieng, Marcel; Bulabula, André N. H.; Katoto, Patrick D. M. C.; Chirambiza, Jean-Paul; Nyota, Rosette; Birembano, Freddy M.; Musafiri, Eric M.; Byadunia, Sifa; Bahizire, Esto; Kaswa, Michel K.; Callens, Steven; Kashongwe, Zacharie M.
    Background Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)–detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). Methods We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. Results Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1–100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5–72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. Conclusions In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.