MPT64 antigen detection test improves routine diagnosis of extrapulmonary tuberculosis in a low-resource setting: A study from the tertiary care hospital in Zanzibar

Abstract

BackgroundExtrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting.MethodsPatients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases.ResultsPatients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%).ConclusionsWe show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.

Diagnosis of extrapulmonary tuberculosis using the MPT64 antigen detection test in a high-income low tuberculosis prevalence setting

“…Thus, the MPT64 test may strengthen the TB diagnosis in a pathology laboratory in the absence of culture confirmation. The MPT64 test performance was lower in the present study compared to previous studies [28][29][30]35]. Against a CRS, the overall sensitivity was 32% (95% CI 17-51) for the MPT64 test, compared to 67-100% in previous studies [28][29][30]35].…”

“…All previous studies were conducted in high TB burden settings, in which a higher pre-test probability of TB combined with potentially more advanced stage of TB disease at the time of diagnosis, may lead to higher test sensitivity. Still, also when using culture as a reference standard, the overall MPT64 test sensitivity was lower (19, compared to previous studies (75-100%) [26,28,30,35,37]. This could partly be explained by different procedures for culture used across the studies.…”

“…Screening was performed at a total magnification of 200x and more detailed evaluation at 400x. Fluid samples screened possibly positive were examined by a designated pathologist, who also evaluated all biopsies and FNAs, according to a previously developed guideline for interpretation [35]. Briefly, a sample was positive if a minimum of two granular red-brown coloured spots, either observed intracytoplasmic in inflammatory cells or extracellularly in necrotic material, were present in the sample.…”

“…The MPT64 test is robust and fast, and can differentiate between NTM and TB disease, as the MPT64 protein is specific for Mycobacterium tuberculosis complex (MTBC) species, and not found in NTM [32][33][34]. A recent study conducted in Zanzibar, Tanzania, has also shown that the MPT64 test is implementable in a routine TB diagnostic setting in a TB high-endemic low-resource country [35]. However, the performance of the MPT64 test has not yet been evaluated in a routine clinical setting in a low TB burden high-income country.…”

Application value of tissue tuberculosis antigen combined with Xpert MTB/RIF detection in differential diagnosis of intestinal tuberculosis and Crohn’s disease

“…Jørstad et al used immunohistochemistry to detect MPT64 antigen in 132 cases of extrapulmonary tuberculosis and non-tuberculosis specimens. MPT64 detection had the best performance in TB lymphadenitis patients and children with TB, suggesting that MPT64 detection could be used for routine diagnosis under low resource allocation to improve the diagnosis of extrapulmonary tuberculosis, especially for tuberculous lymphadenitis and children with TB [39] . Purohit et al studied 51 cases of pulmonary tuberculosis and 38 control specimens of non-pulmonary tuberculosis.The results suggested that anti-MPT64 immunostaining detection was a rapid and sensitive method for early specific diagnosis of Mycobacterium tuberculosis infection [40] .…”