How can gastro-intestinal tuberculosis diagnosis be improved? A prospective cohort study

Abstract

Gastrointestinal tuberculosis (TB) is diagnostically challenging; therefore, many cases are treated presumptively. We aimed to describe features and outcomes of gastrointestinal TB, determine whether a clinical algorithm could distinguish TB from non-TB diagnoses, and calculate accuracy of diagnostic tests. Methods We conducted a prospective cohort study of hospitalized patients in Kota Kinabalu, Sabah, Malaysia, with suspected gastrointestinal TB. We recorded clinical and laboratory characteristics and outcomes. Tissue samples were submitted for histology, microscopy, culture and GeneXpert MTB/RIF®. Patients were followed for up to two years. Results Among 88 patients with suspected gastrointestinal TB, 69 were included in analyses; 52 (75%) had a final diagnosis of gastrointestinal TB; 17 had a non-TB diagnosis. People with TB were younger (42.7 versus 61.5 years, p=0.01) and more likely to have weight loss (91% versus 64%, p=0.03). An algorithm using age <44, weight loss, cough, fever, no vomiting, albumin >26 g/L, platelets >340 x109/L and immunocompromise had good specificity (96.2%) in predicting TB, but very poor sensitivity (16.0%). GeneXpert® performed very well on gastrointestinal biopsies (sensitivity 95.7% versus culture 35.0% against a gold standard case definition of confirmed TB). Most patients (79%) successfully completed treatment and no treatment failure occurred, however adverse events (21%) and mortality (13%) among TB cases were high. We found no evidence that six months of treatment was inferior to longer courses. Conclusions The prospective design provides important insights for clinicians managing gastrointestinal TB. We recommend wider implementation of high-performing diagnostic tests such as GeneXpert® on extra-pulmonary samples.

Epidemiology of tuberculosis in Sabah, Malaysia, 2012–2018

“…Rapidly increasing GeneXpert® coverage should be a priority, especially given that a quarter of cases were not tested by culture, and of those cases that were, culture positivity was extremely low (26% among pulmonary cases). While culture negative pulmonary TB can be an indicator of early disease [27], the concurrent findings of high sputum smear positivity and high proportion of cases with moderate-advanced disease on chest X-ray, suggest the low culture positivity rate may be related to sub-optimal test sensitivity in this setting, noted in Kota Kinabalu previously [28].…”

Epidemiology of tuberculosis in Sabah, Malaysia, 2012–2018

“…While culture negative pulmonary TB can be an indicator of early disease, [27] the concurrent ndings of high sputum smear positivity and high proportion of cases with moderate-advanced disease on chest X-ray, suggest the low culture positivity rate may be related to sub-optimal test sensitivity in this setting, noted in Kota Kinabalu previously. [28] The low coverage of GeneXpert® and high proportion of culture negative or not tested cases, raises concern of drug-resistant TB being missed. The 2018 WHO estimates for MDR-TB in Malaysia for both new (1.5%) and previously treated cases (3.1%), [11] are considerably higher than what we observed in Sabah.…”

An epidemiological review of tuberculosis in Sabah, Malaysia, 2012-2018

“…While culture negative pulmonary TB can be an indicator of early disease,(30) the concurrent findings of high sputum smear positivity and high proportion of cases with moderate-advanced disease on chest x-ray, suggest the low culture positivity rate may be related to sub-optimal test sensitivity in this setting, noted in Kota Kinabalu previously. (31) The low coverage of GeneXpert® and high proportion of culture negative or not tested cases, raises concern of drug-resistant TB being missed. The 2018 WHO estimates for MDR-TB in Malaysia for both new (1.5% [1.2-1.9%]) and previously treated cases (3.1% [1.3-5.9%]),(13) are considerably higher than what we observed in Sabah.…”