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1.  Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008 
BMC Infectious Diseases  2011;11:233.
Background
Data on complications in children with seasonal influenza virus infection are limited. We initiated a nation-wide three-year surveillance of children who were admitted to a paediatric intensive care unit (PICU) with severe seasonal influenza.
Methods
From October 2005 to July 2008, active surveillance was performed using an established reporting system for rare diseases (ESPED) including all paediatric hospitals in Germany. Cases to be reported were hospitalized children < 17 years of age with laboratory-confirmed influenza treated in a PICU or dying in hospital.
Results
Twenty severe influenza-associated cases were reported from 14 PICUs during three pre-pandemic influenza seasons (2005-2008). The median age of the patients (12 males/8 females) was 7.5 years (range 0.1-15 years). None had received vaccination against influenza. In 14 (70%) patients, the infection had been caused by influenza A and in five (25%) by influenza B; in one child (5%) the influenza type was not reported. Patients spent a median of 19 (IQR 12-38) days in the hospital and a median of 11 days (IQR 6-18 days) in the PICU; 10 (50%) needed mechanical ventilation. Most frequent diagnoses were influenza-associated pneumonia (60%), bronchitis/bronchiolitis (30%), encephalitis/encephalopathy (25%), secondary bacterial pneumonia (25%), and ARDS (25%). Eleven (55%) children had chronic underlying medical conditions, including 8 (40%) with chronic pulmonary diseases. Two influenza A- associated deaths were reported: i) an 8-year old boy with pneumococcal encephalopathy following influenza infection died from cerebral edema, ii) a 14-year-old boy with asthma bronchiale, cardiac malformation and Addison's disease died from cardiac and respiratory failure. For nine (45%) patients, possibly permanent sequelae were reported (3 neurological, 3 pulmonary, 3 other sequelae).
Conclusions
Influenza-associated pneumonia and secondary bacterial infections are relevant complications of seasonal influenza in Germany. The incidence of severe influenza cases in PICUs was relatively low. This may be either due to the weak to moderate seasonal influenza activity during the years 2005 to 2008 or due to under-diagnosis of influenza by physicians. Fifty% of the observed severe cases might have been prevented by following the recommendations for vaccination of risk groups in Germany.
doi:10.1186/1471-2334-11-233
PMCID: PMC3175218  PMID: 21880125
2.  Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study 
Background
Bloodstream infection is a common cause of hospitalization, morbidity and death in children. The impact of antimicrobial resistance and HIV infection on outcome is not firmly established.
Methods
We assessed the incidence of bloodstream infection and risk factors for fatal outcome in a prospective cohort study of 1828 consecutive admissions of children aged zero to seven years with signs of systemic infection. Blood was obtained for culture, malaria microscopy, HIV antibody test and, when necessary, HIV PCR. We recorded data on clinical features, underlying diseases, antimicrobial drug use and patients' outcome.
Results
The incidence of laboratory-confirmed bloodstream infection was 13.9% (255/1828) of admissions, despite two thirds of the study population having received antimicrobial therapy prior to blood culture. The most frequent isolates were klebsiella, salmonellae, Escherichia coli, enterococci and Staphylococcus aureus. Furthermore, 21.6% had malaria and 16.8% HIV infection. One third (34.9%) of the children with laboratory-confirmed bloodstream infection died. The mortality rate from Gram-negative bloodstream infection (43.5%) was more than double that of malaria (20.2%) and Gram-positive bloodstream infection (16.7%). Significant risk factors for death by logistic regression modeling were inappropriate treatment due to antimicrobial resistance, HIV infection, other underlying infectious diseases, malnutrition and bloodstream infection caused by Enterobacteriaceae, other Gram-negatives and candida.
Conclusion
Bloodstream infection was less common than malaria, but caused more deaths. The frequent use of antimicrobials prior to blood culture may have hampered the detection of organisms susceptible to commonly used antimicrobials, including pneumococci, and thus the study probably underestimates the incidence of bloodstream infection. The finding that antimicrobial resistance, HIV-infection and malnutrition predict fatal outcome calls for renewed efforts to curb the further emergence of resistance, improve HIV care and nutrition for children.
doi:10.1186/1471-2334-7-43
PMCID: PMC1891109  PMID: 17519011
3.  Predictors of mortality among TB-HIV Co-infected patients being treated for tuberculosis in Northwest Ethiopia: a retrospective cohort study 
BMC Infectious Diseases  2013;13:297.
Background
Tuberculosis (TB) is the leading cause of mortality in high HIV-prevalence populations. HIV is driving the TB epidemic in many countries, especially those in sub-Saharan Africa. The aim of this study was to assess predictors of mortality among TB-HIV co-infected patients being treated for TB in Northwest Ethiopia.
Methods
An institution-based retrospective cohort study was conducted between April, 2009 and January, 2012. Based on TB, antiretroviral therapy (ART), and pre-ART registration records, TB-HIV co-infected patients were categorized into “On ART” and “Non-ART” cohorts. A Chi-square test and a T-test were used to compare categorical and continuous variables between the two groups, respectively. A Kaplan-Meier test was used to estimate the probability of death after TB diagnosis. A log-rank test was used to compare overall mortality between the two groups. A Cox proportional hazard model was used to determine factors associated with death after TB diagnosis.
Results
A total of 422 TB-HIV co-infected patients (i.e., 272 On ART and 150 Non-ART patients) were included for a median of 197 days. The inter-quartile range (IQR) for On ART patients was 140 to 221 days and the IQR for Non-ART patients was 65.5 to 209.5 days. In the Non-ART cohort, more TB-HIV co-infected patients died during TB treatment: 44 (29.3%) Non-ART patients died, as compared to 49 (18%) On ART patients died. Independent predictors of mortality during TB treatment included: receiving ART (Adjusted Hazard Ratio (AHR) =0.35 [0.19-0.64]); not having initiated cotrimoxazole prophylactic therapy (CPT) (AHR = 3.03 [1.58-5.79]); being ambulatory (AHR = 2.10 [1.22-3.62]); CD4 counts category being 0-75cells/micro liter, 75-150cells/micro liter, or 150-250cells/micro liter (AHR = 4.83 [1.98-11.77], 3.57 [1.48-8.61], and 3.07 [1.33-7.07], respectively); and treatment in a hospital (AHR = 2.64 [1.51-4.62]).
Conclusions
Despite the availability of free ART from health institutions in Northwest Ethiopia, mortality was high among TB-HIV co-infected patients, and strongly associated with the absence of ART during TB treatment. In addition cotrimoxazol prophylactic therapy remained important factor in reduction of mortality during TB treatment. The study also noted importance of early ART even at higher CD4 counts.
doi:10.1186/1471-2334-13-297
PMCID: PMC3703293  PMID: 23815342
Predictors; Mortality; TB-HIV; Co-infection
4.  Childhood TB epidemiology and treatment outcomes in Thailand: a TB active surveillance network, 2004 to 2006 
Background
Of the 9.2 million new TB cases occurring each year, about 10% are in children. Because childhood TB is usually non-infectious and non-fatal, national programs do not prioritize childhood TB diagnosis and treatment. We reviewed data from a demonstration project to learn more about the epidemiology of childhood TB in Thailand.
Methods
In four Thai provinces and one national hospital, we contacted healthcare facilities monthly to record data about persons diagnosed with TB, assist with patient care, provide HIV counseling and testing, and obtain sputum for culture and susceptibility testing. We analyzed clinical and treatment outcome data for patients age < 15 years old registered in 2005 and 2006.
Results
Only 279 (2%) of 14,487 total cases occurred in children. The median age of children was 8 years (range: 4 months, 14 years). Of 197 children with pulmonary TB, 63 (32%) were bacteriologically-confirmed: 56 (28%) were smear-positive and 7 (4%) were smear-negative, but culture-positive. One was diagnosed with multi-drug resistant TB. HIV infection was documented in 75 (27%). Thirteen (17%) of 75 HIV-infected children died during TB treatment compared with 4 (2%) of 204 not known to be HIV-infected (p < 0.01).
Conclusion
Childhood TB is infrequently diagnosed in Thailand. Understanding whether this is due to absence of disease or diagnostic effort requires further research. HIV contributes substantially to the childhood TB burden in Thailand and is associated with high mortality.
doi:10.1186/1471-2334-8-94
PMCID: PMC2483984  PMID: 18637205
11.  Arcanobacterium haemolyticum associated with pyothorax: case report 
Arcanobacterium haemolyticum has an established role in the etiology of human pharyngitis. There are increasing reports of systemic infections caused by this organism. From India, we report the first case of Arcanobacterium haemolyticum causing pyothorax in an immunocompetent adolescent male patient. The probable mode of infection is also discussed. The role of A. hemolyticum as an animal pathogen needs further study.
doi:10.1186/1471-2334-5-68
PMCID: PMC1236925  PMID: 16144543
12.  Virulence difference between the prototypic Schu S4 strain (A1a) and Francisella tularensis A1a, A1b, A2 and type B strains in a murine model of infection 
Background
The use of prototypic strains is common among laboratories studying infectious agents as it promotes consistency for data comparability among and between laboratories. Schu S4 is the prototypic virulent strain of Francisella tularensis and has been used extensively as such over the past six decades. Studies have demonstrated virulence differences among the two clinically relevant subspecies of F. tularensis, tularensis (type A) and holarctica (type B) and more recently between type A subpopulations (A1a, A1b and A2). Schu S4 belongs to the most virulent subspecies of F. tularensis, subspecies tularensis.
Methods
In this study, we investigated the relative virulence of Schu S4 in comparison to A1a, A1b, A2 and type B strains using a temperature-based murine model of infection. Mice were inoculated intradermally and a hypothermic drop point was used as a surrogate for death. Survival curves and the length of temperature phases were compared for all infections. Bacterial burdens were also compared between the most virulent type A subpopulation, A1b, and Schu S4 at drop point.
Results
Survival curve comparisons demonstrate that the Schu S4 strain used in this study resembles the virulence of type B strains, and is significantly less virulent than all other type A (A1a, A1b and A2) strains tested. Additionally, when bacterial burdens were compared between mice infected with Schu S4 or MA00-2987 (A1b) significantly higher burdens were present in the blood and spleen of mice infected with MA00-2987.
Conclusions
The knowledge gained from using Schu S4 as a prototypic virulent strain has unquestionably advanced the field of tularemia research. The findings of this study, however, indicate that careful consideration of F. tularensis strain selection must occur when the overall virulence of the strain used could impact the outcome and interpretation of results.
doi:10.1186/1471-2334-14-67
PMCID: PMC3923427  PMID: 24502661
Prototypic strains; Murine model; Fever; Francisella tularensis; Tularemia; Schu S4; A1a
13.  Epidemic characteristics of hemorrhagic fever with renal syndrome in China, 2006–2012 
BMC Infectious Diseases  2014;14:384.
Background
Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses is a serious public health problem in China. The National Notifiable Disease Surveillance System (NNDSS) was established online by China CDC in 2004 and rodent surveillance sites were adjusted to 40 sites in 22 provinces in 2005. Here we analyzed the surveillance data of both human cases and rodents host during 2006–2012 to examine the epidemic trends of HFRS in recent years in China.
Methods
Records on HFRS human cases and surveillance data of rodents host from 2006 to 2012 were analyzed. Phylogenetic tree based on complete sequence of M segment of 58 virus isolates was constructed and analyzed to make a better understanding of the molecular diversity of hantaviruses in China.
Results
During 2006–2012, a total of 77558 HFRS human cases and 866 deaths were reported with the average annual incidence rate of 0.83 cases/100,000 population and case fatality rate of 1.13%. 84.16% of the total cases were clustered in 9 provinces and mainly reported in spring and autumn-winter seasons. HFRS incidence in males was over 3 times higher than in females and farmers still accounted for the largest proportion. The average density of rodents was relatively stable from 2006 to 2012. Apodemus agrarius and Rattus norvegicus were predominant in wild field and residential area, respectively. Both hantaviruses carrying and infection rates in rodents had a rapid increase in 2012. Phylogenetic analysis showed that at least six clades of Hantaan virus and five of Seoul virus were prevalent in China.
Conclusion
HFRS in China was still a natural focal disease with relatively high morbidity and fatality and its distribution and epidemic trends had also changed. Surveillance measures, together with prevention and control strategies should be improved and strengthened to reduce HFRS infection in China.
doi:10.1186/1471-2334-14-384
PMCID: PMC4105051  PMID: 25012160
Hemorrhagic fever with renal syndrome (HFRS); Hantaviruses; Epidemics; Phylogenetic analysis
14.  Inflammatory, procoagulant markers and HIV residual viremia in patients receiving protease inhibitor monotherapy or triple drug therapy: a cross-sectional study 
BMC Infectious Diseases  2014;14:379.
Background
Protease inhibitor monotherapy is associated with more frequent episodes of viral rebounds above 50 copies/mL than triple therapy. Objective: To evaluate if, compared to triple-drug therapy, protease inhibitor monotherapy is associated with increased levels of inflammatory/procoagulant markers and more frequent plasma residual viremia detection.
Methods
In this cross-sectional study, we included patients treated for ≥ 1 year with darunavir/ritonavir or lopinavir/ritonavir as monotherapy (n = 72) or with two nucleos(t)ides (n = 74). All samples were tested for CRP, IL-6, fibrinogen and D-dimer. Residual viremia was determined using an ultrasensitive qualitative nested-PCR of the HIV pol gene with a limit of detection of 1 copy of HIV-RNA.
Results
We found no differences in levels of inflammatory/procoagulant markers or in the proportion of patients with plasma residual viremia detection by treatment group.
Conclusion
The long-term treatment with protease inhibitor monotherapy in the setting of routine clinical practice is not associated with a higher prevalence of plasma residual viremia or more elevated inflammatory/procoagulant markers levels than triple drug therapy.
doi:10.1186/1471-2334-14-379
PMCID: PMC4097047  PMID: 25015544
HIV; Monotherapy; Inflammation; Residual viremia
15.  False positive malaria rapid diagnostic test in returning traveler with typhoid fever 
BMC Infectious Diseases  2014;14:377.
Background
Rapid diagnostic tests play a pivotal role in the early diagnosis of malaria where microscopy or polymerase chain reaction are not immediately available.
Case presentation
We report the case of a 39 year old traveler to Canada who presented with fever, headache, and abdominal pain after visiting friends and relatives in India. While in India, the individual was not ill and had no signs or symptoms of malaria. Laboratory testing upon his return to Canada identified a false positive malaria rapid diagnostic (BinaxNOW® malaria) result for P. falciparum with coincident Salmonella Typhi bacteraemia without rheumatoid or autoimmune factors. Rapid diagnostic test false positivity for malaria coincided with the presence or absence of Salmonella Typhi in the blood.
Conclusions
Clinicians should be aware that Salmonella Typhi infection may result in a false positive malaria rapid diagnostic test. The mechanism of this cross-reactivity is not clear.
doi:10.1186/1471-2334-14-377
PMCID: PMC4094604  PMID: 25005493
Malaria; False positive; Rapid diagnostic test; Typhoid
16.  The use of the temporal scan statistic to detect methicillin-resistant Staphylococcus aureus clusters in a community hospital 
BMC Infectious Diseases  2014;14:375.
Background
In healthcare facilities, conventional surveillance techniques using rule-based guidelines may result in under- or over-reporting of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks, as these guidelines are generally unvalidated. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting MRSA clusters, validate clusters using molecular techniques and hospital records, and determine significant differences in the rate of MRSA cases using regression models.
Methods
Patients admitted to a community hospital between August 2006 and February 2011, and identified with MRSA > 48 hours following hospital admission, were included in this study. Between March 2010 and February 2011, MRSA specimens were obtained for spa typing. MRSA clusters were investigated using a retrospective temporal scan statistic. Tests were conducted on a monthly scale and significant clusters were compared to MRSA outbreaks identified by hospital personnel. Associations between the rate of MRSA cases and the variables year, month, and season were investigated using a negative binomial regression model.
Results
During the study period, 735 MRSA cases were identified and 167 MRSA isolates were spa typed. Nine different spa types were identified with spa type 2/t002 (88.6%) the most prevalent. The temporal scan statistic identified significant MRSA clusters at the hospital (n = 2), service (n = 16), and ward (n = 10) levels (P ≤ 0.05). Seven clusters were concordant with nine MRSA outbreaks identified by hospital staff. For the remaining clusters, seven events may have been equivalent to true outbreaks and six clusters demonstrated possible transmission events. The regression analysis indicated years 2009–2011, compared to 2006, and months March and April, compared to January, were associated with an increase in the rate of MRSA cases (P ≤ 0.05).
Conclusions
The application of the temporal scan statistic identified several MRSA clusters that were not detected by hospital personnel. The identification of specific years and months with increased MRSA rates may be attributable to several hospital level factors including the presence of other pathogens. Within hospitals, the incorporation of the temporal scan statistic to standard surveillance techniques is a valuable tool for healthcare workers to evaluate surveillance strategies and aid in the identification of MRSA clusters.
doi:10.1186/1471-2334-14-375
PMCID: PMC4097048  PMID: 25005247
Methicillin-resistant Staphylococcus aureus; Clusters; Temporal scan statistic; Community hospital; Epidemiology; Spa typing
17.  Type distribution of human papillomavirus among adult women diagnosed with invasive cervical cancer (stage 1b or higher) in New Zealand 
BMC Infectious Diseases  2014;14:374.
Background
Human papillomavirus (HPV) is the necessary cause of cervical cancer. Published data on the epidemiology of HPV in women with invasive cervical cancer (ICC) in New Zealand (NZ) are limited. This cross-sectional study investigated the distribution of high-risk and low-risk HPV types in cervical specimens collected from women throughout NZ who had been diagnosed with ICC between 2004 and 2010.
Methods
Women aged ≥18 years, with ICC International Federation of Gynecology and Obstetrics stage Ib or greater were identified from the five tertiary public hospitals in NZ regularly treating women with ICC. Women were enrolled in the study only after obtaining informed consent. Stored, formalin fixed, paraffin-embedded cervical specimens were retrieved and histopathologically reviewed to confirm the diagnosis of ICC. Cervical specimens were tested for HPV using polymerase chain reaction-short fragment10; HPV DNA was detected using DNA enzyme immunoassay and typed by reverse hybridization line probe assay.
Results
242 women were enrolled and ICC was histologically confirmed in 227 samples. HPV infection was detected in 88.5% (n = 201; 95% CI: 83.7–92.4) of women with ICC; high-risk HPV types were detected in 87.2% of women. The most commonly detected HPV types were HPV-16 (51.1%) and HPV-18 (20.7%), followed by HPV-31 (4.0%), HPV-45 and HPV-52 (3.1% each). Overall, HPV distribution was highest (94.3%) in women aged 30–39 years at diagnosis and a higher distribution of HPV-16 (68.8%) was observed in women younger than 30 years. The overall distribution of HPV types between Maori and non-Maori women were similar. HPV-positive women with ICC stage II or greater were less likely to be infected with HPV-16/18 (P = 0.002) or HPV-18 (P = 0.029) compared with the other high-risk types. Single type infection and multiple infections were detected in 93.5% and 5.5% of women, respectively.
Conclusions
HPV-16, HPV-18, HPV-31, HPV-45 and HPV-52 were the most commonly detected high-risk HPV types. Findings from the study fill an important data gap on HPV type distribution from NZ which will help facilitate better understanding of the epidemiology of HPV in NZ women.
Clinical trial registration
NCT01328028.
doi:10.1186/1471-2334-14-374
PMCID: PMC4099079  PMID: 25000939
Epidemiology; Human papillomavirus; Invasive cervical cancer; New Zealand
18.  Spatial-temporal excess mortality patterns of the 1918–1919 influenza pandemic in Spain 
BMC Infectious Diseases  2014;14:371.
Background
The impact of socio-demographic factors and baseline health on the mortality burden of seasonal and pandemic influenza remains debated. Here we analyzed the spatial-temporal mortality patterns of the 1918 influenza pandemic in Spain, one of the countries of Europe that experienced the highest mortality burden.
Methods
We analyzed monthly death rates from respiratory diseases and all-causes across 49 provinces of Spain, including the Canary and Balearic Islands, during the period January-1915 to June-1919. We estimated the influenza-related excess death rates and risk of death relative to baseline mortality by pandemic wave and province. We then explored the association between pandemic excess mortality rates and health and socio-demographic factors, which included population size and age structure, population density, infant mortality rates, baseline death rates, and urbanization.
Results
Our analysis revealed high geographic heterogeneity in pandemic mortality impact. We identified 3 pandemic waves of varying timing and intensity covering the period from Jan-1918 to Jun-1919, with the highest pandemic-related excess mortality rates occurring during the months of October-November 1918 across all Spanish provinces. Cumulative excess mortality rates followed a south–north gradient after controlling for demographic factors, with the North experiencing highest excess mortality rates. A model that included latitude, population density, and the proportion of children living in provinces explained about 40% of the geographic variability in cumulative excess death rates during 1918–19, but different factors explained mortality variation in each wave.
Conclusions
A substantial fraction of the variability in excess mortality rates across Spanish provinces remained unexplained, which suggests that other unidentified factors such as comorbidities, climate and background immunity may have affected the 1918–19 pandemic mortality rates. Further archeo-epidemiological research should concentrate on identifying settings with combined availability of local historical mortality records and information on the prevalence of underlying risk factors, or patient-level clinical data, to further clarify the drivers of 1918 pandemic influenza mortality.
doi:10.1186/1471-2334-14-371
PMCID: PMC4094406  PMID: 24996457
1918–1919 influenza pandemic; Spain; Spanish influenza; Spring-summer wave; Excess death rates; Relative risk of death; Transmissibility; Provinces; Geography; Spatial heterogeneity
19.  Campylobacter infection in a cohort of rural children in Moramanga, Madagascar 
BMC Infectious Diseases  2014;14:372.
Background
Campylobacter infection is the most common cause of bacterial gastroenteritis in developing countries, including Madagascar. Reports of pathogenicity have not been consistent and repeated exposures over time seem to lead to the development of protective immunity in developing areas. We conducted this study to support evidence for these hypotheses by exploring the association between infection and age, the reoccurrence of infection and the pathogenicity of Campylobacter.
Methods
We carried out a community-based longitudinal study of children under the age of 24 months in two rural villages in Moramanga, Madagascar. Children were visited twice a week and a stool specimen was collected in cases of diarrhoea. Stools specimens were collected bimonthly from all children enrolled, regardless of symptoms. Children were followed-up until the age of 36 months.
Results
Between January 2010 and May 31st 2012, 508 children were included in the cohort. We detected 319 episodes of Campylobacter infection in total, and 43.3% (n = 220) of the children had at least one episode of intestinal Campylobacter infection. The rate of Campylobacter isolation from stool specimens was 9.3%. The annual incidence rate for symptomatic Campylobacter infection was 0.05 episodes/child. The probability of Campylobacter infection was highest between the ages of six and 23 months. Taking children under six months of age as the reference group, the age-specific odds ratio for the association was 5.0 (95% CI: 2.9-8.6) for children aged six to 11 months, 5.7 (95% CI: 3.3-10.0) for children aged 12 to 17 months and 3.3 (95% CI: 1.8-5.8) for children aged 18 to 23 months. A second episode of infection occurred 63 days after the first episode in children with primary infections, and after 137 days in children with multiple infections (p < 0.01). First episodes of Campylobacter infection were associated with diarrhoea (odds ratio = 16.1; 95% CI: 1.8-140.8).
Conclusion
Our findings suggest that protective immunity to Campylobacter may be acquired over time, following repeated exposures. However, Campylobacter infection prevention measures should be reinforced in the first year of life, as this age seems to be associated with the highest risk of diarrhoea during Campylobacter infection.
doi:10.1186/1471-2334-14-372
PMCID: PMC4094412  PMID: 24996559
Campylobacter infection; Cohort study; Diarrhoea; Rural area; Madagascar
20.  Common subclinical hypothyroidism during Whipple’s disease 
BMC Infectious Diseases  2014;14:370.
Background
Classic Whipple’s disease is caused by T. whipplei and likely involves genetic predispositions, such as the HLA alleles DRB1*13 and DQB1*06, that are more frequently observed in patients. T. whipplei carriage occurs in 2-4% of the general population in France. Subclinical hypothyroidism, characterized by high levels of TSH and normal free tetra-iodothyronine (fT4) dosage, has been rarely associated with specific HLA factors.
Methods
We retrospectively tested TSHus in 80 patients and 42 carriers. In cases of dysthyroidism, we tested the levels of free-T4 and anti-thyroid antibodies, and the HLA genotypes were also determined for seven to eight patients.
Results
In this study, 72-74% of patients and carriers were male, and among the 80 patients, 14 (17%) individuals had a high level of TSH, whereas none of the carriers did (p < 0 · 01). In the 14 patients with no clinical manifestations, the T4 levels were normal, and no specific antibodies were present. Four patients treated with antibiotics, without thyroxine supplementation, showed normal levels of TSHus after one or two years. One patient displayed a second episode of subclinical hypothyroidism during a Whipple’s disease relapse five years later, but the subclinical hypothyroidism regressed after antibiotic treatment. HLA typing revealed nine alleles that appeared more frequently in patients than in the control cohort, but none of these differences reached significance due to the small size of the patient group.
Conclusion
Regardless of the substratum, classic Whipple’s disease could lead to subclinical hypothyroidism. We recommend systematically testing the TSH levels in patients with Whipple’s disease.
doi:10.1186/1471-2334-14-370
PMCID: PMC4099391  PMID: 24996424
Tropheryma whipplei; Whipple’s disease; Subclinical hypothyroidism; HLA
21.  HIV and syphilis prevalence trends among men who have sex with men in Guangxi, China: yearly cross-sectional surveys, 2008–2012 
BMC Infectious Diseases  2014;14:367.
Background
Men who have sex with men (MSM) represent the fastest growing key population for incident HIV cases in China. We examined five consecutive years of HIV and syphilis prevalence and risk factors data among MSM in Guangxi Province with the second highest estimated number of people living with HIV/AIDS (PLWHAs) in China in 2011.
Methods
We collected demographic and behavioral data from national sentinel surveillance and HIV/syphilis blood samples in five annual cross-sectional surveys from 2008 to 2012. We analyzed HIV and syphilis prevalence trends stratified by social/behavioral characteristics.
Results
HIV prevalence climbed steadily from 1.7% (95% confidence interval [CI]: 1.0 to 3.0) in 2008 to 3.7% (95% CI: 3.0 to 5.0) in 2012. Syphilis prevalence increased steadily from 5.1% (95% CI: 4.0 to 6.0) in 2008 to 8.4% (95% CI: 7.0 to 10.0) in 2012. HIV prevalence rose notably among MSM who were ≤25 years of age, never married, did not engage in sexual intercourse with women in the past six months, and had not been tested for HIV in the past year. Syphilis prevalence rose notably among MSM who were >25 years of age, ever married or living with a partner, and engaged in sexual intercourse with women in the past six months. HIV prevalence was much higher in MSM with current syphilis than without. Finally, current syphilis was the most significant predictor of HIV infection, and age was the most significant predictor of syphilis infection.
Conclusions
HIV and the syphilis prevalence expansion among MSM suggest an urgent public health prevention challenge for Guangxi provincial health officials. Risk factors for each infection differed such that all MSM, each of whom might be at risk of HIV, syphilis or both, should be targets for heavy intervention.
doi:10.1186/1471-2334-14-367
PMCID: PMC4091643  PMID: 24993252
HIV; Syphilis; Prevalence trends; MSM; China; Guangxi Province
22.  Serological prevalence and persistence of high-risk human papillomavirus infection among women in Santiago, Chile 
BMC Infectious Diseases  2014;14:361.
Background
Human papillomavirus (HPV) serology is a main factor for designing vaccination programs and surveillance strategies; nevertheless, there are few reports of HPV seroprevalence in the general population, especially in Latin America. This study aimed to describe high-risk HPV serological prevalence, persistence, and association with concurrent cervical infection, in Chilean women.
Methods
1021 women from the general population, aged 15–85 years, were studied in 2001 of whom 600 were reexamined in 2006. The assessments at both time points included cervical HPV DNA testing, HPV antibody testing, cervical cytology and a sociodemographic/behavioral questionnaire. HPV DNA and antibodies against L1 protein of types 16, 18, 31, 33, 35, 45, 52, and 58 were assessed by reverse line blot and multiplex serology, respectively.
Results
Seropositivity was high at both baseline (43.2%) and follow-up (50.2%) and increased with age (p < 0.001); corresponding DNA prevalences were 6.7% and 8.7%. DNA and seroprevalence were associated at baseline (p = 0.01 for any HPV). Early age at first sexual intercourse and having had two or more sexual partners were independently associated with seropositivity. Most (82.0%) initially seropositive women remained seropositive at follow-up; 21.6% of initially seronegative women seroconverted, reaching 17.5% among women older than 60 years of age. ASCUS or worse cytology was correlated with HPV DNA positivity but not with HPV seropositivity.
Conclusion
HPV seroprevalence studies are a useful tool for learning about the dynamics of HPV infection in a community. This study contributes to understanding the natural history of HPV infection and provides a baseline assessment before the incorporation of HPV vaccination into a national program.
doi:10.1186/1471-2334-14-361
PMCID: PMC4091743  PMID: 24990706
Human papillomavirus; Seropersistence; Cohort; Serology; Antibodies; Natural history
23.  MRSA carriage among healthcare workers in non-outbreak settings in Europe and the United States: a systematic review 
BMC Infectious Diseases  2014;14:363.
Abstarct
Background
A recent review estimated prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in healthcare workers (HCWs) to be 4.6%. However, MRSA carriage in HCWs in non-outbreak settings is thought to be higher than in an outbreak situation, due to increased hygiene awareness in outbreaks, but valid data are missing. The goals of this paper are to summarise the prevalence of MRSA carriage amongst HCWs in non-outbreak situations and to identify occupational groups in healthcare services associated with a higher risk of MRSA colonisation.
Methods
A systematic search for literature was conducted in the MEDLINE and EMBASE databases. The methodological quality of the studies was assessed using seven criteria. Pooled prevalence rates were calculated. Pooled effect estimates were identified in a meta-analysis.
Results
31 studies were included in this review. The pooled MRSA colonisation rate was 1.8% (95% confidence interval [CI], 1.34%-2.50%). The rate increased to 4.4% (95% CI, 3.98%-4.88%) when one study from the Netherlands was excluded. The pooled MRSA rate was highest in nursing staff (6.9%). Nursing staff had an odds ratio of 1.72 (95% CI, 1.07-2.77) when compared with medical staff and an odds ratio of 2.58 (95%, 1.83-3.66) when compared with other healthcare staff. Seven studies were assessed as being of high quality. The pooled MRSA prevalence in high quality studies was 1.1% or 5.4% if the one large study from the Netherlands is not considered. The pooled prevalence in studies of moderate quality was 4.0%.
Conclusions
MRSA prevalence among HCWs in non-outbreak settings was no higher than carriage rates estimated for outbreaks. Our estimate is in the lower half of the range of the published MRSA rates in the endemic setting. Our findings demonstrate that nursing staff have an increased risk for MRSA colonisation. In order to confirm this finding, more studies are needed, including healthcare professionals with varying degrees of exposure to MRSA. In order to reduce misclassification bias, standardisation of HCWs screening is warranted.
doi:10.1186/1471-2334-14-363
PMCID: PMC4094410  PMID: 24996225
MRSA; Colonisation; Healthcare worker
24.  Severe fever with thrombocytopenia syndrome in children: a case report 
BMC Infectious Diseases  2014;14:366.
Background
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTSV) in China. Humans of all ages living in endemic areas have high risk of acquiring SFTS. Most clinical data so far have been from adults and no clinical study was available from children yet. The present study identified four SFTSV infected children through hospital based surveillance. A prospective observational study was performed to obtain their clinical and laboratory characteristics.
Case presentation
The patients’ age ranged from 4–15 years old and two were male. On hospitalization, fever, malaise and gastrointestinal syndromes were the most commonly presenting symptoms. Hemorrhagic symptoms or neurological manifestation was not recorded in any of the four pediatric patients. Hematological abnormalities at admission into hospital included leucopenia (4 cases), thrombocytopenia (1 case) and bicytopenia (1 case). The abnormal parameters included elevated aminotransferase (1 case), alanine transaminase (2 case), and lactate dehydrogenase (3 case). Laboratory parameters indicative of renal damage was not observed during the hospitalization. All the patients recovered well without sequelae being observed.
Conclusion
Compared with adults, pediatric patients with SFTSV infection seem to have less vague subjective complaints and less aggressive clinical course. Thrombocytopenia is suggested to be used less rigorously in recognizing SFTSV infection in pediatric patients, especially at early phase of disease.
doi:10.1186/1471-2334-14-366
PMCID: PMC4094669  PMID: 24993119
Severe fever with thrombocytopenia syndrome; Bunyavirus; Children
25.  Geographical heterogeneity and influenza infection within households 
BMC Infectious Diseases  2014;14:369.
Background
Although it has been suggested that schoolchildren vaccination reduces influenza morbidity and mortality in the community, it is unknown whether geographical heterogeneity would affect vaccine effectiveness.
Methods
A 3-year prospective, non-randomized sero-epidemiological study was conducted during 2008–2011 by recruiting schoolchildren from both urban and rural areas. Respective totals of 124, 206, and 176 households were recruited and their household contacts were followed. Serum samples were collected pre-vaccination, one-month post-vaccination and post-season from children and household contacts for hemagglutination inhibition (HI) assay. A multivariate logistic model implemented with generalized estimation equations (GEE) was fitted with morbidity or a four-fold increase in HI titer of the household contacts for two consecutive sera as the dependent variable; with geographical location, vaccination status of each household and previous vaccination history as predictor variables.
Results
Although our results show no significant reduction in the proportion of infection or clinical morbidity among household contacts, a higher risk of infection, indicated by odds ratio > 1, was consistently observed among household children contacts from the un-vaccinated households after adjusting for confounding variables. Interestingly, a statistically significant lower risk of infection was observed among household adult contacts from rural area when compared to those from urban area (OR = 0.89; 95% CI: 0.82-0.97 for Year 2 and OR = 0.85; 95% CI: 0.75-0.96 for Year 3).
Conclusions
A significant difference in the risk of influenza infection among household adults due to geographical heterogeneity, independent of schoolchildren vaccination status, was revealed in this study. Its impact on vaccine effectiveness requires further study.
doi:10.1186/1471-2334-14-369
PMCID: PMC4094897  PMID: 24993483
Influenza; Trivalent Inactivated Vaccine (TIV); Children; Household contacts; Geographical heterogeneity

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