Prevalence of latent tuberculosis infection among participants of the national LTBI screening program in South Korea – A problem of low coverage rate with current LTBI strategy

Background The existing estimate of the global burden of latent TB infection (LTBI) as “one-third” of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI. Methods and Findings We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y), and recently infected with isoniazid (INH)-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050. In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%–26.4%), amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%–0.9%) of the global population, amounting to 55.5 (95% UI: 48.2–63.8) million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%–11.8%) was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI data, and limited evidence to inform on potential clearance of LTBI. Conclusions We estimate that approximately 1.7 billion individuals were latently infected with Mycobacterium tuberculosis (M.tb) globally in 2014, just under a quarter of the global population. Investment in new tools to improve diagnosis and treatment of those with LTBI at risk of progressing to disease is urgently needed to address this latent reservoir if the 2050 target of eliminating TB is to be reached.

The target for TB elimination is to reduce annual incidence to less than one case per million population by 2050. Meeting that target requires a 1,000-fold reduction in incidence in little more than 35 years. This can be achieved only by combining the effective treatment of active TB-early case detection and high cure rates to interrupt transmission-with methods to prevent new infections and to neutralize existing latent infections. Vigorous implementation of the WHO Stop TB Strategy is needed to achieve the former, facilitated by the effective supply of, and demand for, health services. The latter calls for new technology, including biomarkers of TB risk, diagnostics, drugs, and vaccines. An important milestone en route to elimination will be reached when there is less than 1 TB death per 100,000 population, marking entry into the elimination phase. This landmark can be reached by many countries within 1-2 decades.

Background: Comorbidities may have an important impact on survival, and comorbidity scores are often implemented in studies assessing prognosis. The Charlson Comorbidity index is most widely used, yet several adaptations have been published, all using slightly different conversions of the International Classification of Diseases (ICD) coding. Objective: To evaluate which coding should be used to assess and quantify comorbidity for the Charlson Comorbidity Index for registry-based research, in particular if older ICD versions will be used. Methods: A systematic literature search was used to identify adaptations and modifications of the ICD-coding of the Charlson Comorbidity Index for general purpose in adults, published in English. Back-translation to ICD version 8 and version 9 was conducted by means of the ICD-code converter of Statistics Sweden. Results: In total, 16 studies were identified reporting ICD-adaptations of the Charlson Comorbidity Index. The Royal College of Surgeons in the United Kingdom combined 5 versions into an adapted and updated version which appeared appropriate for research purposes. Their ICD-10 codes were back-translated into ICD-9 and ICD-8 according to their proposed adaptations, and verified with previous versions of the Charlson Comorbidity Index. Conclusion: Many versions of the Charlson Comorbidity Index are used in parallel, so clear reporting of the version, exact ICD- coding and weighting is necessary to obtain transparency and reproducibility in research. Yet, the version of the Royal College of Surgeons is up-to-date and easy-to-use, and therefore an acceptable co-morbidity score to be used in registry-based research especially for surgical patients.