Performance of nested RT-PCR on CSF for tuberculous meningitis diagnosis in HIV-infected patients.

SETTING: Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. OBJECTIVE: To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. DESIGN: Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. RESULTS: Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. CONCLUSIONS: The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.

Endemic Cryptosporidium infection and drinking water source: a systematic review and meta-analyses.

Cryptosporidium is a well-known cause of diarrhoea in humans. Little is known about risk factors associated with endemic cryptosporidiosis, which constitutes the majority of cases. We carried out meta-analyses to verify if drinking water is also associated with endemic infection and to assess the magnitude of the associations. The global meta-analysis suggests that there is an increased risk of Cryptosporidium infection among unsafe water users (OR 1.40 [1.15, 1.72]). Studies were stratified, according to the exposure to different sources of safe drinking water, due to the heterogeneity presented. The consumption of non-well and unboiled water was associated with an increased chance of endemic cryptosporidiosis, though only the latter was significant (OR 1.45 [0.95, 2.20]; OR 1.61 [1.09, 2.38]). Drinking non-bottled water did not present a risk factor associated with endemic cryptosporidiosis (OR 0.87 [0.72, 1.05]). These meta-analyses present results that could be useful to clarify the epidemiology of Cryptosporidium. We recommend that other risk factors could also be studied by this approach.