International Journal of Infectious Diseases - Articles in Press

Epidemiological and laboratory characterization of a yellow fever outbreak in northern Uganda, October 2010–January 2011 - Corrected Proof

2012-05-10

Summary: Background: In November 2010, following reports of an outbreak of a fatal, febrile, hemorrhagic illness in northern Uganda, the Uganda Ministry of Health established multisector teams to respond to the outbreak.Methods: This was a case-series investigation in which the response teams conducted epidemiological and laboratory investigations on suspect cases. The cases identified were line-listed and a data analysis was undertaken regularly to guide the outbreak response.Results: Overall, 181 cases met the yellow fever (YF) suspected case definition; there were 45 deaths (case fatality rate 24.9%). Only 13 (7.5%) of the suspected YF cases were laboratory confirmed, and molecular sequencing revealed 92% homology to the YF virus strain Couma (Ethiopia), East African genotype. Suspected YF cases had fever (100%) and unexplained bleeding (97.8%), but jaundice was rare (11.6%). The overall attack rate was 13 cases/100000 population, and the attack rate was higher for males than females and increased with age. The index clusters were linked to economic activities undertaken by males around forests.Conclusions: This was the largest YF outbreak ever reported in Uganda. The wide geographical case dispersion as well as the male and older age preponderance suggests transmission during the outbreak was largely sylvatic and related to occupational activities around forests.

Vir typing for the analysis of group C and group G streptococcal genotypes - Corrected Proof

D. Prabu, Thangam Menon — 2012-05-10

Group C and group G streptococci (GCS and GGS) cause a wide variety of suppurative and nonsuppurative infections. The epidemiology of GCS and GGS is considered to be important, since infections caused by GCS and GGS have increased in recent years. Studies in the Aboriginal population of Australia suggest that they may also have rheumatogenic potential. Vir typing is considered to be a good epidemiological tool for the identification of group A Streptococcus (GAS) genotypes and involves strain discrimination based on the vir regulon, which consists of structurally related genes of the emm family. The vir regulon of GCS and GGS can also be amplified using GAS-specific primers. Hence the present study was aimed to determine the genetic variability among the GCS and GGS by vir typing.

Case fatality associated with a hypervirulent strain in patients with culture-positive Clostridium difficile infection: a retrospective population-based study - Corrected Proof

Reetta Huttunen, Risto Vuento, Jaana Syrjänen, Päivi Tissari, Janne Aittoniemi — 2012-05-09

Summary: Background: Clostridium difficile is a major infectious cause of healthcare-associated diarrhea. The epidemiology of C. difficile infection (CDI) is changing, with evidence of increased incidence and severity. The first patient with a hypervirulent strain type in Pirkanmaa Hospital District, Finland was reported in September 2008.Methods: We reviewed all culture-positive C. difficile episodes that occurred in Pirkanmaa Hospital District during the period September 2008 to May 2010.Results: A total of 780 episodes of C. difficile occurred in 622 patients. A hypervirulent strain caused 14.2% of all episodes. The day 30 case fatality associated with CDI was 8.5% in episodes with a non-hypervirulent strain and 20.7% in episodes with a hypervirulent strain type (p<0.001, odds ratio 2.8, 95% confidence interval 1.6–4.8). The median age among those infected by a hypervirulent strain was higher than among those infected by a non-hypervirulent strain (83 vs. 75 years, p<0.001). Hypervirulent strain type remained a significant factor associated with case fatality in a logistic regression model. Blood leukocytes were significantly higher in episodes due to a hypervirulent strain (11.0 vs. 9.4×109/l, p=0.007). Blood leukocytes and C-reactive protein (CRP) on the day of diagnosis were significantly higher in non-survivors compared to survivors in CDI (13.2 vs. 9.6×109/l, p=0.009, and 106.0 vs. 79.4mg/l, p<0.001, respectively).Conclusions: Infection due to a hypervirulent strain is a factor associated with increased case fatality in CDI. Blood leukocytes are significantly higher in CDI caused by a hypervirulent strain. Leukocyte count and CRP are useful prognostic biomarkers in patients with CDI.

Risk factors for tuberculin skin test conversion among HIV-infected patients in New York City - Corrected Proof

2012-04-30

Summary: Background: We assessed the incidence of and risk factors for tuberculin skin test (TST) conversion among HIV-infected adults at a New York City clinic.Methods: All adult HIV-infected patients were eligible for inclusion if they had a negative baseline TST result and at least one subsequent documented TST test result.Results: A total of 414 HIV-infected patients had a negative baseline TST result; 288 (69.6%) were male. Among 348 patients who had a place of birth documented, 50% were born outside of mainland USA. Twenty-two (5.3%) of 414 patients had documented TST conversions, giving a crude incidence rate of 1.77 per 100 person-years. Being a foreign-born Asian individual (p=0.02), having lived in a shelter (p=0.004), and having an increase in CD4 cell count (p=0.02) while under care were independent risk factors for TST conversion.Conclusions: We found a high TST conversion rate among HIV-infected patients attending an urban clinic. Annual TST testing is particularly important for patients who are foreign-born from high-endemic countries, those with a history of homelessness, and those with an increase in CD4 cell count since the baseline negative TST test.

Evaluation of a new interferon-gamma release assay and comparison to tuberculin skin test during a tuberculosis outbreak - Corrected Proof

2012-04-30

Summary: Background: The tuberculin skin test (TST) is commonly used for the diagnosis of latent tuberculosis infection (LTBI) in non-bacille Calmette–Guérin (BCG) vaccination settings. In recent years, attention has been drawn to interferon-gamma release assays (IGRAs), especially in BCG-vaccinated populations. In this study, we evaluated the TST and a new whole blood IGRA in BCG-vaccinated individuals during a tuberculosis (TB) outbreak in China.Methods: A TB outbreak occurred at a university in Dalian, China from March to November 2010. The TST and a whole blood IGRA were used to screen for TB infection. The correlation between exposure levels, TST, and the IGRA were evaluated.Results: We found that agreement between the IGRA and TST was poor (kappa 0.182–0.290). IGRA positivity was associated with the level of exposure, and IGRA positivity and the level of exposure were risk factors for TB incidence. Neither the IGRA nor the TST alone picked up all TB incidences. However, if a 10mm cutoff for the TST was used in the highest risk exposure group and IGRA positivity was used in the other risk groups, 19 of the 20 (95%) TB cases were identified.Conclusions: A recommended preventive treatment regimen for China should be based on the level of exposure in conjunction with IGRA and TST test results.

Estimating incidence rates with misclassified disease status: a likelihood-based approach, with application to hepatitis C virus - Corrected Proof

2012-04-30

Summary: Background: In epidemiologic research, incidence is often estimated from data arising from an imperfect diagnostic test performed at unequally spaced intervals over time.Methods: We developed a likelihood-based method to estimate incidence when disease status is measured imperfectly and assays are performed at multiple unequally spaced visits. We assumed conditional independence, no remission, known constant levels of sensitivity and specificity, and constant incidence rates over time. The method performance was evaluated by examining its bias, accuracy (i.e., mean squared error (MSE)), and coverage probability in a simulation study of 4000 datasets, and then we applied the proposed method to a study of hepatitis C virus (HCV) infection in a cohort of pregnant women in the period 1997–2006.Results: The simulation revealed that our method has minimal bias and low MSE, as well as good coverage probability of the resulting confidence intervals. In the application to HCV study, the standard incidence rate estimate which ignores the imperfections of the diagnostic test (number of events/person-years), was 13.7 new HCV cases per 1000 person-years (95% confidence interval 10.1, 17.4). The adjusted incidence estimates (obtained using our proposed method) ranged from 0.4 cases per 1000 person-years (when sensitivity and specificity were assumed to both be 95%) to 13.7 cases per 1000 person-years (when sensitivity and specificity were both 100%). The magnitude of difference between standard and adjusted estimates varied depending on specificity and sensitivity assumptions. Specificity had the greatest impact on the magnitude of bias.Conclusions: Scientists should be aware of the impact of misclassification on incidence estimates. Appropriate study design, proper selection of the diagnostic test, and adjustment for misclassification probabilities in the analysis is necessary to obtain the most accurate incidence estimates.

A case series of spotted fever rickettsiosis with neurological manifestations in Sri Lanka - Corrected Proof

2012-04-27

Summary: Background: Spotted fever group (SFG) rickettsial infections are increasingly detected in Sri Lanka. We describe 17 patients with SFG who developed neurological manifestations.Methods: The cases were studied prospectively from 2008 at the Teaching Hospital, Peradeniya. An immunofluorescent antibody assay (IFA) was used to confirm the diagnosis.Results: All had an IFA IgG titer ranging from 1/64 to 1/4096 and a positive IFA IgM titer against Rickettsia conorii antigen; in 10 (59%) cases the IgG titers were ≥1/256 (definitive cases). The median age of the patients was 62 years (range 26–82 years); 10 were male and seven female. The median duration of fever was 12 days (range 4–35 days). Neurological manifestations on admission were drowsiness or confusion in 14 (82%) and a semi-comatose state in three (18%). Rigidity of the limbs occurred in 14 (82%), bradykinesia and resting tremors in 12 (71%), which persisted after defervescence, neck stiffness in seven (42%), weakness of the limbs in five (29%), deafness in two (12%), and stupor in three (18%). Electroencephalograms in three (18%) showed generalized slow waves. Cerebrospinal fluid examination showed a cellular reaction, predominantly lymphocytes, in three cases. Two patients died (fatality rate 12%).Conclusion: We have documented for the first time the neurological features of SFG rickettsioses in the Central Province, Sri Lanka. These were predominantly extrapyramidal features in patients of older age.

A mixed methods approach to identifying factors related to voluntary HIV testing among injection drug users in Shanghai, China - Corrected Proof

2012-04-26

Summary: Objectives: Injection drug use is a major route of HIV transmission in China, yet relatively little is known about why so few injection drug users utilize free HIV testing services. This study aimed to examine barriers to HIV testing and voluntary counseling and testing (VCT) service utilization among injection drug users in Shanghai, China.Methods: Utilizing mixed methods, we analyzed data from a survey of 540 compulsory drug abuse treatment patients and data from focus groups with 70 service providers and patients.Results: Only 24.4% of patients expressed willingness to be tested for HIV. Willingness to be tested was associated with younger age and more positive attitudes towards condom use. Patients reported several barriers to utilization of voluntary HIV testing services, including lack of information about these services, perceptions of no risk or low-risk for HIV infection, fear of positive results, and the stigma or discrimination that may be experienced by the patient or their family. Having limited skills related to HIV counseling was reported by service providers as the primary barrier to encouraging patients to utilize HIV testing/VCT services.Conclusions: Special intervention programs targeting injection drug users, their family members, and service providers may increase HIV testing in China.

Association between the risk of congenital toxoplasmosis and the classification of toxoplasmosis in pregnant women and prenatal treatment in Brazil, 1994–2009 - Corrected Proof

Liú Campello Porto, Elisabeth Carmen Duarte — 2012-04-23

Summary: Objectives: The objectives of this study were to analyze the association between the classification of toxoplasmosis in the pregnant woman (TP) according to the classification of Lebech et al. and the incidence of congenital toxoplasmosis (CT), also taking into consideration prenatal treatment.Methods: A clinical cohort study of 524 children followed-up until 1 year of age was conducted. Adjusted odds ratios (OR) were estimated by logistic regression.Results: Of 519 pregnant women, 61.3% were not classified due to the incompleteness of hospital records. Among the pregnant women classified as confirmed cases of TP (n=19), the CT risk was six times greater than in the probable/possible group. No case of CT was identified in the group of pregnant women classified as unlikely to have TP. The children with no prenatal treatment (46.2% n=242/524) presented a risk almost three times greater of CT than the treated children (OR 2.77, 95% confidence interval (CI) 1.54–4.97; p=0.001). Complete prenatal treatment was identified as a protecting factor for CT (OR 0.35, 95% CI 0.19–0.65; p=0.001).Conclusions: A lack or incomplete prenatal treatment was identified as an important risk factor for CT in this study. The proportions of non-classified mothers and children with no prenatal treatment reflect the need to improve prenatal care in Brazil.

Repeated dengue shock syndrome and ‘dengue myocarditis’ responding dramatically to a single dose of methyl prednisolone - Corrected Proof

2012-04-23

Summary: The place of steroids in the management of severe forms of dengue is unclear. A retrospective observational study showed the benefits of a single dose of intravenous methyl prednisolone in a highly selected group of patients who developed severe dengue during the febrile phase of infection. We report the case of a 14-year-old boy with dengue who developed three episodes of severe hemodynamic compromise while having high fever, ‘myocarditis’, third space fluid accumulation, progressive reduction in urine output, and altered mentation, who made a dramatic recovery following a single dose of intravenous methyl prednisolone. Results justify a well powered randomized controlled trial to evaluate the efficacy of this treatment in severe dengue.

Clinical characteristics of influenza A H1N1 versus other influenza-like illnesses amongst outpatients attending a university health center in Oman - Corrected Proof

2012-04-23

Summary: Objectives: To identify the clinical characteristics of outpatients with flu-like illnesses stratified by influenza A H1N1 status.Methods: The study was conducted at the H1N1 staff clinic of Sultan Qaboos University Hospital in Muscat, Oman. The population consisted of university students and university/hospital staff and their family members. All adult patients who presented to the H1N1 clinic with an influenza-like illness over a 4-month period (from August until the end of November 2009) were included. Real-time reverse transcriptase (rRT) PCR was used for the diagnosis of H1N1 influenza. Demographic data, clinical signs and symptoms, history of exposure to H1N1, history of recent travel, and co-morbid conditions were documented. Analyses were conducted using univariate and multivariate statistical techniques.Results: Out of the 2318 patients identified, 27% (n=616) were positive for H1N1 influenza. The mean temperature in the H1N1-positive group was significantly higher than in the negative group (38.3°C vs. 37.2°C; p<0.001). Proportions of patients who reported cough, sore throat, headache, myalgia, gastrointestinal symptoms, exposure to a confirmed case of H1N1, and a history of travel were significantly higher in the H1N1-positive group as compared to the swab-negative group. However, the multivariable logistic model identified only the following significant predictor variables of H1N1 infection: younger age, fever (≥37.8°C), sore throat, myalgia, diarrhea, and exposure to a confirmed H1N1 case within the last 7 days.Conclusions: This study provides useful data on the clinical characteristics of H1N1 influenza in a large outpatient population from the Middle East. Patients who tested positive for H1N1 were more likely to have fever, sore throat, diarrhea, and myalgia compared to those with other influenza-like illnesses.

The epidemiology and clinical characteristics of respiratory syncytial virus infection in children at a public pediatric referral hospital in Mexico - Corrected Proof

2012-04-23

Summary: Objectives: The aim of this study was to determine the epidemiological and clinical characteristics of children with respiratory syncytial virus (RSV) treated at a public referral children's hospital in Mexico.Methods: We reviewed RSV infection in patients aged 0–18 years who were treated at Hospital Infantil from January 2004 to December 2008.Results: During the 5 years, 2797 samples were tested for respiratory viruses; 356 samples were positive for any virus, including 266 (74.7%) positive for RSV. Complete clinical information was available for 205 RSV patients. The mean age was 22 months, and 33.7% of the infections were nosocomially acquired. Hospitalization occurred in 187 children. Of 14 deaths, nine were directly attributed to RSV infection. During the study, RSV infections were seen throughout the year, predominating in the colder months. Of the 205 patients, 79.0% (162/205) had an underlying disease. Congenital heart disease was found in 30.2% (49/162), including three children (33.3%) who died of RSV. Thirty-three patients (16.1%) with RSV required mechanical ventilation. None of the children with RSV received palivizumab or ribavirin.Conclusions: RSV caused high hospitalization rates and admission to intensive care units, especially among those with underlying illnesses and young infants. The data presented here will be useful for strategies to improve outcomes in children at risk of complications.

Unexplained neonatal jaundice as an early diagnostic sign of urinary tract infection - Corrected Proof

Mozhgan Shahian, Parisa Rashtian, Mehdi Kalani — 2012-04-18

Summary: Background: Hyperbilirubinemia is one of the presenting signs of bacterial infection in newborns, and the association of neonatal jaundice with urinary tract infection (UTI) has been particularly emphasized. The aim of this study was to determine the prevalence of UTI in asymptomatic jaundiced neonates younger than 4 weeks old.Methods: We prospectively evaluated 120 asymptomatic jaundiced and 122 healthy neonates without jaundice younger than 4 weeks old for UTI. Patients with UTI, defined as >10 000 colony-forming units of a single pathogen per milliliter urine obtained by bladder catheterization, were evaluated for sepsis.Results: Of 120 asymptomatic jaundiced neonates with a mean age of 7 ± 4 days, 15 (12.5%) had a UTI. Of 122 healthy neonates, positive urine cultures from a urine bag were found in eight cases; however on reevaluation, urine cultures from bladder catheterization were negative. The most common pathogen isolated from the UTI cases was Klebsiella pneumoniae. Also, unconjugated hyperbilirubinemia was detected in all jaundiced patients with UTI.Conclusion: UTI was found in 12.5% of the asymptomatic jaundiced neonates with the onset of unconjugated hyperbilirubinemia in the first week of life. Therefore, we suggest that urine culture should be considered as a part of the diagnostic evaluation of jaundiced neonates older than 3 days with an unexplained etiology.

Emerging clinico-epidemiological trends in melioidosis: analysis of 95 cases from western coastal India - Corrected Proof

K. Vidyalakshmi, S. Lipika, S. Vishal, S. Damodar, M. Chakrapani — 2012-04-18

Summary: Objectives: To study the clinico-epidemiological trends in melioidosis, an emerging disease in the western coastal region of India.Methods: Data of 95 patients with melioidosis in the western coastal region of India were retrospectively analyzed with respect to monthly rainfall, risk factors, clinical presentations, and outcome.Results: A strong linear correlation was seen between average monthly rainfall and the occurrence of cases (p=0.002). Mortality was seen only in patients with bacteremia (p<0.001). Nine (40.9%) patients with septic shock died (p<0.001). Age ≥40 years and diabetes mellitus were seen in 75.8% of cases, each. Pneumonia was the most common clinical presentation (32.6%), followed by musculoskeletal disease (20%), melioidotic lymphadenopathy (7.4%), and dental abscess (6.3%). Only 36.8% of patients had exposure to wet soil/surface water.Conclusions: Melioidosis is quite prevalent in the western coastal region of India, and is strongly associated with rainfall, age, and diabetes mellitus. Higher proportions of musculoskeletal, dental, and lymph node melioidosis were seen in this region as compared to endemic areas. Bacteremic melioidosis has a poorer prognosis than non-bacteremic melioidosis. The presence of septic shock is a strong predictor of mortality. Percutaneous inoculation may not be the main portal of entry for Burkholderia pseudomallei in this region.

WITHDRAWN: Transplant - Corrected Proof

2009-03-27

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.