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1.
N Engl J Med ; 386(24): 2283-2294, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35704480

RESUMO

BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).


Assuntos
Arenavirus do Novo Mundo , Febre Hemorrágica Americana , RNA Viral , Roedores , Animais , Arenavirus do Novo Mundo/genética , Arenavirus do Novo Mundo/isolamento & purificação , Bolívia/epidemiologia , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Transmissão de Doença Infecciosa , Febre Hemorrágica Americana/complicações , Febre Hemorrágica Americana/genética , Febre Hemorrágica Americana/transmissão , Febre Hemorrágica Americana/virologia , Febres Hemorrágicas Virais/genética , Febres Hemorrágicas Virais/transmissão , Febres Hemorrágicas Virais/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genética , RNA Viral/isolamento & purificação , Ratos/virologia , Roedores/virologia , Zoonoses Virais/transmissão , Zoonoses Virais/virologia
2.
Clin Infect Dis ; 76(3): e849-e856, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35639875

RESUMO

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola virus disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within 1 year after discharge from the Ebola treatment unit or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR >1 year after discharge from the Ebola treatment unit or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical examinations and blood work. RESULTS: Compared with early clearers, late clearers were older (median, 42.5 years; P < .001) and experienced fewer severe clinical symptoms (median 2, P = .006). Late clearers had more lens opacifications (odds ratio, 3.9 [95% confidence interval, 1.1-13.3]; P = .03), after accounting for age, higher total serum immunoglobulin G3 (IgG3) titers (P = .005), and increased expression of the HLA-C*03:04 allele (0.14 [.02-.70]; P = .007). CONCLUSIONS: Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Humanos , Masculino , Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Sêmen , Libéria/epidemiologia , Estudos Retrospectivos , Antígenos HLA-C , Sobreviventes , Fatores de Risco
4.
Emerg Infect Dis ; 28(2): 420-424, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35076001

RESUMO

After a pilot study, we tested 443 cadavers using OraQuick Ebola rapid diagnostic tests during surveillance after the 10th Ebola outbreak in the Democratic Republic of the Congo. No false negative and 2% false-positive results were reported. Quickly returning results and engaging the community enabled timely public health actions.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , República Democrática do Congo/epidemiologia , Testes Diagnósticos de Rotina , Surtos de Doenças , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/epidemiologia , Humanos , Projetos Piloto
5.
J Infect Dis ; 222(8): 1311-1319, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32484879

RESUMO

BACKGROUND: During 2017, a multistate outbreak investigation occurred after the confirmation of Seoul virus (SEOV) infections in people and pet rats. A total of 147 humans and 897 rats were tested. METHODS: In addition to immunoglobulin (Ig)G and IgM serology and traditional reverse-transcription polymerase chain reaction (RT-PCR), novel quantitative RT-PCR primers/probe were developed, and whole genome sequencing was performed. RESULTS: Seventeen people had SEOV IgM, indicating recent infection; 7 reported symptoms and 3 were hospitalized. All patients recovered. Thirty-one facilities in 11 US states had SEOV infection, and among those with ≥10 rats tested, rat IgG prevalence ranged 2%-70% and SEOV RT-PCR positivity ranged 0%-70%. Human laboratory-confirmed cases were significantly associated with rat IgG positivity and RT-PCR positivity (P = .03 and P = .006, respectively). Genomic sequencing identified >99.5% homology between SEOV sequences in this outbreak, and these were >99% identical to SEOV associated with previous pet rat infections in England, the Netherlands, and France. Frequent trade of rats between home-based ratteries contributed to transmission of SEOV between facilities. CONCLUSIONS: Pet rat owners, breeders, and the healthcare and public health community should be aware and take steps to prevent SEOV transmission in pet rats and to humans. Biosecurity measures and diagnostic testing can prevent further infections.


Assuntos
Surtos de Doenças , Febre Hemorrágica com Síndrome Renal/transmissão , Doenças dos Roedores/transmissão , Vírus Seoul/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Cruzamento , Criança , Pré-Escolar , Técnicas de Laboratório Clínico/veterinária , Surtos de Doenças/veterinária , Genoma Viral/genética , Febre Hemorrágica com Síndrome Renal/diagnóstico , Febre Hemorrágica com Síndrome Renal/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Pessoa de Meia-Idade , Animais de Estimação/virologia , Filogenia , Prevalência , RNA Viral/genética , Ratos , Doenças dos Roedores/diagnóstico , Doenças dos Roedores/epidemiologia , Vírus Seoul/classificação , Vírus Seoul/genética , Vírus Seoul/imunologia , Estados Unidos/epidemiologia , Zoonoses Virais/diagnóstico , Zoonoses Virais/epidemiologia , Zoonoses Virais/transmissão , Adulto Jovem
6.
Lancet Microbe ; 5(10): 100905, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39236738

RESUMO

BACKGROUND: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence. METHODS: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques. FINDINGS: The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2. INTERPRETATION: We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence. FUNDING: Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, US National Cancer Institute (National Institutes of Health), French National Research Institute for Development, and WHO.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Meningoencefalite , Sobreviventes , Humanos , República Democrática do Congo/epidemiologia , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Meningoencefalite/virologia , Meningoencefalite/epidemiologia , Meningoencefalite/imunologia , Ebolavirus/imunologia , Ebolavirus/isolamento & purificação , Ebolavirus/genética , Masculino , Adulto , Evolução Fatal , Feminino , Anticorpos Antivirais/sangue , Surtos de Doenças , Anticorpos Monoclonais/uso terapêutico
7.
Am J Trop Med Hyg ; 88(1): 116-26, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23149586

RESUMO

West Nile virus ecology has yet to be rigorously investigated in the Caribbean Basin. We identified a transmission focus in Puerto Barrios, Guatemala, and established systematic monitoring of avian abundance and infection, seroconversions in domestic poultry, and viral infections in mosquitoes. West Nile virus transmission was detected annually between May and October from 2005 to 2008. High temperature and low rainfall enhanced the probability of chicken seroconversions, which occurred in both urban and rural sites. West Nile virus was isolated from Culex quinquefasciatus and to a lesser extent, from Culex mollis/Culex inflictus, but not from the most abundant Culex mosquito, Culex nigripalpus. A calculation that combined avian abundance, seroprevalence, and vertebrate reservoir competence suggested that great-tailed grackle (Quiscalus mexicanus) is the major amplifying host in this ecosystem. West Nile virus transmission reached moderate levels in sentinel chickens during 2007, but less than that observed during outbreaks of human disease attributed to West Nile virus in the United States.


Assuntos
Ecossistema , Clima Tropical , Vírus do Nilo Ocidental/fisiologia , Animais , Aves/virologia , Culex/virologia , Guatemala , Humanos , Insetos Vetores , Vírus do Nilo Ocidental/isolamento & purificação
8.
PLoS One ; 7(3): e32873, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22427902

RESUMO

The role wild bird species play in the transmission and ecology of avian influenza virus (AIV) is well established; however, there are significant gaps in our understanding of the worldwide distribution of these viruses, specifically about the prevalence and/or significance of AIV in Central and South America. As part of an assessment of the ecology of AIV in Guatemala, we conducted active surveillance in wild birds on the Pacific and Atlantic coasts. Cloacal and tracheal swab samples taken from resident and migratory wild birds were collected from February 2007 to January 2010.1913 samples were collected and virus was detected by real time RT-PCR (rRT-PCR) in 28 swab samples from ducks (Anas discors). Virus isolation was attempted for these positive samples, and 15 isolates were obtained from the migratory duck species Blue-winged teal. The subtypes identified included H7N9, H11N2, H3N8, H5N3, H8N4, and H5N4. Phylogenetic analysis of the viral sequences revealed that AIV isolates are highly similar to viruses from the North American lineage suggesting that bird migration dictates the ecology of these viruses in the Guatemalan bird population.


Assuntos
Patos , Vírus da Influenza A/genética , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Filogenia , Animais , Sequência de Bases , Análise por Conglomerados , Demografia , Genótipo , Guatemala/epidemiologia , Modelos Genéticos , Dados de Sequência Molecular , Vigilância da População/métodos , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Análise de Sequência de DNA/veterinária
9.
Acta Trop ; 123(1): 62-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22469818

RESUMO

In October 2010, the Ministry of Public Health and Population reported an outbreak of dengue-like acute febrile illness in Al Hodayda governorate. By January 2011, a total of 1542 cases had been recorded from 19 of the 26 districts in the governorate with 104 purportedly associated deaths. In response this event, in January 2011 entomological investigations aimed at identifying the primary vector and the epidemic associated etiological agent were carried out. Based on the reported cases and the progress of the outbreak in the governorate, mosquito collection was undertaken in two of the most recent outbreak areas; Al Khokha district (130km south of Al Hodayda) and Al Muneera district (100km north). Mosquito adults were collected from houses using BG-sentinel™ traps, aspiration of resting mosquitoes and knock-down spraying. Indoor and outdoor containers adjacent to the houses were inspected for larvae. Subsequently mosquito pools were analyzed by RT-PCR for detection of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, DENV-4), and for Chikungunya virus (CHIKV). Aedes aegypti was the dominant mosquito species collected. Four pools represent 40% of the tested pools, all containing adult female Ae. aegypti, were positive for CHIKV. Three CHIKV isolates were obtained from the RNA positive mosquito pools and identified by rRT-PCR. This finding marks the first record of CHIKV isolated from Ae. aegypti in Yemen. The larval container and Breteau indices in the visited localities surveyed were estimated at 53.8 and 100, respectively. The emergence of this unprecedented CHIKV epidemic in Al Hodayda is adding up another arboviral burden to the already existing vector-borne diseases. Considering the governorate as one focal port in the Red Sea region, the spread of the disease to other areas in Yemen and in neighboring countries is anticipated. Public health education and simple measures to detect and prevent mosquito breeding in water storage containers could prevent and reduce the spread of mosquito-borne viruses like CHIKV and DENV in Yemen.


Assuntos
Aedes/virologia , Vírus Chikungunya/isolamento & purificação , Dengue/epidemiologia , Surtos de Doenças , Animais , Feminino , Humanos , Masculino , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Iêmen/epidemiologia
10.
J Clin Virol ; 55(1): 8-11, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22776162

RESUMO

BACKGROUND: In February 2009, a group of Guatemalan school children developed acute gastroenteritis (AGE) after participating in a school excursion. OBJECTIVES: We conducted a retrospective cohort investigation to characterize the outbreak and guide control measures. STUDY DESIGN: A case was defined as an illness with onset of diarrhea or vomiting during February 25-March 5, 2009. Participants were interviewed using a standardized questionnaire, and stool specimens were collected. We inspected the excursion site and tested water samples for total coliforms and Escherichia coli. RESULTS: We identified 119 excursion participants, of which 92 (77%) had been ill. Fifty-six (62%) patients sought care for their illness, and three (3%) were hospitalized. Eighteen (90%) of the 20 specimens from ill children tested positive for norovirus. Among these, 16 (89%) were of the genogroup I (GI.7) and two (11%) were genogroup II (GII.12 and GII.17). One (8%) of the 12 food handlers had norovirus (GI.7). Drinking water samples had 146 most probable numbers (MPN)/100ml of total coliforms and five MPN/100ml of E. coli. CONCLUSION: We describe the first laboratory-confirmed norovirus outbreak in Guatemala. The high illness attack rate, detection of multiple norovirus strains in sick persons, and presence of fecal contamination of drinking water indicate likely waterborne transmission.


Assuntos
Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Água Potável/microbiologia , Gastroenterite/epidemiologia , Norovirus/isolamento & purificação , Adulto , Infecções por Caliciviridae/virologia , Criança , Feminino , Manipulação de Alimentos , Gastroenterite/virologia , Guatemala/epidemiologia , Estâncias para Tratamento de Saúde , Humanos , Masculino , Norovirus/genética , Estudos Retrospectivos
11.
PLoS One ; 6(11): e27459, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22076162

RESUMO

Dengue is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Each serotype is genetically distant from the others, and each has been subdivided into different genotypes based on phylogenetic analysis. The study of dengue evolution in endemic regions is important since the diagnosis is often made by nucleic acid amplification tests, which depends upon recognition of the viral genome target, and natural occurring mutations can affect the performance of these assays. Here we report for the first time a detailed study of the phylogenetic relationships of DENV-2 from Central America, and report the first fully sequenced DENV-2 strain from Guatemala. Our analysis of the envelope (E) protein and of the open reading frame of strains from Central American countries, between 1999 and 2009, revealed that at least two lineages of the American/Asian genotype of DENV-2 have recently circulated in that region. In occasions the co-circulation of these lineages may have occurred and that has been suggested to play a role in the observed increased severity of clinical cases. Our time-scale analysis indicated that the most recent common ancestor for Central American DENV-2 of the American/Asian genotype existed about 19 years ago. Finally, we report positive selection in DENV-2 from Central America in codons of the genes encoding for C, E, NS2A, NS3, and NS5 proteins. Some of these identified codons are novel findings, described for the first time for any of the DENV-2 genotypes.


Assuntos
Vírus da Dengue/classificação , Vírus da Dengue/genética , Dengue/epidemiologia , Dengue/virologia , Evolução Molecular , Seleção Genética , América Central/epidemiologia , Dengue/genética , Vírus da Dengue/patogenicidade , Genoma Viral , Genótipo , Humanos , Filogenia , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo
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