Background

HIV infection induces chronic immune activation which is associated with accelerated disease progression; the causes of this activation, however, are incompletely understood. We investigated the activation status of CD4+ T cells specific for chronic herpes viruses and the non-persistent antigen tetanus toxoid (TT) in HIV positive and HIV negative donors to assess whether persistent infections contribute to chronic CD4+ T cell activation.

Methods

Untreated HIV+ patients and healthy, aged matched controls were recruited and activation levels assessed and compared between cells specific for persistent and non-persistent antigens. Activation levels on antigen-specific CD4+ T cells were measured by intracellular cytokine staining following in vitro stimulation with various recall antigens (CMV, EBV, HSV, VZV and TT) in conjunction with cell surface phenotyping.

Results

Activation levels of herpes virus-specific CD4+ T cell populations, assessed by co-expression of CD38 and HLA-DR, were significantly elevated in HIV+ individuals compared to normal controls and compared to TT-specific responses. In contrast, we found similar levels of activation of TT-specific CD4+ T cells in HIV+ and HIV- donors.

Conclusions

These results show a disparate distribution of immune activation within CD4+ T cell populations depending on their specificity and suggest that the elevated level of immune activation that characterizes chronic HIV infection may be influenced by the persistence of other antigens.

Background

Opt-out HIV testing is offered at 70% of antenatal care (ANC) clinics in Mozambique through the prevention of mother-to-child transmission (PMTCT) program. If routine data from this program were of sufficient quality, their heightened coverage and continuous availability could complement or even replace biannual sentinel serosurveys that currently serve as the primary HIV surveillance system in Mozambique.

Methods

We assessed the efficacy of routine HIV testing data from prevention of mother-to-child transmission programs for estimating the prevalence of HIV infection among pregnant women. The PMTCT program uses sequential point-of-care rapid tests conducted on site while ANC surveillance surveys use dried blood spots tested sequentially for HIV-1/2 antibodies at a central laboratory. We compared matched routine PMTCT and ANC surveillance test results collected during 2007 and 2009 ANC surveillance surveys from 36 sentinel sites.

Results

After excluding 659 women without PMTCT data, including 83 who refused rapid testing, test results from a total of 20,563 women were available. Pooling the data from both years indicated HIV prevalence from routine PMTCT testing was 14.4% versus 15.2% from surveillance testing (relative difference -5.1%; absolute difference -0.78%). Positive percent agreement (PPA) of PMTCT versus surveillance tests was 88.5% (95% Confidence Interval [CI]: 85.7-91.3%), with 19 sites having PPA below 90%; Negative percent agreement (NPA) was 98.9% (CI: 98.5-99.2%). No significant difference was found among three regions (North, Center and South), however both PPA and NPA were significantly higher in 2009 than 2007 (p < 0.05).

Conclusions

We found low PPA of PMTCT test results compared to surveillance data which is indicative either of testing errors or data reporting problems. Nonetheless, PPA improved significantly from 2007 to 2009, a possible positive trend that should be investigated further. Although use of PMTCT test results would not dramatically change HIV prevalence estimates among pregnant women, the impact of site-level differences on surveillance models should be evaluated before these data are used to replace or complement ANC surveillance surveys.

Background

Human babesiosis is a rare tick-borne infectious disease. The clinical presentation ranges from an asymptomatic form to a life threatening infection with severe hemolysis. Human babesiosis due to Babesia microti is the most common and is endemic in North America.

Case presentation

We report a European patient with severe pancytopenia and reactive hemophagocytosis related to a Babesia microti infection. Babesia infection was acquired during a travel in the USA.

Conclusion

Babesiosis should be considered in patients who traveled in endemic areas, especially North America for the most common agent Babesia microti.

Backgrounds

Staff in the hospital itself may be the source of a nosocomial outbreak (NO). But the role of undetected carriers as an outbreak source is yet unknown.

Methods

A systematic review was conducted to evaluate outbreaks caused by health care workers (HCW). The Worldwide Outbreak Database and PubMed served as primary sources of data. Articles in English, German or French were included. Other reviews were excluded. There were no restrictions with respect to the date of publication.

Data on setting, pathogens, route of transmission, and characteristics of the HCW was retrieved. Data from large outbreaks were compared to smaller outbreaks.

Results

152 outbreaks were included, mainly from surgery, neonatology, and gynecology departments. Most frequent corresponding infections were surgical site infections, infection by hepatitis B virus, and septicemia. Hepatitis B virus (27 NO), S. aureus (49 NO) and S. pyogenes (19 NO) were the predominant pathogens involved. 59 outbreaks (41.5%) derived from physicians and 56 outbreaks (39.4%) derived from nurses. Transmission mainly occurred via direct contact. Surgical and pediatric departments were significantly associated with smaller outbreaks, and gynecology with larger outbreaks. Awareness of carrier status significantly decreased the risk of causing large outbreaks.

Conclusions

As NO caused by HCW represent a rare event, screening of personnel should not be performed regularly. However, if certain species of microorganisms are involved, the possibility of a carrier should be taken into account.

Background

Deep eosinophilic granulomatous abscesses, as distinguished from eosinophilic subcutaneous abscesses, are rare. Most reports are from the Far-East and India where the most commonly attributed cause is Toxocara. Sulaimaniyah in Northeastern Iraq has experienced an outbreak of eosinophilic granulomatous liver and gastrointestinal (GI) abscesses beginning in 2009. The purpose of this study was to determine the etiology and guide treatment.

Methods

The study was an ongoing investigation of patients having a histopathologic diagnosis of eosinophilic granulomatous abdominal abscesses in Sulaimaniyah hospitals from May 2009 to August 2012. Tissues were examined for organisms, and Enzyme Linked Immunoabsorbent Assays (ELISA) were performed for serum antibodies to Fasciola hepatica, Toxocara, and Echinococcus granulosus.

Results

Fourteen patients had granulomatous inflammation surrounding a central necrotizing eosinophilic exudate identified in surgical pathology specimens from abdominal surgeries. Two children and four adults had abscesses that formed GI masses. These patients included a 39 year old male with oropharyngeal and transverse colon disease, and a 48 year old male with liver and GI abscesses. All sites demonstrated a Zygomycete fungus surrounded by eosinophilic Splendori-Hoeppli material consistent with basidiobolomycosis. Five of the six patients with fungal disease were treated by surgery and 4 to 7 months of itraconozol. One child died of intestinal perforation while receiving IV amphotericin B; two adults required additional surgery for recurrent GI obstruction. Eight patients had isolated liver abscesses with no organisms identified by histopathology: ELISA results for F. hepatica were positive for five, borderline for one, and negative for two patients. These eight patients were treated for fascioliasis by surgical resection of localized abscesses and albendazol. One patient serologically positive for F. Hepatica was found to have a common duct fluke two years after initial diagnosis. Serological testing for Toxocara and Echinococcus granulosus was negative in all 14 patients.

Conclusions

Basidiobolomycosis and F. hepatica are implicated as the cause of abdominal eosinophilic granulomatous abscesses in 12 of 14 patients identified over a period of 40 months in northern Iraq. Treatment was complicated by chronic biliary tract disease in fascioliasis and perforation and recurrent intestinal obstruction with basidiobolomycosis.

Background

Community Acquired Pneumonia (CAP) is a commonly encountered disease, one third of which is Severe Community Acquired Pneumonia (SCAP) that can be potentially fatal. There is a paucity of data on etiology and outcome of patients with SCAP in South Asian Population.

Methods

A retrospective cross-sectional study was conducted from March 2002 till December 2008 on patients of 16 years and above who were admitted with the diagnosis of SCAP in accordance to the criteria of American Thoracic Society Guidelines (2001). The patients underwent clinical and diagnostic evaluations to detect the severity of illness as well as the etiology and other risk factors influencing the eventual outcome of SCAP.

Results

A total of 189 patients were included in the study. The mean age was 60 ± 18.0 years and 110 (58%) patients were males. The most common isolated pathogens were Staphylococcus aureus (15 patients), Streptococcus pneumoniae (14 patients) and Pseudomonas aeruginosa (9 patients). The highest mortality was seen in patients with Pseudomonas aeruginosa (89%) and Staphylococcus aureus (53%). Overall mortality rate was 51%. On univariate analysis, septic shock (p <0.001), prior antibiotic use (p = 0.04), blood urea nitrogen > 30 mg/dl (p = 0.03), hematocrit < 30% (p = 0.03) and Acute Physiology and Chronic Health Evaluation (APACHE) II score > 20 (p < 0.001) were significantly different between the patients who survived as compared to those who did not. On multivariate analysis, septic shock (p <0.001, OR: 4.70; 95% CI= 2.49-8.87) was found to be independently associated with mortality.

Conclusion

The microbes causing SCAP in our study are different from the usual spectrum. Staphylococcus aureus and Pseudomonas aeruginosa were the common causative pathogens and associated with high mortality. It is important to establish clinical guidelines for managing SCAP according to the etiologic organisms in our setting.

Background

Many HIV patients receiving antiretroviral treatment develop lipodystrophy. NEW-FILL® is a polylactic acid injected to treat facial lipoatrophy. The objectives of this study were to describe (1) change in quality of life (QoL) of HIV patients treated with NEW-FILL® in the management of facial lipoatrophy; (2) efficacy of NEW-FILL® using facial photographs and (3) a patient-reported “Overall Treatment Effect” (OTE) scale; and (4) safety of NEW-FILL®.

Methods

Doctors from 13 treatment centres recruited 230 HIV patients to receive up to 5 sessions of NEW-FILL® injections. Patients self-reported QoL with the ABCD questionnaire before the first set of injections, at 2 months and at 12 to 18 months after the last session of injections. Efficacy was evaluated at each interval through photographs and OTE scale. Safety was evaluated via Case Report Form (CRF) data.

Results

64.4% of patients reported QoL improvements of >10% at 2 months, and 58.8% at 12–18 months. Lipoatrophy grades improved at each visit (“no lipoatrophy” or “limited lipoatrophy”: 20.3% at inclusion, 77.4% at 2 months, 58.4% at 12–18 months). Average OTE scores of 5.3 and 5.0 at 2 and 12–18 months indicated “moderate improvement”. Minimum Important Difference (MID) in QoL score was 7.1 points at 2 months; 7.4 points at 12–18 months. For 911 injection sessions performed, 3.4% resulted in “immediate” adverse events, 7% in “non-immediate” events, and 1.7% in “other” events.

Conclusions

Improvements to quality of life and diminished lipoatrophy visibility were observed in the months immediately following NEW-FILL® treatment and were maintained 12–18 months post-treatment. Most adverse events were mild and transient. ABCD MID thresholds provide clinicians with means to assess the impact of lipoatrophy therapies on QoL.

Background

Recent studies suggest HIV-1 inter-subtype differences in co-receptor usage. We examined the correlation between HIV-1 subtype and co-receptor usage among treatment-naïve HIV-1 subjects in Singapore. Additionally, we investigated whether the subtype co-receptor association was influenced by stage of infection.

Methods

V3 sequences of HIV-1 envelope protein gp120 were obtained from 110 HIV treatment-naïve patients and genotypic co-receptor tropism determination was performed using Geno2pheno. Two false-positive rate (FPR) cut-offs, 10% and 5.75% were selected for tropism testing.

Results

Subtype assignment of viral strains from 110 HIV-infected individuals based on partial sequencing of HIV-1 pol, gp120 and gp41 were as follows: 27 subtype B, 64 CRF01_AE, 10 CRF51_01B, and 9 other subtypes. At FPR=10%, 10 (100%) CRF51_01B-infected subjects and 26 (40.6%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 7 (25.9%) subtype B subjects and 1 (11.1%) CRF33_01B-infected subject (P < 0.001). At FPR=5.75%, 10 (100%) CRF51_01B-infected subjects and 20 (31.3%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 4 (14.8%) subtype B and 1 (11.1%) CRF33_01B-infected subjects (P < 0.001). Among those with evidence of seroconversion within 2 years prior to study enrolment, 100% of CRF51_01B-infected subjects had CXCR4-using virus, independent of Geno2pheno FPR.

Conclusion

CRF51_01B and CRF01_AE-infected individuals have higher prevalence of CXCR4-usage compared to subtype B infected individuals. Further studies examining these differences could help optimise the use of CCR5-antagonist in populations with these subtypes, and increase our understanding of HIV-1 biology.

Background

Bloodstream infections in neonates and infants are life-threatening emergencies. Identification of the common bacteria causing such infections and their susceptibility patterns will provide necessary information for timely intervention. This study is aimed at determining the susceptibilities of bacterial etiological agents to commonly-used antimicrobial agents for empirical treatment of suspected bacterial septicaemia in children.

Methods

This is a hospital based retrospective analysis of blood cultures from infants to children up to 14 years of age with preliminary diagnosis of sepsis and admitted to the Neonatal Intensive Care Unit (NICU) and Paediatric Wards of the Teaching Hospital Tamale from July 2011 to January 2012.

Results

Out of 331 blood specimens cultured, the prevalence of confirmed bacterial sepsis was 25.9% (86/331). Point prevalence for confirmed cases from NICU was 44.4% (28/63) and 21.6% (58/268) from the Paediatric ward. Gram positive cocci (GPC) were the predominant isolates with Coagulase positive (32.2%) and Coagulase-negative (28.7%) Staphylococci accounting for 60.9% of the total isolates. Gram negative rods (GNR) comprised 39.1% of all isolates with Klebsiella, E.coli and Salmonella being the most common organisms isolated. Klebsiella was the most frequent GNR from the NICU and Salmonella typhi was predominantly isolated from the paediatric ward. Acinetobacter showed 100.0% susceptibility to Ceftriaxone and Cefotaxime but was resistant (100.0%) to Ampicillin, Tetracycline and Cotrimoxazole. Escherichia coli and Klebsiella were 80.0% and 91.0% susceptible to Ceftriaxone and Cefotaxime respectively. Klebsiella species showed 8.3% susceptibility to Tetracycline but was resistant to Ampicillin and Cotrimoxazole. Escherichia coli showed 40.0% susceptibility to Ampicillin, Chloramphenicol and Cotrimoxazole; 20.0% susceptibility to Tetracycline and 80.0% susceptible to Gentamicin and Cefuroxime. Coagulase negative Staphylococci was susceptible to Gentamicin (72.0%) but Coagulase positive Staphylococci showed intermediate sensitivity to Gentamicin (42.9%).

Conclusion

Coagulase Negative, Coagulase Positive Staphylococci, Salmonella and Klebsiella were the aetiological agents of bloodstream infection among children at TTH. While gram-positive and gram-negative bacteria showed low susceptibility to Ampicillin, Tetracycline and Cotrimoxazole, the GNR were susceptible to Gentamicin and third-generation cephalosporins.

Background

Smear microscopy, a mainstay of tuberculosis (TB) diagnosis in developing countries, cannot differentiate M. tuberculosis complex from NTM infection, while pulmonary TB shares clinical signs with NTM disease, causing clinical and diagnostic dilemmas. This study used molecular assays to identify species and assess genotypic diversity of non-tuberculous mycobacteria (NTM) isolates from children investigated for pulmonary tuberculosis at a demographic surveillance site in rural eastern Uganda.

Methods

Children were investigated for pulmonary tuberculosis as part of a TB vaccine surveillance program (2009–2011). Two cohorts of 2500 BCG vaccinated infants and 7000 adolescents (12–18 years) were recruited and followed up for one to two years to determine incidence of tuberculosis. Induced sputum and gastric aspirates were processed by the standard N-acetyl L-cysteine (NALC)-NaOH method. Sediments were cultured in the automated MGIT (Becton Dickson) liquid culture system and incubated at 37°C for at least six weeks. Capilia TB assay was used to classify mycobacteria into MTC and NTM. The GenoType CM/AS assays were performed to identify species while Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR genotyping was used to assess genetic diversity of the strains within each species.

Results

Among 2859 infants and 2988 adolescents screened, the numbers of TB suspects were 710 and 1490 infants and adolescents respectively. The prevalence of NTM in infant suspects was 3.7% (26/710) (95% CI 2.5–5.2) while that in adolescent suspects was 4.6% (69/1490) (95% CI 3.6–5.8). On culture, 127 isolates were obtained, 103 of which were confirmed as mycobacteria comprising of 95 NTM and eight M. tuberculosis complex. The Genotype CM/AS assay identified 63 of the 95 NTM isolates while 32 remained un-identified. The identified NTM species were M. fortuitum (40 isolates, 63.5%), M. szulgai (9 isolates, 14.3%), M. gordonae (6 isolates, 9.5%), M. intracellulare (3 isolates, 4.7%), M. scrofulaceum (2 isolates, 3.2%), M. lentiflavum (2 isolates, 3.2%), and M. peregrinum (1 isolate, 1.6%). Genotyping did not reveal any clustering in M. intracellulare, M. gordonae and M. szulgai species. M. fortuitum, on the other hand, had two clusters, one with three isolates of M. fortuitum 1 and the other with two isolates of M. fortuitum 2 subspecies. The remaining 35 of the 40 isolates of M. fortuitum had unique fingerprint patterns.

Conclusion

M. fortuitum is the most common cause of infection by NTM among Infants and adolescents in rural Uganda. There is a varied number of species and genotypes, with minimal clustering within species, suggesting ubiquitous sources of infection to individuals in this community.

Background

Q fever caused by Coxiella burnetii is transmitted to humans by inhalation of aerosols from animal birth products. Q fever in pregnancy is suspected to be a potential cause of fetal and maternal morbidity and fetal mortality but the pathogenesis is poorly understood, and even in Q fever endemic areas, the magnitude of a potential association is not established.

We aimed to examine if presence of antibodies to C. burnetii during pregnancy or seroconversion were associated with adverse pregnancy outcomes.

Methods

The Danish National Birth Cohort collected blood samples and interview data from 100,418 pregnant women (1996–2002). We sampled 397 pregnant women with occupational or domestic exposure to cattle or sheep and a random sample of 459 women with no animal exposure. Outcome measures were spontaneous abortion, preterm birth, birth weight and Small for Gestational Age (SGA).

Blood samples collected in pregnancy were screened for antibodies against C. burnetii by enzyme-linked immunosorbent assay (ELISA). Samples positive for IgG or IgM antibodies in the ELISA were confirmed by immunofluorescence antibody test (IFA).

Results

Among the 856 women, 169 (19.7%) women were IFA positive; 147 (87%) of these had occupational or domestic contact with livestock (IFA cutoff > =1:128).

Two abortions were IFA positive vs. 6 IFA negative (OR: 1.5; 95%CI: 0.3-7.6). Three preterm births were IFA positive vs. 38 IFA negative (OR: 0.4; 95% CI: 0.1-1.1). There was a significant difference in birth weight of 168 g (95% CI: 70-267 g) with IFA positive being heavier, and the risk of being SGA was not increased in the newborns of IFA positive women (OR: 0.4; 95%CI: 0.8-1.0).

Most seropositive women were IgG positive indicating previous exposure. Seroconversion during pregnancy was found in 10 women; they all delivered live babies at term, but two were SGA.

Conclusion

We found no increased risk of adverse pregnancy outcome in women with verified exposure to C. burnetii.

To our knowledge, this is the first population-based seroepidemiologic study evaluating pregnancy outcome in women with serologically verified exposure to C. burnetii against a comparable reference group of seronegative women.

Background

Burkholderia mallei and B. pseudomallei are two closely related species of highly virulent bacteria that can be difficult to detect. Pathogenic Burkholderia are endemic in many regions worldwide and cases of infection, sometimes brought by travelers from unsuspected regions, also occur elsewhere. Rapid, sensitive methods for identification of B. mallei and B. pseudomallei are urgently needed in the interests of patient treatment and epidemiological surveillance.

Methods

Signature sequences for sensitive, specific detection of pathogenic Burkholderia based on published genomes were identified and a qPCR assay was designed and validated.

Results

A single-reaction quadruplex qPCR assay for the detection of pathogenic Burkholderia, which includes a marker for internal control of DNA extraction and amplification, was developed. The assay permits differentiation of B. mallei and B. pseudomallei strains, and probit analysis showed a very low detection limit. Use of a multicopy signature sequence permits detection of less than 1 genome equivalent per reaction.

Conclusions

The new assay permits rapid detection of pathogenic Burkholderia and combines enhanced sensitivity, species differentiation, and inclusion of an internal control for both DNA extraction and PCR amplification.

Background

With declining vectorial transmission, Chagas disease predominantly affects adults nowadays. The efficacy of nifurtimox in the chronic phase in adult patients is poorly known, particularly in regions where there is no risk of reinfection. Recommendations for treatment outcome assessment rely on serological follow-up. We evaluated the serological and parasitological response to nifurtimox in a cohort of adult patients three years post-treatment in Switzerland.

Methods

Patients treated with nifurtimox in 2008 during a cross-sectional study in Geneva, Switzerland, were contacted for follow-up in 2011. Two ELISAs and a rapid immunochromatographic test were used to test 2008 and 2011 serum samples simultaneously. In addition, conventional and real-time PCR were performed on 2011 samples.

Results

Thirty-seven (84.1%) of 44 eligible patients, predominantly female, middle-aged, Bolivians at the indeterminate stage, were enrolled. All 2011 ELISA and immunochromatographic tests were positive. Twenty-eight (75.7%) patients presented a lower optical density (OD) in 2011 compared to 2008. This OD difference was significant in both commercial (P < 0.001) and in-house (P = 0.002) ELISAs. Agreement between the two ELISAs was low (Kappa = 0.469). All patients had negative conventional PCR results but one (2.7%) was positive with real-time PCR.

Conclusion

Our results highlight the inadequacy of serology for assessing response in adults, three years after treatment. In our cohort, 97.3% had results that could either indicate treatment failure or persistant humoral response despite treatment. The lack of accurate early post-treatment tests of cure prevents appropriate patients information and councelling. New follow-up tests are needed to assess treatments efficacy given the large adult population in need of antiparasitic therapy.

Background

Seroreactivity, processes of seroconversion and seroreversion, in the context of HPV infection has been investigated in numerous studies. However, the data resulting from these studies are usually not accounted for in mathematical transmission models of various HPV types due to gaps in our understanding of the nature of seroreactivity and its implications for HPV natural history.

Methods

In this study we selected a number of simple but plausible compartmental transmission models of HPV-16, differing in assumptions regarding the relation between seropositivity and immunity, and attempted to calibrate them to Australian HPV seroprevalence data for females and males, as well as DNA prevalence data for females, using a Bayesian model comparison procedure. We ranked the models according to both their simplicity and ability to be fitted to the data.

Results

Our results demonstrate that models with seroreversion where seropositivity indicates only a partial or very short-term full protection against re-infection generate age-specific HPV DNA prevalence most consistent with the observed data when compared with other models.

Conclusions

Models supporting the notion that seropositive individuals are fully immune to reinfection demonstrated consistently inferior fits to the data than other models making no such assumption.

Background

The chronic use of antifungal agents in the treatment of fungal infection in general and oropharyngeal candidiasis mainly in AIDS patient’s leads to the selection of strain resistant to these therapies and a shift in the spectrum of Candida species. This study determines the species diversity and in vitro susceptibility of Candida isolates from late presenting AIDS patients in northwest Ethiopia.

Methods

Two hundred and twenty one HIV/AIDS patients were assessed with a standardized evaluation form at enrolment. Oral rinses were cultured on CHROMagar plates at 37°C for 48 hours and Candida species identification were made following standard microbiological techniques. In vitro drug susceptibility tests were made using broth microdilution method.

Results

The colonization rate of Candida species was found to be 82.3% (177/215). C. albicans was the predominant species isolated from 139 (81%) patients but there was a diversity of other species. C. glabrata was the most frequent non-albicans species isolated in 22.5% (40/177) of the patients followed by C. tropicalis 14.1% (27/177), C. krusei 5.6% (10) and other unidentifiable Candida species 4% (7/177). Recurrent episodes of oropharyngeal candidiasis and previous exposure to antifungal drugs were found to be predisposing factors for colonization by non-albicans species. Irrespective of the Candida species identified 12.2% (11/90), 7.7% (7/90) and 4.7% (4) of the isolates were resistant to fluconazole, ketoconazole and itraconazole, respectively. In contrast, resistance to micafungin, amphotericin B and 5-Fluorocytosine was infrequent.

Conclusion

HIV/AIDS patients are orally colonized by single or multiple albicans and non- albicans Candida species that are frequently resistant to azoles and occasionally to amphotericin B, 5-Fluorocytosine and micafungin. These highlight the need for national surveillance for examining Candida epidemiology and resistance to antifungal drugs.

Background

Healthcare-associated infections caused by Klebsiella pneumoniae isolates are increasing and few effective antibiotics are currently available to treat patients. We observed decreased carbapenem susceptibility among K. pneumoniae isolated from patients at a tertiary private hospital that showed a phenotype compatible with carbapenemase production although this group of enzymes was not detected in any sample. The aim of this study was to describe the epidemiology and clinical outcomes associated with carbapenem-resistant K. pneumoniae and to determine the antimicrobial resistance mechanisms.

Methods

Risk factors associated with carbapenem-resistant K. pneumoniae infections were investigated by a matched case–control study from January 2006 through August 2008. A cohort study was also performed to evaluate the association between carbapenem resistance and in-hospital mortality. Bacterial identification and antimicrobial susceptibility were determined by Vitek 2 and Etest. Carbapenemase activity was detected using spectrophotometric assays. Production of beta-lactamases and alterations in genes encoding K. pneumoniae outer membrane proteins, OmpK35 and OmpK36, were analyzed by PCR and DNA sequencing, as well as SDS-Page. Genetic relatedness of carbapenem resistant isolates was evaluated by Pulsed Field Gel Electrophoresis.

Results

Sixty patients were included (20 cases and 40 controls) in the study. Mortality was higher for patients with carbapenem-resistant K. pneumoniae infections compared with those with carbapenem-susceptible K. pneumoniae (50.0% vs 25.7%). The length of central venous catheter use was independently associated with carbapenem resistance in the multivariable analysis. All strains, except one, carried blaCTX-M-2, an extended-spectrum betalactamase gene. In addition, a single isolate also possessed blaGES-1. Genes encoding plasmid-mediated AmpC beta-lactamases or carbapenemases (KPC, metallo-betalactamases or OXA-carbapenemases) were not detected.

Conclusions

The K. pneumoniae multidrug-resistant organisms were associated with significant mortality. The mechanisms associated with decreased K. pneumoniae carbapenem susceptibility were likely due to the presence of cephalosporinases coupled with porin alterations, which resulted from the presence of the insertion sequences in the outer membrane encoding genes.

Background

The prevalence of hyperglycemia among HIV-infected persons who are not receiving antiretroviral therapy is unknown. We conducted a cross-sectional survey to estimate the prevalence of hyperglycemia among Chinese adults with newly diagnosed HIV/AIDS.

Methods

Two thousand and six newly diagnosed HIV/AIDS patients from 10 provinces and municipalities in China were selected during 2009 to 2010. After an overnight fast, serum samples were collected to measure glucose concentrations. Demographics and medical histories were recorded. Factors associated with the presence of diabetes were analysed by logistic regression.

Results

Among the 2006 patients, 75.67% were male. Median age was 40 years (range: 18–86 years). 19.99% had hyperglycemia, 9.47% had impaired fasting glucose (IFG) and 10.52% had diabetes. The prevalences of hyperglycemia, of IFG and of diabetes were 21.54%, 10.28% and 11.27% among men and 15.16%, 6.97% and 8.20% among women, respectively. The prevalence of diabetes increased with increasing age (7.00%, 13.36% and 21.21% among patients who were 18–40, 40–60, and ≥60 years of age respectively) and with decreasing CD4 count (6.74%, 8.45%, 9.69%, and 12.66% among patients with CD4 count of ≥350, 200–350, 50–200, and < 50/mm3 respectively). The prevalence of diabetes was higher among ethnic minority patients than among the Han patients (14.37% versus 9.24%). The logistic analysis showed that older age, lower CD4 count and minority ethnicity were significantly associated with an increased risk of diabetes.

Conclusions

Hyperglycemia is highly prevalent among Chinese adults with newly diagnosed HIV/AIDS. Older age, lower CD4 count and minority ethnicity are associated with increased risk of diabetes. All newly diagnosed HIV/AIDS individuals should be routinely evaluated for hyperglycemia.

Background

Dengue is an acute febrile illness caused by an arbovirus that is endemic in more than 100 countries. Early diagnosis and adequate management are critical to reduce mortality. This study aims to identify clinical and hematological features that could be useful to discriminate dengue from other febrile illnesses (OFI) up to the third day of disease.

Methods

We conducted a sectional diagnostic study with patients aged 12 years or older who reported fever lasting up to three days, without any evident focus of infection, attending an outpatient clinic in the city of Rio de Janeiro, Brazil, between the years 2005 and 2008. Logistic regression analysis was used to identify symptoms, physical signs, and hematological features valid for dengue diagnosis. Receiver-operating characteristic (ROC) curve analyses were used to define the best cut-off and to compare the accuracy of generated models with the World Health Organization (WHO) criteria for probable dengue.

Results

Based on serological tests and virus genome detection by polymerase chain reaction (PCR), 69 patients were classified as dengue and 73 as non-dengue. Among clinical features, conjunctival redness and history of rash were independent predictors of dengue infection. A model including clinical and laboratory features (conjunctival redness and leukocyte counts) achieved a sensitivity of 81% and specificity of 71% and showed greater accuracy than the WHO criteria for probable dengue.

Conclusions

We constructed a predictive model for early dengue diagnosis that was moderately accurate and performed better than the current WHO criteria for suspected dengue. Validation of this model in larger samples and in other sites should be attempted before it can be applied in endemic areas.

Background

Strongyloidiasis is commonly a clinically unapparent, chronic infection, but immuno suppressed subjects can develop fatal disease. We carried out a review of literature on hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), in order to describe the most challenging aspects of severe strongyloidiasis.

Methods

We conducted a structured search using PubMed to collect case reports and short case series on HS/DS published from 1991 to 2011. We restricted search to papers in English, Spanish, Italian and French. Case reports were classified as HS/DS according to given definitions.

Results

Records screened were 821, and 311 were excluded through titles and abstract evaluation. Of 510 full-text articles assessed for eligibility, 213 were included in qualitative analysis. As some of them were short case series, eventually the number of cases analyzed was 244.

Steroids represented the main trigger predisposing to HS and DS (67% cases): they were mostly administered to treat underlying conditions (e.g. lymphomas, rheumatic diseases). However, sometimes steroids were empirically prescribed to treat signs and symptoms caused by unsuspected/unrecognized strongyloidiasis. Diagnosis was obtained by microscopy examination in 100% cases, while serology was done in a few cases (6.5%). Only in 3/29 cases of solid organ/bone marrow transplantation there is mention of pre-transplant serological screening. Therapeutic regimens were different in terms of drugs selection and combination, administration route and duration. Similar fatality rate was observed between patients with DS (68.5%) and HS (60%).

Conclusions

Proper screening (which must include serology) is mandatory in high - risk patients, for instance candidates to immunosuppressive medications, currently or previously living in endemic countries. In some cases, presumptive treatment might be justified. Ivermectin is the gold standard for treatment, although the optimal dosage is not clearly defined in case of HS/DS.

Background

Evidence exists regarding the full prevention of HCV transmission to hemodialysis patients by implementing universal precaution. However, little information is available regarding the frequency with which hospitals have adopted evidence-based practices for preventing HCV infection among hemodialysis patients. A cross-sectional survey has been conducted among nurses in Calabria region (Italy) in order to acquire information about the level of knowledge, the attitudes and the frequencies of evidence-based practices that prevent hospital transmission of HCV.

Methods

All 37 hemodialysis units (HDU) of Calabria were included in the study and all nurses were invited to participate in the study and to fill in a self-administered questionnaire.

Results

90% of the nurses working in HDU participated in the study. Correct answers about HCV pattern of transmission ranged from 73.7% to 99.3% and were significantly higher in respondents who knew that isolation of HCV-infected patients is not recommended and among those who knew that previous bloodstream infections should be included in medical record and among nurses with fewer years of practice. Most correctly thought that evidence-based infection control measures provide adequate protection against transmission of bloodborne pathogens among healthcare workers. Positive attitude was significantly higher among more knowledgeable nurses. Self-reporting of appropriate handwashing procedures were significantly more likely in nurses who were aware that transmission of bloodborne pathogens among healthcare workers may be prevented through adoption of evidence-based practices and with a correct knowledge about HCV transmission patterns.

Conclusions

Behavior changes should be aimed at abandoning outdated practices and adopting and maintaining evidence-based practices. Initiatives focused at enabling and reinforcing adherence to effective prevention practices among nurses in HDU are strongly needed.

Background

Infection with HPV 16 and 18, the major causative agents of cervical cancer, can be prevented through vaccination with a bivalent or quadrivalent vaccine. Both vaccines provide cross-protection against HPV-types not included in the vaccines. In particular, the bivalent vaccine provides additional protection against HPV 31, 33, and 45 and the quadrivalent vaccine against HPV31. The quadrivalent vaccine additionally protects against low-risk HPV type 6 and 11, responsible for most cases of genital warts. In this study, we made an analytical comparison of the two vaccines in terms of cost-effectiveness including the additional benefits of cross-protection and protection against genital warts in comparison with a screening-only strategy.

Methods

We used a Markov model, simulating the progression from HPV infection to cervical cancer or genital warts. The model was used to estimate the difference in future costs and health effects of both HPV-vaccines separately.

Results

In a cohort of 100,000 women, use of the bivalent or quadrivalent vaccine (both at 50% vaccination coverage) reduces the cervical cancer incidence by 221 and 207 cases, corresponding to ICERs of €17,600/QALY and €18,900/QALY, respectively. It was estimated that the quadrivalent vaccine additionally prevents 4390 cases of genital warts, reducing the ICER to €16,300/QALY. Assuming a comparable willingness to pay for cancer and genital warts prevention, the difference in ICERs could justify a slightly higher price (~7% per dose) in favor of the quadrivalent vaccine.

Conclusions

Clearly, HPV vaccination has been implemented for the prevention of cervical cancer. From this perspective, use of the bivalent HPV vaccine appears to be most effective and cost-effective. Including the benefits of prevention against genital warts, the ICER of the quadrivalent HPV vaccine was found to be slightly more favourable. However, current decision-making on the introduction of HPV is driven by the primary cervical cancer outcome. New vaccine tenders could consider the benefits of cross-protection and the benefits of genital warts, which requires more balanced decision-making.

Background

Limited data suggest that fluorine-18 fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography combined with computed tomography (PET/CT) scan may be useful for diagnosing infections of the spine. Brucellar spondylodiskitis might be devastating and current imaging techniques lack sensitivity and specificity. The aim of this prospective study was to determine the role of F-18 FDG PET/CT scan in the diagnosis of brucellar spondylodiskitis and in monitoring the efficacy of its treatment.

Methods

Ten consecutive patients with brucellar spondylitis were prospectively evaluated with PET/CT. Baseline evaluation included also magnetic resonance imaging (MRI) of the affected spine, indices of inflammation, the slide agglutination test (SAT), and the standard hematology and biochemistry. All cases were treated with suitable antibiotics until resolution or significant improvement of clinical and radiological (MRI) findings. Upon completion of treatment, they were re-evaluated with follow-up PET/CT scan. The maximum standardized uptake values (SUV) were measured and compared with SAT.

Results

In all patients there was an increased F-18 FDG activity in the infected spine region detected by the initial MRI. F-18 FDG PET/CT provided additional information, compared to MRI, in 4 (40%) patients. More specifically it revealed additional spine lesions (in 3 patients), lymphadenitis, arthritis, organomegaly, as well as new paravertebral soft tissue involvement and epidural masses. This additional information had an impact on the duration of treatment in these patients. At the end of treatment all patients had a complete clinical response; 5 patients had positive serology, 6 patients had residual MRI findings, while 9 had a positive PET/CT but with significantly decreased FDG uptake compared to baseline (median 2.6, range 1.4 – 4.4 vs. median 5.5, range 2.8 – 9.4, p = 0.005). During the follow up period (median 12.5 months) no relapses have been observed. No significant association was observed between the SUV and SAT.

Conclusions

Our study suggests that in patients with brucellar spondylodiskitis F-18 FDG PET/CT scan can provide additional information on the spread of the infection, compared to MRI. Successful treatment is associated with a significant decrease in SUVmax values; thus, PET/CT scan may be a complementary method for determining the efficacy of treatment.

Background

Pre-vaccination information on HPV type-specific prevalence in target populations is essential for designing and monitoring immunization strategies for cervical cancer (CC) prevention. Data on HPV prevalence in Italy are available for women over the age of 24 years, target of the population-based CC screening programmes; while data of HPV prevalence in younger ages are very limited. The present study enrolled Italian women aged 18–26 years in order to assess the prevalence and distribution of high-risk (HR) HPV types. Risk-factors correlated with HR-HPV positivity were also described.

Methods

A sample of 2,289 women was randomly selected from the resident population lists of ten Local Health Units (LHUs) located in six Italian Regions scattered across the country; both rural and urban LHUs were involved. Women aged between 18 and 26 years and living in the selected LHUs were included in the study; pregnant women and women who did not speak Italian were excluded. A total of 1,102 women met the inclusion criteria and agreed to participate. Participants were offered pap test and Hybrid-Capture 2 (HC2) test for HR-HPV types and genotyping was performed on positive smears.

Results

Out of 1,094 valid samples, 205 (18.7%) were HR-HPV positive. Women with 2–4 (ORadj = 4.15, 95%CI: 2.56-6.72) and ≥5 lifetime partners (ORadj = 10.63, 95%CI: 6.16-18.36) and women who have used any contraceptive in the last six months (ORadj = 1.67, 95%CI: 1.09-2.54) had a higher risk to be infected; women living with their partner had a lower risk (ORadj = 0.56, 95%CI: 0.34-0.92) to acquire infection than women living with parents/friends/alone. Among HC2 positive women, HPV16 was the most prevalent type (30.9%), followed by 31 (19.6%), 66 (12.9%), 51 (11.3%), 18 (8.8%), 56 (8.8%). Co-infections of HR-HC2 targeted types were found in 20.4% of positive samples. The HR-HPV prevalence in women with abnormal cytology (52.4%) was significantly higher than in women with normal cytology (14.6%); however 33.0% of HR-HPV infected women had an abnormal cytology.

Conclusion

HR-HPV prevalence in Italian women aged 18–26 years was 19%, higher than what detected for older women, by other studies using the same molecular method and laboratory network; this result supports the choice of electing girls before the sexual debut as the primary target of HPV vaccination. The HPV type distribution found in this study may represent a baseline picture; an accurate post-vaccine surveillance is necessary to early detect a possible genotype replacement. The high prevalence of viral types other than vaccine-HPV types supports the necessity to guarantee the progression of CC screening programmes in vaccinated women.

Background

Ineffective communication of infection control requirements during transitions of care is a potential cause of non-compliance with infection control precautions by healthcare personnel. In this study, interventions to enhance communication during inpatient transfers between wards and radiology were implemented, in the attempt to improve adherence to precautions during transfers.

Methods

Two interventions were implemented, comprising (i) a pre-transfer checklist used by radiology porters to confirm a patient’s infectious status; (ii) a coloured cue to highlight written infectious status information in the transfer form. The effectiveness of the interventions in promoting adherence to standard precautions by radiology porters when transporting infectious patients was evaluated using a randomised crossover trial at a teaching hospital in Australia.

Results

300 transfers were observed over a period of 4 months. Compliance with infection control precautions in the intervention groups was significantly improved relative to the control group (p < 0.01). Adherence rate in the control group was 38%. Applying the coloured cue resulted in a compliance rate of 73%. The pre-transfer checklist intervention achieved a comparable compliance rate of 71%. When both interventions were applied, a compliance rate of 74% was attained. Acceptability of the coloured cue was high, but adherence to the checklist was low (40%).

Conclusions

Simple measures to enhance communication through the provision of a checklist and the use a coloured cue brought about significant improvement in compliance with infection control precautions by transport personnel during inpatient transfers. The study underscores the importance of effective communication in ensuring compliance with infection control precautions during transitions of care.

Background

Low absolute humidity (AH) has been associated with increased influenza virus survival and transmissibility and the onset of seasonal influenza outbreaks. Humidification of indoor environments may mitigate viral transmission and may be an important control strategy, particularly in schools where viral transmission is common and contributes to the spread of influenza in communities. However, the variability and predictors of AH in the indoor school environment and the feasibility of classroom humidification to levels that could decrease viral survival have not been studied.

Methods

Automated sensors were used to measure temperature, humidity and CO2 levels in two Minnesota grade schools without central humidification during two successive winters. Outdoor AH measurements were derived from the North American Land Data Assimilation System. Variability in indoor AH within classrooms, between classrooms in the same school, and between schools was assessed using concordance correlation coefficients (CCC). Predictors of indoor AH were examined using time-series Auto-Regressive Conditional Heteroskedasticity models. Classroom humidifiers were used when school was not in session to assess the feasibility of increasing indoor AH to levels associated with decreased influenza virus survival, as projected from previously published animal experiments.

Results

AH varied little within classrooms (CCC >0.90) but was more variable between classrooms in the same school (CCC 0.81 for School 1, 0.88 for School 2) and between schools (CCC 0.81). Indoor AH varied widely during the winter (range 2.60 to 10.34 millibars [mb]) and was strongly associated with changes in outdoor AH (p < 0.001). Changes in indoor AH on school weekdays were strongly associated with CO2 levels (p < 0.001). Over 4 hours, classroom humidifiers increased indoor AH by 4 mb, an increase sufficient to decrease projected 1-hour virus survival by an absolute value of 30% during winter months.

Conclusions

During winter, indoor AH in non-humidified grade schools varies substantially and often to levels that are very low. Indoor results are predicted by outdoor AH over a season and CO2 levels (which likely reflects human activity) during individual school days. Classroom humidification may be a feasible approach to increase indoor AH to levels that may decrease influenza virus survival and transmission.