Cost-effectiveness analysis of universal adult immunization with tetanus-diphtheria-acellular pertussis vaccine (Tdap) versus current practice in Brazil.

BACKGROUND: A pertussis outbreak occurred in Brazil from 2011 to 2014, despite high coverage of whole-cell pertussis containing vaccines in early childhood. Infants were the most affected. This study aimed to evaluate the cost-effectiveness of introducing universal adult vaccination with Tdap into the National Immunization Program in Brazil. METHODS: Economic evaluation using a dynamic model to compare two strategies: (1) universal vaccination with single dose of Tdap at 20 years of age and (2) current practice (only pregnant women pertussis vaccination). The health system perspective was adopted. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Vaccine effectiveness (VE) was obtained from a population-based observational study. Epidemiological, resource utilization and cost estimates were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS), based on life expectancy at birth in Brazil in 2015. Univariate and multivariate sensitivity analysis were performed. RESULTS: Adult vaccination with VE of 82.6% and coverage of 40%, at price of US$7.01 per dose, and assuming herd protection would avoid 167 infant deaths by pertussis, saving 12,325 years of life and costing a total of US$105495891.61, from the health system perspective. The universal immunization would result in ICER of US$8459.13. The results were highly sensitive to disease incidence. CONCLUSIONS: The results suggest that universal adult vaccination with Tdap would not be a cost-effective intervention for preventing pertussis cases and deaths in infants in Brazil.

Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases.

BACKGROUND: Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVE: The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS: Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS: In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913). MAIN CONCLUSIONS: YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases

BACKGROUND Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of São Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVE The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913). MAIN CONCLUSIONS YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.

Are CYP1A1, CYP17 and CYP1B1 mutation genes involved on girls with precocious puberty? A pilot study.

OBJECTIVES: To investigate three genes associated with puberty timing in girls with central precocious puberty by evaluating the association between polymorphism in the gene sequence codifying the enzymes participating in steroidogenesis, CYP1A1, CYP17, and CYP1B1 and central precocious puberty. STUDY DESIGN: A total of 177 patients was included and divided into two groups: Case group with 73 girls diagnosed with central precocious puberty; Control group with 104 girls with puberty onset after 8 years of age who were followed at the Sector of Gynecology of Childhood and Adolescence, Division of Gynecology Clinic, HC-FMUSP. Polymorphism presence was assessed in the genes involved in estrogen metabolism (CYP1A1, CYP17, and CYP1B1) by the restriction fragment length polymorphism (RFLP) technique using DNA from peripheral blood. RESULTS: No significant difference in the distribution of the CYP1A1 Mspl (p=0.86) and CYP17 (p=0.12) genotypes was detected between the two study groups. As for CYP1B1 Eco571, the mutated C/C genotype was found to be more frequent in the control group than in the case group (p=0.03). CONCLUSION: Our data suggest the CYP1B1 Eco571 gene variant is associated with puberty timing.

Hepatitis B (HBV), hepatitis C (HCV) and hepatitis delta (HDV) viruses in the Colombian population--how is the epidemiological situation?

BACKGROUND: Viral hepatitis B, C and delta still remain a serious problem worldwide. In Colombia, data from 1980s described that HBV and HDV infection are important causes of hepatitis, but little is known about HCV infection. The aim of this study was to determine the currently frequency of HBV, HCV and HDV in four different Colombian regions. METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted in 697 habitants from 4 Colombian departments: Amazonas, Chocó, Magdalena and San Andres Islands. Epidemiological data were obtained from an interview applied to each individual aiming to evaluate risk factors related to HBV, HCV or HDV infections. All samples were tested for HBsAg, anti-HBc, anti-HBs and anti-HCV markers. Samples that were positive to HBsAg and/or anti-HBc were tested to anti-HDV. Concerning the geographical origin of the samples, the three HBV markers showed a statistically significant difference: HBsAg (p = 0.033) and anti-HBc (p<0.001) were more frequent in Amazonas and Magdalena departments. Isolated anti-HBs (a marker of previous vaccination) frequencies were: Chocó (53.26%), Amazonas (32.88%), Magdalena (17.0%) and San Andrés (15.33%)--p<0.001. Prevalence of anti-HBc increased with age; HBsAg varied from 1.97 to 8.39% (p = 0.033). Amazonas department showed the highest frequency for anti-HCV marker (5.68%), while the lowest frequency was found in San Andrés Island (0.66%). Anti-HDV was found in 9 (5.20%) out of 173 anti-HBc and/or HBsAg positive samples, 8 of them from the Amazonas region and 1 from them Magdalena department. CONCLUSIONS/SIGNIFICANCE: In conclusion, HBV, HCV and HDV infections are detected throughout Colombia in frequency levels that would place some areas as hyperendemic for HBV, especially those found in Amazonas and Magdalena departments. Novel strategies to increase HBV immunization in the rural population and to strengthen HCV surveillance are reinforced by these results.

Karyotypic and fluorescent in situ hybridization study of the centromere of chromosome 7 in secondary myeloid neoplasms.

BACKGROUND: Secondary myeloid neoplasms comprise a group of secondary diseases following exposure to myelotoxic agents or due to congenital diseases. The improvement of anticancer agents and immunosuppressive drugs seem to be associated with an increased incidence of secondary myeloid neoplasms. Karyotyping of bone marrow is essential for diagnosis and prognosis. Previous use of alkylating agents and radiation are associated with clonal abnormalities such as recurrent unbalanced -5/5q-, -7/7q- and complex karyotypes, whereas topoisomerase-II inhibitors lead to changes such as the balanced 11q23 rearrangement, t(8;21), t(15;17) and inv(16). OBJECTIVE: To study the clinical and cytogenetic data of patients with secondary myeloid neoplasms who took antineoplastic and/or immunosuppressive drugs or progressed from aplastic anemia. METHODS: The clinical and cytogenetic characteristics of 42 patients diagnosed with secondary myeloid neoplasms in one institution were retrospectively evaluated. Of these, 25, 11 and 6 patients had had oncological diseases, aplastic anemia and other diseases, respectively. Conventional cytogenetic and FISH analyses were performed for monosomy 7. RESULTS: The cytogenetic study was conclusive in 32 cases with 84.4% of clonal abnormalities. Monosomy 7 and complex karyotypes were present in 44.4% and 37%, respectively. A high prevalence of unbalanced abnormalities (96.3%) was observed. Monosomy 7 was more prevalent in patients with myelodysplastic syndromes/myeloid neoplasms after aplastic anemia (66.6%). The median survival after diagnosis of myeloid neoplasms was only 5.7 months. Normal cytogenetics was associated to better survival (p-value = 0.03). There was a slightly worse trend of survival for patients with complex karyotypes (p-value = 0.057). Abnormal karyotype was an independent risk factor for poor survival (p-value = 0.012). CONCLUSION: This study enhances the importance of cytogenetic analysis of patients at the time of diagnosis of secondary myeloid neoplasms.