Search

BackgroundThe extent of inappropriate prescribing observed in geriatric medicine has not been thoroughly evaluated in people ageing with HIV. We determined the prevalence of and risk factors for inappropriate prescribing in individuals aged ≥75 years enrolled in the Swiss HIV Cohort Study.MethodsRetrospective review of medical records was performed to gain more insights into non-HIV comorbidities. Inappropriate prescribing was screened using the Beers criteria, the STOPP/START criteria and the Liverpool drug–drug interactions (DDIs) database.ResultsFor 175 included individuals, the median age was 78 years (IQR 76–81) and 71% were male. The median number of non-HIV comorbidities was 7 (IQR 5–10). The prevalence of polypharmacy and inappropriate prescribing was 66% and 67%, respectively. Overall, 40% of prescribing issues could have deleterious consequences. Prescribing issues occurred mainly with non-HIV drugs and included: incorrect dosage (26%); lack of indication (21%); prescription omission (drug not prescribed although indicated) (17%); drug not appropriate in elderly individuals (18%) and deleterious DDIs (17%). In the multivariable logistic regression, risk factors for prescribing issues were polypharmacy (OR: 2.5; 95% CI: 1.3–4.7), renal impairment (OR: 2.7; 95% CI: 1.4–5.1), treatment with CNS-active drugs (OR: 2.1; 95% CI: 1.1–3.8) and female sex (OR: 8.3; 95% CI: 2.4–28.1).ConclusionsPolypharmacy and inappropriate prescribing are highly prevalent in elderly people living with HIV. Women are at higher risk than men, partly explained by sex differences in the occurrence of non-HIV comorbidities and medical care. Medication reconciliation and periodic review of prescriptions by experienced physicians could help reduce polypharmacy and inappropriate prescribing in this vulnerable, growing population.

BACKGROUND Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain. OBJECTIVE To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF. DESIGN Cohort study. SETTING 5 university hospitals, affiliated hospitals, and private physicians in Switzerland. PARTICIPANTS 4375 adults living with HIV who received TDF-containing ART for 6 months or longer. MEASUREMENTS Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions Z tests. RESULTS 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months. LIMITATION Short follow-up, small subgroup analyses, and potential residual confounding. CONCLUSION Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels. PRIMARY FUNDING SOURCE Swiss National Science Foundation.

Background: Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with human immunodeficiency virus (HIV) (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRSs) and by considering genetic variants associated with successful aging and longevity., Methods: In the Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (ORs) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRSs. PRSs were built from CAD-associated single-nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both., Results: We included 269 patients with CAD events between 2000 and 2017 (median age, 54 years; 87% male; 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (ie, traditional and HIV-related) risk factors and PRSs, built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (P < .001). Participants with the most unfavorable clinical risk factor profile (top quintile) had an adjusted CAD-OR of 17.82 (95% confidence interval [CI], 8.19-38.76), compared with participants in the bottom quintile. Participants with the most unfavorable CAD-PRSs (top quintile) had an adjusted CAD-OR of 3.17 (95% CI, 1.74-5.79), compared with the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had an adjusted CAD-OR of 3.67 (95% CI, 2.00-6.73), compared with the bottom quintile., Conclusions: In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related, and genetic risk factors provided the most powerful CAD prediction.

OBJECTIVES The aim of the study was to assess the feasibility of a national pre-exposure prophylaxis (PrEP) programme using smartphone-compatible data collection. METHODS This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone-compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV-negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow-up (number with first follow-up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. RESULTS Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52-137]. Retention at first follow-up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33-47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. CONCLUSIONS In a national PrEP programme using smartphone-compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at high risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.

Background In people with human immunodeficiency virus (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction (ie, estimated glomerular filtration rate [eGFR] decrease of >5mL/min/1.73m2 per year for ≥3 consecutive years). Methods We obtained univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical D:A:D chronic kidney disease (CKD) risk score, antiretroviral exposures, and a polygenic risk score based on 14 769 genome-wide single nucleotide polymorphisms in white Swiss HIV Cohort Study participants. Results We included 225 participants with rapid progression and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with low D:A:D risk, participants with high risk had rapid progression (HR = 1.82 [95% CI, 1.28–2.60]). Compared to the first (favorable) polygenic risk score quartile, participants in the second, third, and fourth (unfavorable) quartiles had rapid progression (HR = 1.39 [95% CI, 0.94–2.06], 1.52 [95% CI, 1.04–2.24], and 2.04 [95% CI, 1.41–2.94], respectively). Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR = 1.36 [95% CI, 1.06–1.76]). Discussion An individual polygenic risk score is associated with rapid progression in Swiss PWH, when analyzed in the context of clinical and antiretroviral risk factors.

Nocardiosis is primarily an opportunistic infection affecting immunosuppressed individuals, in whom it most commonly presents as pulmonary infection and sometimes cerebral abscesses. Isolated abdominal or retroperitoneal nocardiosis is rare. Here, we report the second case, to our knowledge, of isolated abdominal nocardiosis due to Nocardia paucivorans and provide a comprehensive review of intra-abdominal nocardiosis. The acquisition of abdominal nocardiosis is believed to occur via hematogenous spreading after pulmonary or percutaneous inoculation or possibly via direct abdominal inoculation. Cases of Nocardia peritonitis have been reported in patients on peritoneal dialysis. Accurate diagnosis of abdominal nocardiosis requires histological and/or microbiological examination of appropriate, radiologically or surgically obtained biopsy specimens. Malignancy may initially be suspected when the patient presents with an abdominal mass. Successful therapy usually includes either percutaneous or surgical abscess drainage plus prolonged combination antimicrobial therapy.

Recurrent Campylobacter enteritis is a well-recorded complication of primary hypogammaglobulinemia but has only rarely been reported with other types of immunodeficiency, and no cases have been reported after rituximab-associated secondary hypogammaglobulinemia. We therefore reviewed our local microbiology laboratory databases and conducted a literature search, to provide a detailed characterization of the immunodeficiency states associated with recurrent Campylobacter enteritis. Published cases had primary hypogammaglobulinemia, most frequently in the setting of common variable immunodeficiency, x-linked agammaglobulinemia, and Good syndrome. No cases were identified in the literature after rituximab or secondary hypogammaglobulinemia. We report a 73-year-old patient with recurrent Campylobacter enteritis and hypogammaglobulinemia in the setting of non-Hodgkin lymphoma, chemotherapy, and maintenance rituximab. Physicians should be aware of the association of recurrent Campylobacter enteritis and immunodeficiency, most commonly in primary hypogammaglobulinemia. Rituximab alone may not be sufficiently immunosuppressive for recurrent campylobacteriosis to occur; additional factors, including hematological malignancy and its treatment, appear necessary. Patients with recurrent Campylobacter enteritis and those starting rituximab should be investigated for hypogammaglobulinemia and B-lymphopenia.

Background: Kaposi's sarcoma, the most common AIDS-related cancer, represents a major public concern in resource-limited countries. Single nucleotide polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the expression, function of IFNL4, and influence the clinical course of an increasing number of viral infections., Objectives: To analyze whether IFNL3/4 variants are associated with susceptibility to AIDS-related Kaposi's sarcoma among MSM enrolled in the Swiss HIV Cohort Study (SHCS)., Methods: The risk of developing Kaposi's sarcoma according to the carriage of IFNL3/4 SNPs rs8099917 and rs12980275 and their haplotypic combinations was assessed by using cumulative incidence curves and Cox regression models, accounting for relevant covariables., Results: Kaposi's sarcoma was diagnosed in 221 of 2558 MSM Caucasian SHCS participants. Both rs12980275 and rs8099917 were associated with an increased risk of Kaposi's sarcoma (cumulative incidence 15 versus 10%, P=0.01 and 16 versus 10%, P=0.009, respectively). Diplotypes predicted to produce the active P70 form (cumulative incidence 16 versus 10%, P=0.01) but not the less active S70 (cumulative incidence 11 versus 10%, P=0.7) form of IFNL4 were associated with an increased risk of Kaposi's sarcoma, compared with those predicted not to produce IFNL4. The associations remained significant in a multivariate Cox regression model after adjustment for age at infection, combination anti retrovi ral therapy, median CD4(+) T-cel I count nadir and CD4(+) slopes (hazard ratio 1.42, 95% confidence interval 1.06-1.89, P=0.02 for IFLN P70 versus no IFNL4)., Conclusion: This study reports for the first time an association between IFNL3/4 polymorphisms and susceptibility to AIDS-related Kaposi's sarcoma. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

BackgroundIn human immunodeficiency virus (HIV), the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown.MethodsWe applied a case-control design and performed genome-wide genotyping in white Swiss HIV Cohort participants with normal baseline estimated glomerular filtration rate (eGFR >90 mL/minute/1.73 m2). Univariable and multivariable CKD odds ratios (ORs) were calculated based on the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) score, which summarizes clinical CKD risk factors, and a polygenic risk score that summarizes genetic information from 86 613 single-nucleotide polymorphisms.ResultsWe included 743 cases with confirmed eGFR drop to ConclusionsGenetic score increased CKD risk similar to clinical D:A:D score and potentially nephrotoxic antiretrovirals. Irrespective of D:A:D score, individuals with the most favorable genetic background may be protected against CKD.

BackgroundSelf-reported neurocognitive impairment (SRNI) in people living with human immunodeficiency virus type 1 (HIV-1) infection is frequent. We use longitudinal information on SRNI in the Swiss HIV Cohort Study (SHCS) to identify and characterize groups of patients with persisting SRNI over time.MethodsWe included all SHCS patients who were assessed for SRNI during at least 5 visits spanning at least 2.5 years in 2013–2017. We first compared patients with SRNI to those without SRNI over the whole study period. Second, we used a hierarchical cluster algorithm to identify groups of patients with similar changes of SRNI over time. In both analyses, we studied clinical and demographic factors potentially influencing SRNI.ResultsIn total, 79 683 questionnaires of 11 029 patients contained information about SRNI, and 8545 of 11 029 (77.5%) patients had longitudinal information. The overall percentage of patients with SRNI decreased from 19.6% in 2013 to 10.7% in 2017. Compared to patients in the cluster with low-level SRNI over time, patients in the cluster with high-level persisting SRNI more often had a prior opportunistic infection of the central nervous system (CNS) (odds ratio [OR], 3.7; P < .001), imperfect adherence to antiretroviral therapy (ART) (OR, 2.8; P < .001), and depression (OR, 1.9; P < .001).ConclusionsAlthough overall SRNI is decreasing in the SHCS, there is a group of patients with persisting SRNI over time. Past opportunistic infections of the CNS, imperfect adherence to ART, and depression were associated most with persisting SRNI. Patients with these characteristics should be preferentially tested for neurocognitive impairment.Although overall self-reported neurocognitive impairment (SRNI) is decreasing in the Swiss HIV Cohort Study, there is a group of patients with persisting SRNI over time, characterized by more past opportunistic infections of the central nervous system, imperfect adherence to antiretroviral therapy, and depression.

Infections may constitute a serious complication in patients with chronic lymphocytic leukemia (CLL). New treatment agents including obinutuzumab and ibrutinib have improved the progression-free survival in CLL, and data suggest a similar overall infection risk and a limited risk of opportunistic infections when compared to standard chemo-immunotherapy. Nevertheless, cases of opportunistic infections including non-tuberculous mycobacterial (NTM) in CLL patients have recently been published. We present a case of a 74-year old man with extensive prior CLL treatment history, including most recently obinutuzumab. He developed an abscess of the psoas muscle and inguinal lymphadenopathy. An inguinal node biopsy specimen showed infection with Mycobacterium avium, confirmed by broad-spectrum mycobacterial PCR, M. avium-specific PCR, and mycobacterial culture. This case and our literature review suggest that physicians should be aware of opportunistic infections in patients with CLL. Diagnostic differentiation from CLL disease progression, Richter’s transformation to aggressive lymphoma, and secondary malignancy relies on histological and appropriate microbiological studies from biopsy material of affected organs. Infection prophylaxis in CLL should be considered, including vaccinations and intravenous immune globulin replacement.

Abstract. We describe the case of a 23-year old woman with a newly diagnosed thrombosis of the inferior vena cava associated with a Brucella melitensis infection. We suggest possible mechanisms leading to brucellosis-associated venous thrombosis and review 14 previously reported cases.

By learning from CAM physicians, we could improve the quality of our vaccination counselling, and health authorities should be able to avoid unnecessary vaccination mandates in Switzerland.

Ever since the introduction of highly active antiretroviral therapy (ART) in 1995, HIV infection has been linked to “metabolic” complications (insulin resistance, dyslipidemia, osteoporosis, and others). Studies suggested increased rates of myocardial infarction, renal insufficiency, neurocognitive dysfunction, and fractures in HIV-postitive patients. Even long-term suppression of HIV seemed to be accompanied by an excess of deleterious inflammation that could promote these complications. The aims of this viewpoint paper are to summarize recent data and to examine the possibility that the problem of aging-related morbidity in HIV might not be as dramatic as previously believed.

The Swiss National Guidelines 2013 for chronic obstructive pulmonary disease have been revised in order to acknowledge recent progress in diagnosis and management of this disease. The resulting new Swiss recommendations are based on best evidence from the literature, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 report and other published national guidelines. Misdiagnosis of chronic obstructive pulmonary disease is common and means that patients do not always receive optimal treatment. To improve the management of patients with chronic obstructive pulmonary disease in Switzerland, these recommendations encourage a more comprehensive assessment of patients, based on the combined assessment of symptoms, degree of airflow limitation, risk of exacerbation and the presence of comorbidities. Recommendations for evidence-based preventive measures, as well as pharmacological and non-pharmacological strategies for the management of both stable and acute exacerbations of chronic obstructive pulmonary disease are provided in this update.

BackgroundIncidental findings on coronary computed tomography angiography (CCTA) have a great impact on the benefits and costs of testing for cardiovascular disease. The number of incidental findings might be increased in human immunodeficiency virus (HIV)-positive individuals compared with the general population. Data are limited regarding the association between incidental findings and HIV infection.MethodsWe assessed the prevalence and factors associated with incidental findings among HIV-positive and HIV-negative participants ≥45 years undergoing CCTA. Logistic regression was performed to evaluate the factors associated with incidental findings in the HIV-positive and HIV-negative groups. For the analysis of the HIV effect, a propensity score-matched dataset of HIV-positive/HIV-negative participants was used.ResultsWe included 553 participants, 341 with and 212 without HIV infection. Incidental findings were observed in 291 of 553 (53%) patients. In 42 of 553 (7.6%) participants, an incidental finding resulted in additional workup. A malignancy was diagnosed in 2 persons. In the HIV-positive group, age (1.31 per 5 years, 1.10–1.56) and smoking (2.29, 1.43–3.70) were associated with incidental findings; in the HIV-negative group, age (1.26, 1.01–1.59) and a CAC score >0 (2.08, 1.09–4.02) were associated with incidental findings. Human immunodeficiency virus seropositivity did not affect the risk of incidental findings.ConclusionsIncidental findings were highly prevalent among HIV-positive and HIV-negative persons. Human immunodeficiency virus infection was not associated with an increased risk of incidental findings.

HIV-positive persons have increased cardiovascular event rates but data on the prevalence of subclinical atherosclerosis compared with HIV-negative persons are not uniform. We assessed subclinical atherosclerosis utilizing coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) in 428 HIV-positive participants of the Swiss HIV Cohort Study and 276 HIV-negative controls concurrently referred for clinically indicated CCTA.We assessed the association of HIV infection, cardiovascular risk profile, and HIV-related factors with subclinical atherosclerosis in univariable and multivariable analyses. HIV-positive participants (median duration of HIV infection, 15 years) were younger than HIV-negative participants (median age 52 vs. 56 years; P 0.01) but had similar median 10-year Framingham risk scores (9.0% vs. 9.7%; P = 0.40). The prevalence of CAC score0 (53% vs. 56.2%; P = 0.42) and median CAC scores (47 vs. 47; P = 0.80) were similar, as was the prevalence of any, non-calcified/mixed, and high-risk plaque. In multivariable adjusted analysis, HIV-positive participants had a lower prevalence of calcified plaque than HIV-negative participants [36.9% vs. 48.6%, P 0.01; adjusted odds ratio (aOR) 0.57; 95% confidence interval (CI) 0.40-0.82; P 0.01], lower coronary segment severity score (aOR 0.72; 95% CI 0.53-0.99; P = 0.04), and lower segment involvement score (aOR 0.71, 95% CI 0.52-0.97; P = 0.03). Advanced immunosuppression was associated with non-calcified/mixed plaque (aOR 1.97; 95% CI 1.09-3.56; P = 0.02).HIV-positive persons in Switzerland had a similar degree of non-calcified/mixed plaque and high-risk plaque, and may have less calcified coronary plaque, and lower coronary atherosclerosis involvement and severity scores than HIV-negative persons with similar Framingham risk scores.

Background. The impact of human genetic background on low-trauma fracture (LTF) risk has not been evaluated in the context of human immunodeficiency virus (HIV) and clinical LTF risk factors. Methods. In the general population, 6 common single-nucleotide polymorphisms (SNPs) associate with LTF through genome-wide association study. Using genome-wide SNP arrays and imputation, we genotyped these SNPs in HIV-positive, white Swiss HIV Cohort Study participants. We included 103 individuals with a first, physician-validated LTF and 206 controls matched on gender, whose duration of observation and whose antiretroviral therapy start dates were similar using incidence density sampling. Analyses of nongenetic LTF risk factors were based on 158 cases and 788 controls. Results. A genetic risk score built from the 6 LTF-associated SNPs did not associate with LTF risk, in both models including and not including parental hip fracture history. The contribution of clinical LTF risk factors was limited in our dataset. Conclusions. Genetic LTF markers with a modest effect size in the general population do not improve fracture prediction in persons with HIV, in whom clinical LTF risk factors are prevalent in both cases and controls.

A 54-year-old woman sustained an open fracture of the right femoral shaft after a bicycle accident in 1985. Several operations were performed, the last including internal fixation using a plate and screws. In 2002, acute diverticulitis was treated with ciprofloxacin/metronidazole. In 2007, she presented with pain and swelling of the right thigh. Plain radiographs showed radiolucent femoral areas (Figure ​(Figure1a1a and b). Treatment was with debridement and removal of orthopedic hardware except for a difficult-to-remove screw fragment. Gentamicin beads were temporarily placed along the femur. Eight intraoperative specimens showed no growth after 10 days. Because of poor wound healing, a computed tomography scan was obtained, showing a sinus tract, femoral cortical defects, and intramedullary air (Figure ​(Figure1c–e).1c–e). Additional debridement was done; cultures of intraoperative biopsy specimens again remained sterile. Amoxicillin/clavulanate was prescribed for 2 weeks, and ciprofloxacin/rifampin was prescribed for 10 weeks.

Four Gram-stain-positive, catalase-negative, coccus-shaped bacterial strains were isolated from multiple blood cultures of patients with endocarditis, meningitis and spondylodiscitis. The isolates were tentatively identified as viridans streptococci on the basis of phenotypic characteristics. Comparative 16S rRNA gene sequencing studies showed that the organisms were members of theStreptococcus mitisgroup but did not correspond to any recognized species. The nearest phylogenetic relative wasS. mitisATCC 49456T, with 98.6 % sequence similarity. The representative strain AZ_3aTshowed less than 96.8, 97.6, 94.5 and 95.5 % similarity to the phylogenetically most closely related species byrecA,rpoB,sodAandgroELgene sequence analysis, respectively. DNA–DNA hybridization analyses showed a low reassociation value of 32.2 % between strain AZ_3aTandS. mitisDSM 12643T. Reassociation values with members of otherS. mitisgroup species ranged from 27.3 to 49.7 %. The G+C content of the DNA was 40.0 mol%. Based on our biochemical and molecular analyses, the isolates represent a novel species, for which the nameStreptococcustigurinussp. nov. is proposed. The type strain is AZ_3aT( = CCOS 600T = DSM 24864T).

We recently described the novel species Streptococcus tigurinus sp. nov. belonging to the Streptococcus mitis group. The type strain AZ_3a T of S. tigurinus was originally isolated from a patient with infective endocarditis. According to its phenotypic and molecular characteristics, S. tigurinus is most closely related to Streptococcus mitis , Streptococcus pneumoniae , Streptococcus pseudopneumoniae , Streptococcus oralis , and Streptococcus infantis . Accurate identification of S. tigurinus is facilitated by 16S rRNA gene analysis. We retrospectively analyzed our 16S rRNA gene molecular database, which contains sequences of all clinical samples obtained in our institute since 2003. We detected 17 16S rRNA gene sequences which were assigned to S. tigurinus , including sequences from the 3 S. tigurinus strains described previously. S. tigurinus originated from normally sterile body sites, such as blood, cerebrospinal fluid, or heart valves, of 14 patients and was initially detected by culture or broad-range 16S rRNA gene PCR, followed by sequencing. The 14 patients had serious invasive infections, i.e., infective endocarditis ( n = 6), spondylodiscitis ( n = 3), bacteremia ( n = 2), meningitis ( n = 1), prosthetic joint infection ( n = 1), and thoracic empyema ( n = 1). To evaluate the presence of Streptococcus tigurinus in the endogenous oral microbial flora, we screened saliva specimens of 31 volunteers. After selective growth, alpha-hemolytic growing colonies were analyzed by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and subsequent molecular methods. S. tigurinus was not identified among 608 strains analyzed. These data indicate that S. tigurinus is not widely distributed in the oral cavity. In conclusion, S. tigurinus is a novel agent of invasive infections, particularly infective endocarditis.

AA-amyloidosis in the setting of chronic visceral leishmaniasis (VL) has been reported in animal models but documentation in humans is unavailable. Here, we report on a Portuguese man who in 1996 was diagnosed with both human immunodeficiency virus (HIV)-infection and VL. Antiretroviral treatment led to sustained suppression of HIV viremia but CD4+ lymphocytes rose from 8 to only 160 cells/mL. Several courses of antimony treatment did not prevent VL relapses. Renal failure developed in 2006 and renal biopsy revealed AA-amyloidosis. The patient had cryoglobulinemia and serum immune complexes containing antibodies directed against seven leishmanial antigens. Antimony plus amphotericin B, followed by oral miltefosine resulted in a sustained VL treatment response with elimination of circulating Leishmania infantum DNA and CD4+ recovery. The concomitant reduction of serum AA levels and disappearance of circulating leishmanial immune complexes suggests that prolonged VL may lead to AA-amyloidosis in immunocompromised humans.

BACKGROUND: Atherosclerosis has been assessed in human immunodeficiency virus (HIV)-infected persons by using various methods. Peripheral arterial disease (PAD) has not been evaluated, however. We studied the cross-sectional prevalence of lower limb PAD in an HIV-infected population. METHODS: PAD was assessed using the Edinburgh Claudication Questionnaire and by measuring the systolic ankle-brachial blood pressure index (ABI) at rest and after exercise. Patients with PAD were further evaluated by duplex scan of lower limb arteries. RESULTS: Ninety-two consecutive HIV-infected patients were evaluated (23.9% women; mean age, 49.5 years; 61.9% current smokers). Claudication was reported by 15.2% of the patients. PAD was found in 20.7% of the patients: 9.8% had an abnormal ABI (25% decrease after exercise. Of the patients with PAD, 84.2% were investigated with duplex scan, all of whom had atherosclerotic occlusions or stenoses of the iliac or femoral arteries. Age, diabetes, smoking, and low CD4+ T lymphocyte counts were identified as independent predictors of PAD. CONCLUSIONS: The prevalence of symptomatic and asymptomatic PAD is high in the HIV-infected population and is much higher than expected (prevalence in the general population, approximately 3% at 60 years). This study suggests the presence of an epidemic of PAD approximately 20 years earlier in the HIV-infected than in the general population. Larger epidemiological studies are needed to better define risk factors and to evaluate whether PAD is associated with increased mortality, as it is in the general population.

In this study, we report the first case of reptile-associated maxillary sinusitis due to Salmonella enterica subspecies diarizonae in a snake handler and the third case of salmonella-associated sinusitis worldwide. The case highlights the potential of respiratory transmission and atypical salmonellosis presentations.

Metabolic complications of antiretroviral therapy (ART) have emerged as a major concern for long-term, successful management of HIV infection. Variability in the response to ART between individuals has been increasingly linked to the genetic background of patients, as regards efficacy and susceptibility to adverse reactions (toxicogenetics). This review summarizes the biological and methodological background for the genetic prediction of metabolic toxicity of ART. Recent studies are discussed which suggest that single-nucleotide polymorphisms (SNPs) in several genes involved in lipid metabolism and lipid transport in the general population (ABCA1, APOA5, APOC3, APOE, CETP) might modulate plasma triglyceride and high-density lipoprotein cholesterol levels in HIV-infected patients. At present, genetic prediction of lipodystrophy is not possible. Lipodystrophy has been linked to an accumulation of mtDNA mutations, a finding causally associated with ageing phenotypes in animal models. No mutations in LMNA, a gene linked to rare, inherited forms of lipodystrophy, have been identified in small studies of patients with lipodystrophy, and a possible link to a TNF promoter SNP remains to be confirmed. With the rapidly decreasing cost of genetic testing, the main issues that need to be addressed prior to introduction of toxicogenetic prediction in HIV clinical practice include reproducibly high predictive values of SNP associations with clinically relevant and well defined metabolic outcomes, studies that evaluate the contribution of SNPs in the context of multi-SNP and haplotype analysis, and the validation of genetic markers in independent, large patient cohorts. Comprehensive, whole genome approaches are increasingly being used.

Since the introduction of effective antiretroviral therapy (ART), HIV-infected individuals are travelling more frequently and international travel has become much safer. Specific concerns include the safety of ART during travel, drug adherence and interaction considerations, and effects of immunosuppression. This review describes potentially important infections, vaccine effectiveness, safety and special approaches for their use, and HIV-related issues regarding predeparture counselling. With advanced immunosuppression (CD4+ T-cell count < 200/microl or < 14%), the immunogenicity of several vaccines is reduced, complications could occur after live attenuated vaccines and certain infections acquired during travel may be more frequent or severe. Challenges include the best options for malaria chemoprophylaxis, standby treatment and medical follow-up of the increasing number of HIV-infected long-term travellers.

Enterococci are a major cause of bacteraemia and endocarditis and are increasingly being implicated in bone and joint infections. Hematogenous enterococcal vertebral osteomyelitis, however, has been only rarely reported. Here we present the first 2 patients from the United States and review the literature on 10 additional cases that have been published since 1967. The clinical presentation of enterococcal vertebral osteomyelitis was similar to cases due to other bacteria. Enterococcus faecalis caused most cases, consistent with its presumably increased virulence. All enterococcal cases in the literature were reported from Europe, which may be due to epidemiological differences related to antibiotic utilization and infection control practices between the US and Europe. Nine of all 12 cases were reported since 1995, which may be consistent with the increase in occurrence of enterococcal infections in general, in association with increasing patient co-morbidities, invasive procedures, and indwelling vascular devices.

Clinical trials yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of community-acquired pneumonia. We assessed whether short-term corticosteroid treatment reduces time to clinical stability in patients admitted to hospital for community-acquired pneumonia.In this double-blind, multicentre, randomised, placebo-controlled trial, we recruited patients aged 18 years or older with community-acquired pneumonia from seven tertiary care hospitals in Switzerland within 24 h of presentation. Patients were randomly assigned (1:1 ratio) to receive either prednisone 50 mg daily for 7 days or placebo. The computer-generated randomisation was done with variable block sizes of four to six and stratified by study centre. The primary endpoint was time to clinical stability defined as time (days) until stable vital signs for at least 24 h, and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00973154.From Dec 1, 2009, to May 21, 2014, of 2911 patients assessed for eligibility, 785 patients were randomly assigned to either the prednisone group (n=392) or the placebo group (n=393). Median time to clinical stability was shorter in the prednisone group (3·0 days, IQR 2·5-3·4) than in the placebo group (4·4 days, 4·0-5·0; hazard ratio [HR] 1·33, 95% CI 1·15-1·50, p0·0001). Pneumonia-associated complications until day 30 did not differ between groups (11 [3%] in the prednisone group and 22 [6%] in the placebo group; odds ratio [OR] 0·49 [95% CI 0·23-1·02]; p=0·056). The prednisone group had a higher incidence of in-hospital hyperglycaemia needing insulin treatment (76 [19%] vs 43 [11%]; OR 1·96, 95% CI 1·31-2·93, p=0·0010). Other adverse events compatible with corticosteroid use were rare and similar in both groups.Prednisone treatment for 7 days in patients with community-acquired pneumonia admitted to hospital shortens time to clinical stability without an increase in complications. This finding is relevant from a patient perspective and an important determinant of hospital costs and efficiency.Swiss National Science Foundation, Viollier AG, Nora van Meeuwen Haefliger Stiftung, Julia und Gottfried Bangerter-Rhyner Stiftung.

Background Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. Methods 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow-up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20–40 ng/ml during 12 months of follow-up and several dosage regimens were evaluated by simulation. Results A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharma-cokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates, and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300,000 IU two times per year. Conclusions This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

BACKGROUND Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting. METHODS/DESIGN This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint. DISCUSSION This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects. TRIAL REGISTRATION 7 September 2009 on ClinicalTrials.gov: NCT00973154.

Pylephlebitis - suppurative thrombophlebitis of the portal and/or mesenteric veins - is a rare complication of abdominal infections, especially diverticulitis. It can lead to severe complications such as hepatic abscess, sepsis, peritonitis, bowel ischemia, etc., which increase the mortality rate. Here we present a case of suppurative thrombophlebitis of the inferior mesenteric vein, as a complication of sigmoid diverticulitis. The epidemiology, clinical and radiological features as well as treatment strategies are discussed. We also review the anatomy of the mesenteric vein given its anatomic variation in the present case and how this anatomic knowledge might influence the operative approach should surgery be necessary.

We report on the ongoing epidemic of typhoid fever in Tajikistan that started in 1996. It has involved more than 24,000 cases to date, and is characterized by multiple point sources, overflow of sewage, contaminated municipal water, and person-to-person spread. Of the Salmonella typhi isolates available for testing in western laboratories, more than 90% are multidrug-resistant (MDR). Most recently, 28 (82%) of 34 isolates are resistant to ciprofloxacin, representing the first reported epidemic of quinolone-resistant typhoid fever. In the past, mass immunization during typhoid fever epidemics has been discouraged. A review of this policy is recommended in light of the alarming emergence of quinolone-resistant strains of S. typhi, the availability of improved vaccines, and the ongoing epidemic in Tajikistan. Mass immunization may be a useful measure for the control of prolonged MDR typhoid fever epidemics, as an adjunct to correction of municipal infrastructure and public health intervention.

Pancreatic tuberculosis is rare and can occur in the absence of evidence of tuberculosis elsewhere in the body. Here we review the radiological appearance of pancreatic tuberculosis and compare it with other cystic pancreatic lesions, including common lesions (pseudocysts, serous or mucinous cystadenomas, intraductal papillary mucinous neoplasm) and rare lesions such as solid pseudopapillary tumors, etc. Their typical localizations within the pancreas and their malignant potential are presented. Knowledge of these can assist radiologists and clinicians in selecting the best approach towards making the correct diagnosis.

Strongyloides hyperinfection syndrome may be complicated by paralytic ileus that interferes with the absorption of oral anti-helminthics. We report on the administration of ivermectin as a rectal enema preparation to a renal transplant recipient with Strongyloides hyperinfection syndrome and progressive ileus. Attempts at treatment using nasogastric albendazole and ivermectin were unsuccessful despite clamping the nasogastric tube after drug administration. Ivermectin tablets were ground to a powder, resuspended in a commercially available suspending agent, and administered per rectum. The suspending agent was chosen for its near-physiologic osmolality to allow longer retention, in contrast to many enema preparations that have a laxative effect. The patient improved markedly within 72 hours of initiation of the therapy per rectum and recovered fully. Ivermectin administered as an enema may be beneficial in patients with severe strongyloidiasis who are unable to absorb or tolerate oral therapy.

Objectives: Whether zidovudine (AZT)-associated lipoatrophy occurrence differs by concomitant exposure to protease (Pis) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains unclear. Baseline body composition data from a randomized trial in subjects stable on first-line AZT-based therapy were used to explore this issue. Methods: In this substudy of the PREPARE trial, centrally read baseline whole-body dual energy x-ray aborptiometry (DXA) and single-slice abdominal CT scans were analyzed with respect to duration and type of prior AZT/lamivudine (3TC) combination antiretroviral therapy (cART), including by multivariate linear regression adjusted for age, gender, ethnicity, body mass index (BMI), and nadir CD4. Results: DXA and CT, from 134 and 136 patients, respectively [87% male; 82% Caucasian; mean (SD) age, 45.6 years (10); BM I, 24.3 kg/m(2) (3.2)], were analyzed. Prior AZT/3TC cART exposure was 5.5 (2.2) years. Seventy-eight and 27 patients had concomitantly and exclusively used NNRTIs and Pls, respectively. AZT/3TC cART, AZT/3TC/NNRTI, and AZT/3TC/PI, respectively, were associated with the presence of a mean (95% Cl) of 247 g (-438 to 56; P = .012), 267 g (-467 to 66; P = .010), and 216 g (-430 to 1.7; P = .048) less baseline limb fat per additional year of prior exposure. Although abdominal subcutaneous (SAT) adipose tissue was likewise less with longer AZT/3TC cART, this was only significant for AZT/3TC/ NNRTI but not AZT/3TC/Pl. Visceral adipose tissue (VAT) amount was not clearly associated to prior treatment. Increased age and male gender were independently associated with lower limb fat and SAT, but more VAT. Conclusions: Longer exposure to AZT/3TC, regardless of whether in combination with PI or NNRTI, as well as increased age and male gender are independently associated with lower limb fat mass.

The potential for mitochondrial (mt) DNA mutation accumulation during antiretroviral therapy (ART), and preferential accumulation in patients with lipoatrophy compared with control participants, remains controversial. We sequenced the entire mitochondrial genome, both before ART and after ART exposure, in 29 human immunodeficiency virus (HIV)-infected Swiss HIV Cohort Study participants initiating a first-line thymidine analogue-containing ART regimen. No accumulation of mtDNA mutations or deletions was detected in 13 participants who developed lipoatrophy or in 16 control participants after significant and comparable ART exposure (median duration, 3.3 and 3.7 years, respectively). In HIV-infected persons, the development of lipoatrophy is unlikely to be associated with accumulation of mtDNA mutations detectable in peripheral blood.

Suggested citation for this article: Ogredici O, Erb S, Langer I, Pilo P, Kerner A, Haack HG,.et al. Brucellosis reactivation after 28 years. Emerg Infect Dis [serial on the Internet]. 2010 Dec [date cited]. http://dx.doi.org/10.3201/eid1612.100678

Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) were enrolled in an anorectal Chlamydia trachomatis screening study. Anorectal Chlamydia DNA was detected in 16 (10.9%) of 147 men, mainly among asymptomatic patients and patients having >20 sexual partners. These results support routine anorectal Chlamydia screening in HIV-infected MSM who report unprotected anal intercourse.

BACKGROUND/AIMS: Alveolar echinococcosis (AE) is a serious liver disease. The aim of this study was to explore the long-term prognosis of AE patients, the burden of this disease in Switzerland and the cost-effectiveness of treatment. METHODS: Relative survival analysis was undertaken using a national database with 329 patient records. 155 representative cases had sufficient details regarding treatment costs and patient outcome to estimate the financial implications and treatment costs of AE. RESULTS: For an average 54-year-old patient diagnosed with AE in 1970 the life expectancy was estimated to be reduced by 18.2 and 21.3 years for men and women, respectively. By 2005 this was reduced to approximately 3.5 and 2.6 years, respectively. Patients undergoing radical surgery had a better outcome, whereas the older patients had a poorer prognosis than the younger patients. Costs amount to approximately Euro108,762 per patient. Assuming the improved life expectancy of AE patients is due to modern treatment the cost per disability-adjusted life years (DALY) saved is approximately Euro6,032. CONCLUSIONS: Current treatments have substantially improved the prognosis of AE patients compared to the 1970s. The cost per DALY saved is low compared to the average national annual income. Hence, AE treatment is highly cost-effective in Switzerland.

Fungal arteritis is a rare entity, associated with significant morbidity and mortality, that typically involves graft arteries in solid organ transplant recipients. Here, we report the first case of Candida carotid arteritis and review 22 other cases of Candida arteritis reported since 1966 in patients who have not received transplants. Most patients had serious underlying conditions. All cases were anatomically characterized by pseudoaneurysm formation. Patients presented with fever (n=17), local pain (n=13), and an expanding pulsatile mass (n=4), with subsequent rupture and hemorrhage (n=7). Evidence of Candida colonization or infection was present in 15 patients before arteritis occurred. Treatment typically included a combined surgical and antifungal approach. The outcome was favorable in 11 patients, but follow-up was limited. A high index of suspicion, early diagnosis, and prompt antifungal and surgical treatment seem crucial to efforts to avoid life-threatening arterial rupture and hemorrhage

OBJECTIVE: Hierarchical modeling has been proposed as a solution to the multiple exposure problem. We estimate associations between metabolic syndrome and different components of antiretroviral therapy using both conventional and hierarchical models. STUDY DESIGN AND SETTING: We use discrete time survival analysis to estimate the association between metabolic syndrome and cumulative exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical model where the drug class provides a prior model of the association between metabolic syndrome and exposure to each antiretroviral. RESULTS: One thousand two hundred and eighteen patients were followed for a median of 27 months, with 242 cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years. Metabolic syndrome was more likely to develop in patients exposed to stavudine, but was less likely to develop in those exposed to atazanavir. The estimate for exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81 when using spline-based covariate adjustment). CONCLUSION: These results are consistent with trials that show the disadvantage of stavudine and advantage of atazanavir relative to other drugs in their respective classes. The hierarchical model gave more plausible results than the equivalent conventional model.

BACKGROUND: HIV-1 infected individuals have an increased cardiovascular risk which is partially mediated by dyslipidemia. Single nucleotide polymorphisms in multiple genes involved in lipid transport and metabolism are presumed to modulate the risk of dyslipidemia in response to antiretroviral therapy. METHODS: The contribution to dyslipidemia of 20 selected single nucleotide polymorphisms of 13 genes reported in the literature to be associated with plasma lipid levels (ABCA1, ADRB2, APOA5, APOC3, APOE, CETP, LIPC, LIPG, LPL, MDR1, MTP, SCARB1, and TNF) was assessed by longitudinally modeling more than 4400 plasma lipid determinations in 438 antiretroviral therapy-treated participants during a median period of 4.8 years. An exploratory genetic score was tested that takes into account the cumulative contribution of multiple gene variants to plasma lipids. RESULTS: Variants of ABCA1, APOA5, APOC3, APOE, and CETP contributed to plasma triglyceride levels, particularly in the setting of ritonavir-containing antiretroviral therapy. Variants of APOA5 and CETP contributed to high-density lipoprotein-cholesterol levels. Variants of CETP and LIPG contributed to non-high-density lipoprotein-cholesterol levels, a finding not reported previously. Sustained hypertriglyceridemia and low high-density lipoprotein-cholesterol during the study period was significantly associated with the genetic score. CONCLUSIONS: Single nucleotide polymorphisms of ABCA1, APOA5, APOC3, APOE, and CETP contribute to plasma triglyceride and high-density lipoprotein-cholesterol levels during antiretroviral therapy exposure. Genetic profiling may contribute to the identification of patients at risk for antiretroviral therapy-related dyslipidemia.

We describe the case of a kidney transplant recipient who developed meningococcemia, without meningeal signs, 2 months after transplantation. Plasma levels of complement components C3, C4, and CH 50 were within the normal range. However, using a method to screen for the functional activity of all 3 pathways of complement, no activation via the mannose-binding lectin (MBL) pathway could be detected (0%). A subsequent quantification of MBL pathway components revealed normal levels of MASP 2 but undetectable amounts of MBL. To our knowledge, this is the first report of meningococcal disease after organ transplantation in a patient with MBL deficiency.

An increase in fox population has led to an increase in incidence of human alveolar echinococcosis., We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case-finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12– 0.15 during 1956–1992 and a mean of 0.10 during 1993–2000 to a mean of 0.26 during 2001–2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10–15 years later.

Background Good syndrome (GS) refers to a constellation of thymoma and adult-onset immunodeficiency characterized by low or absent B cells, hypogammaglobulinemia, and variable defects in cell-mediated immunity with an inverted CD4/CD8 + T-cell ratio. Patients may develop severe or chronic infections as a result of this immunodeficiency. Objective To describe a patient with GS who developed cytomegalovirus (CMV) encephalitis and showed a periodic electroencephalographic pattern and myoclonus. Design Case report. Setting Outpatient neurology clinic at a university medical center. Patient A 64-year-old man who developed periodic myoclonus involving the right half of his body and the left arm. Results Five years previously, the patient had undergone resection of a pathologically confirmed epithelial thymoma. Quantitative CMV polymerase chain reaction of the serum and cerebrospinal fluid showed strongly positive results (1:10 000), allowing the diagnosis of CMV encephalitis. Conclusions To the best of our knowledge, myoclonus and periodic electroencephalographic pattern have not previously been reported in CMV encephalitis. Opportunistic CMV infection should be considered early in the evaluation of patients with GS or a history of thymoma who develop unusual neurological symptoms.

Clinical trials yielded conflicting data about the benefit of adding systemic corticosteroids for community-acquired pneumonia (CAP). We evaluated whether short-term corticosteroid treatment reduces time to clinical stability in patients hospitalized for CAP.

Immunodeficiency with thymoma (Good syndrome, GS) is a rare, adult-onset condition that is characterized by thymoma, hypogammaglobulinemia, and low numbers of peripheral B cells. CD4+ T lymphopenia and an inverted CD4:CD8+ T-cell ratio may be present. Here we report 5 patients with GS and infectious complications who were seen at 3 institutions between 1983 and 1999. Three patients had recurrent sinopulmonary infections, 3 had severe cytomegalovirus (CMV) disease, and 1 had Pneumocystis carinii pneumonia. Review of the literature identified 46 other reports of infections in GS patients. The infections reported in all 51 patients included recurrent sinopulmonary infection (19 cases with documented respiratory pathogens), generally with encapsulated bacteria, most often Haemophilus influenzae (11 cases); CMV disease (5 cases); bacteremia (7 cases); oral or esophageal candidiasis (6 cases); persistent mucocutaneous candidiasis (5 cases); chronic diarrhea (5 cases with documented stool pathogens); urinary tract infections (4 cases); P. carinii pneumonia (3 cases); tuberculosis (2 cases); Kaposi sarcoma (1 case); disseminated varicella (1 case); candidemia (1 case); wound infection with Clostridium perfringens (1 case); Mycoplasma arthritis (1 case); and other infections. Patients with GS present with a spectrum of sinopulmonary infections and pathogens similar to common variable immunodeficiency (CVID). Compared with patients with CVID, opportunistic infections, including severe CMV disease, P. carinii pneumonia, and mucocutaneous candidiasis, appear to be more common in patients with GS, and patients with GS may have a worse prognosis. GS should be ruled out in patients with thymoma or CVID who develop severe, especially opportunistic, infections. Treatment with intravenous immune globulin is recommended for all patients with GS.

To the Editor: Increased risk for reactivation of tuberculosis (TB) after treatment with tumor necrosis factor (TNF) antagonists, particularly infliximab, is well documented (1). We describe a case of peritoneal TB, probably resulting from reactivation of Mycobacterium bovis infection after infliximab treatment. In retrospect, reactivation might have been preventable had physicians been aware of the patient’s history of regularly drinking fresh cow’s milk from a local farm in Switzerland during 1944–45, when bovine TB was prevalent. The patient was a 69-year-old Swiss woman who was examined for weakness, abdominal pain, increasing abdominal girth, and weight loss in April 2008. Her history included a diagnosis of Crohn disease in 1978 and treatment with glucocorticoids, cyclosporine, and mercaptopurine. In November 2007, during a recurrence of Crohn disease and while receiving treatment with azathioprine, the patient had a negative interferon gamma release assay (IGRA) result (QuantiFERON-TB in Tube test; Cellestis International, Carnegie, Victoria, Australia) and an unremarkable chest radiograph. On November 30, 2007, she was given prednisone (40 mg/d for 2 weeks, then tapered) and prescribed 3 doses of infliximab because of severe inflammation seen during colonoscopy (5 mg/kg on November 30, 2007, January 4, 2008, and February 15, 2008). She was hospitalized on April 25, 2008, at which time she had ascites; the fluid contained 1.4 × 109/L leukocytes (79.5% lymphocytes) but was negative for acid-fast bacilli on direct examination and PCR testing for Mycobacterium tuberculosis complex. Laparoscopy on May 2, 2008, showed extensive peritoneal inflammation. Peritoneal biopsy samples contained acid-fast bacilli and caseating granulomas; PCR for M. tuberculosis complex was positive. At this time, results of a repeat QuantiFERON-TB in Tube test and a tuberculin skin test (TST) were negative, but a T-SPOT.TB (Oxford Immunotec, Abingdon, UK) test was positive (6-kDa early secretory antigenic target [ESAT-6], >20 spots; 10-kDa culture filtrate protein [CFP-10], 11 spots). M. bovis ssp. bovis was grown in cultures of peritoneal biopsy samples. For culture, the MGIT 960 automated culture system (Becton Dickinson, Sparks, MD, USA) was used. The isolate was identified by use of a multiplex PCR-based, solid-phase, reverse-hybridization assay (GenoType MTBC, Hain Lifescience GmbH, Nehren, Germany), excluding M. bovis BCG (2). The patient was discharged May 30, 2008. In January 2009, she was much improved after treatment with isoniazid/rifampin/ethambutol for 3 months and moxifloxacin/rifampin for 5 months. This case of presumed reactivation of peritoneal TB caused by M. bovis in a patient treated with infliximab highlights the need to be aware of local epidemiology with regard to transmissible infectious diseases. It particularly emphasizes the value of careful history taking regarding consumption of unpasteurized dairy products in assessing risk for latent TB infection (LTBI) before starting anti-TNF treatment. Some infectious diseases experts (3) recommend considering LTBI treatment before prescribing anti-TNF therapy even when TST is negative or only minimally positive (

Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) has been shown to augment antigen presentation by macrophages and dendritic cells in vitro, and to increase antibody responses to injected antigens in experimental animals. To evaluate the usefulness of rhGM-CSF as a vaccine adjuvant, 108 healthy volunteers were randomly assigned to receive an injection of rhGM-CSF (n = 81) or placebo (control group; n = 27), followed by an injection with recombinant hepatitis B vaccine into the same site. During the study period of 28 days, protective antibody titers to hepatitis surface antigen (anti-HBs10 mIU ml-1) were observed in 11 of 81 subjects receiving rhGM-CSF, but in none of the controls (P = 0.035). Injections were well tolerated. A single i.m. or s.c. injection of 20-40 micrograms of rhGM-CSF significantly enhances antibody responses when given at the same site as recombinant hepatitis B vaccination.