Time to Develop and Predictors for Incidence of Tuberculosis among Children Receiving Antiretroviral Therapy

Infection by the human immune deficiency virus (HIV) is the strongest risk factor for latent or new infection of tuberculosis (TB) through reduction of CD4 T-lymphocytes and cellular immune function. Almost one-third of deaths among people living with HIV are attributed to tuberculosis. Despite this evidence, in Ethiopia, there is a scarcity of information regarding the incidence of tuberculosis for children living with HIV. Thus, this study assessed time to develop and predictors for incidence of tuberculosis in children attending HIV/AIDS care in public hospitals: North West Ethiopia 2021. Methods. A facility-based retrospective cohort study was conducted among 421 seropositive children on antiretroviral therapy in two hospitals between January 1, 2011 and December 31, 2020. EPI-DATA version 3.2 and STATA/14 software were used for data entry and analysis, respectively. Tuberculosis-free survival time was estimated using the Kaplan-Meier survival curve. Bivariate and multivariable Cox regression model was fitted to identify predictors at a P value <0.05 within 95% CI. Results. In the final analysis, a total of 421 seropositive children were included, of whom, 64 (15.2%) developed tuberculosis at the time of follow-up. The mean (±SD) age of the children was 10.62 ± 3.32 years, with a median (IQR) time to develop TB that was 23.5 ( IQR = ± 19 ) months. This study found that the incidence of tuberculosis was 5.9 (95% CI: 4.7; 7.6) per 100 person-years (PY) risk of observation. Cases at baseline not taking cotrimoxazol preventive therapy (CPT) ( AHR = 2.5 ; 95% CI, 1.4-4.7, P < 0.021 ), being severely stunted ( AHR = 2.9 : 95% CI, 1.2-7.8, P < 0.03 ), and having low hemoglobin level ( AHR = 4.0 ; 95% CI, 2.1-8.1, P < 0.001 ) were found to be predictors of tuberculosis. Conclusion. A higher rate of tuberculosis incidence was reported in our study as compared with previous studies in Ethiopia. Cases at baseline not taking cotrimoxazol preventive therapy (CPT), being severely stunted, and having low hemoglobin (≤10 mg/dl) levels were found to be at higher risk to developed TB incidence.

Mycobacterial Lineages Associated with Drug Resistance in Patients with Extrapulmonary Tuberculosis in Addis Ababa, Ethiopia

Background. In Ethiopia, tuberculosis (TB) is one of the most common causes of illness and death. However, there is limited information available on lineages associated with drug resistance among extrapulmonary tuberculosis patients in Ethiopia. In this study, researchers looked into Mycobacterium tuberculosis lineages linked to drug resistance in patients with extrapulmonary tuberculosis in Addis Ababa, Ethiopia. Methods. On 151 Mycobacterium tuberculosis isolates, a cross-sectional analysis was performed. Spoligotyping was used to characterize mycobacterial lineages, while a phenotypic drug susceptibility test was performed to determine the drug resistance pattern. Data were analyzed using SPSS version 23. Results. Among 151 Mycobacterium tuberculosis complex (MTBC) genotyped isolates, four lineages (L1–L4), and Mycobacterium bovis were identified. The predominantly identified lineage was Euro-American (73.5%) followed by East-African-Indian (19.2%). Any drug resistance (RR) and multidrug-resistant (MDR) tuberculosis was identified among 16.2% and 7.2% of the Euro-American lineage, respectively, while it was 30.8% and 15.4% among the East-African-Indian lineages. Among all three preextensively drug-resistance (pre-XDR) cases identified, two isolates belong to T3-ETH, and the other one strain was not defined by the database. There was no statistically significant association between any type of drug resistance and either lineage or sublineages of Mycobacterium tuberculosis. Conclusion. A higher proportion of any type of drug resistance and MDR was detected among the East-African-Indian lineage compared to others. However, there was no statistically significant association between any type of drug resistance and either lineages or sublineages. Thus, the authors recommend a large-scale study.

Treatment Outcomes and Associated Factors in Tuberculosis Patients at Atwima Nwabiagya District, Ashanti Region, Ghana: A Ten-Year Retrospective Study

Introduction. Tuberculosis poses a great threat to public health around the globe and affects persons mostly in their productive age, notwithstanding; everyone is susceptible to tuberculosis (TB) infection. To assess the effectiveness and performance of the tuberculosis control program activities, the percentage of cases with treatment success outcome is key. To control tuberculosis, interrupting transmission through effective treatment cannot be overemphasized. The study was conducted to determine factors associated with TB treatment outcome, in the Atwima Nwabiagya District from 2007–2017. Method. A Retrospective review of routine/standard TB registers was carried out in five directly observed therapy short-course (DOTS) centres at the Atwima Nwabiagya District from January 2007 to December 2017. Demographic characteristics, clinical characteristics, and treatment outcomes were assessed. Bivariate and multivariate logistic regression was conducted to determine the predictors of successful treatment outcome. Results. Of the 891 TB client’s data that was assessed in the district, the treatment success rate was 68.46%. Patients, aged ≤ 20 years (adjusted odds ratio aOR = 4.74 , 95 % CI = 1.75 − 12.83 ) and 51-60 years ( aOR = 1.94 , 95 % CI = 1.12 − 3.39 ), having a pretreatment weight of 35-45 kg ( aOR = 2.54 , 95 % CI = 1.32 − 4.87 ), 46-55 kg ( aOR = 2.75 , 95 % CI = 1.44 − 5.27 ) and 56-65 kg ( aOR = 3.04 , 95 % CI = 1.50 − 6.14 ) were associated with treatment success. However, retreatment patients ( aOR = 0.31 , 95 % CI = 0.11 − 0.84 ) resulted in unsuccessful treatment outcome. Conclusion. Successful treatment outcome among TB patients was about 20.00% and 30.00% lower compared to the national average treatment success rate and WHO target, respectively. Active monitoring, motivation, and counselling of retreatment patients and patients with advanced age are key to treatment success.

Diversity of Mycobacterium tuberculosis Complex Lineages Associated with Pulmonary Tuberculosis in Southwestern, Uganda

Uganda is among the 22 countries in the world with a high burden of tuberculosis. The southwestern region of the country has consistently registered a high TB/HIV incidence rate. This study is aimed at characterizing the Mycobacterium tuberculosis complex (MTBC) genotypic diversity in southwestern Uganda. A total of 283 sputum samples from patients with pulmonary tuberculosis were genotyped using specific single nucleotide polymorphism markers for lineages 3 and 4. Most of the patients were males with a mean age of 34. The lineage 4 Ugandan family was found to be the most dominant strains accounting for 59.7% of all cases followed by lineage 3 at 15.2%. The lineage 4 non-Ugandan family accounted for 14.5% of all cases while 4.2% showed amplification for both lineage 4 and lineage 3. Eighteen samples (6.4%) of the strains remained unclassified since they could not be matched to any lineage based on the genotyping technique used. This study demonstrates that a wide diversity of strains is causing pulmonary tuberculosis in this region with those belonging to the lineage 4 Ugandan family being more predominant. However, to confirm this, further studies using more discriminative genotyping methods are necessary.

Engaging Informal Private Health Care Providers for TB Case Detection: Experiences from RIPEND Project in India

Background. Informal (unqualified) health care providers are an important source of medical care for persons with presumptive TB (PPTB) in India. A project (titled RIPEND) was implemented to engage informal providers for the identification of PPTBs and TB patients in 4 districts of Telangana State, India, during October 2018-December 2019 project period. Engagement involved sensitizing the informal providers about TB, providing them financial incentives to identify PPTBs, and linking these PPTBs to diagnostic and treatment services provided by the Government of India’s National TB Elimination Programme. Objectives. To describe (a) the characteristics of the informal providers, along with their self-reported practices on TB diagnosis, treatment, and challenges encountered by the RIPEND project staff in engaging them in the project and (b) the outputs and outcomes of this engagement. Methods. We used a combination of one-on-one interviews with informal providers, group interviews with RIPEND project staff, and secondary analysis of data available within the project’s recording and reporting systems. Results. A total of 555 informal providers were actively engaged under the project. The majority (87%) had a nonmedicine-related graduate degree and had been providing medical care for more than 10 years. Most (95%) were aware that a cough for 2 weeks or more is a symptom of pulmonary TB and that such patients should be referred for sputum-smear microscopy at a government health facility. Challenges in engaging the informal providers included motivating them to participate in the study, suboptimal mobile usage for referral services, and delays in providing financial incentives to them for referring PPTBs. During the project period (October 2018-December 2019), 8342 PPTBs were identified of which 1003 TB patients were detected and linked to TB treatment services. Conclusion. This project showed that engaging informal providers is feasible and that a large number of PPTB and TB patients can be identified through this effort. The Government of India should consider engaging informal providers for the early diagnosis of TB to reduce the missing TB cases in the country.

Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory

Background. To cure drug-resistant (DR) tuberculosis (TB), the antituberculous treatment should be guided by Mycobacterium tuberculosis drug-susceptibility testing (DST). In this study, we compared conventional DST performed in Minsk, Belarus, a TB DR high-burden country, with extensive geno- and phenotypic analyses performed at the WHO TB Supranational Reference Laboratory in Copenhagen, Denmark, for TB/HIV coinfected patients. Subsequently, DST results were related to treatment regimen and outcome. Methods. Thirty TB/HIV coinfected patients from Minsk were included and descriptive statistics applied. Results. Based on results from Minsk, 10 (33%) TB/HIV patients had drug-sensitive TB. Two (7%) had isoniazid monoresistant TB, 8 (27%) had multidrug-resistant (MDR) TB, 5 (17%) preextensive drug-resistant (preXDR) TB, and 5 (17%) had extensive drug-resistant (XDR) TB. For the first-line drugs rifampicin and isoniazid, there was DST agreement between Minsk and Copenhagen for 90% patients. For the second-line anti-TB drugs, discrepancies were more pronounced. For 14 (47%) patients, there were disagreements for at least one drug, and 4 (13%) patients were classified as having MDR-TB in Minsk but were classified as having preXDR-TB based on DST results in Copenhagen. Initially, all patients received standard anti-TB treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. However, this was only suitable for 40% of the patients based on DST. On average, DR-TB patients were changed to 4 (IQR 3-5) active drugs after 1.5 months (IQR 1-2). After treatment adjustment, the treatment duration was 8 months (IQR 2-11). Four (22%) patients with DR-TB received treatment for >18 months. In total, sixteen (53%) patients died during 24 months of follow-up. Conclusions. We found high concordance for rifampicin and isoniazid DST between the Minsk and Copenhagen laboratories, whereas discrepancies for second-line drugs were more pronounced. For patients with DR-TB, treatment was often insufficient and relevant adjustments delayed. This example from Minsk, Belarus, underlines two crucial points in the management of DR-TB: the urgent need for implementation of rapid molecular DSTs and availability of second-line drugs in all DR-TB high-burden settings. Carefully designed individualized treatment regimens in accordance with DST patterns will likely improve patients’ outcome and reduce transmission with drug-resistant Mycobacterium tuberculosis strains.

Factors Influencing Adherence to Tuberculosis Treatment in the Ketu North District of the Volta Region, Ghana

Annually, ten million cases of tuberculosis (TB) and about 1.8 million mortalities are recorded. Adherence to TB treatment not only reduces death outcomes but prevents prolonged sickness, transmission to others, and the development of multidrug-resistant TB. This study is aimed at determining the rate of treatment adherence, knowledge of TB infection, and the possible factors influencing adherence to TB treatment in the Ketu North District in the Volta Region of Ghana. A cross-sectional study design was employed. A semistructured questionnaire was used to obtain data from respondents. Adherence to TB treatment and knowledge level about TB infection were assessed. A Chi-square test analysis was used to determine the variables that were associated with treatment adherence. Logistic regression analysis was used to determine potential factors that contribute to treatment adherence. A total of 125 TB registrants were enrolled in the study. The majority (102 (81.6%)) adhered to the TB treatment regimen. However, the level of knowledge about night sweat being a symptom of TB infection was relatively low (78 (62.4%)). Logistic regression analysis revealed that the male gender was about three times more likely ( OR = 2.978 , 95 % CI = 1.173 ‐ 7.561 ; p = 0.022 ) to be associated with adherence to TB treatment. However, food availability ( OR = 2.208 , 95% CI (0.848-5.753); p = 0.10 ) and household size ( OR = 0.538 , 95% CI (0.195-1.483); p = 0.23 ) were not significantly associated with treatment adherence. In this study, adherence to TB treatment and the knowledge level of TB infection were high. However, the knowledge level of night sweat being a symptom of TB infection was relatively low. Being a male was significantly associated with treatment adherence. An intensified health education on the symptoms of TB infection is therefore recommended.

Accuracy and Incremental Yield of the Chest X-Ray in Screening for Tuberculosis in Uganda: A Cross-Sectional Study

The WHO END TB strategy requires ≥90% case detection to combat tuberculosis (TB). Increased TB case detection requires a more sensitive and specific screening tool. Currently, the symptoms recommended for screening TB have been found to be suboptimal since up to 44% of individuals with TB are asymptomatic. The chest X-ray (CXR) as a screening tool for pulmonary TB was evaluated in this study, as well as its incremental yield in TB diagnosis using a cross-sectional study involving secondary analysis of data of 4512 consented/assented participants ≥15 years who participated in the Uganda National TB prevalence survey between 2014 and 2015. Participants with a cough ≥2 weeks, fever, weight loss, and night sweats screened positive for TB using the symptoms screening method, while participants with a TB defining abnormality on CXR screened positive for TB by the CXR screening method. The Löwenstein-Jensen (LJ) culture was used as a gold standard for TB diagnosis. The CXR had 93% sensitivity and 65% specificity compared to LJ culture results, while symptoms had 76% sensitivity and 31% specificity. The screening algorithm involving the CXR in addition to symptoms led to a 38% increment in the yield of diagnosed tuberculosis. The number needed to screen using the CXR and symptoms screening algorithm was 32 compared to 45 when the symptoms are used alone. Therefore, the CXR in combination with symptoms is a good TB screening tool and increases the yield of diagnosed TB.

Knowledge, Attitude, and Practices on Drug-Resistant Tuberculosis Infection Control in Nepal: A Cross-Sectional Study

Drug-resistant tuberculosis (DR-TB) transmission is an important problem, particularly in low-income settings. This study is aimed at assessing the knowledge, attitude, and practices of DR-TB infection control among the healthcare workers under the National Tuberculosis Control Program in Nepal. In this cross-sectional study, we studied the healthcare workers from all the 11 functioning DR-TB treatment centers across Nepal in March 2018. Through face-to-face interviews, trained data collectors collected data on the characteristics of healthcare workers, their self-reported knowledge, attitude, and practice on DR-TB infection control. We entered the data in Microsoft Excel and analyzed in the R statistical software. We assigned a score of one to the correct response and zero to the incorrect or no response and calculated a composite score in each of the knowledge, attitude, and practice domains. We ascertained the healthcare workers as having good knowledge, appropriate attitude, and optimal practices when the composite score was ≥50%. We summarized the numerical variables with median (interquartile range (IQR)) and the categorical variables with proportions. We ran appropriate correlation tests to identify relationships between knowledge, attitude, and practice scores. We regarded a p value of <0.05 as significant. A total of 95 out of 102 healthcare workers responded. There were 46 male respondents. The median age was 33 years (IQR 26-42). Most of them (53, 55.79%) were midlevel paramedics. We found 91 (95.79%) respondents had good knowledge, 49 (51.58%) had an appropriate attitude, and 35 (36.84%) had optimal practices on DR-TB infection control. We found a statistically significant positive correlation between attitude and practice scores ( ρ = 0.37 , p ≤ 0.001 ). The healthcare workers at the DR-TB treatment centers in Nepal have good knowledge of DR-TB infection control, but it did not translate into an appropriate attitude or optimal practices.

Comparison of Interferon-Gamma Release Assay and Tuberculin Skin Test for the Screening of Latent Tuberculosis in Inflammatory Bowel Disease Patients: Indian Scenario

Background. In a country like India, where the prevalence of tuberculosis is very high, the role of screening tools for detection of latent tuberculosis infection (LTBI) like TST and IGRA is still unclear, especially in inflammatory bowel disease (IBD) patients. Our study is aimed at comparing the interferon-gamma release assay (IGRA) and tuberculin skin test (TST) to determine the prevalence of LTBI in IBD patients in the Indian subset of the population. Methods. It was a prospective observational analysis. A total of 257 participants were included in the study. Both TST and IGRA were performed in consecutive patients diagnosed with IBD (131 patients) and in 126 healthy individuals. Both tests were performed on the same day. LTBI diagnosis was considered if any one of TST or IGRA was found to be positive. Results. Out of 131 IBD patients, 121 patients had ulcerative colitis and 10 patients had Crohn’s disease. 29% of the IBD patients and 22% of the control subjects had LTBI. The study demonstrated concordance between TST and IGRA. Agreement test kappa value for IBD patients was 0.656 (CI 0.50-0.81), with a p value of <0.001, suggestive of a fair agreement. Mean IFN-γ release was lower in the immunosuppressed group as compared to non-immunosuppressed individuals ( 0.26 ± 0.17 vs. 0.45 ± 0.07 , p = 0.02 ). Cohen’s kappa coefficient values in IBD cases and control subjects were 0.66 and 0.79, respectively. TST was found to be negatively correlated to BMI. Conclusion. Agreement between TST and IGRA was fair in IBD patients. For LTBI screening in IBD patients, TST and IGRA are complementary methods.