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1.
J Virol ; 95(17): e0071421, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34160256

RESUMO

Ebola virus (EBOV), of the family Filoviridae, is an RNA virus that can cause a hemorrhagic fever with a high mortality rate. Defective viral genomes (DVGs) are truncated genomes that have been observed during multiple RNA virus infections, including in vitro EBOV infection, and have previously been associated with viral persistence and immunostimulatory activity. As DVGs have been detected in cells persistently infected with EBOV, we hypothesized that DVGs may also accumulate during viral replication in filovirus-infected hosts. Therefore, we interrogated sequence data from serum and tissue samples using a bioinformatics tool in order to identify the presence of DVGs in nonhuman primates (NHPs) infected with EBOV, Sudan virus (SUDV), or Marburg virus (MARV). Multiple 5' copy-back DVGs (cbDVGs) were detected in NHP serum during the acute phase of filovirus infection. While the relative abundance of total DVGs in most animals was low, serum collected during acute EBOV and SUDV infections, but not MARV infections, contained a higher proportion of short trailer sequence cbDVGs than the challenge stock. This indicated an accumulation of these DVGs throughout infection, potentially due to the preferential replication of short DVGs over the longer viral genome. Using reverse transcriptase PCR (RT-PCR) and deep sequencing, we also confirmed the presence of 5' cbDVGs in EBOV-infected NHP testes, which is of interest due to EBOV persistence in semen of male survivors of infection. This work suggests that DVGs play a role in EBOV infection in vivo and that further study will lead to a better understanding of EBOV pathogenesis. IMPORTANCE The study of filovirus pathogenesis is critical for understanding the consequences of infection and for the development of strategies to ameliorate future outbreaks. Defective viral genomes (DVGs) have been detected during EBOV infections in vitro; however, their presence in in vivo infections remains unknown. In this study, DVGs were detected in samples collected from EBOV- and SUDV-infected nonhuman primates (NHPs). The accumulation of these DVGs in the trailer region of the genome during infection indicates a potential role in EBOV and SUDV pathogenesis. In particular, the presence of DVGs in the testes of infected NHPs requires further investigation as it may be linked to the establishment of persistence.


Assuntos
Vírus Defeituosos/genética , Ebolavirus/genética , Genoma Viral , Doença pelo Vírus Ebola/virologia , Interações Hospedeiro-Patógeno , Macaca mulatta/virologia , Replicação Viral , Animais , Feminino , Masculino
2.
Popul Health Metr ; 15(1): 3, 2017 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-28183307

RESUMO

BACKGROUND: Low-cost, cross-culturally comparable measures of the motor, cognitive, and socioemotional skills of children under 3 years remain scarce. In the present paper, we aim to develop a new caregiver-reported early childhood development (ECD) scale designed to be implemented as part of household surveys in low-resourced settings. METHODS: We evaluate the acceptability, test-retest reliability, internal consistency, and discriminant validity of the new ECD items, subscales, and full scale in a sample of 2481 18- to 36-month-old children from peri-urban and rural Tanzania. We also compare total and subscale scores with performance on the Bayley Scales of Infant Development (BSID-III) in a subsample of 1036 children. Qualitative interviews from 10 mothers and 10 field workers are used to inform quantitative data. RESULTS: Adequate levels of acceptability and internal consistency were found for the new scale and its motor, cognitive, and socioemotional subscales. Correlations between the new scale and the BSID-III were high (r > .50) for the motor and cognitive subscales, but low (r < .20) for the socioemotional subscale. The new scale discriminated between children's skills based on age, stunting status, caregiver-reported disability, and adult stimulation. Test-retest reliability scores were variable among a subset of items tested. CONCLUSIONS: Results of this study provide empirical support from a low-income country setting for the acceptability, reliability, and validity of a new caregiver-reported ECD scale. Additional research is needed to test these and other caregiver reported items in children in the full 0 to 3 year range across multiple cultural and linguistic settings.


Assuntos
Desenvolvimento Infantil , Cognição , Países em Desenvolvimento , Emoções , Destreza Motora , Habilidades Sociais , Inquéritos e Questionários/normas , Cuidadores , Pré-Escolar , Comparação Transcultural , Crianças com Deficiência , Feminino , Transtornos do Crescimento , Humanos , Lactente , Masculino , Mães , Relações Pais-Filho , Psicometria/métodos , Reprodutibilidade dos Testes , População Rural , Tanzânia
3.
Am J Phys Anthropol ; 163(3): 510-518, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28374441

RESUMO

OBJECTIVES: Fecal particle size (FPS) as quantified by wet sieving analysis is a measure of chewing efficiency relevant for the understanding of physiological adaptations and constraints in herbivores. FPS has not been investigated systematically in frugivores, and important methodological problems remain. In particular, food items that are not chewed may skew estimates of FPS. We address such methodological issues and also assess the influence of diet type and age on FPS in wild chimpanzees. MATERIALS AND METHODS: About 130 fecal samples of 38 individual chimpanzees (aged from 1.3 to ∼55 years) from the Kanyawara community of Kibale National Park (Uganda) were collected during three fruit seasons and analyzed using standardized wet sieves (pores from 16 to 0.025 mm). The effects of using different sieve series and excluding large seeds were investigated. We also assessed the relationship between FPS and sex, age, and fruit season. RESULTS: The treatment of seeds during the sieving process had a large influence on the results. FPS was not influenced by chimpanzee sex or age, but was smaller during a fig season (0.88 ± 0.31 mm) than during two drupe-fruit seasons (1.68 ± 0.37 mm) (0.025-4 mm sieves, excluding seeds). DISCUSSION: The absence of an age effect on FPS suggests that dental senescence might be less critical in chimpanzees, or in frugivores in general, than in folivorous herbivores. To increase the value of FPS studies for understanding frugivore and hominoid dietary evolution we propose modifications to prior herbivore protocols.


Assuntos
Antropologia Física/métodos , Dieta , Fezes/química , Frutas , Herbivoria/fisiologia , Animais , Ecologia , Feminino , Masculino , Pan troglodytes , Tamanho da Partícula , Uganda
4.
Front Pediatr ; 12: 1379131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756971

RESUMO

Introduction: Respiratory illness is the most common childhood disease globally, especially in developing countries. Previous studies have detected viruses in approximately 70-80% of respiratory illnesses. Methods: In a prospective cohort study of 234 young children (ages 3-11 years) and 30 adults (ages 22-51 years) in rural Western Uganda sampled monthly from May 2019 to August 2021, only 24.2% of nasopharyngeal swabs collected during symptomatic disease had viruses detectable by multiplex PCR diagnostics and metagenomic sequencing. In the remaining 75.8% of swabs from symptomatic participants, we measured detection rates of respiratory bacteria Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae by quantitative PCR. Results: 100% of children tested positive for at least one bacterial species. Detection rates were 87.2%, 96.8%, and 77.6% in children and 10.0%, 36.7%, and 13.3% for adults for H. influenzae, M. catarrhalis, and S. pneumoniae, respectively. In children, 20.8% and 70.4% were coinfected with two and three pathogens, respectively, and in adults 6.7% were coinfected with three pathogens but none were coinfected with two. Detection of any of the three pathogens was not associated with season or respiratory symptoms severity, although parsing detection status by symptoms was challenged by children experiencing symptoms in 80.3% of monthly samplings, whereas adults only reported symptoms 26.6% of the time. Pathobiont colonization in children in Western Uganda was significantly more frequent than in children living in high-income countries, including in a study of age-matched US children that utilized identical diagnostic methods. Detection rates were, however, comparable to rates in children living in other Sub-Saharan African countries. Discussion: Overall, our results demonstrate that nonviral colds contribute significantly to respiratory disease burden among children in rural Uganda and that high rates of respiratory pathobiont colonization may play a role. These conclusions have implications for respiratory health interventions in the area, such as increasing childhood immunization rates and decreasing air pollutant exposure.

5.
Sci Rep ; 14(1): 10431, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714841

RESUMO

Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park. We collected 2047 respiratory symptoms surveys to quantify clinical severity and simultaneously collected 1989 nasopharyngeal swabs approximately monthly for multiplex viral diagnostics. Throughout the course of the study, we also collected 445 faecal samples from 55 wild chimpanzees living nearby in Kibale in social groups that have experienced repeated, and sometimes lethal, epidemics of human-origin respiratory viral disease. We characterized respiratory pathogens in each cohort and examined statistical associations between PCR positivity for detected pathogens and potential risk factors. Children exhibited high incidence rates of respiratory infections, whereas incidence rates in adults were far lower. COVID-19 lockdown in 2020-2021 significantly decreased respiratory disease incidence in both people and chimpanzees. Human respiratory infections peaked in June and September, corresponding to when children returned to school. Rhinovirus, which caused a 2013 outbreak that killed 10% of chimpanzees in a Kibale community, was the most prevalent human pathogen throughout the study and the only pathogen present at each monthly sampling, even during COVID-19 lockdown. Rhinovirus was also most likely to be carried asymptomatically by adults. Although we did not detect human respiratory pathogens in the chimpanzees during the cohort study, we detected human metapneumovirus in two chimpanzees from a February 2023 outbreak that were genetically similar to viruses detected in study participants in 2019. Our data suggest that respiratory pathogens circulate in children and that adults become asymptomatically infected during high-transmission times of year. These asymptomatic adults may then unknowingly carry the pathogens into forest and infect chimpanzees. This conclusion, in turn, implies that intervention strategies based on respiratory symptoms in adults are unlikely to be effective for reducing reverse zoonotic transmission of respiratory viruses to chimpanzees.


Assuntos
Resfriado Comum , Pan troglodytes , Animais , Humanos , Criança , Feminino , Masculino , Pré-Escolar , Resfriado Comum/epidemiologia , Resfriado Comum/virologia , Adulto , Uganda/epidemiologia , Estudos Prospectivos , Zoonoses/epidemiologia , Zoonoses/virologia , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/transmissão , Doenças dos Símios Antropoides/epidemiologia , Doenças dos Símios Antropoides/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/veterinária , Rhinovirus/isolamento & purificação , Rhinovirus/genética , SARS-CoV-2/isolamento & purificação , Incidência
6.
Front Pediatr ; 12: 1336009, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650995

RESUMO

Introduction: Respiratory disease is a major cause of morbidity and mortality in the developing world, but prospective studies of temporal patterns and risk factors are rare. Methods: We studied people in rural Western Uganda, where respiratory disease is pervasive. We followed 30 adults (ages 22-51 years; 534 observations) and 234 children (ages 3-11 years; 1,513 observations) between May 2019 and July 2022 and collected monthly data on their respiratory symptoms, for a total of 2,047 case records. We examined associations between demographic and temporal factors and respiratory symptoms severity. Results: The timing of our study (before, during, and after the emergence of COVID-19) allowed us to document the effects of public health measures instituted in the region. Incidence rates of respiratory symptoms before COVID-19 lockdown were 568.4 cases per 1,000 person-months in children and 254.2 cases per 1,000 person-months in adults. These rates were 2.6 times higher than the 2019 global average for children but comparable for adults. Younger children (ages 3-6 years) had the highest frequencies and severities of respiratory symptoms. Study participants were most likely to experience symptoms in February, which is a seasonal pattern not previously documented. Incidence and severity of symptoms in children decreased markedly during COVID-19 lockdown, illustrating the broad effects of public health measures on the incidence of respiratory disease. Discussion: Our results demonstrate that patterns of respiratory disease in settings such as Western Uganda resemble patterns in developed economies in some ways (age-related factors) but not in others (increased incidence in children and seasonal pattern). Factors such as indoor air quality, health care access, timing of school trimesters, and seasonal effects (rainy/dry seasons) likely contribute to the differences observed.

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