Chronic airflow obstruction in Tanzania - a cross-sectional study

Chronic obstructive pulmonary disease is a global problem and available data from sub-Saharan Africa is very limited.; A cross-sectional facility-based pilot study among patients and visitors to an urban and a rural primary healthcare facility was conducted in coastal Tanzania. The primary outcome was the prevalence of chronic airflow obstruction.; The final analysis included 598 participants with valid post-bronchodilator spirometry. Applying ATS/ERS spirometric criteria, chronic airflow obstruction was found in n = 24 (4%, CI95 2.7-5.9) participants and in n = 30 (5%, CI95 3.5-7.1) applying GOLD spirometric criteria. To analyse risk factors for chronic airflow obstruction including those not meeting ATS/ERS or GOLD criteria, FEF25-75 and FEV1% predicted was analysed in participants without evidence of pulmonary restriction among those exposed or not exposed to risk factors (n = 552). FEV1% predicted, but in particular FEF25-75 decreased with increasing symptom severity of shortness of breath as well as limitations in daily activities of participants. Cooking in general and cooking with biomass fuels vs. gas or electricity was associated with significantly lower FEF25-75, but not with lower FEV1% predicted. Participants having refrained from taking a job because of shortness of breath exhibited lower FEF25-75 (p < 0.01). A history of prior active TB was the most relevant risk factor associated with a decrease in FEF25-75 as well as FEV1% predicted.; This study demonstrated a relevant prevalence of chronic airflow obstruction in primary healthcare attendants and healthy visitors of a Tanzanian hospital. Using the baseline data provided, larger and population-based studies are needed to validate these findings. TB may have more impact on development of chronic airway obstruction than smoking in Africa. Due to the influence of age on the GOLD definition of chronic airflow obstruction, studies should report results using both ATS/ERS and GOLD definitions and include age-stratified analysis. Analysis of FEV1 and in particular FEF25-75 may yield additional information on risk factors and earlier stages of chronic airflow obstruction

Host-Directed Therapies for tackling Multi-Drug Resistant TB – learning from the Pasteur-Bechamp debates

Tuberculosis (TB) remains a global emergency causing an estimated 1.5 million deaths annually. For several decades the major focus of TB treatment has been on antibiotic development targeting Mycobacterium tuberculosis (M.tb). The lengthy TB treatment duration and poor treatment outcomes associated with multi-drug resistant TB (MDR-TB) are of major concern. The sparse new TB drug pipeline and widespread emergence of MDR-TB signal an urgent need for more innovative interventions to improve treatment outcomes. Building on the historical Pasteur-Bechamp debates on the role of the ‘microbe’ versus the ‘host internal milieu’ in disease causation, we make the case for parallel investments into host-directed therapies (HDTs). A range of potential HDTs are now available which require evaluation in randomized controlled clinical trials as adjunct therapies for shortening the duration of TB therapy and improving treatment outcomes for drug-susceptible TB and MDR-TB. Funder initiatives that may enable further research into HDTs are described

Towards host-directed therapies for tuberculosis

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies. Despite the availability of effective antibiotics for tuberculosis (TB) for the past half century, it remains an important global health problem; there are ~9 million active TB cases and ~1.5 million TB-induced deaths per year (see the World Health Organization (WHO) Global Tuberculosis Report in Further information). Health services around the world face major barriers to achieving optimal outcomes from current TB treatment regimens. These barriers include: the spread of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB); complex and toxic treatment regimens for MDR-TB; HIV co-infection; pharmacokinetic interactions between TB drugs and antiretroviral drugs; relapse; permanent damage to lung and other tissues; long-term functional disability; immune reconstitution inflammatory syndrome (IRIS); and co-morbidity with non-communicable diseases such as diabetes and chronic obstructive airway diseases. Another fundamental problem is the long duration of TB drug treatment (6 months for drug-sensitive TB and at least 18 months for drug-resistant TB) to achieve a cure, owing to the presence of dormant Mycobacterium tuberculosis bacilli that are phenotypically resistant to current classes of anti-TB drugs, which can only target bacterial replication. There is therefore an urgent need for new TB treatments. However, the TB drug pipeline is thin1, 2. For the past 60 years, efforts to develop new treatments have focused on compounds and regimens that target M. tuberculosis directly. Recently, however, attention has focused on investigating a range of adjunct treatment interventions known as host-directed therapies (HDTs) that instead target the host response to infection. Here, we highlight the rationale for HDTs, the current portfolio of HDTs and their mechanisms of action, and a consortium-based approach to drive forward their evaluation in clinical trials