Panton-Valentine leukocidin-positive Staphylococcus aureus in skin and soft tissue infections from primary care patients.

OBJECTIVES: To characterize deep skin and soft tissue infections (dSSTI) caused by Panton-Valentine leukocidin (PVL)-positive versus PVL-negative Staphylococcus aureus isolates. METHODS: We performed a retrospective analysis of patients' records including S. aureus isolates from outpatients with dSSTI. Samples had been submitted by primary care physicians, i.e. general practitioners, surgeons, dermatologists and paediatricians, located in Berlin, Germany, in 2007-2017. Bacterial isolates were identified and tested for antimicrobial susceptibility by VITEK 2; PVL was detected by PCR. RESULTS: In total, 1199 S. aureus isolates from 1074 patients with dSSTI were identified, and 613 (51.1%) of 1199 samples were PVL+. The median age of patients with PVL+S. aureus was lower than in patients with PVL- S. aureus (34 years, range 0-88 years, vs. 44 years, range 0-98 years; p < 0.0001). PVL was associated with repeated/multiple samples compared to single sample submission (69/92, 75% vs. 448/982, 45.6%, p < 0.0001; odds ratio (OR), 3.6; 95% confidence interval (CI), 2.2-5.8). Interestingly, the highest PVL positivity rate was found in isolates from gluteal (82/108, 75.9%; OR, 3.6; 95% CI, 2-5) or axillary (76/123, 61.8%; OR, 2; 95% CI, 1.1-3.3) localizations compared to isolates from the arm. The PVL positivity rate did not increase over time. Yet we noticed an increase in the trimethoprim/sulfamethoxazole (SXT) resistance rate in PVL+ isolates, mainly methicillin-sensitive S. aureus, when considering SXT resistance rates of 2007-2012 versus 2013-2017 (35/226, 15.5% vs. 74/289, 25.6%; p 0.01). CONCLUSIONS: In outpatients, gluteal and axillary dSSTI are indicative of PVL+S. aureus. Providing SXT as a complementary treatment for dSSTI should be based on susceptibility testing.

A novel NFKBIA variant substituting serine 36 of IκBα causes immunodeficiency with warts, bronchiectasis and juvenile rheumatoid arthritis in the absence of ectodermal dysplasia.

Genetic studies have led to identification of an increasing number of monogenic primary immunodeficiency disorders. Monoallelic pathogenic gain-of-function (GOF) variants in NFKBIA, the gene encoding IκBα, result in an immunodeficiency disorder, typically accompanied by anhidrotic ectodermal dysplasia (EDA). So far, 14 patients with immunodeficiency due to NFKBIA GOF mutations have been reported. In this study we report three patients from the same family with immunodeficiency, presenting with recurrent respiratory tract infections, bronchiectasis and viral skin conditions due to a novel pathogenic NFKBIA variant (c.106 T > G, p.Ser36Ala), which results in reduced IκBα degradation. Immunological investigations revealed inadequate antibody responses against vaccine antigens, despite hypergammaglobulinemia. Interestingly, none of the studied patients displayed features of EDA. Therefore, missense NFKBIA variants substituting serine 36 of IκBα, differ from the rest of pathogenic GOF NFKBIA variants in that they cause combined immunodeficiency, even in the absence of EDA.

Aspirin vs. P2Y12 Inhibitor Rivalry: Which One Can be Continued During Gastrointestinal Bleeding.

Dual antiplatelet therapy (DAPT) is the mainstay of secondary prevention treatment for acute coronary syndrome (ACS) and ischemic stroke, especially after coronary intervention. DAPT consists of aspirin and P2Y12 receptor inhibitor (e.g. clopidogrel), and the use of DAPT has been increased over time. The most serious and common adverse effect is gastrointestinal bleeding. Guidelines in managing such condition are available among Gastroenterologist Societies and Cardiologist Societies. Most guidelines are consistent with each other to continue the use of aspirin while withholding P2Y12. However, European Society of Cardiologist (ESC) guideline in 2017 recommends P2Y12 receptor inhibitor as the preferred antiplatelet for patient with upper gastrointestinal bleeding. This review will look on the guidelines and other supporting evidence for the justification on the antiplatelet of choice.

Evaluation of the Roche LightMix Gastro parasites multiplex PCR assay detecting Giardia duodenalis, Entamoeba histolytica, cryptosporidia, Dientamoeba fragilis, and Blastocystis hominis.

OBJECTIVES: Multiplex PCR assays offer highly sensitive and specific tools for the detection of enteric pathogens. This prospective study aimed at comparing the novel Roche LightMix Modular Assay Gastro Parasites (LMAGP) detecting Giardia duodenalis, Entamoeba histolytica, Cryptosporidium spp., Blastocystis hominis, and Dientamoeba fragilis with routine laboratory procedures. METHODS: Stool specimens (n = 1062 from 1009 patients) were consecutively examined by LMAGP, R-Biopharm Ridascreen enzyme immunoassays (EIAs) detecting G. duodenalis or E. histolytica/dispar, and microscopy of wet mounts. Discrepant results were analysed by in-house PCR. RESULTS: D. fragilis or B. hominis were detected by LMAGP in 131 (14.4%) and 179 (19.9%; 16 samples positive by microscopy; p < 0.0001) of 909 samples, respectively. Of 918 samples analysed for Cryptosporidium spp., six were positive by LMAGP (three could be confirmed by Kinyoun staining and one by in-house PCR). G. duodenalis was detected by LMAGP, EIA, or microscopy in 20, 16, or 9 of 1039 stool samples, respectively; all four samples missed by EIA were confirmed by in-house PCR. In total, 938 stool samples were analysed for E. histolytica/dispar. Nine of ten EIA-positive samples were negative by LMAGP but positive by in-house PCR for E. dispar. One E. histolytica infection (positive by both LMAGP and in-house PCR) was missed by EIA and microscopy. Parasites only detected by microscopy included Enterobius vermicularis eggs (n = 3) and apathogenic amoebae (n = 27). CONCLUSIONS: The data call for routine use of multiplex PCR assays for the detection of enteric protozoan parasites in laboratory diagnostics.

Treatment Response Monitoring of Chronic Hepatitis B Patients using Transient Elastography and Aspartate Aminotransferase-to-Platelet Ratio Index (APRI).

BACKGROUND: Hepatitis B is endemic in Indonesia and treatment response need to be monitored during and after antiviral therapy. Liver stiffness measurement and alanine aminotransferase-to-platelet ratio index (APRI) are noninvasive method to detect liver fibrosis available in Indonesia. However, little is known about their ability to evaluate treatment response in chronic hepatitis B (CHB) patients in Indonesia. This study aimed to investigate liver stiffness changes by transient elastography (TE) and APRI before and after one-year oral antiviral treatment in CHB patients and the correlation between TE and APRI. METHODS: this study was retrospective cohort on CHB patients in CiptoMangunkusumo Hospital, Jakarta who uderwent treatment between January 2012 and December 2014. Patients received oral antiviral treatment with newer nucleoside analogues (entecavir or telbivudine) for at least one year. TE and APRI were obtained before and after treatment. TE and APRI reductions were analyzed statistically with Spearman's test. RESULTS: a total of 41 patients were enrolled in this study. Median liver stiffness value was significantly reduced from 10.8 to 5.9 kPa after oral antiviral treatment (p<0.001, Wilcoxon's test). Median APRI was also significantly reduced from 1.13 to 0.43 after treatment (p<0.001, Wilcoxon's test). The correlation between liver stiffness and APRI before treatment was weak (r=0.40), but it was strong after treatment (r=0.73). CONCLUSION: the liver stiffness measured with transient elastography and APRI significantly decreased after one year of antiviral treatment in chronic HBV patients. There was a significant correlation between TE and APRI after one year of treatment.

[Chronic skin ulcer in a 24-year-old man after a journey to Southeast Asia]. / Chronisches Ulkus nach Südostasienreise bei 24­jährigem Mann.

Our report concerns a 24-year-old man with a chronic exsudative skin lesion after a journey to Southeast Asia. The diagnosis of melioidosis was made by the identification of Burkholderia pseudomallei from the ichor. The diagnosis was confirmed by polymerase change reaction. The patient was treated with meropenem i. v. for about 10 days and with trimethoprim/sulfamethoxazole for the following 12 weeks. Melioidosis is an endemic disease in Southeast Asia and North Australia which in some cases can run a severe course and can have a high fatality rate. The relevance of melioidosis becomes more important against the background of the increasing global movement of travelers and migration.

[Fever of unknown origin in 74-year-old multimorbid man]. / Fieber unklarer Genese bei einem 74-jährigen multimorbiden Patienten.

A 74-year-old multimorbid man was admitted with fever of unknown origin. Over time the fever ceased spontaneously. The patient developed signs of a right heart failure without evidence of a primarily cardiac pathogenesis and died of acute right heart failure. Miliary tuberculosis that had lead to pulmonary artery hypertension was diagnosed at autopsy.

Detection of Giardia duodenalis assemblage A and B isolates by immunochromatography in stool samples from Rwandan children.

We evaluated the performance of an immunochromatographic assay (ICA) in comparison with light microscopy and PCR for the detection of Giardia duodenalis in stool samples from 558 Rwandan children. The association of infection with clinical symptoms was similar for the three diagnostic tools. The ICA equally detected parasites of assemblages A and B and was more sensitive than light microscopy (50.4 versus 29.5% of PCR-positive samples considered true positive; p <0.0001). Hence, the ICA shows superior sensitivity compared with microscopy but still misses half of the G. duodenalis infections detected by PCR in this hyperendemic area.

Hookworm-related cutaneous larva migrans in patients living in an endemic community in Brazil: immunological patterns before and after ivermectin treatmen.

Hookworm-related cutaneous larva migrans (Hr-CLM) is caused by animal hookworm larvae migrating in the human epidermis where they elicit an inflammatory response. This study describes the immunological profile in Hr-CLM patients. In 77 Hr-CLM patients from Manaus, Brazil, peripheral eosinophils were counted, and serum concentrations of total immunoglobulin E (IgE) and selected cytokines were determined by ELISA before and after treatment with ivermectin. Controls included patients' household members (endemic controls), non-endemic Brazilian and Japanese individuals. Eosinophil counts and total IgE in Hr-CLM patients were higher than in controls and correlated with disease severity. Concentrations of interleukin (IL)-4, IL-5, IL-6, and IL-10 were higher in Hr-CLM patients than in endemic controls (p < 0.001) while no differences were detected for interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-1ß, IL-2, or transforming growth factor (TGF)-ß. Following ivermectin treatment, numbers of eosinophils and concentrations of IL-4, IL-5, and IL-10 decreased whereas IgE, IFN-γ, and TGF-ß concentrations increased. The IL-5/IFN-γ ratio declined from 5.9 (interquartile range [IQR] 0.8-31.6) before to 0.1 (IQR 0.05-0.2; p = 0.001) after treatment. Thus, although an impact of other infections on the immune parameters determined cannot be excluded, Hr-CLM in endemic areas is associated with eosinophilia and elevated cytokine levels, particularly of IL-5 and IL-10, which decrease following ivermectin treatment.

Human papillomavirus genotype distribution and risk factors for infection in women from a small municipality in north east Brazil.

In order to assess the prevalence of human papillomavirus (HPV) infection, the HPV genotypes and factors associated with infection, we conducted a population-based survey in a small municipality in north east Brazil among women aged between 12 and 49 years. A questionnaire regarding socioeconomic variables, reproductive life and sexual behaviour was used, and women were examined gynaecologically, followed by collection of vaginal lavage with saline solution for HPV DNA determination. HPV DNA was detected by the Digene(®) SHARP Signal(TM)-System, and further genotyped by INNO-LiPA Genotyping System(®). Of 579 women, HPV infection was present in 68 (prevalence: 11.7%; 95% CI: 9.3-14.7). The most common HPV types were 16, 31 and 74, each accounting for 14.7% of infections. Of all HPV-positive women, 35.3% showed multiple HPV genotypes. Variables independently associated with HPV infection were: ≥3 partners in life (adjusted OR [aOR]: 3.06; 95% CI: 1.68-5.60) and the use of oral contraception in the last 12 months (aOR: 2.39; 95% CI: 1.33-4.30). Previous participation in a cervical cancer screening programme was protective (aOR: 0.28; 95% CI: 0.13-0.60). HPV infection is common among women from rural Brazil, and HPV genotypes identified indicate that immunization could be an important preventive measure in this population.

Delusional infestation and the specimen sign: a European multicentre study in 148 consecutive cases.

BACKGROUND: Systematic studies of delusional infestation (DI), also known as delusional parasitosis, are scarce. They lack either dermatological or psychiatric detail. Little is known about the specimens that patients provide to prove their infestation. There is no study on the current presentation of DI in Europe. OBJECTIVES: To determine the number of true infestations, to assess with which pathogens patients believe themselves to be infested, and to gather details about the frequency and nature of the specimens and the containers used to store them, based on European study centres. METHODS: Retrospective study of consecutive cases with suspected DI from six centres (Dermatology, Psychiatry, Tropical Medicine) in four European countries (U.K., Germany, Italy, France). RESULTS: In total, 148 consecutive cases of suspected DI were included, i.e. the largest cohort reported. None of the patients had evidence of a genuine infestation, as shown by examinations by dermatologists and/or infectious disease specialists. Only 35% believed themselves to be infested by parasites; the majority reported a large number of other living or inanimate (17%) pathogens. Seventy-one patients (48%) presented with what they believed was proof of their infestation. These specimens were mostly skin particles or hair, and rarely insects (only very few of which were human pathogenic or anthropophilic, and none of these could be correlated with the clinical presentation), and only 4% were stored in matchboxes (three of 71). CONCLUSIONS: This first multicentre study of DI in Europe confirms that the term 'delusional infestation' better reflects current and future variations of this entity than 'delusional parasitosis'. The presentation of proofs of infestation, commonly referred to as 'the matchbox sign', is typical but not obligatory in DI and might better be called 'the specimen sign'.

Amoebic liver abscess with negative serologic markers for Entamoeba histolytica: mind the gap!

A 38-year-old male German traveller returning from Asia presented with fever, night sweats and abdominal complaints. Abdominal ultrasonography revealed several fast-growing abscesses of the liver. Three blood cultures as well as serologic investigations for the detection of antibodies to Entamoeba histolytica, performed on day 3 and 7 after the onset of clinical symptoms, remained negative. Stool microscopy revealed the presence of amoeba cysts compatible with E. histolytica infection. Taking both the amoebic and bacterial etiology of the abscesses into consideration, the patient was treated with metronidazole and ciprofloxacin followed by paromomycin. Antibodies to E. histolytica tested positive shortly after anti-amoebic therapy was initiated. The patient fully recovered, and ultrasound follow-up showed complete resolution of the abscesses within 50 days. This case leads to the conclusion that amoebic liver abscess should be considered despite negative amoeba serology and that ultrasonography is an important diagnostic tool for the early diagnosis of extraintestinal amoebiasis.

[Neurotuberculosis: a continuing clinical challenge]. / Neurotuberkulose : Eine anhaltende klinische Herausforderung.

In Germany neurotuberculosis is quite rare. Familiarity with the disease is nonetheless important because of many differential diagnoses and therapeutic implications. The diagnosis of neurotuberculosis is made by considering of clinical presentation, CSF, and cerebral imaging. Early diagnosis, prompt initiation of effective antitubercular therapy, and clinical staging are necessary for establishing a long-term treatment prognosis. The results of neurotuberculosis therapy are often unsatisfactory despite the availability of effective drugs. Lasting damage or death can be averted in fewer than half of the patients. Studies now confirm that early adjuvant corticoid therapy reduces lethality and morbidity. Resistant new strains of the pathogen, Mycobacterium tuberculosis, complicate therapy. Recent discoveries especially in diagnosis and therapy are explained using case evidence.

The central nervous system in mucosal vaccination of rhesus macaques with simian immunodeficiency virus Deltanef.

We studied the central nervous system (CNS) of rhesus macaques during series of vaccination experiments in which attenuated simian immunodeficiency virus (SIV), SIVmac239Deltanef, was applied to the tonsils and the animals were later challenged with pathogenic SIVmac251 or SHIV/89.6P via tonsils or rectum. The pathologic lesions were graded on a scale of 0-5. The lesions were in general very mild, with a score of 0.5, except for one case, in which the animal had progressed to simian AIDS (SAIDS) and had severe lesions of grade 4. Except for the SAIDS case, the most common lesions were meningitis, ependymitis, inflammation of choroid plexus, and astrocytosis. Invasion of the challenge virus, SIVmac251, and pathologic lesions were detected 4 days post infection. The main features of the pathological lesions were similar during short-term follow-up (4 days to 2 weeks) and long-term follow-up (23 to 56 weeks) after challenge. No significant difference was found between unvaccinated controls infected with the challenge viruses and vaccinated and challenged animals. The pathological lesions in the one SAIDS case consisted of extensive lesions of the white matter in connection with confluent ependymitis, indicating an invasion through the choroid plexus. The lesions were characterized by a myriad of multinucleated giant cells of macrophage origin, which showed, together with individual macrophages, strong labelling for viral RNA and proteins. Productive infection of astrocytes was a very rare finding. In three cases infected via tonsils with SIVmac239Deltanef without challenge, we detected expression of Nef-derived peptides, indicating a selective pressure for Nef functions in the CNS.

[Typing for HLA matching. Advantages for keratoplasty]. / Typisierung beim HLA-Matching. Vorteile für die Keratoplastik.

Matching of human leukocyte antigens of donors and recipients (HLA matching) plays a significant role in kidney, heart, lung, and stem cell transplantation. New data demonstrate that HLA matching also significantly prolongs the survival of corneal grafts. The reasons for the late recognition of the significance of HLA matching in corneal transplantation are on the one hand the immune privilege of the eye, which allows corneal transplantation under certain conditions without immunosuppressive therapy, and on the other hand highly erroneous serological typing. Recent molecular DNA typing is almost without errors, and the selection of grafts on the basis of results obtained using this method will improve the long-time survival of future corneal grafts. Today, there are several reasons arguing for the general practice of HLA matching in keratoplasty.

Seroprevalence of human granulocytic anaplasmosis in Berlin/Brandenburg, Germany: an 8-year survey.

This study investigated the seroprevalence of antibodies against Anaplasma phagocytophilum in Berlin/Brandenburg, north-eastern Germany. During 1994-2001, 422 sera from patients with proven tick-exposure (specimens with antibodies against Borrelia burgdorferi) were compared with 249 control sera. Using indirect fluorescent antibody testing, significantly more positive samples were detected among Borrelia antibody-positive specimens (4.5%, 95% CI 2.5-6.5%) than among controls (1.2%, 95% CI 0.5-1.9%; p < 0.05). While six (2.2%, 95% CI 1.3-3.1%) samples were positive among Borrelia antibody-positive sera between 1994 and 1997, 13 (8.7%, 95% CI 6.9-10.5%) were positive between 1998 and 2001 (p < 0.01), indicating an uneven annual seroprevalence.

[27-year-old man with high fever and septic shock after returning from vacation]. / 27-jähriger Reiserückkehrer mit hohem Fieber und septischem Schock im Verlauf.

A 27-year-old man was admitted with high fever and shivers eleven days after returning from vacation in Indonesia. Physical examination, laboratory values, abdominal ultrasound, and chest x-ray were not conclusive. All blood cultures yielded growth of Salmonella enterica serovar Typhi, and typhoid fever was diagnosed. Subsequently, the patient developed septic shock and pulmonary edema. In this case report epidemiological, clinical, and therapeutic aspects of typhoid fever are discussed with special emphasis on criteria for severe typhoid fever, which is treated with additional glucocorticoids.

Macaque dendritic cells infected with SIV-recombinant canarypox ex vivo induce SIV-specific immune responses in vivo.

Dendritic cells (DCs) infected with recombinant avipox vectors express the introduced genes and activate antigen-specific T cells. DCs exhibit distinct differentiation-dependent immune functions. Moreover, immature DCs are readily infected by canarypox vectors, but undergo tumor necrosis factor (TNF)-alpha-dependent death, while fewer mature DCs get infected and resist dying. A pilot study was performed using the rhesus macaque system to explore whether immature and mature DCs infected with SIV-recombinant canarypox (vCP180) ex vivo could induce primary virus-specific immune responses in vivo. After subcutaneous (sc) reinjection, functional monocyte-derived DCs migrated to lymph nodes (LNs) within 1-2 days and primed T cells in vivo. This was observed by monitoring dye-labeled DCs in the draining LNs and tetanus toxoid (TT)-specific T cell responses after injection of TT-loaded DCs. DCs from simian immunodeficiency virus (SIV)-naïve rhesus macaques were infected with vCP180 (SIVmac142 gag, pol, and env genes), and sc reinjected into donor animals. Low-level SIV-specific T cell proliferation, but little if any interferon (IFN)-gamma production was detected. DCs pulsed with vCP180 in combination with TT and keyhole limpet hemocyanin (KLH) (to activate additional T cells and provide "helper" cytokines) induced SIV-, TT-, and KLH-specific T cell responses, including IFN-gamma responses not seen when vCP180-carrying DCs were used alone. Interleukin (IL)-10 and low-level antibody responses were also observed. This pilot study provides the proof of principle that sc injected ex vivo SIV-recombinant canarypox-infected DCs safely induce low-level SIV-specific immune responses in vivo.