Building leadership capacity and future leaders in operational research in low-income countries: why and how?

Very limited operational research (OR) emerges from programme settings in low-income countries where the greatest burden of disease lies. The price paid for this void includes a lack of understanding of how health systems are actually functioning, not knowing what works and what does not, and an inability to propose adapted and innovative solutions to programme problems. We use the National Tuberculosis Control Programme as an example to advocate for strong programme-level leadership to steer OR and build viable relationships between programme managers, researchers and policy makers. We highlight the need to create a stimulating environment for conducting OR and identify some of the main practical challenges and enabling factors at programme level. We focus on the important role of an OR focal point within programmes and practical approaches to training that can deliver timely and quantifiable outputs. Finally, we emphasise the need to measure successful OR leadership development at programme level and we propose parameters by which this can be assessed. This paper 1) provides reasons why programmes should take the lead in coordinating and directing OR, 2) identifies the practical challenges and enabling factors for implementing, managing and sustaining OR and 3) proposes parameters for measuring successful leadership capacity development in OR

Bacille Calmette-Guérin (BCG) vaccine and potential cross-protection against SARS-CoV-2 infection - Assumptions, knowns, unknowns and need for developing an accurate scientific evidence base

After a century of controversies on its usefulness in protection against TB, underlying mechanisms of action, and benefits in various groups and geographical areas, the BCG vaccine is yet again a focus of global attention- this time due to the global COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-g) production and its effects on CD4+ T-cells and these non-specific immune responses through adjuvant effect could be harnessed as cross protection against severe forms of COVID-19.The completion of ongoing BGG trials is important as they may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of other ways of combining BCG with other immunotherapies

Bronchoscopic study on aetiology of chronic cough in HIV-infected adults with negative sputum smears for Mycobacterium tuberculosis at Kenyatta National Hospital, Nairobi

Objective: To establish the aetiology of chronic cough in HIV-infected patients with negative sputum smears for Acid Fast Bacilli (AFB). Design: A cross-sectional descriptive study. Setting: Kenyatta National Hospital, a tertiary referral centre in Kenya Subjects: Sixty five HIV-infected adults presenting with chronic cough and negative sputum smears for AFBs. Results: Sixty-two patients were included in the final analysis. Aetiology of chronic cough was established in 42 (68%) patients. Pneumocystis jiroveci, bacterial pneumonia and Mycobacterium tuberculosis were diagnosed in 22 (35.5%),17 (27.4%) and 14 (22.5%) patients respectively. Majority (98%) of patients with a diagnosis had multiple causes established in them. Ciprofloxacin had activity against 91% of the isolated organisms while Penicillin was active against 35% only. Conclusion: This study documents Pneumocystis jiroveci pneumonia as a common cause of morbidity in a subset of HIV infected patients with chronic cough and negative sputum smears for AFB in Kenya

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools

International research and guidelines on post-tuberculosis chronic lung disorders: a systematic scoping review.

Introduction: Pulmonary tuberculosis (TB) is an important risk factor for chronic respiratory disease due to residual lung damage. Yet, the WHO End TB strategy does not mention post-TB chronic lung disorders (PTBLDs) and programmatic interventions to address PTBLD are lacking. This study assessed the scope of current guidelines and evidence on PTBLD to inform policy and research action. Methods: A systematic literature search was conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Eight databases (TRIP, International Guideline Library, MEDLINE/PubMed, EMBASE, Web of Science, Global Health, Cochrane Library) were searched for records on PTBLD published between 1 January 1990 and 1 December 2017. Non-English records, case series, conference abstracts and letters to editors were excluded. Data were extracted and charted on publication year, location, PTBLD condition(s) and main study outcome. Results: A total of 212 guidelines and 3661 articles were retrieved. After screening, only three international TB guidelines mentioned TB sequelae, but none described how to identify or manage the condition. A total of 156 articles addressed PTBLD: 54 (35%) mentioned unspecified TB sequelae; 47 (30%) specific post-TB conditions including aspergillosis, bronchial stenosis or bronchiectasis; 52 (33%) post-TB obstructive disorders or lung function impairment; and 20 (13%) post-TB respiratory symptoms or chest X-ray abnormalities. The first two groups mostly assessed surgery or ventilation techniques for patient management, while the last two groups typically assessed prevalence or predictors of disease. Conclusion: This is the first review to provide a comprehensive overview of the current literature on PTBLD. The scope of evidence around the burden of PTBLD warrants inclusion and recognition of the problem in international TB guidelines. Research is now needed on early detection of PTBLD and patient management options that are suitable for high-burden TB countries

Skin prick reactivity among asthmatics in East Africa

Background: The burden of asthma in Africa is high, and yet the disease is not universally prioritised. Data on allergic asthma and its impact on asthma morbidity are limited in Africa. Our aim was to describe the distribution of skin prick positivity among asthmatics in Eastern Africa. Methods: From August 2016 to May 2018, 1671 asthmatic patients were enrolled from Uganda, Kenya, and Ethiopia as part of the African Severe Asthma Program clinical study. Skin prick testing was performed at baseline using a panel of 12 allergens, and factors associated with skin prick reactivity determined. Results: Of the 1, 671 patients recruited, 71% were female with a median age of 40 years, 93.6% were aged >15 years and the patterns of asthma symptom frequency was intermittent in 2.9%, mild persistent in 19.9%, moderate persistent in 42.6% and severe persistent in 34.6% at baseline. Self-reported triggers, were dust (92%), cold weather (89%), upper respiratory infections (84%), strong smells (79%) and exposure to tobacco (78%). The majority (90%) of the participants had at least 1 positive allergen reaction, with 0.9% participants reacting to all the 12 allergens. Participants commonly reacted to house dust mites (66%), Blomia tropicalis (62%), and the German cockroach (52%). Patients sensitized to more allergens (>2) had significantly reduced lung function (FEV ≤ 80%; p = 0.001) and were more likely to visit the emergency department due to asthma (p = 0.012). There was no significant relationship between number of allergens and measures of asthma control, quality of life, and other clinical outcomes. Only the country of origin was independently associated with atopy among African asthmatics. Conclusion: There is a high prevalence of skin prick positivity among East African patients with asthma, with the commonest allergen being house dust mite. Skin reactivity did not correlate well with asthma severity and poor asthma control. The relation between atopy, measured through skin prick testing, and measures of asthma control among asthma patients in Eastern Africa is unclear and needs further study. Trial registration: The ASAP study was registered prospectively. ClinicalTrials.gov Identifier: NCT03065920; Registration date: February 28, 2017; Last verified: February 28, 2017

Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods