Investigation of contacts of patients with tuberculosis (TB) is a priority for TB control in high-income countries, and is increasingly being considered in resource-limited settings. This review was commissioned for a World Health Organization Expert Panel to develop global contact investigation guidelines.

We performed a systematic review and meta-analysis of all studies reporting the prevalence of TB and latent TB infection, and the annual incidence of TB among contacts of patients with TB.

After screening 9,555 titles, we included 203 published studies. In 95 studies from low- and middle-income settings, the prevalence of active TB in all contacts was 3.1% (95% CI 2.2–4.4%, I2=99.4%), microbiologically proven TB was 1.2% (95% CI 0.9–1.8%, I2=95.9%), and latent TB infection was 51.5% (95% CI 47.1–55.8%, I2=98.9%). The prevalence of TB among household contacts was 3.1% (95% CI 2.1–4.5%, I2=98.8%) and among contacts of patients with multidrug-resistant or extensively drug-resistant TB was 3.4% (95% CI 0.8–12.6%, I2=95.7%). Incidence was greatest in the first year after exposure. In 108 studies from high-income settings, the prevalence of TB among contacts was 1.4% (95% CI 1.1–1.8%, I2=98.7%), and the prevalence of latent infection was 28.1% (95% CI 24.2–32.4%, I2=99.5%). There was substantial heterogeneity among published studies.

Contacts of TB patients are a high-risk group for developing TB, particularly within the first year. Children <5 yrs of age and people living with HIV are particularly at risk. Policy recommendations must consider evidence of the cost-effectiveness of various contact tracing strategies, and also incorporate complementary strategies to enhance case finding.

https://erj.ersjournals.com/content/erj/41/1/140.full.pdf

Contact investigation for tuberculosis: a systematic review and meta-analysis.

New scientific articles about tuberculosis (TB) are published daily worldwide. However, it is difficult for health care workers, overloaded with work, to stay abreast of the latest research findings and to discern which information can and should be used in their daily practice on assisting TB patients. The purpose of the III Brazilian Thoracic Association (BTA) Guidelines on TB is to critically review the most recent national and international scientific information on TB, presenting an updated text with the most current and useful tools against TB to health care workers in our country. The III BTA Guidelines on TB have been developed by the BTA Committee on TB and the TB Work Group, based on the text of the II BTA Guidelines on TB (2004). We reviewed the following databases: LILACS (SciELO) and PubMed (Medline). The level of evidence of the cited articles was determined, and 24 recommendations on TB have been evaluated, discussed by all of the members of the BTA Committee on TB and of the TB Work Group, and highlighted. The first version of the present Guidelines was posted on the BTA website and was available for public consultation for three weeks. Comments and critiques were evaluated. The level of scientific evidence of each reference was evaluated before its acceptance for use in the final text.

/pdf/iii-brazilian-thoracic-association-guidelines-on-1wl1liy1qa.pdf

III Brazilian Thoracic Association Guidelines on tuberculosis.

Background 
Infectious disease incidence is often male-biased. Two main hypotheses have been proposed to explain this observation. The physiological hypothesis (PH) emphasizes differences in sex hormones and genetic architecture, while the behavioral hypothesis (BH) stresses gender-related differences in exposure. Surprisingly, the population-level predictions of these hypotheses are yet to be thoroughly tested in humans.
Methods and Findings 
For ten major pathogens, we tested PH and BH predictions about incidence and exposure-prevalence patterns. Compulsory-notification records (Brazil, 2006–2009) were used to estimate age-stratified ♂:♀ incidence rate ratios for the general population and across selected sociological contrasts. Exposure-prevalence odds ratios were derived from 82 published surveys. We estimated summary effect-size measures using random-effects models; our analyses encompass ∼0.5 million cases of disease or exposure. We found that, after puberty, disease incidence is male-biased in cutaneous and visceral leishmaniasis, schistosomiasis, pulmonary tuberculosis, leptospirosis, meningococcal meningitis, and hepatitis A. Severe dengue is female-biased, and no clear pattern is evident for typhoid fever. In leprosy, milder tuberculoid forms are female-biased, whereas more severe lepromatous forms are male-biased. For most diseases, male bias emerges also during infancy, when behavior is unbiased but sex steroid levels transiently rise. Behavioral factors likely modulate male–female differences in some diseases (the leishmaniases, tuberculosis, leptospirosis, or schistosomiasis) and age classes; however, average exposure-prevalence is significantly sex-biased only for Schistosoma and Leptospira.
Conclusions 
Our results closely match some key PH predictions and contradict some crucial BH predictions, suggesting that gender-specific behavior plays an overall secondary role in generating sex bias. Physiological differences, including the crosstalk between sex hormones and immune effectors, thus emerge as the main candidate drivers of gender differences in infectious disease susceptibility.

/pdf/sex-bias-in-infectious-disease-epidemiology-patterns-and-mz46dn93of.pdf

Sex bias in infectious disease epidemiology: patterns and processes.

Tuberculosis ranges among the leading causes of morbidity and mortality worldwide. A diagnostic approach to a patient with possible tuberculosis includes a detailed medical history and clinical examination as well as radiological, microbiological, immunological, molecular-biological and histological investigations, where available. Recently, important advances have been achieved in these fields that have led to substantial improvements in the accuracy and the timing of the diagnosis of tuberculosis. Novel methods allow for a better identification of latently infected individuals who are at risk of developing active tuberculosis, they also offer the possibility for a rapid diagnosis of active tuberculosis in patients with negative sputum smears for acid-fast bacilli and enable prompt identification of drug-resistant strains of Mycobacterium tuberculosis directly from respiratory specimen with a high accuracy. In addition, promising methods that will further optimize the diagnosis of tuberculosis are under development. In the future, therapeutic interventions based on the results of novel diagnostic procedures can be made earlier leading to improvements in patient care.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1440-1843.2009.01692.x

Advances in the diagnosis of tuberculosis.

A profusion of articles have been published on the accuracy and uses of interferon-gamma releasing assays. Here we review the clinical applications, advantages, and limitations of the tuberculin skin test and interferon-gamma release assays and provide an overview of the most recent systematic reviews conducted for different indications for the use of these tests. We conclude that both tests are accurate to detect latent tuberculosis, although interferon-gamma release assays have higher specificity than tuberculin skin testing in BCG-vaccinated populations, particularly if BCG is received after infancy. However, both tests perform poorly to predict risk for progression to active tuberculosis. Interferon-gamma release assays have significant limitations in serial testing because of spontaneous variability and lack of a validated definition of conversion and reversion, making it difficult for clinicians to interpret changes in category (conversions and reversions). So far, the most important clinical evidence, that is, that isoniazid preventive therapy reduces the risk for progression to disease, has been produced only in tuberculin skin test-positive individuals.

https://downloads.hindawi.com/journals/pm/2013/601737.pdf

Interferon-Gamma Release Assays versus Tuberculin Skin Testing for the Diagnosis of Latent Tuberculosis Infection: An Overview of the Evidence

To analyze factors associated with discordance between tuberculin skin test (TST) and interferon-gamma release assay (IGRA) results among household contacts of pulmonary tuberculosis (PTB) patients. DESIGN: TST (purified protein derivative) and IGRA (QuantiFERON-TB Gold) were performed on household contacts of PTB patients diagnosed between 2006 and 2007 in Salvador, Brazil. Discordant test groups were compared with the TST-/IGRA- group. RESULTS: Of 261 household contacts satisfactorily tested by TST, 145 (55.6%) had positive TST results; of 298 satisfactorily tested by IGRA, 127 (43.1%) had positive results. The test agreement was 0.76 (kappa = 0.53, 95%CI 0.43-0.63). Sixty-one (24%) were discordant: 44 (72%) with TST+/IGRA- and 17 (28%) with TST-/IGRA+ results. Compared to the TST-/IGRA- group, the TST+/IGRA- and TST+/IGRA+ groups were significantly more likely to have a chest X-ray showing old lung scars (OR = 6.8, 95%CI 1.3-35.0; OR = 7.4, 95%CI 2.2-24.4, respectively). The TST-/IGRA+ group was exposed to their index cases for significantly longer than the TST-/IGRA- group (OR = 7.2, 95%CI 1.7-29.3). CONCLUSION: The TST+/IGRA- and TST+/IGRA+ groups shared more similar characteristics with each other than with the TST-/IGRA- group. In a setting endemic for TB, TST results appear to be more suitable in the decision to treat latent TB infection.

/pdf/analysis-of-discordance-between-the-tuberculin-skin-test-and-2w0c7yjbog.pdf

Analysis of discordance between the tuberculin skin test and the interferon-gamma release assay.

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Analysis of discordance between the tuberculin skin test and the interferon-gamma release assay.