A latest study has estimated that at least 67 million children are infected by Mycobacterium tuberculosis with 850,000 developing active disease. Of these children, two million were estimated to be infected with multi drug-resistant (MDR)-tuberculosis strains, leading to 25,000 cases of MDR-TB disease requiring expensive and toxic treatment, according to a new study by The Lancet Infectious Diseases.
TB in children is increasingly being recognised as a significant public health problem, and an important element of the total global burden of the disease. Improved estimates of the rates of drug resistance in children are important because paediatric tuberculosis can be more difficult to diagnose, more challenging to test for drug sensitivity, and more likely to cause extra-pulmonary infection.
Africa and South East Asia have the highest numbers of children with TB, but the WHO Eastern Mediterranean region, Europe and Western Pacific region also contribute substantially to the burden of drug-resistant tuberculosis because of their much higher proportions of resistance, the study says. Far more drug-resistant tuberculosis occurs in children than is diagnosed, and there is a large pool of drug-resistant infection. This finding has implications for approaches to empirical treatment and preventive therapy in some regions of the world.
After infection with Mycobacterium tuberculosis, children are at an increased risk of progression to tuberculosis disease; a condition that can be challenging to diagnose. New estimation approaches for children have highlighted the gap between incidence and notifications of M tuberculosis, and suggest there are more cases of isoniazid-resistant and multidrug-resistant (MDR) disease than are identified. No work has yet quantified the burden of drug-resistant infection, or accounted for other types of drug resistance or sampling uncertainty.
The researchers combined a mathematical model of tuberculosis in children with an analysis of drug-resistance patterns to produce country-level, regional, and global estimates of drug-resistant infection and disease. They then determined drug resistance using data from the Global Project on Antituberculosis Drug Resistance Surveillance at WHO, from surveys and surveillance reported between 1988 and 2014 and combined 1000 sampled proportions for each country to estimate the proportions of tuberculosis cases at a country level with isoniazid monoresistance, rifampicin monoresistance, multidrug resistance (MDR), fluoroquinolone-resistant multidrug resistance, second-line injectable-resistant multidrug resistance, and extensive multidrug resistance with resistance to both a fluoroquinolone and a second-line injectable (XDR).
The innovative modelling and statistical analysis was carried out by researchers from the University of Sheffield, Imperial College London, and the World Health Organisation. Peter Dodd, an infectious disease epidemiologist from the Universityâ€™s School of Health and Related Research (ScHARR), said: â€œOur report shows far more drug-resistant TB occurs in children than is diagnosed, and there is a large pool of drug-resistant infection. If they are not identified as having drug-resistant TB, children are unlikely to receive appropriate and effective treatment.
â€œAfter infection with Mycobacterium tuberculosis, young children are at particularly high risk of progressing to tuberculosis disease. â€œThey are also more likely to develop more severe forms of disease such as TB meningitis and disseminated TB.â€
The report, published in The Lancet Infectious Diseases, concludes that the identified cases of drug-resistant TB in children are the tip of the iceberg, and there is a large unmet need for diagnosis, drug-susceptibility testing, and appropriate treatment.”