Rheumatic fever: a multicenter study in the State of São Paulo

Rheumatic fever is still the most commonly seen rheumatic disease in Brazilian pediatric rheumatology clinics. It remains a significant health problem since subsequent cardiac sequelae represent one of the most important causes of chronic heart disease in children. We reviewed the clinical manifestations of rheumatic fever in 786 patients, followed at seven pediatric rheumatology clinics in the state of São Paulo, Brazil. All patients were diagnosed according to revised Jones' criteria. Regarding major criteria, 396 (50.4%) children exhibited carditis, 453 (57.6%) polyarthritis, 274 (34.8%) chorea, 13 (1.6%) erythema marginatum, and 12 (1.5%) subcutaneous nodules. Valvular lesions documented by echocardiography in the absence of accompanying auscultatory findings were found in 144 (18.3%) patients. Migratory polyarthritis was observed in 290 (64.0%) patients with articular involvement. Documented previous streptococcal infection assessed by serum antistreptolysin (ASO) titers occurred in 531 (67.5%) patients. Even though prophylaxis with benzathine penicillin was recommended to all patients, recurrent attacks were observed in 147 (18.7%). We emphasize the high frequency of chorea, silent carditis and recurrences in our series as well as the variable clinical presentation of arthritis in rheumatic fever. Multicenter studies should be encouraged to improve our understanding of the clinical features of rheumatic diseases in children and adolescents.

Prevalence of Rheumatic Heart Disease in a Public School of Belo Horizonte

Background: Previous studies indicate that compared with physical examination, Doppler echocardiography identifies a larger number of cases of rheumatic heart disease in apparently healthy individuals. Objectives: To determine the prevalence of rheumatic heart disease among students in a public school of Belo Horizonte by clinical evaluation and Doppler echocardiography. Methods: This was a cross-sectional study conducted with 267 randomly selected school students aged between 6 and 16 years. students underwent anamnesis and physical examination with the purpose of establishing criteria for the diagnosis of rheumatic fever. They were all subjected to Doppler echocardiography using a portable machine. Those who exhibited nonphysiological mitral regurgitation (MR) and/or aortic regurgitation (AR) were referred to the Doppler echocardiography laboratory of the Hospital das Clínicas of the Universidade Federal of Minas Gerais (HC-UFMG) to undergo a second Doppler echocardiography examination. According to the findings, the cases of rheumatic heart disease were classified as definitive, probable, or possible. Results: Of the 267 students, 1 (0.37%) had a clinical history compatible with the diagnosis of acute rheumatic fever (ARF) and portable Doppler echocardiography indicated nonphysiological MR and/or AR in 25 (9.4%). Of these, 16 (6%) underwent Doppler echocardiography at HC-UFMG. The results showed definitive rheumatic heart disease in 1 student, probable rheumatic heart disease in 3 students, and possible rheumatic heart disease in 1 student. Conclusion: In the population under study, the prevalence of cases compatible with rheumatic involvement was 5 times higher on Doppler echocardiography (18.7/1000; 95% CI 6.9/1000-41.0/1000) than on clinical evaluation (3.7/1000-95% CI).

Streptococcal acute pharyngitis

Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci) is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine.

Immediate and long term evolution of valve replacement in children less than 12 years old

OBJECTIVE: The aim of this work was the follow-up and evaluation of valve replacement in children under 12 years of age. METHODS: Forty-four children less than 12 years old were underwent valve replacement at INCOR-HCFMUSP between January 1986 and December 1992. Forty (91%) were rheumatic, 39 (88.7%) were in functional classes II or IV, 19 (43.2%) were operated upon on an emergency basis, and 6 (13.6%) had atrial fibrillation. Biological prostheses (BP) were employed in 26 patients (59.1%), and mechanical prostheses (MP) in 18 (40.9%). Mitral valves were replaced in 30 (68.7%), aortic valves in 8 (18.2%), a tricuspid valve in 1 (2.3%), and double (aortic and mitral) valves in 5 (11.4) of the patients. RESULTS: Hospital mortality was of 4.5% (2 cases). The mean follow-up period was 5.8 years. Re-operations occurred in 63.3% of the patients with BP and in 12.5% of those with MP (p=0.002). Infectious endocarditis was present in 26.3% of the BP, but in none of the cases of MP (p=0.049). Thrombosis occurred in 2 (12.5%) and hemorrhage in one (6.5%) of the patients with a MP. Delayed mortality occurred in 5 (11.9%) of the patients over a mean period of 2.6 years; four had had BP and one had a MP (NS). Actuarial survival and re-operation-free curves after 10 years were respectively, 82.5±7.7 (SD)% and 20.6±15.9%. CONCLUSION: Patients with MP required fewer re-operation, had less infectious endocarditis and lower late mortality rates compared with patients with bioprostheses. The former, therefore, appear to be the best valve replacement for pediatric patients.

Mortality due to cardiovascular disease in women during the reproductive age (15 to 49 years), in the State of São Paulo, Brazil, from 1991 to 1995

OBJECTIVE: To describe mortality due to cardiovascular diseases in women during the reproductive age (15 to 49 years) in the state of São Paulo, Brazil, from 1991 to 1995. METHODS: A list of all deaths and their underlying causes, coded according to the International Classification of Diseases, 9th revision, multiple causes of death, and estimates of the female population according to age groups were provided by the SEADE Foundation. Specific coefficients for 100 thousand women for each year as well as the medians of these coefficients related to 5 years, and the percentage of death by subgroups were calculated. RESULTS: Cerebrovascular diseases have the highest coefficients (14.24 for 100 thousand females), followed by ischemic heart disease (7.37), other heart diseases (6.39), hypertensive disease (3.03), chronic rheumatic heart disease (1.58), pulmonary vascular diseases (1.29), and active rheumatic fever (0.05). Systemic arterial hypertension, as an associated cause, occurred in 55.3% to 57.8% of all the deaths due to intracerebral hemorrhage and in 30.4% to 30.8% due to subarachnoid hemorrhage. CONCLUSION: The significance of cerebrovascular diseases, coronary artery disease, and systemic arterial hypertension as causes of mortality suggests the need to emphasize preventive actions for young women who have the potential to reproduce to avoid possible complications in future pregnancies, and premature mortality.

Comparison of a Recombinant-antigen Enzyme Immunoassay with Treponema pallidum Hemagglutination Test for Serological Confirmation of Syphilis

A recombinant-antigen enzyme immunoassay (EIA), BioSCREEN TM anti-Treponema pallidum, was compared favorably with the T. pallidum hemagglutination test, in the detection of specific antibodies in different groups of sera from patients with primary (n = 38), secondary (n = 10), early latent (n = 28) and congenital syphilis (n = 2), patients with leptospirosis ( n= 8), infectious mononucleosis (n = 7), hepatitis (n = 9), diabetes mellitus (n = 11), rheumatoid arthritis (n = 13), leprosy (n = 11), tuberculosis (n = 9), HIV/Aids ( n= 12), systemic lupus erythematosus (n = 4), rheumatic fever (n = 3), old-persons (n = 9), pregnant women (n = 29) and blood donors (n = 164). The coincidence between them was 95.1%. The sensitivity and specificity of the EIA were 93.3% and 95.5%, respectively. Fifteen serum specimens belonging to old-persons, pregnant women, blood donors, and patients with human leptospirosis, hepatitis, diabetes mellitus, tuberculosis and rheumatic fever gave false-positive results by Venereal Disease Research Laboratory and/or Rapid Plasma Reagin. The EIA can be used as alternative method for the serological confirmation of syphilis.

Brain SPECT imaging in Sydenham's chorea

The objective of the present study was to determine whether brain single-photon emission computed tomography (SPECT) imaging is capable of detecting perfusional abnormalities. Ten Sydenham's chorea (SC) patients, eight females and two males, 8 to 25 years of age (mean 13.4), with a clinical diagnosis of SC were submitted to brain SPECT imaging. We used HMPAO labeled with technetium-99m at a dose of 740 MBq. Six examinations revealed hyperperfusion of the basal ganglia, while the remaining four were normal. The six patients with abnormal results were females and their data were not correlated with severity of symptoms. Patients with abnormal brain SPECT had a more recent onset of symptoms (mean of 49 days) compared to those with normal SPECT (mean of 85 days) but this difference did not reach statistical significance. Brain SPECT can be a helpful method to determine abnormalities of the basal ganglia in SC patients but further studies on a larger number of patients are needed in order to detect the phase of the disease during which the examination is more sensitive.

Typhoid fever in children of low and high socieconomic strata: comparison of hygiene habits

The relationship between the hygienic habits of children who had typhoid fever (TF) who had recently begun attending school and their family group, is assessed. It is supposed that children, independently of their SES, acquired TF because of inadequate habits which facilitated the oral-fecal cycle. The sample was formed of 40 child-mother dyads: 20 of low SES (group A) and 20 of high SES (group B), the child of each of which had had TF. Results showed that the hygienic habits of children with respect to the oral-fecal cycle, their perception of school toilet cleanliness as well as the mothers' explanation of their children's hygienic habits is very similar in the two groups. The importance of these results is that the SES is seem to be irrelevant in the case of TF but that the hygienic habits of the children are of importance. Public health policy should be modified to include the teaching of proper hygienic habits (oral-fecal cycle).

Hygiene habits and carriers in families with a child who has had typhoid fever

The relationship between asymptomatic shedding of bacterial enteropathogens and the hygiene habits of families who have had a child with typhoid fever (TF) are investigated. The sample was made up of 80 families: 40 families in which one child had had TF (Group A) and 40 in which no children or either of the parents had had a history of TF (Group B). In each group 20 families belonged to a low socieconomic status (SES) and 20 to a high SES. A structured interview was used to evaluate the SES and the hygiene habits of the child; observations were made to measure the hygiene habits of the family (toilet, kitchen and food preparation) and bacteriological studies (fecal samples and hand markers). Results show that carriers were more frequent in Group A than in Group B. The bacterial species found were significantly more numerous in Group A than in Group B (fecal samples: E. coli, the classic serotypes, Shigella ssp, and hand markers: E. coli). Families of Group A had higher carriage rates than those of Group B. Finally there exists a significantly higher association between inadequate hygiene habits and carrier families. These results show the need to teach specific habits of proper hygiene to the entire population, because the fact of belonging to the high SES does not in itself preclude inadequate hygiene habits.

Dengue and the risk of urban yellow fever reintroduction in São Paulo State, Brazil

OBJECTIVE: To propose a mathematical method for the estimation of the Basic Reproduction Number, R0, of urban yellow fever in a dengue-infested area. METHODS: The method is based on the assumption that, as the same vector (Aedes aegypti) causes both infections, all the quantities related to the mosquito, estimated from the initial phase of dengue epidemic, could be applied to yellow fever dynamics. It is demonstrated that R0 for yellow fever is, on average, 43% lower than that for dengue. This difference is due to the longer dengue viremia and its shorter extrinsic incubation period. RESULTS: In this study the analysis was expanded to the epidemiological situation of dengue in São Paulo in the year 2001. The total number of dengue cases increased from 3,582 in 2000 to 51,348 in 2001. It was then calculated R0 for yellow fever for every city which have shown R0 of dengue greater than 1. It was also estimated the total number of unprotected people living in highly risky areas for urban yellow fever. CONCLUSIONS: Currently there is a great number of non-vaccinated people living in Aedes aegypti infested area in the state of São Paulo.

Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vaccines: a randomized trial

OBJECTIVE: To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots). METHODS: An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind). Neutralizing yellow fever antibody titters were compared in pre- and post-immunization serum samples. Equivalence was defined as a difference of no more than five percentage points in seroconversion rates, and ratio between Geometric Mean Titters (GMT) higher than 0.67. RESULTS: Seroconversion rates were 98% or higher among subjects previously seronegative, and 90% or more of the total cohort of vaccinees, including those previously seropositive. Differences in seroconversion ranged from -0.05% to -3.02%. The intensity of the immune response was also very similar across vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the placebo group into account, the vaccines explained 93% of seroconversion. Viremia was detected in 2.7% of vaccinated subjects from Day 3 to Day 7. CONCLUSIONS: The equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD substrains was demonstrated for the first time in placebo-controlled double-blind randomized trial. The study completed the clinical validation process of a new vaccine seed-lot, provided evidence for use of alternative attenuated virus substrains in vaccine production for a major manufacturer, and for the utilization of the 17DD vaccine in other countries.

Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial

OBJECTIVE: To compare the reactogenicity of three yellow fever (YF) vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots) and placebo. METHODS: The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro, Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered ("day 0") following standardized procedures adapted to allow blinding and blocked randomization of participants to coded vaccine types. Adverse events after immunization were ascertained in an interview and in diary forms filled in by each participant. Liver enzymes were measured on days 0, 4-20 and 30 of the study. Viremia levels were measured on days 4 to 20 of follow-up. The immune response was verified through serologic tests. RESULTS: Participants were mostly young males. The seroconversion rate was above 98% among those seronegative before immunization. Compared to placebo, the excess risk of any local adverse events ranged from 0.9% to 2.5%, whereas for any systemic adverse events it ranged from 3.5% to 7.4% across vaccine groups. The excess risk of events leading to search for medical care or to interruption of work activities ranged from 2% to 4.5%. Viremia was detected in 3%-6% of vaccinees up to 10 days after vaccination. Variations in liver enzyme levels after vaccination were similar in placebo and vaccine recipients. CONCLUSIONS: The frequency of adverse events post-immunization against YF, accounting for the background occurrence of nonspecific signs and symptoms, was shown for the first time to be similar for vaccines from 17D and 17DD substrains. The data also provided evidence against viscerotropism of vaccine virus.

Yellow fever in Brazil: thoughts and hypotheses on the emergence in previously free areas

This article describes and discusses factors associated to the reemergence of yellow fever and its transmission dynamics in the states of São Paulo (Southeastern Brazil) and Rio Grande do Sul (Southern) during 2008 and 2009. The following factors have played a pivotal role for the reemergence of yellow fever in these areas: large susceptible human population; high prevalence of vectors and primary hosts (non-human primates); favorable climate conditions, especially increased rainfall; emergence of a new genetic lineage; and circulation of people and/or monkeys infected by virus. There is a need for an effective surveillance program to prevent the reemergence of yellow fever in other Brazilian states.

Evaluation of dengue fever reports during an epidemic, Colombia

OBJECTIVE To assess the validity of dengue fever reports and how they relate to the definition of case and severity. METHODS Diagnostic test assessment was conducted using cross-sectional sampling from a universe of 13,873 patients treated during the fifth epidemiological period in health institutions from 11 Colombian departments in 2013. The test under analyses was the reporting to the National Public Health Surveillance System, and the reference standard was the review of histories identified by active institutional search. We reviewed all histories of patients diagnosed with dengue fever, as well as a random sample of patients with febrile syndromes. The specificity and sensitivity of reports were estimated for this purpose, considering the inverse of the probability of being selected for weighting. The concordance between reporting and the findings of the active institutional search was calculated using Kappa statistics. RESULTS We included 4,359 febrile patients, and 31.7% were classified as compatible with dengue fever (17 with severe dengue fever; 461 with dengue fever and warning signs; 904 with dengue fever and no warning signs). The global sensitivity of reports was 13.2% (95%CI 10.9;15.4) and specificity was 98.4% (95%CI 97.9;98.9). Sensitivity varied according to severity: 12.1% (95%CI 9.3;14.8) for patients presenting dengue fever with no warning signs; 14.5% (95%CI 10.6;18.4) for those presenting dengue fever with warning signs, and 40.0% (95%CI 9.6;70.4) for those with severe dengue fever. Concordance between reporting and the findings of the active institutional search resulted in a Kappa of 10.1%. CONCLUSIONS Low concordance was observed between reporting and the review of clinical histories, which was associated with the low reporting of dengue fever compatible cases, especially milder cases.

Use of MAC-ELISA for evaluation of yellow fever vaccination

An evaluation of the IgM antibody immune response against yellow fever using strain 17D was carried out by MAC-ELISA and PRNT. The results showed an agreement of 97% between both tests and the authors conclude that MAC-ELISA can be used as a specific and sensitive asssay to replace the PRNT for detecting yellow fever antibodies in human sera, after vaccination programs.