Browsing by Author "Zumla, Alimuddin"

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    Artemisia Spp. derivatives for COVID-19 treatment : anecdotal use, political hype, treatment potential, challenges, and road map to randomized clinical trials
    (American Society of Tropical Medicine and Hygiene, 2020) Kapepula, Paulin M.; Kabengele, Jimmy K.; Kingombe, Micheline; Van Bambeke, Francoise; Tulkens, Paul M.; Kishabongo, Antoine Sadiki; Decloedt, Eric; Zumla, Adam; Tiberi, Simon; Suleman, Fatima; Tshilolo, Leon; Muyembe-TamFum, Jean-Jacques; Zumla, Alimuddin; Nachega, Jean B.
    The world is currently facing a novel COVID-19 pandemic caused by SARS-CoV-2 that, as of July 12, 2020, has caused a reported 12,322,395 cases and 556,335 deaths. To date, only two treatments, remdesivir and dexamethasone, have demonstrated clinical efficacy through randomized controlled trials (RCTs) in seriously ill patients. The search for new or repurposed drugs for treatment of COVID-19 continues. We have witnessed anecdotal use of herbal medicines, including Artemisia spp. extracts, in low-income countries, and exaggerated claims of their efficacies that are not evidence based, with subsequent political controversy. These events highlight the urgent need for further research on herbal compounds to evaluate efficacy through RCTs, and, when efficacious compounds are identified, to establish the active ingredients, develop formulations and dosing, and define pharmacokinetics, toxicology, and safety to enable drug development. Derivatives from the herb Artemisia annua have been used as traditional medicine over centuries for the treatment of fevers, malaria, and respiratory tract infections. We review the bioactive compounds, pharmacological and immunological effects, and traditional uses for Artemisia spp. derivatives, and discuss the challenges and controversies surrounding current efforts and the scientific road map to advance them to prevent or treat COVID-19.
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    A broad profile of co-dominant epitopes shapes the peripheral Mycobacterium tuberculosis specific CD8+ T-Cell immune response in South African patients with active tuberculosis
    (Public Library of Science, 2013-03-26) Axelsson-Robertson, Rebecca; Loxton, Andre G.; Walzl, Gerhard; Ehlers, Marthie M.; Kock, Marleen M.; Zumla, Alimuddin; Maeurer, Markus
    We studied major histocompatibility complex (MHC) class I peptide-presentation and nature of the antigen-specific CD8+ T-cell response from South African tuberculosis (TB) patients with active TB. 361 MHC class I binding epitopes were identified from three immunogenic TB proteins (ESAT-6 [Rv3875], Ag85B [Rv1886c], and TB10.4 [Rv0288], including amino acid variations for Rv0288, i.e., A10T, G13D, S27N, and A71S for MHC allotypes common in a South African population (e.g., human leukocyte antigen [HLA]-A*30, B*58, and C*07). Inter-allelic differences were identified regarding the broadness of the peptide-binding capacity. Mapping of frequencies of Mycobacterium tuberculosis (M. tb) antigen-specific CD8+ T-cells using 48 different multimers, including the newly constructed recombinant MHC class I alleles HLA-B*58:01 and C*0701, revealed a low frequency of CD8+ T-cell responses directed against a broad panel of co-dominant M. tb epitopes in the peripheral circulation of most patients. The antigen-specific responses were dominated by CD8+ T-cells with a precursor-like phenotype (CD45RA+CCR7+). The data show that the CD8+ T-cell response from patients with pulmonary TB (prior to treatment) is directed against subdominant epitopes derived from secreted and non-secreted M. tb antigens and that variant, natural occurring M. tb Rv0288 ligands, have a profound impact on T-cell recognition.
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    Chloroquine and hydroxychloroquine for the prevention or treatment of Novel Coronavirus Disease (COVID-19) in Africa : caution for inappropriate off-label use in healthcare settings
    (American Society of Tropical Medicine and Hygiene, 2020) Abena, Pascale M.; Decloedt, Eric H.; Bottieau, Emmanuel; Suleman, Fatima; Adejumo, Prisca; Sam-Agudu, Nadia A.; TamFum, Jean-Jacques Muyembe; Seydi, Moussa; Eholie, Serge P.; Mills, Edward J.; Kallay, Oscar; Zumla, Alimuddin; Nachega, Jean B.
    ENGLISH ABSTRACT: The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) havebecome the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by theWHOas an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic.
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    Clinical characteristics and outcomes of patients hospitalized for COVID-19 in Africa : early insights from the Democratic Republic of the Congo
    (American Society of Tropical Medicine and Hygiene, 2020) Nachega, Jean B.; Ishoso, Daniel Katuashi; Otokoye, John Otshudiema; Hermans, Michel P.; Machekano, Rhoderick Neri; Sam-Agudu, Nadia A.; Nswe, Christian Bongo-Pasi; Mbala-Kingebeni, Placide; Madinga, Joule Ntwan; Mukendi, Stephane; Koli, Marie Claire; Nkwembe, Edith N.; Mbuyi, Gisele M.; Nsio, Justus M.; Tshialala, Didier Mukeba; Pipo, Michel Tshiasuma; Ahuka-Mundeke, Steve; Muyembe-Tamfum, Jean-Jacques; Mofenson, Lynne; Smith, Gerald; Mills, Edward J.; Mellors, John W.; Zumla, Alimuddin; Landu, Don Jethro Mavungu; Kayembe, Jean-Marie
    ENGLISH ABSTRACT: Little is known about the clinical features and outcomes of SARS-CoV-2 infection in Africa. We conducted a retrospective cohort study of patients hospitalized for COVID-19 between March 10, 2020 and July 31, 2020 at seven hospitals in Kinshasa, Democratic Republic of the Congo (DRC). Outcomes included clinical improvement within 30 days (primary) and in-hospital mortality (secondary). Of 766 confirmed COVID-19 cases, 500 (65.6%) were male, with a median (interquartile range [IQR]) age of 46 (34–58) years. One hundred ninety-one (25%) patients had severe/critical disease requiring admission in the intensive care unit (ICU). Six hundred twenty patients (80.9%) improved and were discharged within 30 days of admission. Overall in-hospital mortality was 13.2% (95% CI: 10.9–15.8), and almost 50% among those in the ICU. Independent risk factors for death were age < 20 years (adjusted hazard ratio [aHR] = 6.62, 95% CI: 1.85–23.64), 40–59 years (aHR = 4.45, 95% CI: 1.83–10.79), and ³ 60 years (aHR = 13.63, 95% CI: 5.70–32.60) compared with those aged 20–39 years, with obesity (aHR = 2.30, 95% CI: 1.24–4.27), and with chronic kidney disease (aHR = 5.33, 95% CI: 1.85–15.35). In marginal structural model analysis, there was no statistically significant difference in odds of clinical improvement (adjusted odds ratio [aOR] = 1.53, 95% CI: 0.88–2.67, P = 0.132) nor risk of death (aOR = 0.65, 95% CI: 0.35–1.20) when comparing the use of chloroquine/azithromycin versus other treatments. In this DRC study, the high mortality among patients aged < 20 years and with severe/critical disease is of great concern, and requires further research for confirmation and targeted interventions.
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    The colliding epidemics of COVID-19, Ebola, and measles in the Democratic Republic of the Congo
    (Elsevier, 2020) Nachega, Jean B.; Mbala-Kingebeni, Placide; Otshudiema, John; Zumla, Alimuddin; Tam-Fum, Jean-Jacques Muyembe
    ENGLISH ABSTRACT: The Democratic Republic of the Congo is facing major public health challenges due to a confluence of major outbreaks of Ebola virus disease, measles, and COVID-19.1–4 The tenth Ebola outbreak in eastern DR Congo began on Aug 1, 2018, and as of May 28, 2020, there have been 3406 Ebola virus disease cases with 2243 deaths. The Ebola virus disease outbreak was well controlled in northeast DR Congo following a multisectoral response, but four new confirmed Ebola cases were detected in northwest DR Congo on June 1, 2020, and an outbreak response is underway.4 Additionally, the DR Congo has been burdened with recurrent measles outbreaks: 13 3802 cases in 2011, 88381 cases in 2013, and 311471 cases in 2019.2 The first confirmed case of COVID-19 in DR Congo was diagnosed on March 10, 2020, and the government declared a state of emergency on March 24, 2020. A national multisectoral response committee instituted lockdown in the capital, Kinshasa, the epicentre of the epidemic in DR Congo, in which daily confirmed cases now average 100. As of June 16, 2020, 4777 COVID-19 cases with 106 deaths have been reported from the DR Congo.
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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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    Frequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatment
    (Elsevier, 2015) Axelsson-Robertson, Rebecca; Rao, Martin; Loxton, Andre G.; Walzl, Gerhard; Bates, Matthew; Zumla, Alimuddin; Maeurer, Markus
    Anti-tuberculosis drug treatment is known to affect the number, phenotype, and effector functionality of antigen-specific T-cells. In order to objectively gauge Mycobacterium tuberculosis (MTB)-specific CD8+ T-cells at the single-cell level, we developed soluble major histocompatibility complex (MHC) class I multimers/peptide multimers, which allow analysis of antigen-specific T-cells without ex vivo manipulation or functional tests. We constructed 38 MHC class I multimers covering some of the most frequent MHC class I alleles (HLA-A*02:01, A*24:02, A*30:01, A*30:02, A*68:01, B*58:01, and C*07:01) pertinent to a South African or Zambian population, and presenting the following MTB-derived peptides: the early expressed secreted antigens TB10.4 (Rv0288), Ag85B (Rv1886c), and ESAT-6 (Rv3875), as well as intracellular enzymes, i.e., glycosyltransferase 1 (Rv2957), glycosyltransferase 2 (Rv2958c), and cyclopropane fatty acid synthase (Rv0447c). Anti-TB treatment appeared to impact on the frequency of multimer-positive CD8+ T-cells, with a general decrease after 6 months of therapy. Also, a reduction in the total central memory CD8+ T-cell frequencies, as well as the antigen-specific compartment in CD45RA−CCR7+ T-cells was observed. We discuss our findings on the basis of differential dynamics of MTB-specific T-cell frequencies, impact of MTB antigen load on T-cell phenotype, and antigen-specific T-cell responses in tuberculosis.
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    From easing lockdowns to scaling up community-based coronavirus disease 2019 screening, testing, and contact tracing in Africa-shared approaches, innovations, and challenges to minimize morbidity and mortality
    (Oxford University Press, 2020-05) Nachega, Jean B.; Grimwood, Ashraf; Mahomed, Hassan; Fatti, Geoffrey; Preiser, Wolfgang; Kallay, Oscar; Mbala, Placide K.; Muyembe, Jean-Jacques T.; Rwagasore, Edson; Nsanzimana, Sabin; Ngamije, Daniel; Condo, Jeanine; Sidat, Mohsin; Noormahomed, Emilia V.; Reid, Michael; Lukeni, Beatrice; Suleman, Fatima; Mteta, Alfred; Zumla, Alimuddin
    The arrival of coronavirus disease 2019 (COVID-19) on the African continent resulted in a range of lockdown measures that curtailed the spread of the infection but caused economic hardship. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Pandemic control will require efficient community screening, testing, and contact tracing; behavioral change interventions; adequate resources; and well-supported, community-based teams of trained, protected personnel. We discuss COVID-19 control approaches in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality. This crisis presents a unique opportunity to align COVID-19 services with those already in place for human immunodeficiency virus, tuberculosis, malaria, and non communicable diseases through mobilization of Africa's interprofessional healthcare workforce. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.
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    From easing lockdowns to scaling-up community-based COVID-19 screening, testing, and contact tracing in Africa : shared approaches, innovations, and challenges to minimize morbidity and mortality
    (Oxford University Press, 2020) Nachega, Jean B.; Grimwood, Ashraf; Mahomed, Hassan; Fatti, Geoffrey; Preiser, Wolfgang; Kallay, Oscar; Mbala, Placide K.; Muyembe, Jean-Jacques T.; Rwagasore, Edson; Nsanzimana, Sabin; Ngamije, Daniel; Condo, Jeanine; Sidat, Moshin; Noormahomed, Emilia V.; Reid, Michael; Lukeni, Beatrice; Suleman, Fatima; Mteta, Alfred; Zumla, Alimuddin
    The arrival of COVID-19 to the African continent resulted in a range of locally relevant lockdown measures, which curtailed the spread of SARS-CoV-2 but caused economic hardship for large sections of the population. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Control of the COVID-19 pandemic will require efficient community screening, testing, contact tracing, and behavioral change interventions, adequate resources, and a well-supported, community-based team of trained, protected personnel. We discuss COVID-19 screening-testing-contact tracing approaches used in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality rates. This crisis presents a unique opportunity to align COVID-19 services with those already in place for HIV, TB, Malaria, and other non-communicable diseases (NCDs) through mobilization of Africa's inter-professional healthcare workforce to contain the pandemic. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.
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    The late arrival of coronavirus disease 2019 (COVID-19) in Africa : mitigating pan-continental spread
    (Oxford University Press, 2020-07) Nachega, Jean; Seydi, Moussa; Zumla, Alimuddin
    The novel coronavirus disease 2019 (COVID-19) has rapidly spread to all 7 continents. Due to yet unknown reasons, the African continent has remained relatively unaffected. We discuss the importance of mitigating pan-continental spread in light of the fragile healthcare systems.
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    Limiting the spread of COVID-19 in Africa : one size mitigation strategies do not fit all countries
    (Elsevier, 2020) Mehtar, Shaheen; Preiser, Wolfgang; Lakhe, Ndeye Aissatou; Bousso, Abdoulaye; TamFum, Jean-Jacques Muyembe; Kallay, Oscar; Seydi, Moussa; Zumla, Alimuddin; Nachega, Jean B.
    On March 11, 2020, when coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by WHO, there were comparatively few cases reported from Africa. Our Comment draws on early imported COVID-19 cases in South Africa, Senegal, Democratic Republic of the Congo, and Egypt as case studies to discuss important mitigation strategies of COVID-19 in Africa.
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    MDR/XDR-TB management of patients and contacts : challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network
    (Elsevier, 2020-03) Migliori, Giovanni Battista; Tiberi, Simon; Zumla, Alimuddin; Petersen, Eskild; Chakaya, Jeremiah Muhwa; Wejse, Christian; Torrico, Marcela Munoz; Duarte, Raquel; Alffenaar, Jan Willem; Schaaf, H. Simon; Marais, Ben J.; Cirillo, Daniela Maria; Alagna, Riccardo; Rendon, Adrian; Pontali, Emanuele; Piubello, Alberto; Figueroa, Jose; Ferlazzo, Gabriella; García-Basteiro, Alberto; Centis, Rosella; Visca, Dina; D’Ambrosio, Lia; Sotgiu, Giovanni
    The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.
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    Mobile health technology for enhancing the COVID-19 response in Africa : a potential game changer?
    (American Society of Tropical Medicine and Hygiene, 2020) Nachega, Jean B.; Leisegang, Rory; Kallay, Oscar; Mills, Edward J.; Zumla, Alimuddin; Lester, Richard T.
    The WHO Africa Region is experiencing an increase in the number of novel COVID-19 cases. As of May 20, 2020, 63,521 cases with 1,796 deaths (2.8% case fatality) have been reported from 45 countries.1 Although these numbers are small compared with those in United States or Europe, the WHO recently estimated that up to 190,000 people could die of COVID-19 in Africa if the pandemic is not controlled.2 These projections are threatening the already overstretched health services in Africa, where governments have been implementing mitigating strategies to flatten epidemic curves at manageable levels. These include education, personal hygiene practices, social distancing, travel bans, and partial or total lockdowns.3 However, as lockdowns and social distancing measures are currently being lifted in stages by most African countries, governments will need to ensure that public health infrastructure and needed resources are put in place for community surveillance to identify cases and clusters of new infections through active case finding, large-scale testing, and contact tracing.
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    Translational research for tuberculosis elimination : priorities, challenges, and actions
    (Public Library of Science, 2016) Lienhardt, Christian; Lonnroth, Knut; Menzies, Dick; Balasegaram, Manica; Chakaya, Jeremiah; Cobelens, Frank; Cohn, Jennifer; Denkinger, Claudia M.; Evans, Thomas G.; Kallenius, Gunilla; Kaplan, Gilla; Kumar, Ajay M. V.; Matthiessen, Line; Mgone, Charles S.; Mizrahi, Valerie; Mukadi, Ya-diul; Nguyen, Viet Nhung; Nordstrom, Anders; Sizemore, Christine F.; Spigelman, Melvin; Squire, S. Bertel; Swaminathan, Soumya; Van Helden, Paul D.; Zumla, Alimuddin; Weyer, Karin; Weil, Diana; Raviglione, Mario
    Summary Points: • The WHO End TB Strategy, endorsed by the World Health Assembly in May 2014, has the ambitious goal of ending the global tuberculosis (TB) epidemic by 2035, with targets of a 95% decline in deaths due to TB (compared with 2015) and a 90% reduction in incidence of TB to ten cases/100,000 or less and no TB-affected household experiencing catastrophic costs due to TB. • Achieving this goal will only be possible through the development and rapid uptake of new tools, including rapid point-of-care diagnostics, safe and shorter treatment of latent TB infection and disease, and an efficacious TB vaccine, combined with efficient health systems and care provision, and actions on the social determinants of TB. • Research for TB elimination requires an intensification of efforts across a continuum from fundamental research to clinical, epidemiological, implementation, health system, and social science research. • Enhancing research along the full spectrum, from basic to implementation, and strengthening research capacity, particularly in low- and middle-income countries severely affected by the TB epidemics, is crucial for TB elimination. • The creation of a research-enabling environment that fosters and rewards high-quality research requires a broad-based, concerted effort by national governments and international donors to develop and promote TB research and research capacity at the country level and the effective engagement of all stakeholders.
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    Why healthcare workers are sick of TB
    (Elsevier, 2015) Von Delft, Arne; Dramowski, Angela; Khosa, Celso; Kotze, Koot; Lederer, Philip; Mosidi, Thato; Peters, Jurgens A.; Smith, Jonathan; Van der Westhuizen, Helene-Mari; Von Delft, Dalene; Willems, Bart; Bates, Matthew; Craig, Gill; Maeurer, Markus; Marais, Ben J.; Mwaba, Peter; Nunes, Elizabete A.; Nyirenda, Thomas; Oliver, Matt; Zumla, Alimuddin
    Dr Thato Mosidi never expected to be diagnosed with tuberculosis (TB), despite widely prevalent exposure and very limited infection control measures. The life-threatening diagnosis of primary extensively drug-resistant TB (XDR-TB) came as an even greater shock. The inconvenient truth is that, rather than being protected, Dr Mosidi and thousands of her healthcare colleagues are at an increased risk of TB and especially drug-resistant TB. In this viewpoint paper we debunk the widely held false belief that healthcare workers are somehow immune to TB disease (TB-proof) and explore some of the key factors contributing to the pervasive stigmatization and subsequent non-disclosure of occupational TB. Our front-line workers are some of the first to suffer the consequences of a progressively more resistant and fatal TB epidemic, and urgent interventions are needed to ensure the safety and continued availability of these precious healthcare resources. These include the rapid development and scale-up of improved diagnostic and treatment options, strengthened infection control measures, and focused interventions to tackle stigma and discrimination in all its forms. We call our colleagues to action to protect themselves and those they care for.
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    World TB Day 2010 : eradicating tuberculosis in sub-Saharan Africa needs effective and committed north-south partnerships
    (Health and Medical Publishing Group (HMPG), 2010) Marais, Ben; Hoelscher, Michael; Mwaba, Peter; Dheda, Keertan; Zumla, Alimuddin