Association between human leukocyte antigen class II (HLA-DRB and -DQB) alleles and outcome of exposure to Mycobacterium tuberculosis: a cross-sectional study in Nairobi, Kenya.

Introduction: human leukocyte antigen (HLA) class II alleles play an important role in the early immune response to tuberculosis (TB) by presenting antigenic peptides to CD4+ T cells, hence polymorphisms in those genes can influence the efficiency of the immune response to infection and progression to active disease. Methods: an analytical cross-sectional study of adult pulmonary tuberculosis (PTB) patients at Mbagathi County Hospital, Nairobi and their HHCs. Sociodemographic data were captured on questionnaires and clinical data extracted from patient files. Intravenous blood samples were drawn for interferon-gamma release assay (IGRA) to determine latent tuberculosis infection (LTBI) among HHCs, and for extraction of DNA used in typing of HLA-DQB1 and HLA-DRB1 alleles by PCR sequence specific primer amplification. Chi-square and Fisher's exact test were used to compare the HLA type II allele frequencies of LTBI negative HHCs, LTBI positive HHCs and active TB patients. Logistic regression was used to adjust for HIV status. Results: the HLA-DQB1 and HLA-DRB1 alleles were analyzed in 17 PTB and 37 HHCs. Nineteen (19) HHCs were LTBI positive, while 18 were LTBI negative. The frequency of DRB3*1 was 0.17-fold lower [95% CI=0.03-0.83] among PTB patients compared to HHCs before adjustment for HIV status (p=0.048). The frequency of the DRB5*2 allele was significantly higher (p=0.013) among PTB patients (23.5%) compared to HHCS (0.00%). After adjusting for HIV status, the frequency of DRB1*14 was 12-fold higher [95% CI=1.11-138.2] among PTB patients compared to HHCs (p=0.040). Conclusion: the higher frequencies of HLA-DRB5*2 and HLA-DRB1*14 alleles in PTB patients suggest a likely association with progression to active PTB. The higher frequency of HLA-DRB3*1 allele among LTBI negative HHCs shows its likely protective role against M. tuberculosis infection in this population.

Antifungal susceptibilities of Cryptococcus neoformans cerebrospinal fluid isolates from AIDS patients in Kenya.

Poor susceptibility of Cryptococcus neoformans to fluconazole (FLC) is a matter of concern among clinicians in Africa. The emergence of resistance to FLC was recently reported in Kenya, but it is not known whether it is widespread. Thus, there is need for more antifungal drug susceptibility studies in Kenya. The aim of this study was to measure the in vitro antifungal drug susceptibilities of incident C. neoformans isolates from acquired immunodeficiency syndrome patients in Kenya. Antifungal susceptibility testing was performed in 67 C. neoformans isolates by broth microdilution method as outlined in the Clinical and Laboratory Standards Institute document M27-A3 using FLC, amphotericin B (AMB), voriconazole (VOR), ravuconazole (RAV) and flucytosine (5-FC). Isolates were grown on l-canavanine glycine bromothymol blue medium for serotype identification. Six per cent of the isolates were identified as C. neoformans var. gattii serotype B or C and 94% as C. neoformans var. neoformans. All isolates tested were susceptible to AMB, VOR and RAV (100%), and high susceptibilities were seen to FLC (97%), and 5-FC (90%). Only 3% and 10% of the isolates' susceptibility to FLC and 5-FC, respectively, was dose-dependent or intermediate. These results demonstrate high susceptibilities of incident C. neoformans isolates to FLC and AMB, antifungals used for treatment of cryptococcal meningitis in Kenya.

Latent tuberculosis among household contacts of pulmonary tuberculosis cases in Nairobi, Kenya.

INTRODUCTION: Household Contacts (HHCs) of Pulmonary Tuberculosis (PTB) patients have a higher risk of latent tuberculosis infection (LTBI). However, its prevalence and risk factors among adults living with PTB patients are poorly documented in Kenya. OBJECTIVE: to determine the prevalence and risk factors for LTBI among adult HHCs of PTB patients in Kenya. METHODS: this was an analytical cross-sectional study of HHCs of PTB patients in Nairobi, Kenya. Socio-demographic data was captured on questionnaires and blood samples drawn for Interferon gamma (IFN-γ) quantification. Univariate and multivariate analyses using the Statistical Package for Social Scientists (SPSS) was used to determine the prevalence of LTBI and risk factors at 95% Confidence Interval (CI). RESULTS: a total of 166 PTB patients yielded 175 HHCs of whom 29.7% (52/125) were males and 70.3% (123/125) were females. A majority of HHCs [65.7% (115/175)] lived in a single-room house with the patient and [37.7% (66/175)] were in the age group 30-39-years. The overall prevalence of LTBI was 55.7%, peaking among spouses of the patients [70.0% (14/20) and the 30-39 year age group [63.5% (42/66)]. Potential risk factors for LTBI included cohabiting with a PTB patient for 8 to 12 weeks [OR = 3.6 (0.70-18.5), p = 0.107], being a spouse of the patient [OR = 2.0 (0.72-5.47), p = 0.173] and sharing a single room with the patient [OR = 1.58 (0.84 - 2.97), p = 0.158]. CONCLUSION: the high prevalence of LTBI among adult HHCs of PTB patients in this population demonstrates the need for targeted contact-screening programs in high TB transmission settings.

Prevalence of Drug Resistance Mycobacterium Tuberculosis among Patients Seen in Coast Provincial General Hospital, Mombasa, Kenya.

BACKGROUND: Although prevention and control of spread of multi-drug resistant tuberculosis strains is a global challenge, there is paucity of data on the prevalence of DR-TB in patients diagnosed with TB in referral hospitals in Kenya. The present study assessed patients' characteristics and prevalence of drug resistant TB in sputa smear positive TB patients presenting to Coast Provincial General Hospital (CPGH) in Mombasa, Kenya. METHODS: Drug resistance was evaluated in 258 randomly selected sputa smear TB positive cases between the periods of November 2011 to February 2012 at the CPGH-Mombasa. Basic demographic data was obtained using administered questionnaires, and clinical history extracted from the files. For laboratory analyses, 2mls of sputum was obtained, decontaminated and subjected to mycobacteria DNA analyses. Detection of first line drug resistance genes was done using MDRTDR plus kit. This was followed with random selection of 83 cases for second line drug resistance genes testing using Genotype MDRTBsl probe assay kit (HAINS Lifesciences, GmbH, Germany), in which ethambutol mutation probes were included. The data was then analyzed using SPSS statistical package version 19.0. RESULTS: Male to female ratio was 1:2. Age range was 9 to 75 years, with median of 30 years. New treatment cases constituted 253(98%), among which seven turned out to be PTB negative, and further grouped as 4 (1.6%) PTB negative and 3(1.1%) NTM. 237(91.7%) new cases were fully susceptible to INH and RIF. The remaining, 8 (3.1%) and 1(0.4%) had mono- resistance to INH and RIF, respectively. All the retreatment cases were fully susceptible to the first line drugs. HIV positivity was found in 48 (18.6%) cases, of which 46(17.8%) were co-infected with TB. Of these, 44 (17.1%) showed full susceptibility to TB drugs, while 2 (0.8%) were INH resistant. For the second line drugs, one case each showed mono resistance to both and FQ. Also, one case each showed drug cross poly resistance to both ETH and FQ, with second line injectable antibiotics. However, no significant statistical correlation was established between TB and resistance to the second line drugs p = 0.855. CONCLUSION: The findings of this study showed the existence of resistance to both first and second line anti-tubercular drugs, but no MDR-TB and XDR-TB was detected among patients attending TB clinic at CPGH using molecular techniques.