Epidemiological, clinical and laboratory characteristics of acute Q fever in an endemic area in Israel, 2006-2016.

Our purpose was to describe the clinical, epidemiological and laboratory characteristics of patients hospitalised with acute Q fever in an endemic area of Israel. We conducted a historical cohort study of all patients hospitalised with a definite diagnosis of acute Q fever, and compared them to patients suspected to have acute Q fever, but diagnosis was ruled out. A total of 38 patients had a definitive diagnosis, 47% occurred during the autumn and winter seasons, only 18% lived in rural regions. Leucopaenia and thrombocytopaenia were uncommon (16% and 18%, respectively), but mild hepatitis was common (mean aspartate aminotransferase 76 U/l, mean alanine aminotransferase 81 U/l). We compared them with 74 patients in which acute Q fever was ruled out, and found that these parameters were not significantly different. Patients with acute Q fever had a shorter hospitalisation and they were treated more often with doxycycline than those without acute Q fever (6.4 vs. 14 days, P = 0.007, 71% vs. 38%, P = 0.001, respectively). In conclusion, acute Q fever can manifest as an unspecified febrile illness, with no seasonality. We suggest that in endemic areas, Q fever should be considered in the differential diagnosis in any febrile patient with risk factors for a persistent infection.

Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel.

OBJECTIVES: HIV elite controllers (ECs) are a unique subgroup of HIV-positive patients who are long-term virologically suppressed in the absence of antiretroviral treatment (ART). The prevalence of this subgroup is estimated to be < 1%. Various cohorts of ECs have been described in developed countries, most of which have been demographically heterogeneous. The aim of this study was to identify ECs in two large African cohorts and to estimate their prevalence in a relatively genetically homogenous population. METHODS: We screened two cohorts of HIV-positive Ethiopian patients. The first cohort resided in Mekelle, Ethiopia. The second was comprised of HIV-positive Ethiopian immigrants in Israel. In the Mekelle cohort, ART-naïve subjects with stable CD4 counts were prospectively screened using two measurements of viral load 6 months apart. Subjects were defined as ECs when both measurements were undetectable. In the Israeli cohort, subjects with consistently undetectable viral loads (mean of 17 viral load measurements/patient) and stable CD4 count > 500 cells/µL were defined as ECs. RESULTS: In the Mekelle cohort, 16 of 9515 patients (0.16%) fitted the definition of EC, whereas seven of 1160 (0.6%) in the Israeli cohort were identified as ECs (P = 0.011). CONCLUSIONS: This is the first large-scale screening for HIV-positive ECs to be performed in entirely African cohorts. The overall prevalence of ECs is within the range of that previously described in developing countries. The significant difference in prevalence between the two cohorts of similar genetic background is probably a consequence of selection bias but warrants further investigation into possible environmental factors which may underlie the EC state.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae carriage upon hospital admission: prevalence and risk factors.

The aim of this study was to assess the value of surveillance cultures in identifying extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL) carriers upon admission to hospital, and to identify risk factors for carriage. This prospective cross-sectional study included all hospital admissions over one week. Of 525 patients screened, 56 were positive for ESBLs. Half were only identified through screening. Four independent risk factors were identified: nursing home residency, hospitalization in the previous year, prior antibiotic treatment and prior ESBL carriage. Over 50% of the screened patients had at least one risk factor. By screening this targeted population, 87.5% of positive patients would have been identified.

Successful therapeutic splenectomy in an HIV patient with relapsing visceral leishmaniasis.

A 43-year-old HIV-positive Ethiopian immigrant presented with persistent diarrhoea, hepatosplenomegaly and pancytopaenia. Visceral leishmaniasis was diagnosed by multiple gastrointestinal tract biopsies. Blood polymerase chain reaction (PCR) was positive for Leishmania donovani. Despite highly active antiretroviral therapy (HAART) and multiple courses of antileishmanial treatments, including liposomal amphotericin and sodium stibogluconate, the patient had multiple relapses. CD4 counts remained at 40-60 cells/µL although viral loads were undetectable. Splenectomy resulted in resolution of the patient's pancytopaenia and in rising CD4 levels, which enabled a long-lasting remission.

MRSA SCCmec epidemiology in Israel: development and implementation of an MRSA SCCmec typing strategy.

Staphylococcal cassette chromosome mec (SCCmec) typing is essential for investigating the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). Published assays were often found to be limited in their ability to characterize isolates that were not collected locally. We aimed to develop, test, and implement a molecular method which would enable the SCCmec classification of a large collection of MRSA isolates in a routine clinical laboratory. A multistep working algorithm consisting of two main steps and four additional supplementary steps was developed, using previously reported primers. A total of 1,008 isolates obtained locally, by both clinical and screening cultures, were tested. The majority of isolates (82.54%) could be classified using two main reactions. Overall, our MRSA SCCmec typing strategy was able to classify 917/1,008 (90.97%) of the MRSA isolates. The most predominant was type II SCCmec (41%); a high prevalence of type V SCCmec (16.37%) was also found. PVL gene carriage was found among two type IV SCCmec isolates only. We present a logistically feasible, multistep, MRSA SCCmec typing algorithm which can be used to type a large collection of MRSA isolates. The distinctly higher prevalence of SCCmec type V might reflect a unique MRSA distribution pattern in Israel.

The effect of empiric antibiotic therapy on mortality in debilitated patients with dementia.

The purpose of this investigation was to assess the effect of empirical antibiotic treatment on 30-day mortality among debilitated inpatients with dementia and Gram-negative bacteremia. A retrospective cohort study in the years 2005-2007 was undertaken. Data were collected through patient chart review. The association between individual variables and 30-day mortality was assessed through univariate analysis. Variables significantly associated with mortality (p < 0.05) were entered into a logistic regression analysis. Adjusted odds ratios (ORs) for mortality with 95% confidence intervals (CIs) are shown. Subgroup analysis of patients with and without decubitus ulcers was performed. In our cohort of 378 patients with dementia and Gram-negative bacteremia, the 30-day mortality was 39% overall and 61% in the subgroup of patients with decubitus ulcers. Inappropriate empirical therapy was associated with higher mortality, although this effect was not statistically significant (OR 1.41, 95% CI 0.86-2.29). Inappropriate empirical therapy did not affect mortality in the subgroup of patients with decubitus ulcers (OR 0.37, 95% CI 0.11-1.28). Other factors found to independently affect mortality included age, co-morbidities, source of infection, sepsis severity, and hospital-acquired infection. Appropriate empirical antibiotic therapy for patients with dementia and severe bacterial infection did not have a clear advantage, especially in the sickest group of patients with decubitus ulcers.

Nucleoside reverse transcriptase inhibitors in combination therapy for HIV patients: systematic review and meta-analysis.

Treatment guidelines recommend dual nucleoside reverse transcriptase inhibitors (NRTI ) as a part of combination antiretroviral therapy. The objective of this study was to assess the relative efficacy and toxicity of the dual NRTI part of the regimen in antiretroviral-naïve HIV-1-infected adults. A systematic review and meta-analysis of randomized controlled trials assessing highly active antiretroviral therapy (HAART) for treatment-naïve HIV-infected adults with a 48-week follow-up were done. We searched the PubMed, CENTRAL, and EMBASE electronic databases up to April 2009. Proceedings from conferences were reviewed. Data were extracted independently by two reviewers. Primary outcome was viral suppression at 48 weeks. The odds ratio (OR) is reported with its corresponding 95% confidence interval (CI). Twenty-two randomized controlled trials, including 8,184 HIV-treatment-naïve patients, were included. The combination didanosine + lamivudine/emtricitabine (four trials, 1,148 patients) was more effective (OR 0.53, 95% CI 0.41-0.68) for viral load (VL) >50 copies/ml and less toxic (OR 0.52, 95% CI 0.36-0.76) for discontinuation due to adverse events (AE) than its comparators. The combination tenofovir + lamivudine/emtricitabine was more effective and less toxic (OR 0.75, 95% CI 0.58-0.96) only in the 144-week follow-up data (two trials, 1,119 patients). Abacavir + lamivudine had similar efficacy to its comparators (OR 0.81, 95% CI 0.8-1.1), but more AIDS-defining events (OR 3.22, 95% CI 1.24, 8.40). The once-daily combination didanosine + lamivudine/emtricitabine was found to be effective and tolerable. This combination, soon to be generic, should be compared to the current standard of care in a large randomized trial. An effective, safe, and inexpensive alternative to current options is needed.

Persistent Helicobacter canis bacteremia in a patient with gastric lymphoma.

A 78-year-old man with gastric diffuse large B cell lymphoma presented with persistent Helicobacter canis bacteremia while receiving chemotherapy. An examination of his medical history revealed a close exposure to dogs. The patient recovered after 4 weeks of antibiotic therapy. Immunocompromised persons who maintain close contacts with dogs maybe at risk for this infection.

Prevention of human immunodeficiency virus mother-to-child transmission in Israel.

The objective of the study was to investigate the HIV-mother-to-child transmission (MTCT) rate in Israel. This was a retrospective study of HIV-infected pregnant women, mainly immigrants from Ethiopia, in six Israeli AIDS centres, in 2000-2005. Medical records of mothers and newborns were evaluated for HIV status, treatment and MTCT rates. Three hundred pregnancies of 241 HIV-infected women, resulting in 304 live births, were studied. In 86/241(36%) women, HIV diagnosis was made during the current pregnancy or shortly after labour. Thirty others were diagnosed during previous pregnancies. Highly active antiretroviral therapy (HAART) was prescribed in 76% of pregnancies. The mean viral load before labour was 23,000 +/- 100,000 copies/mL with a mean CD4 of 406 +/- 223 (range 4-1277) cells/mm(3). Caesarian sections were preformed in 175/300 pregnancies (103/175 with viral load <1000 copies/mL). During labour, azidothymidine (AZT) was given to 80% and nevirapine to 8% of the women. Eighty-eight percent of the neonates received AZT for six weeks. The overall HIV-MTCT rate was 3.6%. MTCT correlated significantly with delayed HIV diagnosis, low CD4, lack of HAART during pregnancy and lack of perinatal treatment. HIV treatment of mothers and their newborns throughout pregnancy, labour and perinatal period are crucial for effective prevention of MTCT, emphasizing the need for early HIV screening, diagnosis and treatment.

SCCmec and spa types of methicillin-resistant Staphylococcus aureus strains in Israel. Detection of SCCmec type V.

Molecular characterization of methicillin-resistant Staphylococcus aureus isolates from three hospitals in Israel was the aim of the study presented here. We identified 11 distinct genetic clones by pulsed-field gel electrophoresis. Molecular typing identified four different SCCmec types-I, II, IV, and V-and nine spa types. Spa type t002 was the most common.

Drug-resistant HIV infection among drug-naive patients in Israel.

BACKGROUND: In Israel, <0.06% of the general population is infected with human immunodeficiency virus (HIV), with a much higher prevalence among specific groups. These groups are distinguished demographically by risk behavior category and by virus subtype. We investigated transmission of drug resistance within groups to assess the impact of these factors. METHODS: Plasma samples from >15% of all patients with new diagnoses of HIV infection were randomly collected between June 1999 and June 2003. Sequences from 176 drug-naive patients included 20 of subtype A, 20 of subtype AE, 2 of subtype AC, 29 of subtype B, 100 of subtype C, and 5 of subtype F. RESULTS: Major drug resistance mutations (protease: L90M; reverse transcriptase: M41L, K103N, V106M, M184V, Y181S, G190A, L210W, T215Y/F, and K219R) were detected in 1 subject with A subtype, 3 with subtype B, and 9 with subtype C. In addition, 1 subject with A subtypes, 2 with subtype B, and 10 with subtype C had secondary mutations (protease: M46I; reverse transcriptase: A98G, K101Q, and V108I). Only 1 patient had mutations associated with >1 class of drugs. Among subjects who contracted HIV infection in Israel, 16 of 56 (1 of 7 with subtypes A or AE, 4 of 17 with subtype B, and 11 of 32 with subtype C; P=.7-1.0) carried resistant virus--a significantly higher proportion (P<.001) than in subjects infected in other countries (10 of 120 infected). CONCLUSIONS: Drug-resistant virus was detected in 14.8% of patients with new diagnoses of HIV infection but in 28.6% of patients known to have been infected in Israel. The implications include a need for pretreatment resistance testing and for better programs aimed at prevention of transmission, directed particularly at patients. We did not find significant differences in transmission of resistant virus between those infected with subtypes B and C, despite the different demographic background. A conclusive analysis and interpretation should await a more extensive study.

Unique TCRDV1-positive lymphocytes that infiltrate colonic neoplasia originate from a selected cell population present in the intestinal mucosa and the peripheral blood.

TCRDV1-positive lymphocytes, which infiltrate colon carcinomas, were recently shown to be cytolytic for tumour cells. However, the immune compartment from which these cells originate is unknown. The aim of the present studies was to determine the origin of TCRDV1-positive cells in colonic neoplasia. Biopsies were obtained from normal colon, polyps or carcinomas, concurrently with a sample from the peripheral blood. RNA was extracted and a TCRDV1-specific reverse transcriptase-polymerase chain reaction (RT-PCR) was performed. Amplification products were analysed by a CDR3 display and sequence analysis. In five out of six patients, the TCRDV1 CDR3 display of the whole cell population within the neoplastic tissue was distinct from that in the normal mucosa and the peripheral blood. The nucleotide sequences of CDR3 domains from the three compartments were distinct as well. In one patient, a pattern similar to the CDR3 display was detected in neoplastic and normal intestinal tissues. However, using junction-specific RT-PCR of CDR3 sequences derived from the neoplastic cells, such sequences could be detected in all three compartments. These findings suggest that in contrast to the current paradigm, a unique TCRDV1 cell population circulates in the peripheral blood and normal intestinal tissue and infiltrates colon neoplasia rather than being restricted to a single compartment as previously thought.

Persistent bacteremia in the absence of defined intravascular foci: clinical significance and risk factors.

The clinical significance of and the risk factors for persistent bacteremia were assessed in 299 episodes. Persistent bacteremia was defined as at least two positive blood cultures obtained on different calendar days during the same infectious episode. Short-term bacteremia was defined as positive blood cultures solely on the first day of the infectious episode. A total of 4,277 episodes of bloodstream infections were detected, of which 299 episodes (7%) were persistent bacteremia. The following were independent risk factors were for persistent bacteremia: burns, presence of a central vascular catheter, cirrhosis, infections caused by Salmonella spp., polymicrobial infections, and inappropriate empirical antibiotic treatment. Irrespective of the source of infection, the presence of a central vascular catheter was correlated with an increased risk for persistent bacteremia. Mortality among patients with persistent bacteremia was 50%, compared to 35% among patients with short-term bacteremia. Because of the high mortality associated with persistent bacteremia, a thorough search for the source of infection is essential to ensure timely and appropriate therapy.

Clinical characteristics of the West Nile fever outbreak, Israel, 2000.

West Nile (WN) virus is endemic in Israel. The last reported outbreak had occurred in 1981. From August to October 2000, a large-scale epidemic of WN fever occurred in Israel; 417 cases were confirmed, with 326 hospitalizations. The main clinical presentations were encephalitis (57.9%), febrile disease (24.4%), and meningitis (15.9%). Within the study group, 33 (14.1%) hospitalized patients died. Mortality was higher among patients >70 years (29.3%). On multivariate regressional analysis, independent predictors of death were age >70 years (odds ratio [OR] 7.7), change in level of consciousness (OR 9.0), and anemia (OR 2.7). In contrast to prior reports, WN fever appears to be a severe illness with high rate of central nervous system involvement and a particularly grim outcome in the elderly.

Computerized tomography findings of abdominal tuberculosis: report of 19 cases.

BACKGROUND: Abdominal tuberculosis usually presents with general symptoms and obscure abdominal complaints for which computerized tomography is often the first imaging study. OBJECTIVE: To evaluate the CT findings of abdominal tuberculosis. METHODS: The CT scans of 19 patients (10 men and 9 women aged 20-85 years) with proven abdominal tuberculosis were retrospectively reviewed to define the location and extent of the disease. The patients were referred for the study mainly with general systemic symptoms. Additional abdominal complaints were present in four, including acute abdomen in one. Two had symptoms deriving from the urinary tract. Nine patients had recently arrived from high prevalence countries; five of them and two others were positive for human immunodeficiency virus. Three patients had a family history of tuberculosis; one had previously been treated for tuberculosis and four others had an underlying chronic disease. The diagnosis of tuberculosis was established by standard microbiological and histological techniques. RESULTS: We divided the disease manifestations into intraperitoneal (n = 13) and genitourinary involvement (n = 6). Peritoneal tuberculosis was fairly common, characterized by ascites, omental and mesenteric infiltration, and smooth thickening of the parietal peritoneum. One oncology patient had a false positive Tc-99m CEA isotope scanning, suggesting tumor recurrence. Genitourinary disease manifested mainly as hydronephrosis and calcifications. Three patients had pulmonary tuberculosis as well. CONCLUSION: The CT findings of abdominal tuberculosis may mimic various diseases, mainly diffuse peritoneal malignancy. We emphasize the need to consider tuberculosis in the differential diagnosis in patients with obscure abdominal symptoms, especially with multi-organ involvement. A high degree of clinical suspicion and familiarity with the abdominal CT manifestations allow early diagnosis of this treatable disease.

Human gastrin: a Helicobacter pylori--specific growth factor.

BACKGROUND & AIMS: Helicobacter pylori resides within the gastric mucosa, a niche hostile to other microorganisms. Human gastrin levels are elevated after infection and return to normal after eradication. The aim of this study was to test the direct effect of gastrin on the growth of H. pylori. METHODS: H. pylori and control bacteria were grown with gastrin or control peptides and growth rate was determined. (125)I-labeled gastrin was used to determine uptake. RESULTS: Human gastrin stimulated H. pylori growth in a specific, dose-dependent manner. Gastrin shortened the lag time, increased growth rate in the logarithmic phase, and increased final bacterial concentration at the stationary phase. These effects were shown over a wide concentration range, including physiological luminal and serum levels. Labeled gastrin uptake was inhibited by unlabeled gastrin. Controls consisting of cholecystokinin and pentagastrin inhibited gastrin uptake but did not stimulate growth. In contrast, somatostatin and epidermal growth factor had no effect on either gastrin uptake or bacterial growth. These results suggest a structurally restricted, receptor-mediated, gastrin-specific effect. CONCLUSIONS: Human gastrin is a specific growth factor for H. pylori and may have a role in the adaptation of H. pylori to its unique habitat.

Aztreonam plus piperacillin--empiric treatment of neutropenic fever in gynecology-oncology patients receiving cisplatin-based chemotherapy.

Antibiotic therapy must be instituted promptly and on an empiric basis in neutropenic patients. We evaluated the efficacy of a combined antibiotic regimen of monobactam (aztreonam) and antipseudomonal penicillin (piperacillin) in treating neutropenic fever episodes in gynecologic-oncology patients receiving cisplatin-based chemotherapy. A retrospective analysis of response to this regimen was performed. The rationale of this combination is the lack of nephrotoxicity and ototoxicity in patients who are or were previously treated with other nephrotoxic/ototoxic agents like cisplatin. A total of 19 courses of this regimen was administered to 13 patients with neutropenic fever following a complete fever work-up. Aztreonam (1-2gr q8h) plus piperacillin (4gr q8h) were administered intravenously for 6-8 days. Blood cultures were positive in four febrile episodes, and urine cultures were positive in seven. Gram negative organisms accounted for all positive cultures. The cultured organism showed in-vitro sensitivity to at least one of the drugs in all positive isolates. Clinical response with defervescence was noted during therapy in 18/19 courses (94.7%). Although the two drugs share a common bactericidal mechanism they were found to be highly active in this subgroup of patients. A double blind prospective evaluation of this empiric combination is warranted.

The growth advantage conferred by HIV-1 nef is determined at the level of viral DNA formation and is independent of CD4 downregulation.

Recent data on the phenotype of nef-defective HIV-1 in vitro indicate a new function of the Nef gene product: enhancement of viral infectivity. Single-cycle replication studies have suggested that Nef enhances the efficiency of an early step during viral replication, a step that leads to the establishment of viral DNA. To test this interpretation, the accumulation of low-molecular-weight (unintegrated) viral DNA was measured in cells following exposure to wild-type and nef-defective viruses. nef-defective virus accumulated less DNA than the wild type. This difference was observed after as little as 5 hr of exposure to virus. However, the reverse transcriptase activities of wild-type and nef-defective viruses were equal when measured in cell-free assays using either exogenous or endogenous templates. In addition, the abilities of these viruses to bind and enter cells were not significantly different. Together, these data suggest that Nef optimizes postentry events that are required for efficient synthesis of viral DNA. To determine if these effects were related to the property of Nef-mediated downregulation of CD4, growth curves of these viruses were determined using cells that express a CD4 molecule unable to respond to Nef. nef-defective virus remained attenuated in these cells, indicating that Nef-mediated downregulation of CD4 is not required for Nef-mediated enhancement of viral propagation in vitro.