Evaluation of the tuberculosis control programme in prisons and the post-release continuation of tuberculosis treatment in Malaysia

Background: Poorly managed tuberculosis (TB) control programmes in prisons have detrimental health consequences, placing prisoners at an increased risk for TB morbidity and mortality. This situation could further fuel the TB epidemic in the general population when prisoners are released with uncompleted treatment in prisons and default from treatment in the community. Despite the recognised risk, limited information exists about the burden of TB, the performance of TB control programmes, and the continuity of TB care after release from prisons in Malaysia, a country with an increasing TB burden over the past two decades. Objectives: This PhD project was designed to investigate the prevalence and correlates of active TB among new prison entrants, to assess gaps in the performance of the prison’s TB programme using standardised parameters, to investigate the proportion of released prisoners who continue treatment in the community, and to evaluate factors influencing the continuation of TB treatment after release from prisons in Malaysia. Methods: In the first study, we screened prisoners entering the largest prison in Malaysia to determine those who needed further TB assessment. All HIV-infected and symptomatic non-HIV infected prisoners were asked to submit sputum specimens to be examined using GeneXpert MTB/RIF (Xpert) or culture. Factors associated with TB disease, define as Xpert- or culture-positive tests, were assessed using regression analyses. In the second study, we developed parameters and assessable indicators to evaluate gaps in the performance of the TB control programme in the same prison. The parameters include policies and human resources; screening, case detection and notification; treatment initiation, follow-up, and outcome; TB care for HIV-infected prisoners; and knowledge about TB. Data gathering tools and data sources (local and international TB guidelines and TB system assessment publications) were utilised to measure the performance indicators under these parameters and determine system performance gaps. In the third study, prisoners who were due to be released from five prisons were recruited and followed up to identify the proportion of former prisoners who continued treatment in the community. Factors associated with failure to register at a TB clinic within 30 days of release were assessed in regression analyses. In the fourth study, factors influencing the continuation of TB treatment in the community were evaluated in a group of prisoners with previous TB episodes using in-depth interviews. We utilised a thematic framework analysis to identify relevant themes. Results: In the first study, 10,335 participants were recruited. Among HIV-infected prisoners (N=214), 12.6% had TB disease compared with 0.29% of non-HIV-infected prisoners. Among non-HIV infected prisoners, prevalent TB disease was independently associated with older age, current drug use, a previous TB episode, and being underweight. In the second study, we found that the national TB guidelines did not include a section on TB in prisons and that there was an average of 2.19 healthcare workers for every 1,000 prisoners. Furthermore, only 54.2% of new entrants were screened for TB, there was a 37.6% case detection ratio, and only 45.5% of TB cases were notified to the national TB programme. While treatment initiation was high (91%), only half (50.7%) were followed up after two months inside the prison, the treatment success rate was 72.8%, the mortality ratio was 125 per 100,000 prisoners, and only 73.3% were offered TB documentation before release. TB care for HIV-infected prisoners was similarly suboptimal with 22.1% screened for TB disease at entry, only 1.6% were provided with preventive therapy, and 12.9% were prescribed HIV treatment while on TB treatment. Knowledge about TB was very limited, particularly among prisoners compared to prison officers (6.8% and 67.2% correctly answered TB questions, respectively). In the third study, 106 participants recruited. Of these, 47 (44.3%) did not register at a TB clinic to continue treatment after release, and this was independently associated with younger age, pre-incarceration unstable housing and employment, failure to provide contact details, a previous TB episode, and not being supplied with TB documentation at the time of the release from prisons. In the fourth study, we recruited five prisoners who continued, and seven who discontinued treatment of their TB after release from prisons. Key themes related to the continuation of TB treatment after release were the prison environment and attention to prisoner care, prisoner perception and attitude, the presence of a supportive environment during the transition to the community, social support, and welcoming community healthcare services. Conclusion There is a high prevalence of TB disease among new entrants to prison in Malaysia, likely representing cases missed by the community health services. There are several gaps in the performance of the TB control programme in prisons; a situation that may promote TB transmission in prisons and the larger general population. Almost half of the prisoners who are released while still on TB treatment abandons treatment after release and that several factors influence whether they continue treatment in the community. These findings warrant the establishment of an effective TB control programme in prisons supported with policy changes, proper funding, trained healthcare workers and adequate communication between the prisons and the public health department

Evaluation of the tuberculosis control programme in prisons and the post-release continuation of tuberculosis treatment in Malaysia

Background: Poorly managed tuberculosis (TB) control programmes in prisons have detrimental health consequences, placing prisoners at an increased risk for TB morbidity and mortality. This situation could further fuel the TB epidemic in the general population when prisoners are released with uncompleted treatment in prisons and default from treatment in the community. Despite the recognised risk, limited information exists about the burden of TB, the performance of TB control programmes, and the continuity of TB care after release from prisons in Malaysia, a country with an increasing TB burden over the past two decades. Objectives: This PhD project was designed to investigate the prevalence and correlates of active TB among new prison entrants, to assess gaps in the performance of the prison’s TB programme using standardised parameters, to investigate the proportion of released prisoners who continue treatment in the community, and to evaluate factors influencing the continuation of TB treatment after release from prisons in Malaysia. Methods: In the first study, we screened prisoners entering the largest prison in Malaysia to determine those who needed further TB assessment. All HIV-infected and symptomatic non-HIV infected prisoners were asked to submit sputum specimens to be examined using GeneXpert MTB/RIF (Xpert) or culture. Factors associated with TB disease, define as Xpert- or culture-positive tests, were assessed using regression analyses. In the second study, we developed parameters and assessable indicators to evaluate gaps in the performance of the TB control programme in the same prison. The parameters include policies and human resources; screening, case detection and notification; treatment initiation, follow-up, and outcome; TB care for HIV-infected prisoners; and knowledge about TB. Data gathering tools and data sources (local and international TB guidelines and TB system assessment publications) were utilised to measure the performance indicators under these parameters and determine system performance gaps. In the third study, prisoners who were due to be released from five prisons were recruited and followed up to identify the proportion of former prisoners who continued treatment in the community. Factors associated with failure to register at a TB clinic within 30 days of release were assessed in regression analyses. In the fourth study, factors influencing the continuation of TB treatment in the community were evaluated in a group of prisoners with previous TB episodes using in-depth interviews. We utilised a thematic framework analysis to identify relevant themes. Results: In the first study, 10,335 participants were recruited. Among HIV-infected prisoners (N=214), 12.6% had TB disease compared with 0.29% of non-HIV-infected prisoners. Among non-HIV infected prisoners, prevalent TB disease was independently associated with older age, current drug use, a previous TB episode, and being underweight. In the second study, we found that the national TB guidelines did not include a section on TB in prisons and that there was an average of 2.19 healthcare workers for every 1,000 prisoners. Furthermore, only 54.2% of new entrants were screened for TB, there was a 37.6% case detection ratio, and only 45.5% of TB cases were notified to the national TB programme. While treatment initiation was high (91%), only half (50.7%) were followed up after two months inside the prison, the treatment success rate was 72.8%, the mortality ratio was 125 per 100,000 prisoners, and only 73.3% were offered TB documentation before release. TB care for HIV-infected prisoners was similarly suboptimal with 22.1% screened for TB disease at entry, only 1.6% were provided with preventive therapy, and 12.9% were prescribed HIV treatment while on TB treatment. Knowledge about TB was very limited, particularly among prisoners compared to prison officers (6.8% and 67.2% correctly answered TB questions, respectively). In the third study, 106 participants recruited. Of these, 47 (44.3%) did not register at a TB clinic to continue treatment after release, and this was independently associated with younger age, pre-incarceration unstable housing and employment, failure to provide contact details, a previous TB episode, and not being supplied with TB documentation at the time of the release from prisons. In the fourth study, we recruited five prisoners who continued, and seven who discontinued treatment of their TB after release from prisons. Key themes related to the continuation of TB treatment after release were the prison environment and attention to prisoner care, prisoner perception and attitude, the presence of a supportive environment during the transition to the community, social support, and welcoming community healthcare services. Conclusion There is a high prevalence of TB disease among new entrants to prison in Malaysia, likely representing cases missed by the community health services. There are several gaps in the performance of the TB control programme in prisons; a situation that may promote TB transmission in prisons and the larger general population. Almost half of the prisoners who are released while still on TB treatment abandons treatment after release and that several factors influence whether they continue treatment in the community. These findings warrant the establishment of an effective TB control programme in prisons supported with policy changes, proper funding, trained healthcare workers and adequate communication between the prisons and the public health department

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

BackgroundThe 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.MethodsIn 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.FindingsWe 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 (2), 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.InterpretationC-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.FundingWorld Health Organization

Automaattisen hitsauskoneen modernisointi

Tämä insinöörityö tehtiin Insinööritoimisto Ketema Oy:lle (Ketema). Ketema on pieni suomalainen yritys jonka päätoimiala on teollisuuden sähkökäyttöjen suunnittelu ja toteutus asiakkaan yksilöllisten tarpeiden mukaisesti. Tämän insinöörityön tavoitteena oli suunnitella ja toteuttaa automaattisen hitsauskoneen liikkeenohjauslaitteistojen modernisointi. Modernisoinnissa käytettäviksi laitteistoiksi oli valittu jo ennen tämän työn aloitusta Siemensin uudemmat version aiemmin käytetyistä laitteista. Modernisoinnin yhteydessä ohjaus- ja käyttölaitteistojen välinen kommunikaatio muutettiin Profinet -väyläpohjaiseksi ratkaisuksi, joka osaltaan vähentää työmäärää sekä sähkösuunnittelun että -asennusten osalta. Työn tuloksena saatiin laadittua suunnitelmat ja ohjelmistototeutus hitsauskoneen modernisoimiseksi. Suunnittelun lähestymistavaksi otettiin tarpeettomien muutosten minimointi alkuperäisen ja uuden koneen välillä. Tämä lähestymistapa mahdollisti kaksi käytännöllistä asiaa: 1) saavutettiin aikaisemmin tehdyn ohjelmistototeutuksen mahdollisimman suuri uudelleenkäyttöaste ja 2) pidettiin koneen käytettävyys operaattorin kannalta ennallaan. Työn suunnitteluosuuden aikana kävi ilmeiseksi, että modernisoinnin kohteeksi ajateltua konetta ei voida vapauttaa päivittäisestä tuotantokäytöstä johtuen asiakasyrityksen tuotantotilanteesta. Asiakasyrityksellä oli muutenkin tarve lisätä automaattista hitsauskapasiteettia, joten ratkaisuksi tilanteeseen tuli uuden koneen rakentaminen. Mekaniikka kopioidaan vanhasta koneesta minimaalisin muutoksin ja ohjaus- ja käyttölaitteistot toteutetaan tämän työn suunnitelmien mukaisesti. Insinöörityön tekemisen ja alkuperäisen tavoitteen kannalta asiassa ei kuitenkaan ole eroa. Tämän työn valmistumisen aikaan uusi kone on kokoonpanossa, joten koneen käyttöönotosta ei tämän työn tekemisen aikana saatu kokemusta. Perustavanlaatuisia ongelmia aikaisempien koneiden kohdalla saadun kokemuksen perusteella ei ole odotettavissa, mutta joitain pieniä yllätyksiä lähes varmasti.This thesis work was done for Insinööritoimisto Ketema Oy (Ketema). Ketema is small Finnish company that has specialized in planning and implementing industrial automation systems according to customers’ needs. The goal of this thesis work was to design and implement modernization of motion control devices in an automatic welding machine. The new devices are manufactured by Siemens. As part of the project, the communication between control unit and drive units was changed to Profinet. This change helps in reducing the work load both in electric design as well as in wiring the equipment during the device installation work. The thesis work resulted in appropriate design plans and software implementation fulfilling the set goal. All unnecessary changes were minimized. This approach gave two practical benefits: 1) maximal re-use of existing SW implementation and 2) daily operation of the machine is as close to original machine as possible. During the design phase it became obvious that the target machine could not be released from daily production for the modernization work. Since the client had clear need for in-creasing welding capacity, the solution was to build a new welding machine where the me-chanics was were copied from old machine and the motion control systems were as de-signed in this project. However, this makes no significant change considering the original goal of the thesis work. At the time of completing the thesis work, the new machine is under construction. Because of this, the introduction of the machine into production use remains to be done. No major challenges are expected but naturally there will be some minor surprises to cope with

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

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

<div><p>Background</p><p>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.</p> <p>Methods</p><p>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.</p> <p>Results</p><p>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).</p> <p>Conclusions</p><p>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.</p> </div

The recruitment and findings flowchart.

<p>The recruitment and findings flowchart.</p

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

<div><p>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 <i>gag-pol</i> and <i>nef</i> 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 Bʹ 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.</p></div

Plausible genetic recombination events leading to the generation of HIV-1 CRF74_01B.

<p>Using information on the recombination structures and phylogenetic inference of CRF74_01B and other genetically related CRFs as possible parental lineages, a chronology of recombination events leading to the emergence of CRF74_01B was proposed. The diagram highlights CRF74_01B as a second-generation recombinant with an estimated tMRCA between 1994 and 1996.</p

Recombination structures and sub-genomic maximum clade credibility tree reconstructions.

<p>Recombination structures of HIV-1 CRF33_01B, CRF53_01B and CRF74_01B were shown. Shared recombination breakpoints between these CRFs were indicated by dashed lines. Maximum clade credibility trees for the <i>gag</i> region (region I; HXB2: 790–2052) and <i>pol-env</i> region (region VII; HXB2: 3326–9012) of CRF74_01B and other relevant reference sequences were reconstructed. The means of tMRCA of CRF74_01B for region I and region VII were estimate around 1996.2 and 1993.9, respectively, with the 95% credibility intervals stated in parentheses.</p