RESUMEN
BACKGROUND: The duration of the protective effect of tuberculosis preventive therapy (TPT) is controversial. Some studies have found that the protective effect of TPT is lost after cessation of therapy among people with human immunodeficiency virus (HIV) in settings with very high tuberculosis incidence, but others have found long-term protection in low-incidence settings. METHODS: We estimated the incidence rate (IR) of new tuberculosis disease for up to 12 years after randomization to 4 months of rifampin or 9 months of isoniazid, among 991 Brazilian participants in a TPT trial in the state of Rio de Janeiro, with an incidence of 68.6/100 000 population in 2022. The adjusted hazard ratios (aHRs) of independent variables for incident tuberculosis were calculated. RESULTS: The overall tuberculosis IR was 1.7 (95% confidence interval [CI], 1.01- 2.7) per 1000 person-years (PY). The tuberculosis IR was higher among those who did not complete TPT than in those who did (2.9 [95% CI, 1.3-5.6] vs 1.1 [.4-2.3] per 1000 PY; IR ratio, 2.7 [1.0-7.2]). The tuberculosis IR was higher within 28 months after randomization (IR, 3.5 [95% CI, 1.6-6.6] vs 1.1 [.5-2.1] per 1000 PY between 28 and 143 months; IR ratio, 3.1 [1.2-8.2]). Treatment noncompletion was the only variable associated with incident tuberculosis (aHR, 3.2 [95% CI, 1.1-9.7]). CONCLUSIONS: In a mostly HIV-noninfected population, a complete course of TPT conferred long-term protection against tuberculosis.
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Antituberculosos , Infecciones por VIH , Isoniazida , Tuberculosis , Humanos , Masculino , Incidencia , Femenino , Tuberculosis/prevención & control , Tuberculosis/epidemiología , Adulto , Antituberculosos/uso terapéutico , Brasil/epidemiología , Isoniazida/uso terapéutico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Rifampin/uso terapéutico , Persona de Mediana Edad , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Indicators of extensive disease-acid fast bacilli (AFB) smear positivity and lung cavitation-have been inconsistently associated with clinical rifampin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) outcomes. We evaluated the association of these indicators with end-of-treatment outcomes. METHODS: We did an individual participant data meta-analysis of people treated for RR/MDR-TB with longer regimens with documented AFB smear and chest radiography findings. We compared people AFB smear-negative without cavities to people: (1) smear-negative with lung cavities; (2) smear-positive without lung cavities and (3) AFB smear-positive with lung cavities. Using multivariable logistic regression accounting for demographic, treatment and clinical factors, we calculated adjusted ORs (aOR) for any unfavourable outcome (death, lost to follow-up, failure/recurrence), and mortality and treatment failure/recurrence alone. RESULTS: We included 5596 participants; included participants significantly differed from excluded participants. Overall, 774 (13.8%) were AFB smear-negative without cavities, 647 (11.6%) only had cavities, 1424 (25.4%) were AFB smear-positive alone and 2751 (49.2%) were AFB smear-positive with cavities. The median age was 37 years (IQR: 28-47), 3580 (64%) were male and 686 (12.5%) had HIV. Compared with participants AFB smear-negative without cavities, aOR (95% CI) for any unfavourable outcome was 1.0 (0.8 to 1.4) for participants smear-negative with lung cavities, 1.2 (0.9 to 1.5) if smear-positive without cavities and 1.6 (1.3 to 2.0) if AFB smear-positive with lung cavities. Odds were only significantly increased for mortality (1.5, 95% CI 1.1 to 2.1) and failure/recurrence (2.2, 95% CI 1.5 to 3.3) among participants AFB smear-positive with lung cavities. CONCLUSION: Only the combination of AFB smear-positivity and lung cavitation was associated with unfavourable outcomes, suggesting they may benefit from stronger regimens.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Humanos , Masculino , Adulto , Femenino , Rifampin/uso terapéutico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , EsputoRESUMEN
BACKGROUND: Nasopharyngeal swabs are the primary sampling method used for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but they require a trained health care professional and extensive personal protective equipment. PURPOSE: To determine the difference in sensitivity for SARS-CoV-2 detection between nasopharyngeal swabs and saliva and estimate the incremental cost per additional SARS-CoV-2 infection detected with nasopharyngeal swabs. DATA SOURCES: Embase, Medline, medRxiv, and bioRxiv were searched from 1 January to 1 November 2020. Cost inputs were from nationally representative sources in Canada and were converted to 2020 U.S. dollars. STUDY SELECTION: Studies including at least 5 paired nasopharyngeal swab and saliva samples and reporting diagnostic accuracy for SARS-CoV-2 detection. DATA EXTRACTION: Data were independently extracted using standardized forms, and study quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). DATA SYNTHESIS: Thirty-seven studies with 7332 paired samples were included. Against a reference standard of a positive result on either sample, the sensitivity of saliva was 3.4 percentage points lower (95% CI, 9.9 percentage points lower to 3.1 percentage points higher) than that of nasopharyngeal swabs. Among persons with previously confirmed SARS-CoV-2 infection, saliva's sensitivity was 1.5 percentage points higher (CI, 7.3 percentage points lower to 10.3 percentage points higher) than that of nasopharyngeal swabs. Among persons without a previous SARS-CoV-2 diagnosis, saliva was 7.9 percentage points less (CI, 14.7 percentage points less to 0.8 percentage point more) sensitive. In this subgroup, if testing 100 000 persons with a SARS-CoV-2 prevalence of 1%, nasopharyngeal swabs would detect 79 more (95% uncertainty interval, 5 fewer to 166 more) persons with SARS-CoV-2 than saliva, but with an incremental cost per additional infection detected of $8093. LIMITATION: The reference standard was imperfect, and saliva collection procedures varied. CONCLUSION: Saliva sampling seems to be a similarly sensitive and less costly alternative that could replace nasopharyngeal swabs for collection of clinical samples for SARS-CoV-2 testing. PRIMARY FUNDING SOURCE: McGill Interdisciplinary Initiative in Infection and Immunity. (PROSPERO: CRD42020203415).
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Prueba de COVID-19/economía , COVID-19/diagnóstico , Nasofaringe/virología , Saliva/virología , Antígenos Virales/análisis , Reacciones Falso Negativas , Reacciones Falso Positivas , Humanos , Sistemas de Atención de Punto , SARS-CoV-2 , Sensibilidad y Especificidad , Manejo de Especímenes/métodosRESUMEN
BACKGROUND: Tuberculosis preventive therapy (TPT) reduces TB-related morbidity and mortality in people living with HIV (PLHIV). Cascade-of-care analyses help identify gaps and barriers in care and develop targeted solutions. A previous latent tuberculosis infection (LTBI) cascade-of-care analysis showed only 18% of persons in at-risk populations complete TPT, but a similar analysis for TPT among PLHIV has not been completed. We conducted a meta-analysis to provide this evidence. METHODS AND FINDINGS: We first screened potential articles from a LTBI cascade-of-care systematic review published in 2016. From this study, we included cohorts that reported a minimum of 25 PLHIV. To identify new cohorts, we used a similar search strategy restricted to PLHIV. The search was conducted in Medline, Embase, Health Star, and LILACS, from January 2014 to February 2021. Two authors independently screened titles and full text and assessed risk of bias using the Newcastle-Ottawa Scale for cohorts and Cochrane Risk of Bias for cluster randomized trials. We meta-analyzed the proportion of PLHIV completing each step of the LTBI cascade-of-care and estimated the cumulative proportion retained. These results were stratified based on cascades-of-care that used or did not use LTBI testing to determine eligibility for TPT. We also performed a narrative synthesis of enablers and barriers of the cascade-of-care identified at different steps of the cascade. A total of 71 cohorts were included, and 70 were meta-analyzed, comprising 94,011 PLHIV. Among the PLHIV included, 35.3% (33,139/94,011) were from the Americas and 29.2% (27,460/94,011) from Africa. Overall, 49.9% (46,903/94,011) from low- and middle-income countries, median age was 38.0 [interquartile range (IQR) 34.0;43.6], and 65.9% (46,328/70,297) were men, 43.6% (29,629/67,947) were treated with antiretroviral therapy (ART), and the median CD4 count was 390 cell/mm3 (IQR 312;458). Among the cohorts that did not use LTBI tests, the cumulative proportion of PLHIV starting and completing TPT were 40.9% (95% CI: 39.3% to 42.7%) and 33.2% (95% CI: 31.6% to 34.9%). Among cohorts that used LTBI tests, the cumulative proportions of PLHIV starting and completing TPT were 60.4% (95% CI: 58.1% to 62.6%) and 41.9% (95% CI:39.6% to 44.2%), respectively. Completion of TPT was not significantly different in high- compared to low- and middle-income countries. Regardless of LTBI test use, substantial losses in the cascade-of-care occurred before treatment initiation. The integration of HIV and TB care was considered an enabler of the cascade-of-care in multiple cohorts. Key limitations of this systematic review are the observational nature of the included studies, potential selection bias in the population selection, only 14 cohorts reported all steps of the cascade-of-care, and barriers/facilitators were not systematically reported in all cohorts. CONCLUSIONS: Although substantial losses were seen in multiple stages of the cascade-of-care, the cumulative proportion of PLHIV completing TPT was higher than previously reported among other at-risk populations. The use of LTBI testing in PLHIV in low- and middle-income countries was associated with higher proportion of the cohorts initiating TPT and with similar rates of completion of TPT.
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Antirretrovirales/uso terapéutico , Antituberculosos/uso terapéutico , Coinfección , Infecciones por VIH/tratamiento farmacológico , Sobrevivientes de VIH a Largo Plazo , Tuberculosis Latente/prevención & control , Servicios Preventivos de Salud , Adulto , Antirretrovirales/efectos adversos , Antituberculosos/efectos adversos , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/microbiología , Masculino , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Less than 19% of those needing tuberculosis (TB) preventive treatment complete it, due to losses in several steps of the cascade of care for latent TB infection. A cluster randomized trial of a programmatic public health intervention to improve management of latent TB infection in household contacts was conducted in Rio de Janeiro. Interventions included contact registry, initial and in-service training, and a TB booklet. We conducted a follow-up study starting one month after the conclusion of this trial, to measure the effect of interventions implemented, and to identify remaining barriers and facilitators to latent TB infection treatment, from different perspectives. METHODS: In two health clinics in Rio de Janeiro that received the interventions in the trial, data for the latent TB infection cascade of care for household contacts was collected over a five-month period. The number of household contacts initiating treatment per 100 index-TB patients was compared with the cascade of care data obtained before and during the intervention trial. Semi-structured open-ended questionnaires were administered to healthcare workers, household contacts and index-TB patients regarding knowledge and perceptions about TB and study interventions. RESULTS: In this follow-up study, 184 household contacts per 100 index-TB patients were identified. When compared to the intervention period, there were 65 fewer household contacts per 100 index-TB patients, (95% CI -115, - 15) but the number starting latent TB infection treatment was sustained (difference -2, 95% CI -8,5). A total of 31 index-TB patients, 22 household contacts and 19 health care workers were interviewed. Among index-TB patients, 61% said all their household contacts had been tested for latent TB infection. All health care workers said it was very important to test household contacts, and 95% mentioned that possessing correct knowledge on the benefits of latent TB infection treatment was the main facilitator to enable them to recommend this treatment. CONCLUSION: In this follow-up study, we observed a sustained effect of interventions to strengthen the latent TB infection cascade of care on increasing the number of household contacts starting latent TB infection treatment.
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Tuberculosis Latente , Brasil/epidemiología , Trazado de Contacto , Estudios de Seguimiento , Personal de Salud , Humanos , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Tuberculosis Latente/prevención & control , Salud PúblicaRESUMEN
BACKGROUND: Four months of rifampin treatment for latent tuberculosis infection is safer, has superior treatment completion rates, and is as effective as 9 months of isoniazid. However, daily medication costs are higher for a 4-month rifampin regimen than a 9-month isoniazid regimen. OBJECTIVE: To compare health care use and associated costs of 4 months of rifampin and 9 months of isoniazid. DESIGN: Health system cost comparison using all health care activities recorded during 2 randomized clinical trials. (ClinicalTrials.gov: NCT00931736 and NCT00170209). SETTING: High-income countries (Australia, Canada, Saudi Arabia, and South Korea), middle-income countries (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea). PARTICIPANTS: Adults and children with clinical or epidemiologic factors associated with increased risk for developing tuberculosis that warranted treatment for latent tuberculosis infection. MEASUREMENTS: Health system costs per participant. RESULTS: A total of 6012 adults and 829 children were included. In both adults and children, greater health system use and higher costs were observed with 9 months of isoniazid than with 4 months of rifampin. In adults, the ratios of costs of 4 months of rifampin versus 9 months of isoniazid were 0.76 (95% CI, 0.70 to 0.82) in high-income countries, 0.90 (CI, 0.85 to 0.96) in middle-income countries, and 0.80 (CI, 0.78 to 0.81) in African countries. Similar findings were observed in the pediatric population. LIMITATION: Costs may have been overestimated because the trial protocol required a minimum number of follow-up visits, although fewer than recommended by many authoritative guidelines. CONCLUSION: A 4-month rifampin regimen was safer and less expensive than 9 months of isoniazid in all settings. This regimen could be adopted by tuberculosis programs in many countries as first-line therapy for latent tuberculosis infection. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.
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Antituberculosos/uso terapéutico , Costos de la Atención en Salud , Isoniazida/uso terapéutico , Tuberculosis Latente/economía , Rifampin/uso terapéutico , Adulto , Antituberculosos/economía , Niño , Costos y Análisis de Costo/economía , Países Desarrollados/economía , Países en Desarrollo/economía , Esquema de Medicación , Femenino , Costos de la Atención en Salud/estadística & datos numéricos , Humanos , Isoniazida/administración & dosificación , Isoniazida/economía , Tuberculosis Latente/tratamiento farmacológico , Masculino , Rifampin/administración & dosificación , Rifampin/economíaRESUMEN
BACKGROUND: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely passive, which impedes epidemic control. We defined active testing strategies for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) for groups at increased risk of acquiring SARS-CoV-2 in all Canadian provinces. METHODS: We identified 5 groups who should be prioritized for active RT-PCR testing: contacts of people who are positive for SARS-CoV-2, and 4 at-risk populations - hospital employees, community health care workers and people in long-term care facilities, essential business employees, and schoolchildren and staff. We estimated costs, human resources and laboratory capacity required to test people in each group or to perform surveillance testing in random samples. RESULTS: During July 8-17, 2020, across all provinces in Canada, an average of 41 751 RT-PCR tests were performed daily; we estimated this required 5122 personnel and cost $2.4 million per day ($67.8 million per month). Systematic contact tracing and testing would increase personnel needs 1.2-fold and monthly costs to $78.9 million. Conducted over a month, testing all hospital employees would require 1823 additional personnel, costing $29.0 million; testing all community health care workers and persons in long-term care facilities would require 11 074 additional personnel and cost $124.8 million; and testing all essential employees would cost $321.7 million, requiring 25 965 added personnel. Testing the larger population within schools over 6 weeks would require 46 368 added personnel and cost $816.0 million. Interventions addressing inefficiencies, including saliva-based sampling and pooling samples, could reduce costs by 40% and personnel by 20%. Surveillance testing in population samples other than contacts would cost 5% of the cost of a universal approach to testing at-risk populations. INTERPRETATION: Active testing of groups at increased risk of acquiring SARS-CoV-2 appears feasible and would support the safe reopening of the economy and schools more broadly. This strategy also appears affordable compared with the $169.2 billion committed by the federal government as a response to the pandemic as of June 2020.
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Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/economía , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/economía , Tamizaje Masivo/economía , Pandemias/economía , Neumonía Viral/diagnóstico , Neumonía Viral/economía , COVID-19 , Prueba de COVID-19 , Canadá , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Humanos , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Reacción en Cadena en Tiempo Real de la Polimerasa/economía , Medición de Riesgo/economía , Factores de Riesgo , SARS-CoV-2RESUMEN
This systematic review aimed to update the current evidence for multidrug-resistant tuberculosis (MDR-TB) treatment.We searched for studies that reported treatment information and clinical characteristics for at least 25 patients with microbiologically confirmed pulmonary MDR-TB and either end of treatment outcomes, 6-month culture conversion or severe adverse events (SAEs). We assessed the association of these outcomes with patients' characteristics or treatment parameters. We identified 74 studies, including 17â494 participants.The pooled treatment success was 26% in extensively drug-resistant TB (XDR-TB) patients and 60% in MDR-TB patients. Treatment parameters such as number or duration and individual drugs were not associated with improved 6-month sputum culture conversion or end of treatment outcomes. However, MDR-TB patients that received individualised regimens had higher success than patients who received standardised regimens (64% versus 52%; p<0.0.01). When reports from 20 cohorts were pooled, proportions of SAE ranged from 0.5% attributed to ethambutol to 12.2% attributed to para-aminosalicylic acid. The lack of significant associations of treatment outcomes with specific drugs or regimens may reflect the limitations of pooling the data rather than a true lack of differences in efficacy of regimens or individual drugs.This analysis highlights the need for stronger evidence for treatment of MDR-TB from better-designed and reported studies.
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Antituberculosos/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Antituberculosos/efectos adversos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a threat for the global TB epidemic control. Despite existing evidence that individualized treatment of MDR-TB is superior to standardized regimens, the latter are recommended in Brazil, mainly because drug-susceptibility tests (DST) are often restricted to first-line drugs in public laboratories. We compared treatment outcomes of MDR-TB patients using standardized versus individualized regimens in Brazil, a high TB-burden, low resistance setting. METHODS: The 2007-2013 cohort of the national electronic database (SITE-TB), which records all special treatments including drug-resistance, was analysed. Patients classified as MDR-TB in SITE-TB were eligible. Treatment outcomes were classified as successful (cure/treatment completed) or unsuccessful (failure/relapse/death/loss to follow-up). The odds for successful treatment according to type of regimen were controlled for demographic and clinical variables. RESULTS: Out of 4029 registered patients, we included 1972 recorded from 2010 to 2012, who had more complete outcome data. The overall success proportion was 60%. Success was more likely in non-HIV patients, sputum-negative at baseline, with unilateral disease and without prior DR-TB. Adjusted for these variables, those receiving standardized regimens had 2.7-fold odds of success compared to those receiving individualized treatments when failure/relapse were considered, and 1.4-fold odds of success when death was included as an unsuccessful outcome. When loss to follow-up was added, no difference between types of treatment was observed. Patients who used levofloxacin instead of ofloxacin had 1.5-fold odds of success. CONCLUSION: In this large cohort of MDR-TB patients with a low proportion of successful outcomes, standardized regimens had superior efficacy than individualized regimens, when adjusted for relevant variables. In addition to the limitations of any retrospective observational study, database quality hampered the analyses. Also, decision on the use of standard or individualized regimens was possibly not random, and may have introduced bias. Efforts were made to reduce classification bias and confounding. Until higher-quality evidence is produced, and DST becomes widely available in the country, our findings support the Brazilian recommendation for the use of standardized instead of individualized regimens for MDR-TB, preferably containing levofloxacin. Better quality surveillance data and DST availability across the country are necessary to improve MDR-TB control in Brazil.
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Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Brasil , Estudios de Cohortes , Femenino , Humanos , Levofloxacino/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Esputo/microbiología , Resultado del TratamientoRESUMEN
BACKGROUND: Shortened treatment regimens for tuberculosis are under development to improve treatment outcomes and reduce costs. We estimated potential savings from a societal perspective in Brazil following the introduction of a hypothetical four-month regimen for tuberculosis treatment. METHODS: Data were gathered in ten randomly selected health facilities in Rio de Janeiro. Health service costs were estimated using an ingredient approach. Patient costs were estimated from a questionnaire administered to 126 patients. Costs per visits and per case treated were analysed according to the type of therapy: self-administered treatment (SAT), community- and facility-directly observed treatment (community-DOT, facility-DOT). RESULTS: During the last 2 months of treatment, the largest savings could be expected for community-DOT; on average USD 17,351-18,203 and USD 43,660-45,856 (bottom-up and top-down estimates) per clinic. Savings to patients could also be expected as the median (interquartile range) patient-related costs during the two last months were USD 108 (13-291), USD 93 (36-239) and USD 11 (7-126), respectively for SAT, facility-DOT and community-DOT. CONCLUSION: Introducing a four-month regimen may result in significant cost savings for both the health service and patients, especially the poorest. In particular, a community-DOT strategy, including treatment at home, could maximise health services savings while limiting patient costs. Our cost estimates are likely to be conservative because a 4-month regimen could hypothetically increase the proportion of patients cured by reducing the number of patients defaulting and we did not include the possible cost benefits from the subsequent prevention of costs due to downstream transmission averted and rapid clinical improvement with less side effects in the last two months.
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Ahorro de Costo/economía , Terapia por Observación Directa , Financiación Personal , Servicios de Salud/economía , Tuberculosis/tratamiento farmacológico , Adulto , Brasil , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
CONTEXTE: Le dépistage du coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est en grande partie passif, ce qui nuit au contrôle de l'épidémie. Nous avons élaboré des stratégies de dépistage actif du SRAS-CoV-2 au moyen d'une amplification en chaîne par polymérase couplée à une transcription inverse (RT-PCR) chez les groupes courant un risque accru de contracter le virus dans les provinces canadiennes. MÉTHODES: Nous avons identifié 5 groupes qui devraient être prioritaires pour le dépistage actif au moyen d'une RTPCR, soit les gens ayant été en contact avec une personne infectée par le SRAS-CoV-2 et ceux qui appartiennent à 4 populations à risque : employés d'hôpitaux, travailleurs en soins de santé communautaires ainsi qu'employés et résidents d'établissements de soins de longue durée, employés d'entreprises essentielles, et élèves et personnel scolaire. Nous avons estimé les coûts, les ressources humaines et la capacité de laboratoire nécessaires au dépistage des membres de ces groupes ou au dépistage sur des échantillons aléatoires aux fins de surveillance. RÉSULTATS: Du 8 au 17 juillet 2020, 41 751 dépistages par RT-PCR étaient réalisés chaque jour en moyenne dans les provinces canadiennes; nous avons estimé que ces tests mobilisaient 5122 employés et coûtaient 2,4 millions de dollars par jour (67,8 millions de dollars par mois). La recherche et le dépistage systématiques des contacts requerraient 1,2 fois plus de personnel et porteraient les coûts mensuels à 78,9 millions de dollars. S'il était réalisé en 1 mois, le dépistage de tous les employés des hôpitaux nécessiterait 1823 travailleurs supplémentaires et coûterait 29,0 millions de dollars. Pour la même période de temps, le dépistage de tous les travailleurs en soins de santé communautaires et de tous les employés et résidents des établissements de soins de longue durée nécessiterait 11 074 employés supplémentaires et coûterait 124,8 millions de dollars, et celui de tous les travailleurs essentiels nécessiterait 25 965 employés supplémentaires et coûterait 321,7 millions de dollars. Enfin, le dépistage sur 6 semaines de la population scolaire nécessiterait 46 368 employés supplémentaires et coûterait 816,0 millions de dollars. Les interventions visant à pallier les inefficacités, comme le dépistage à partir d'échantillons de salive et le regroupement des échantillons, pourraient réduire les coûts de 40 % et les besoins en personnel, de 20 %. Le dépistage de surveillance sur des échantillons de la population autre que les contacts coûterait 5 % des coûts associés à l'adoption d'une approche universelle de dépistage auprès des populations à risque. INTERPRÉTATION: Le dépistage actif des groupes courant un risque accru de contracter le SRAS-CoV-2 semble faisable et favoriserait la réouverture sûre et à grande échelle de l'économie et des écoles. Cette stratégie semble également abordable lorsque comparée aux 169,2 milliards de dollars versés par le gouvernement fédéral dans la lutte contre la pandémie en date de juin 2020.
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Background: Pulmonary tuberculosis (PTB) can result in long-term health consequences, even after successful treatment. We conducted a systematic review and meta-analysis to estimate the occurrence of respiratory impairment, other disability states, and respiratory complications following successful PTB treatment. Methods: We identified studies from January 1, 1960, to December 6, 2022, describing populations of all ages that successfully completed treatment for active PTB and had been assessed for at least one of the following outcomes: occurrence of respiratory impairment, other disability states, or respiratory complications following PTB treatment. Studies were excluded if they reported on participants with self-reported TB, extra-pulmonary TB, inactive TB, latent TB, or if participants had been selected on the basis of having more advanced disease. Study characteristics and outcome-related data were abstracted. Meta-analysis was performed using a random effects model. We adapted the Newcastle Ottawa Scale to evaluate the methodological quality of the included studies. Heterogeneity was assessed using the I2 statistic and prediction intervals. Publication bias was assessed using Doi plots and LFK indices. This study is registered with PROSPERO (CRD42021276327). Findings: 61 studies with 41,014 participants with PTB were included. In 42 studies reporting post-treatment lung function measurements, 59.1% (I2 = 98.3%) of participants with PTB had abnormal spirometry compared to 5.4% (I2 = 97.4%) of controls. Specifically, 17.8% (I2 = 96.6%) had obstruction, 21.3% (I2 = 95.4%) restriction, and 12.7% (I2 = 93.2%) a mixed pattern. Among 13 studies with 3179 participants with PTB, 72.6% (I2 = 92.8%) of participants with PTB had a Medical Research Council dyspnoea score of 1-2 and 24.7% (I2 = 92.2%) a score of 3-5. Mean 6-min walk distance in 13 studies was 440.5 m (I2 = 99.0%) in all participants (78.9% predicted, I2 = 98.9%) and 403.0 m (I2 = 95.1%) among MDR-TB participants in 3 studies (70.5% predicted, I2 = 97.6%). Four studies reported data on incidence of lung cancer, with an incidence rate ratio of 4.0 (95% CI 2.1-7.6) and incidence rate difference of 2.7 per 1000 person-years (95% CI 1.2-4.2) when compared to controls. Quality assessment indicated overall low-quality evidence in this field, heterogeneity was high for pooled estimates of nearly all outcomes of interest, and publication bias was considered likely for almost all outcomes. Interpretation: The occurrence of post-PTB respiratory impairment, other disability states, and respiratory complications is high, adding to the potential benefits of disease prevention, and highlighting the need for optimised management after successful treatment. Funding: Canadian Institutes of Health Research Foundation Grant.
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Background: In Brazil, investigation and treatment of tuberculosis infection (TBI) in households contacts (HHC) of TB patients is not a priority. We estimated the cost-effectiveness and budget-impact of scaling-up an enhanced HHC management in Brazil. Methods: We conceptualized a cascade-of-care that captures how HHC of tuberculosis patients are investigated in Brazil (status quo) and two enhanced strategies for management of HHC focusing on: (1) only tuberculosis disease (TBD) detection and, (2) TBD and TBI detection and treatment. Effectiveness was the number of HHC diagnosed with TBD and completing TBI treatment. Proportions in the cascades-of-care were derived from a meta-analysis. Health-system costs (2019 US$) were based on literature and official data from Brazil. The impact of enhanced strategies was extrapolated using reported data from 2019. Findings: With the status quo, 0 (95% uncertainty interval: 0-1) HHC are diagnosed with TBD and 2 (0-16) complete TBI treatment. With strategy(1), an additional 15 (3-45) HHC would be diagnosed with TBD at a cost of US$346 each. With strategy(2), 81 (19-226) additional HHC would complete TBI treatment at a cost of US$84 each. A combined strategy, implemented nationally to enhance TBD detection and TBI treatment would result in an additional 9,711 (845-28,693) TBD being detected, and 51,277 (12,028-143,495) more HHC completing TBI treatment each year, utilizing 10.9% and 11.6% of the annual national tuberculosis program budget, respectively. Interpretation: Enhanced detection and treatment of TBD and TBI among HHC in Brazil can be achieved at a national level using current tools at reasonable cost. Funding: None.
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BACKGROUND: The World Health Organization recommends tuberculosis (TB) preventive treatment (TPT) for all people living with HIV (PLH) and household contacts (HHC) of index TB patients. Tests for TB infection (TBI) or to rule out TB disease (TBD) are preferred, but if not available, this should not be a barrier if access to these tests is limited for high-risk people, such as PLH and HHC under 5 years old. There is equipoise on the need for these tests in different risk populations, especially HHC aged over 5. METHODS: This superiority cluster-randomized multicenter trial with three arms of equal size compares, in Benin and Brazil, three strategies for HHC investigation aged 0-50: (i) tuberculin skin testing (TST) or interferon gamma release assay (IGRA) for TBI and if positive, chest X-Ray (CXR) to rule out TBD in persons with positive TST or IGRA; (ii) same as (i) but GeneXpert (GX) replaces CXR; and (iii) no TBI testing. CXR for all; if CXR is normal, TPT is recommended. All strategies start with symptom screening. Clusters are defined as HHC members of the same index patients with newly diagnosed pulmonary TBD. The main outcome is the proportion of HHC that are TPT eligible who start TPT within 3 months of the index TB patient starting TBD treatment. Societal costs, incidence of severe adverse events, and prevalence of TBD are among secondary outcomes. Stratified analyses by age (under versus over 5) and by index patient microbiological status will be conducted. All participants provide signed informed consent. The study was approved by the Research Ethic Board of the Research Institute of the McGill University Health Centre, the Brazilian National Ethical Board CONEP, and the "Comité Local d'Éthique Pour la Recherche Biomédicale (CLERB) de l'Université de Parakou," Benin. Findings will be submitted for publication in major medical journals and presented in conferences, to WHO and National and municipal TB programs of the involved countries. DISCUSSION: This randomized trial is meant to provide high-quality evidence to inform WHO recommendations on investigation of household contacts, as currently these are based on very low-quality evidence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04528823.
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Tuberculosis Latente , Tuberculosis , Preescolar , Humanos , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis Latente/complicaciones , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/epidemiología , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Tuberculina , Prueba de Tuberculina/métodos , Tuberculosis/diagnóstico , Rayos XRESUMEN
Although tuberculosis preventive therapy is one of the cornerstones for eliminating the disease, many barriers exist in the cascade of care for latent tuberculosis infection, including the need to certify healthcare professionals for reading tuberculin skin tests (TST). This paper proposes and evaluates a simple protocol for TST reading training. Primary care workers from different backgrounds received a 2-hour theoretical course, followed by a practical course on bleb reading. Blebs were obtained by injecting saline into sausages and then in volunteers. A certified trainer then evaluated the effectiveness of this protocol by analyzing the trainees' ability to read TST induration in clinical routine, blinded to each other's readings. Interobserver agreement was analyzed using the Bland-Altman test. The trainees' reading accuracy was calculated using two cut-off points - 5 and 10mm - and the effect of the number of readings was analyzed using a linear mixed model. Eleven healthcare workers read 53 saline blebs and 88 TST indurations, with high agreement for TST reading (0.07mm average bias). Sensitivity was 100% (94.6; 100.0) at 5mm cut-off and 87.3% (75.5; 94.7) at 10mm cut-off. The regression model found no effect of the number of readings [coefficient: -0.007 (-0.055; 0.040)]. A simple training protocol for reading TST with saline blebs simulations in sausages and volunteers was sufficient to achieve accurate TST induration readings, with no effect observed for the number of readings. Training with saline blebs injected into voluntary individuals is safer and easier than the traditional method.
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Tuberculosis Latente , Prueba de Tuberculina , Brasil , Certificación , Humanos , Atención Primaria de SaludRESUMEN
GeneXpert® Edge (GX-Edge) is a new point-of-care platform not yet tested in the field. In this proof-of-concept study conducted for the diagnosis of tuberculosis in communities living alongside two large rivers of the Brazilian Amazon, we demonstrate that GX-Edge implemented in boats to offer onsite testing is a feasible strategy to investigate potentially devastating diseases such as tuberculosis in difficult-to-reach populations, such as riverside communities.
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Técnicas de Diagnóstico Molecular/métodos , Sistemas de Atención de Punto , Tuberculosis/diagnóstico , Brasil , Atención a la Salud , Estudios de Factibilidad , HumanosRESUMEN
OBJECTIVE: To synthesize data about the prevalence of sexual violence (SV) among refugees around the world. METHODS: A systematic review was conducted from the search in seven bibliographic databases. Studies on the prevalence of SV among refugees and asylum seekers of any country, sex or age, whether in English, French, Spanish and Portuguese, were eligible. RESULTS: Of the 2,906 titles found, 60 articles were selected. The reported prevalence of SV was largely variable (0% to 99.8%). Reports of SV were collected in all continents, with 42% of the articles mentioning it in refugees from Africa (prevalence from 1.3% to 100%). The rape was the most reported SV in 65% of the studies (prevalence from 0% to 90.9%). The main victims were women in 89% of the studies, all the way, especially when still in the countries of origin. The SV was perpetrated particularly by intimate partners, but also by agents of supposed protection. Few studies have reported SV in men and children; the prevalence reached up to 39.3% and 90.9%, respectively. Approximately one-third of the studies (32%) were carried out in refugee camps and more than half (52%) in health services using mental health assessment tools. No study has addressed the most recent migratory crisis. Meta-analysis was not performed due to the methodological heterogeneity of the studies. CONCLUSIONS: SV is a prevalent problem affecting refugees of both sexes, of all ages, throughout the migratory journey, particularly those from Africa. Protection measures are urgently needed, and further studies, with more appropriate tools, may better measure the current magnitude of the problem.
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Refugiados/estadística & datos numéricos , Delitos Sexuales/estadística & datos numéricos , Femenino , Humanos , Masculino , Prevalencia , Factores de Riesgo , Factores SexualesRESUMEN
BACKGROUND: Brazil has the largest public health-system in the world, with 120 million people covered by its free primary care services. The Family Health Strategy (FHS) is the main primary care model, but there is no consensus on its impact on health outcomes. We systematically reviewed published evidence regarding the impact of the Brazilian FHS on selective primary care sensitive conditions (PCSC). METHODS: We searched Medline, Web of Science and Lilacs in May 2016 using key words in Portuguese and English, without language restriction. We included studies if intervention was the FHS; comparison was either different levels of FHS coverage or other primary health care service models; outcomes were the selected PCSC; and results were adjusted for relevant sanitary and socioeconomic variables, including the national conditional cash transfer program (Bolsa Familia). Due to differences in methods and outcomes reported, pooling of results was not possible. RESULTS: Of 1831 records found, 31 met our inclusion criteria. Of these, 25 were ecological studies. Twenty-one employed longitudinal quasi-experimental methods, 27 compared different levels the FHS coverage, whilst four compared the FHS versus other models of primary care. Fourteen studies found an association between higher FHS coverage and lower post-neonatal and child mortality. When the effect of Bolsa Familia was accounted for, the effect of the FHS on child mortality was greater. In 13 studies about hospitalizations due to PCSC, no clear pattern of association was found. In four studies, there was no effect on child and elderly vaccination or low-birth weight. No included studies addressed breast-feeding, dengue, HIV/AIDS and other neglected infectious diseases. CONCLUSIONS: Among these ecological studies with limited quality evidence, increasing coverage by the FHS was consistently associated with improvements in child mortality. Scarce evidence on other health outcomes, hospitalization and synergies with cash transfer was found.
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Salud de la Familia/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Brasil , HumanosRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0182336.].
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Although tuberculosis preventive therapy is one of the cornerstones for eliminating the disease, many barriers exist in the cascade of care for latent tuberculosis infection, including the need to certify healthcare professionals for reading tuberculin skin tests (TST). This paper proposes and evaluates a simple protocol for TST reading training. Primary care workers from different backgrounds received a 2-hour theoretical course, followed by a practical course on bleb reading. Blebs were obtained by injecting saline into sausages and then in volunteers. A certified trainer then evaluated the effectiveness of this protocol by analyzing the trainees' ability to read TST induration in clinical routine, blinded to each other's readings. Interobserver agreement was analyzed using the Bland-Altman test. The trainees' reading accuracy was calculated using two cut-off points - 5 and 10mm - and the effect of the number of readings was analyzed using a linear mixed model. Eleven healthcare workers read 53 saline blebs and 88 TST indurations, with high agreement for TST reading (0.07mm average bias). Sensitivity was 100% (94.6; 100.0) at 5mm cut-off and 87.3% (75.5; 94.7) at 10mm cut-off. The regression model found no effect of the number of readings [coefficient: -0.007 (-0.055; 0.040)]. A simple training protocol for reading TST with saline blebs simulations in sausages and volunteers was sufficient to achieve accurate TST induration readings, with no effect observed for the number of readings. Training with saline blebs injected into voluntary individuals is safer and easier than the traditional method.
A terapia preventiva da tuberculose é uma das bases para a eliminação da tuberculose. Entretanto, existem muitas barreiras na cascata de cuidados da infecção latente de tuberculose, incluindo a necessidade de certificação dos profissionais de saúde para a leitura da prova tuberculínica (PPD). Aqui, propomos e avaliamos um protocolo simples para capacitação na leitura do PPD. Profissionais na atenção primária com diferentes formações receberam um curso teórico de duas horas, seguido por um curso prático sobre a leitura da enduração. Nas sessões práticas, as pápulas foram obtidas pela injeção de solução salina em salsichas, e depois em voluntários. Depois, a eficácia do protocolo foi avaliada por um instrutor credenciado, com base na capacidade do aluno de ler a enduração do PPD na rotina clínica (em formato duplo-cego em relação às respectivas leituras). A concordância inter-observador foi analisada com o teste de Bland-Altman. A acurácia das leituras dos alunos foi calculada com dois pontos de corte: 5 e 10mm. O efeito do número de leituras foi analisado com um modelo linear misto. Onze profissionais de saúde leram 53 pápulas de solução salina e 88 endurações de PPD. A concordância na leitura dos PPDs foi alta (média de 0,07mm de viés). A sensibilidade foi 100% (94,6; 100,0) com o ponto de corte de 5mm e 87,3% (75,5; 94,7) com o ponto de corte de 10mm. No modelo de regressão, não houve efeito do número de leituras [coeficiente: -0,007 (-0,055; 0,040)]. Um protocolo simples de treinamento em leitura da prova tuberculínica com simulações usando pápulas criadas com solução salina em salsichas e em voluntários foi suficiente para alcançar leituras acuradas da enduração da prova, sem efeito observado pelo número de leituras. O treinamento com pápulas criadas com solução salina em voluntários é mais seguro e mais fácil, comparado com o treinamento tradicional.
La terapia preventiva de la tuberculosis es una de las piedras angulares para la erradicación de la tuberculosis. No obstante, existen muchas barreras en la cascada de cuidado de una infección latente de tuberculosis, incluyendo la necesidad de certificación, en el caso de los profesionales de atención en salud, para la lectura de la prueba cutánea de tuberculina (TST). Aquí proponemos y evaluamos un protocolo simple para el entrenamiento en la lectura de TST. Trabajadores de salud de atención primaria de diferentes contextos recibieron un curso de 2 horas teórico, seguido de una práctica en la lectura de la ampolla. Las ampollas se obtienen inyectado una solución salina en salchichas y luego en voluntarios. Posteriormente, la eficacia de este protocolo fue evaluada mediante un formador certificado a través de la habilidad del personal en formación para la lectura de induración del TST en la rutina clínica, con lecturas cegadas entre ellos. Se analizó la concordancia entre los observadores usando el test Bland-Altman. La precisión de la lectura por parte del personal en formación se calculó usando dos puntos de corte: 5 y 10mm. El efecto del número de lecturas fue analizado usando un modelo lineal mixto. Once trabajadores de salud leyeron 53 soluciones salinas en ampollas y 88 induraciones TST. La concordancia en la lectura del TST fue alta (0,07mm promedio de sesgo). La sensibilidad fue de un 100% (94,6; 100,0) usando los 5mm de corte y 87,3% (75,5; 94,7) usando los 10mm de corte. En el modelo de regresión, no hubo efecto del número de lecturas [coeficiente: -0,007 (-0,055; 0,040)]. Un simple protocolo de entrenamiento para la lectura TST con simulaciones, usando solución salina en ampollas en salchichas y voluntarios fue suficiente para alcanzar lecturas precisas de induración TST, sin efectos observados por el número de lecturas. El entrenamiento con ampollas salinas en personas voluntarias es más seguro y más fácil que el entrenamiento tradicional.