Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen.

Background: Mycobacterium tuberculosis and human immunodeficiency virus (HIV) are known to cause abnormal thyroid function. There is little information on whether HIV infection aggravates alteration of thyroid function in patients with MDRTB. Objectives: This study was carried out to determine if HIV co-infection alters serum levels of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH) in patients with MDR-TB patients and to find out the frequency of subclinical thyroid dysfunction before the commencement of MDR-TB therapy. Methods: This observational and cross-sectional study involved all the newly admitted patients in MDR-TB Referral Centre, University College Hospital, Ibadan, Nigeria between July 2010 and December 2014. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined using ELISA. Results: Enrolled were 115 patients with MDR-TB, out of which 22 (19.13%) had MDR-TB/HIV co-infection. Sick euthyroid syndrome (SES), subclinical hypothyroidism and subclinical hyperthyroidism were observed in 5 (4.35%), 9 (7.83%) and 2 (1.74%) patients respectively. The median level of TSH was insignificantly higher while the median levels of T3 and T4 were insignificantly lower in patients with MDR-TB/HIV co-infection compared with patients with MDRT-TB only. Conclusion: It could be concluded from this study that patients with MDR-TB/HIV co-infection have a similar thyroid function as patients having MDR-TB without HIV infection before commencement of MDR-TB drug regimen. Also, there is a possibility of subclinical thyroid dysfunction in patients with MDR-TB/HIV co-infection even, before the commencement of MDR-TB therapy.

Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 μg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

PCR-Internal Transcribed Spacer (ITS) genes sequencing and phylogenetic analysis of clinical and environmental Aspergillus species associated with HIV-TB co infected patients in a hospital in Abeokuta, southwestern Nigeria.

Background: Aspergillosis has been identified as one of the hospital acquired infections but the contribution of water and inhouse air as possible sources of Aspergillus infection in immunocompromised individuals like HIV-TB patients have not been studied in any hospital setting in Nigeria. Objective: To identify and investigate genetic relationship between clinical and environmental Aspergillus species associated with HIV-TB co infected patients. Methods: DNA extraction, purification, amplification and sequencing of Internal Transcribed Spacer (ITS) genes were performed using standard protocols. Similarity search using BLAST on NCBI was used for species identification and MEGA 5.0 was used for phylogenetic analysis. Results: Analyses of sequenced ITS genes of selected fourteen (14) Aspergillus isolates identified in the GenBank database revealed Aspergillus niger (28.57%), Aspergillus tubingensis (7.14%), Aspergillus flavus (7.14%) and Aspergillus fumigatus (57.14%). Aspergillus in sputum of HIV patients were Aspergillus niger, A. fumigatus, A. tubingensis and A. flavus. Also, A. niger and A. fumigatus were identified from water and open-air. Phylogenetic analysis of sequences yielded genetic relatedness between clinical and environmental isolates. Conclusion: Water and air in health care settings in Nigeria are important sources of Aspergillus sp. for HIV-TB patients.

Prevalence and associated factors of TB/HIV co-infection among HIV Infected patients in Amhara region, Ethiopia.

Background: Tuberculosis is one of the world’s most common causes of death in the era of Human immunodeficiency virus. The purpose of this study was to determine the prevalence and associated factors of TB/HIV co-infection. Methods: Hospital based retrospective studies were conducted among adult HIV-positive patients. Logistic regression method and Chi square test were applied. Results: A total of 571 HIV positive study participants were enrolled. Of these, 158 (27.7%) were found to have pulmonary tuberculosis. Lower baseline CD4 count<200cell/μl, patients who drunk alcohol, patients who were ambulatory at the initiation of ART, patients whose marital status was single were significant predictors for increased risk of tuberculosis in PLWHIV (P <0.05). Non smoker patients, patients in WHO clinical stage I, patients in WHO clinical stage II and ownership of the house had significant protective benefit against risk of TB (P <0.05). Conclusion: The prevalence of TB/HIV co-infection in adults on ART in our study was moderately high. Having advanced clinical status and presence of risk factors were found to be the predicting factors for co-infection. The health office should open TB/HIV co-infection units in the hospitals and health workers should be cautious when a patient has an advanced disease.

Five years retrospective cohort analysis of treatment outcomes of TB-HIV patients at a PEPFAR/DOTS Centre in South Eastern Nigeria.

Background: Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in the diagnosis and treatment of patients. Objectives: The aim of this study was to assess treatment outcomes of a cohort of smear positive TB-HIV co-infected patients over a five-year study period. Methods: A retrospective cohort study of 600 smear-positive tuberculosis patients registered at the chest unit of the University of Nigeria Teaching Hospital, Enugu from January 2008 to December 2012 was done. The data was analyzed using SPSS Version 17. Results: One hundred and three (17.2%) of the patients were co-infected with TB/HIV, while 398 (66.3%) and 99 (16.5%) were HIV negative and unknown respectively. Among the co-infected patients, 45(43.7%) were cured as against 222(55.8%) in the TBHIV negatives (Z=4.53, p=0.000, 95%CI= 0.12-0.34). Respectively in the TB-HIV co-infected and TB-HIV negative patients, treatment completed were 21(20.4%) and 71(17.8%) (Z=9.15, p=0.000, 95%= 0.4035-0.60); defaulted 19(18.5%) vs 70 (17.6%) (Z=9.29, p=0.000, 95%CI=0.42-0.60), died 10(9.7%) vs. 6(1.5%) (Z=1.22, p=0.224, 95%CI= -0.0286-0.1086), and failures were 1(0.9%) vs. 7(1.8%) (Z=2.48, p=0.013, 95%CI=0.04-0.10). Treatment success rate was lower in TB-HIV co-infected patients, 64.1% compared to TB-HIV negative patients with 73.6%. Also those that defaulted among the TB-HIV co-infected patients (18.5%) were higher than 17.6% among TB-HIV negative patients, a difference of 0.9%. Conclusion: Findings demonstrate that HIV co-infection affects TB treatment outcomes adversely. Treatment adherence, timely and sustained access to antiretroviral therapy for TB/HIV co-infected patients are important.

A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis

Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB) control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR) and extensively drug-resistant TB based on single nucleotide polymorphism (SNP) mutations present in the rpoB, katG, inhA, ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 for rpoB, katG, inhA, ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours.