Experiences from Bangladesh, Bhutan, Egypt and Mongolia
Implementation research teams funded by the TDR’s impact grants for regional priorities in four countries have studied different aspects of integrating GeneXpert* molecular testing technology into national health systems so as to improve the speed and precision of detecting Mycobacterium tuberculosis (which causes TB) and resistance to the antibiotic rifampicin.
The four studies: (1) explored the use of filter paper-based diagnosis of smear-negative pulmonary tuberculosis (TB) (Bangladesh); (2) assessed what is needed for the setup and integration of GeneXpert in a national healthcare system (Bhutan); (3) evaluated the cost effectiveness of adopting the GeneXpert diagnostic algorithm versus use of the standard algorithm to diagnose TB (Egypt); and (4) integrated GeneXpert in a new standard operating procedure in the national health system that improves the precision of identifying TB in young children (Mongolia).
These experiences offer insight and tools that can benefit health services in other countries that either already work with GeneXpert or plan to integrate it into their own national health systems.
The importance of GeneXpert in the diagnosis of TB
TB is one of the world’s most infectious diseases, affecting millions of people every year – particularly in low-income countries where access to health care is limited. In 2014 there were 9.6 million new cases of TB and 1.5 million TB deaths. The global incidence of TB is decreasing at a critically-slow pace – by less than 2% yearly. Effective TB control is compromised by the inefficiency of traditional diagnostic tests (which can take more than two months to deliver results) and the emergence of multidrug-resistant (MDR) TB.
GeneXpert is a rapid molecular test that allows the detection of M. tuberculosis and simultaneously detects resistance to the antibiotic rifampicin, all in less than two hours. DNA sequences that are specific to M. tuberculosis are detected by polymerase chain reaction (PCR). The technology is viewed as being cost-effective: its use requires minimal laboratory equipment, space and technician time.
GeneXpert is recommended by WHO for effective diagnosis of TB in TB-endemic countries. The tool enables healthcare professionals to improve the speed and quality of TB diagnosis and helps diagnose TB in patients that are likely to be missed by traditional screening tests. The fact that it allows diagnosis of TB at the same time as pinpointing resistance to rifampicin treatment is key to minimizing the transmission of drug-resistant TB in TB-endemic countries.
Bangladesh: Assessing the efficacy of filter paper-based MTB/RIF TB diagnosis for smear-negative pulmonary TB
Researchers at the International Centre for Diarrhoeal Disease Research in Bangladesh (icddr,b) investigated the efficacy of filter paper-based MTB/RIF TB (M. tuberculosis TB [MTB] and resistance to rifampicin [RIF]) in diagnosing smear-negative pulmonary TB cases using GeneXpert technology.
Bhutan: Data and operational protocols: how to integrate GeneXpert in the national health system
The research team from the Royal Center for Disease Control in Bhutan guided the integration of GeneXpert in the national healthcare system to improve the diagnosis and management of drug-resistant TB. GeneXpert outputs were integrated with the national Tuberculosis Information & Surveillance System database to allow sharing across all TB laboratories nationally, giving physicians rapid access to all TB-related information
A key challenge for the team was to convert paper-based data into a digital format in order to integrate GeneXpert outputs with the national database. This digital transformation of TB reporting data and services called on the expertise of a group of international experts that advised and trained Bhutanese health professionals. The experts also advised the staff of Bhutanese laboratories on gene sequencing. Physicians were invited to train in the Philippines at the National Tuberculosis Reference Laboratory and the Research Institute for Tropical Medicine, as well as at the London School of Hygiene & Tropical Medicine.
The learning from the project resulted in the reassessment of the country’s protocol for TB management, using GeneXpert for enhanced TB case detection. The focus on high-risk suspects of MDR TB was expanded to use GeneXpert for detecting all areas of drug resistance.
Egypt: Analysing the cost effectiveness of using GeneXpert to diagnose MDR TB
The research team at Egypt’s National Tuberculosis Control Programme evaluated the cost effectiveness of adopting the GeneXpert diagnostic algorithm incorporated with sputum microscopy (smear microscopy) compared with using the standard algorithm of smear microscopy and culture. Their specific focus was on low- and middle-income settings.
The team confirmed that GeneXpert is more cost effective than conventional smear microscopy for HIV-negative individuals suspected to have TB. In this study, the tool proved to be effective in identifying people who are TB-positive and in confirming when patients do not have TB. Total treatment costs, including hospitalization and costs related to complications of TB, were reduced by 53.4%.
During the project the researchers developed a decision analysis model of the diagnostic process, starting with TB suspects, progressing to TB cases, and ending with treatment (also taking into account associated complications). The model presents incremental cost per Disability Adjusted Life Year (DALY), comparing the GeneXpert algorithm incorporated with smear microscopy with the standard algorithm of smear microscopy and culture used to detect suspected TB cases. The model was used to calculate the incremental cost effectiveness ratio for GeneXpert with smear compared to the base case of smear and culture. A group of junior health economists were trained to use this approach to carry out economic evaluation studies as part of this work. The team reported that their model suggests that GeneXpert is cost effective in a variety of settings; however, the TB diagnostic costs can increase as GeneXpert use is scaled up.
At the national level, the research recommends GeneXpert as very cost effective in different scenarios. It advises that further cost-effectiveness studies will be useful, especially for high prevalence countries. In Egypt, additional studies are needed to measure the quality of life for Egyptians and to address the prevalence of complications caused by TB.
Mongolia: Improving TB diagnosis in young children
The research team at Mongolia’s National Center for Communicable Diseases focused on how GeneXpert can improve TB diagnosis in young children. Their research developed a standard operating procedure (SOP) for the GeneXpert ultra version (that has a new algorithm and improved cartridge design) to diagnose M. tuberculosis and extrapulmonary TB.
The goal was to convert study results into guidelines for use in the Ministry of Health’s algorithm in order to increase the detection of TB in children. (This approach is especially useful when clinicians have to make decisions for children without bacteriological evidence.)
TB mortality is under-recognized in the paediatric population as diagnosis is difficult for younger patients – specimen collection depends on the physician’s experience. Pulmonary TB should be diagnosed with sputum, but how the sputum is produced has a major effect on the presence of mycobacteria in the laboratory specimen.
By including children in the research, investigators demonstrated practices for diagnosing younger patients. Using GeneXpert, they determined the percentage of drug resistance by testing for drug sensitivity when the presence of TB is confirmed by microbiology.
These findings allowed the algorithm for detecting paediatric TB in Mongolia to be updated. These modifications and a description of GeneXpert’s efficacy are now included in the national TB care guidelines, approved by the Mongolian Ministry of Health, and applied in daily practice in the health services.
*GeneXpert for detecting Mycobacterium tuberculosis and resistance to the antibiotic rifampicin is also known as Xpert MTB/RIF.
THE FOUR PROJECTS FUNDED BY TDR’S IMPACT GRANTS FOR REGIONAL PRIORITIES
Exploring the efficacy of filter paper-based GeneXpert MTB/RIF in diagnosing smear negative pulmonary tuberculosis cases
Golam HASNAIN – mdgolam.hasnain@uon.edu.au
International Centre for Diarrhoeal Disease Research
BANGLADESH (2014)
Assessment and optimization of first-time implementation of GeneXpert to improve the diagnosis and management of drug-resistant TB in Bhutan
Lila ADHIKARI – l.adhikari@massey.ac.nz; lila09phl@gmail.com
Royal Center for Disease Control, Thimphu
BHUTAN (2016)
Cost effectiveness analysis of adopting GeneXpert (GX) in different regimens for the diagnosis of multi-drug resistant tuberculosis in Egypt
Amal MOAWAD, Ahmed Salem DRAMANY– amalnewlife82@gmail.com; amal_newlife82@yahoo.com
National Tuberculosis Control Programme
EGYPT (2017)
Study for improvement of tuberculosis diagnosis among children using GeneXpert MTB/RIF in Ulaanbaatar
Buyanshishig BURNEEBAATAR – bb_buyankhishig@yahoo.com; toyuntuya_4@yahoo.com
National Center for Communicable Diseases
MONGOLIA (2016)
For more information, please contact Dr Garry Aslanyan