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Immunoinformatics study on highly expressed Mycobacterium tuberculosis genes during infection

Nguyen Thi le T, Sarmiento ME, Calero R, Camacho F, Reyes F, Hossain MM, et al.

Tuberculosis (Edinb), 2014 Sep;94(5):475-81.
PMID: 25034135 DOI: 10.1016/j.tube.2014.06.004

The most important targets for vaccine development are the proteins that are highly expressed by the microorganisms during infection in-vivo. A number of Mycobacterium tuberculosis (Mtb) proteins are also reported to be expressed in-vivo at different phases of infection. In the present study, we analyzed multiple published databases of gene expression profiles of Mtb in-vivo at different phases of infection in animals and humans and selected 38 proteins that are highly expressed in the active, latent and reactivation phases. We predicted T- and B-cell epitopes from the selected proteins using HLAPred for T-cell epitope prediction and BCEPred combined with ABCPred for B-cell epitope prediction. For each selected proteins, regions containing both T- and B-cell epitopes were identified which might be considered as important candidates for vaccine design against tuberculosis.

Matched MeSH terms: Tuberculosis/prevention & control
Risk factors of tuberculosis among health care workers in Sabah, Malaysia

Jelip J, Mathew GG, Yusin T, Dony JF, Singh N, Ashaari M, et al.

Tuberculosis (Edinb), 2004;84(1-2):19-23.
PMID: 14670342

Tuberculosis (TB) is one of the main public health problems in Sabah; 30% of the total number of TB cases reported in Malaysia every year occur in Sabah. The average incidence of TB among health care workers over the past 5 years is 280.4 per 100,000 population (1, Annual Report of Sabah State TB Control Programme, 1998). At present, there are no specific measures for the prevention of TB transmission in health care facilities. A case-control study was conducted among health care workers in Sabah in 2000-2001. Cases were health care workers with TB diagnosed between January 1990 and June 2000. Controls were health care workers without TB and working in the same facility as cases during the disease episode. The study attempted to identify risk factors for TB among the study population. Data were collected through structured interviews and review of patients' records. The notification rate of TB among health care workers was significantly higher than that to the general population (Z=4.893, p<0.01). The average notification rate of TB among health care workers over the last 5 years was two times higher than in the general population (280.4/100,000 compared to 153.9/100,000). Regression results showed that ethnicity, designation, family contact and TB related knowledge did not significantly contribute to the risk of contracting TB in this study. However, after controlling for the above factors, age, gender, history of TB contact outside the workplace (other than family contact), duration of service and failure to use respiratory protection when performing high-risk procedures, were the main risk factors of TB among health care workers. This study succeeded in identifying some of the risk factors of TB among health care workers. We managed to include the large ratio of controls to case (3:1) and those cases spanned over a period of 10 years. However, the findings from the study have to be applied with caution due to the limitations of this study, which include recall bias, dropouts, and small sample size. Based on the study findings, we recommend that health care workers in the first 10 years of service should take extra precautions, such as using respiratory protection when performing procedures that are considered to be of high risk with respect to TB infection. They should also undergo TB screening at least once every 2 years and, if symptomatic, offered prophylactic treatment. The Respiratory Protection Programme should be fully implemented to help reduce the risk of TB among health care workers in Sabah.

Matched MeSH terms: Tuberculosis/prevention & control
Tuberculosis in Malaysia: problems and prospect of treatment and control

Iyawoo K

Tuberculosis (Edinb), 2004;84(1-2):4-7.
PMID: 14670340

In the early 1940s and 1950s, tuberculosis (TB) was the number one cause of death in Malaysia. Patients with TB were admitted to the many sanatoria we had in various parts of the country and were often managed by surgical means. TB chemotherapy became available only in the late 1950s. At this time, TB was already a major cause of morbidity and mortality. Realizing its seriousness, the Malaysian government launched its National TB Control Programme (NTP) in 1961. At that time, the recommended treatment for TB was a combination of three drugs, namely, streptomycin, isoniazid and paraaminosalicylic acid (PAS) given for 2 months followed by isoniazid and PAS given for 12 months. Generally the treatment used to last for 1-2 years. The National TB Centre in Kuala Lumpur functioned as the headquarters of the NTP, and the state general hospitals with their chest clinics functioned as the state directorates. From the operational point of view, every state has a state TB directorate which is known as the State TB Managerial Team (Fig. 1). This team is responsible for the implementation of the activities of the NTP at the state and district levels. Ever since 1995, the national TB directorate has been shifted to the Public Health Division of the Ministry of Health (MOH) and is now under the Director of Disease Control (Fig. 2). The National TB Centre has now been renamed as The Institute of Respiratory Medicine. Over the years from being the number one cause of death, TB has dropped to being below number 10 (Fig. 3).

Matched MeSH terms: Tuberculosis/prevention & control*
Approaches towards the development of a vaccine against tuberculosis: recombinant BCG and DNA vaccine

Mohd Nor N, Musa M

Tuberculosis (Edinb), 2004;84(1-2):102-9.
PMID: 14670351 DOI: 10.1016/j.tube.2003.08.011

The last few years have witnessed intense research on vaccine development against tuberculosis. This has been driven by the upsurge of tuberculosis cases globally, especially those caused by multi-drug-resistant Mycobacterium tuberculosis strains. Various vaccine strategies are currently being developed which can be broadly divided into the so-called living and non-living vaccines. Examples are attenuated members of the M. tuberculosis complex, recombinant mycobacteria, subunit proteins and DNA vaccines. Given current developments, we anticipate that recombinant BCG and DNA vaccines are the most promising. Multiple epitopes of M. tuberculosis may need to be cloned in a vaccine construct for the desired efficacy to be achieved. The technique of assembly polymerase chain reaction could facilitate such a cloning procedure.

Matched MeSH terms: Tuberculosis/prevention & control*
Tuberculosis vaccine candidates based on mycobacterial cell envelope components

Sarmiento ME, Alvarez N, Chin KL, Bigi F, Tirado Y, García MA, et al.

Tuberculosis (Edinb), 2019 03;115:26-41.
PMID: 30948174 DOI: 10.1016/j.tube.2019.01.003

Even after decades searching for a new and more effective vaccine against tuberculosis, the scientific community is still pursuing this goal due to the complexity of its causative agent, Mycobacterium tuberculosis (Mtb). Mtb is a microorganism with a robust variety of survival mechanisms that allow it to remain in the host for years. The structure and nature of the Mtb envelope play a leading role in its resistance and survival. Mtb has a perfect machinery that allows it to modulate the immune response in its favor and to adapt to the host's environmental conditions in order to remain alive until the moment to reactivate its normal growing state. Mtb cell envelope protein, carbohydrate and lipid components have been the subject of interest for developing new vaccines because most of them are responsible for the pathogenicity and virulence of the bacteria. Many indirect evidences, mainly derived from the use of monoclonal antibodies, support the potential protective role of Mtb envelope components. Subunit and DNA vaccines, lipid extracts, liposomes and membrane vesicle formulations are some examples of technologies used, with encouraging results, to evaluate the potential of these antigens in the protective response against Mtb.

Matched MeSH terms: Tuberculosis/prevention & control*
Isoniazid preventive therapy in correctional facilities: a systematic review

Al-Darraji HA, Kamarulzaman A, Altice FL

Int J Tuberc Lung Dis, 2012 Jul;16(7):871-9.
PMID: 22410101 DOI: 10.5588/ijtld.11.0447

Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide and the main cause of death in correctional facilities in middle- and low-income countries. Due to the closed environment and the concentration of individuals with TB-related risk factors, effective measures are required to control TB in such settings. Isoniazid preventive therapy (IPT) represents an effective and cost-effective measure. Despite international recommendations that IPT be integral to TB control, it is seldom deployed. A systematic review of interventions used to assess IPT initiation and completion in correctional facilities was conducted using published studies from two biomedical databases and relevant keywords. Additional references were reviewed, resulting in 18 eligible studies. Most (72%) studies were conducted in the United States and in jail settings (60%), with the main objective of improving completion rates inside the facility or after release. Studies that provided data about initiation and completion rates showed poor success in correctional facilities. Adverse consequences and treatment interruption ranged from 1% to 55% (median 5%) in reported studies; hepatotoxicity was the most prevalent adverse reaction. Despite its accelerating effect on the development of active TB, information on human immunodeficiency virus (HIV) status was provided in only half of the studies. Among the four studies where IPT effectiveness was assessed, the results mirror those described in community settings. Future studies require thorough assessments of IPT initiation and completion rates and adverse effects, particularly in low- and middle-income countries and where comorbid viral hepatitis may contribute significantly to outcomes, and in settings where TB and HIV are more endemic.

Matched MeSH terms: Tuberculosis/prevention & control*
Fulltext Factors contributing to poor compliance with anti-TB treatment among tuberculosis patients

Naing NN, D'Este C, Isa AR, Salleh R, Bakar N, Mahmod MR

Southeast Asian J. Trop. Med. Public Health, 2001 Jun;32(2):369-82.
PMID: 11556591

Tuberculosis (TB) has made a comeback. It has become a resurgent public health problem in developing countries in the tropics and is the leading cause of death from any single infectious agent. Non-compliance to anti-tuberculosis treatment is the most serious problem in TB control. A cross-sectional study was conducted to investigate the determinants of poor compliance with anti-tuberculosis treatment among tuberculosis patients in Kota Bharu, Kelantan, Malaysia in 1999. A total of 390 patients were included in the study of which 130 were tuberculosis patients who defaulted treatment and 260 were those compliant to treatment. Data collection was done by interviewing the patients and collecting clinical and laboratory data from their medical records. Using multiple logistic regression analysis, patients who were not on direct observed therapy (DOT) lived distant to the health facility, were non-intravenous drug users (IVDU) and were HIV positive had statistically significant higher odds of being non-compliant. Patients should be given treatment under direct supervision with special attention to IVDU and HIV positive groups. Anti-TB treatment should be accessible to patients at the nearest health center from their residence. Interventions with health education programs emphasizing the benefits of treatment compliance should be implemented by further large-scale multicentered studies.
Study site: Chest clinic, Hospital Kota Bharu, Kelantan, Malaysia

Matched MeSH terms: Tuberculosis/prevention & control
The delivery of a total tuberculosis service in a scattered rural community with poor communications

Webb AH

N Z Med J, 1973 Nov 14;78(502):412-4.
PMID: 4129253
Matched MeSH terms: Tuberculosis/prevention & control
Fulltext An evaluation of the tuberculosis control programme of Selangor State, Malaysia for the year 2001

Venugopalan B

Med J Malaysia, 2004 Mar;59(1):20-5.
PMID: 15535331 MyJurnal

In the year 2001, 1459 Tuberculosis (TB) cases (43.1/100,000 population) were notified in Selangor. The highest age specific incidence rate was among those aged above 60 years and foreigners accounted for 15% of the cases notified. Fifteen percent of the TB cases were treated in the private sector where treatment efficacy and compliance could not be evaluated. Co- infection of Human Immunodeficiency Virus (HIV) infection with TB accounted for 51% of the TB deaths notified. Screening programmes in prisons and drug rehabilitation centres had detected 11.7% of HIV/TB coinfection among HIV positive inmates screened in these institutions.

Matched MeSH terms: Tuberculosis/prevention & control*
Fulltext Tuberculosis in Malaysia: combating the old nemesis

Aziah AM

Med J Malaysia, 2004 Mar;59(1):1-3.
PMID: 15535327 MyJurnal
Matched MeSH terms: Tuberculosis/prevention & control*
Fulltext Risk of tuberculosis to healthcare workers

Liam CK

Med J Malaysia, 2001 Mar;56(1):107-11; quiz 112.
PMID: 11503290
Matched MeSH terms: Tuberculosis/prevention & control
Priorities in a modern tuberculosis program in developing countries

Sodhy JS

Med J Malaya, 1970 Mar;24(3):171-5.
PMID: 4246795
Matched MeSH terms: Tuberculosis/prevention & control*
3-year defaulters from a tuberculosis out-patient clinic

McDougall C

Med J Malaya, 1954 Dec;9(2):132-8.
PMID: 14355276
Matched MeSH terms: Tuberculosis/prevention & control*
Tuberculosis in Muruts of Pensiangan in Sabah

Roy RN

Med J Aust, 1969 Apr 26;1(17):842-8.
PMID: 4977736
Matched MeSH terms: Tuberculosis/prevention & control
Fifth meeting of the Eastern Regional Committee of the International Union against Tuberculosis

Harvey C

Med J Aust, 1967 Feb 11;1(6):302-4.
PMID: 4381144
Matched MeSH terms: Tuberculosis/prevention & control*
Is targeted removal a suitable means for tuberculosis control in wild boar?

Che'Amat A, Armenteros JA, González-Barrio D, Lima JF, Díez-Delgado I, Barasona JA, et al.

Prev Vet Med, 2016 Dec 01;135:132-135.
PMID: 27843020 DOI: 10.1016/j.prevetmed.2016.11.002

We assessed the suitability of targeted removal as a means for tuberculosis (TB) control on an intensely managed Eurasian wild boar (Sus scrofa) hunting estate. The 60km(2) large study area included one capture (treatment) site, one control site, and one release site. Each site was fenced. In the summers of 2012, 2013 and 2014, 929 wild boar were live-captured on the treatment site. All wild boar were micro-chipped and tested using an animal side lateral flow test immediately after capture in order to detect antibodies to the Mycobacterium tuberculosis complex (MTC). The wild boar were released according to their TB status: Seropositive individuals onto the release site (hunted after summer), and seronegative individuals back onto the treatment site. The annual summer seroprevalence of antibodies to the MTC declined significantly in live-captured wild boar piglets from the treatment site, from 44% in 2012 to 27% in 2013 (a reduction of 39%). However, no significant further reduction was recorded in 2014, during the third capture season. Fall-winter MTC infection prevalence was calculated on the basis of the culture results obtained for hunter-harvested wild boar. No significant changes between hunting seasons were recorded on either the treatment site or the control site, and prevalence trends over time were similar on both sites. The fall-winter MTC infection prevalence on the release site increased significantly from 40% in 2011-2012 to 64% in 2012-2013 and 2013-2014 (60% increase). Recaptures indicated a persistently high infection pressure. This experiment, the first attempt to control TB in wild boar through targeted removal, failed to reduce TB prevalence when compared to the control site. However, it generated valuable knowledge on infection pressure and on the consequences of translocating TB-infected wild boar.

Matched MeSH terms: Tuberculosis/prevention & control
Fulltext Agents of change: The role of healthcare workers in the prevention of nosocomial and occupational tuberculosis

Nathavitharana RR, Bond P, Dramowski A, Kotze K, Lederer P, Oxley I, et al.

Presse Med, 2017 Mar;46(2 Pt 2):e53-e62.
PMID: 28256382 DOI: 10.1016/j.lpm.2017.01.014

Healthcare workers (HCWs) play a central role in global tuberculosis (TB) elimination efforts but their contributions are undermined by occupational TB. HCWs have higher rates of latent and active TB than the general population due to persistent occupational TB exposure, particularly in settings where there is a high prevalence of undiagnosed TB in healthcare facilities and TB infection control (TB-IC) programmes are absent or poorly implemented. Occupational health programmes in high TB burden settings are often weak or non-existent and thus data that record the extent of the increased risk of occupational TB globally are scarce. HCWs represent a limited resource in high TB burden settings and occupational TB can lead to workforce attrition. Stigma plays a role in delayed diagnosis, poor treatment outcomes and impaired well-being in HCWs who develop TB. Ensuring the prioritization and implementation of TB-IC interventions and occupational health programmes, which include robust monitoring and evaluation, is critical to reduce nosocomial TB transmission to patients and HCWs. The provision of preventive therapy for HCWs with latent TB infection (LTBI) can also prevent progression to active TB. Unlike other patient groups, HCWs are in a unique position to serve as agents of change to raise awareness, advocate for necessary resource allocation and implement TB-IC interventions, with appropriate support from dedicated TB-IC officers at the facility and national TB programme level. Students and community health workers (CHWs) must be engaged and involved in these efforts. Nosocomial TB transmission is an urgent public health problem and adopting rights-based approaches can be helpful. However, these efforts cannot succeed without increased political will, supportive legal frameworks and financial investments to support HCWs in efforts to decrease TB transmission.

Matched MeSH terms: Tuberculosis/prevention & control*
Prevention of transmission of HIV, hepatitis B virus, hepatitis C virus, and tuberculosis in prisoners

Kamarulzaman A, Reid SE, Schwitters A, Wiessing L, El-Bassel N, Dolan K, et al.

Lancet, 2016 Sep 10;388(10049):1115-1126.
PMID: 27427456 DOI: 10.1016/S0140-6736(16)30769-3

The prevalence of HIV, hepatitis B virus, hepatitis C virus, and tuberculosis are higher in prisons than in the general population in most countries worldwide. Prisons have emerged as a risk environment for these infections to be further concentrated, amplified, and then transmitted to the community after prisoners are released. In the absence of alternatives to incarceration, prisons and detention facilities could be leveraged to promote primary and secondary prevention strategies for these infections to improve prisoners health and reduce risk throughout incarceration and on release. Effective treatment of opioid use disorders with opioid agonist therapies (eg, methadone and buprenorphine) prevents blood-borne infections via reductions in injection in prison and after release. However, large gaps exist in the implementation of these strategies across all regions. Collaboration between the criminal justice and public health systems will be required for successful implementation of these strategies.

Matched MeSH terms: Tuberculosis/prevention & control*
Fulltext Cotrimoxazole prophylaxis decreases tuberculosis risk among Asian patients with HIV

Ku SW, Jiamsakul A, Joshi K, Pasayan MKU, Widhani A, Chaiwarith R, et al.

J Int AIDS Soc, 2019 Mar;22(3):e25264.
PMID: 30924281 DOI: 10.1002/jia2.25264

INTRODUCTION: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV-infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear.
METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.
RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.
CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.

Matched MeSH terms: Tuberculosis/prevention & control*
Fulltext New opportunities in tuberculosis prevention: implications for people living with HIV

González Fernández L, Casas EC, Singh S, Churchyard GJ, Brigden G, Gotuzzo E, et al.

J Int AIDS Soc, 2020 Jan;23(1):e25438.
PMID: 31913556 DOI: 10.1002/jia2.25438

INTRODUCTION: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally.
DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary.
CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.

Matched MeSH terms: Tuberculosis/prevention & control*

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