RESUMO
OBJECTIVES: This review article summarizes what has been published on Alkhumra hemorrhagic fever virus (AHFV), a novel flavivirus that was discovered in Saudi Arabia in 1995. METHODS: PubMed was used to search for studies published from January 1995 to June 2019 using the key words Alkhumra virus, Alkhurma virus, novel flavivirus, and tick-borne encephalitis virus. Additionally, records of the Saudi Ministry of Health were reviewed. RESULTS: Thirty-two articles on AHFV were identified. Acute febrile flu-like illness, hepatitis, hemorrhagic manifestations, and, less commonly, encephalitis are the main clinical features. The virus seems to be transmitted from livestock animals to humans by direct contact with these animals or their raw meat, or perhaps by tick or mosquito bites. The ability of ticks and mosquitoes to serve as vectors for AHFV needs to be confirmed by biological studies. The exact role of animals such as sheep, goats, camels, and other mammals in the transmission and maintenance of the virus remains to be elucidated. Preventive measures require an interdisciplinary approach involving the human and veterinary health sectors, the municipality, the ministry of agriculture, the vector control sector, and academic and research institutes. CONCLUSIONS: AHFV has been well characterized; nevertheless, some aspects remain to be elucidated.
Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Animais , Anticorpos Antivirais , Bases de Dados Factuais , Vírus da Encefalite Transmitidos por Carrapatos/classificação , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Encefalite Transmitida por Carrapatos/transmissão , Encefalite Transmitida por Carrapatos/virologia , Humanos , Filogenia , Arábia Saudita , Doenças Transmitidas por Carrapatos/prevenção & controle , Doenças Transmitidas por Carrapatos/transmissão , Doenças Transmitidas por Vetores/prevenção & controle , Doenças Transmitidas por Vetores/transmissãoRESUMO
Risk factors for human-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) are largely unknown. After MERS-CoV infections occurred in an extended family in Saudi Arabia in 2014, relatives were tested by using real-time reverse transcription PCR (rRT-PCR) and serologic methods. Among 79 relatives, 19 (24%) were MERS-CoV positive; 11 were hospitalized, and 2 died. Eleven (58%) tested positive by rRT-PCR; 8 (42%) tested negative by rRT-PCR but positive by serology. Compared with MERS-CoV-negative adult relatives, MERS-CoV-positive adult relatives were older and more likely to be male and to have chronic medical conditions. Risk factors for household transmission included sleeping in an index patient's room and touching respiratory secretions from an index patient. Casual contact and simple proximity were not associated with transmission. Serology was more sensitive than standard rRT-PCR for identifying infected relatives, highlighting the value of including serology in future investigations.
Assuntos
Busca de Comunicante , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Família , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Adolescente , Adulto , Anticorpos Antivirais/sangue , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Arábia Saudita/epidemiologia , Testes SorológicosRESUMO
Alkhumra hemorrhagic fever virus (AHFV) is an emerging flavivirus that was isolated originally from Saudi Arabia in 1994-1995. The main tests used for the detection of AHFV are the real time (rt) RT-PCR and virus isolation in cell culture. In the present study the detection of AHFV by rtRT-PCR was compared with virus isolation in BHK-21, HEp-2, and LLC-MK2 cell lines. AHFV suspensions grown in BHK-21, HEp-2, and LLC-MK2 cell lines were serially diluted 10-fold from 10(-1) to 10(-11) . Samples from each dilution were used to inoculate four cell culture tubes and were also examined by the rtRT-PCR for AHFV RNA. Fifteen non-inoculated cell culture samples (five from each cell line) were included blindly in both tests. Thus, a total of 132 AHFV-positive and 15 negative control samples were tested. The rtRT-PCR could detect the viral RNA in all diluted specimens up to and including the 10(-10) dilution (40 specimens for each cell line), whereas, cell cultures were positive in 70% of specimens for BHK-21, 65% for LLC-MK2, and 45% for HEp-2 at this dilution. None of the three cell cultures nor the rtRT-PCR was positive at 10(-11) dilution. The specificity and positive predictive values of virus isolation compared to rtRT-PCR were each 100%, whereas the negative predictive values were 29.4% for BHK-21, 26.3% for LLC-MK2, and 18.5% for HEp-2. In conclusion, the rtRT-PCR is more sensitive than virus isolation for detecting AHFV.
Assuntos
Técnicas de Laboratório Clínico/métodos , Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Encefalite Transmitida por Carrapatos/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Animais , Linhagem Celular , Vírus da Encefalite Transmitidos por Carrapatos/genética , Vírus da Encefalite Transmitidos por Carrapatos/crescimento & desenvolvimento , Humanos , Valor Preditivo dos Testes , Arábia Saudita , Sensibilidade e Especificidade , Cultura de Vírus/métodosRESUMO
The physico-chemical and biological characteristics of Alkhumra hemorrhagic fever virus (AHFV) are not yet known. The present study describes the thermal stability of this virus at different temperatures for different periods. The kinetics of thermal inactivation were studied, linear regressions were plotted, the Arrhenius equation was applied, and the activation energy was calculated accordingly. Titers of the residual virus were determined in median tissue culture infective dose (TCID50), and the rate of destruction of infectivity at various temperatures was determined. Infectivity of AHFV was completely lost upon heating for 3 minutes at 60 °C and for 30 min at 56 °C. However, the virus could maintain 33.2 % of its titer after heating for 60 min at 45 °C and 32 % of its titer after heating for 60 min at 50 °C. In conclusion, AHFV is thermo-labile, and its inactivation follows first-order kinetics.
Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Temperatura Alta , Inativação de Vírus , Animais , Linhagem Celular , Chlorocebus aethiops , Vírus da Encefalite Transmitidos por Carrapatos/patogenicidade , HumanosRESUMO
Background: Camel-to-human transmission of the Middle East Respiratory Syndrome coronavirus (MERS-CoV) was confirmed as a cause of primary infection in humans. There is a dearth of information regarding the behavior of the virus in camels and the mode of spread among them under natural conditions. The aim of this study was to monitor exposure of camels to the MERS-CoV under field conditions. Methods: From January 1 to November 30, 2015, a secluded herd of 20 pregnant female camels and their neonate calves was established. Nasal and rectal swabs were collected from calves daily for 90 days after birth, then weekly until the end of the study. Nasal and rectal samples were collected from the dams at outset and then weekly until the end of the study. The samples were tested with rtRT-PCR to detect the MERS-CoV RNA. Results: All purchased pregnant camels were MERS-CoV RNA negative at outset. Nineteen dams and 15 calves completed the study. Seven (46.7%) of the 15 calves developed a rise in rectal temperature (39-40°C), shivering, rhinitis, anorexia, and general weakness at a mean ± standard deviation of 18.9 ± 4.9 days of age and their MERS-CoV RNA test was positive on the first day of illness. Three of the seven infected calves died 14 ± 9.1 days postonset of illness at age 17, 14, and 46 days, respectively. The remaining four infected calves fully recovered and they were MERS-CoV RNA positive for 17.5 ± 8.8 days. Four (21.1%) of the 19 dams had positive tests; three dams had no clinical signs, whereas the fourth dam exhibited signs not compatible with MERS-CoV infection and died three days after the positive test, 33 days after parturition. All MERS-CoV infections occurred within 22 days. Conclusions: This study has expanded our understanding of the MERS-CoV epidemiology among camels, which is an important step forward to device effective preventive measures.
Assuntos
Infecções por Coronavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Animais , Camelus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Feminino , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , NarizRESUMO
Alkhumra hemorrhagic fever virus (AHFV) is an emerging novel flavivirus that was discovered in Saudi Arabia in 1995. The virus has since caused several outbreaks in the country that resulted in case fatality rates ranging from 1% to 25%. Meager information has been published on the ultrastructural features of the virus on cells under in vitro or in vivo conditions. The present electron microscopic study examined and compared the intracellular growth of the AHFV on the LLC-MK2 cells and brain cells of new born Wistar rats, inoculated intracerebrally. The cytopathological changes in both cell systems were noted, and localization of the virus particles in different cellular components was observed. Both apoptotic and lytic cell interactions were seen in the electron micrographs of both the LLC-MK2 and the rat brain cells. The results were discussed in relation to similar situations reported for other virus members of the genus Flavivirus.
Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/ultraestrutura , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Encéfalo/virologia , Linhagem Celular , Vírus da Encefalite Transmitidos por Carrapatos/crescimento & desenvolvimento , Encefalite Transmitida por Carrapatos/patologia , Encefalite Transmitida por Carrapatos/virologia , Macaca mulatta , Ratos WistarRESUMO
Alkhumra hemorrhagic fever virus (AHFV) is a newly described zoonotic flavivirus that was first isolated during 1994-1995 from the Alkhumra district south of Jeddah, Saudi Arabia. Subsequently, the virus was also isolated from Makkah city (2001-2003) and Najran (2008-2009), Saudi Arabia. The virus causes acute febrile illness with hepatitis, hemorrhagic manifestations, and encephalitis. A case fatality rate of 25% was reported among hospitalized patients. Although several biological and molecular characteristics of the virus have been published, no data are available on electron microscopic features of the virus. In this article, we describe the morphological features and metrics of the AHFV particles under electron microscopy, and localization of the virus particles in brain cells of newborn Wistar rats and in Rhesus monkey (Macaca mulatta) kidney epithelial cells (LLC-MK2). Virus particles in both the LLC-MK2 cells and the rat brain cells showed dark hexagonal core (capsid) and a translucent envelope. The mean diameter of the enveloped virus particle was 40.59 ± 1.29 nm in the rat brain cells (n = 154) and 40.97 ± 1.40 nm in the LLC-MK2 cells (n = 105; p > 0.05). The virus particles, both in vitro and in vivo, were enclosed into cytoplasmic vesicles. In conclusion, the shape, size, and diameter of the AHFV particle lie within the framework of the genus Flavivirus, family Flaviviridae.
Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/ultraestrutura , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Encéfalo/virologia , Linhagem Celular , Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Macaca mulatta , Ratos , Ratos WistarRESUMO
BACKGROUND: Alkhumra hemorrhagic fever virus (AHFV) is a flavivirus that was discovered in 1995 in Saudi Arabia. Clinical manifestations of AHFV infection include hemorrhagic fever, hepatitis, and encephalitis with a reported mortality rate as high as 25%. There are no published data on the growth characteristics of AHFV in mammalian cell lines. The objective of this study was to examine the ability of AHFV to grow and propagate in four of the commonly used mammalian cell culture lines and to determine the virus growth curve characteristics in each. MATERIALS AND METHODS: Human epidermoid carcinoma (HEp-2), LLC-MK2, Madin-Darby canine kidney (MDCK), and Vero cell lines were inoculated with AHFV. The virus production by each cell line was determined by growth curve studies. Mean titers were calculated and expressed as median tissue culture infective dose per mL (TCID50/mL). RESULTS: AHFV grew and propagated to variable titers in the employed cell lines. The highest mean titers were observed in the LLC-MK2, followed by the MDCK, Vero, and HEP-2, in descending order. CONCLUSIONS: The growth curve studies showed that AHFV can propagate in the four types of cell lines to variable titers. LLC-MK2 cells are superior to MDCK, Vero, and HEP-2 for propagation of AHFV.
Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Cultura de Vírus/métodos , Replicação Viral/fisiologia , Animais , Linhagem Celular , Chlorocebus aethiops , Efeito Citopatogênico Viral/fisiologia , Cães , HumanosRESUMO
The epidemiology of orf virus infection in Saudi Arabia (SA) has been researched since 1990. The results obtained during this period indicate that the disease is widespread, has great economic impact and that no vaccine has been used against it. The present study compares the immunogenicity and protective efficacy of three locally developed live orf virus vaccines. Two of them differ in their passage history in Vero cell culture and the third was used as a virulent virus in glycerine buffer. To the best of the authors' knowledge, no similar comparative study has been conducted in the Middle East utilising three types of vaccines prepared from the same virus strain. Selection of the candidate seed orf virus and performance of the quality control tests were as laid out by the OIE for veterinary vaccine production. The vaccine seed virus was a field orf virus isolated from a previous orf outbreak in Saudi Arabia. A simple novel formula was developed to calculate the rate of reduction in the healing time (RHT %) in the challenged sheep. This allowed direct comparison of the efficacy of the three types of vaccines employed in the present study. The efficacy of each vaccine was tested on a cohort of local Noemi sheep.
Assuntos
Ectima Contagioso/prevenção & controle , Vírus do Orf/imunologia , Vacinas Virais/imunologia , Animais , Chlorocebus aethiops , Ectima Contagioso/epidemiologia , Arábia Saudita/epidemiologia , Ovinos , Resultado do Tratamento , Vacinação/veterinária , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Células Vero , Vacinas Virais/administração & dosagemRESUMO
The dairy industry is a large and important business in Saudi Arabia. Although farms are administered to high international standards, some reproduction problems, of uncertain aetiology, are encountered. The most frequently seen are conception failures, abortions, stillbirths and the birth of weak or malformed calves. These conditions are suggestive of bovine viral diarrhoea virus (BVDV) infection. Unfortunately, very little published information is available regarding the impact of this disease on cattle populations in Saudi Arabia. As a consequence, the present study was carried out and is the first of its kind in Saudi Arabia and the Gulf region. The aim of the study was to elucidate the role of in utero BVDV infection leading to the birth of weak or malformed calves on a large dairy farm in Saudi Arabia. The study was divided into two parts. Firstly, apparently healthy neonatal calves were sampled for the detection of pre-colostral serum antibodies to BVDV. The presence of these antibodies indicates exposure of the foetus to BVDV during the last two trimesters of gestation. Secondly, tissue samples from malformed neonatal calves were examined for the presence of BVDV antigens. Detection of such antigens confirms exposure of the foetus to the virus during the first trimester of gestation. The results of the investigation indicated that 36.1% of the neonatal calves were exposed to BVDV infection in utero. This is higher than what has been reported in the literature and suggests that dairy farmers in the Arabian Peninsula need to be made aware of the dangers of BVDV infections in their herds. The epidemiological significance of the results is discussed.