Parallels and Mutual Lessons in Tuberculosis and COVID-19 Transmission, Prevention, and Control.

The coronavirus disease (COVID-19) pandemic has had unprecedented negative effects on global health and economies, drawing attention and resources from many other public health services. To minimize negative effects, the parallels, lessons, and resources from existing public health programs need to be identified and used. Often underappreciated synergies relating to COVID-19 are with tuberculosis (TB). COVID-19 and TB share commonalities in transmission and public health response: case finding, contact identification, and evaluation. Data supporting interventions for either disease are, understandably, vastly different, given the diseases' different histories. However, many of the evolving issues affecting these diseases are increasingly similar. As previously done for TB, all aspects of congregate investigations and preventive and therapeutic measures for COVID-19 must be prospectively studied for optimal evidence-based interventions. New attention garnered by the pandemic can ensure that knowledge and investment can benefit both COVID-19 response and traditional public health programs such as TB programs.

Implementing the End TB Strategy in the Western Pacific Region: Translating vision into reality.

The End TB Strategy aims to end the global tuberculosis (TB) epidemic by 2035 in line with the sustainable development goals targets and has been implemented in the World Health Organization (WHO) Western Pacific Region since 2015. Significant progress has been made in implementing this strategy. However, several challenges still remain. In 2016, an estimated 1.8 million people developed TB in the region, and of these about 20% were missed by national TB programmes. The gap in diagnosis and enrolment as well as treatment completion is greater with drug-resistant TB. Many TB-affected families face catastrophic costs due to the disease. Sustaining financing for TB care is a long-term challenge in many countries. This article emphasizes targeted interventions in high-risk populations, including systematic screening and patient-centred TB care. Several other approaches including improving TB diagnostic tools and algorithm, and engaging all care providers are suggested to find missing TB patients. Drug-resistant TB requires additional resourcing for laboratories, enrolment and patient support. Specific measures are required at different levels to mitigate financial burden due to TB including linking TB to overall social protection schemes. The Moscow Ministerial conference in 2017 and upcoming United Nations (UN) 2018 high-level meeting provide an opportunity to raise TB higher on the global agenda, forge partnerships and move towards universal health coverage.

Old ideas to innovate tuberculosis control: preventive treatment to achieve elimination.

The introduction of new rapid diagnostic tools for tuberculosis (TB) and the promising TB drugs pipeline together with the development of a new World Health Organization Strategy post 2015 allows new discussions on how to direct TB control. The European Respiratory Society's European Forum for TB Innovation was created to stimulate discussion on how to best take advantage of old and new opportunities, and advances, to improve TB control and eventually progress towards the elimination of TB. While TB control is aimed at reducing the incidence of TB by early diagnosis and treatment of infectious cases of TB, TB elimination requires focus on sterilising the pool of latently infected individuals, from which future TB cases would be generated. This manuscript describes the three core components that are necessary to implement the elimination strategy fully. 1) Improve diagnosis of latent TB infected individuals. 2) Improve regimens to treat latent TB infection. 3) ensure public health commitment to make both 1) and 2) possible. Old and new evidence is critically described, focusing on the European commitment to reach elimination and on the innovative experiences and best practices available.

In vitro inhibition of mumps virus by retinoids.

BACKGROUND: Mumps virus (MuV) is a highly infectious paramyxovirus closely related to measles virus (MeV). Despite the availability of a mumps vaccine, outbreaks continue to occur and no treatment options are available. Vitamin A and other naturally occurring retinoids inhibit the replication of MeV in vitro. METHODS: Anti-viral effects of retinoids were observed in cell culture using the myelomonocytic U937, NB4/R4, and Huh7/7.5 cells. Observations of anti-viral effect were quantified using TCID50 analysis. Molecular properties of the antiviral effect were analysed using quantitative RT-PCR and western blot. RESULTS: The current work demonstrates that retinoids inhibit MuV in vitro due to up-regulation of type I interferon (IFN) and IFN stimulated genes. This effect is mediated by nuclear retinoid receptor signalling and RIG-I is required. The antiviral retinoid-induced state makes cells less permissive to viral replication from subsequent challenge with either MuV or MeV for less than 12 hours. CONCLUSIONS: These results demonstrate that retinoids inhibit MuV replication in uninfected bystander cells through a retinoid inducible gene I (RIG-I), retinoic acid receptor (RAR) and IFN dependent manner making them refractory to subsequent rounds of viral replication. These observations raise the possibility that pharmacological doses of retinoids might have clinical benefit in MuV infection.

Diagnosis of Latent Tuberculosis Infection.

For 2015, tuberculosis (TB) incidence in the United States has plateaued at 3.0 per 100,000. This remains the lowest case rate since recording started. On the global level, although the TB epidemic is larger than previously estimated, TB deaths and incidence rate continue to fall. For both low and high incidence countries, accelerating the decline in TB incidence towards elimination goals requires that more emphasis be placed on strengthening systems for detection and treatment of latent TB infection (LTBI) in addition to improving TB care globally. Here, we review the tuberculin skin test and gamma interferon release assays currently available for the detection of LTBI.

Enhancement of treatment completion for latent tuberculosis infection with 4 months of rifampin.

BACKGROUND: Isoniazid is the standard medication used to treat latent tuberculosis infection (LTBI). The lengthy treatment with isoniazid, its perceived hepatotoxicity, and the increasing influx of foreign-born persons from countries with a higher prevalence of isoniazid resistance have compromised this regimen. In 2000, the Centers for Disease Control and Prevention guidelines recommended 4 months of rifampin (4R) as an acceptable alternative regimen to 9 months of isoniazid (9H). In a county chest clinic in northern New Jersey, a self-administered 9H regimen for patients with LTBI was generally prescribed until the year 2002. After recognizing poor completion rates, LTBI treatment was shifted predominantly to the alternative 4R regimen. METHODS: Medical records of patients placed on LTBI treatment during 2000 (predominantly a 9H regimen) and 2003 (predominantly a 4R regimen) were reviewed. A total of 474 patients were included in the study. chi(2), Fishers exact, two-sample t, and Wilcoxon rank-sum tests and logistic regression were used to analyze the data. The main outcome variable was treatment completion. RESULTS: A total of 80.5% of patients receiving 4R and 53.1% receiving 9H completed treatment (p < 0.0001); 34.7% of patients receiving 9H were unavailable for follow-up, compared to 12.6% receiving 4R (p = <0.0001). Fewer drug reactions were observed in the group receiving 4R compared to the group receiving 9H (3.1% vs 5.8%), although this was not statistically significant. Logistic regression analysis identified treatment regimen as a significant predictor for treatment completion (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.3 to 8.1). Employment was negatively associated with treatment completion in the same model (OR, 0.54; 95% CI, 0.34 to 0.94). CONCLUSIONS: Patients receiving 4R were significantly more likely to complete therapy than those receiving 9H.

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy.

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

Update: prevention and treatment of tuberculosis.

Tuberculosis remains one of the leading infectious disease killers globally. A significant reservoir of infected individuals and disease activity remains, particularly in the countries of the world which have the least economic resources to treat latent and active disease. This has set the stage, over the decades, for the development of multi-drug resistant isolates now easily spread around the world with increased trans-national migration.Tuberculosis treatment and control requires a global approach with international organizations such as the World Health Organization (WHO), and the International Union Against Tuberculosis and Lung Disease (IUATLD) overseeing National Tuberculosis Control Programs and seeking financial support from governmental as well as non-governmental sources. Directly Observed Therapy Short Course (DOTS) and DOTS Plus remain the cornerstones in the treatment of drug sensitive and drug resistant diseases respectively.Research activity should focus in developing early diagnostic tools and drugs which would be able to effectively treat tuberculosis cases for shorter periods of time in the new millennium.

A summary of meeting proceedings on addressing variability around the cut point in serial interferon-γ release assay testing.

On June 13, 2012, a group of key stakeholders, leaders, and national experts on tuberculosis (TB), occupational health, and laboratory science met in Atlanta, Georgia, to focus national discussion on the higher than expected positive results occurring among low-risk, unexposed healthcare workers undergoing serial testing with interferon-γ release assays (IGRAs). The objectives of the meeting were to present the latest clinical and operational research findings on the topic, to discuss evaluation and treatment algorithms that are emerging in the absence of national guidance, and to develop a consensus on the action steps needed to assist programs and physicians in the interpretation of serial testing IGRA results. This report summarizes its proceedings.