Journal Article > ReviewSubscription Only
Curr Opin HIV AIDS. 2019 January 1; Volume 14 (Issue 1); 21-27.; DOI:10.1097/COH.0000000000000517
Fargher J, Reuter A, Furin J
Curr Opin HIV AIDS. 2019 January 1; Volume 14 (Issue 1); 21-27.; DOI:10.1097/COH.0000000000000517
PURPOSE OF REVIEW
More than two billion people are infected with Mycobacterium tuberculosis and few of them are ever offered therapy in spite of such treatment being associated with reduced rates of morbidity and mortality. This article reviews the current recommendations on the diagnosis and treatment of TB infection (or what is commonly referred to as 'prophylaxis' or 'preventive therapy' of latent TB) and discusses barriers to implementation that have led to low demand for this life-saving therapeutic intervention.
RECENT FINDINGS
Treatment of infection for both TB and drug-resistant TB is well tolerated and effective, and several new, shorter regimens - including rfiapenitine-based regimens of 1 month and 12 weeks duration - have been shown to be effective. Not all persons infected with TB go on to develop disease and the risk is the highest in the first 2 years after infection. Given this, additional work is needed to better identify those at the highest risk of developing active TB.
SUMMARY
Practitioners should offer newer, shorter regimens to persons who are infected with TB and at high risk of developing disease, including people living with HIV and household contacts of people living with TB who are age 5 years and under. This includes individuals who have been exposed to drug-resistant forms of disease. Socioeconomic risk factors may play a key role in the development of TB disease and should also be addressed.
More than two billion people are infected with Mycobacterium tuberculosis and few of them are ever offered therapy in spite of such treatment being associated with reduced rates of morbidity and mortality. This article reviews the current recommendations on the diagnosis and treatment of TB infection (or what is commonly referred to as 'prophylaxis' or 'preventive therapy' of latent TB) and discusses barriers to implementation that have led to low demand for this life-saving therapeutic intervention.
RECENT FINDINGS
Treatment of infection for both TB and drug-resistant TB is well tolerated and effective, and several new, shorter regimens - including rfiapenitine-based regimens of 1 month and 12 weeks duration - have been shown to be effective. Not all persons infected with TB go on to develop disease and the risk is the highest in the first 2 years after infection. Given this, additional work is needed to better identify those at the highest risk of developing active TB.
SUMMARY
Practitioners should offer newer, shorter regimens to persons who are infected with TB and at high risk of developing disease, including people living with HIV and household contacts of people living with TB who are age 5 years and under. This includes individuals who have been exposed to drug-resistant forms of disease. Socioeconomic risk factors may play a key role in the development of TB disease and should also be addressed.
Journal Article > CommentaryFull Text
Bull World Health Organ. 2015 July 1; Volume 93 (Issue 7); 491-497.; DOI:10.2471/BLT.14.138925
Cox HS, Furin J, Mitnick CD, Daniels C, Cox V, et al.
Bull World Health Organ. 2015 July 1; Volume 93 (Issue 7); 491-497.; DOI:10.2471/BLT.14.138925
Approximately half a million people are thought to develop multidrug-resistant tuberculosis annually. Barely 20% of these people currently receive recommended treatment and only about 10% are successfully treated. Poor access to treatment is probably driving the current epidemic, via ongoing transmission. Treatment scale-up is hampered by current treatment regimens, which are lengthy, expensive, poorly tolerated and difficult to administer in the settings where most patients reside. Although new drugs provide an opportunity to improve treatment regimens, current and planned clinical trials hold little promise for developing regimens that will facilitate prompt treatment scale-up. In this article we argue that clinical trials, while necessary, should be complemented by timely, large-scale, operational research that will provide programmatic data on the use of new drugs and regimens while simultaneously improving access to life-saving treatment. Perceived risks - such as the rapid development of resistance to new drugs - need to be balanced against the high levels of mortality and transmission that will otherwise persist. Doubling access to treatment and increasing treatment success could save approximately a million lives over the next decade.
Journal Article > CommentaryFull Text
Lancet Infect Dis. 2019 March 1; Volume 19 (Issue 3); 224-225.; DOI:10.1016/S1473-3099(18)30742-4
Acquah R, Furin J
Lancet Infect Dis. 2019 March 1; Volume 19 (Issue 3); 224-225.; DOI:10.1016/S1473-3099(18)30742-4
A universal regimen. At times this appears to be the Holy Grail in tuberculosis treatment. For decades, policy makers, public health specialists, and donors have argued that in order to control—and these days to “End TB”—a simplified approach that offers everyone the same regimen is our best bet. They argue that countries, programmes, and the people who work in them, are incapable of managing complexity when it comes to tackling tuberculosis. Fears abound that recommending anything other than a basic treatment algorithm will lead to mismanagement and a tuberculosis crisis worse that what we see now. Never mind that such an approach erases patient individuality and unique human treatment needs. “Keep it simple” remains the mantra in tuberculosis control to this day.
Journal Article > ResearchAbstract Only
Int J Tuberc Lung Dis. 2022 October 1; Volume 26 (Issue 10); 956-962.; DOI:DOI: 10.5588/ijtld.22.0115
Mangochi P, Bossard C, Catacutan C, Van Laeken D, Kwitonda C, et al.
Int J Tuberc Lung Dis. 2022 October 1; Volume 26 (Issue 10); 956-962.; DOI:DOI: 10.5588/ijtld.22.0115
BACKGROUND
Incarcerated individuals, especially in high HIV and TB burden settings, are at increased risk of latent TB infection and/or TB disease. We implemented a comprehensive HIV-TB intervention in a Malawi prison and studied its feasibility.
METHODS
Between February and December 2019, consenting individuals underwent screening for HIV, TB infection and TB disease. HIV-positive individuals without TB disease were treated with a fixed-dose combination of isoniazid, cotrimoxazole and vitamin B6 (INH-CTX-B6). HIV-negative persons with TB infection received 12 weeks of isoniazid and rifapentine (3HP).
RESULTS
Of 1,546 consenting individuals, 1,498 (96.9%) were screened and 1,427 (92.3%) included in the analysis: 96.4% were male, the median age was 31 years (IQR 25–38). Twenty-nine (2.1%) participants were diagnosed with TB disease, of whom 89.7% started and 61.5% completed TB treatment. Of the 1,427 included, 341 (23.9%) were HIV-positive, of whom 98.5% on antiretroviral therapy and 95% were started on INH-CTX-B6. Among 1,086 HIV-negative participants, 1,015 (93.5%) underwent the tuberculin skin test (TST), 670 (65.9%) were TST-positive, 666 (99.4%) started 3HP and 570 (85.5%) completed 3HP treatment.
CONCLUSION
A comprehensive TB screening and treatment package among incarcerated individuals was acceptable and feasible, and showed high prevalence of HIV, TB disease and TB infection. Treatment uptake was excellent, but treatment completion needs to be improved. Greater investment in comprehensive HIV-TB services, including access to shorter TB regimens and follow-up upon release, is needed for incarcerated individuals.
Incarcerated individuals, especially in high HIV and TB burden settings, are at increased risk of latent TB infection and/or TB disease. We implemented a comprehensive HIV-TB intervention in a Malawi prison and studied its feasibility.
METHODS
Between February and December 2019, consenting individuals underwent screening for HIV, TB infection and TB disease. HIV-positive individuals without TB disease were treated with a fixed-dose combination of isoniazid, cotrimoxazole and vitamin B6 (INH-CTX-B6). HIV-negative persons with TB infection received 12 weeks of isoniazid and rifapentine (3HP).
RESULTS
Of 1,546 consenting individuals, 1,498 (96.9%) were screened and 1,427 (92.3%) included in the analysis: 96.4% were male, the median age was 31 years (IQR 25–38). Twenty-nine (2.1%) participants were diagnosed with TB disease, of whom 89.7% started and 61.5% completed TB treatment. Of the 1,427 included, 341 (23.9%) were HIV-positive, of whom 98.5% on antiretroviral therapy and 95% were started on INH-CTX-B6. Among 1,086 HIV-negative participants, 1,015 (93.5%) underwent the tuberculin skin test (TST), 670 (65.9%) were TST-positive, 666 (99.4%) started 3HP and 570 (85.5%) completed 3HP treatment.
CONCLUSION
A comprehensive TB screening and treatment package among incarcerated individuals was acceptable and feasible, and showed high prevalence of HIV, TB disease and TB infection. Treatment uptake was excellent, but treatment completion needs to be improved. Greater investment in comprehensive HIV-TB services, including access to shorter TB regimens and follow-up upon release, is needed for incarcerated individuals.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2014 October 3; Volume 19 (Issue 10); 1479-84.; DOI:10.5588/ijtld.14.0277
Furin J, Isaakidis P, Reid AJ, Kielmann K
Int J Tuberc Lung Dis. 2014 October 3; Volume 19 (Issue 10); 1479-84.; DOI:10.5588/ijtld.14.0277
OBJECTIVES
To understand the impact of past experiences of anti-tuberculosis treatment among patients co-infected with the human immunodeficiency virus and multidrug-resistant tuberculosis (MDR-TB) on perceptions and attitudes towards treatment.
METHODS
Qualitative study using in-depth interviews with 12 HIV-MDR-TB co-infected patients in Mumbai, India.
RESULTS
Patients reported unnecessarily long pathways to care and fatigue with diagnostic and treatment procedures. In particular, they expressed concerns over the lack of efficacy of their current treatment regimen based on their experiences with anti-tuberculosis treatment regimens in the past.
CONCLUSION
Patients reported negative experiences with previous HIV and anti-tuberculosis treatment. Access to early diagnosis and rapid initiation of integrated care for HIV-MDR-TB co-infected patients, with a strong, patient-centered support system, could help to combat the low morale and lack of faith in treatment described in this group of patients.
To understand the impact of past experiences of anti-tuberculosis treatment among patients co-infected with the human immunodeficiency virus and multidrug-resistant tuberculosis (MDR-TB) on perceptions and attitudes towards treatment.
METHODS
Qualitative study using in-depth interviews with 12 HIV-MDR-TB co-infected patients in Mumbai, India.
RESULTS
Patients reported unnecessarily long pathways to care and fatigue with diagnostic and treatment procedures. In particular, they expressed concerns over the lack of efficacy of their current treatment regimen based on their experiences with anti-tuberculosis treatment regimens in the past.
CONCLUSION
Patients reported negative experiences with previous HIV and anti-tuberculosis treatment. Access to early diagnosis and rapid initiation of integrated care for HIV-MDR-TB co-infected patients, with a strong, patient-centered support system, could help to combat the low morale and lack of faith in treatment described in this group of patients.
Journal Article > CommentaryFull Text
Lancet Respir Med. 2020 September 1; Volume 8 (Issue 9); 844-846.; DOI:10.1016/S2213-2600(20)30311-8
Keene CM, Mohr-Holland E, Cassidy T, Scott V, Nelson AM, et al.
Lancet Respir Med. 2020 September 1; Volume 8 (Issue 9); 844-846.; DOI:10.1016/S2213-2600(20)30311-8
Journal Article > LetterFull Text
Int J Tuberc Lung Dis. 2021 May 1; Volume 25 (Issue 5); 409-412.; DOI:10.5588/ijtld.21.0010
Mohr-Holland E, Daniels J, Douglas-Jones B, Mema N, Scott V, et al.
Int J Tuberc Lung Dis. 2021 May 1; Volume 25 (Issue 5); 409-412.; DOI:10.5588/ijtld.21.0010
Journal Article > ResearchFull Text
Lancet Respir Med. 2017 March 15 (Issue 4)
Dheda K, Gumbo T, Maartens G, Dooley KE, McNerney R, et al.
Lancet Respir Med. 2017 March 15 (Issue 4)
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.
Journal Article > ResearchFull Text
Trop Med Infect Dis. 2022 January 31; Volume 7 (Issue 2); 21.; DOI: 10.3390/tropicalmed7020021
Reuter A, Beko B, Memani B, Furin J, Daniels J, et al.
Trop Med Infect Dis. 2022 January 31; Volume 7 (Issue 2); 21.; DOI: 10.3390/tropicalmed7020021
Substance use (SU) is associated with poor rifampicin-resistant tuberculosis (RR-TB) treatment outcomes. In 2017, a SBIRT (SU screening-brief intervention-referral to treatment) was integrated into routine RR-TB care in Khayelitsha, South Africa. This was a retrospective study of persons with RR-TB who were screened for SU between 1 July 2018 and 30 September 2020 using the ASSIST (Alcohol, Smoking and Substance Involvement Screening Test). Here we describe outcomes from this program. Persons scoring moderate/high risk received a brief intervention and referral to treatment. Overall, 333 persons were initiated on RR-TB treatment; 38% (n = 128) were screened for SU. Of those, 88% (n = 113/128) reported SU; 65% (n = 83/128) had moderate/high risk SU. Eighty percent (n = 103/128) reported alcohol use, of whom 52% (n = 54/103) reported moderate/high risk alcohol use. Seventy-seven persons were screened for SU within ≤2 months of RR-TB treatment initiation, of whom 69%, 12%, and 12% had outcomes of treatment success, loss to follow-up and death, respectively. Outcomes did not differ between persons with no/low risk and moderate/high risk SU or based on the receipt of naltrexone (p > 0.05). SU was common among persons with RR-TB; there is a need for interventions to address this co-morbidity as part of "person-centered care". Integrated, holistic care is needed at the community level to address unique challenges of persons with RR-TB and SU.
Journal Article > CommentaryFull Text
Lancet HIV. 2018 September 8; Volume 392 (Issue 10150); 797-798.; DOI:10.1016/S0140-6736(18)31670-2
Reuter A, Furin J
Lancet HIV. 2018 September 8; Volume 392 (Issue 10150); 797-798.; DOI:10.1016/S0140-6736(18)31670-2