SNPT often gets missed from the diagnosis of consideration—particularly in developing countries like Nepal—though it accounts 30-65% of total PTB cases(7)(6). With this backdrop, the study was conducted to discover the actual incidence of PTB among presumptive cases which was not done before in Nepal. The application of Xpert MTB/RIF assay, in our setting, substantially increases the confirmed PTB cases. During our research period, 4.6% smear-positive PTB cases were reported at TUTH while upon execution of gene Xpert as a diagnostic tool, the rate surged to 16.5% (n=85/515). Our study is consistent with other studies, conducted in developing countries, which have suggested the benefit of Xpert in smear-negative patients(9)(10)(11)(12).
We aimed to include all presumptive cases, the infective forms i.e. PTB and tries to break the transmission chain with speedy diagnosis as far as possible. Hence, we opted for the Xpert MTB/RIF assay. In most, research studies and meta-analysis performed to this date, higher specificity of the test up to 99% has been observed on sputum samples(13)(14)(15)(10). Since, our study was not an evaluation, comparisons and implementation testing of gene Xpert assay against other diagnostic tests, limited studies found conducted in Nepal encompassing like our rationale(4).
In our study, we compare, likely occurring clinical features present in PTB patients with that gene Xpert results in SNPT cases. The only clinical feature to show a statistically significant difference between the groups was cough and chest pain. As portrayed with the latest meta-analysis and perspectives study where the sensitivity of cough as a positive predictive PTB ranges from 79.9% to 82% (16)(17). Hence, these clinical features could be one of the triaging features in optimizing the test where gene Xpert was not accessible to anyone—particularly in low-income-countries.
The cost expense of the test is another tethering truth with which the developing countries are being suffering. In most developing countries, the limited public hospital (covered with Global Fund) provides gene Xpert testing facility owing to expensive test cartridge and running cost which is nearly impossible for private health centers to afford. The test accessibility to every patient is the fundamental right and should be guaranteed by every nation. Therefore, government policy with a public-private partnership for the infection eradication is obligatory.
Ironically, in Nepal as NTP, with a policy to economize cost per cartridge on par to patient’s number and also to make accessible on targeted population, had endorsed a guideline for the test. Patient with abnormal chest X-ray, presumed MDR patient, people living with HIV/AIDS (PLHA) and those with treatment failure cases were eligible for the test as described in the method section. Relying upon the guideline, we included the chest X-ray as a triaging test. In our study, common radiological findings evident in positive cases were upper lobe infiltrates (36.4%) and pleural effusion (40.4%). A similar study was conducted in our nearby hospital and neighboring country(India) where upper-lobe infiltrates and cavitary lesions were the common features(4)(18). Further, as to extrapolate the role of X-ray in PTB diagnosis, we compared the relationship between abnormal impressions vs. positive cases. We found, 23.38% of patients with abnormal chest X-ray had acquired PTB while Dutta et al. reported 34.4% in patients with similar features (18).
Although, higher percentage of new suspects 63(23.5%) found positive on Gene Xpert testing compared to previously treated cases 20(22.5%); 2(2.2%) MDR cases were recovered from the patient with a previous history of ATT, of total 89 previously treated cases enrolled. However, a small population of previously-treated case was included in our study, the findings portrayed similar view of resistance-trend as surveyed in 1992–1993 in the Western Cape Province where 8.6% acquired and 3.2% initial drug resistance was noted in among these patients (19). In another studies, the highest in range from 15-27.7%, MDR-TB was found to be associated in previously treated cases, however(20)(21). Furthermore, the previously treated patients may be at high risk of extensively drug-resistant(XDR)TB too (19). Hence, the clinicians must be cautious in treating the previously treated cases.
Of total positive cases, 3.5% (n=3) were valid rifampicin-resistant (confirmed with Line probe assay); no false-positive rifampicin resistance was noted as reported in different literature with gene Xpert testing(15)(13)(22)(23). Round the globe, about one-third of the countries had surveyed on the incidence of MDR-TB which was in between 2-14%(24)(25)(26) ; our findings coincide within this range.
For improving patient care and abbreviating the disease transmission chain, speedy detection of tuberculosis and its drug-resistance with precision is crucial. In this perspective, endorsing gene Xpert as a diagnostic tool by WHO is the commendable action in curbing the global threat to some extent. Further, a long-distance yet to be traveled: making it more accessible, affordable, and upgrading sensitivity of Xpert MTB/RIF assay also covering disseminated TB. Only then billions of dollars expended could be a wise investment.
Limitations
Inability to include large samples was the major drawback of our study. Additional SNPT cases could be still missing from our study frame since is the test is not of absolute accuracy. Also, we could not run the phenotypic DST and Line Probe assay for all Xpert MTB/RIF positive specimens. If it was possible, clear MDR status could be traced which might be missed even from Xpert MTB/RIF assay.