Community-Wide Universal HIV Test and Treat Intervention Reduces Tuberculosis Transmission in Rural Uganda: A Cluster-Randomized Trial.

BACKGROUND: Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. METHODS: In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. RESULTS: Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. CONCLUSIONS: A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.

An overview of tuberculosis outbreaks reported in the years 2011-2020.

BACKGROUND: In many countries tuberculosis (TB) remains a highly prevalent disease and a major contributor to infectious disease mortality. The fight against TB requires surveillance of the population of strains circulating worldwide and the analysis of the prevalence of certain strains in populations. Nowadays, whole genome sequencing (WGS) allows for accurate tracking of TB transmission. Currently, there is a lack of a comprehensive summary of the characteristics of TB outbreaks. METHODS: We systematically analyzed studies reporting TB outbreaks worldwide, monitored through WGS of Mycobacterium tuberculosis. We 1) mapped the reported outbreaks from 2011- 2020, 2) estimated the average size of the outbreaks, 3) indicated genetic lineages causing the outbreaks, and 4) determined drug-resistance patterns of M. tuberculosis strains involved in the outbreaks. RESULTS: Most data originated from Europe, Asia, and North America. We found that TB outbreaks were reported throughout the globe, on all continents, and in countries with both high and low incidences. The detected outbreaks contained a median of five M. tuberculosis isolates. Most strains causing the outbreaks belonged to lineage four, more rarely to lineage two. Reported outbreak isolates were often drug resistant. CONCLUSIONS: We conclude that more WGS surveillance of M. tuberculosis outbreaks is needed. Globally standardized procedures might improve the control of M. tuberculosis infections.

Time to diagnosis and treatment of pulmonary tuberculosis in indigenous peoples: a systematic review.

BACKGROUND: Time to diagnosis and treatment is a major factor in determining the likelihood of tuberculosis (TB) transmission and is an important area of intervention to reduce the reservoir of TB infection and prevent disease and mortality. Although Indigenous peoples experience an elevated incidence of TB, prior systematic reviews have not focused on this group. We summarize and report findings related to time to diagnosis and treatment of pulmonary TB (PTB) among Indigenous peoples, globally. METHODS: A Systematic review was performed using Ovid and PubMed databases. Articles or abstracts estimating time to diagnosis, or treatment of PTB among Indigenous peoples were included with no restriction on sample size with publication dates restricted up to 2019. Studies that focused on outbreaks, solely extrapulmonary TB alone in non-Indigenous populations were excluded. Literature was assessed using the Hawker checklist. Registration Protocol (PROSPERO): CRD42018102463. RESULTS: Twenty-four studies were selected after initial assessment of 2021 records. These included Indigenous groups from five of six geographical regions outlined by the World Health Organization (all except the European Region). The range of time to treatment (24-240 days), and patient delay (20 days-2.5 years) were highly variable across studies and, in at least 60% of the studies, longer in Indigenous compared to non-Indigenous peoples. Risk factors associated with longer patient delays included poor awareness of TB, type of health provider first seen, and self-treatment. CONCLUSION: Time to diagnosis and treatment estimates for Indigenous peoples are generally within previously reported ranges from other systematic reviews focusing on the general population. However among literature examined in this systematic review that stratified by Indigenous and non-Indigenous peoples, patient delay and time to treatment were longer compared to non-Indigenous populations in over half of the studies. Studies included were sparse and highlight an overall gap in literature important to interrupting transmission and preventing new TB cases among Indigenous peoples. Although, risk factors unique to Indigenous populations were not identified, further investigation is needed as social determinants of health among studies conducted in medium and high incidence countries may be shared across both population groups. Trial registration N/a.

Impact of Reversion of Mycobacterium tuberculosis Immunoreactivity Tests on the Estimated Annual Risk of Tuberculosis Infection.

A key metric in tuberculosis epidemiology is the annual risk of infection (ARI), which is usually derived from tuberculin skin test (TST) and interferon-γ release assay (IGRA) prevalence surveys carried out in children. Derivation of the ARI assumes that immunoreactivity is persistent over time; however, reversion of immunoreactivity has long been documented. We used a deterministic, compartmental model of Mycobacterium tuberculosis (Mtb) infection to explore the impact of reversion on ARI estimation using age-specific reversion probabilities for the TST and IGRA. Using empirical data on TST reversion (22.2%/year for persons aged ≤19 years), the true ARI was 2-5 times higher than that estimated from immunoreactivity studies in children aged 8-12 years. Applying empirical reversion probabilities for the IGRA (9.9%/year for youths aged 12-18 years) showed a 1.5- to 2-fold underestimation. ARIs are increasingly underestimated in older populations, due to the cumulative impact of reversion on population reactivity over time. Declines in annual risk did not largely affect the results. Ignoring reversion leads to a stark underestimation of the true ARI in populations and our interpretation of Mtb transmission intensity. In future surveys, researchers should adjust for the reversion probability and its cumulative effect with increasing age to obtain a more accurate reflection of the burden and dynamics of Mtb infection.

A New Surveillance Model of Tuberculosis Transmission Control Based on Geographic Information System in the Primary Health Care.

Background: Tuberculosis can cause a substantial challenge against public health, especially in the developing countries which have low level of socio-economic condition that does not support the control over tuberculosis transmission and infection. Objective: To find a new surveillance model of tuberculosis transmission control based on geographic information system data in improving the tuberculosis transmission control and treatment outcome. Methods: Effectiveness test of the self-monitoring of calendar documentation on the tuberculosis transmission control and outcome treatment with quasi-experimental post-test only with control group design. The analytical unit consisted of 96 tuberculosis cases as the self-monitoring group of calendar documentation (intervention) and 87 tuberculosis cases as the control group sourced of two different primary health care. Results: The self-monitoring intervention of calendar documentation increased the average treatment effect on medicines intake control 0.11 (95% CI: 0.01-0.21), environment control 0.32 (95% CI: 0.19-46), droplets nuclei control 0.49 (95% CI: 0.36-0.61), cured 0.22 (95% CI: 0.09-0.36), completed 0.18 (95% CI: 0.09-0.26), drop out 0.09 (95% CI: 0.01-0.16), and failure of treatment 0.18 (95% CI: 0.09-0.26) of the control group (baseline). Conclusion: The final result of this research found a new surveillance model of tuberculosis transmission control in google earth mapping aplication based on Geographic Information system.

A synthesized model of tuberculosis transmission featuring treatment abandonment.

In this paper, we propose and justify a synthesized version of the tuberculosis transmission model featuring treatment abandonment. In contrast to other models that account for the treatment abandonment, our model has only four state variables or classes (susceptible, latent, infectious, and treated), while people abandoning treatment are not gathered into an additional class. The proposed model retains the core properties that are highly desirable in epidemiological modeling. Namely, the disease transmission dynamics is characterized by the basic reproduction number $ \mathscr{R}_0 $, a threshold value that determines the number of possible steady states and their stability properties. It is shown that the disease-free equilibrium is globally asymptotically stable (GAS) only if $ \mathscr{R}_0 < 1 $, while a strictly positive endemic equilibrium exists and is GAS only if $ \mathscr{R}_0 > 1. $ Analysis of the dependence of $ \mathscr{R}_0 $ on the treatment abandonment rate shows that a reduction of the treatment abandonment rate has a positive effect on the disease incidence and results in avoiding disease-related fatalities.

Estimating tuberculosis drug resistance amplification rates in high-burden settings.

BACKGROUND: Antimicrobial resistance develops following the accrual of mutations in the bacterial genome, and may variably impact organism fitness and hence, transmission risk. Classical representation of tuberculosis (TB) dynamics using a single or two strain (DS/MDR-TB) model typically does not capture elements of this important aspect of TB epidemiology. To understand and estimate the likelihood of resistance spreading in high drug-resistant TB incidence settings, we used epidemiological data to develop a mathematical model of Mycobacterium tuberculosis (Mtb) transmission. METHODS: A four-strain (drug-susceptible (DS), isoniazid mono-resistant (INH-R), rifampicin mono-resistant (RIF-R) and multidrug-resistant (MDR)) compartmental deterministic Mtb transmission model was developed to explore the progression from DS- to MDR-TB in The Philippines and Viet Nam. The models were calibrated using data from national tuberculosis prevalence (NTP) surveys and drug resistance surveys (DRS). An adaptive Metropolis algorithm was used to estimate the risks of drug resistance amplification among unsuccessfully treated individuals. RESULTS: The estimated proportion of INH-R amplification among failing treatments was 0.84 (95% CI 0.79-0.89) for The Philippines and 0.77 (95% CI 0.71-0.84) for Viet Nam. The proportion of RIF-R amplification among failing treatments was 0.05 (95% CI 0.04-0.07) for The Philippines and 0.011 (95% CI 0.010-0.012) for Viet Nam. CONCLUSION: The risk of resistance amplification due to treatment failure for INH was dramatically higher than RIF. We observed RIF-R strains were more likely to be transmitted than acquired through amplification, while both mechanisms of acquisition were important contributors in the case of INH-R. These findings highlight the complexity of drug resistance dynamics in high-incidence settings, and emphasize the importance of prioritizing testing algorithms which allow for early detection of INH-R.

Reactivation of Pulmonary Tuberculosis During Treatment of Chronic Myelomonocytic Leukemia.

A 76-year-old woman from a tuberculosis (TB) endemic region with chronic myelomonocytic leukemia (CMML) on Azacitidine presented with a non-productive cough. A CT scan of the chest revealed a lobulated opacity in the right upper lobe and antibiotic therapy was initiated for a potential bacterial pneumonia. However, a high suspicion for pulmonary TB remained given her nation of origin, immunosuppression, and imaging findings. Three sputum and bronchoalveolar lavage (BAL) acid-fast bacilli (AFB) smears with PCR testing for Mycobacterium tuberculosis were negative, as were examinations for other potential fungal or bacterial etiologies of the patient's symptoms and imaging findings. While awaiting final TB culture results from BAL, her CMML underwent a transformation to acute myeloid leukemia (AML). Given the urgent need for initiation of chemotherapy, empiric treatment for TB was commenced while awaiting the final TB culture. Within 48-hours of initiating therapy for TB, the patient's fevers subsided. One week after discharge our team was notified of a positive M. tuberculosis culture from BAL. We suspect that our patient had a latent TB infection which reactivated due to her CMML. This case highlights the importance of maintaining a high clinical suspicion for TB in high-risk patients, even in the case of initially negative laboratory examinations. Further, it demonstrates the importance of screening and treating latent TB in patients with leukemias.

Determinants of self-reported correct knowledge about tuberculosis transmission among men and women in Malawi: evidence from a nationwide household survey.

BACKGROUND: Correct knowledge about transmission of tuberculosis (TB) can influence better health-seeking behaviors, and in turn, it can aid TB prevention in society. Therefore, this study aimed to examine the prevalence and predictors of self-reported correct knowledge about TB transmission among adults in Malawi. METHODS: We conducted a secondary analysis of the data obtained from the Malawi Demographic and Health Survey, 2015/16 (MDHS 2015/16). Questions regarding self-reported TB transmission were computed to evaluate the correct knowledge about TB transmission. The factors associated with the correct knowledge about Tb were assessed using univariate and multivariable logistic regression. RESULTS: Overall, the prevalence of correct knowledge about TB transmission in the general population of Malawian adults was 61.5%. Specifically, the prevalence of correct knowledge about TB transmission was 63.6 and 60.8% in men and women, respectively. Those aged 35-44 years, having secondary or high education, belonging to the richest household, being exposed to mass media, being in professional/technical/managerial, having knowledge that "TB can be cured", and those living in urban areas were significantly associated with correct knowledge about TB transmission. CONCLUSIONS: The findings of this study show that if appropriate strategies for TB communication and education to address the rural masses, young individuals, poor individuals, and individuals in the agriculture sector are put it place, can enhance TB prevention in Malawi.

Concordance of Drug-resistance Profiles Between Persons With Drug-resistant Tuberculosis and Their Household Contacts: A Systematic Review and Meta-analysis.

BACKGROUND: Household contacts of patients with drug-resistant tuberculosis (TB) are at high risk for being infected with Mycobacterium tuberculosis and for developing TB disease. To guide regimen composition for the empirical treatment of TB infection and disease in these household contacts, we estimated drug-resistance profile concordance between index patients with drug-resistant TB and their household contacts. METHODS: We performed a systematic review and meta-analysis of studies published through 24 July 2018 that reported resistance profiles of drug-resistant TB index cases and secondary cases within their households. Using a random-effects meta-analysis, we estimated resistance profile concordance, defined as the percentage of secondary cases whose M. tuberculosis strains were resistant to the same drugs as strains from their index cases. We also estimated isoniazid/rifampin concordance, defined as whether index and secondary cases had identical susceptibilities for isoniazid and rifampin only. RESULTS: We identified 33 eligible studies that evaluated resistance profile concordance between 484 secondary cases and their household index cases. Pooled resistance profile concordance was 54.3% (95% confidence interval [CI], 40.7-67.6%; I2 = 85%). Pooled isoniazid/rifampin concordance was 82.6% (95% CI, 72.3-90.9%; I2 = 73%). Concordance estimates were similar in a subanalysis of 16 studies from high-TB-burden countries. There were insufficient data to perform a subanalysis among pediatric secondary cases. CONCLUSIONS: Household contacts of patients with drug-resistant TB should receive treatment for TB infection and disease that assumes that they, too, are infected with a drug-resistant M. tuberculosis strain. Whenever possible, drug susceptibility testing should be performed for secondary cases to optimize regimen composition.

Mutation of Mycobacterium tuberculosis and Implications for Using Whole-Genome Sequencing for Investigating Recent Tuberculosis Transmission.

Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission.

History of household member with tuberculosis or related death in newly diagnosed patients in India.

Among new smear-positive pulmonary tuberculosis (TB) patients aged ⩾15 years from marginalised populations in India, one in four had a history of a household member with TB and one in 10 had a TB-related death in the household. This contribution of household transmission to overall TB transmission provides evidence for a potential population-level benefit of TB preventive treatment for all household contacts (without active TB). Females with TB had a significantly higher household TB exposure than males. Targeted TB preventive treatment (if implemented in a phased manner) among female household contacts may be explored after considering other factors.

Parmi les nouveaux cas de tuberculose (TB) pulmonaire confirmés par bactériologie de patients (⩾15 ans) de populations marginalisées en Inde, un quart avait eu un membre du foyer atteint de TB et un sur 10, un décès dû à la TB au sein du foyer. La contribution de la transmission domiciliaire à l'ensemble de la transmission de la TB est en faveur d'un bénéfice potentiel pour la population, du traitement préventif de la TB pour tous les membres du foyer (sans TB active). Les patients TB de sexe féminin ont une exposition domiciliaire à la TB significativement plus élevée que les hommes. Un traitement préventif de la TB ciblé (s'il est mis en œuvre par phases) sur les contacts féminins du foyer pourrait être évalué après avoir tenu compte des autres facteurs.

Modeling Missing Cases and Transmission Links in Networks of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.

Patterns of transmission of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases worldwide in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa, diagnosed in 2011-2014. We tested scenarios in which cases were missing at random, missing differentially by clinical characteristics, or missing differentially by transmission (i.e., cases with many links were under- or oversampled). Under the assumption that cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases, and models provided evidence for super-spreading. To our knowledge, this is the first analysis to have assessed support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving super-spreading.

Concurrent adult pulmonary tuberculosis prevalence survey using digital radiography and Xpert MTB/RIF Ultra and child interferon-gamma release assay Mycobacterium tuberculosis infection survey in Karachi, Pakistan: a study protocol.

Background: Assessment of the effectiveness of tuberculosis control strategies requires the periodic measurement of M. tuberculosis transmission in populations, which is notoriously difficult. One well-established method is to measure the prevalence of infectious pulmonary tuberculosis in the population which is then repeated at a second time point after a period of 'intervention', such as scale up of the Search-Treat-Prevent strategy of the Zero TB Cities initiative, allowing for a 'before and after' comparison.  Protocol: The concurrent adult pulmonary tuberculosis prevalence survey (using digital radiography and Xpert MTB/RIF Ultra) and child M. tuberculosis infection survey (using QuantiFERON-TB® Gold Plus) will primarily provide a baseline measure of the burden of adult infectious tuberculosis in Karachi and assess whether a large-scale interferon gamma release assay survey in children aged 2 to 4 years is feasible. The target population for the prevalence survey is comprised of a stratified random sample of all adults aged 15 years and above and all children aged 2 to 4 years resident in four districts in Karachi. The survey procedures and analyses to estimate pulmonary tuberculosis prevalence are based on the World Health Organization methodology for tuberculosis prevalence surveys. Ethics and dissemination: The study protocol has been approved by the Interactive Research Development / The Indus Hospital Research Centre Research Ethics Committee in Karachi, Pakistan and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Due to non-representative sampling in this setting, where a large proportion of the population are illiterate and are reluctant to provide fingerprints due to concerns about personal security, verbal informed consent will be obtained from each eligible participant or guardian. Results will be submitted to international peer-reviewed journals, presented at international conferences and shared with participating communities and with the Provincial and National TB programme.

Social Mixing and Clinical Features Linked With Transmission in a Network of Extensively Drug-resistant Tuberculosis Cases in KwaZulu-Natal, South Africa.

BACKGROUND: Tuberculosis (TB) is the leading infectious cause of death globally, and drug-resistant TB strains pose a serious threat to controlling the global TB epidemic. The clinical features, locations, and social factors driving transmission in settings with high incidences of drug-resistant TB are poorly understood. METHODS: We measured a network of genomic links using Mycobacterium tuberculosis whole-genome sequences. RESULTS: Patients with 2-3 months of cough or who spent time in urban locations were more likely to be linked in the network, while patients with sputum smear-positive disease were less likely to be linked than those with smear-negative disease. Associations persisted using different thresholds to define genomic links and irrespective of assumptions about the direction of transmission. CONCLUSIONS: Identifying factors that lead to many transmissions, including contact with urban areas, can suggest settings instrumental in transmission and indicate optimal locations and groups to target with interventions.

Network analysis of dairy cattle movement and associations with bovine tuberculosis spread and control in emerging dairy belts of Ethiopia.

BACKGROUND: Dairy cattle movement could be a major risk factor for the spread of bovine tuberculosis (BTB) in emerging dairy belts of Ethiopia. Dairy cattle may be moved between farms over long distances, and hence understanding the route and frequency of the movements is essential to establish the pattern of spread of BTB between farms, which could ultimately help to inform policy makers to design cost effective control strategies. The objective of this study was, therefore, to investigate the network structure of dairy cattle movement and its influence on the transmission and prevalence of BTB in three emerging areas among the Ethiopian dairy belts, namely the cities of Hawassa, Gondar and Mekelle. METHODS: A questionnaire survey was conducted in 278 farms to collect data on the pattern of dairy cattle movement for the last 5 years (September 2013 to August 2018). Visualization of the network structure and analysis of the relationship between the network patterns and the prevalence of BTB in these regions were made using social network analysis. RESULTS: The cattle movement network structure display both scale free and small world properties implying local clustering with fewer farms being highly connected, at higher risk of infection, with the potential to act as super spreaders of BTB if infected. Farms having a history of cattle movements onto the herds were more likely to be affected by BTB (OR: 2.2) compared to farms not having a link history. Euclidean distance between farms and the batch size of animals moved on were positively correlated with prevalence of BTB. On the other hand, farms having one or more outgoing cattle showed a decrease on the likelihood of BTB infection (OR = 0.57) compared to farms which maintained their cattle. CONCLUSION: This study showed that the patterns of cattle movement and size of animal moved between farms contributed to the potential for BTB transmission. The few farms with the bulk of transmission potential could be efficiently targeted by control measures aimed at reducing the spread of BTB. The network structure described can also provide the starting point to build and estimate dynamic transmission models for BTB, and other infectious diseases.

Improving natural ventilation in hospital waiting and consulting rooms to reduce nosocomial tuberculosis transmission risk in a low resource setting.

BACKGROUND: TB transmission in healthcare facilities is an important public health problem, especially in the often-overcrowded settings of HIV treatment scale-up. The problem is compounded by the emergence of drug resistant TB. Natural ventilation is a low-cost environmental control measure for TB infection control where climate permits that is suited to many different areas in healthcare facilities. There are no published data on the effect of simple structural modifications to existing hospital infrastructure to improve natural ventilation and reduce the risk of nosocomial TB transmission. The purpose of this study was to measure the effect of simple architectural modifications to existing hospital waiting and consulting rooms in a low resource setting on (a) improving natural ventilation and (b) reducing modelled TB transmission risk. METHODS: Room ventilation was measured pre- and post-modification using a carbon dioxide tracer-gas technique in four waiting rooms and two consulting rooms in two hospitals in Lima, Peru. Modifications included additional windows for cross-ventilation (n = 2 rooms); removing glass from unopenable windows (n = 2); creation of an open skylight (n = 1); re-building a waiting-room in the open air (n = 1). Changes in TB transmission risk for waiting patients, or healthcare workers in consulting rooms, were estimated using mathematical modelling. RESULTS: As a result of the infrastructure modifications, room ventilation in the four waiting rooms increased from mean 5.5 to 15; 11 to 16; 10 to 17; and 9 to 66 air-changes/hour respectively; and in the two consulting rooms from mean 3.6 to 17; and 2.7 to 12 air-changes/hour respectively. There was a median 72% reduction (inter-quartile range 51-82%) in calculated TB transmission risk for healthcare workers or waiting patients. The modifications cost

Nosocomial Mycobacterium tuberculosis transmission by brief casual contact identified using comparative genomics.

This paper reports a case of nosocomial transmission of Mycobacterium tuberculosis by brief casual contact. Routine variable number tandem repeat typing in Yamagata Prefecture, Japan found that M. tuberculosis clinical isolates from two patients showed indistinguishable genotypes. The patients had an epidemiological relationship of sharing a waiting room in a hospital on the same day. As comparative genomics detected only two single nucleotide variants between the isolates, it was concluded that recent tuberculosis transmission occurred in the waiting room. These results indicate that the physical separation of infectious tuberculosis patients is an essential control measure for preventing unpredictable nosocomial transmission by casual contact.

Caracterización de aislamientos clínicos de Mycobacterium tuberculosis obtenidos de individuos positivos para HIV en Colombia, 2012 / Characterization of clinical isolates of Mycobacterium tuberculosis from HIV positive individuals in Colombia, 2012

Resumen Introducción: Una tercera parte de los casos nuevos de tuberculosis se atribuye a la propagación del HIV. En 2012, se presentaron en Colombia 1.397 casos de tuberculosis concomitante con la infección por HIV, es decir, 11,8 % del total de notificados. El uso de las herramientas de epidemiología molecular contribuye a una mejor comprensión de la transmisión de la enfermedad. Objetivo: Caracterizar los aislamientos clínicos de Mycobacterium tuberculosis de individuos positivos para HIV recibidos en el Laboratorio Nacional de Referencia del Instituto Nacional de Salud. Materiales y métodos: Se hizo un estudio observacional descriptivo. Se estudiaron 63 aislamientos de individuos con tuberculosis e infección por HIV mediante pruebas de identificación, sensibilidad y genotipificación. Resultados: Dos de los casos nuevos (3,3 %) eran resistentes a rifampicina y uno (1,6 %) a isoniacida, en tanto que tres (5,0 %) lo eran a la isoniacida combinada con estreptomicina. Los casos previamente tratados fueron sensibles. No se evidenció multirresistencia. Hubo 20 (31,7 %) aislamientos de la familia genética LAM9, 8 (12,7 %) de la H1 y 7 (11,1 %) de la T1 . Diecinueve aislamientos correspondieron a patrones huérfanos. Se observó un único agrupamiento entre los aislamientos analizados. No se encontraron diferencias estadísticamente significativas entre la resistencia a fármacos y las familias genéticas. Conclusión: La resistencia encontrada demostró la transmisión de cepas resistentes a rifampicina e isoniacida. Las familias genéticas LAM9, T1 y H1 corresponden a las descritas en la población general. No se evidenció transmisión activa en los aislamientos estudiados. Se necesitan estudios más completos para conocer la situación real de la infección concomitante de tuberculosis y HIV en el país.

Abstract Introduction: One third of the increase in tuberculosis cases is attributed to the spread of HIV. In 2012, 1,397 HIV-associated tuberculosis cases were reported in Colombia, i.e., 11.8% of the total cases. Molecular epidemiology tools help to understand the transmission of tuberculosis. Objective: To characterize clinical isolates of Mycobacterium tuberculosis derived from HIV-infected individuals, received at the Laboratorio Nacional de Referencia in the Instituto Nacional de Salud. Materials and methods: This was a descriptive observational study. We analyzed 63 isolates of M. tuberculosis from HIV-infected individuals. Identification, drug susceptibility and genotyping assays were performed. Results: Of the new cases evaluated, three (5.0%) were resistant to isoniazid combined with streptomycin; two (3.3%) to rifampicin, and one (1.6%) to isoniazid. Previously treated cases were sensitive. No multidrug resistance was evident. Among the predominant genotypes, 20 isolates were (31.7%) LAM9, eight (12.7%), H1, and seven (11.1%), T1. Nineteen isolates corresponded to orphan patterns. One single grouping was observed among tested isolates. We found no statistically significant difference between the proportions of the antituberculous drug resistance and genotypes. Conclusion: We found resistant isolates to the most powerful drugs, rifampicin and isoniazid, among new cases, showing the transmission of resistant strains. Genetic families of M. tuberculosis LAM9, T1 and H1 correspond to those described in the general population. We detected no active transmission among studied isolates. More comprehensive studies are needed to assess the real situation of HIV associated tuberculosis in the country regarding sensitivity and transmission.

Institutional Tuberculosis Transmission. Controlled Trial of Upper Room Ultraviolet Air Disinfection: A Basis for New Dosing Guidelines.

RATIONALE: Transmission is driving the global tuberculosis epidemic, especially in congregate settings. Worldwide, natural ventilation is the most common means of air disinfection, but it is inherently unreliable and of limited use in cold climates. Upper room germicidal ultraviolet (UV) air disinfection with air mixing has been shown to be highly effective, but improved evidence-based dosing guidelines are needed. OBJECTIVES: To test the efficacy of upper room germicidal air disinfection with air mixing to reduce tuberculosis transmission under real hospital conditions, and to define the application parameters responsible as a basis for proposed new dosing guidelines. METHODS: Over an exposure period of 7 months, 90 guinea pigs breathed only untreated exhaust ward air, and another 90 guinea pigs breathed only air from the same six-bed tuberculosis ward on alternate days when upper room germicidal air disinfection was turned on throughout the ward. MEASUREMENTS AND MAIN RESULTS: The tuberculin skin test conversion rates (>6 mm) of the two chambers were compared. The hazard ratio for guinea pigs in the control chamber converting their skin test to positive was 4.9 (95% confidence interval, 2.8-8.6), with an efficacy of approximately 80%. CONCLUSIONS: Upper room germicidal UV air disinfection with air mixing was highly effective in reducing tuberculosis transmission under hospital conditions. These data support using either a total fixture output (rather than electrical or UV lamp wattage) of 15-20 mW/m(3) total room volume, or an average whole-room UV irradiance (fluence rate) of 5-7 µW/cm(2), calculated by a lighting computer-assisted design program modified for UV use.