Journal of Tuberculosis Research

Journal Information
ISSN / EISSN : 2329-843X / 2329-8448
Published by: Scientific Research Publishing, Inc. (10.4236)
Total articles ≅ 220
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Evarist Chiweka, Thomas Maroa, Hosiana Temba, Joseph Ponera, Sharifa Athumani, Lujeko Kamwela, Mohamed Sasamalo, Rastard Naftari, Mirambi Tito, Francis Mhimbira, et al.
Journal of Tuberculosis Research, Volume 10, pp 28-44;

Background: The current screening tools for tuberculosis (TB) are inadequate resulting in insufficient TB case detection and continued community transmission of TB. As the world is geared into finding missing TB cases, new strategies are called for to aid in rapid identification of TB cases. This study aimed to evaluate the role C-reactive protein (CRP) in triaging patients to get a definitive test for active pulmonary TB diagnosis in urban Tanzania. Methods: A case-control study was conducted among pulmonary TB (PTB) patients and contacts without active PTB. The diagnosis of PTB was performed using GeneXpert MTB/RIF assay and culture. Blood was collected from cases and controls for measuring CRP levels during recruitment. We compared socio-demographic characteristics, clinical and laboratory parameters obtained during recruitment and performed diagnostic accuracy analyses for CRP. Results: Out of all 193 study participants who were involved in final analysis, 147 (76.2%) were males. Pulmonary TB cases had significantly lower median BMI than controls (median 17.4 kg/m2 [IQR: 15.8 - 19.2 kg/m2] vs., 24.9 kg/m2 [IQR: 22.1 - 28.5 kg/m2), p i.e., 13.33% vs., 11.7%, p = 0.48. CRP was significantly higher in PTB cases vs., controls (median 67.8 mg/L, [IQR: 36.5 - 116.9 mg/L] vs., 1.55 mg/L, [IQR: 0.59 - 6.0 mg/L], p = 0.003). Furthermore, CRP at cut-off ≥10 mg/L was associated with best combination of sensitivity, specificity and area under the curve of 89.9%, 95% CI: 82.2 - 95.0, 80.9%, CI: 71.4 - 88.2 and 0.85, 95% CI: 0.80 - 0.90 respectively. A multivariate logistic regression model adjusted for fever, night sweats and body mass index showed that CRP above 10 mg/L was significantly associated with PTB, aOR 5.2, 95% CI 1.2 - 22.8. Conclusions: CRP at cut-off ≥10 mg/L can be used to screen pulmonary TB. These findings can be used to improve TB screening algorithm by incorporating CRP in combination with TB symptoms to identify patients who need further confirmatory TB tests. However, additional prospective studies are required to support our findings and contribute into policy recommendations on use of CRP in a screening algorithm for pulmonary TB.
Zeinab H. Alfaham, Elhadi A. Ahmed, Elamin M. Ibrahim, Mohamed Soud Mohamed, Ameer A. Mohamed, Ayman Mahjob, Mubarak A. Elshafia, Bakri Y. M. Nour
Journal of Tuberculosis Research, Volume 10, pp 18-27;

Introduction: The increase in cases of drug-resistant pulmonary tuberculosis, especially in endemic areas, is mainly associated with re-treatment, although resistant tubercle bacilli can be easily transmitted between all susceptible persons. Objective: The study aimed to describe pulmonary tuberculosis, risk factors and MDR in new and re-treated suspected patients attending Wad Madani Tuberculosis Center that provides service in central Sudan. Methods: Cross-sectional laboratory based study among 300 presumptive pulmonary tuberculosis patients during 2018 and 2019 was conducted. Cases were divided into new and re-treated. Mycobacterium tuberculosis DNA and rpoB gene of multi-drug resistance (MDR) were detected in sputum samples by GeneXpert assay as manufacturer instructions. Results: Out of 300 suspected participants, 34% (103/300) were diagnosed as pulmonary tuberculosis using GeneXpert method. The frequency of males, the age group from 21 to 40 and rural housing were the most with percentage reach 68% (70/103), 51% (53/103) and 58.3% (60/103) respectively. All observed symptoms were significantly associated with pulmonary tuberculosis. New cases represented 59.2% (61/103) while re-treated was 40.8% (39/103). The overall frequency of MDR patients was 9.7% (10/103) of which 50% (5/103) had relapse situation. Conclusion: It appeared that the cases of MDR pulmonary tuberculosis are on the increase compared to previous findings, recommended measures must be taken to control the spread of tuberculosis and the causes of re-treatment and relapse must be studied.
Vivian S. Lofranco, Vincent M. Balanag Jr, Lawrence O. Raymond, Noel G. Macalalad, Alex Golubkov, Mary Rosary T. Santiago, Anna Marie Celina G. Garfin
Journal of Tuberculosis Research, Volume 10, pp 75-86;

Background: The Philippines has a burden of drug-resistant tuberculosis (DR-TB). One of the key challenges in the programmatic management of DR-TB (PMDT) is the high rate of loss to follow-up (38% in the 2010 cohort). An urgent need for a shorter, more tolerable, less expensive treatment regimen exists. The aim of the operational study is to determine the efficacy and safety of the short treatment regimen among drug resistant TB. Methods: This is a prospective single-arm cohort study evaluating the effectiveness and safety of a shorter 9 - 11-month treatment regimen (9MTR) for rifampicin-resistant/multi-drug resistant TB (RR/MDR-TB) in 10 PMDT facilities. All eligible consenting adult patients with rifampicin-resistant TB were enrolled and received the standardized 9-month treatment regimen (9MTR), including injectables, with a follow-up after 12 months of treatment completion. Results: A total of 329 patients were enrolled from July 2015 to December 2016. At the 6th month post-enrollment, 256 (77.8%) of them had culture-negative test results. The end-of-treatment success rate was 74.1% (224 [68.0%] were cured and 20 [6.1%] completed the treatment). On the other hand, 10 (3.0%) died, 41 (12.5%) lost to follow-up, 33 (10.0%) withdrawn, 1 (0.3%) treatment failure. In the 12th month after 9MTR completion, among the 244 patients with successful treatment, 198 (81.1%) had culture-negative results, while there were 46 patients whose culture tests were not done. One patient developed TB relapse with fluoroquinolone resistance. The majority of the adverse events were mild that occurred mostly during the first 6 months of treatment. Conclusion: The 9-month treatment regimen had a high treatment success rate with a favorable safety profile. The loss to follow-up was reduced; however, it was still a challenge. The introduction of the 9MTR via operational research had a major impact on building national capacity and infrastructure for the programmatic adoption of a new regimen. Ten PMDT centers received training and experience, created diagnostic pathways, and active drug safety monitoring and management were built.
Sizwe Vincent Mbona, Henry Mwambi, Retius Chifurira
Journal of Tuberculosis Research, Volume 10, pp 1-17;

Setting: Four decentralised sites are located in rural areas and one centralised hospital in KwaZulu-Natal province, South Africa. Objective: To analyse risk factors associated with multidrug-resistant tuberculosis (MDR-TB) using competing risks analysis. Understanding factors associated with MDR-TB and obtaining valid parameter estimates could help in designing control and intervention strategies to lower TB mortality. Method: A prospective study was performed using a competing risk analysis in patients receiving treatment for MDR-TB. The study focused on 1542 patients (aged 18 years and older) who were diagnosed of MDR-TB between July 2008 and June 2010. Time to cure MDR-TB was used as the dependent variable and time to death was the competing risk event. Results: The Fine-Gray regression model indicated that baseline weight was highly significant with sub-distribution hazard ration (SHR) = 1.02, 95% CI: 1.01 - 1.02. This means that weight gain in a month increased chances of curing MDR-TB by 2%. Results show that lower chances to cure MDR-TB were among patients between 41 to 50 years compared to those patients who were between 18 to 30 years old (SHR = 0.80, 95% CI: 0.61 - 1.06). The chances of curing MDR-TB in female patients were low compared to male patients (SHR = 0.84, 95% CI = 0.68 - 1.03), however this was not significant. Furthermore, HIV negative patients had higher chances to cure MDR-TB (SHR = 1.07, 95% CI: 0.85 - 1.35) compared to HIV positive patients. Patients who were treated in the decentralised sites had lower chances to be cured of MDR-TB (SHR = 0.19, 95% CI: 0.07 - 0.54) as compared to patients who were treated in the centralised hospital. Conclusion: Identifying key factors associated with TB and specifying strategies to prevent them can reduce mortality of patients due to TB disease, hence positive treatment outcomes leading to the goal of reducing or end TB deaths. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people with drug-resistant TB.
Obioma Chijioke-Akaniro, Emperor Ubochioma, Amos Omoniyi, Oluwafunmilayo Omosebi, Olawumi Olarewaju, Mary Etolue, Sunday Asuke, Elias Aniwada, Anyaele Uwaezuoke Ndubuisi, Victor Ombeka, et al.
Journal of Tuberculosis Research, Volume 10, pp 99-110;

Introduction: Finding the missing Tuberculosis (TB) cases remains the single most important priority for TB control in Nigeria. Between 66% - 92% of all cases of respiratory diseases including those with symptoms suggestive of TB are first seen byprivate health providers. Dependable, quality surveillance systems and notification are key roles in health services delivery, particularly as it is related to TB control. However, poor notification has been a challenge. This study was to assess the contribution of the public private mix (PPM) to Nigeria Tuberculosis national case notification. Methods: It was a national cross-sectional study. Data were extracted from the National database and reviewed. Private facilities were engaged in 2017 and assessed over 2018-2020. Interventions included: enrolling private practitioners (Private-For-Profit, Faith Based Organization, Private Medicine Vendors and Community Pharmacists), engaging a private standalone Laboratory for Gene Xpert testing within the network of private facilities, use of Mobile App for easy screening and reporting, instituting a HUB and spoke, and incentives to private providers for participating. Each private provider had a customized approach. Trend analysis was performed using Cochran-Armitage χ2 test for linear trends. Level of significance was at a p value of Results: Total case notification increased from 104,904 cases in 2017 to 138,591 in 2020. There were 2.0% increase in 2018, 13.0% in 2019 and 15.0% in 2020 (p ). PPM contribution to case notification increased from 10,699 cases in 2017 to 12,625 in 2018, then 17,250 in 2019 and 38,865 in 2020. There were 18.0% increase in 2018, 36.6% in 2019 and 125.3% increase in 2020 (p ). Conclusion: Effective engagement of the private sector in TB control efforts in Nigeria using a variety of approaches resulting in improved TB notification is possible. The National TB Programme should engage all private practitioners such that each practitioner will practice at least one TB service model.
Chukwuebuka Emmanuel Nwoke
Journal of Tuberculosis Research, Volume 10, pp 87-98;

The UNHCR 2017 report stated that about 44,400 people are displaced from their homes daily and about 68.5 million people are currently displaced globally. This article aims at critically analyzing the tuberculosis risks among displaced people especially as there is an increase in the number of migrants globally and proliferation of man-made and natural disasters. Research conducted among displaced persons and most of the studies concluded that active surveillance and proper case follow-up are the best ways to ensure adequate tuberculosis case management. In conclusion, the application of diverse methods in tackling tuberculosis risks should be especially through a culturally, acceptable precise and feasible plans without compromising international standards.
Dianguina Soumare, Bocar Baya, Khadidia Ouattara, Tenin Kanoute, Cheick M. Sy, Seydou Karembé, Ibrahima Guindo, Lamine Coulibaly, Youssouf Kamian, aiMe P. Dakouo, et al.
Journal of Tuberculosis Research, Volume 10, pp 45-59;

Background: Tuberculosis was the deadliest infectious agent before covid-19; 1.5 million deaths in 2020. Despite, a variety, of easy and cheap diagnostic tools, detection rates still fall below 90%; diagnosis delays are long exceeding 30 days in many continents. This study aimed to determine risk factors for pulmonary TB diagnosis delays in Mali. Methods: A cross-sectional study was conducted in Bamako to include pulmonary TB patients at treatment initiation centers. Verbal consent was obtained before the interview. Demographics, clinical, treatment cost, and patient, medical, and diagnostic delays were computed using SPSS 25.0 considering a significance level p Results: In total 266 patients were included, 80.8% were male, mean age was 40.5 ± 12 years, primary education level was 50.4%, treatment cost before diagnosis was 100 - 200 thousand CFA in 65.4%, smokers were 42.1%, median patient, medical and total diagnostic delays were 58, 57 and 114 days respectively. Education level below university, social reasons, and non-request of health workers were identified as independent risk factors for diagnostic delay > 100 days in Mali. Conclusion: Diagnostic delay is relatively very long in Mali, there is an urgent need for identification and action to shorten the delays to limit the transmission chain and avoid disabling pulmonary sequels.
Vivian S. Lofranco, Maria Rhoda A. Torres-Cervas, Katherine A. Asence, Khrizza Marianne A. Del Mundo, Vincent M. Balanag, Mary Rosary T. Santiago, Anna Marie Celina G. Garfin
Journal of Tuberculosis Research, Volume 10, pp 61-74;

Objectives: This study aimed to assess the interim outcomes for drug-resistant tuberculosis (DR-TB) patients treated with bedaquiline regimen under the operational research conditions compared to DR-TB patients treated without bedaquiline in their regimen, and to describe the adverse events that occurred among patients treated with bedaquiline in the Philippines. Design: Patients who were treated with a bedaquiline-containing regimen from June 2016 to May 2017 were included in this study as the intervention group, while patients who were treated without bedaquiline regimen from January 2013 to May 2016 were included as the comparison group. The interim treatment outcomes were compared using Chi-square test. The analysis of time to culture conversion within 6 months of treatment was conducted. A Cox proportional hazard model was constructed to identify the variables associated with a favorable interim treatment outcome. The R program was used for statistical analysis. Results: On the 6th month of treatment, the culture conversion for patients treated with a bedaquiline-containing regimen was significantly higher than with the comparison group [63/75 (84.0%) vs 84/117 (71.8%), p = 0.012)]. Nearly 15% of the patients treated with bedaquiline were lost to follow-up. Frequent adverse events included vomiting, dizziness, nausea, joint pain, and abdominal pain. Conclusion: The patients who were treated with bedaquiline-containing regimen have better interim treatment outcomes than those treated without bedaquiline, but the proportion of patients who were lost to follow-up remains substantial.
Sekossounon Sanni, Haziz Sina, Lamine Baba-Moussa
Journal of Tuberculosis Research, Volume 10, pp 124-145;

Introduction: Polymorphisms are the main genetic factors associated with toxicities of antituberculosis drugs. This literature review summarizes the polymorphisms of the genes that code for the enzymes of the metabolism of antituberculosis drugs and their transmembrane transporters. Some mechanisms of drug-associated toxicities and strategies for their management have also been described in this review. Methods: The bibliographic searches were exclusively carried out in PubMed, over a period of ten years (2010-2020). The search terms were the words “toxicity + antituberculosis drug + one or two word(s) among the following: polymorphism, genetics, mutation, SNP, HLA or haplotype”. Publications in English or French, relating to the various toxicities associated with first-line anti-tuberculosis drugs (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) administered to patients with pulmonary tuberculosis, extrapulmonary tuberculosis or co-infected with TB/HIV were included in this review. Duplicates, in vitro, in silico or drug-induced toxicity studies other than antituberculosis drugs and genetic mutations of Mycobacteria strains were not included. Results: The studies selected and included were case reports, cohort studies, original research, systematic reviews and meta-analyses on human subjects of different ethnic origins. Hepatotoxicity is the most common toxicity associated with NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms in patients on antituberculosis drugs. Other forms of toxicity, less frequent, occurring in certain patients under concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), antiretrovirals (ARVs), antibiotics or antiepileptics have also been identified. Conclusion: The genetic polymorphisms associated with the toxicities of antituberculosis drugs concern both the main enzymes of the metabolic pathways (NAT2, CYP2E1, GST) and the transmembrane transporters (SLCO1B1 and ABCB1). Other genetic polymorphisms (TXNRD1, SOD2, TYMP) have been suspected but their mechanisms are not yet well understood.
Sekossounon Sanni, Ablo Prudence Wachinou, Corinne Simone Colette Merle, Lamine Baba-Moussa, Dissou Affolabi
Journal of Tuberculosis Research, Volume 10, pp 111-123;

SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic (PK). The objective of this study was to identify in African patients with tuberculosis (TB) or TB/HIV co-infection, the SLCO1B1 and NAT2 polymorphisms, associated with the variability of Rifampicin and Isoniazid pharmacokinetic. TB or TB/HIV co-infected patients from Benin, Guinea, Senegal, and South Africa were included in this study. The blood samples collected were stored at -80˚C until DNA extractions. The DNA extracts were then frozen at -80˚C after quality control. Double stranded DNA of the samples were quantified using a fluorimetric method to select suitable samples for the preparation of 96-well microplates, containing 100 μl of DNA extract per well at the concentration of 20 ng/μl. Illumina HumanOmniExpress-24 v1.2 microarray genotyping was performed by an external vendor. The genotyping data were analyzed and the polymorphisms with a call rate Hardy-Weinberg Equilibrium (HWE) were excluded. The correlation between significant genetic polymorphisms, the clearance, and the AUC were tested by a multiple linear regression model using the PLINK2 software. Out of 385 samples, five (05) were excluded after quality controls. After the frequency test, 384,586 SNPs failed the Hardy-Weinberg Equilibrium. Finally, 378 samples and 318,751 SNPs were included in the genetic analyses. The SLCO1B1 and NAT2 polymorphisms were associated with the variability of Rifampicin and Isoniazid PK parameters. There are SLCO1B1 and NAT2 polymorphisms carriers among TB and TB/HIV co-infected patients from Sub-Saharan Africa.
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