Haider Abdulrazzaq Abed Al-Darraji

Attrition of TCR Vα7.2+ CD161++ MAIT cells in HIV- tuberculosis co-infection is associated with elevated levels of PD-1 expression.

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8+ T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161++CD8+ T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.

The Diagnostic Performance of a Single GeneXpert MTB/RIF Assay in an Intensified Tuberculosis Case Finding Survey among HIV-Infected Prisoners in Malaysia

Background Delays in tuberculosis (TB) diagnosis, particularly in prisons, is associated with detrimental outcomes. The new GeneXpert MTB/RIF assay (Xpert) offers accurate and rapid diagnosis of active TB, but its performance in improving case detection in high-transmission congregate settings has yet to be evaluated. We assessed the diagnostic accuracy of a single Xpert assay in an intensified case finding survey among HIV-infected prisoners in Malaysia. Methods HIV-infected prisoners at a single site provided two early-morning sputum specimens to be examined using fluorescence smear microscopy, BACTEC MGIT 960 liquid culture and a single Xpert. The sensitivity, specificity, negative and positive predictive values of Xpert were calculated relative to gold-standard results using MGIT 960 liquid culture. Relevant clinical and demographic data were used to examine correlates of active TB disease. Results The majority of enrolled subjects with complete data (N=125) were men (90.4%), age <40 years (61.6%) and had injected drugs (75.2%). Median CD4 lymphocyte count was 337 cells/µL (IQR 149-492); only 19 (15.2%) were receiving antiretroviral therapy. Of 15 culture-positive TB cases, single Xpert assay accurately detected only eight previously undiagnosed TB cases, resulting in a sensitivity, specificity, positive predictive value and negative predictive value of 53.3% (95% CI 30.12-75.2%), 100% (95% CI 96.6-100%), 100% (95% CI 67.56-100%) and 94.0% (95% CI 88.2-97.1%), respectively. Only 1 of 15 (6.7%) active TB cases was smear-positive. The prevalence (12%) of undiagnosed active pulmonary TB (15 of 125 prisoners) was high and associated with longer duration of drug use (AOR 1.14, 95% CI 1.03-1.26, for each year of drug use). Conclusions Single Xpert assay improved TB case detection and outperformed AFB smear microscopy, but yielded low screening sensitivity. Further examination of the impact of HIV infection on the diagnostic performance of the new assay alongside other screening methods in correctional settings is warranted.

Tuberculosis control in prisons: current situation and research gaps.

BACKGROUND Tuberculosis (TB) in penitentiary services (prisons) is a major challenge to TB control. This review article describes the challenges that prison systems encounter in TB control and provides solutions for the more efficient use of limited resources based on the three pillars of the post-2015 End TB Strategy. This paper also proposes research priorities for TB control in prisons based on current challenges. METHODS Articles (published up to 2011) included in a recent systematic review on TB control in prisons were further reviewed. In addition, relevant articles in English (published 1990 to May 2014) were identified by searching keywords in PubMed and Google Scholar. Article bibliographies and conference abstracts were also hand-searched. RESULTS Despite being a serious cause of morbidity and mortality among incarcerated populations, many prison systems encounter a variety of challenges that hinder TB control. These include, but are not limited to, insufficient laboratory capacity and diagnostic tools, interrupted supply of medicines, weak integration between civilian and prison TB services, inadequate infection control measures, and low policy priority for prison healthcare. CONCLUSIONS Governmental commitment, partnerships, and sustained financing are needed in order to facilitate improvements in TB control in prisons, which will translate to the wider community.

Genome Sequences of a Novel HIV-1 CRF53_01B Identified in Malaysia

ABSTRACT A novel HIV-1 genotype designated CRF53_01B was recently characterized from three epidemiologically unrelated persons in Malaysia. Here we announced three recently isolated full-length genomes of CRF53_01B, which is likely to be phylogenetically linked to CRF33_01B, circulating widely in Southeast Asia. The genome sequences may contribute to HIV-1 molecular surveillance and future vaccine development in the region.

Prevalence of tuberculosis symptoms and latent tuberculous infection among prisoners in northeastern Malaysia

SETTING There are currently no routine screening procedures for active tuberculosis (TB) or latent tuberculous infection (LTBI) in Malaysian prisons. OBJECTIVE To determine the prevalence and correlates of LTBI and active TB symptoms among Malaysian prisoners with and without human immunodeficiency virus (HIV) infection using the tuberculin skin test (TST) and the World Health Organization TB symptom-based screening instrument. DESIGN A cross-sectional survey of 266 prisoners was performed in Kelantan, Malaysia. Consenting participants underwent two-step TST and were screened for active TB symptoms. Standardized cut-offs of respectively ≥5 and ≥10 mm were used to define reactive TST among prisoners with and without HIV. Clinical and behavioral data were assessed and HIV-infected prisoners were stratified by CD4 status. RESULTS Overall LTBI prevalence was 87.6%, with significantly lower TST reactivity among HIV-infected than non-HIV-infected prisoners (83.6% vs. 91.5%, P < 0.05); however, TB symptoms were similar (16.9% vs. 10.1%, P = 0.105). On multivariate analysis, previous incarceration (aOR 4.61, 95%CI 1.76-12.1) was the only significant correlate of LTBI. Increasing age (aOR 1.07, 95%CI 1.01-1.13), lower body mass index (aOR 0.82, 95%CI 0.70-0.96) and TST-reactive status (aOR 3.46, 95%CI 1.20-9.97) were correlated with TB symptoms. CONCLUSION LTBI is highly prevalent, associated with previous incarceration, and suggests the need for routine TB screening on entry to Malaysian prisons.

Time to act to prevent and control tuberculosis among inmates

* World Health Organization, Regional Office for Europe, Copenhagen, Denmark; † International Union Against Tuberculosis and Lung Disease, South-East Asia Regional Office, New Delhi, India; ‡ Department of Global Health, University of Amsterdam, Amsterdam, § PharmAccess Foundation, Amsterdam, The Netherlands; ¶ Ministry of Justice, Baku, Republic of Azerbaijan; # University of Malaya, Kuala Lumpur, Malaysia; ** AIDS Foundation East-West, Amsterdam, The Netherlands

A Newly Emerging HIV-1 Recombinant Lineage (CRF58_01B) Disseminating among People Who Inject Drugs in Malaysia

The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B–D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes—subtype B (including subtype B′, the Thai variant of subtype B), CRF01_AE, and CRF33_01B—have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B′ and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.

Tuberculosis screening in a novel substance abuse treatment center in Malaysia: Implications for a comprehensive approach for integrated care

People who use drugs (PWUD) represent a key high risk group for tuberculosis (TB). The prevalence of both latent TB infection (LTBI) and active disease in drug treatment centers in Malaysia is unknown. A cross-sectional convenience survey was conducted to assess the prevalence and correlates of LTBI among attendees at a recently created voluntary drug treatment center using a standardized questionnaire and tuberculin skin testing (TST). Participants (N=196) were mostly men (95%), under 40 (median age=36 years) and reported heroin use immediately before treatment entry (75%). Positive TST prevalence was 86.7%. Nine (4.6%) participants were HIV-infected. Previous arrest/incarcerations (AOR=1.1 for every entry, p<0.05) and not being HIV-infected (AOR=6.04, p=0.03) were significantly associated with TST positivity. There is an urgent need to establish TB screening and treatment programs in substance abuse treatment centers and to tailor service delivery to the complex treatment needs of patients with multiple medical and psychiatric co-morbidities.

Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters.

Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B′ of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B′ (11%) and CRF01_AE (5%)] and CRF01_AE/B′ unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B′ recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating genetic complexity of HIV-1 in the Southeast Asian region.

Prevalence and correlates of latent tuberculosis infection among employees of a high security prison in Malaysia

Objectives Although prison employees share the same tuberculosis (TB) risk environment with prisoners, the magnitude of TB problems among prison employees is unknown in most resource-limited prisons. This survey was conducted to investigate the prevalence and correlates of tuberculin skin test (TST) positivity among employees in Malaysias largest prison. Methods Consented, full-time prison employees were interviewed using a structured questionnaire that included sociodemographic data, history of working in the correctional system and TB-related risk. TST was placed intradermally and read after 48–72 h. Induration size of ≥10 mm was considered positive. Logistic regression analyses were conducted to explore associations with TST positivity. Results Of the 445 recruited prison employees, 420 (94.4%) had complete data. Most were young (median=30.0 years) men (88.8%) who had only worked at this prison (76.4%) for a median total employment period of 60 months (IQR 34.5–132.0). The majority were correctional officers, while civilian employees represented only 7.6% of the sample. Only 26 (6.2%) reported having ever been screened for TB since employment. Prevalence of TST positivity was 81% and was independently associated with longer (≥12 months) prison employment (AOR 4.9; 95% CI 1.5 to 15.9) and current tobacco smoking (AOR=1.9, 95% CI 1.2 to 3.2). Conclusions Latent TB prevalence was high in this sample, approximating that of prisoners in this setting, perhaps suggesting within prison TB transmission in this facility. Formal TB control programmes for personnel and prisoners alike are urgently needed within the Malaysian correctional system.