Date Published: February 14, 2018
Publisher: Public Library of Science
Author(s): Hester Korthals Altes, Serieke Kloet, Frank Cobelens, Martin Bootsma, David W. Dowdy.
While tuberculosis (TB) represents a significant disease burden worldwide, low-incidence countries strive to reach the WHO target of pre-elimination by 2035. Screening for TB in immigrants is an important component of the strategy to reduce the TB burden in low-incidence settings. An important option is the screening and preventive treatment of latent TB infection (LTBI). Whether this policy is worthwhile depends on the extent of transmission within the country, and introduction of new cases through import. Mathematical transmission models of TB have been used to identify key parameters in the epidemiology of TB and estimate transmission rates. An important application has also been to investigate the consequences of policy scenarios. Here, we formulate a mathematical model for TB transmission within the Netherlands to estimate the size of the pool of latent infections, and to determine the share of importation–either through immigration or travel- versus transmission within the Netherlands. We take into account importation of infections due to immigration, and travel to the country of origin, focusing on the three ethnicities most represented among foreign-born TB cases (after exclusion of those overrepresented among asylum seekers): Moroccans, Turkish and Indonesians. We fit a system of ordinary differential equations to the data from the Netherlands Tuberculosis Registry on (extra-)pulmonary TB cases from 1995–2013. We estimate that about 27% of Moroccans, 25% of Indonesians, and 16% of Turkish, are latently infected. Furthermore, we find that for all three foreign-born communities, immigration is the most important source of LTBI, but the extent of within-country transmission is much lower (about half) for the Turkish and Indonesian communities than for the Moroccan. This would imply that contact investigation would have a greater yield in the latter community than in the former. Travel remains a minor factor contributing LTBI, suggesting that targeting returning travelers might be less effective at preventing LTBI than immigrants upon entry in the country.
Revised estimates of the burden of latent tuberculosis infection (LTBI) indicate that about a quarter of the world population is infected with tuberculosis (TB) . Recently, guidelines for the management of LTBI were formulated against the background of the World Health Organization’s (WHO) End TB Strategy [2, 3]. With the post-2015 targets of TB elimination, even low-incidence countries are seeking to decrease TB incidence. Some of these countries have already implemented screening for latent TB infection at entry in the country, others are envisaging implementing this measure. The Netherlands, for example, is starting pilots among different immigrant groups to evaluate feasibility of LTBI screening at entry. For the critical assessment of LTBI screening policies, it is necessary to quantify the extent to which screening at entry is better than searching for infections in the context of contact investigation. Essentially, we wish to know what fraction of new LTBI in immigrants results from importation of infections, from transmission within the country, or from travel to the country of origin while living in the Netherlands. Cohort studies have provided estimates for the percentage of immigrants with a positive interferon-gamma release assay (IGRA) test at entry . However, the coverage of contact investigation in foreign-born groups is poor  and estimates of LTBI in this context are therefore incomplete.
We formulate a system of ordinary differential equations that is as realistic as possible, yet simple enough to allow the fit to time series data, i.e., the number of unknown parameters is limited. First, we focused our model on the 1st generation immigrants, to avoid the need to describe the birth process in the immigrant population leading to 2nd generation immigrants, and the complexities associated with mixed marriages. For all three ethnicities considered, the number of 2nd generation cases from non-mixed marriages represent about 5% of cases from the country in question (S1 Table).
The aim of our study was to estimate, based on a dynamic transmission model of TB in a low-incidence country, the size of the LTBI pool for three immigrant communities contributing most TB cases. Also, we derived the share of transmission within the Netherlands, versus immigration from and travel to country of origin, in the LTBI pool for these ethnic groups. We estimated that about 27% of Moroccans and 25% of Indonesians in the Netherlands are latently infected, of which 2% and 0.6% recently–in our definition less than 5 years ago- respectively. 16% of Turkish have LTBI, of which 0.7% recent. This may be set against results from Houben and Dodd , who provide estimates for the latent TB pool by world region: South East Asia (which includes Indonesia) has highest LTBI burden, with 30.8% prevalence; next is the Eastern Mediterranean region (Morocco) with 16% prevalence, and the European region (Turkey) with 13.7% prevalence.