Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Rathke's cleft cyst infections and pituitary abscesses: case series and review of the literature.

PURPOSE: Pituitary abscesses (PAs) are a rare clinical entity which may arise from normal pituitary tissue or underlying lesions within the gland. Rathke's cleft cysts (RCCs) are not commonly associated with the development of PA. METHODS: Retrospective chart review of three patients with PAs within RCCs at a single university center and review of the literature. RESULTS: Three cases are reported. The first case presented with fever and headache and a history of prior surgery due to RCC and a recent respiratory tract infection. The second case had a history of recent skin infections and presented with sudden onset headache and hypopituitarism. In the third case, chronic visual field impairment prompted an ophthalmologic evaluation resulting in a diagnosis of an adenoma and an infected RCC. In all three cases, an endoscopic endonasal approach was performed to drain infected tissue and allowed microbiological identification of gram-positive cocci, followed by treatment with antibiotics for at least three weeks. Cases in the literature are scarce and the diagnosis is usually made intraoperatively due to non-specific manifestations and imaging. PAs arising from underlying pituitary lesions are less common than primary PAs. Differential diagnosis should include pituitary apoplexy, hypophysitis and other cystic lesions. CONCLUSION: PAs occurring in RCCs are infrequent. Clinical manifestations are commonly subacute, without septic symptoms. Imaging is usually non-specific. Preoperative diagnosis is infrequent and a broad differential diagnosis should be considered. Empirical antimicrobial therapy should be initiated and adjusted after obtaining cultures to reduce the rate of recurrence and improve clinical outcomes.

Diagnostic accuracy of the Xpert® MTB/RIF cycle threshold level to predict smear positivity: a meta-analysis.

SETTING: Xpert® MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, CT) correlates with the bacillary burden.OBJECTIVE To investigate the association between Xpert CT values and smear status through a systematic review and individual-level data meta-analysis. DESIGN: Studies on the association between CT values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated. RESULTS: Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off CT values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%CI 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples. CONCLUSION: Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.

Regional solar radiation is inversely correlated with incidence and severity of tuberculosis in Chile.

Vitamin D (VD) deficiency has been linked to increased incidence and morbidity of tuberculosis (TB). Chile has large variations in solar radiation (SR; a proxy of VD status) and high prevalence of VD deficiency in its southernmost regions with low SR. We investigated the correlation between regional SR and rates of TB incidence, admissions and deaths in Chile by reviewing national records on prospectively collected mandatory disease notifications, admissions and mortality between 2001 and 2011. Over the study period, 26 691 new TB notifications were registered. The TB incidence rate was 14·77 (95% confidence intervals (CIs) 14·60-14·95), admission rate was 12·12 (95% CI 11·96-12·28) and mortality rate was 1·61 (95% CI 1·55-1·67) per 100 000 population per year. Multivariable linear regressions adjusting for significant demographic TB risk factors in Chile (regional prevalence of HIV infection, rates of migration from TB-endemic countries and rates of imprisonment) revealed an independent and highly statistically significant inverse association between SR and TB incidence rate (ß -1·05, 95% CI -1·73 to -0·36, P = 0·007), admission rate (ß -1·58, 95% CI -2·23 to -0·93, P < 0·001), and mortality rate (ß -0·15, 95% CI -0·23 to -0·07, P = 0·002). These findings support a potential pathogenic role of VD deficiency in TB incidence and severity.

Thrombotic microangiopathy as first manifestation of acute human immunodeficiency virus infection: a case report and review of the literature.

BACKGROUND: We present the case of a patient with acute human immunodeficiency virus infection and a thrombotic microangiopathy as the first clinical manifestation, a presentation that has not, to the best of our knowledge, been previously reported. CASE PRESENTATION: A 35-year-old Bolivian man presented with epistaxis and thrombocytopenia. We found microangiopathic anemia, lymphopenia, elevated lactate dehydrogenase, progressive acute renal failure, negative direct antiglobulin test, and normal activity of ADAMTS13. An human immunodeficiency virus ELISA test was negative, with an human immunodeficiency virus viral load of 10,000,000 RNA copies/mL. Antiretroviral therapy and three sessions of therapeutic plasma exchange were able to control thrombotic microangiopathy. CONCLUSIONS: Hematologic manifestations of human immunodeficiency virus infection are frequent. However, the debut of acute human immunodeficiency virus infection with thrombotic microangiopathy is a rare event. A high index of suspicion and early treatment is required.

M. tuberculosis DNA detection in nasopharyngeal mucosa can precede tuberculosis development in contacts.

BACKGROUND: The nasopharynx is a known gateway for some mycobacterial species such as Mycobacterium bovis and M. leprae. M. tuberculosis can cross lymphoepithelial barriers in vitro, but its ability to colonise the nasopharyngeal mucosa in vivo has not been established. OBJECTIVE: To determine if M. tuberculosis can be transiently detected in nasopharyngeal mucosa of tuberculosis (TB) contacts as a preliminary step in the development of tuberculous infection. DESIGN: Exploratory study conducted among asymptomatic household contacts of pulmonary TB cases. A chest X-ray, QuantiFERON(®) TB-Gold or tuberculin skin test and a bilateral nasopharyngeal swab for Xpert(®) MTB/RIF and mycobacterial culture were performed at baseline and repeated 8-12 weeks later. RESULTS: Eighty-nine contacts were enrolled a median of 9 days after the diagnosis of the index case. At baseline, 29.9% were positive for latent tuberculous infection and one subject (1.1%) had a positive Xpert in the nasopharyngeal swab with a normal chest X-ray, negative QuantiFERON and negative induced sputum. After 12 weeks' follow-up, this subject developed a new cough and upper lobe infiltrates and M. tuberculosis grew in sputum. No other cases of active TB were detected at follow-up. CONCLUSION: The detection of M. tuberculosis DNA in the nasopharyngeal mucosa of contacts is an infrequent event that in this instance preceded the development of pulmonary TB. Its pathogenic role requires further investigation.

Rapid molecular detection of pulmonary tuberculosis in HIV-infected patients in Santiago, Chile.

SETTING: Santiago, Chile, has a mean annual tuberculosis (TB) rate of 13 per 100 000 population; however, TB incidence in human immunodeficiency virus (HIV) infected individuals is at least 20 times higher. OBJECTIVE: To assess the accuracy of rapid molecular testing for pulmonary TB (PTB) detection in routine care in HIV-infected patients. DESIGN: Cross-sectional study, conducted prospectively in five hospitals between March 2010 and June 2011. HIV-positive subjects with suspected PTB provided sputum or mouth wash samples that were directly processed for acid-fast smear, mycobacterial cultures and Xpert® MTB/RIF. Positive test results were reported on the same day. RESULTS: We enrolled 166 subjects into the study; 50.6% provided two sputum samples, 33.1% only one sputum sample and 16.3% a mouth wash sample. The prevalence of TB was 8.1% (13/160). Diagnostic sensitivity increased from 66.7% (95%CI 39.1-86.2) for acid-fast smear to 91.7% (95%CI 64.6-98.5) for Xpert MTB/RIF, with comparable specificity at 98.6% (146/148, 95%CI 95.2-99.6) and 99.3% (147/148, 95%CI 96.3-99.9). Xpert MTB/RIF allowed early detection of rifampicin resistance in 16.6% of cases, with rapid adjustment to multidrug-resistant treatment. CONCLUSION: Xpert MTB/RIF provided earlier TB diagnosis in 25% more cases than acid-fast smear alone. Its implementation should be considered for TB diagnosis in HIV-positive patients even outside TB-endemic areas.