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Purpose of Review: The debate on the merits of observational studies as compared with randomized trials is ongoing. We will briefly touch on this subject, and demonstrate the role of cohort studies for the description of infectious disease patterns after transplantation. The potential benefits of cohort studies for the clinical management of patients outside of the expected gain in epidemiological knowledge are reviewed. The newly established Swiss Transplantation Cohort Study and in particular the part focusing on infectious diseases will serve as an illustration., Recent Findings: A neglected area of research is the indirect value of large, multicenter cohort studies. These benefits can range from a deepened collaboration to the development of common definitions and guidelines. Unfortunately, very few data exist on the role of such indirect effects on improving quality of patient management., Summary: This review postulates an important role for cohort studies, which should not be viewed as inferior but complementary to established research tools, in particular randomized trials. Randomized trials remain the least bias-prone method to establish knowledge regarding the significance of diagnostic or therapeutic measures. Cohort studies have the power to reflect a real-world situation and to pinpoint areas of knowledge as well as of uncertainty. Prerequisite is a prospective design requiring a set of inclusive data coupled with the meticulous insistence on data retrieval and quality.

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.

Kaposi's sarcoma-associated herpesvirus (KSHV) specific T cell responses and KSHV viremia were analyzed in seven HIV-infected patients with active Kaposi's sarcoma lesions who initiated highly active antiretroviral therapy, and were compared between patients with improved Kaposi's sarcoma and those with progressive Kaposi's sarcoma requiring further systemic chemotherapy. Patients with controlled Kaposi's sarcoma disease demonstrated undetectable Kaposi's sarcoma viremia together with KSHV-specific CD8 T cells secreting interferon-gamma and tumor necrosis factor-alpha, whereas progressors showed increasing viremia with weak or no T-cell responses. These data point toward a potential role of KSHV-specific immunity in the control of AIDS-associated Kaposi's sarcoma.

The management of acute appendicitis in the febrile neutropenic patient after intensive chemotherapy is controversial. We report our single-center-experience of 5 children diagnosed with appendicitis during febrile neutropenia after chemotherapy for acute leukemia or lymphoma. All patients presented with an isolated appendicitis without signs of overt mucositis or more diffuse enterocolitis. The clinical diagnosis was confirmed by ultrasonography. Perforation with retrocecal abscess was present in 1 patient. Administration of combination antimicrobial regimens including meropenem resulted in complete resolution in all patients. Our observations indicate that acute appendicitis in clinically stable neutropenic cancer patients can be managed conservatively without surgery.

Purpose: Chronic recurrent parotitis (CRP) is a rare inflammatory disease characterized by multiple episodes of unilateral or bilateral parotid inflammation over a period of years. The objective of this study was to evaluate the parotid glands using MRI during acute inflammation as well as during symptom-free intervals., Method: Twelve children with a history of CRP were included. Four patients were examined during the acute phase and eight children during symptom-free intervals. MR findings were correlated with the clinical status., Results: Two different patterns were identified by MRI: acute inflammation versus chronic inflammation. Contrast enhancement of the parotid gland indicated acute inflammation. Cysts due to chronic inflammation were encountered in children who suffered multiple episodes of inflammation., Conclusion: Our findings suggest that CRP is characterized by recurrent, acute exacerbations of inflammation, resulting in a slowly progressive destruction of the parotid gland.

Two children with atypical neuroborreliosis (cranial polyneuritis and acute transverse myelitis) are presented. The diagnosis was confirmed by the determination of specific antibodies against Borrelia burgdorferi in both serum and CSF. Neuroimaging findings were nonspecific, indicating, however, that neuroborreliosis should be included in the differential diagnosis of cases with cranial polyneuritis and acute transverse myelitis in childhood.

Objective: To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission., Design: Prospective study., Setting: Obstetric and paediatric clinics in Switzerland., Participants: Children of mothers with HIV infection identified before or at delivery., Interventions: Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994., Main Outcome Measure: HIV infection status of children., Results: In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention., Conclusions: Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.

Our objective was to determine the diagnostic value of CSF examinations in the diagnosis of neuroborreliosis in children with peripheral facial palsy (PFP). Paired serum and CSF samples from 21 children with PFP were investigated for antibody responses to Borrelia burgdorferi antigens using three different ELISA systems and one Western blot assay. Twenty of the children (95%) had detectable immunoglobin (Ig) M or IgG in the acute-phase serum, but discrepancies between serologic assays were noted in 33% for IgM and 22 to 50% for IgG. Intrathecal specific-antibody production was detected in five of the 20 seropositive children (25%). These five patients showed seroconversion in convalescent sera in at least one assay. Similar seroconversion suggesting recent infection with B. burgdorferi was observed in eight of the 10 children (80%) without intrathecal specific-antibody production, from whom convalescent serum samples could be obtained. All patients with intrathecal antibodies or seroconversion had shown lymphocytic pleocytosis in the acute phase of PFP. In the acute phase of PFP the detection of intrathecal production of antibodies to B. burgdorferi allows prompt diagnosis of neuroborreliosis. For patients with lymphocytic pleocytosis but no detectable intrathecal antibodies, analysis of convalescent serum may help to establish this diagnosis.

Petrous bone fractures (PBF) in children are relatively frequent. They are mostly diagnosed after collisions and falls. The complications typically associated with PBF were different types of hearing disorders in 69.1% of the patients who had audiometry, liquorrhea in 16.5%, palsy of cranial nerves in 10.8% (facial nerve palsy in 9.4%), bacterial meningitis, stenosis of the external ear canal, and posttraumatic cholesteatoma in 0.7% of the fractures each. Most complications were transient; 8.6% of the patients underwent surgery because of PBF-related complications and 9.4% suffered from severe, irreversible sequelae. Management of PBF in children requires an interdisciplinary approach between pediatric surgeons and pediatric ear, nose, and throat (ENT) specialists. It basically includes daily examination for cranial nerve palsy, liquorrhea, and meningitis during hospitalization as well as routine audiometric examination and antibiotic prophylaxis. Routine vaccination against Streptococcus pneumoniae as a new standard procedure and subtotal petrosectomy after transverse fracture as a new surgical modality are strongly recommended in order to lower the incidence of posttraumatic meningitis. Severe complications such as persistent hearing loss, persistent liquorrhea, cranial nerve palsy, and posttraumatic meningitis require aggressive diagnostic and therapeutic measures in order to minimize further morbidity and irreversible deficits.

Children born to HIV-infected women in Switzerland were tested every 3 months for HIV-reactive serum immunoglobulin (Ig) G, IgM and IgA antibodies by Western blot, viral antigen, virus replicating in T-lymphocyte cultures, and immunologic and clinical parameters. At birth, 27% were isolation-positive, 68% had IgM, 48% IgA and 10% circulating antigen. The proportion of IgM and IgA declined to about 18 and 27%, respectively, during the first 2 years. Detection of circulating antigen was less frequently positive than virus isolation in all age and disease groups. Clinical symptoms were only seen in infants or children who were or had been positive for IgM and/or IgA, but only 39% of children positive for these markers have developed disease so far. Clinical symptoms combined with signs of immunodeficiency were seen only in children who were isolation-positive or had evidence of HIV-reactive IgA or child-produced IgG. Absorption studies showed that Western blot-detected IgM and IgA antibodies were of two types: 42% were directed against various HIV proteins, while the rest represented rheumatoid-factor-like IgM or IgA binding to HIV-specific IgG. HIV-specific IgG antibodies were detected in all samples up to the age of 12 months and were still found in 83% of infants 13-18 months old. We observed weak HIV-specific IgG above the age of 15 months with no other signs of HIV infection, suggesting that the demonstration of antibodies in children beyond this age does not necessarily indicate HIV infection.