Importance of whole genome sequencing for the assessment of outbreaks in diagnostic laboratories: analysis of a case series of invasive Streptococcus pyogenes infections.

Outbreaks of Streptococcus pyogenes hypervirulent clones are constant public health threats. In western Switzerland, an increase of severe cases of S. pyogenes invasive infections was observed between December 2015 and March 2016. Our aim was (i) to investigate these cases by the use of Whole Genome Sequencing (WGS) and (ii) to determine the specific virulome and resistome of each isolate in order to undertake adequate public health measures. Eleven Streptococcus pyogenes strains isolated from 11 patients with severe invasive infections between December 13, 2015 and March 12, 2016 were included in our study. Practically, emm-typing, MLST and WGS were used to investigate the relatedness between the isolates. The presence of virulence and antibiotic resistance genes as well as mutations in transcriptional regulators of virulence and in genes encoding for antibiotic targets were assessed. Three and two groups of isolates shared the same emm-type and ST type, respectively. Single Nucleotide Polymorphism (SNP) analysis revealed 14 to 32 SNPs between the strains of the same emm-type group, ruling out the possibility of a clonal outbreak. Mutations found in covS and rocA could partially explain an increased virulence. As these reassuring results were obtained in less than 10 days, no specific hospital hygiene and no dedicated public health measures had to be undertaken. WGS is a powerful technique to discriminate between closely related strains, excluding an outbreak in less than 10 days. Moreover, WGS provided extensive data on the virulome and resistome of all these strains.

[Eosinophilia: from neoplastic disease to anguillulosis]. / Eosinophilie: de la néoplasie à l'anguillulose.

Hypereosinophilia (HE), defined as eosinophil count above 0.5 G/l in the peripheral blood. Most cases are secondary to other diseases. Etiological diagnosis remains complex especially as causes of HE vary across the population. Allergic diseases and parasitic infections are the predominant causes. However up to 10% of HE are secondary to tumors. Here, we describe a case of HE initially attributed to a breast cancer that turn out to be due to an angillulosis acquired just before the diagnosis of the tumor.

[Q fever: a cause of fever of unknown origin in Switzerland]. / La fièvre Q: une cause d'état fébrile sans foyer en Suisse.

We describe two cases of Q fever in previously healthy women presenting with fever of unknown origin. The diagnosis was made after several days of investigations. Symptoms and signs of acute or chronic Coxiella burnetii infection are protean and non-specific. Q fever should be included in the differential diagnosis of fever of unknown origin and appropriate serologic studies should be done. We review the clinical presentation of Q fever. Use of serology for the diagnosis and the follow-up is discussed.

[H1N1 (continued), multiresistant Enterobacteriacea, new diagnostic tools]. / Infectiologie. Grippe H1N1 (suite), entérobactéries multirésistantes, nouveautés pour le diagnostic.

The pandemic was declared over in October 2010. In this article we review some publications that describe the specificity of the 2009 A(H1N1) virus or suggest new approaches to design more efficacious and better accepted vaccines. Antibiotics resistance continue to increase with the emergence of enterobacteria resistant to almost all available agents. Use of old drugs like fosfomycin is reconsidered. 2010 has also brought progress in the diagnosis of infectious diseases.

[Severe CMV infection: not only in immunocompromised patients]. / Infection grave à cytomégalovirus (CMV): pas seulement chez les patients immunosupprimés.

In presence of immunosuppression Cytomegalovirus (CMV) infection can cause severe and potentially fatal infection involving multiple organs. In healthy immunocompetent individuals CMV usually causes an asymptomatic or mild infection with spontaneous cure. No specific therapy is needed. Rarely, however, the primary infection can be severe with multiple organs injuries and fatal cases are described. In these situations antiviral therapy is indicated and the clinical and biological response is very rapidly good. We describe a clinical case and present a review of the literature.

[Diagnostic of Pneumocystis jirovecii pneumonia in a non HIV patient]. / Diagnostic de la pneumonie à Pneumocystis jirovecii chez le patient non VIH.

Pneumocystis jirovecii pneumonia is an opportunistic infection affecting not only HIV patient but also patients with others causes of immunosuppression. The reference method for the diagnostic is the direct visualization of the pathogen in induced sputum or in bronchoalveolar lavage with a low sensibility. Direct immunofluorescence does not increase significantly this sensibility on IS. The PCR has been demonstrated to have 100% sensitivity. This gives rise to the problem of falsely positive results in patients, colonized by P. jiroveci (8,9-26,9%) but suffering from a pneumonia due to another pathogen. Use of quantitative PCR or serum beta-D-glucan, might be helpful to distinguish colonization from infection. This paper reviews the literature on the diagnostic of PCP in non HIV patients.

[Various causes of fever of unknown origin]. / Fièvre qui dure: que faire?

Fever of unknown origin is defined by fever lasting more than 3 weeks, with no diagnose despite a consequent work-up. 4 subgroups were determined: infectious fever, such as subacute bacterial endocarditis, tuberculosis or intra-abdominal abcess, inflammatory diseases such as temporal arteritis or adult Still's disease, neoplastic disorders, and miscellaneous causes. About one third of patients have no diagnosis at the end of the work up, and for those the prognose is usually good. There is no algorithm to know which tests to order: focused history and detailled physical status give important clues to decide about additionnal laboratories testing. An empirical treatment is justified only in case of vital risk.

Risk of Borrelia burgdorferi infection in western Switzerland following a tick bite.

The aim of this study was to define the risk of developing Lyme borreliosis after a tick bite. A survey was conducted from 1993 to 1995 in the western part of Switzerland in a group of patients who presented for treatment of a recent tick bite. Only patients with negative serological tests (enzyme-linked fluorescent assay screening test, and IgG and IgM immunoblots) at the first consultation and for whom a second blood sample was available 2 months later were included in the study. Of the 376 patients included, 266 had no clinical manifestation (group 1) and 110 had a small local cutaneous reaction (<2 cm) (group 2). The tick was available for 160 patients. Seroconversion was observed in 4.5% of 376 patients, 3.4% in group 1 and 7.2% in group 2. Typical erythema migrans, confirmed by seroconversion, was observed in three of 376 (0.8%) patients, while five of 376 (1.3%) patients developed a skin lesion without seroconversion. No other clinical manifestation of Lyme borreliosis was observed among these 376 patients. Borrelia detection in ticks did not correlate significantly with the risk of Lyme borreliosis. In conclusion, the risk of developing Lyme borreliosis in western Switzerland after a tick bite is low, and therefore, prophylactic antibiotics are not required.

Usefulness of procalcitonin serum level for the diagnosis of bacteremia.

The predictive value of procalcitonin serum levels to detect or rule out bacteremia was investigated prospectively in a case-control study with 200 hospitalized adults from whom blood samples were taken for culture. Fifty bacteremic patients (cases) had higher procalcitonin serum levels than the 150 controls with sterile blood cultures (11.7 vs. 0.7 ng/ml; P=0.0001), a difference that remained significant after controlling for potential confounders in multivariate analysis. At cut-off values of 0.5 and 0.2 ng/ml, the sensitivity of procalcitonin was 56 and 92%, and the specificity was 83 and 43%, respectively. These results yielded low positive (22 and 12%) and high negative predictive values (96 and 99%), reflecting primarily the low prevalence of bacteremia among patients who undergo blood cultures in hospitals (low pretest probability). Although caution is mandatory when using such markers at the individual level, procalcitonin, possibly together with other parameters, could nonetheless prove useful in future studies to rapidly rule out bacteremia.

[Epidemiology of Lyme borreliosis in French-speaking Switzerland]. / Epidémiologie de la borréliose de Lyme en Suisse romande.

The purpose of this study was to assess the number of cases and the clinical aspects of Lyme borreliosis in French-speaking Switzerland. From July 1996 to December 1997, all laboratories performing serological tests for Lyme borreliosis sent a questionnaire to the treating physicians whenever the tests were positive. In addition, the physicians who diagnosed a case on clinical grounds only were also asked to report these cases. During this period, 1460 positive serological tests were recorded among approximately 10,360 performed (14%). A total of 775 questionnaires were returned (53%). In 3/4 of the cases, the test was ordered because of an acute clinical manifestation or a tick bite. The rest related to chronic symptoms or follow-up. In 504 cases (65%), diagnosis was considered certain or probable. These were erythema migrans in 46%, clinical manifestations of stage II in 33% (26 facial palsy, 20 acute arthritis, 5 benign cutaneous lymphocytoma) and chronic symptoms in 21% (23 acrodermatitis, 26 neuropathies, and 8 arthritis). The adjusted incidence, estimated on the basis of the treating physician's place of residence, ranged from 9/100,000 in Valais to 95/100,000 in Neuchâtel. This study indicates that Lyme borreliosis is a diagnosis frequently looked for and established in French-speaking Switzerland. Although erythema migrans is the main clinical manifestation, symptoms of stage II and III indicate that Lyme borreliosis is also responsible for relatively major systemic morbidity.

Prospective randomized comparison of imipenem-cilastatin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis.

Nosocomial pneumonia and acute peritonitis may be caused by a wide array of pathogens, and combination therapy is often recommended. We have previously shown that imipenem-cilastatin monotherapy was as efficacious as the combination of imipenem-cilastatin plus netilmicin in these two settings. The efficacy of imipenem-cilastatin is now compared to that of piperacillin-tazobactam as monotherapy in patients with nosocomial pneumonia or acute peritonitis. Three hundred seventy one patients with nosocomial pneumonia or peritonitis were randomly assigned to receive either imipenem-cilastatin (0.5 g four times a day) or piperacillin-tazobactam (4.5 g three times a day). Three hundred thirteen were assessable (154 with nosocomial pneumonia and 159 with peritonitis). For nosocomial pneumonia, clinical-failure rates in the piperacillin-tazobactam group (13 of 75 [17%]) and in the imipenem-cilastatin group (23 of 79 [29%]) were similar (P = 0.09), as were the numbers of deaths due to infection (6 in the imipenem-cilastatin group [8%], 7 in the piperacillin-tazobactam group [9%]) (P = 0.78). For acute peritonitis, clinical success rates were comparable (piperacillin-tazobactam, 72 of 76 [95%]; imipenem-cilastatin, 77 of 83 [93%]). For infections due to Pseudomonas aeruginosa, 45 patients had nosocomial pneumonia (21 in the piperacillin-tazobactam group and 24 in the imipenem-cilastatin group) and 10 had peritonitis (5 in each group). In the patients with nosocomial pneumonia, clinical failure was less frequent in the piperacillin-tazobactam group (2 of 21 [10%]) than in the imipenem-cilastatin [corrected] group (12 of 24 [50%]) (P = 0.004). Bacterial resistance to allocated regimen was the main cause of clinical failure (1 in the piperacillin-tazobactam group and 12 in the imipenem-cilastatin group). For the patients with peritonitis, no difference in clinical outcome was observed (five of five cured in each group). The overall frequencies of adverse events related to treatment in the two groups were similar (24 in the piperacillin-tazobactam group, 22 in the imipenem-cilastatin group). Diarrhea was significantly more frequent in the piperacillin-tazobactam group (10 of 24) than in the imipenem-cilastatin group (2 of 22). This study suggests that piperacillin-tazobactam monotherapy is at least as effective and safe as imipenem-cilastatin monotherapy in the treatment of nosocomial pneumonia or peritonitis. In P. aeruginosa pneumonia, piperacillin-tazobactam achieved a better clinical efficacy than imipenem-cilastatin, due to reduced development of microbiological resistance. Tolerance was comparable, with the exception of diarrhea, which was more frequent with piperacillin-tazobactam.

[Q fever with endocarditis: clinical presentation and serologic follow-up of 21 patients]. / Fièvre Q avec endocardite: présentation clinique et suivi sérologique de 21 patients.

AIM OF THE STUDY: The purpose of this study was to analyse the clinical and serological follow-up in 21 patients with Q fever endocarditis in Switzerland from 1981 to 1993. PATIENTS AND METHODS: Criteria for Q fever endocarditis were the following: Coxiella burnetii phase I IgG > 1 : 2560 and IgA > 1 : 20 by indirect immunofluorescence. Methods to confirm the diagnosis include immunohistochemical demonstration of C. burnetii by microscopy in valvular material (1 case) and inoculation of this material in experimental animals (10 cases). Information on clinical course of the disease, laboratory abnormalities and treatment were obtained by chart review and a questionnaire sent to physicians who requested the serological tests for Q fever. RESULTS: The average age of the patients was 47 years (15 men and 6 women). 64% of patients had a history of environmental exposure to C. burnetii. The median time of symptomatology before diagnosis was 5 months (1-108). 19/21 patients had valvular lesions, and 2/21 vascular Dacron prosthesis. Most patients presented with fever (18/21), congestive cardiac failure (14/21), weight loss (12/21), anemia (6/19), or thrombocytopenia (6/19). All the patients required antibiotic treatment. Cardiac surgery was performed in 15/21 patients. For 10 patients the geometric mean serological follow-up included at least titers at time of diagnosis (IgG anti-phase I antibodies 1 : 27024, IgA anti-phase I antibodies 1 : 685), at the end of therapy (IgG anti-phase I antibodies 1 : 2941, IgA anti-phase I antibodies 1 : 153) and 6 months after the end of therapy (IgG anti-phase I antibodies 1 : 368, IgA anti-phase I antibodies 1 : 40). The fall in anti-phase I titers was significant. During the clinical and serological outcome (median of 60 months and 69 months respectively) there was no recurrence of endocarditis and antibody titers to C. burnetii phase I remained low. Two patients died during the observation period, one from lung cancer, while the cause of death in the other was unknown. CONCLUSIONS: Serology is the key to Q fever diagnosis. The duration of treatment, and the values to be used to establish cure of endocarditis, are not clearly defined. During the clinical and serological outcome (median of 60 months and 69 months respectively) there was no recurrence of endocarditis and antibody titers to C. burnetii phase I remained low.

Disseminated histoplasmosis in an adopted infant from El Salvador.

UNLABELLED: An HIV-negative 4-month-old infant recently adopted from El Salvador was admitted for high fever. Hepatosplenomegaly, anaemia, leucopenia, thrombocytopenia, increased transaminases, and diffuse interstitial pulmonary infiltration were present on admission. Granulomas were seen in bone marrow and liver biopsies without any organism. Disseminated histoplasmosis was diagnosed 2 weeks later when bone marrow and blood cultures taken on admission became positive for Histoplasma capsulatum and when histoplasmic antigen was detected in blood. The outcome was good after treatment with amphotericin B followed by itraconazole which was administered for a 6-month period without significant toxicity. CONCLUSION: Disseminated histoplasmosis is very rarely seen in Europe but should be suspected in case of unexplained fever in immigrants from the endemic areas in the world, particularly when hepatosplenomegaly and pancytopenia are present. Bone marrow examination and culture, blood cultures, and antigen testing are the mainstays of the diagnosis.

[Epidemic of type B botulism: Sion, December 1993-January 1994]. / Epidémie de botulisme de type B: Sion, décembre 1993-janvier 1994.

12 cases of food-borne botulism were registered in Sion, Switzerland, between 31 December, 1993 and 12 January, 1994. A type B toxin was isolated from the serum of one patient and from the incriminated ham. Clinical data of 10 male patients aged 21 to 54 years and some epidemiologic data are reported. The clinical course was mild to moderate with predominant autonomic and gastro-intestinal symptoms and signs: blurred vision (10 patients of 10), dry mouth with dysphagia (9/10), asthenia (7/10), diarrhea and/or constipation (7/10), nausea and vomiting (6/10), abdominal cramps (5/10), impaired sexual function (5/10), dilated pupils (4/10). Some discomfort (mainly blurred vision, asthenia and impaired sexual function) persisted for several months in most patients. Neuromuscular involvement was never the reason for seeking medical assistance and had often disappeared at the time of the first visit. Two patients were hospitalized, one for transient ileus of unknown origin and the second (first suspected case) for monitoring and infusion of trivalent equine botulinum antitoxin. This treatment was administered on day eight after intoxication and had no effect on this patient's outcome when compared with others. No patient died. Epidemiology, diagnosis, treatment and prognosis of botulism are discussed.

Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus-infected patients.

To evaluate combined prophylaxis for Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis, 533 patients with symptomatic human immunodeficiency virus infection and/or CD4 lymphocyte counts of < 200/microL were randomized to receive dapsone/pyrimethamine (200/75 mg once weekly) or aerosolized pentamidine (300 mg every 4 weeks). The median CD4 lymphocyte count was 110/microL; 47.5% were seropositive for toxoplasma antibodies. The median duration of follow-up was 483 days. In the intent-to-treat analysis, 12 cases of PCP and 14 of toxoplasmic encephalitis occurred in the dapsone/pyrimethamine group and 13 and 20 cases, respectively, in the aerosolized pentamidine group (adjusted relative risk for toxoplasmosis, 0.56; P = .10). However, only two of the 14 cases of toxoplasmic encephalitis in the dapsone/pyrimethamine group developed during actual treatment. The mortality among the two groups was similar. Dapsone/pyrimethamine was not tolerated by 30% of participants. A subanalysis of 240 matched, tolerant patients yielded a relative risk for toxoplasmosis of 0.21 (P = .014), a result favoring the use of dapsone/pyrimethamine. Dapsone/pyrimethamine was as effective as aerosolized pentamidine as prophylaxis for PCP and significantly reduced the incidence of toxoplasmic encephalitis among those participants who tolerated it.