Prevalence of Anaplasma phagocytophilum and coinfection with Borrelia burgdorferi sensu lato in the hard tick Ixodes ricinus in the city of Hanover (Germany).

The castor bean tick Ixodes ricinus has been found to be the main vector for Lyme borreliosis spirochetes and Anaplasma phagocytophilum in Central Europe. 1646 I. ricinus ticks from Hanover, a city located in Northern Germany, were examined for infection with A. phagocytophilum and coinfection with Borrelia burgdorferi sensu lato (sl) to obtain so far missing prevalence data for this region. The total A. phagocytophilum infection rate was 3.2% (52/1646 ticks), divided into 4.1% (32/777) adults and 2.3% (20/869) nymphs. Coinfections with B. burgdorferi sl were found in 0.9% of all tick stages. The detected genospecies were B. afzelii, B. garinii, B. burgdorferi sensu stricto (ss), and B. garinii, which was the most frequent species in coinfected ticks.

Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children.

CD31(+)CD45RA(+)RO(-) lymphocytes contain high numbers of T cell receptor circle (TREC)-bearing T cells; however, the correlation between CD31(+)CD4(+) lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31(+) and CD31(-) CD4(+) lymphocytes in healthy individuals from birth to old age. Sorted CD31(+)CD45RA(+)RO(-) naive CD4(+) lymphocytes contained high TREC numbers, whereas CD31(+)CD45RA(-)RO(+) cells (comprising < or =5% of CD4(+) cells during aging) did not contain TREC. CD31(+) overall CD4(+) cells remained TREC rich despite an age-related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31(+)CD45RA(+)RO(-)CD4(+) cells exhibited significantly longer telomeres and higher telomerase activity than CD31(-)CD45RA(+)RO(-)CD4(+) cells, suggesting that CD31(+)CD45RA(+)RO(-)CD4(+) cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4(+) as well as naive CD45RA(+)RO(-)CD4(+) cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5-12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC-rich lymphocytes essentially in lymphopenic children after HSCT.

Transient hemophagocytosis with deficient cellular cytotoxicity, monoclonal immunoglobulin M gammopathy, increased T-cell numbers, and hypomorphic NEMO mutation.

X-linked osteopetrosis, anhydrotic ectodermal dysplasia, and immunodeficiency (XL-O-EDA-ID) is a disorder that is caused by hypomorphic mutations in the nuclear factor kappaB essential modulator (NEMO). These mutations lead to an impaired NF-kappaB activation. In vitro analyses and studies in animal models show that inhibition of NF-kappaB leads to a decrease of cytokine production and T-cell proliferation. Patients classically display poor or delayed inflammatory response to infections. We describe a boy with XL-O-EDA-ID, 1167-1168insC NEMO mutation, and recurrent infections. In early infancy, he experienced hemophagocytosis with transient deficiency of natural killer activity. Increased immunoglobulin M levels in blood resulted from a monoclonal immunoglobulin M gammopathy. Blood T-cell numbers were constantly increased, most probably resulting from a peripheral T-cell expansion. Our observations suggest that patients with hypomorphic NEMO mutations and repeated infections may experience inflammatory dysregulation.

The spectrum of hypoxaemia in children admitted to hospital in The Gambia, West Africa.

OBJECTIVE: Hypoxia predicts mortality in children with acute lower respiratory infections (ALRIs). We investigated the prevalence and predictive value of hypoxia in ALRI and other acute infectious diseases. METHODS: We studied the spectrum of hypoxaemia in 4,047 children admitted to a tertiary hospital in The Gambia. Oxygen saturation was measured shortly after admission. Severe hypoxaemia was defined as an oxygen saturation below 90%. RESULTS: 5.8% of all admissions had severe hypoxaemia. Prevalence of hypoxaemia varied between disease groups: it was 11.7% in ALRI cases, 16.5% in neonates; 2.9% in malaria cases overall but 6.5% in cerebral malaria patients; and 2.7% in children with meningitis. Hypoxaemia predicted a poor outcome; the odds ratio for death among paediatric admissions overall was 7.45 [95% confidence intervals (CI) 5.40-10.29]. Surprisingly, it was lowest for children with ALRI [OR 3.53 (95% CI 1.13-10.59)], and higher for those with malaria 9.90 [95% CI 4.39-22.35]. CONCLUSION: Hypoxaemia is common among Gambian children admitted to hospital and it is often associated with a poor outcome. A similar situation is likely in many other developing countries. Thus, equipment for measuring oxygen saturation, and facilities and equipment for effective oxygen delivery need to be made available in developing countries.

Successful low toxicity hematopoietic stem cell transplantation for high-risk adult chronic granulomatous disease patients.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation for chronic granulomatous disease (CGD) is associated with a significant risk of transplant-related mortality. Adult age, overt infection, and residual inflammatory disease at transplant are major risk factors. METHODS: Here we report the favorable outcome after bone marrow transplantation in three high-risk adult CGD patients (ages 18, 35, and 39) with severe disease-related complications (overt pneumonia, liver abscess, steroid-dependent granulomatous colitis, diabetes, restrictive lung disease, renal insufficiency, epilepsia). Bone marrow donors were human leukocyte antigen-matched related or unrelated. The conditioning regimen consisted of 2 x 4 mg/kg oral busulphan (d -3, -2), fludarabine 6 x 30 mg/qm (d -7 to -2), rabbit anti-T-cell-globulin (Fresenius) 4 x 10 mg/kg (d -4 to -1). Graft versus host disease prophylaxis consisted of cyclosporine A and mycophenolate-mofetil. RESULTS: Mean neutrophil and platelet engraftment was observed at day +18.5 and +22.5, respectively. All infectious and inflammatory lesions resolved and restrictive lung disease improved. No signs of grade II-IV acute or chronic graft versus host disease were observed. With a follow-up of 12 to 27 months, all patients are alive and well with full donor chimerism, normalized superoxide production, and documented T- and B-cell function. CONCLUSION: This modified reduced intensity conditioning protocol is a promising treatment modality for high-risk adult CGD patients.