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Background: There are few data on tuberculosis (TB) incidence in HIV-infected children on antiretroviral therapy (ART). Observational studies suggest co-trimoxazole prophylaxis may prevent TB, but there are no randomized data supporting this. The ARROW trial, which enrolled HIV-infected children initiating ART in Uganda and Zimbabwe and included randomized cessation of co-trimoxazole prophylaxis, provided an opportunity to estimate the incidence of TB over time, to explore potential risk factors for TB, and to evaluate the effect of stopping co-trimoxazole prophylaxis.Methods: Of 1,206 children enrolled in ARROW, there were 969 children with no previous TB history. After 96 weeks on ART, children older than 3 years were randomized to stop or continue co-trimoxazole prophylaxis; 622 were eligible and included in the co-trimoxazole analysis. Endpoints, including TB, were adjudicated blind to randomization by an independent endpoint review committee (ERC). Crude incidence rates of TB were estimated and potential risk factors, including age, sex, center, CD4, weight, height, and initial ART strategy, were explored in multivariable Cox proportional hazards models.Results: After a median of 4 years follow-up (3,632 child-years), 69 children had an ERC-confirmed TB diagnosis. The overall TB incidence was 1.9/100 child-years (95% CI, 1.5-2.4), and was highest in the first 12 weeks following ART initiation (8.8/100 child-years (5.2-13.4) versus 1.2/100 child-years (0.8-1.6) after 52 weeks). A higher TB risk was independently associated with younger age (<3 years), female sex, lower pre-ART weight-for-age Z-score, and current CD4 percent; fewer TB diagnoses were observed in children on maintenance triple nucleoside reverse transcriptase inhibitor (NRTI) ART compared to standard non-NRTI + 2NRTI. Over the median 2 years of follow-up, there were 20 ERC-adjudicated TB cases among 622 children in the co-trimoxazole analysis: 5 in the continue arm and 15 in the stop arm (hazard ratio (stop: continue) = 3.0 (95% CI, 1.1-8.3), P = 0.028). TB risk was also independently associated with lower current CD4 percent (P <0.001).Conclusions: TB incidence varies over time following ART initiation, and is particularly high during the first 3 months post-ART, reinforcing the importance of TB screening prior to starting ART and use of isoniazid preventive therapy once active TB is excluded. HIV-infected children continuing co-trimoxazole prophylaxis after 96 weeks of ART were diagnosed with TB less frequently, highlighting a potentially important role of co-trimoxazole in preventing TB. [ABSTRACT FROM AUTHOR]

Background: Rotavirus is the most common cause of severe gastroenteritis in children under the age of 5 years worldwide. It is well recognised that rotavirus can cause signs and symptoms beyond the gastrointestinal tract, including neurological manifestations such as encephalopathy. Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome that has been associated with rotavirus. We report a case of a 4-year-old boy with clinically mild encephalopathy, who had an isolated splenial lesion in the corpus callosum on neuroimaging, and rotavirus RNA detected in faeces. We use this case as an opportunity to review the literature on rotavirus-associated MERS.Case Presentation: A previously healthy 4-year-old boy presented with a 2-day history of vomiting, diarrhoea, and fever, complicated by reduced level of consciousness. Magnetic resonance imaging of the brain showed a marked hyperintensity in the splenium of the corpus callosum on T2 and diffusion-weighted images. Rotavirus genome was detected by polymerase chain reaction in a stool specimen, but not in the cerebrospinal fluid. The genotype was identified as G1P8. His clinical condition improved with gradual resolution of his symptoms. No neurological complications were evident upon discharge and the patient had no recurring symptoms or significant residual defects when followed up 2 months later.Conclusion: MERS is a novel clinic-radiological syndrome first described in Japan. A transient splenial lesion with reduced diffusion that appears as a high signal intensity in diffusion-weighted MRI is the main diagnostic feature. Rotavirus is one of the most common agents associated with MERS, although to our knowledge only one previous case has been reported from Europe. The majority of patients appear to achieve full recovery following rotavirus-associated MERS, irrespective of treatment. This case, together with other published reports, supports the hypothesis that rotavirus-associated MERS is unlikely to be the result of direct viral invasion of the CNS. It has been suggested that MERS may be caused by intra-myelinic axonal oedema or local inflammatory cell infiltration; however, the pathogenesis remains incompletely understood. [ABSTRACT FROM AUTHOR]