Immigration from areas of high incidence is thought to have fueled the resurgence of tuberculosis (TB) in areas of low incidence. To reduce the risk of disease in low-incidence areas, the main countermeasure has been the screening of immigrants on arrival. This measure is based on the assumption of a prompt decline in the incidence of TB in immigrants during their first few years of residence in a country with low overall incidence. We have documented that this assumption is not true for 619 Somali immigrants reported in Denmark as having TB. The annual incidence of TB declined only gradually during the first 7 years of residence, from an initial 2,000 per 100,000 to 700 per 100,000. The decline was described by an exponential function with a half-time of 5.7 (95% confidence interval 4.0 to 9.7) years. This finding seriously challenges the adequacy of the customary practice of screening solely on arrival.

As countries approach the elimination phase of tuberculosis, specific problems and challenges emerge, due to the steadily declining incidence in the native population, the gradually increasing importance of the importation of latent tuberculosis infection and tuberculosis from other countries and the emergence of groups at particularly high risk of tuberculosis. Therefore, a Working Group of the World Health Organization (WHO), the International Union Against Tuberculosis and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association (KNCV) have developed a new framework for low incidence countries based on concepts and definitions consistent with those of previous recommendations from WHO/IUATLD Working Groups. In low-incidence countries, a broader spectrum of interventions is available and feasible, including: 1) a general approach to tuberculosis which ensures rapid detection and treatment of all the cases and prevention of unnecessary deaths; 2) an overall control strategy aimed at reducing the incidence of tuberculosis infection (risk-group management and prevention of transmission of infection in institutional settings) and 3) a tuberculosis elimination strategy aimed at reducing the prevalence of tuberculosis infection (outbreak management and provision of preventive therapy for specified groups and individuals). Government and private sector commitment towards elimination, effective case detection among symptomatic individuals together with active case finding in special groups, standard treatment of disease and infection, access to tuberculosis diagnostic and treatment services, prevention (e.g. through screening and bacille Calmette-Guéria immunization in specified groups), surveillance and treatment outcome monitoring are prerequisites to implementing the policy package recommended in this new framework document.

Infliximab is a humanized antibody against tumor necrosis factor alpha (TNF-alpha) that is used in the treatment of Crohn's disease and rheumatoid arthritis. Approximately 147,000 patients throughout the world have received infliximab. Excess TNF-alpha in association with tuberculosis may cause weight loss and night sweats, yet in animal models it has a protective role in the host response to tuberculosis. There is no direct evidence of a protective role of TNF-alpha in patients with tuberculosis.

Does immigration from a high-prevalence area contribute to an increased risk of tuberculosis in a low-incidence country? The tuberculosis incidence in Somalia is among the highest ever registered. Due to civil war and starvation, nearly half of all Somalis have been forced from their homes, causing significant migration to low-incidence countries. In Denmark, two-thirds of all tuberculosis patients are immigrants, half from Somalia. To determine the magnitude of Mycobacterium tuberculosis transmission between Somalis and Danes, we analyzed DNA fingerprint patterns of isolates collected in Denmark from 1992 to 1999, comprising >97% of all culture-positive patients (n = 3,320). Of these, 763 were Somalian immigrants, 55.2% of whom shared identical DNA fingerprint patterns; 74.9% of these were most likely infected before their arrival in Denmark, 23.3% were most likely infected in Denmark by other Somalis, and 1.8% were most likely infected by Danes. In the same period, only 0.9% of all Danish tuberculosis patients were most likely infected by Somalis. The Somalian immigrants in Denmark could be distributed into 35 different clusters with possible active transmission, of which 18 were retrieved among Somalis in the Netherlands. This indicated the existence of some internationally predominant Somalian strains causing clustering less likely to represent recent transmission. In conclusion, M. tuberculosis transmission among Somalis in Denmark is limited, and transmission between Somalis and Danes is nearly nonexistent. The higher transmission rates between nationalities found in the Netherlands do not apply to the situation in Denmark and not necessarily elsewhere, since many different factors may influence the magnitude of active transmission.

The whole-genome fingerprinting technique, fluorescent amplified-fragment length polymorphism (FAFLP) analysis, was applied to Mycobacterium tuberculosis. Sixty-five clinical isolates were analyzed to determine the value of FAFLP as a stand-alone genotyping technique and to compare it with the well-established IS6110 typing system. The genome sequence of M. tuberculosis strain H37Rv (S. T. Cole et al., Nature 393:537-544, 1998) was used to model computer-generated informative primer combination(s), and the precision and reproducibility of FAFLP were evaluated by comparing the results of in vitro and computer-generated experiments. Multiplex FAFLP was used to increase resolving power in a predictable and systematic fashion. FAFLP analysis was broadly congruent with IS6110 typing for those strains with multiple IS6110 copies. It was also able to resolve an epidemiologically unlinked group of strains with only one copy of IS6110; up to 10% of clinical isolates may fall into this category. For certain epidemiological investigations, it was concluded that a combination of FAFLP and IS6110 typing would give higher resolution than would either alone. FAFLP data were digital, precise, reproducible, and suitable for rapid electronic dissemination, manipulation, interlaboratory comparison, and storage in national or international epidemiological databases. Because FAFLP samples and analyzes base substitution across the genome as a whole, FAFLP could generate new information about the microevolution of the M. tuberculosis complex.

To estimate the risk and prevalence of Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB) incidence, prevalence, and mortality, including disease attributable to human immunodeficiency virus (HIV), for 212 countries in 1997.

The present study is based on notified cases of tuberculosis (TB) in the National tbc. register 1972-1996. A decline in Tb incidence was seen from 1972 and until the mid-1980's. Subsequently the trend has reversed due to an increasing number of TB cases in foreigners. In 1996, 60% of all cases of TB in Denmark were found in foreigners reflecting the rising number of refugees and their families arriving in Denmark from highly endemic areas, mainly Somalia. Among native Danes the TB incidence fell from 14 per 100,000 in 1972 to 4 per 100,000 in the 1980's and stabilized at this very low level. The unchanged incidence in Danes covers a falling incidence in the older and a rising incidence in the younger and middle-aged adult population, mainly in the capital. Approximately half of the cases occur in high-risk groups. The TB-epidemic is close to elimination in the indigenous Danish population, but the disease is maintained at a low level probably due to increased patient and doctor delay and resulting microepidemics primarily in high-risk populations.

N. Boonthanapat, K. Soontornmon, P. Pungrassami, J. Sukhasitwanichkul, S. Mahasirimongkol, C. Jiraphongsa, P. Monkongdee, K. Angchokchatchawal, A. Wiratsudakul

Abstract Objective To characterize an MDR‐TB outbreak and incorporate social network analysis with contact investigation to detect case‐contact linkages and clusters. Methods MDR‐TB cases registered in the district hospital between October 2012 and September 2015 were interviewed and their contacts were investigated. A relationship‐based weighted network was constructed. Results Among 43 interviewed MDR‐TB cases, 20 (47%) were male, five (12%) were asymptomatic (and discovered incidentally), and 22 (51%) had underlying diseases. From the documented 115 contacts, 61 (53%) were household contacts, and 49 (43%) were close (non‐household) contacts; 70 (61%) were screened for TB using various tests. In this network, we prioritized 37 contacts connected with more than one MDR‐TB patient. The largest cluster was identified in the pharmacy unit of the hospital. Conclusion This investigation yielded a significant number of MDR‐TB contacts, and social network analysis facilitated the prioritization for screening. Social network analysis is useful and feasible in this program setting and complements MDR‐TB contact investigation. This article is protected by copyright. All rights reserved.

Abstract Background Contact tracing for tuberculosis (TB) is a recommended measure to improve the case detection rate; however, actual implementation in Myanmar is limited and low detection rates have been reported. Household contacts of a known index TB case are at high risk of infection, thus a more strategic action for contact tracing is required to achieve the goal of the World Health Organization End TB Strategy. This study aimed to assess TB case detection rates among household contacts by an integrated approach and identify risk factors for TB. Methods A cross-sectional study was conducted in Mandalay City, Myanmar. Household contacts of index TB cases who had been receiving treatment for at least 3 months were prospectively investigated by an integrated approach which included modification of screening methods and active facilitation of screening investigations as follows. Initial chest x-ray (CXR) was performed for all contacts at the responsible facilities followed by sputum specimen collection for those aged ≥15 years and gene Xpert MTB/RIF examination. Transportation of all household contacts to health facilities and transportation of sputum samples for smear and gene Xpert MTB/RIF examination at centers were arranged by the research team to ensure that all household contacts received all investigations. Risk factors for TB among household contacts were identified by multiple logistic regression models. Results Of 174 household contacts, 115 were ≥ 15 years and 59 were 

Abstract Background The most prevalent strains of Mycobacterium tuberculosis (M.tb) in Beijing belong to the Beijing genotype family. The influence of Beijing genotype prevalence on the development of drug resistance, and the association of infection with Beijing genotype M.tb with population characteristics, in Beijing, however, are still unclear. Methods In this retrospective study, 1189 isolates were subjected to drug susceptibility testing (DST) and molecular epidemiological analysis, and differences in the percentage of drug resistance between Beijing and non-Beijing genotype strains were compared. The association between the occurrence of drug resistance and the prevalence of Beijing genotype M.tb was analyzed using statistical methods. Results The Beijing genotype family was the dominant genotype (83.3%) among the 1189 M.tb isolates. Beijing genotype M.tb strains were more likely to spread among males [p = 0.018, OR (95% CI):1.127(1.004–1.264)] and people in the 45–64 age group [p = 0.016, OR (95% CI): 1.438 (1.027–2.015)]. On the contrary, non-Beijing genotype M.tb strains were more probably disseminated among the over 65 [p = 0.005, OR (95% CI):0.653 (0.474–0.9)] and non-resident population [p = 0.035, OR (95% CI):1.185(0.985–1.427)]. DST results showed that 849 (71.4%) strains were fully sensitive to first-line drugs, while 340 (28.6%) strains were resistant to at least one drug, and 9% (107/1189) were MDR-TB. The frequency of INH-resistance among Beijing genotype strains was significantly lower than that among non-Beijing genotype strains (p = 0.032). In addition, the Beijing genotype family readily formed clusters. Conclusions Our findings indicate that male and middle-aged people were more probably be infected by Beijing genotype M.tb, older people and non-residents were more probably be infected by non-Beijing genotype M.tb. The high percentage of resistance to INH occurring in non-Beijing genotype strains suggested that non-Beijing genotype strains should be given much more interest in Beijing.…

Palwasha Y Khan, Tom A Yates, Muhammad Osman, Robin M Warren, Yuri van der Heijden, Nesri Padayatchi, Edward A Nardell, David Moore, Barun Mathema, Neel Gandhi, Vegard Eldholm, Keertan Dheda, Anneke C Hesseling, Valerie Mizrahi, Roxana Rustomjee, Alexander Pym

The emergence and expansion of the multidrug-resistant tuberculosis epidemic is a threat to the global control of tuberculosis. Multidrug-resistant tuberculosis is the result of the selection of resistance-conferring mutations during inadequate antituberculosis treatment. However, HIV has a profound effect on the natural history of tuberculosis, manifesting in an increased rate of disease progression, leading to increased transmission and amplification of multidrug-resistant tuberculosis. Interventions specific to HIV-endemic areas are urgently needed to block tuberculosis transmission.

Julian S Peters, Jason R Andrews, Mark Hatherill, Sabine Hermans, Leonardo Martinez, Erwin Schurr, Yuri van der Heijden, Robin Wood, Roxana Rustomjee, Bavesh D Kana

Tuberculosis claims more human lives than any other infectious disease. This alarming epidemic has fuelled the development of novel antimicrobials and diagnostics. However, public health interventions that interrupt transmission have been slow to emerge, particularly in HIV-endemic settings. Transmission of tuberculosis is complex, involving various environmental, bacteriological, and host factors, among which concomitant HIV infection is important. Preventing person-to-person spread is central to halting the epidemic and, consequently, tuberculosis transmission is now being studied with renewed interest.

Patrick G T Cudahy, Jason R Andrews, Alyssa Bilinski, David W Dowdy, Barun Mathema, Nicolas A Menzies, Joshua A Salomon, Sourya Shrestha, Ted Cohen

As the leading infectious cause of death worldwide and the primary proximal cause of death in individuals living with HIV, tuberculosis remains a global concern. Existing tuberculosis control strategies that rely on passive case-finding appear insufficient to achieve targets for reductions in tuberculosis incidence and mortality. Active case-finding strategies aim to detect infectious individuals earlier in their infectious period to reduce onward transmission and improve treatment outcomes. Empirical studies of active case-finding have produced mixed results and determining how to direct active screening to those most at risk remains a topic of intense research.

Xia Qiu, Ying Tang, Yan Yue, Yan Zeng, Wenxing Li, Yi Qu, Dezhi Mu

Effective diagnostic methods for detecting latent tuberculosis infection (LTBI) are important for its eradication. A number of studies have evaluated the use of interferon gamma-induced protein 10 (IP-10), which is elevated after tuberculosis infection, as a biomarker for LTBI, but conclusive results regarding its effectiveness have not been reported.

Abstract Background This study investigated the treatment outcomes, and factors affecting the outcomes, of new tuberculosis (TB) patients in Busan, South Korea. Methods We retrospectively analysed the citywide TB registry data (collected for the Korean National TB Surveillance System) of new TB patients registered in Busan from January 2014 to December 2015. Results A total of 4732 patients were included in this study (mean age, 52.5 ± 19.9 years; 58.4% male). The overall treatment success rate was 83.9% (cured, 20.2%; completed, 63.7%); 8.0% of patients died, and 3.6% were lost to follow-up. In multivariate analyses, a higher rate of loss to follow-up was associated with foreign nationality, registered as TB-positive at least twice, and being in Q4 (fourth quintile) or Q5 (fifth quintile) of the regional deprivation index. Conversely, a lower rate of loss to follow-up was associated with female gender, smear-positive for pulmonary TB (PTB), and the treatment outcome being reported by a public health centre. Higher mortality was associated with old age (≥ 75 years), smear-positive PTB, treatment outcome being reported by the hospital, and being registered as TB-positive twice. Lower mortality was associated with female gender, treatment outcome being reported by a public health centre or clinic, and Q5 of the regional deprivation index. Conclusions Treatment outcomes of new TB patients were sub-optimal in Busan. TB control programs should maintain close monitoring and provide greater socioeconomic support to patients at high risk of poor treatment outcomes.…

Bassirou Diarra, Mahamadou Kone, Antieme Combo Georges Togo, Yeya dit Sadio Sarro, Aissata Boubakar Cisse, Amadou Somboro, Boureima Degoga, Mohamed Tolofoudie, Bourahima Kone, Moumine Sanogo, Bocar Baya, Ousmane Kodio, Mamoudou Maiga, Michael Belson, Susan Orsega, Meryam Krit, Sounkalo Dao, Ibrahim Izétiegouma Maiga, Robert L. Murphy, Leen Rigouts, Seydou Doumbia, Souleymane Diallo, Bouke Catherine de Jong

by Bassirou Diarra, Mahamadou Kone, Antieme Combo Georges Togo, Yeya dit Sadio Sarro, Aissata Boubakar Cisse, Amadou Somboro, Boureima Degoga, Mohamed Tolofoudie, Bourahima Kone, Moumine Sanogo, Bocar Baya, Ousmane Kodio, Mamoudou Maiga, Michael Belson, Susan Orsega, Meryam Krit, Sounkalo Dao, Ibrahim Izétiegouma Maiga, Robert L. Murphy, Leen Rigouts, Seydou Doumbia, Souleymane Diallo, Bouke Catherine de Jong Objective Ancestral M. tuberculosis complex lineages such as M. africanum are underrepresented among retreatment patients and those with drug resistance. To test the hypothesis that they respond faster to TB treatment, we determined the rate of smear conversion of new pulmonary tuberculosis patients in Bamako, Mali by the main MTBc lineages. Methods Between 2015 and 2017, we conducted a prospective cohort study of new smear positive pulmonary tuberculosis patients in Bamako. Confirmed MTBc isolates underwent genotyping by spoligotyping for lineage classification. Patients were followed at 1 month (M), 2M and 5M to measure smear conversion in auramine (AR) and Fluorescein DiAcetate (FDA) vital stain microscopy. Result All the first six human MTBc lineages were represented in the population, plus M. bovis in 0.8% of the patients. The most widely represented lineage was the modern Euro-American lineage (L) 4, 57%, predominantly the T family, followed by L6 (M. africanum type 2) in 22.9%. Ancestral lineages 1, 5, 6 and M. bovis combined amounted to 28.8%. Excluding 25 patients with rifampicin resistance, smear conversion, both by AR and FDA, occurred later in L6 compared to L4 (HR 0.80 (95% CI 0.66–0.97) for AR, and HR 0.81 (95%CI 0.68–0.97) for FDA). In addition we found that HIV negative status, higher BMI at day 0, and patients with smear grade at baseline ≤ 1+ were associated with earlier smear conversion. Conclusion The six major human lineages of the MTBc all circulate in Bamako. Counter to our hypothesis, we found that patients diseased with modern M. tuberculosis complex L4 respond faster to TB treatment than those with M. africanum L6.…

Koeken V, Lachmandas E, Riza A, et al.

AbstractBackgroundRewiring cellular metabolism is important for activation of immune cells during host defense against Mycobacterium tuberculosis. Glutamine has been implicated as an immunomodulatory nutrient, but its role in response to M. tuberculosis is unknown. MethodsWe assessed expression of glutamine pathway genes in M. tuberculosis infected macrophages and blood transcriptomics from individuals with latent or active tuberculosis. Subsequently, we studied the effect of blocking glutaminolysis on M. tuberculosis-induced cytokines. Finally, we examined whether polymorphisms in genes involved in the glutamine pathway influence M. tuberculosis-induced cytokines in a cohort of 500 individuals.ResultsGlutamine pathway genes were differentially expressed in infected macrophages and patients with active tuberculosis. Human peripheral blood mononuclear cells stimulated with M. tuberculosis displayed decreased cytokine responses (IL-1β, IFN-γ, and IL-17) when medium was devoid of glutamine. Specific inhibitors of the glutamine pathway led to decreased cytokine responses, especially T-cell cytokines (IFN-γ, IL-17, and IL-22). Finally, genetic polymorphisms in glutamine metabolism genes (including GLS2, SLC1A5, and SLC7A5) influenced ex-vivo cytokine responses to M. tuberculosis, especially for T-cell cytokines. ConclusionsCellular glutamine metabolism is implicated in effective host responses against M. tuberculosis. Targeting immunometabolism may represent new strategies for TB prevention and/or treatment.

Hestad, Knut A.; Chinyama, Jonathan; Anitha, Menon J.; Ngoma, Mary S.; McCutchan, J. Allen; Franklin, Donald R. Jr; Heaton, Robert K.

Background: HIV-infection may result in cognitive deficits, but the effects of pulmonary tuberculosis (TB+), a common co-morbid condition in HIV infection, on cognition in HIV infections are unknown . Accordingly, we examined the effects of TB+, on neurocognitive functioning in HIV-infected (HIV+) Zambian adults. Setting: All participants were drawn from HIV clinics in and around Lusaka, the capital of Zambia. Methods: Participants were 275 HIV+ volunteeers, of whom 237 were HIV+ and TB negative (HIV+/TB-), and 38 also had pulmonary TB+ (HIV+/TB+). Controls were 324 HIV and TB-uninfected (HIV-) healthy controls. All HIV+ were prescribed combination antiretroviral treatment (cART). Published, demographically corrected Zambian neuropsychological (NP) norms were used to correct for effects of age, education, sex and urban/rural residence. Results: NP deficits, assessed by global deficit scores (GDS), were more prevalent in this order: 14% (46 of 324) of HIV- controls, 34% (80 of 237) of HIV+/TB-, and 55% (21 of 38) of HIV+/TB+ group. Thus, both HIV-infected groups evidenced more impairment than HIV- controls, and the HIV+/TB+ group had a higher rate of cognitive impairment than the HIV+/TB- group. HIV+/TB+ patients were more likely to be male, younger, less educated, and have lower CD4 counts and detectable HIV RNA in blood compared to the HIV+/TB- patients. Conclusion: In HIV infection, TB may contribute to cognitive impairment, even after controlling for lower CD4 counts and viral load. Nevertheless, systemic inflammation from HIV and TB and more advanced immune deficiency at diagnosis of HIV, may contribute to impaired cognition in HIV+/TB+ patients. Corresponding author: Knut A. Hestad, E-mail address: Knut.Hestad@inn.no Telephone:+4741210640 Some preliminary date from this project was presented at the two conferences: “The International Neuropsychological Society”. INS 2016, Boston, USA, February 3-6th 2016 and “The International Neuropsychological Society” INS 2017 Mid-Year Congress, July 5-8th 2017, Cape Town, South Africa. Conflicts of Interest: None of the authors has a conflict of interest. Funding: This study was supported by the NORAD’s master program (NOMA) NOMAPRO-2007/10046 and The Inland Norway University of Applied Sciences (to Knut A. Hestad). Additional support was provided by the National Institutes of Health grant 5P30MH062512-15 (to Robert Heaton). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Catalina Arango-Ferreira, Claudia M. Zapata-Muñoz and Eduardo Gotuzzo

Alana Sharp, J. Travis Donahoe, Amanda Milliken, Jacqueline Barocio, Salome Charalambous and Zoë M. McLaren

Abstract. Tuberculosis (TB) prevalence among incarcerated populations is as much as 1,000 times higher than in the general population. This study evaluates whether correctional facilities serve as a reservoir through which TB is transmitted to surrounding communities. Tuberculosis test data were extracted from the South African National Health Laboratory Service database for patients tested for TB between 2005 and 2011. We conducted graphical analysis to assess the relationship of TB rates between incarcerated and non-incarcerated populations over time. We performed generalized linear modeling with a log link function to assess TB risk in communities surrounding correctional facilities, net of confounders. We assessed linkages between incarcerated and non-incarcerated populations over time using Granger causality analysis. Tuberculosis prevalence among incarcerated populations was four times higher than in the general population. Tuberculosis incidence rates in incarcerated and non-incarcerated populations followed similar trends over time. The presence of a correctional facility in a municipality was associated with 34.9% more detected TB cases (confidence interval: 11.6–63.2; P < 0.01), controlling for potential confounders. Detected TB in incarcerated populations did not have predictive power in explaining detected TB rates in the non-incarcerated population after controlling for serial correlation in the time series data. Despite high TB prevalence, trends in correctional facilities do not appear to be driving temporal trends in the general population. However, correctional facilities still act as a TB reservoir that raises the overall TB risk in the vicinity. Intensified TB control policies for correctional facilities, formerly incarcerated individuals, and surrounding communities will reduce TB prevalence overall.…

Trinh Quynh Mai, Elena Martinez, Ranjeeta Menon, Nguyen Thi Van Anh, Nguyen Tran Hien, Ben J. Marais and Vitali Sintchenko

Abstract. Vietnam has a high burden of tuberculosis (TB) and multidrug-resistant (MDR) TB, but drug resistance patterns and TB transmission dynamics among TB/human immunodeficiency virus (HIV) coinfected patients are not well described. We characterized 200 Mycobacterium tuberculosis isolates from TB/HIV coinfected patients diagnosed at the main TB referral hospital in Ho Chi Minh City, Vietnam. Phenotypic drug susceptibility testing (DST) for first-line drugs, spoligotyping, and 24-locus mycobacterial interspersed repetitive unit (MIRU-24) analysis was performed on all isolates. The 24-locus mycobacterial interspersed repetitive unit clusters and MDR isolates were subjected to whole genome sequencing (WGS). Most of the TB/HIV coinfected patients were young (162/174; 93.1% aged < 45 years) males (173; 86.5% male). Beijing (98; 49.0%) and Indo-Oceanic (70; 35.0%) lineage strains were most common. Phenotypic drug resistance was detected in 84 (42.0%) isolates, of which 17 (8.5%) were MDR; three additional MDR strains were identified on WGS. Strain clustering was reduced from 84.0% with spoligotyping to 20.0% with MIRU-24 typing and to 13.5% with WGS. Whole genome sequencing identified five additional clusters, or members of clusters, not recognized by MIRU-24. In total, 13 small (two to three member) WGS clusters were identified, with less clustering among drug susceptible (2/27; 7.4%) than among drug-resistant strains (25/27; 92.6%). On phylogenetic analysis, strains from TB/HIV coinfected patients were interspersed among strains from the general community; no major clusters indicating transmission among people living with HIV were detected. Tuberculosis/HIV coinfection in Vietnam was associated with high rates of drug resistance and limited genomic evidence of ongoing M. tuberculosis transmission among HIV-infected patients.…

Zoë M. McLaren, Alana Sharp, Elizabeth Brouwer and Ananta Nanoo

Abstract. Human immunodeficiency virus/tuberculosis (HIV/TB) coinfection is particularly prevalent in South Africa, where TB has been the leading cause of death for more than a decade. The 2004–2008 national rollout of antiretroviral therapy (ART) provides a unique opportunity to examine the population-level impact of ART on the TB epidemic. We performed longitudinal regression analysis to follow the evolution of TB outcomes before and after the introduction of ART using a large data set from the National Health Laboratory Service. This is the first study to produce estimates of the impact of the ART rollout by exploiting staggered timing and geographic variation in the rollout. After ART became available in a health facility, 3.7% (P < 0.0001) more patients were tested for TB and 3.2% (P < 0.0001) more received repeat testing; however, there was a steep rise in testing before the introduction of ART. Although the number of TB-positive patients increased by 4.3% (P = 0.0002) in the first year post-ART, the TB rate among tested patients fell by 2 percentage points (8%, P = 0.001) after 2 years. Sputum smear testing declined relative to more technologically advanced diagnostics post-ART. Antiretroviral therapy availability increased the attention to TB screening and drew new patients into the health-care system. Small increases in the numbers of repeat patients are indicative of retention in care. The decline in TB rates post-ART suggests that the reduction in TB risk due to improved immune functioning and health-care contact likely outweighed the increased TB risk because of the longer lifespan of ART initiators.…

Igor Mokrousov, Anna Vyazovaya, Oksana Pasechnik, Alena Gerasimova, Maya Dymova, Ekaterina Chernyaeva, Marina Tatarintseva, Vladimir Stasenko

The Mycobacterium tuberculosis Beijing family is an epidemiologically important lineage subdivided into large-scale phylogenetic sublineages: ancient, endemic in East Asia, and global modern. Here, we analyzed ancient sublineages of the Beijing genotype in the Omsk region of southwestern Siberia, an intriguing area at the intersection of European Russia, Siberia, and Central Asia.

Jose Gabriel Cornejo Garcia, Valentina Antonieta Alarcón Guizado, Alberto Mendoza Ticona, Edith Alarcon, Einar Heldal, David A. J. Moore

by Jose Gabriel Cornejo Garcia, Valentina Antonieta Alarcón Guizado, Alberto Mendoza Ticona, Edith Alarcon, Einar Heldal, David A. J. Moore Background Resistance to isoniazid is the most common form of drug-resistance in tuberculosis. However only a tiny proportion of TB patients in the world have access to isoniazid drug susceptibility testing—the widely implemented Xpert MTB/RIF technology only tests for resistance to rifampicin. Patients with isoniazid mono resistance that is not identified at baseline are treated with a standard regimen that effectively results in rifampicin mono-therapy during the latter four months of the six month treatment course, exposing remaining viable organisms to a single agent and greatly increasing the risk of development of multi drug-resistant TB. Unusually, Peru has pioneered universal pre-treatment drug susceptibility testing with methods that identify isoniazid resistance and has thus identified a large number of individuals requiring tailored therapy. Since 2010, treatment in Peru for isoniazid-resistant tuberculosis without multidrug-resistant tuberculosis (Hr-TB) has been with a standardized nine-month regimen of levofloxacin, rifampicin, ethambutol and pyrazinamide. The objectives of this study were to evaluate the outcomes of treatment for patients with Hr-TB initiating treatment with this regimen between January 2012 and December 2014 and to determine factors affecting these outcomes. Methods Retrospective cross-sectional study; case data were obtained from the national registry of drug-resistant tuberculosis. Patients diagnosed with isoniazid resistant TB without resistance to rifampicin, pyrazinamide, ethambutol and quinolones as determined by either a rapid drug susceptibility testing (DST) (nitrate reductase test, MODS, Genotype MTBDRplus) or by the proportion method were included. Findings A total of 947 cases were evaluated (a further 403 without treatment end date were excluded), with treatment success in 77.2% (731 cases), loss to follow-up in 19.7% (186 cases), treatment failure in 1.2% (12 cases), and death in 1.9% (18 cases). Unfavorable outcomes were associated in multivariate analysis with male gender (OR 0.50, 95% CI 0.34–0.72, p

Abstract Background Tuberculosis (TB) caused an estimated 1.4 million deaths and 10.4 million new cases globally in 2015. TB rates in the United States continue to steadily decline, yet rates in the State of Hawaii are perennially among the highest in the nation due to a continuous influx of immigrants from the Western Pacific and Asia. TB in Hawaii is composed of a unique distribution of genetic lineages, with the Beijing and Manila families of Mycobacterium tuberculosis (Mtb) comprising over two-thirds of TB cases. Standard fingerprinting methods (spoligotyping plus 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats [MIRU-VNTR] fingerprinting) perform poorly when used to identify actual transmission clusters composed of isolates from these two families. Those typing methods typically group isolates from these families into large clusters of non-linked isolates with identical fingerprints. Next-generation whole-genome sequencing (WGS) provides a new tool for molecular epidemiology that can resolve clusters of isolates with identical spoligotyping and MIRU-VNTR fingerprints. Methods We performed WGS and SNP analysis and evaluated epidemiological data to investigate 19 apparent TB transmission clusters in Hawaii from 2003 to 2017 in order to assess WGS’ ability to resolve putative Mtb clusters from the Beijing and Manila families. This project additionally investigated MIRU-VNTR allele prevalence to determine why standard Mtb fingerprinting fails to usefully distinguish actual transmission clusters from these two Mtb families. Results WGS excluded transmission events in seven of these putative clusters, confirmed transmission in eight, and identified both transmission-linked and non-linked isolates in four. For epidemiologically identified clusters, while the sensitivity of MIRU-VNTR fingerprinting for identifying actual transmission clusters was found to be 100%, its specificity was only 28.6% relative to WGS. We identified that the Beijing and Manila families’ significantly lower Shannon evenness of MIRU-VNTR allele distributions than lineage 4 was the cause of standard fingerprinting’s poor performance when identifying transmission in Beijing and Manila family clusters. Conclusions This study demonstrated that WGS is necessary for epidemiological investigation of TB in Hawaii and the Pacific.…

Paul T. Elkington

American Journal of Respiratory and Critical Care Medicine, Volume 198, Issue 11, Page 1451-1453, December 1, 2018. …

Abstract Background Diabetes mellitus (DM) is recognized as an important comorbidity for the development of tuberculosis (TB). With the increase of DM burden globally, concerns have been raised about the emerging co-epidemics of DM and TB, especially in low- and middle-income countries. Methods A facility-based, cross-sectional study was carried out in all 30 district TB units in Hanoi, Vietnam. All eligible, diagnosed TB patients aged 15 years old or older were asked to provide consent and were screened for diabetes using fasting blood glucose (FBG). Pre-tested semi-structured questionnaires were used for collecting demographic data, lifestyle habits and clinical data. Identification of pre-diabetes or diabetes in TB patients was done in accordance to parameters set by the American Diabetes Association (2016). Results Of 870 eligible TB patients, 831 (95.5%) participated in the study. Of those, 241 (29%; 95%CI: 25.9–32.1%) were prediabetic and 114 (13.7%; 95%CI: 11.4–16.1%) were found to have DM. The risk of DM was higher in patients belonging to the age group 40–64 years (OR 6.09; 95%CI 2.81–13.2); or the age group 65 years or older (OR 2.65; 95%CI 1.65–4.25) or who have a family history of DM (OR 2.71; 95%CI 1.33–5.50). Conclusions This study demonstrated high prevalence of DM and prediabetes among TB patients in Hanoi, Vietnam. National Tuberculosis Programme needs to establish a systematic screening process for DM among TB patients.…