The value of lateral flow urine lipoarabinomannan assay and empirical treatment in Xpert MTB/RIF ultra negative patients with presumptive TB : a prospective cohort study

The value of Lateral Flow urine Lipoarabinomannan (LF-LAM) assay and the role of empiric tuberculosis (TB) treatment in the era of the highly sensitive Xpert MTB/RIF Ultra (Xpert Ultra) assay is unclear. This study aimed to assess the additional yield of LF-LAM assay when used in combination with Xpert Ultra, and the role of empiric TB treatment when Xpert Ultra used as the initial diagnostic in presumptive TB cases admitted to a tertiary hospital in Ethiopia. We performed a secondary analysis of a cohort of hospitalized Xpert MTB/RIF-negative patients. Sputum samples were examined for Mycobacterium tuberculosis by culture and Xpert Ultra. In HIV positive and severely ill patients, a urine sample was collected for the LF-LAM assay. Treatment outcome was assessed six months after enrollment. Logistic regression was used to identify factors predictive of deaths among Xpert Ultra negative patients. The Xpert Ultra assay diagnosed 31 of the 35 culture positive among the 250 hospitalized Xpert MTB/RIF-negative participants. The LF-LAM assay did not identify any case not detected by Xpert Ultra among the 52 (21.4%) participants living with HIV and the 16 patients with severe disease. Among Xpert Ultra negative patients, those who received empirical TB treatment had a similar odds of death (aOR 0.74, 95% CI: 0.1–2.7) as those not started on TB treatment. Low body mass index (≤ 18.5 kg/m(2)) was the only significant predictor of death in Xpert Ultra negative patients (aOR 4. 0, 95% CI: 1.08–14.6). In this prospective cohort, LF-LAM did not improve the diagnostic yield when used in combination with Xpert Ultra. Empiric TB treatment for Xpert Ultra negative presumptive TB cases was not associated with death at six months. Future studies in diverse settings should be to determine the optimal management of Xpert Ultra negative patients

Methicillin-resistant Staphylococcus aureus carriage among medical students of Jimma University, Southwest Ethiopia

Objectives: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are often difficult to manage due to its resistance to multiple antibiotics. This study aimed to determine the nasal carriage of MRSA and its antimicrobial susceptibility patterns among medical students at the Jimma University medical center (JUMC), Southwest Ethiopia. Methods: An institution based cross-sectional study was conducted at the JUMC from May to August; 2016. A total of 371 participants were systematically selected. Demographic data was collected using pre-designed questionnaire. Nasal swabs were collected following standard microbiological methods. MRSA was detected using cefoxitin (30μg) disc (Oxoid, UK); and antimicrobial susceptibility tests were performed by disc diffusion method. Results: A total of 371 students were included. Of these, 84.9% (315/371) were males. The overall prevalence of nasal carriage of S. aureus and MRSA among medical students at JUMC were 22.1% (82/371) and 8.4 % (31/371), respectively. The carriage rate of MRSA among medical intern (20% (16/80)) was higher compared with clinical year-I (3.6% (6/166)) and year-II (7.2% (9/125)) students. Resistance against trimethoprim-sulfamethoxazole, tetracycline and ciprofloxacin were 83.9%, 64.5% and 51.6%, respectively. Longer stay in hospital was significantly associated with the acquisition of MRSA (X2 = 6.93, P value = 0.031). Conclusion: The prevalence of nasal carriage of MRSA was high. Longer stay in hospital environment was associated with the acquisition of MRSA. These findings suggest that infection control efforts focusing the performance of antimicrobial stewardship could have a significant impact on MRSA incidence in this setting

Ewunetu T: Acceptance of Provider Initiated HIV Testing and Counseling among Tuberculosis Patients

Human immunodeficiency virus (HIV) is a powerful risk factor for the development of tuberculosis. This study assessed the acceptance and associated factors that can affect provider initiated HIV testing and counseling (PITC) among tuberculosis patients at the East Wollega administrative zone, Oromia regional state, western Ethiopia, from January to August, 2010. A single population proportion formula is used to calculate the total sample size of 406 and the cluster sampling technique was used to select 13 health centers that provide PITC services. The sample size was proportionally allocated to each health center. The study participants were selected using a simple random sampling technique using the lottery method. Structured questionnaire was used for collection of sociodemographic data. From the total of study subjects, 399 (98.2%) TB patients were initiated for HIV test and 369 (92.5%) patients accepted the initiation. Of those, 353 (95.5%) patients had taken HIV test and received their results. According to the reviewed documents, the prevalence of HIV among tuberculosis (TB) patients in the study area was 137 (33.7%). The logistic regression result showed the PITC was significantly associated with their knowledge about HIV (AOR = 3.22, 95% CI: 1.3-7.97), selfperceived risk (AOR = 2.93, 95% CI: 1.12-7.66), educational status (AOR = 3.51, 95% CI: 1.13-10.91), and knowledge on transmission of HIV/AIDS (AOR = 7.56, 95% CI: 1.14-40.35) which were significantly associated with the acceptance of PITC among TB patients. Therefore, this study's results showed, the prevalence of HIV among TB patient was high; to enhance the acceptance of PITC among TB patients, health extension workers must provide health education during home-to-home visiting. TB treatment supervisors also provide counseling intensively for all forms of TB patients during their first clinical encounter

Acceptance of Provider Initiated HIV Testing and Counseling among Tuberculosis Patients in East Wollega Administrative Zone, Oromia Regional State, Western Ethiopia

Human immunodeficiency virus (HIV) is a powerful risk factor for the development of tuberculosis. This study assessed the acceptance and associated factors that can affect provider initiated HIV testing and counseling (PITC) among tuberculosis patients at the East Wollega administrative zone, Oromia regional state, western Ethiopia, from January to August, 2010. A single population proportion formula is used to calculate the total sample size of 406 and the cluster sampling technique was used to select 13 health centers that provide PITC services. The sample size was proportionally allocated to each health center. The study participants were selected using a simple random sampling technique using the lottery method. Structured questionnaire was used for collection of sociodemographic data. From the total of study subjects, 399 (98.2%) TB patients were initiated for HIV test and 369 (92.5%) patients accepted the initiation. Of those, 353 (95.5%) patients had taken HIV test and received their results. According to the reviewed documents, the prevalence of HIV among tuberculosis (TB) patients in the study area was 137 (33.7%). The logistic regression result showed the PITC was significantly associated with their knowledge about HIV (AOR = 3.22, 95% CI: 1.3–7.97), self-perceived risk (AOR = 2.93, 95% CI: 1.12–7.66), educational status (AOR = 3.51, 95% CI: 1.13–10.91), and knowledge on transmission of HIV/AIDS (AOR = 7.56, 95% CI: 1.14–40.35) which were significantly associated with the acceptance of PITC among TB patients. Therefore, this study’s results showed, the prevalence of HIV among TB patient was high; to enhance the acceptance of PITC among TB patients, health extension workers must provide health education during home-to-home visiting. TB treatment supervisors also provide counseling intensively for all forms of TB patients during their first clinical encounter

Discordance between genotypic and phenotypic methods for the detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis and the correlation with patient treatment outcomes

Background: Accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis (MTB) is essential for proper patient management. We investigated discordance between genotypic (Xpert MTB/RIF and MTBDRplus) and phenotypic (MGIT 960) methods for the detection of rifampicin (RIF) and isoniazid (INH) resistant MTB and its correlation with patient treatment outcomes in Jimma, Southwest Oromia, Ethiopia. Methods: A retrospective study was conducted on 57 stored MTB isolates with known Xpert RIF resistance status (45 RIF resistant and 12 RIF susceptible) at Jimma University Mycobacteriology Research Center from November 2, 2021, to December 28, 2022. We did MTBDRplus and phenotypic DST (using the Mycobacterial Growth Indicator Tube (MGIT) system). The Xpert and MTBDRplus results were compared using phenotypic DST as a reference standard method. The treatment outcome was determined as per national guideline. The discordance between the genotypic and phenotypic DST was calculated using GraphPad software. Results: Among the 57 MTB isolates, six (10.5 %) had discordant results between the two DST methods. Xpert yielded five discordant results for RIF when compared with phenotypic DST (kappa coefficient (κ) = 0.76, 95 % confidence interval 0.56–0.96). The MTBDRplus compared with phenotypic DST gave three discordant results for RIF (κ = 0.86, 95 % confidence interval 0.71–1.00) and three for INH (κ = 0.86, 95 % confidence interval 0.70–1.00). Compared with Xpert, MTBDRplus yielded lower discordance with phenotypic DST for RIF. Out of six patients with discordant results, three had unfavorable outcomes while the other three were cured. Of the three patients with unfavorable outcomes, only one patient has received an inappropriate treatment regimen. There was no correlation between unfavorable outcomes and incorrect treatment regimens due to discordant results (Χ2 = 0.404; P = 0.525). Conclusions: Discordance between genotypic and phenotypic DST for RIF or INH occurred in 10.5 % of isolates. Only one patient with discordant results has received an inappropriate treatment regimen, resulting in an unfavorable outcome. The impact of parallel use of rapid molecular assay with phenotypic DST on patient treatment outcomes requires further study

Bacterial pathogens in Xpert MTB/RIF Ultra-negative sputum samples of patients with presumptive tuberculosis in a high TB burden setting : a 16S rRNA analysis

Abstract: In patients with presumptive tuberculosis (TB) in whom the diagnosis of TB was excluded, understanding the bacterial etiology of lower respiratory tract infections (LRTIs) is important for optimal patient management. A secondary analysis was performed on a cohort of 250 hospitalized patients with symptoms of TB. Bacterial DNA was extracted from sputum samples for Illumina 16S rRNA sequencing to identify bacterial species based on amplicon sequence variant level. The bacterial pathogen most likely to be responsible for the patients' LRTI could only be identified in a minority (6.0%, 13/215) of cases based on 16S rRNA amplicon sequencing: Mycoplasma pneumoniae (n = 7), Bordetella pertussis (n = 2), Acinetobacter baumanii (n = 2), and Pseudomonas aeruginosa (n = 2). Other putative pathogens were present in similar proportions of Xpert Ultra-positive and Xpert Ultra-negative sputum samples. The presence of Streptococcus (pseudo)pneumoniae appeared to increase the odds of radiological abnormalities (aOR 2.5, 95% CI 1.12-6.16) and the presence of S. (pseudo)pneumoniae (aOR 5.31, 95% CI 1.29-26.6) and Moraxella catarrhalis/nonliquefaciens (aOR 12.1, 95% CI 2.67-72.8) increased the odds of 6-month mortality, suggesting that these pathogens might have clinical relevance. M. pneumoniae, B. pertussis, and A. baumanii appeared to be the possible causes of TB-like symptoms. S. (pseudo)pneumoniae and M. catarrhalis/nonliquefaciens also appeared of clinical relevance based on 16S rRNA amplicon sequencing. Further research using tools with higher discriminatory power than 16S rRNA sequencing is required to develop optimal diagnostic and treatment strategies for this population.IMPORTANCEThe objective of this study was to identify possible bacterial lower respiratory tract infection (LRTI) pathogens in hospitalized patients who were initially suspected to have TB but later tested negative using the Xpert Ultra test. Although 16S rRNA was able to identify some less common or difficult-to-culture pathogens such as Mycoplasma pneumoniae and Bordetella pertussis, one of the main findings of the study is that, in contrast to what we had hypothesized, 16S rRNA is not a method that can be used to assist in the management of patients with presumptive TB having a negative Xpert Ultra test. Even though this could be considered a negative finding, we believe it is an important finding to report as it highlights the need for further research using different approaches

Drug resistance-conferring mutations in Mycobacterium tuberculosis from pulmonary tuberculosis patients in Southwest Ethiopia

Objective/background: The nature and frequency of mutations in rifampicin (RIF) and isoniazid (INH) resistant Mycobacterium tuberculosis isolates vary considerably according to geographic locations. However, information regarding specific mutational patterns in Ethiopia remains limited. Methods: A cross-sectional prospective study was carried out among confirmed pulmonary tuberculosis cases in Southwest Ethiopia. Mutations associated with RIF and INH resistances were studied using GenoType MTBDRplus line probe assay in 112 M. tuberculosis isolates. Culture (MGIT960) and identification tests were performed at the Mycobacteriology Research Center of Jimma University, Jimma, Ethiopia. Results: Mutations conferring resistance to INH, RIF, and multidrug resistance were detected in 36.6% (41/112), 30.4% (34/112), and 27.7% (31/112) of M. tuberculosis isolates respectively. Among 34 RIF-resistant isolates, 82.4% (28/34) had rpoB gene mutations at S531L, 2.9% (1/34) at H526D, and 14.7% (5/34) had mutations only at wild type probes. Of 41 INH-resistant strains, 87.8% (36/41) had mutations in the katG gene at Ser315Thr1 and 9.8% (4/41) had mutations in the inhA gene at C15T. Mutations in inhA promoter region were strongly associated with INH monoresistance. Conclusion: A high rate of drug resistance was commonly observed among failure cases. The most frequent gene mutations associated with the resistance to INH and RIF were observed in the codon 315 of the katG gene and codon 531 of the rpoB gene, respectively. Further studies on mutations in different geographic regions using DNA sequencing techniques are warranted to improve the kit by including more specific mutation probes in the kit

Resistance to pyrazinamide in Mycobacterium tuberculosis complex isolates from previously treated tuberculosis cases in Southwestern Oromia, Ethiopia

Objective: Pyrazinamide (PZA) susceptibility testing is important to develop evidence-based algorithms for case management. We aimed to assess the prevalence of PZA-resistance and its impact on treatment outcomes in previously treated tuberculosis (TB) cases in southwestern Oromia, Ethiopia. Methods: A Phenotypic Drug Susceptibility Testing (DST) of PZA with BACTEC MGIT 960 was conducted at the Mycobacteriology Research Center of Jimma University (MRC-JU) from June to November 2021 on sixty-six Mycobacterium tuberculosis complex (MTBC) isolates from previously treated TB cases. SPSS software package version 21 was used. The differences in the proportion of PZA resistance between the groups were compared using the chi squared test. Logistic regression was used to identify the association between PZA resistance and treatment outcomes. Results: Among 66 MTBC isolates (49 rifampicin-resistant and 17 rifampicin-sensitive) included in this study, 31.8 % were resistant to PZA. The proportion of PZA resistance was almost three times higher in previously treated TB cases with rifampicin resistance than in rifampicin-sensitive patients (38.8 % vs. 11.8 %, p = 0.039). An unfavorable treatment outcome was documented for 23 % (15/65) of the participants. Patients with PZA resistance were almost four times more likely to have an unfavorable treatment outcome than patients with PZA sensitive (aOR 4.2, 95 % CI: 1.13–15.3). Conclusions: The prevalence of PZA resistance was high compared to the pooled PZA resistance estimated worldwide. The majority of TB cases with PZA resistance had an unfavorable treatment outcome. PZA susceptibility testing should be included in the multidrug-resistant TB diagnostic algorithm to improve management of these patients