Central nervous system manifestations of LRBA deficiency: case report of two siblings and literature review.

BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disease (PID) characterized by a regulatory T cell defect resulting in immune dysregulation and autoimmunity. We present two siblings born to consanguineous parents of North African descent with LRBA deficiency and central nervous system (CNS) manifestations. As no concise overview of these manifestations is available in literature, we compared our patient's presentation with a reviewed synthesis of the available literature. CASE PRESENTATIONS: The younger brother presented with enteropathy at age 1.5 years, and subsequently developed Evans syndrome and diabetes mellitus. These autoimmune manifestations led to the genetic diagnosis of LRBA deficiency through whole exome sequencing with PID gene panel. At 11 years old, he had two tonic-clonic seizures. Brain MRI showed multiple FLAIR-hyperintense lesions and a T2-hyperintense lesion of the cervical medulla.  His sister presented with immune cytopenia at age 9 years, and developed diffuse lymphadenopathy and interstitial lung disease. Genetic testing confirmed the same mutation as her brother. At age 13 years, a brain MRI showed multiple T2-FLAIR-hyperintense lesions. She received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) 3 months later. Follow-up MRI showed regression of these lesions. CONCLUSIONS: Neurological disease is documented in up to 25% of patients with LRBA deficiency. Manifestations range from cerebral granulomas to acute disseminating encephalomyelitis, but detailed descriptions of neurological and imaging phenotypes are lacking. LRBA deficiency amongst other PIDs should be part of the differential diagnosis in patients with inflammatory brain lesions. We strongly advocate for a more detailed description of CNS manifestations in patients with LRBA deficiency, when possible with MR imaging. This will aid clinical decision concerning both anti-infectious and anti-inflammatory therapy and in considering the indication for allo-HSCT.

Impact of HIV on clinical presentation and outcomes of tuberculosis treatment at primary care level.

Little is known on how human immunodeficiency virus (HIV) infection impacts pediatric tuberculosis (TB) in primary care. We compared TB type, HIV care and case fatality rates between 5685 adults and 830 children with TB treated at primary care clinics in Kinshasa, Democratic Republic of Congo. Children represented a substantial burden (13%) of TB, and presented predominantly with difficult to diagnose smear-negative TB and extra-pulmonary TB. The HIV co-infection rate was lower in children than in adults, and fewer children than adults received antiretroviral therapy during anti-tuberculosis treatment. Case fatality was four times higher in HIV-infected than non-infected children. Child-friendly point-of-care TB diagnostics and decentralized pediatric TB-HIV care should receive greater attention.

Outcomes of integrated treatment for tuberculosis and HIV in children at the primary health care level.

BACKGROUND: Little is known about the integration of tuberculosis (TB) and human immunodeficiency virus (HIV) treatment in pediatric populations. METHODS: Prospective cohort of 31 HIV-infected children aged 3-18 years initiating anti-tuberculosis treatment at five primary health care (PHC) clinics in Kinshasa, Democratic Republic of Congo, to describe survival, clinical and immunological outcomes of nurse-centered integrated TB-HIV treatment. RESULTS: Almost all of the children (87.1%) were diagnosed with HIV during TB diagnosis. Most (87.0%) were successfully treated for TB. Two (6.5%) died during anti-tuberculosis treatment; both presented with low CD4 counts (36 and 59 cells/mm(3) compared to a median of 228 cells/mm(3) in the entire cohort). Most (74.2%) initiated antiretroviral therapy (ART) during anti-tuberculosis treatment. Overall, a median CD4 count increase of 106 cells/mm(3) was observed (P = 0.014), an increase of 113 cells/mm(3) among children on ART and of 71.5 cells/mm(3) in those not on ART (P = 0.78). Median body mass index increase during anti-tuberculosis treatment was 2.1 kg/m(2) overall (P = 0.002), 2.2 kg/m(2) among children on ART and 0.72 kg/m(2) in those not on ART (P = 0.08). CONCLUSION: Integrated, nurse-centered, pediatric TB-HIV treatment at the PHC level in highly resource-limited settings is feasible and effective in achieving successful outcomes, including high ART uptake, low mortality, and immunological and clinical improvement.

The Cough Cylinder: a tool to study measures against airborne spread of (myco-) bacteria.

BACKGROUND: 'Covering your cough' reduces droplet number, but its effect on airborne pathogen transmission is less clear. The World Health Organization specifically recommends cough etiquette to prevent the spread of Mycobacterium tuberculosis, but implementation is generally poor and evidence supporting its value is lacking. METHODS: We constructed a model to assess 'real life' transmission risk by counting viable pathogens from aerosols produced by coughing patients, thus allowing the assessment of outward protection measures in a standardised fashion. During the validation process, we focused on rod-shaped bacteria as surrogates for M. tuberculosis. RESULTS: The Cough Cylinder enabled us to sample Pseudomonas aeruginosa, Escherichia coli and mycobacteria from aerosols produced by patients with cystic fibrosis, primary ciliary dyskinesia and tuberculosis. Pathogens in droplets and in airborne particles could be sampled. Delayed air sampling allowed specific measurement of persistent airborne particles. CONCLUSION: This novel experimental system allows measurement of aerosol pathogen spread in a highly standardised fashion. It also offers the possibility to assess the impact of different interventions to limit aerosol transmission.

Mortality among tuberculosis patients in the Democratic Republic of Congo.

SETTING: Kinshasa, Democratic Republic of Congo. OBJECTIVE: To identify programmatic interventions for improved survival in patients receiving treatment for tuberculosis (TB) at primary care clinics. DESIGN: Retrospective cohort of adult patients initiating anti-tuberculosis treatment between January 2006 and May 2007. RESULTS: Among 5685 patients, 390 deaths occurred during anti-tuberculosis treatment, of which half (52%) did so during the first 2 months. Patients with smear-negative pulmonary TB were at greater risk of death in the first 2 months of treatment (human immunodeficiency virus [HIV] positive HR 1.49, 95%CI 0.89-2.49; HIV-negative HR 1.77 95%CI 1.06-2.95), but not thereafter. Patients with extra-pulmonary TB were at increased risk of death in the first 2 months of anti-tuberculosis treatment if they were non-HIV-infected (HR 2.42, 95%CI 1.52-3.85), and were half as likely to die during the remainder of treatment (HIV-positive HR 0.46, 95%CI 0.22-0.97; HIV-negative HR 0.47, 95%CI 0.23-0.94). Antiretroviral therapy (ART) reduced the risk of death by an estimated 36% (HR 0.64, 95%CI 0.37-1.11). CONCLUSION: High mortality in the first months of anti-tuberculosis treatment could be reduced by addressing diagnostic delays, particularly for extra-pulmonary and smear-negative TB cases and, in HIV-infected patients, by initiation of ART soon after starting anti-tuberculosis treatment.