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BACKGROUND: More than 95% of malaria transmission in Brazil occurs in the Legal Amazon Region, which in 2010 recorded around 333,429 cases reported in the Epidemiological Surveillance Information System-Malaria (Sivep_malaria), presenting an annual parasitic incidence (IPA) of 13.1 cases/1000 inhabitants. METHODS: This was a descriptive study that measured the community prevalence of Plasmodium infection and its relationship with land use in Três Fronteiras District, Colniza Municipality, Mato Grosso State. Data were collected during household visits in July 2011, with blood collection from finger pricks for the preparation of thick smear slides, and completion of a standardized case notification form. A georeferenced database was analysed, with land use evaluated as categorical variables. A kernel density map was built to show the density of cases and their location. RESULTS: Of the 621 respondents, 68(11%) had Plasmodium infection: 39 (57.4%) with Plasmodium vivax, 27(39.7%) with Plasmodium falciparum and two (2.9%) with mixed infections. Among infected individuals, 49 (72.1%) were men. Cases of malaria were distributed over the district, with greater occurrence of cases per household in open areas close to the mining company and artisanal mining sites. The was a greater density of cases located in the gold mining region. CONCLUSION: Transmission of malaria in Três Fronteiras District has a heterogeneous distribution. Individuals residing in mining and timber extraction sites have increased occurrence of Plasmodium infection.
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Malária Falciparum , Malária Vivax , População Rural , Brasil/epidemiologia , Humanos , Feminino , Masculino , Adolescente , Adulto , População Rural/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem , Criança , Pré-Escolar , Malária Vivax/epidemiologia , Malária Vivax/parasitologia , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Prevalência , Lactente , Idoso , Incidência , Idoso de 80 Anos ou mais , Plasmodium vivax , Malária/epidemiologia , Malária/transmissãoRESUMO
BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16â363 participants assessed for eligibility, 16â235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10â259 participants) or placebo (5976 participants). 16â162 participants (Butantan-DV n=10â215; placebo n=5947) were included in the per-protocol population and 16â235 (Butantan-DV n=10â259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.
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OBJECTIVES: Primaquine is essential for the radical cure of Plasmodium vivax malaria and must be metabolized into its bioactive metabolites. Accordingly, polymorphisms in primaquine-metabolizing enzymes can impact the treatment efficacy. This pioneering study explores the influence of monoamine oxidase-A (MAO-A) on primaquine metabolism and its impact on malaria relapses. METHODS: Samples from 205 patients with P. vivax malaria were retrospectively analysed by genotyping polymorphisms in MAO-A and cytochrome P450 2D6 (CYP2D6) genes. We measured the primaquine and carboxyprimaquine blood levels in 100 subjects for whom blood samples were available on the third day of treatment. We also examined the relationship between the enzyme variants and P. vivax malaria relapses in a group of subjects with well-documented relapses. RESULTS: The median carboxyprimaquine level was significantly reduced in individuals carrying low-expression MAO-A alleles plus impaired CYP2D6. In addition, this group experienced significantly more P. vivax relapses. The low-expression MAO-A status was not associated with malaria relapses when CYP2D6 had normal activity. This suggests that the putative carboxyprimaquine contribution is irrelevant when the CYP2D6 pathway is fully active. CONCLUSIONS: We found evidence that the low-expression MAO-A variants can potentiate the negative impact of impaired CYP2D6 activity, resulting in lower levels of carboxyprimaquine metabolite and multiple relapses. The findings support the hypothesis that carboxyprimaquine may be further metabolized through CYP-mediated pathways generating bioactive metabolites that act against the parasite.
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Antimaláricos , Citocromo P-450 CYP2D6 , Malária Vivax , Monoaminoxidase , Primaquina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antimaláricos/uso terapêutico , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Genótipo , Malária Vivax/tratamento farmacológico , Malária Vivax/genética , Monoaminoxidase/genética , Plasmodium vivax/genética , Polimorfismo Genético , Primaquina/uso terapêutico , Recidiva , Estudos RetrospectivosRESUMO
Abstract Objective: To determine the reference intervals (RI) for serum levels of IgG, IgM, and IgE in healthy children aged 1-10 years living in central Brazil. Method: A sample of 1743 healthy children was randomly selected from kindergartens and public schools. Reference intervals were defined by non-parametric rank (Clinical Laboratory Standards Institute, USA), bootstrapping, and Horn's robust methods. Results: By the rank method, the IgG RI was 792-1771 mg/dL for children of both sexes aged 1-10 years. IgM RI were different for gender and age groups, being 45-196 mg/dL and 34-190 mg/dL for boys aged 1-2 years and 3-10 years, respectively. For girls, the IgM RI were 50-212 mg/dL and 39-212 mg/dL, for ages 1-4 and 5-10 years, respectively. The IgE RI for both sexes and ages 1-10 years was 6-1005 mg/dL. The bootstrap method showed RI similar to the rank method but with slightly different confidence intervals. Horn's robust method determined RI different from those obtained by previous methods. Conclusion: RI for serum concentrations of IgG, IgM, and IgE were established for Brazilian children aged 1-10 years. This definition will be useful for Brazilian physicians, who will have more adequate parameters for their clinical decision-making.
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BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).
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Vacinas contra Dengue , Vírus da Dengue , Dengue , Vacinas Atenuadas , Adulto , Criança , Pré-Escolar , Humanos , Anticorpos Antivirais , Dengue/prevenção & controle , Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/uso terapêutico , Vírus da Dengue/imunologia , Método Duplo-Cego , Vacinação , Vacinas , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/uso terapêutico , Brasil , Eficácia de Vacinas , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , SeguimentosRESUMO
Sickle cell disease (SCD) is associated with a high occurrence of complications due to vaso-occlusive phenomenon such as stroke. This retrospective cohort study aimed to examine the clinical and laboratory characteristics of 120 children and adolescents with SCD and analyze the factors associated with overt stroke incidence. All relevant data were obtained from patient medical records. Survival analysis was used to compare the demographic, clinical, and laboratory characteristics between patients with and those without overt stroke. The patients were 52.5% female with a mean (SD) age of 11.2 (4.3) years. The incidence of overt stroke in this cohort was nine out of 956.7 patient-years, resulting in an incidence density of 0.94 cases/100 patient-years. Reports of greater than or equal to two previous attacks of dactylitis and greater than or equal to three episodes of acute chest syndrome (ACS)/pneumonia were associated with overt stroke and an increase in reticulocyte count and red blood cell distribution width (RDW). In conclusion, a history of a high number of dactylitis, ACS/pneumonia, increased RDW, and reticulocytosis was associated with overt stroke occurrence in children and adolescents with SCD. Future studies with a higher stroke incidence in the evaluated sample are necessary to confirm this hypothesis.
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Síndrome Torácica Aguda , Anemia Falciforme , Pneumonia , Acidente Vascular Cerebral , Criança , Humanos , Adolescente , Feminino , Masculino , Estudos Retrospectivos , Hidroxiureia , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Síndrome Torácica Aguda/etiologia , Síndrome Torácica Aguda/complicações , Pneumonia/complicaçõesRESUMO
OBJECTIVE: To determine the reference intervals (RI) for serum levels of IgG, IgM, and IgE in healthy children aged 1-10 years living in central Brazil. METHOD: A sample of 1743 healthy children was randomly selected from kindergartens and public schools. Reference intervals were defined by non-parametric rank (Clinical Laboratory Standards Institute, USA), bootstrapping, and Horn's robust methods. RESULTS: By the rank method, the IgG RI was 792-1771 mg/dL for children of both sexes aged 1-10 years. IgM RI were different for gender and age groups, being 45-196 mg/dL and 34-190 mg/dL for boys aged 1-2 years and 3-10 years, respectively. For girls, the IgM RI were 50-212 mg/dL and 39-212 mg/dL, for ages 1-4 and 5-10 years, respectively. The IgE RI for both sexes and ages 1-10 years was 6-1005 mg/dL. The bootstrap method showed RI similar to the rank method but with slightly different confidence intervals. Horn's robust method determined RI different from those obtained by previous methods. CONCLUSION: RI for serum concentrations of IgG, IgM, and IgE were established for Brazilian children aged 1-10 years. This definition will be useful for Brazilian physicians, who will have more adequate parameters for their clinical decision-making.
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Imunoglobulina E , Imunoglobulina G , Imunoglobulina M , Humanos , Masculino , Feminino , Valores de Referência , Brasil , Pré-Escolar , Imunoglobulina G/sangue , Criança , Lactente , Imunoglobulina E/sangue , Imunoglobulina M/sangue , Fatores Sexuais , Fatores Etários , Estudos TransversaisRESUMO
Leprosy is a chronic infectious disease characterized by acute inflammatory episodes that affect the skin and peripheral nerves and can develop progressive and irreversible disabilities and deformities. In addition, drug therapy and physiotherapy offer resources and techniques capable of mitigating the consequences of neural lesions, but neural lesions can occur before, during, and even after drug treatment. Thus, new treatments are needed. Photobiomodulation (PBM) might be a promissor therapy since it aims to reduce the inflammatory process and restore motor and sensory functions in the affected area. This study aims to compare the evolution of neural status, pain, and functionality in patients with leprosy and neuritis after a physiotherapeutic protocol and PBM treatment. This was a randomized controlled clinical trial that analyzed a group of patients receiving a physiotherapeutic protocol (PPG) and another receiving physiotherapeutic protocol associated with PBM (PLG) (wavelength 904 nm, potency 70 mW, time per point 9 s). Our results showed when evaluating functional capacity limitations with the SALSA scale, the PLG patients improved from moderate to mild limitations. On the other hand, the PPG remained as moderate limitations. Also, the PLG showed a significant reduction in pain on the VAS scale. The neurological assessment showed that PLG improved palpation of the median, radial, and peroneal nerves. In the strength test, PLG patients improved in the 5th finger abduction and ankle dorsiflexion. Assessing sensitivity, it was identified an improvement in PLG for the ulnar nerve and tibial nerve. All those changes were statistically significant when compared to the PPG patients. Finally, the PLG patients improved disabilities, identified by the neurological assessment of the eyes, hands, and feet. In conclusion, this study demonstrated that combining a physiotherapeutic protocol with PBM treatment effectively improved functional status and reduced pain in leprosy patients.
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Hanseníase , Terapia com Luz de Baixa Intensidade , Humanos , Hanseníase/radioterapia , Hanseníase/complicações , Nervos Periféricos , Pele/patologia , Dor/complicações , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Objective: The objective of this study was to determine the serum thyroid-stimulating hormone (TSH) concentration reference intervals (RIs) of healthy children aged 1 to 10 years of both sexes, living in the Central Region of Brazil. Subjects and methods: 1,735 children [869 (50.1%) female; 866 (49.9%) male] enrolled in the morning shift of 47 pre- and 83 public elementary schools in the municipality of Cuiabá, Mato Grosso, were studied by gathering anthropometric and social data and their medical history. A blood sample was collected from each child to determine the TSH concentration using the electrochemiluminescence method on a Cobas® 6000 modular analyzer (Analyzer series, Roche Diagnostics). Results: The RIs were determined using the 2.5 and 97.5 percentile and the mean ± 2 standard deviations methods. After identifying the homoscedastic groups by age and sex, outliers higher or lower than three standard deviations were excluded. The distribution of serum TSH concentrations showed no significant age or sex differences. Based on the percentile method, TSH RI ranged from 0.93 to 5.86 µIU/mL. Based on the mean ± 2 standard deviations, TSH RI ranged from 0.30 to 5.29 µIU/mL. Conclusion: The normal serum TSH concentration of the Brazilian children evaluated in this study differ from those of populations from other countries. Other regional population studies may validate the RIs found in this study and enable its safer use in pediatric clinical practice.
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Caracteres Sexuais , Tireotropina , Humanos , Masculino , Criança , Feminino , Brasil , Valores de Referência , Antropometria , TiroxinaRESUMO
OBJECTIVE: To determine reference intervals (RI) for serum immunoglobulin A (IgA) levels in healthy children aged 1 to 1 0 years residing in the central region of Brazil. METHODS: This cross-sectional study was conducted on 1,743 healthy children randomly selected from kindergartens and public schools in Cuiabá, MT, Brazil. The IgA RIs were defined using the statistical methods postulated by the guidelines of the United States Clinical and Laboratory Standards Institute, the nonparametric bootstrap method, and Horn's robust method after the correction of discrepancies by Tukey's, Dixon's, and Horn's methods, respectively. The results were defined based on the values contained between the 2.5th and 97.5th percentiles and their respective 95% confidence intervals. RESULTS: Partition by sex was not necessary to determine the IgA RI of the studied children. Homogeneous subgroups were identified among children aged 1-<2, 2-<5, and 5-<11 years, whose IgA-specific RIs were determined. CONCLUSION: The serum IgA RIs were established for three groups of Brazilian children aged 1-11 years, which differed from those currently applied in Brazilian pediatric practice and from those defined by international studies. This definition will help Brazilian pediatricians formulate an accurate diagnosis and facilitate decision-making.