Molecular detection of multidrug resistance pattern and associated gene mutations in M. tuberculosis isolates from newly diagnosed pulmonary tuberculosis patients in Addis Ababa, Ethiopia.

INTRODUCTION: Multi-drug resistance is a major challenge in the control of tuberculosis. Despite newer modalities for diagnosis and treatment, people are still suffering from this disease. Understanding the common gene mutations conferring rifampicin and isoniazid resistance is crucial for the implementation of effective molecular tools at local and national levels. Hence, this study aimed to evaluate the molecular detection of rifampicin and isoniazid-resistant gene mutations in M.tuberculosis isolates in Addis Ababa, Ethiopia. METHOD: Health Center-based cross-sectional study was conducted between January and September 2017 in Addis Ababa, Ethiopia. The collected sputum samples were processed for mycobacterial isolation and Region of difference 9 based polymerase chain reaction for species identification. To characterize the rifampicin and isoniazid-resistant M. tuberculosis isolates, a molecular genetic assay (GenoType MTBDRplus) was used; the assay is based on DNA-STRIP technology. RESULT: Culture positivity was confirmed in 82.6% (190/230) of smear-positive newly diagnosed pulmonary tuberculosis cases enrolled in the study. From 190 isolates 93.2% were sensitive for both rifampicin and isoniazid, and 6.8% of the isolates were resistant to at least one of the tested anti-TB drugs. Gene mutations were observed in all studied multidrug resistance-associated gene loci (rpoB, katG, and inhA). Two isolates exhibited heteroresistance, a mutated, as well as wild type sequences, were detected in the respective strains. MDR-TB case was observed in 1.1% (2/190) of the cases. All the MDR-TB cases were positive for HIV and found to have a history of prior hospital admission. CONCLUSION: In our finding a relatively high prevalence of any drug resistance was observed and the overall prevalence of multidrug-resistant tuberculosis was 1.1%.The majority of drug-resistant isolates demonstrated common mutations. Heteroresistant strains were detected, signaling the existence of an M.tuberculosis population with variable responses to anti-tuberculosis drugs or of mixed infections.

Risk factors for tuberculosis: A case-control study in Addis Ababa, Ethiopia.

BACKGROUND: Tuberculosis remains a major public-health problem in the world, despite several efforts to improve case identification and treatment compliance. It is well known cause of ill-health among millions of people each year and ranks as the second leading cause of death from infectious disease worldwide. Despite implementation of the World health organization recommended strategy, the reductions in the incidence of TB have been minimal in high burden countries. OBJECTIVES AND METHODS: A case control study was carried out to assess the risk factors of TB, where cases were newly registered bacteriologically confirmed pulmonary TB patients with age greater than 15 years who present at twenty health centres in Addis Ababa. Controls were age and sex matched attendees who presented in the same health centers for non-TB health problems. RESULTS: A total of 260 cases and 260 controls were enrolled in the study and 45.8% of cases and 46.2% of controls were in the 26-45 years age bracket. According to the multivariable logistic regression analysis, seven variables were found to be independent predictors for the occurrence of TB after controlling possible confounders. Patients who live in house with no window or one window were almost two times more likely to develop tuberculosis compared to people whose house has multiple windows (AOR = 1.81; 95% CI:1.06, 3.07). Previous history of hospital admission was found to pose risk almost more than three times (AOR = 3.39; 95% CI: 1.64-7.03). Having a household member who had TB was shown to increase risk of developing TB by three fold (AOR = 3.00; 95% CI: 1.60, 5.62). The study showed that illiterate TB patients were found to be more than twice more likely to develop TB compared to subjects who can atleast read and write (AOR, 95% CI = 2.15, 1.05, 4.40). Patients with household income of less than 1000 birrs per month were more than two times more likely to develop TB compared to those who had higher income (AOR = 2.2; 95% CI: 1.28, 3.78). Smoking has also been identified as important risk factor for developing TB by four times (AOR = 4.43; 95% CI: 2.10, 9.3). BCG was found to be protective against TB reducing the risk by one-third (AOR = 0.34; 95% CI: 0.22, 0.54). CONCLUSION: This study showed that TB is more common among the most agile and economically active age group, and number of windows, history of hospital admission, a household member who had TB, illiteracy, low household income and smoking and lack of BCG scar were identified as independent risk factors. Therefore it is imperative that the TB control effort need a strategy to address socio economic issues such as poverty, overcrowding, smoking, and infection control at health care facilities level is an important intervention to prevent transmission of TB within the facilities.

Missed pulmonary tuberculosis: a cross sectional study in the general medical inpatient wards of a large referral hospital in Ethiopia.

BACKGROUND: Every year around 4 million people with tuberculosis (TB) are not detected. Thus may not get the medical care that they need and deserve from their respective health systems. Ethiopia is included in the 12 countries who contribute 75% of the globally estimated "missed" cases. This study assessed if there are missed Pulmonary TB (PTB) cases among inpatients of a large referral hospital in Ethiopia. METHOD: A cross sectional survey was conducted in the general medical wards of the large referral hospital from June to August 2015. Inpatients not diagnosed with TB were screened for TB symptoms and requested to submit a morning sputum sample for smear microscopy and molecular testing by GeneXpert MTB/RIF assay. The results of the symptom screening, smear and GeneXpert testing were analyzed as the main outcome characteristics for "missed" PTB cases. RESULT: Over the 3-month period, 300 inpatients were evaluated for TB. The patients median age was 38 years (IQR 26-51.5), 41% were female, median reported duration of sickness before admission was 30 days (IQR 14-240), and median body mass index (BMI) was 21.5 (IQR 20-22.67). HIV status was documented for 198/300 (66%) of patients, 37 (18.7%) were found to be HIV positive, with a median CD4 count of 176 (IQR 52-400). All 300 inpatients submitted a sputum sample and 10 (3.3%) were found to be GeneXpert MTB positive, with 4/10 also being smear positive. All GeneXpert positive inpatients reported having a cough of > 2 weeks duration. Eight had at least 3 common symptoms of TB (i.e. cough, fever, weight loss or night sweat). Co-morbidity with Diabetes Mellitus (DM) and HIV was found in 1/10 and 4/10 cases respectively. CONCLUSION: Bacteriological confirmed TB cases were found to have been "missed" amongst the general medical ward inpatients in the hospital. The identified TB cases all reported typical signs and symptoms of TB. Basic clinical practices were not being followed (i.e. history taking/documentation and requesting of appropriate laboratory tests) by the attending health care workers (HCWs) in the hospital. The index of suspicion for TB disease needs to improve and the use of more sensitive technologies, such as GeneXpert could assist the diagnosis of TB. However, the findings of the study need to be investigated in other hospital settings in Ethiopia.