A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil

We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

Waiting for chikungunya fever in Argentina: spatio-temporal risk maps

Chikungunya virus (CHIKV) transmission has been detected in America in 2013 and recently reached south up to Bolivia, Brazil and Paraguay, bordering countries of Argentina. The presence of the mosquito Aedes aegyptiin half of the country together with the regional context drove us to make a rapid assessment of transmission risk. Temperature thresholds for vector breeding and for virus transmission, together with adult activity from the literature, were mapped on a monthly basis to estimate risk. Transmission of chikungunya byAe. aegyptiin the world was seen at monthly mean temperatures from 21-34ºC, with the majority occurring between 26-28ºC. In Argentina temperatures above 21ºC are observed since September in the northeast, expanding south until January and retreating back to the northeast in April. The maximum area under risk encompasses more than half the country and around 32 million inhabitants. Vector adult activity was registered where monthly means temperatures exceeded 13ºC, in the northeast all over the year and in the northern half from September-May. The models herein proposed show that conditions for transmission are already present. Considering the regional context and the historic inability to control dengue in the region, chikungunya fever illness seems unavoidable.

A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old

This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose.

Yellow fever impact on brown howler monkeys (Alouatta guariba clamitans) in Argentina: a metamodelling approach based on population viability analysis and epidemiological dynamics

In South America, yellow fever (YF) is an established infectious disease that has been identified outside of its traditional endemic areas, affecting human and nonhuman primate (NHP) populations. In the epidemics that occurred in Argentina between 2007-2009, several outbreaks affecting humans and howler monkeys (Alouatta spp) were reported, highlighting the importance of this disease in the context of conservation medicine and public health policies. Considering the lack of information about YF dynamics in New World NHP, our main goal was to apply modelling tools to better understand YF transmission dynamics among endangered brown howler monkey (Alouatta guariba clamitans) populations in northeastern Argentina. Two complementary modelling tools were used to evaluate brown howler population dynamics in the presence of the disease: Vortex, a stochastic demographic simulation model, and Outbreak, a stochastic disease epidemiology simulation. The baseline model of YF disease epidemiology predicted a very high probability of population decline over the next 100 years. We believe the modelling approach discussed here is a reasonable description of the disease and its effects on the howler monkey population and can be useful to support evidence-based decision-making to guide actions at a regional level.

Rickettsia amblyommii infecting Amblyomma sculptum in endemic spotted fever area from southeastern Brazil

The Rickettsia bacteria include the aetiological agents for the human spotted fever (SF) disease. In the present study, a SF groupRickettsia amblyommii related bacterium was detected in a field collected Amblyomma sculptum (Amblyomma cajennense species complex) tick from a Brazilian SF endemic site in southeastern Brazil, in the municipality of Juiz de Fora, state of Minas Gerais. Genetic analysis based on genes ompA,ompB and htrA showed that the detected strain, named R. amblyommii str. JF, is related to the speciesR. amblyommii.

Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-β during acute phase

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-α similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), IFN- β were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN- β which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN- β in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis.

Targeting inflammasomes in rheumatic diseases.

Inflammasomes are key inducers of inflammation in response to exogenous and endogenous stimuli, because they regulate the processing and secretion of the proinflammatory cytokines IL-1β and IL-18. Thus, inflammasomes have a crucial role in host defence against infection, but they can also be involved in inflammatory diseases. Indeed, the NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome has been shown to play a part in several inflammatory rheumatic disorders, although the mechanisms involved are better elucidated in some of these diseases than in others. In particular, the pathogenesis of cryopyrin-associated periodic syndromes and microcrystal-induced arthritides is thought to be dependent on activation of the NLRP3 inflammasome, and IL-1 inhibition has shown efficacy as a therapeutic strategy in both groups of conditions. In this Review, we describe the current understanding of the mechanisms that trigger the inflammasome, and consider the relevance of the inflammasome to a variety of rheumatic diseases. In addition, we discuss the current therapies targeting this molecular complex, as well as future therapeutic prospects.

African tick-bite fever: a new entity in the differential diagnosis of multiple eschars in travelers. Description of five cases imported from South Africa to Switzerland.

African tick-bite fever (ATBF) is a newly described spotted fever rickettsiosis that frequently presents with multiple eschars in travelers returning from sub-Saharan Africa and, to a lesser extent, from the West Indies. It is caused by the bite of an infected Amblyomma tick, whose hunting habits explain the typical presence of multiple inoculation skin lesions and the occurrence of clustered cases. The etiological agent of ATBF is Rickettsia africae, an emerging tick-borne pathogenic bacterium. We describe herein a cluster of five cases of ATBF occurring in Swiss travelers returning from South Africa. The co-incidental infections in these five patients and the presence of multiple inoculation eschars, two features pathognomonic of this rickettsial disease, suggested the diagnosis of ATBF. Indeed, the presence of at least one inoculation eschar is observed in 53-100% of cases and multiple eschars in 21-54%. Two patients presented regional lymphadenitis and one a mild local lymphangitis. Though a cutaneous rash is described in 15-46% of cases, no rash was observed in our series. ATBF was confirmed by serology. Thus, ATBF has recently emerged as one of the most important causes of flu-like illness in travelers returning from Southern Africa. The presence of one or multiple eschars of inoculation is an important clinical clue to the diagnosis. It can be confirmed by serology or by PCR of a biopsy of the eschar. Culture can also be done in reference laboratories. Dermatologists and primary care physicians should know this clinical entity, since an inexpensive and efficient treatment is available.

Is it worth treating fever in intensive care unit patients? Preliminary results from a randomized trial of the effect of external cooling.

BACKGROUND: Antipyresis is a common clinical practice in intensive care, although it is unknown if fever is harmful, beneficial, or a negligible adverse effect of infection and inflammation. METHODS: In a randomized study, rectal temperature and discomfort were assessed in 38 surgical intensive care unit patients without neurotrauma or severe hypoxemia and with fever (temperature >/=38.5 degrees C) and systemic inflammatory response syndrome. Eighteen patients received external cooling while 20 received no antipyretic treatment. RESULTS: Temperature and discomfort decreased similarly in both groups after 24 hours. No significant differences in recurrence of fever, incidence of infection, antibiotic therapy, intensive care unit and hospital length of stay, or mortality were noted between the groups. CONCLUSIONS: These results suggest that the systematic suppression of fever may not be useful in patients without severe cranial trauma or significant hypoxemia. Letting fever take its natural course does not seem to harm patients with systemic inflammatory response syndrome or influence the discomfort level and may save costs.

Feasibility and clinical outcomes when using practice guidelines for evaluation of fever in returning travelers and migrants : a validation study.

BACKGROUND: Practice guidelines for examining febrile patients presenting upon returning from the tropics were developed to assist primary care physicians in decision making. Because of the low level of evidence available in this field, there was a need to validate them and assess their feasibility in the context they have been designed for. OBJECTIVES: The objectives of the study were to (1) evaluate physicians' adherence to recommendations; (2) investigate reasons for non-adherence; and (3) ensure good clinical outcome of patients, the ultimate goal being to improve the quality of the guidelines, in particular to tailor them for the needs of the target audience and population. METHODS: Physicians consulting the guidelines on the Internet (www.fevertravel.ch) were invited to participate in the study. Navigation through the decision chart was automatically recorded, including diagnostic tests performed, initial and final diagnoses, and clinical outcomes. The reasons for non-adherence were investigated and qualitative feedback was collected. RESULTS: A total of 539 physician/patient pairs were included in this study. Full adherence to guidelines was observed in 29% of the cases. Figure-specific adherence rate was 54.8%. The main reasons for non-adherence were as follows: no repetition of malaria tests (111/352) and no presumptive antibiotic treatment for febrile diarrhea (64/153) or abdominal pain without leukocytosis (46/101). Overall, 20% of diversions from guidelines were considered reasonable because there was an alternative presumptive diagnosis or the symptoms were mild, which means that the corrected adherence rate per case was 40.6% and corrected adherence per figure was 61.7%. No death was recorded and all complications could be attributed to the underlying illness rather than to adherence to guidelines. CONCLUSIONS: These guidelines proved to be feasible, useful, and leading to good clinical outcomes. Almost one third of physicians strictly adhered to the guidelines. Other physicians used the guidelines not to forget specific diagnoses but finally diverged from the proposed attitudes. These diversions should be scrutinized for further refinement of the guidelines to better fit to physician and patient needs.

Impact of a telenursing service on satisfaction and health outcomes of children with inflammatory rheumatic diseases and their families: a crossover randomized trial study protocol.

BACKGROUND: Pediatric rheumatic diseases have a significant impact on children's quality of life and family functioning. Disease control and management of the symptoms are important to minimize disability and pain. Specialist clinical nurses play a key role in supporting medical teams, recognizing poor disease control and the need for treatment changes, providing a resource to patients on treatment options and access to additional support and advice, and identifying best practices to achieve optimal outcomes for patients and their families. This highlights the importance of investigating follow-up telenursing (TN) consultations with experienced, specialist clinical nurses in rheumatology to provide this support to children and their families. METHODS/DESIGN: This randomized crossover, experimental longitudinal study will compare the effects of standard care against a novel telenursing consultation on children's and family outcomes. It will examine children below 16 years old, recently diagnosed with inflammatory rheumatic diseases, who attend the pediatric rheumatology outpatient clinic of a tertiary referral hospital in western Switzerland, and one of their parents. The telenursing consultation, at least once a month, by a qualified, experienced, specialist nurse in pediatric rheumatology will consist of providing affective support, health information, and aid to decision-making. Cox's Interaction Model of Client Health Behavior serves as the theoretical framework for this study. The primary outcome measure is satisfaction and this will be assessed using mixed methods (quantitative and qualitative data). Secondary outcome measures include disease activity, quality of life, adherence to treatment, use of the telenursing service, and cost. We plan to enroll 56 children. DISCUSSION: The telenursing consultation is designed to support parents and children/adolescents during the course of the disease with regular follow-up. This project is novel because it is based on a theoretical standardized intervention, yet it allows for individualized care. We expect this trial to confirm the importance of support by a clinical specialist nurse in improving outcomes for children and adolescents with inflammatory rheumatisms. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT01511341 (December 1st, 2012).

The value of serum procalcitonin level for differentiation of infectious from noninfectious causes of fever after orthopaedic surgery.

BACKGROUND: Early diagnosis of postoperative orthopaedic infections is important in order to rapidly initiate adequate antimicrobial therapy. There are currently no reliable diagnostic markers to differentiate infectious from noninfectious causes of postoperative fever. We investigated the value of the serum procalcitonin level in febrile patients after orthopaedic surgery. METHODS: We prospectively evaluated 103 consecutive patients with new onset of fever within ten days after orthopaedic surgery. Fever episodes were classified by two independent investigators who were blinded to procalcitonin results as infectious or noninfectious origin. White blood-cell count, C-reactive protein level, and procalcitonin level were assessed on days 0, 1, and 3 of the postoperative fever. RESULTS: Infection was diagnosed in forty-five (44%) of 103 patients and involved the respiratory tract (eighteen patients), urinary tract (eighteen), joints (four), surgical site (two), bloodstream (two), and soft tissues (one). Unlike C-reactive protein levels and white blood-cell counts, procalcitonin values were significantly higher in patients with infection compared with patients without infection on the day of fever onset (p = 0.04), day 1 (p = 0.07), and day 3 (p = 0.003). Receiver-operating characteristics demonstrated that procalcitonin had the highest diagnostic accuracy, with a value of 0.62, 0.62, and 0.71 on days 0, 1, and 3, respectively. In a multivariate logistic regression analysis, procalcitonin was a significant predictor for postoperative infection on days 0, 1, and 3 of fever with an odds ratio of 2.3 (95% confidence interval, 1.1 to 4.4), 2.3 (95% confidence interval, 1.1 to 5.2), and 3.3 (95% confidence interval, 1.2 to 9.0), respectively. CONCLUSIONS: Serum procalcitonin is a helpful diagnostic marker supporting clinical and microbiological findings for more reliable differentiation of infectious from noninfectious causes of fever after orthopaedic surgery.

Predicting Bacteremia in Children With Cancer and Fever in Chemotherapy-induced Neutropenia: Results of the Prospective Multicenter SPOG 2003 FN Study.

STUDY AIM:: To develop a score predicting the risk of bacteremia in cancer patients with fever and neutropenia (FN), and to evaluate its performance. METHODS:: Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of bacteremia was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. RESULTS:: Bacteremia was reported in 67 (16%) of 423 FN episodes. In 34 episodes (8%), bacteremia became known only after reassessment after 8 to 24 hours of inpatient management. Predicting bacteremia at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The reassessment score predicting future bacteremia in 390 episodes without known bacteremia used the following 4 variables: hemoglobin ≥90 g/L at presentation (weight 3), platelet count <50 G/L (3), shaking chills (5), and other need for inpatient treatment or observation according to the treating physician (3). Applying a threshold ≥3, the score-simplified into a low-risk checklist-predicted bacteremia with 100% sensitivity, with 54 episodes (13%) classified as low-risk, and a specificity of 15%. CONCLUSIONS:: This reassessment score, simplified into a low-risk checklist of 4 routinely accessible characteristics, identifies pediatric patients with FN at risk for bacteremia. It has the potential to contribute to the reduction of use of antimicrobials in, and to shorten the length of hospital stays of pediatric patients with cancer and FN.

Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study.

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.