Seroprevalence for dengue virus in a hyperendemic area and associated socioeconomic and demographic factors using a cross-sectional design and a geostatistical approach, state of São Paulo, Brazil.

BACKGROUND: São José do Rio Preto is one of the cities of the state of São Paulo, Brazil, that is hyperendemic for dengue, with the presence of the four dengue serotypes. OBJECTIVES: to calculate dengue seroprevalence in a neighbourhood of São José do Rio Preto and identify if socioeconomic and demographic covariates are associated with dengue seropositivity. METHODS: A cohort study to evaluate dengue seroprevalence and incidence and associated factors on people aged 10 years or older, was assembled in Vila Toninho neighbourhood, São José do Rio Preto. The participant enrolment occurred from October 2015 to March 2016 (the first wave of the cohort study), when blood samples were collected for serological test (ELISA IgG anti-DENV) and questionnaires were administrated on socio-demographic variables. We evaluated the data collected in this first wave using a cross-sectional design. We considered seropositive the participants that were positive in the serological test (seronegative otherwise). We modelled the seroprevalence with a logistic regression in a geostatistical approach. The Bayesian inference was made using integrated nested Laplace approximations (INLA) coupled with the Stochastic Partial Differential Equation method (SPDE). RESULTS: We found 986 seropositive individuals for DENV in 1322 individuals surveyed in the study area in the first wave of the cohort study, corresponding to a seroprevalence of 74.6% (95%CI: 72.2-76.9). Between the population that said never had dengue fever, 68.4% (566/828) were dengue seropositive. Older people, non-white and living in a house (instead of in an apartment), were positively associated with dengue seropositivity. We adjusted for the other socioeconomic and demographic covariates, and accounted for residual spatial dependence between observations, which was found to present up to 800 m. CONCLUSIONS: Only one in four people aged 10 years or older did not have contact with any of the serotypes of dengue virus in Vila Toninho neighbourhood in São José do Rio Preto. Age, race and type of house were associated with the occurrence of the disease. The use of INLA in a geostatistical approach in a Bayesian context allowed us to take into account the spatial dependence between the observations and identify the associated covariates to dengue seroprevalence.

Comparison between the traditional (1997) and revised (2009) WHO classifications of dengue disease: a retrospective study of 30 670 patients.

OBJECTIVE: To compare WHO's traditional (1997) and revised (2009) guidelines for dengue classification, using a large sample of patients of all ages with varying clinical conditions from a dengue-endemic area in Brazil. METHODS: We compared 30 670 laboratory-confirmed dengue cases (1998-2012) using both WHO's dengue classification guidelines. Stereotype ordinal logistic regressions were used to analyse the association between patients' demographics and signs and symptoms related to dengue infection severity, as defined in the 1997 and 2009 guidelines. We then compared the degree of agreement in dengue classification of both guidelines. RESULTS: Dengue signs and symptoms in patients were poorly correlated to disease severity as defined by both guidelines (Cramer's V test <0.2). Hypotensive shock was the exception for both classifications, presenting dependence (Z = 56.42; P < 0.001, and Z = 55.24; P < 0.001) and high agreement (Cramers's V = 1; P < 0.001, and Cramers's V = 0.97; P < 0.001) for WHO 1997 and 2009, respectively. Last, we also found substantial agreement in disease classification between both guidelines (Kendall tau-b = 0.79; P < 0.001), although 2009 guidelines were more sensitive in the detection of severe cases. CONCLUSIONS: We hope our results will inform the debate about dengue classification guidelines, particularly concerning clinical value, study comparability, and ways in which future guidelines can support the clinical management of dengue. Our results suggest that caution should be taken when using WHO guidelines to assess dengue severity to improve clinical management of patients.

Evaluation of the importance of fever with respect to dengue prognosis according to the 2009 WHO classification: a retrospective study.

BACKGROUND: The 2009 revised World Health Organization (WHO) guidelines for dengue describe fever as the core symptom. Accordingly, the diagnosis of non-febrile patients is complicated. The aim of this study was to evaluate the importance of fever in patients with dengue according to the 2009 revised WHO classification. METHODS: In this study, we assessed 30,670 dengue cases using enzyme-linked immunosorbent assay, detection of the non-structural protein 1, or polymerase chain reaction for diagnostic confirmation. Fisher's exact test was used to evaluate associations between fever and related clinical manifestations. The Mann-Whitney U test was used to assess the association of dengue classification with fever and time to treatment. The effects of fever and time to treatment on the risk of progression were analyzed using an ordinal logistic regression to stereotype the model. RESULTS: Disease classification was found to associate significantly with both fever and time to treatment (both P < 0.001). Non-febrile patients were nearly four-fold more likely to exhibit "dengue without warning signs" than "severe dengue" (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 3.20-4.36). Patients who received treatment within 7 days were twice as likely to have "dengue without warning signs" as opposed to "severe dengue" when compared to those who waited >7 days (OR = 2.23; 95% CI: 1.78-2.80). However, this difference was negligible in the multivariate analysis (OR = 1.02; 95% CI: 0.98-1.07). CONCLUSIONS: Fever is a risk factor for disease progression in patients with dengue. However, non-febrile patients should not be neglected because this may delay treatment and could lead to more severe disease.

Low sensitivity of the tourniquet test for differential diagnosis of dengue: an analysis of 28,000 trials in patients.

BACKGROUND: The aim of this study was to evaluate the utility of the tourniquet test (TT) for dengue diagnosing. To our knowledge, no previous study with such a large sample, of this duration, with as many laboratory methods referenced, or relating the results of the TT to the 2009 WHO classification of severity has been conducted thus far. METHODS: In this study, we analyzed the records of 119,589 suspected dengue cases in a Brazilian city, with 30,670 confirmed cases. The Cohen's Kappa test was applied to evaluate the degree of agreement between the tests, and the sensitivity and specificity was calculated for the TT. RESULTS: Twenty-eight thousand six hundred thirty-five TT were performed. No association between the outcome of the TT and greater severity of infection, according to the 2009 guideline, was observed (P = 0.28); furthermore, relevant agreement with the final diagnosis (κ = 0.01; 95 % CI = 0.00 to 0.02) or individually with the IgM enzyme-linked immunoassay was not observed (κ = 0.05; 95 % CI = 0.04 to 0.06), and was even lower with PCR (κ = 0.27; 95 % CI = 0.06 to 0.49). Most importance of the TT was shown in relation to specificity (88.9 %; 95 % CI = 0.88 to 0.89) and negative predictive value (70.3 %; CI 95 % = 0.70 to 0.71). CONCLUSIONS: TT was more effective in detecting cases that were truly negative than positive. These results suggest that the TT should not be used as diagnosis of dengue.

Endemicity of the High-Risk Clone Klebsiella pneumoniae ST340 Coproducing QnrB, CTX-M-15, and KPC-2 in a Brazilian Hospital.

The dissemination of multiresistant Klebsiella pneumoniae carbapenemase (KPC)-2-producing Klebsiella pneumoniae isolates belonging to international high-risk clones poses a major health care threat. In this study, 48 nonduplicated, carbapenem-resistant K. pneumoniae isolated from 2011 to 2014 in a tertiary hospital were investigated. The blaKPC-2 gene was the only determinant for carbapenem resistance. The blaCTX-M-15 gene was the main determinant for the production of extended-spectrum beta-lactamase (ESBL), whereas aph(3')-Ia and qnrB were the most common genes associated with resistance to aminoglycosides and quinolones, respectively. Nine different sequence types (STs) were identified. The most common was ST340. Molecular typing by enterobacterial repetitive intergenic consensus-PCR placed 48 strains among 10 different clusters. In the studied hospital, the high-risk clone of KPC-2-producing K. pneumoniae ST340, harboring genes that codify aminoglycoside modifying enzymes, QnrB and CTX-M-15 plus CTXM-2-type ESBLs, is disseminated and acts as a major agent of infections in critically ill patients.

Clinical, laboratory, and demographic determinants of hospitalization due to dengue in 7613 patients: A retrospective study based on hierarchical models.

In Brazil, the incidence of hospitalization due to dengue, as an indicator of severity, has drastically increased since 1998. The objective of our study was to identify risk factors associated with subsequent hospitalization related to dengue. We analyzed 7613 dengue confirmed via serology (ELISA), non-structural protein 1, or polymerase chain reaction amplification. We used a hierarchical framework to generate a multivariate logistic regression based on a variety of risk variables. This was followed by multiple statistical analyses to assess hierarchical model accuracy, variance, goodness of fit, and whether or not this model reliably represented the population. The final model, which included age, sex, ethnicity, previous dengue infection, hemorrhagic manifestations, plasma leakage, and organ failure, showed that all measured parameters, with the exception of previous dengue, were statistically significant. The presence of organ failure was associated with the highest risk of subsequent dengue hospitalization (OR=5·75; CI=3·53-9·37). Therefore, plasma leakage and organ failure were the main indicators of hospitalization due to dengue, although other variables of minor importance should also be considered to refer dengue patients to hospital treatment, which may lead to a reduction in avoidable deaths as well as costs related to dengue.

Clinical, laboratory and virological data from suspected ZIKV patients in an endemic arbovirus area.

BACKGROUND: The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between the diseases caused by ZIKV, dengue (DENV) and chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. Brazilian authorities largely rely on clinical and epidemiological data for the epidemiological and clinical classifications of most ZIKV cases. OBJECTIVE: To report the laboratory and clinical profiles of patients diagnosed with Zika fever based only on clinical and epidemiological data. STUDY DESIGN: We analyzed 433 suspected cases of ZIKV identified by the attending physician based on proposed clinical criteria. The samples were also screened for ZIKV, DENV and CHIKV using PCR. RESULTS: Of the 433 patients analyzed, 168 (38.8%) were laboratory-confirmed for arboviruses: 96 were positive for ZIKV, 67 were positive for DENV (56 for DENV-2, 9 for DENV-1, and 2 for DENV-4), four were positive for co-infection with ZIKV/DENV-2, and one was positive for CHIKV. The most common signs or symptoms in the patients with laboratory-confirmed ZIKV were rash (100%), arthralgia (77.1%), fever (74.0%), myalgia (74.0%) and non-purulent conjunctivitis (69.8%). In patients with laboratory-confirmed DENV infections, the most frequently observed symptoms were rash (100%), fever (79.1%), myalgia (74.6%), headache (73.1%) and arthralgia (70.1%). The measure of association between clinical manifestations and laboratory manifestations among patients with ZIKV and DENV detected a statistically significant difference only in abdominal pain (p=0.04), leukopenia (p=0.003), and thrombocytopenia (p=0.01). CONCLUSION: Our data suggests that clinical and epidemiological criteria alone are not a good tool for ZIKV and DENV differentiation, and that laboratory diagnosis should be mandatory.

Identification of temporal clusters and risk factors of bacteremia by nosocomial vancomycin-resistant enterococci.

BACKGROUND: This study aimed to evaluate a different methodology for addressing the evolution of nosocomial bacteremia by vancomycin-resistant enterococci (VRE) in a hospital setting. METHODS: In this retrospective cohort study, data were collected from the date of first registration up to December 2008 from the electronic medical records of patients with VRE bacteremia in a school hospital. RESULTS: Thirty cases of VRE bacteremia and 274 cases of vancomycin-susceptible enterococci (VSE) bacteremia were identified. The average age of the patients was 56 years. The rates of Enterococcus faecium and Enterococcus faecalis in the hospital's intensive care unit (ICU) and wards showed no statistically significant differences. The risk of acquiring VRE bacteremia was at least 3-fold higher in the ICU than in the wards. The risk of death was 2.73-fold higher in patients with VRE bacteremia compared with those with VSE bacteremia. Only one temporal cluster statistically significant of VRE bacteremia was found in the study period. CONCLUSIONS: The identification of temporal clusters can be an important tool to optimize health actions and thereby reduce the burden of operating costs.

Recurrent parasitemias and population dynamics of Plasmodium vivax polymorphisms in rural Amazonia.

Clinical trials documented alarming post-treatment Plasmodium vivax recurrence rates caused by recrudescence of surviving asexual blood stages, relapse from hypnozoites, or new infections. Here we describe high rates of P. vivax recurrence (26-40% 180 days after treatment) in two cohorts of rural Amazonians exposed to low levels of malaria transmission after a vivax malaria episode treated with chloroquine-primaquine. Microsatellite analysis of 28 paired acute infection and recurrence parasites showed only two pairs of identical haplotypes (consistent with recrudescences or reactivation of homologous hypnozoites) and four pairs of related haplotypes (sharing alleles at 11-13 of 14 microsatellites analyzed). Local isolates of P. vivax were extraordinarily diverse and rarely shared the same haplotype, indicating that frequent recurrences did not favor the persistence or reappearance of clonal lineages of parasites in the population. This fast haplotype replacement rate may represent the typical population dynamics of neutral polymorphisms in parasites from low-endemicity areas.