A Case Report on Fish Bone Perforating Meckel's Diverticulum Mimicking Appendicitis.

Meckel's diverticulum (MD) is the most frequent congenital abnormality of the digestive tract. Although it is silent, it can rarely come up as a complicated case including but not limited to obstruction, inflammation, and neoplasm. Perforation as a consequence of MD is extremely infrequent and mostly related to foreign objects. We report a case of a 24-year-old man who presented to the emergency department with signs and symptoms suggestive of acute appendicitis. Computed tomography (CT) of the abdomen demonstrated foreign body perforation from a protrusion outside the small bowel. The patient underwent laparoscopy and a fish bone perforating MD was found which was removed.

Pleomorphic Adenoma of Breast: Report of Two Cases, One in A Male Patient.

Pleomorphic adenoma of breast (PAB) is a rare mammary tumor of a mixed epithelial-myoepithelial nature. We report two patients with PAB, one of which is male. We believe our male patient is the sixth case of PAB in male breast in the literature. The two cases expressed heterogeneous clinical and radiological characteristics while showing similar histology and immunohistochemical staining profile. The first case was managed with surgical resection while the second underwent interventional radiology excision. PAB is usually a benign entity with occasional cases of recurrence. Malignant transformation is rare but has been reported in a few cases.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

Brown tumor due to primary hyperparathyroidism resulting in acute paraparesis: Case report and literature review.

BACKGROUND: Brown tumor (Osteoclastoma) is a rare benign, focal, lytic bone lesion most commonly attributed to a parathyroid adenoma; it occurs in approximately 5% of patients with primary hyperparathyroidism, and 13% of patients with secondary hyperparathyroidism. Most tumors are located in the mandible, pelvis, ribs, and large bones; only rarely is it found in the axial spine. CASE DESCRIPTION: A 37-year-old male with primary hyperparathyroidism presented with an MR-documented T4 and T5 brown tumor (Osteitis Fibrosa Cystica) resulting in an acute paraparesis. The patient successfully underwent excisional biopsy of an expansile, enhancing, bony destructive lesion at the T4-5 level. Subsequently, he required subtotal excision of a left upper parathyroid tumor. CONCLUSION: Patient with primary hyperparathyroidism may acutely present with paraparesis attributed to brown tumors of the spine warranting emergent operative decompression.

Rosai-Dorfman disease of cranial and spinal origin - A case series.

BACKGROUND: Rosai-Dorfman disease (RDD) is an idiopathic nonneoplastic lymphadenopathy disorder which is characterized by lymph node enlargement, but it may also presents primarily involving a variety of extranodal sites, including central nerves system and craniospinal axis. This study reports five cases of craniospinal RDD, with review of epidemiology, clinical presentation, imaging, and histopathological features with current management strategies. CASE DESCRIPTION: Five cases of RDD are diagnosed at Hamad General Hospital, Qatar, during 2013-2018. Two cases had dural-based cranial lesions with overlying cranial involvement while three cases were having extradural thoracic spine lesions. All cases underwent surgical intervention and confirmed by histopathology. CONCLUSION: Craniospinal RDD is a rare clinical presentation and poses significant diagnostic challenges preoperatively due to its similarity with other neoplastic or inflammatory diseases. Surgical option to remove compressive neural pathology provides a good clinical outcome with no recurrence in long-term follow-up.

Paget's "Seed and Soil" Theory of Cancer Metastasis: An Idea Whose Time has Come.

The concept that the pattern of metastatic spread of cancer is not random and that cancer cells exhibit preferences when metastasizing to organs, dates back to 1889 when Steven Paget published his "seed and soil" hypothesis. He proposed that the spread of tumor cells is governed by interaction and cooperation between the cancer cells (seed) and the host organ (soil). Extensive studies during the last several decades have provided a better understanding of the process of metastatic spread of cancer and several stages such as intravasation, extravasation, tumor latency, and development of micrometastasis and macrometastasis have been defined. Furthermore, recent studies have shown that the target organs may be prepared for metastatic deposits by the development of premetastatic niches. This specialized microenvironment is involved in promoting tumor cell homing, colonization, and subsequent growth at the target organ. The premetastatic niche consists of accumulation of aberrant immune cells and extracellular matrix proteins in target organs. The primary tumor plays a key role in the development of premetastatic niches by producing tumor-derived soluble factors which mobilize bone marrow-derived hematopoietic cells to the premetastatic niche. Exosomes-derived from the primary tumor also contribute to cancer-favorable microenvironment in the premetastatic niches. These changes prime the initially healthy organ microenvironment and render it amenable for subsequent metastatic cell colonization.

Solitary Primary Central Nervous System Lymphoma Mimicking Third Ventricular Colloid Cyst-Case Report and Review of Literature.

BACKGROUND: Primary central nervous system lymphoma is a rare malignant tumor of the central nervous system. It is associated with poor prognosis and accounts for 0.7%-0.9% of all lymphomas and only 0.3%-1.5% of intracranial tumors. Typically, these lesions are in the cerebral white matter near the corpus callosum, the central gray matter, the basal ganglia-thalamus-hypothalamic region, the posterior fossa and the periventricular region. Only 2 cases with pure third ventricular lymphoma have been reported in the literature. CASE DESCRIPTION: A 72-year-old female patient known to have type II diabetes mellitus treated with insulin, hypertension, chronic kidney disease, dyslipidemia, and obesity presented with a history of acute confusion and urinary incontinence. No headache was reported on admission, but previously she had intermittent mild headaches and generalized body aches. She had no history of visual symptoms. Her family said she was mildly confused and had memory difficulties that started acutely 2 days before presentation to the hospital. The patient had urgent computed tomography of the brain, which showed a hyperdense lesion in the region of the foramen of Monro. Pre-operative images diagnosed the case as colloid cyst, but post-operative histopathology proved the lesion to be primary CNS lymphoma. CONCLUSIONS: Eleven months after surgery, the patient is fully consciousness and oriented, with no memory issues or neurologic deficit. She is back to her baseline activities. We are reporting this case for the rarity of the disease and the unusual location of it.

Modelling the Impact of Different Tuberculosis Control Interventions on the Prevalence of Tuberculosis in an Overcrowded Prison.

The aim of this study was to simulate the effects of tuberculosis (TB) treatment strategies interventions in an overcrowded and poorly ventilated prison with both high (5 months) and low (3 years) turnover of inmates against improved environmental conditions. We used a deterministic transmission model to simulate the effects of treatment of latent TB infection and active TB, or the combination of both treatment strategies. Without any intervention, the TB prevalence is estimated to increase to 8.8% for a prison with low turnover of inmates but modestly stabilize at 5.8% for high-turnover prisons in a 10-year period. Reducing overcrowding from 6 to 4 inmates per housing cell and increasing the ventilation rate from 2 to 12 air changes per hour combined with any treatment strategy would further reduce the TB prevalence to as low as 0.98% for a prison with low inmate turnover.

High-Grade B-Cell Neoplasm with Surface Light Chain Restriction and Tdt Coexpression Evolved in a MYC-Rearranged Diffuse Large B-Cell Lymphoma: A Dilemma in Classification.

According to World Health Organization (WHO) classification (2008), B-cell neoplasms are classified into precursor B-cell or a mature B-cell phenotype and this classification was also kept in the latest WHO revision (2016). We are reporting a male patient in his fifties, with tonsillar swelling diagnosed as diffuse large B-cell lymphoma (DLBCL), germinal center. He received 6 cycles of RCHOP and showed complete metabolic response. Two months later, he presented with severe CNS symptoms. Flow cytometry on bone marrow (BM) showed infiltration by CD10-positive Kappa-restricted B-cells with loss of CD20 and CD19, and downregulation of CD79b. Moreover, the malignant population showed Tdt expression. BM Cytogenetics revealed t(8;14)(q24;q32) within a complex karyotype. Retrospectively, MYC and Tdt immunostains performed on original diagnostic tissue and came negative for Tdt and positive for MYC. It has been rarely reported that mature B-cell neoplasms present with features of immaturity; however the significance of Tdt acquisition during disease course was not addressed before. What is unique in this case is that the emerging disease has acquired an immaturity marker while retaining some features of the original mature clone. No definitive WHO category would adopt high-grade neoplasms that exhibit significant overlapping features between mature and immature phenotypes.

Undiagnosed pulmonary tuberculosis among prisoners in Malaysia: an overlooked risk for tuberculosis in the community.

OBJECTIVES: To investigate the prevalence of previously undiagnosed active tuberculosis (TB) cases among prisoners in Malaysia's largest prison using an intensified TB case-finding strategy. METHODS: From October 2012 to May 2013, prisoners housed in two distinct units (HIV-negative and HIV-positive) were approached to participate in the TB screening study. Consenting prisoners submitted two sputum samples that were examined using GeneXpert MTB/RIF, smear microscopy and liquid culture. Socio-demographic and clinical information was collected and correlates of active TB, defined as having either a positive GeneXpert MTB/RIF or culture results, were assessed using regression analyses. RESULTS: Among the total of 559 prisoners, 442 (79.1%) had complete data; 28.7% were HIV-infected, 80.8% were men and the average age was 36.4 (SD 9.8) years. Overall, 34 (7.7%) had previously undiagnosed active TB, of whom 64.7% were unable to complete their TB treatment in prison due to insufficient time (<6 months) remaining in prison. Previously undiagnosed active TB was independently associated with older age groups (AOR 11.44 and 6.06 for age ≥ 50 and age 40-49 years, respectively) and with higher levels of immunosuppression (CD4 < 200 cells/ml) in HIV-infected prisoners (AOR 3.07, 95% CI 1.03-9.17). CONCLUSIONS: The high prevalence of previously undiagnosed active TB in this prison highlights the inadequate performance of internationally recommended case-finding strategies and suggests that passive case-finding policies should be abandoned, especially in prison settings where HIV infection is prevalent. Moreover, partnerships between criminal justice and public health treatment systems are crucial to continue TB treatment after release.

Genome Sequence of Complex HIV-1 Unique Recombinant Forms Sharing a Common Recombination Breakpoint Identified in Malaysia.

Three strains of HIV-1 unique recombinant forms (URFs) descended from subtypes B, B', and CRF01_AE were identified among people who inject drugs in Kuala Lumpur, Malaysia. These three URFs shared a common recombination breakpoint in the reverse transcriptase region, indicating frequent linkage within the drug-injecting networks in Malaysia.

Co-infections and transmission networks of HCV, HIV-1 and HPgV among people who inject drugs.

Co-infections with human immunodeficiency virus type 1 (HIV-1) and human pegivirus (HPgV) are common in hepatitis C virus (HCV)-infected individuals. However, analysis on the evolutionary dynamics and transmission network profiles of these viruses among individuals with multiple infections remains limited. A total of 228 injecting drug users (IDUs), either HCV- and/or HIV-1-infected, were recruited in Kuala Lumpur, Malaysia. HCV, HIV-1 and HPgV genes were sequenced, with epidemic growth rates assessed by the Bayesian coalescent method. Based on the sequence data, mono-, dual- and triple-infection were detected in 38.8%, 40.6% and 20.6% of the subjects, respectively. Fifteen transmission networks involving HCV (subtype 1a, 1b, 3a and 3b), HIV-1 (CRF33_01B) and HPgV (genotype 2) were identified and characterized. Genealogical estimates indicated that the predominant HCV, HIV-1 and HPgV genotypes were introduced into the IDUs population through multiple sub-epidemics that emerged as early as 1950s (HCV), 1980s (HIV-1) and 1990s (HPgV). By determining the difference in divergence times between viral lineages (ΔtMRCA), we also showed that the frequency of viral co-transmission is low among these IDUs. Despite increased access to therapy and other harm reduction interventions, the continuous emergence and coexistence of new transmission networks suggest persistent multiple viral transmissions among IDUs.

Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the 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 Malaysia's 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.

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.

Latent tuberculosis infection in a Malaysian prison: implications for a comprehensive integrated control program in prisons.

BACKGROUND: Prisons continue to fuel tuberculosis (TB) epidemics particularly in settings where access to TB screening and prevention services is limited. Malaysia is a middle-income country with a relatively high incarceration rate of 138 per 100,000 population. Despite national TB incidence rate remaining unchanged over the past ten years, data about TB in prisons and its contribution to the overall national rates does not exist. This survey was conducted to address the prevalence of latent TB infection (LTBI) in Malaysia's largest prison. METHODS: From July to December 2010, all HIV-infected and a comparative group of HIV-uninfected prisoners housed separately in Kajang prison were asked to participate in the survey after explaining the study protocol. Subjects providing informed consent were interviewed using a structured questionnaire followed by the placement of tuberculin skin test (TST) with 2 TU of PPD RT-23 to subjects not being treated for active TB. TST was read after 48-72 hours and indurations of ≥ 5 mm and ≥ 10 mm were considered positive among HIV-infected and HIV-uninfected subjects, respectively. Additionally, HIV-infected inmates underwent phlebotomy for CD4 lymphocyte count assessment. A logistic regression model was explored to determine factors associated with TST positivity. RESULTS: Overall, 286 subjects (138 HIV-infected and 148 HIV-uninfected) had complete data and TST results. The majority were men (95.1%), less than 40 years old (median age 36.0, SD 7.87), and Malaysians (93.3%). Most (82.5%) had been previously incarcerated and more than half (53.1%) reported sharing needles just prior to their incarceration. TST was positive in 88.8% (84.7% among HIV-infected and 92.5% among HIV-uninfected subjects) and was independently associated with being HIV-uninfected (AOR = 2.97, p = 0.01) and with frequent previous incarcerations (AOR = 1.22 for every one previous incarceration, p = 0.01) after adjusting for other potential confounding factors. CONCLUSIONS: The prevalence of LTBI was extraordinary high in this sample of Malaysian prisoners, regardless of their age or HIV status. This warrants further examination of the size of the problem of TB in other congregate settings and the establishment of an evidence-based TB control program in Malaysian prisons with integrated TB, HIV and substance abuse components.

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.

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.

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.

Genome sequence of the hepatitis C virus subtype 6n isolated from malaysia.

We report the full genome sequence of hepatitis C virus (HCV) subtype 6n from Kuala Lumpur, Malaysia. Phylogenetic analysis of the isolate 10MYKJ032 suggests that Southeast Asia might be the origin for the HCV subtype 6n and highlights the possible spread of this lineage from Southeast Asia to other regions.