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Project
Innovative diagnostic and therapeutic measures to improve MDR-TB diagnosis and management in Conakry, Guinea
Tuberculosis remains underdiagnosed despite the increase of notified drug-susceptible and rifampicin-resistant (RR) tuberculosis cases in 2017. According to the 2018 World Health Organization (WHO) report, 64% and 28.7% of the estimated number of incident drug susceptible and RR-TB cases were diagnosed. Therefore, WHO recommends contact tracing as an essential component of the End TB Strategy, and recommends to systematically screen household contacts and other close contacts for active TB (Systematic screening for active tuberculosis, WHO).
However, in most high TB burden settings, contact tracing is not yet implemented. In Guinea, diagnosis of TB mainly relies on passive case finding among patients who present with presumptive TB at the health facility and only 65% and 40% of the estimated incident number of drug-susceptible and RR-TB cases were diagnosed in 2018.
WHO recommends the use of Gene Xpert as the initial diagnostic test for all people suspected of having pulmonary TB. I However, in Guinea, microscopy still remains the initial diagnostic test for presumptive TB patients while Xpert MTB/RIF indications are limited to RR-TB risk group patients and other special TB risk groups (HIV patients, children, health workers and prisoners). Moreover, some patients may have TB but are sputum-negative, also on Xpert.
Recently, a new strategy using masks for aerosol sampling was developed. Early results showed that 65% of patients with confirmed pulmonary TB had masks positive by Xpert MTB/RIF. Another pilot investigation in South Africa in 20 patients with presumptive TB, showed that two patients had a positive Xpert MTB/RIF test on sputum while seven had a positive mask. Hence, even though aerosol sampling may not replace sputum sampling, it may increase substantially the diagnosis of TB, if used in parallel with sputum sampling. So far, no formal study assessed the systematic use of mask sampling for TB diagnosis.
RR TB management remains challenging as well. Although shorter regimens and new drugs become available, treatment outcomes are still poor. Globally, in the 2015 RR cohort, 55% completed successfully the treatment, 8% failed, 15% died, 14% were lost to follow-up and for 7% there was no outcome information. In Guinea, the WHO long regimen was used since 2008 but from August 2016, a 9-month regimen was adopted by the country. It is different from regimens used by other countries, as it relies on high-dose moxifloxacin. Treatment success rate was 76% for the 2017 RR-TB cohort. However death and lost to follow-up rate remain high: 8% and 14% respectively.
Since 2019, WHO recommends a total oral 20-month (or longer) regimen to treat RR-TB patients, but no evidence of the effectiveness of this regimen exist. In the same guideline, WHO allows countries which already implemented the 9-month shorter regimen to continue it by replacing kanamycin by amikacin, and conduct operational research on modified regimens. In Guinea, the National Tuberculosis Programme and Damien Foundation agree to continue with the 9-month regimen. Moreover, taking into account the occurrence of ototoxicity (caused by second-line injectables, such as amikacin) and the diagnosis if initial fluoroquinolone resistance, modified shorter regimens will be used in those with early signs of ototoxicity on audiometry and with a diagnosis of initial resistance to fluoroquinolone. Such a phased approach to RR-TB treatment is new and has not yet been evaluated.
Therefore, to address the RR-TB diagnostic we will evaluate with quantitative and qualitative methods an active case finding strategy using mask sampling among household contacts of RR-TB index patients. Moreover, we will study treatment outcomes of RR-TB patients with and without modified shorter treatment regimens.
To conduct this research, I apply for the 2019 PhD scholarship. I will benefit from the support of local university promotors and promotors of the ITM. We foresee a budget to cover additional expenses, and costs related to routine TB care will be covered by the Damien Foundation project.
However, in most high TB burden settings, contact tracing is not yet implemented. In Guinea, diagnosis of TB mainly relies on passive case finding among patients who present with presumptive TB at the health facility and only 65% and 40% of the estimated incident number of drug-susceptible and RR-TB cases were diagnosed in 2018.
WHO recommends the use of Gene Xpert as the initial diagnostic test for all people suspected of having pulmonary TB. I However, in Guinea, microscopy still remains the initial diagnostic test for presumptive TB patients while Xpert MTB/RIF indications are limited to RR-TB risk group patients and other special TB risk groups (HIV patients, children, health workers and prisoners). Moreover, some patients may have TB but are sputum-negative, also on Xpert.
Recently, a new strategy using masks for aerosol sampling was developed. Early results showed that 65% of patients with confirmed pulmonary TB had masks positive by Xpert MTB/RIF. Another pilot investigation in South Africa in 20 patients with presumptive TB, showed that two patients had a positive Xpert MTB/RIF test on sputum while seven had a positive mask. Hence, even though aerosol sampling may not replace sputum sampling, it may increase substantially the diagnosis of TB, if used in parallel with sputum sampling. So far, no formal study assessed the systematic use of mask sampling for TB diagnosis.
RR TB management remains challenging as well. Although shorter regimens and new drugs become available, treatment outcomes are still poor. Globally, in the 2015 RR cohort, 55% completed successfully the treatment, 8% failed, 15% died, 14% were lost to follow-up and for 7% there was no outcome information. In Guinea, the WHO long regimen was used since 2008 but from August 2016, a 9-month regimen was adopted by the country. It is different from regimens used by other countries, as it relies on high-dose moxifloxacin. Treatment success rate was 76% for the 2017 RR-TB cohort. However death and lost to follow-up rate remain high: 8% and 14% respectively.
Since 2019, WHO recommends a total oral 20-month (or longer) regimen to treat RR-TB patients, but no evidence of the effectiveness of this regimen exist. In the same guideline, WHO allows countries which already implemented the 9-month shorter regimen to continue it by replacing kanamycin by amikacin, and conduct operational research on modified regimens. In Guinea, the National Tuberculosis Programme and Damien Foundation agree to continue with the 9-month regimen. Moreover, taking into account the occurrence of ototoxicity (caused by second-line injectables, such as amikacin) and the diagnosis if initial fluoroquinolone resistance, modified shorter regimens will be used in those with early signs of ototoxicity on audiometry and with a diagnosis of initial resistance to fluoroquinolone. Such a phased approach to RR-TB treatment is new and has not yet been evaluated.
Therefore, to address the RR-TB diagnostic we will evaluate with quantitative and qualitative methods an active case finding strategy using mask sampling among household contacts of RR-TB index patients. Moreover, we will study treatment outcomes of RR-TB patients with and without modified shorter treatment regimens.
To conduct this research, I apply for the 2019 PhD scholarship. I will benefit from the support of local university promotors and promotors of the ITM. We foresee a budget to cover additional expenses, and costs related to routine TB care will be covered by the Damien Foundation project.
Datum:1 jan 2020 → Heden
Trefwoorden:B780-tropische-geneeskunde
Project type:PhD project