RESUMO

In recent years, machine learning (ML) algorithms have emerged as powerful tools for predicting and modeling complex data. Therefore, the aim of this study was to evaluate the prediction ability of different ML algorithms and a traditional empirical model to estimate the parameters of lactation curves. A total of 1186 monthly records from 156 sheep lactations were used. The model development process involved training and testing models using ML algorithms. In addition to these algorithms, lactation curves were also fitted using the Wood model. The goodness of fit was assessed using correlation coefficient (r), mean absolute error (MAE), root mean square error (RMSE), relative absolute error (RAE), and relative root mean square error (RRSE). SMOreg was the algorithm with the best estimates of the characteristics of the sheep lactation curve, with higher values of r compared to the Wood model (0.96 vs. 0.68) for the total milk yield. The results of the current study showed that ML algorithms are able to adequately predict the characteristics of the lactation curve, using a relatively small number of input data. Some ML algorithms provide an interpretable architecture, which is useful for decision-making at the farm level to maximize the use of available information.

RESUMO

BACKGROUND: Takeda's live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across 8 dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year postvaccination. This exploratory analysis provides an update with cumulative and third-year data. METHODS: Healthy 4-16 year olds (n = 20099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific reverse transcriptase-polymerase chain reaction. RESULTS: Cumulative efficacy after 3 years was 62.0% (95% confidence interval, 56.6-66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8-88.4) against hospitalized VCD. Efficacy was 54.3% (41.9-64.1) against VCD and 77.1% (58.6-87.3) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9-70.1) against VCD and 86.0% (78.4-91.0) against hospitalized VCD in baseline seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5-54.7), whereas efficacy against hospitalized VCD was sustained at 70.8% (49.6-83.0). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (ie, second half of the 3 years following vaccination), but none were related. No important safety risks were identified. CONCLUSIONS: TAK-003 was efficacious against symptomatic dengue over 3 years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.

Assuntos

Vacinas contra Dengue , Vírus da Dengue , Dengue , Anticorpos Antivirais , Humanos , Sorogrupo , Resultado do Tratamento , Vacinas Atenuadas/efeitos adversos , Vacinas Combinadas

RESUMO

BACKGROUND: Takeda's dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update. METHODS: Children (20 099, 4-16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR. RESULTS: Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%-77.3%), including 67.0% (95% CI, 53.6%-76.5%) in dengue-naive and 89.2% (95% CI, 82.4%-93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%-66.8%) with the largest decline in 4-5 year olds (24.5%; 95% CI, -34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%-72.4%) in 6-11 year and 71.2% (95% CI, 41.0%-85.9%) in 12-16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adverse events occurred during the second year. CONCLUSIONS: TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further.Clinical Trials Registration. NCT02747927.Takeda's tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy during the second year in 4-16 year olds in dengue-endemic countries.

Assuntos

Vacinas contra Dengue , Vírus da Dengue , Dengue , Adolescente , Anticorpos Neutralizantes , Anticorpos Antivirais , Criança , Pré-Escolar , Vírus da Dengue/genética , Método Duplo-Cego , Humanos , Vacinação , Vacinas Atenuadas

RESUMO

BACKGROUND: A substantial unmet need remains for safe and effective vaccines against dengue virus disease, particularly for individuals who are dengue-naive and those younger than 9 years. We aimed to assess the efficacy, safety, and immunogenicity of a live attenuated tetravalent dengue vaccine (TAK-003) in healthy children aged 4-16 years. METHODS: We present data up to 18 months post-vaccination from an ongoing phase 3, randomised, double-blind trial of TAK-003 in endemic regions of Asia and Latin America (26 medical and research centres across Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). Healthy children aged 4-16 years were randomly assigned 2:1 (stratified by age and region) to receive two doses of TAK-003 or two doses of placebo, 3 months apart. Investigators, participants and their parents or guardians, and sponsor representatives advising on trial conduct were masked to trial group assignments. Participants presenting with febrile illness were tested for virologically confirmed dengue (VCD) by serotype-specific RT-PCR. In timeframes beginning 30 days post-second dose, the primary endpoint (overall vaccine efficacy) was assessed in the first 11 months, and the secondary endpoints (efficacy by baseline serostatus, serotype, hospitalised dengue, and severe dengue) in the first 17 months. This study is registered with ClinicalTrials.gov, NCT02747927. FINDINGS: 20 099 participants were randomly assigned and vaccinated between Sept 7, 2016, and Aug 18, 2017; 19 021 (94·6%) were included in the per protocol analysis, and 20 071 (99·9%) in the safety set. The primary endpoint was achieved with an overall vaccine efficacy of 80·2% (95% CI 73·3 to 85·3; 61 cases of VCD in the TAK-003 group vs 149 cases of VCD in the placebo group). In the secondary endpoint assessment timeframe, an overall vaccine efficacy of 73·3% (95% CI 66·5 to 78·8) was observed. Analysis of secondary endpoints showed efficacies of 76·1% (95% CI 68·5 to 81·9) in individuals who were seropositive at baseline, 66·2% (49·1 to 77·5) in individuals who were seronegative at baseline, 90·4% (82·6 to 94·7) against hospitalised dengue, and 85·9% (31·9 to 97·1) against dengue haemorrhagic fever. Efficacy varied by individual serotypes (DENV 1, 69·8% [95% CI 54·8 to 79·9]; DENV 2, 95·1% [89·9 to 97·6]; DENV 3, 48·9% [27·2 to 64·1]; DENV 4, 51·0% [-69·4 to 85·8]). Cumulative rates of serious adverse events were similar in TAK-003 (4·0%) and placebo (4·8%) recipients, and were consistent with expected medical disorders in the study population. Infection was the most frequent reason leading to serious adverse events. 20 participants (<0·1% of the safety set) were withdrawn from the trial due to 21 adverse events by the end of part two; 14 of these participants received TAK-003 and six received placebo. INTERPRETATION: TAK-003 was well tolerated and efficacious against symptomatic dengue in children regardless of serostatus before immunisation. Vaccine efficacy varied by serotype, warranting continued follow-up to assess longer-term vaccine performance. FUNDING: Takeda Vaccines.

Assuntos

Vacinas contra Dengue/efeitos adversos , Vírus da Dengue/imunologia , Dengue/prevenção & controle , Vacinação/efeitos adversos , Adolescente , Brasil/epidemiologia , Criança , Pré-Escolar , Colômbia/epidemiologia , Vacinas contra Dengue/uso terapêutico , Vírus da Dengue/genética , República Dominicana/epidemiologia , Método Duplo-Cego , Hospitalização/estatística & dados numéricos , Humanos , Nicarágua/epidemiologia , Panamá/epidemiologia , Filipinas/epidemiologia , Placebos/administração & dosagem , Sorogrupo , Índice de Gravidade de Doença , Sri Lanka/epidemiologia , Tailândia/epidemiologia , Resultado do Tratamento , Vacinação/métodos

RESUMO

Motivated by the importance of studying the relationship between habits of students and their academic performance, daily activities of undergraduate participants have been tracked with smartwatches and smartphones. Smartwatches collect data together with an Android application that interacts with the users who provide the labeling of their own activities. The tracked activities include eating, running, sleeping, classroom-session, exam, job, homework, transportation, watching TV-Series, and reading. The collected data were stored in a server for activity recognition with supervised machine learning algorithms. The methodology for the concept proof includes the extraction of features with the discrete wavelet transform from gyroscope and accelerometer signals to improve the classification accuracy. The results of activity recognition with Random Forest were satisfactory (86.9%) and support the relationship between smartwatch sensor signals and daily-living activities of students which opens the possibility for developing future experiments with automatic activity-labeling, and so forth to facilitate activity pattern recognition to propose a recommendation system to enhance the academic performance of each student.

Assuntos

Desempenho Acadêmico , Análise de Dados , Monitorização Fisiológica/tendências , Smartphone , Acelerometria/métodos , Algoritmos , Humanos , Aprendizado de Máquina , Estudantes , Máquina de Vetores de Suporte

RESUMO

This research aims at contributing to the use of Polymesoda arctata, Anadara tuberculosa, and Larkinia grandis as prospective biomonitors and sentinels, surrogate of Crassostrea rhizophorae for pollution biomonitoring in mangrove-lined coastal systems. Localities were selected along the Nicaraguan coastline in the rainy and dry seasons during 2012-2013: A. tuberculosa and L. grandis were collected in the Pacific, and P. arctata in the Caribbean. The tissue concentration of metals, polycyclic aromatic hydrocarbons (PAHs) and persistent organic pollutants (POPs) were integrated into pollution indices (chemical pollution index -CPI- and pollution load index -PLI-) and biological endpoints (flesh-condition, reproduction, histopathology and stress-on-stress) were determined as biomarkers of ecosystem health disturbance. In the Caribbean, contaminant tissue concentration was low in P. arctata, with some exceptions. Ag, As, Cd, Hg, Ni and V were mainly recorded during dry season, and PAHs and POPs (HCHs, DDTs, AHTN, PCBs and BDE85) during rainy season. Metals and PAHs were not a major threat in the study area; in contrast, high levels of HCHs and DDTs and low-to-moderate levels of musk fragrances and PBDEs were recorded. Minor differences were found in biological parameters albeit during the rainy season the LT50 values were low and seemingly associated to high PLI and CPI values. In the Pacific, the main pollutants recorded in A. tuberculosa and L. grandis were HCHs, DDTs, AHTN and PDBEs in rainy season and Cd in dry season. Although basic research is needed to understand the general biology, ecology and diseases in these Pacific species, biological endpoints comparable to those used in other sentinel bivalves are seemingly suitable biomarkers of health disturbance. Overall, Caribbean P. arctata and Pacific A. tuberculosa and L. grandis seem to be potential target species for pollution monitoring and ecosystem health disturbance assessment in mangrove-lined Nicaraguan coastal systems. Their use together with C. rhizophorae would provide opportunities for common approaches to be applied in inter-ocean countries of the Mesoamerican region.

Assuntos

Bivalves/metabolismo , Ecossistema , Monitoramento Ambiental/métodos , Metais/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Nicarágua , Projetos Piloto , Estações do Ano , Espécies Sentinelas/metabolismo , Poluição Química da Água/análise , Áreas Alagadas

RESUMO

This paper aims to contribute to the use of mangrove cupped oyster, Crassostrea rhizophorae, as a biomonitor species for chemical contamination assessment in mangrove-lined Caribbean coastal systems. Sampling was carried out in eight localities (three in Nicaragua and five in Colombia) with different types and levels of contamination. Oysters were collected during the rainy and dry seasons of 2012-2013 and the tissue concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and persistent organic pollutants (POPs) were determined. Low tissue concentrations of metals (except Hg) and PAHs; moderate-to-high tissue concentrations of Hg, hexachlorocyclohexanes (HCHs), and dichlorodiphenyl-trichloroethanes (DDTs); detectable levels of chlorpyrifos, polychlorinated biphenyls (PCBs) (mainly CB28, CB118, CB138 and CB 153) and brominated diphenyl ethers 85 (BDE85); and negligible levels of musks were recorded in Nicaraguan oysters. A distinct profile of POPs was identified in Colombia, where the tissue concentrations of PCBs and synthetic musk fragrances were low to moderate, and Ag, As, Cd, Pb, and PAHs ranged from moderate to extremely high. Overall, the values recorded for HCHs, DDTs and PCBs in Nicaraguan mangrove cupped oysters greatly exceeded the reference values in tissues of C. rhizophorae from the Wider Caribbean Region, whereas only the levels of PCBs were occasionally surpassed in Colombia. Different contaminant profiles were distinguished between oysters from Nicaragua and Colombia in radar plots constructed using the main groups of contaminants (metals, PAHs, musks, PCBs, and organochlorine pesticides (OCPs)). Likewise, integrated pollution indices revealed differences in the levels of contaminants. Moreover, the profiles and levels in oyster tissues also varied with season. Thus, principal component analysis clearly discriminated Nicaraguan and Colombian localities and, especially in Colombia, seasonal trends in chemical contamination and differences amongst localities were evidenced. The geographical and environmental disparity of the studied scenarios may represent to a large extent the diversity of mangrove-lined Caribbean coastal systems and therefore the present results support the use of C. rhizophorae as suitable biomonitor species at Caribbean regional scale, where seasonal variability is a major factor controlling pollutant mobility and bioavailability.

Assuntos

Crassostrea/química , Éteres Difenil Halogenados/análise , Hexaclorocicloexano/análise , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Animais , Região do Caribe , Colômbia , Éteres Difenil Halogenados/química , Hexaclorocicloexano/química , Hidrocarbonetos Clorados/química , Metais , Praguicidas/química , Bifenilos Policlorados , Hidrocarbonetos Policíclicos Aromáticos/química , Alimentos Marinhos , Índias Ocidentais

RESUMO

OBJECTIVES: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015. METHODS: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children≤7years with AGE from 6 hospitals in Nicaragua (n=538), and 3 community clinics (n=919) and households (n=333) in León, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n=162) and households (n=105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene. RESULTS: Norovirus was found in 19% (n=338) and 12% (n=32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend. CONCLUSIONS: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12months of age, implicating GII.4 as the main norovirus vaccine target.

Assuntos

Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Gastroenterite/epidemiologia , Gastroenterite/virologia , Norovirus , Adolescente , Infecções por Caliciviridae/história , Criança , Pré-Escolar , Gastroenterite/história , Genótipo , História do Século XXI , Humanos , Incidência , Lactente , Recém-Nascido , Nicarágua/epidemiologia , Norovirus/genética , Razão de Chances , Vigilância em Saúde Pública , Estudos Retrospectivos , Estações do Ano

RESUMO

Understanding how the gut microbiota is affected by diarrhea episodes may help explain alterations in intestinal function among children in low-income settings. This study examined the composition of the gut microbiome of Nicaraguan children both during diarrhea episodes and while free of diarrhea for at least 2 months. Relative abundances of bacterial taxa, phylogenetic diversity, and species richness were determined by 16S amplicon sequencing and compared between paired diarrhea and recovery samples. A total of 66 stools were provided by 25 children enrolled in a 1-year cohort study of diarrhea etiologies. Children in our cohort had a mean age of 21.9 months; 64% were breast-fed, and 10% had received an antibiotic during the diarrhea episode. Overall, phylogenetic diversity and species richness did not differ significantly between diarrhea and recovery stools. However, of children who had a bacterial enteropathogen detected in any diarrhea stool, none experienced an increase in phylogenetic diversity in recovery, whereas of those in whom no bacterial enteropathogens were detected in their diarrhea stool(s), 59% experienced an increase in phylogenetic diversity in recovery (P = 0.008). This preliminary study suggests that recovery of the gut microbiota after a diarrhea episode may take longer time than previously thought and may be pathogen specific.

Assuntos

Diarreia Infantil/microbiologia , Microbioma Gastrointestinal , DNA Ribossômico/genética , Diarreia/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Lactente , Masculino , Nicarágua/epidemiologia , Filogenia

RESUMO

BACKGROUND: Nicaragua was the first developing nation to implement routine immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized population, understanding infectious etiologies of childhood diarrhea is necessary to direct diarrhea treatment and prevention efforts. METHODS: We followed a population-based sample of children <5 years in León, Nicaragua for diarrhea episodes through household visits. Information was obtained on RV5 history and sociodemographics. Stool samples collected during diarrhea episodes and among healthy children underwent laboratory analysis for viral, bacterial and parasitic enteropathogens. Detection frequency and incidence of each enteropathogen was calculated. RESULTS: The 826 children in the cohort experienced 677 diarrhea episodes during 607.5 child-years of exposure time (1.1 episodes per child-year). At least 1 enteropathogen was detected among 61.1% of the 337 diarrheal stools collected. The most common enteropathogens among diarrheal stools were: norovirus (20.4%), sapovirus (16.6%), enteropathogenic Escherichia coli (11.3%), Entamoeba histolytica/dispar (8.3%), Giardia lamblia (8.0%) and enterotoxigenic E. coli (7.7%), with rotavirus detected among 5.3% of diarrheal stools. Enteropathogenic Escherichia coli and enterotoxigenic E. coli were frequently detected among stools from healthy children. Among children with diarrhea, norovirus was more commonly detected among younger children (< 2 years) and G. lamblia was more commonly detected among older children (2-4 years). The mean age of rotavirus detection was 34.6 months. CONCLUSIONS: In this Central American community after RV5 introduction, rotavirus was not commonly detected among children with diarrhea. Prevention and appropriate management of norovirus and sapovirus should be considered to further reduce the burden of diarrheal disease.

Assuntos

Infecções por Caliciviridae/complicações , Diarreia/microbiologia , Diarreia/parasitologia , Entamebíase/complicações , Infecções por Escherichia coli/complicações , Gastroenterite/complicações , Giardíase/complicações , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus , Fatores Etários , Infecções por Caliciviridae/virologia , Pré-Escolar , Entamoeba histolytica/isolamento & purificação , Escherichia coli Enteropatogênica/isolamento & purificação , Escherichia coli Enterotoxigênica/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Fezes/parasitologia , Feminino , Gastroenterite/virologia , Giardia lamblia/isolamento & purificação , Humanos , Lactente , Masculino , Nicarágua , Norovirus/isolamento & purificação , Estudos Prospectivos , Rotavirus/isolamento & purificação , Infecções por Rotavirus/complicações , Sapovirus/isolamento & purificação

RESUMO

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhoea among young children in developing countries. ETEC vaccines offer promise in reducing the burden of ETEC disease, but the development of these vaccines relies on the characterization of ETEC isolates from a variety of settings. To best reflect the full spectrum of ETEC disease in León, Nicaragua, the aim of this study was to characterize ETEC strains isolated from children with diarrhoea attending different settings (hospital, primary care clinics and in the community) and children from different age groups. We characterized ETEC isolates in terms of their colonization factors (CFs) and enterotoxins, and determined whether these factors varied with setting and age group. Diarrhoeal stool samples were obtained from children under the age of 60 months from: (1) the regional public hospital, (2) four public primary care clinics, and (3) a population-based cohort. In total, 58 ETEC-positive isolates were analysed by multiplex-PCR assays for the identification of CFs (CS1, CS2, CS3, CS4, CS5, CS6, CS7, CS8, CS12, CS13, CS14, CS15, CS17, CS18, CS19, CS20, CS21, CS22 and CFA/I), and enterotoxins [heat-labile toxin (LT) and heat-stable variants STh and STp]. The frequency of CFs and enterotoxins was compared among the three settings and for different age groups, using Fisher's exact test or a χ(2) test. At least one CF was detected among one-half of samples; CS19 was detected among all strains in which a CF was identified, either alone or in combination with another CF. Among all CFs detected, 91.7 % were identified as members of the class 5 fimbrial family. CFs were detected more commonly among samples from infants captured in the health facility setting compared with the community setting. Overall, LT was detected among 67.2 % of samples, STh was detected among 20.7 % and both enterotoxins were detected among 12.1 %. The enterotoxin STh was detected more commonly among cases in the community, whilst a combination of STh and LT was detected more commonly among cases treated in health facilities. Our results suggest that, to protect against diarrhoeal cases associated with this E. coli pathotype in León, Nicaragua, an ETEC vaccine that effectively targets the archeotype CFA/I of the class 5 fimbrial family would be the most effective in this setting.

Assuntos

Diarreia/microbiologia , Escherichia coli Enterotoxigênica/classificação , Escherichia coli Enterotoxigênica/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Toxinas Bacterianas/genética , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Escherichia coli Enterotoxigênica/genética , Enterotoxinas/genética , Proteínas de Escherichia coli/genética , Vacinas contra Escherichia coli/imunologia , Vacinas contra Escherichia coli/isolamento & purificação , Fezes/microbiologia , Feminino , Proteínas de Fímbrias/genética , Variação Genética , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase Multiplex , Nicarágua , Atenção Primária à Saúde

RESUMO

We estimated the incidence of watery diarrhea in the community before and after introduction of the pentavalent rotavirus vaccine in León, Nicaragua. A random sample of households was selected before and after rotavirus vaccine introduction. All children < 5 years of age in selected households were eligible for inclusion. Children were followed every 2 weeks for watery diarrhea episodes. The incidence rate was estimated as numbers of episodes per 100 child-years of exposure time. A mixed effects Poisson regression model was fit to compare incidence rates in the pre-vaccine and vaccine periods. The pre-vaccine cohort (N = 726) experienced 36 episodes per 100 child-years, and the vaccine cohort (N = 826) experienced 25 episodes per 100 child-years. The adjusted incidence rate ratio was 0.60 (95% confidence interval [CI] 0.40, 0.91) during the vaccine period versus the pre-vaccine period, indicating a lower incidence of watery diarrhea in the community during the vaccine period.

Assuntos

Diarreia/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Pré-Escolar , Estudos de Coortes , Diarreia/epidemiologia , Diarreia/virologia , Feminino , Humanos , Incidência , Lactente , Masculino , Nicarágua/epidemiologia , Infecções por Rotavirus/epidemiologia

RESUMO

Nicaragua was the first developing nation to implement universal infant rotavirus immunization with the pentavalent rotavirus vaccine (RV5). Initial studies of vaccine effectiveness in Nicaragua and other developing nations have focused on the prevention of hospitalizations and severe rotavirus diarrhea. However, rotavirus diarrhea is more commonly treated in the primary care setting, with only 1-3% of rotavirus cases receiving hospital care. We measured the prevalence of rotavirus infection in primary care clinics in León, Nicaragua, after introduction of the immunization program. In the post-vaccine period, 3.5% (95% confidence interval = 1.9-5.8) of children seeking care for diarrhea tested positive for rotavirus. A high diversity of rotavirus genotypes was encountered among the few positive samples. In conclusion, rotavirus was an uncommon cause of childhood diarrhea in this primary care setting after implementation of a rotavirus immunization program.

Assuntos

Programas de Imunização , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Diarreia/etiologia , Feminino , Humanos , Lactente , Masculino , Nicarágua/epidemiologia , Vigilância da População , Prevalência , Atenção Primária à Saúde

RESUMO

BACKGROUND: In 2006, Merck & Co., Inc., partnered with the Nicaraguan Ministry of Health to demonstrate the public health impact of routine universal vaccination by delivering more than 1.3 million doses of the oral, pentavalent rotavirus vaccine (RV5) in a 3-year period. METHODS: A matched case-control study evaluated the effectiveness of RV5 in reducing the risk for severe wild-type rotavirus gastroenteritis (RGE) resulting in hospitalizations and emergency department visits among children who completed the recommended 3-dose regimen as part of the routine national vaccine program. Cases were identified from 6 hospitals from February 2007 to October 2009 and were age-matched with hospital controls and community controls. Vaccine effectiveness was calculated using conditional logistic regression. RESULTS: Three hundred RGE cases eligible for analysis were matched to 792 hospital and 851 community controls. Vaccine coverage of RV5 in the community reached 92%. Vaccine effectiveness during 2 years of follow-up against severe disease in children receiving 3 doses of RV5 was 87% (95% confidence interval [CI], 74-93) for community controls, 64% (95% CI, 44-78) for hospital controls, and 76% (95% CI, 63-84) when the groups were combined. For the combined groups, vaccine effectiveness was 85% (95% CI, 66-93) among children <12 months old at the time of RGE onset. CONCLUSIONS: The Merck-Nicaragua Rotavirus Vaccine Partnership promoted rapid and widespread uptake of a novel vaccine in a developing country. Vaccine effectiveness was greatest for children younger than 12 months of age who were at the highest risk for severe rotavirus disease.

Assuntos

Infecções Comunitárias Adquiridas/prevenção & controle , Gastroenterite/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Vacinação , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/imunologia , Infecções Comunitárias Adquiridas/virologia , Países em Desenvolvimento , Indústria Farmacêutica/economia , Indústria Farmacêutica/organização & administração , Feminino , Seguimentos , Gastroenterite/epidemiologia , Gastroenterite/imunologia , Gastroenterite/virologia , Humanos , Lactente , Modelos Logísticos , Masculino , Nicarágua/epidemiologia , Saúde Pública , Parcerias Público-Privadas/economia , Parcerias Público-Privadas/organização & administração , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento

RESUMO

BACKGROUND: Although the pentavalent rotavirus vaccine was highly efficacious against rotavirus diarrhea in clinical trials, the effectiveness of vaccine under field conditions in the developing world is unclear. In October 2006, Nicaragua became the first developing nation to implement universal infant immunization with the pentavalent rotavirus vaccine. To assess the effect of the immunization program, we examined the incidence of diarrhea episodes between 2003 and 2009 among children in the state of León, Nicaragua. METHODS: We extracted data on diarrhea episodes from health ministry records. We used scaled Poisson regression models to estimate diarrhea incidence rate ratios for the period following the program's implementation to the period before implementation. RESULTS: Following implementation of the immunization program, diarrhea episodes among infants were reduced (incidence rate ratios: 0.85, 95% confidence interval: 0.71-1.02) during the rotavirus season, but appear to have increased during other months. CONCLUSIONS: Although the immunization program appears effective in reducing diarrhea episodes during the rotavirus season, a large burden of diarrhea still persists during the remainder of the year.

Assuntos

Diarreia/epidemiologia , Imunização/estatística & dados numéricos , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia , Pré-Escolar , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Nicarágua/epidemiologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia

RESUMO

In this study, 574 stool samples from children with gastroenteritis were obtained from different hospitals in Costa Rica, Honduras, Nicaragua and the Dominican Republic during 2005-2006. Diarrhea stool samples were analyzed for rotavirus (RV) by ELISA and typed by the RT-PCR-based method. Unusual strains were detected: G1P6, G2P8, G3P6, G9P4, and mixed infections. Recent studies have indicated that unusual human RV strains are emerging as global strains, which has important implications for effective vaccine development. In this context, the next generation of RV vaccines will need to provide adequate protection against diseases caused not only by mixed infections, but also by unusual G/P combinations.

Assuntos

Diarreia/virologia , Gastroenterite/epidemiologia , Gastroenterite/virologia , Infecções por Rotavirus/virologia , Rotavirus/genética , Antígenos Virais/genética , Antígenos Virais/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Criança , Costa Rica/epidemiologia , República Dominicana/epidemiologia , Gastroenterite/prevenção & controle , Genótipo , Honduras/epidemiologia , Humanos , Nicarágua/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções por Rotavirus/prevenção & controle

RESUMO

BACKGROUND: Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib). METHODS: This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months. RESULTS: One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses. CONCLUSIONS: Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00332566.

Assuntos

Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/imunologia , Imunização Secundária/métodos , Vacinação/métodos , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Argentina , Pré-Escolar , Chile , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Feminino , Vacinas Anti-Haemophilus/efeitos adversos , Vacinas contra Hepatite B/efeitos adversos , Humanos , Lactente , Masculino , Nicarágua , Vacina Antipólio Oral/administração & dosagem

RESUMO

In this study, 574 stool samples from children with gastroenteritis were obtained from different hospitals in Costa Rica, Honduras, Nicaragua and the Dominican Republic during 2005-2006. Diarrhea stool samples were analyzed for rotavirus by ELISA and typed by the RT-PCR-based method. Unusual strains were detected: G1P6, G2P8, G3P6, G9P4 and mixed infections. Recent studies have indicated that unusual human rotavirus strains are emerging as global strains, which has important implications for effective vaccine development. In this context, the next generation of rotavirus vaccines will need to provide adequate protection against diseases caused not only by mixed infections, but also by unusual G/P combinations.

Assuntos

Gastroenterite/epidemiologia , Gastroenterite/virologia , RNA Viral/genética , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/virologia , Rotavirus/classificação , Rotavirus/isolamento & purificação , Criança , Pré-Escolar , Costa Rica/epidemiologia , República Dominicana/epidemiologia , Ensaio de Imunoadsorção Enzimática , Fezes/virologia , Genótipo , Honduras/epidemiologia , Humanos , Lactente , Nicarágua/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rotavirus/genética

RESUMO

Information about norovirus (NoV) infections in Central America is limited. Through a passive community and hospital pediatric diarrhea surveillance program, a total of 542 stool samples were collected between March 2005 and February 2006 in León, Nicaragua. NoV was detected in 12% (65/542) of the children; of these, 11% (45/409) were in the community and 15% (20/133) were in the hospital, with most strains (88%) belonging to genogroup II. NoV infections were age and gender associated, with children of <2 years of age (P < 0.05) and girls (P < 0.05) being most affected. Breast-feeding did not reduce the number of NoV infections. An important proportion (57%) of NoV-infected children were coinfected with diarrheagenic Escherichia coli. A significant proportion (18/31) of NoV-positive children with dehydration required intravenous rehydration. Nucleotide sequence analysis (38/65) of the N-terminal and shell region in the capsid gene revealed that at least six genotypes (GI.4, GII.2, GII.4, GII.7, GII.17, and a potentially novel cluster termed "GII.18-Nica") circulated during the study period, with GII.4 virus being predominant (26/38). The majority (20/26) of those GII.4 strains shared high nucleotide homology (99%) with the globally emerging Hunter strain. The mean viral load was approximately 15-fold higher in children infected with GII.4 virus than in those infected with other G.II viruses, with the highest viral load observed for the group of children infected with GII.4 and requiring intravenous rehydration. This study, the first of its type from a Central American country, suggests that NoV is an important etiological agent of acute diarrhea among children of <2 years of age in Nicaragua.

Assuntos

Infecções por Caliciviridae/virologia , Diarreia/virologia , Gastroenterite/virologia , Norovirus/isolamento & purificação , Fatores Etários , Infecções por Caliciviridae/epidemiologia , Proteínas do Capsídeo/genética , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/virologia , Comorbidade , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Diarreia/epidemiologia , Infecções por Escherichia coli/microbiologia , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Epidemiologia Molecular , Dados de Sequência Molecular , Nicarágua/epidemiologia , Norovirus/classificação , Norovirus/genética , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Fatores Sexuais

RESUMO

BACKGROUND: Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. METHODS: 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). FINDINGS: 897 infants were excluded from the according-to-protocol analysis. Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). No cases of intussusception were reported during the second year of follow-up. INTERPRETATION: Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide.

Assuntos

Gastroenterite/prevenção & controle , Gastroenterite/virologia , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/virologia , Rotavirus/classificação , Vacinas Atenuadas/administração & dosagem , Causas de Morte , Pré-Escolar , Método Duplo-Cego , Fezes/microbiologia , Feminino , Seguimentos , Humanos , Lactente , América Latina , Masculino , Vacinas contra Rotavirus , Especificidade da Espécie , Resultado do Tratamento , Vacinas Atenuadas/imunologia