For Tuberculosis, Not "To Screen or Not to Screen?" but "Who?" and "How?"

Active case finding leveraging new molecular diagnostics and chest X-rays with automated interpretation algorithms is increasingly being developed for high-risk populations to drive down tuberculosis incidence. We consider why such an approach did not deliver a decline in tuberculosis prevalence in Brazilian prison populations and what to consider next.

Seroepidemiological Survey of Chronic Chagas Disease in a Rural Community in Southern Bahia, Brazil, Using Recombinant Chimeric Antigens.

Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is a neglected tropical disease with life-threatening implications. In this study, we conducted a seroepidemiological survey to determine the prevalence and clinical profiles of CD in 217 individuals from an impoverished rural community in Southern Bahia, Brazil. The overall prevalence of CD in the studied community was 0.92%, detected through latent class analysis (LCA). Two individuals tested positive for anti-T. cruzi IgG, both being male farmers. One case was a 22-year-old man born in Camamu, with no evidence of congenital transmission, suggesting other routes of transmission such as vector-borne transmission due to migratory activities. The other case was a 69-year-old man born in São Felipe, who had lived in an adobe/brick house and had a pacemaker due to cardiac involvement caused by CD. The prevalence in this community was lower than expected, given the socioeconomic conditions and environmental factors that contribute to T. cruzi transmission. This could be attributed to the implementation of preventive measures and vector control programs by the Brazilian Government. However, continuous monitoring and surveillance are essential to sustain control efforts and detect any potential re-emergence of the disease. While the overall prevalence was low, the detection of positive cases underscores the need for continued surveillance and control measures in vulnerable populations, such as rural communities. Active surveillance, early diagnosis, and timely treatment are crucial in preventing disease progression and complications, thereby enhancing the effectiveness of screening and treatment programs.

Seroepidemiology of Chagas disease in at-risk individuals in Caraíbas, a city with high endemicity in Bahia State, Brazil.

Introduction: In Brazil, an estimated 1.1 million people are infected with Trypanosoma cruzi, the causative agent of Chagas disease (CD). Despite the high number of cases, the estimated prevalence of infection per 100 inhabitants is low (0.03). However, the actual number of chronically infected individuals is still unknown. Therefore, we sought to determine the prevalence of chronic CD in at-risk individuals in Caraíbas (Bahia, Brazil) through active case finding. Methods: A total of 572 individuals living in rural or urban areas of Caraíbas were eligible for the study. A serum sample was collected from 226 individuals, and the diagnosis performed according to international guidelines. Results: The overall prevalence of anti-T. cruzi IgG was 4.42%. The median age of anti-T. cruzi IgG-positive individuals was 54.5 years, and the female-to-male ratio was 1.5:1. The prevalence of anti-T. cruzi IgG was similar in rural (4.29%) and urban areas (4.65%). Discussion: Compared with national estimates, we concluded that Caraíbas had a high prevalence for chronic CD and a high risk for persistent transmission. Through our study, it was possible to monitor individuals who were unaware of their clinical condition, thus improving their quality of life.

Leprosy among children in an area without primary health care coverage in Caratateua Island, Brazilian Amazon.

Introduction: The detection of leprosy in children is an important epidemiological marker of the disease, indicating the community's early exposure to Mycobacterium leprae and active transmission of the infection. Methods: In order to detect new cases among children by combining clinical evaluation and laboratory tests, we conducted an active case finding among individuals under 15 years old on Caratateua Island, located in the city of Belém, in the Pará state, an endemic region in the Amazon. Dermato-neurological examination, collection of 5 mL of peripheral blood for IgM anti-PGL-I antibody titration, and intradermal scraping for bacilloscopy and amplification of the specific RLEP region by qPCR were performed. Results: Out of the 56 examined children, 28/56 (50%) new cases were identified. At the time of evaluation, 38/56 (67.8%) children presented one or more clinical alterations. Seropositivity was detected in 7/27 (25.9%) new cases and 5/24 (20.8%) undiagnosed children. DNA amplification of Mycobacterium leprae was observed in 23/28 (82.1%) of new cases and in 5/26 (19.2%) of non-cases. Out of the total cases, 11/28 (39.2%) were exclusively diagnosed by clinical evaluation performed during the active case finding. Seventeen new cases (60.8%) were detected considering the clinical alterations found in addition to positive results for qPCR. In this group, 3/17 (17.6%) qPCR-positive children presented significant clinical changes 5.5 months after the first evaluation. Discussion: Our research detected a number of cases 5.6 times higher compared to the total number of pediatric cases recorded throughout the year 2021 in the municipality of Belém, which shows a critical scenario of underdiagnosing of leprosy among children under 15 years old in the region. We propose the use of qPCR technique to identify new cases among children with oligosymptomatic or early disease in endemic areas, in addition to the training of Primary Health Care professionals and the implementation of the Family Health Strategy coverage in the visited area.

Sensitivity of Various Case Detection Algorithms for Community-based Tuberculosis Screening.

Using data from 388 people diagnosed with tuberculosis through a community-based screening program in Lima, Peru, we estimated that cough screening followed by sputum smear microscopy would have detected only 23% of cases found using an algorithm of radiographic screening followed by rapid nucleic acid amplification testing and clinical evaluation.

Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis: A diagnostic case-control study.

BACKGROUND: There is a need to identify scalable tuberculosis screening strategies among high burden populations. The WHO has identified a non-sputum-based triage test as a development priority. METHODS: We performed a diagnostic case-control study of point-of-care C-reactive protein (CRP) and Prototype-Xpert-MTB-Host-Response (Xpert-MTB-HR) assays in the context of a mass screening program for tuberculosis in two prisons in Brazil. All incarcerated individuals irrespective of symptoms were screened by sputum Xpert MTB/RIF and sputum culture. Among consecutive, Xpert MTB/RIF or culture-confirmed cases and Xpert MTB/RIF and culture-negative controls, CRP was quantified in serum by a point-of-care assay (iChroma-II) and a 3-gene expression score was quantified from whole blood using the Xpert-MTB-HR cartridge. We evaluated receiver operating characteristic area under the curve (AUC) and assessed specificity at 90% sensitivity and sensitivity at 70% specificity, consistent with WHO target product profile (TPP) benchmarks. FINDINGS: Two hundred controls (no TB) and 100 culture- or Xpert MTB/RIF-positive tuberculosis cases were included. Half of tuberculosis cases and 11% of controls reported any tuberculosis symptoms. AUC for CRP was 0·79 (95% CI: 0·73-0·84) and for Xpert-MTB-HR was 0·84 (95% CI: 0·79-0·89). At 90% sensitivity, Xpert-MTB-HR had significantly higher specificity (53·0%, 95% CI: 45·0-69·0%) than CRP (28·1%, 95% CI: 20·2-41·8%) (p = 0·003), both well below the TPP benchmark of 70%. Among individuals with medium or high sputum Xpert MTB/RIF semi-quantitative load, sensitivity (at 70% specificity) of CRP (90·3%, 95% CI: 74·2-98·0) and Xpert-MTB-HR (96·8%, 95% CI: 83·3-99·9%) was higher. INTERPRETATION: For active case finding in this high tuberculosis-burden setting, CRP and Xpert-MTB-HR did not meet TPP benchmarks for a triage test. However, Xpert-MTB-HR was highly sensitive in detecting individuals with medium or high sputum bacillary burden. FUNDING: National Institutes of Health (R01 AI130058 and R01 AI149620) and Brazilian National Council for Scientific and Technological Development (CNPq-404182/2019-4).

A pragmatic stepped-wedge cluster randomized trial to evaluate the effectiveness and cost-effectiveness of active case finding for household contacts within a routine tuberculosis program, San Juan de Lurigancho, Lima, Peru.

BACKGROUND: Active case finding (ACF) in household contacts of tuberculosis (TB) patients is now recommended for National TB Programs (NTP) in low- and middle-income countries. However, evidence supporting these recommendations remains limited. This study evaluates the effectiveness and cost-effectiveness of ACF for household contacts of TB cases in a large TB endemic district of Lima, Peru. METHODS: A pragmatic stepped-wedge cluster randomized controlled trial was conducted in 34 health centers of San Juan de Lurigancho district. Centers were stratified by TB rate and randomly allocated to initiate ACF in groups of eight or nine centers at four-month intervals. In the intervention arm, NTP providers visited households of index patients to screen contacts for active TB. The control arm was routine passive case finding (PCF) of symptomatic TB cases. The primary outcomes were the crude and adjusted active TB case rates among household contacts. Program costs were directly measured, and the cost-effectiveness of the ACF intervention was determined. FINDINGS: 3222 index TB cases and 12,566 household contacts were included in the study. ACF identified more household contact TB cases than PCF, 199.29/10,000 contacts/year vs. 132.13 (incidence rate ratio of 1.51 (95% CI 1.21-1.88)). ACF was associated with an incremental cost-effectiveness ratio of US $16,400 per disability-adjusted life year averted and not cost-effective assuming a willingness-to-pay threshold for Peru of US $6360. CONCLUSION: ACF of TB case household contacts detected significantly more secondary TB cases than PCF alone, but was not cost-effective in this setting. In threshold analyses, ACF becomes cost-effective if associated with case detection rates 2.5 times higher than existing PCF programs.

Assessment of children exposed to adult pulmonary tuberculosis in Cali, Colombia.

BACKGROUND: There is a lack of uniform criteria for the diagnosis and management of tuberculosis (TB) in children in Cali, Colombia. Addressing TB in children is a challenge in this setting, under both programmatic and research conditions. OBJECTIVES: To facilitate the diagnostic assessment of TB in a paediatric cohort of TB household contacts. METHODS: A diagnostic and management algorithm (DMA) was used to assess children exposed to adult TB cases, according to clinical and epidemiological findings and under programmatic conditions. On the basis of diagnostic tests, cases were classified as TB exposure, TB infection, suspected TB, possible TB or confirmed TB and then submitted to a management plan. This was a prospective pilot study nested within a national cohort study of the transmission dynamics of Mycobacterium tuberculosis, undertaken in Colombia during 2005-2008. RESULTS: During 24 months of follow-up, 54 of 217 children met the criteria for assessment by DMA, 18 of whom (33%) were considered to be TB incident cases (new TB cases among household contacts). The main clinical findings were failure to thrive and cough lasting >21 days. Only one case was smear-positive and culture-confirmed TB. TB treatment was given to 16 children and they demonstrated clinical and radiographic resolution at follow-up. Conducting the study under programmatic conditions demonstrated barriers to accessing competent radiological evaluation, correct interpretation of the tuberculin skin test, and proper specimen collection. CONCLUSION: Structured assessment using DMA facilitated the detection of incident TB cases. The study identified potential barriers to addressing childhood TB in Cali.

Prevalence of patients with respiratory symptoms through active case finding and diagnosis of pulmonary tuberculosis among prisoners and related predictors in a jail in the city of Carapicuíba, Brazil / Prevalência de sintomáticos respiratórios através da busca ativa, diagnóstico de tuberculose pulmonar entre pessoas privadas de liberdade e fatores associados em uma cadeia pública no município de Carapicuíba, Brasil

BACKGROUND: Prisons offer a fertile setting for the transmission of tuberculosis due to the presence of many classic risk factors for both infection and disease: overcrowding, poor ventilation, and little sunlight. Prisoners are often malnourished and have poor hygiene and are more likely to have a background of alcohol and drug abuse. OBJECTIVES: To determine the prevalence of prisoners with respiratory symptoms and pulmonary tuberculosis (PTB) through active case finding in a prisoner population of the county jail of Carapicuíba, and to study possible related variables. METHODS: This was a cross-sectional study, and respiratory symptomatic individuals (RSI) were detected through active case finding. Socio-demographic data were collected from inmates' judicial history using a specific questionnaire. The RSI provided sputum specimens for detection of acid fast bacilli and culture for mycobacterium identification. RESULTS: Among the 397 prisoners studied, 154 reported respiratory symptoms for more than three weeks, and were considered RSI; the variables associated with RSI were: having already been tried and incarcerated for more than six months and seven were diagnosed as PTB (1,763 cases/ 100,000 inhabitants). CONCLUSIONS: The prevalence of RSI and PTB cases were respectively 39 and 35 times greater than the general population.

INTRODUÇÃO: Estabelecimentos prisionais são um campo favorável para a transmissão de tuberculose (TB), devido a presença de vários fatores de risco clássicos, tanto para a infecção como para a doença: aglomeração, falta de ventilação e de iluminação, como também o fato de os detentos receberem uma nutrição deficitária e os locais possuí-rem condições de higiene precárias; uma grande proporção dos detentos apresentam história pregressa de alcoolismo e uso de drogas ilícitas nas dependências desses estabelecimentos. OBJETIVOS: Determinar a prevalência de sintomáticos respiratórios (RSI) e casos de tuberculose pulmonar (TBP) através da busca ativa em população privada de liberdade na cadeia pública do município de Carapicuíba e estudar os prováveis fatores associados. MÉTODO: O desenho de estudo foi do tipo corte transversal, realizou-se a busca ativa de RSI e os dados sociodemográficos foram coletados em questionários específicos a partir dos processos judiciais dos participantes. Os RSI foram submetidos ao exame de baciloscopia e cultura para micobactérias do escarro. RESULTADOS: Dos 397 detentos estudados, 154 relataram tosse por mais de três semanas, considerados RSI. Os fatores associados à presença de sintomas respiratórios foram estar preso há mais de seis meses e ter sido julgado. Foram diagnosticados 7 casos de tuberculose pulmonar, 1.763 casos por 100.000 detentos. CONCLUSÕES: A prevalência de RSI e casos de TBP foram 39 e 35 vezes superior ao encontrado na população em geral respectivamente.