Hepatitis: Ksiazek TG

Bird BH, Ksiazek TG, Nichol ST, Maclachlan NJ. · Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. · J Am Vet Med Assoc. · Pubmed #19335238 No free full text.

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Bird BH, Githinji JW, Macharia JM, Kasiiti JL, Muriithi RM, Gacheru SG, Musaa JO, Towner JS, Reeder SA, Oliver JB, Stevens TL, Erickson BR, Morgan LT, Khristova ML, Hartman AL, Comer JA, Rollin PE, Ksiazek TG, Nichol ST. · Special Pathogens Branch, Division of Viral and Rickettsial Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-14, Atlanta, GA 30329, USA. · J Virol. · Pubmed #18786992 links to  free full text

Abstract: Rift Valley fever (RVF) virus historically has caused widespread and extensive outbreaks of severe human and livestock disease throughout Africa, Madagascar, and the Arabian Peninsula. Following unusually heavy rainfall during the late autumn of 2006, reports of human and animal illness consistent with RVF virus infection emerged across semiarid regions of the Garissa District of northeastern Kenya and southern Somalia. Following initial RVF virus laboratory confirmation, a high-throughput RVF diagnostic facility was established at the Kenyan Central Veterinary Laboratories in Kabete, Kenya, to support the real-time identification of infected livestock and to facilitate outbreak response and control activities. A total of 3,250 specimens from a variety of animal species, including domesticated livestock (cattle, sheep, goats, and camels) and wildlife collected from a total of 55 of 71 Kenyan administrative districts, were tested by molecular and serologic assays. Evidence of RVF infection was found in 9.2% of animals tested and across 23 districts of Kenya, reflecting the large number of affected livestock and the geographic extent of the outbreak. The complete S, M, and/or L genome segment sequence was obtained from a total of 31 RVF virus specimens spanning the entire known outbreak period (December-May) and geographic areas affected by RVF virus activity. Extensive genomic analyses demonstrated the concurrent circulation of multiple virus lineages, gene segment reassortment, and the common ancestry of the 2006/2007 outbreak viruses with those from the 1997-1998 east African RVF outbreak. Evidence of recent increases in genomic diversity and effective population size 2 to 4 years prior to the 2006-2007 outbreak also was found, indicating ongoing RVF virus activity and evolution during the interepizootic/epidemic period. These findings have implications for further studies of basic RVF virus ecology and the design of future surveillance/diagnostic activities, and they highlight the critical need for safe and effective vaccines and antiviral compounds to combat this significant veterinary and public health threat.

Bird BH, Albariño CG, Hartman AL, Erickson BR, Ksiazek TG, Nichol ST. · Special Pathogens Branch, Division of Viral and Rickettsial Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS G-14, Atlanta, GA 30329, USA. · J Virol. · Pubmed #18199647 links to  free full text

Abstract: Rift Valley fever (RVF) virus is a mosquito-borne human and veterinary pathogen associated with large outbreaks of severe disease throughout Africa and more recently the Arabian peninsula. Infection of livestock can result in sweeping "abortion storms" and high mortality among young animals. Human infection results in self-limiting febrile disease that in approximately 1 to 2% of patients progresses to more serious complications including hepatitis, encephalitis, and retinitis or a hemorrhagic syndrome with high fatality. The virus S segment-encoded NSs and the M segment-encoded NSm proteins are important virulence factors. The development of safe, effective vaccines and tools to screen and evaluate antiviral compounds is critical for future control strategies. Here, we report the successful reverse genetics generation of multiple recombinant enhanced green fluorescent protein-tagged RVF viruses containing either the full-length, complete virus genome or precise deletions of the NSs gene alone or the NSs/NSm genes in combination, thus creating attenuating deletions on multiple virus genome segments. These viruses were highly attenuated, with no detectable viremia or clinical illness observed with high challenge dosages (1.0 x 10(4) PFU) in the rat lethal disease model. A single-dose immunization regimen induced robust anti-RVF virus immunoglobulin G antibodies (titer, approximately 1:6,400) by day 26 postvaccination. All vaccinated animals that were subsequently challenged with a high dose of virulent RVF virus survived infection and could be serologically differentiated from naïve, experimentally infected animals by the lack of NSs antibodies. These rationally designed marker RVF vaccine viruses will be useful tools for in vitro screening of therapeutic compounds and will provide a basis for further development of RVF virus marker vaccines for use in endemic regions or following the natural or intentional introduction of the virus into previously unaffected areas.

Evans A, Gakuya F, Paweska JT, Rostal M, Akoolo L, Van Vuren PJ, Manyibe T, Macharia JM, Ksiazek TG, Feikin DR, Breiman RF, Kariuki Njenga M. · University of Minnesota School of Public Health, Minneapolis, MN, USA. · Epidemiol Infect. · Pubmed #17988425 No free full text.

Abstract: Rift Valley fever virus (RVFV) is an arbovirus associated with periodic outbreaks, mostly on the African continent, of febrile disease accompanied by abortion in livestock, and a severe, fatal haemorrhagic syndrome in humans. However, the maintenance of the virus during the inter-epidemic period (IEP) when there is low or no disease activity detected in livestock or humans has not been determined. This study report prevalence of RVFV-neutralizing antibodies in sera (n=896) collected from 16 Kenyan wildlife species including at least 35% that were born during the 1999-2006 IEP. Specimens from seven species had detectable neutralizing antibodies against RVFV, including African buffalo, black rhino, lesser kudu, impala, African elephant, kongoni, and waterbuck. High RVFV antibody prevalence (>15%) was observed in black rhinos and ruminants (kudu, impala, buffalo, and waterbuck) with the highest titres (up to 1:1280) observed mostly in buffalo, including animals born during the IEP. All lions, giraffes, plains zebras, and warthogs tested were either negative or less than two animals in each species had low (<or= 1:16) titres of RVFV antibodies. Of 249 sera collected from five wildlife species during the 2006-2007 outbreak, 16 out of 19 (84%) of the ruminant (gerenuk, waterbuck, and eland) specimens had RVFV-neutralizing titres >or= 1:80. These data provide evidence that wild ruminants are infected by RVFV but further studies are required to determine whether these animals play a role in the virus maintenance between outbreaks and virus amplification prior to a noticeable outbreak.

Bird BH, Khristova ML, Rollin PE, Ksiazek TG, Nichol ST. · Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road MS G-14, Atlanta, GA 30329, USA. · J Virol. · Pubmed #17192303 links to  free full text

Abstract: Rift Valley fever (RVF) virus is a mosquito-borne RNA virus responsible for large explosive outbreaks of acute febrile disease in humans and livestock in Africa with significant mortality and economic impact. The successful high-throughput generation of the complete genome sequence was achieved for 33 diverse RVF virus strains collected from throughout Africa and Saudi Arabia from 1944 to 2000, including strains differing in pathogenicity in disease models. While several distinct virus genetic lineages were determined, which approximately correlate with geographic origin, multiple exceptions indicative of long-distance virus movement have been found. Virus strains isolated within an epidemic (e.g., Mauritania, 1987, or Egypt, 1977 to 1978) exhibit little diversity, while those in enzootic settings (e.g., 1970s Zimbabwe) can be highly diverse. In addition, the large Saudi Arabian RVF outbreak in 2000 appears to have involved virus introduction from East Africa, based on the close ancestral relationship of a 1998 East African virus. Virus genetic diversity was low (approximately 5%) and primarily involved accumulation of mutations at an average of 2.9 x 10(-4) substitutions/site/year, although some evidence of RNA segment reassortment was found. Bayesian analysis of current RVF virus genetic diversity places the most recent common ancestor of these viruses in the late 1800s, the colonial period in Africa, a time of dramatic changes in agricultural practices and introduction of nonindigenous livestock breeds. In addition to insights into the evolution and ecology of RVF virus, these genomic data also provide a foundation for the design of molecular detection assays and prototype vaccines useful in combating this important disease.

Vogt TM, Guerra MA, Flagg EW, Ksiazek TG, Lowther SA, Arguin PM. · Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MD G-37, Atlanta, GA 30333, USA. · J Travel Med. · Pubmed #16987125 No free full text.

Abstract: BACKGROUND: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) was introduced to the United States through air travel. Although the risk of SARS-CoV transmission within aircraft cabins has been addressed by several studies, the magnitude of the risk remains unclear. METHODS: We attempted to contact all persons with working US telephone numbers aboard seven US-bound flights carrying SARS patients. Consenting participants responded to a questionnaire, and a serum sample was collected at least 38 days after the flight and tested for SARS-CoV-associated antibodies. Participants reporting an illness compatible with SARS, with onset during the 2- to 10-day incubation period, were considered suspect cases; positive serology was required for confirmed cases. RESULTS: Among 1,766 passengers and crew, 339 (19%) persons were contacted. Of these, 312 (92%) completed questionnaires, and blood was collected from 127 (37%). Serology was negative for all 127 participants, including three of four who met the clinical case criteria for SARS, and the fourth had a mild illness that lasted only 5 days. CONCLUSIONS: Transmission of SARS-associated CoV was not observed, suggesting that the risk of transmission is not amplified aboard aircraft.

Jupp PG, Grobbelaar AA, Leman PA, Kemp A, Dunton RF, Burkot TR, Ksiazek TG, Swanepoel R. · National Institute for Virology, Department of Virology, University of the Witwatersrand, Private Bag X4, Sandringham, Johannesburg 2131, South Africa. · J Med Entomol. · Pubmed #15535594 No free full text.

Abstract: A reverse transcription-polymerase chain reaction (RT-PCR) was assessed in laboratory tests to detect the presence of single Aedes aegypti (L.) or Eretmapodites quinquevittatus Theobald mosquitoes infected with Rift Valley fever virus in pools of mosquitoes, 50-600 in size, from laboratory colonies or mixed field collections. The viral RNA was detected in all pools containing infected mosquitoes and was shown to be as sensitive as infant mice but more sensitive than Vero cell cultures for virus detection. Pools diluted down to the equivalent of 1:16 000 mosquitoes were also positive by RT-PCR. RNAs from 4 other phleboviruses were negative, there were no false positives and the procedure followed, with the 2 particular primers chosen, gave consistently clear bands of the PCR products on agarose gels without nested PCR being necessary.

Paweska JT, Burt FJ, Anthony F, Smith SJ, Grobbelaar AA, Croft JE, Ksiazek TG, Swanepoel R. · Special Pathogens Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, South Africa. · J Virol Methods. · Pubmed #14553896 No free full text.

Abstract: The recent occurrence of the first confirmed outbreaks of Rift Valley fever in humans and livestock outside the African region, namely in the Kingdom of Saudi Arabia and Yemen, is of global medical and veterinary concern. Disadvantages of classical techniques for serological diagnosis of Rift Valley fever include health risk to laboratory personnel, restrictions for their use outside endemic areas and inability to distinguish between different classes of immunoglobulins. We report on the development and validation of sandwich and capture ELISAs (both based on inactivated antigen) for detection of IgG and IgM antibody to Rift Valley fever virus in bovine, caprine and ovine sera. Compared to virus neutralisation and haemagglutination-inhibition tests, the IgG sandwich ELISA was more sensitive in detection of the earliest immunological responses to infection or vaccination with Rift Valley fever virus. Its sensitivity and specificity derived from field data sets ranged in different ruminant species from 99.05 to 100% and from 99.1 to 99.9%, respectively. The specificity of IgM-capture ELISA varied between different species from 97.4 to 99.4%; its sensitivity was 100% in sheep tested 5-42 days post-infection. Our results in field-collected, experimental and post-vaccination sera demonstrate that these assays will be useful for epidemiological surveillance and control programmes, import/export veterinary certification, early diagnosis of infection, and for monitoring of immune response in vaccinated animals. As highly accurate and safe tests, they have the potential to replace traditional diagnostic methods, which pose biohazard risks limiting their use outside of endemic areas to high containment facilities.

Madani TA, Al-Mazrou YY, Al-Jeffri MH, Mishkhas AA, Al-Rabeah AM, Turkistani AM, Al-Sayed MO, Abodahish AA, Khan AS, Ksiazek TG, Shobokshi O. · Ministry of Health, Riyadh, Saudi Arabia.( · Clin Infect Dis. · Pubmed #14523773 No free full text.

Abstract: This cohort descriptive study summarizes the epidemiological, clinical, and laboratory characteristics of the Rift Valley fever (RVF) epidemic that occurred in Saudi Arabia from 26 August 2000 through 22 September 2001. A total of 886 cases were reported. Of 834 reported cases for which laboratory results were available, 81.9% were laboratory confirmed, of which 51.1% were positive for only RVF immunoglobulin M, 35.7% were positive for only RVF antigen, and 13.2% were positive for both. The mean age (+/- standard deviation) was 46.9+/-19.4 years, and the ratio of male to female patients was 4:1. Clinical and laboratory features included fever (92.6% of patients), nausea (59.4%), vomiting (52.6%), abdominal pain (38.0%), diarrhea (22.1%), jaundice (18.1%), neurological manifestations (17.1%), hemorrhagic manifestations (7.1%), vision loss or scotomas (1.5%), elevated liver enzyme levels (98%), elevated lactate dehydrogenase level (60.2%), thrombocytopenia (38.4%), leukopenia (39.7%), renal impairment or failure (27.8%), elevated creatine kinase level (27.3%), and severe anemia (15.1%). The mortality rate was 13.9%. Bleeding, neurological manifestations, and jaundice were independently associated with a high mortality rate. Patients with leukopenia had significantly a lower mortality rate than did those with a normal or high leukocyte count (2.3% vs. 27.9%; odds ratio, 0.09; 95% confidence interval, 0.01-0.63).

Miller BR, Godsey MS, Crabtree MB, Savage HM, Al-Mazrao Y, Al-Jeffri MH, Abdoon AM, Al-Seghayer SM, Al-Shahrani AM, Ksiazek TG. · Centers for Disease Control and Prevention, Atlanta, Georgia, USA. · Emerg Infect Dis. · Pubmed #12498669 links to  free full text

Abstract: An outbreak of Rift Valley fever in the Kingdom of Saudi Arabia and Yemen in 2000 was the first recognized occurrence of the illness outside of Africa and Madagascar. An assessment of potential mosquito vectors in the region yielded an isolate from Aedes vexans arabiensis, most closely related to strains from Madagascar (1991) and Kenya (1997).

Shoemaker T, Boulianne C, Vincent MJ, Pezzanite L, Al-Qahtani MM, Al-Mazrou Y, Khan AS, Rollin PE, Swanepoel R, Ksiazek TG, Nichol ST. · Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. · Emerg Infect Dis. · Pubmed #12498657 links to  free full text

Abstract: The first confirmed Rift Valley fever outbreak outside Africa was reported in September 2000, in the Arabian Peninsula. As of February 2001, a total of 884 hospitalized patients were identified in Saudi Arabia, with 124 deaths. In Yemen, 1,087 cases were estimated to have occurred, with 121 deaths. Laboratory diagnosis of Rift Valley fever virus (RVFV) infections included virus genetic detection and characterization of clinical specimens by reverse transcription-polymerase chain reaction, in addition to serologic tests and virus isolation. Genetic analysis of selected regions of virus S, M, and L RNA genome segments indicated little genetic variation among the viruses associated with disease. The Saudi Arabia and Yemen viruses were almost identical to those associated with earlier RVF epidemics in East Africa. Analysis of S, M, and L RNA genome segment sequence differences showed similar phylogenetic relationships among these viruses, indicating that genetic reassortment did not play an important role in the emergence of this virus in the Arabian Peninsula. These results are consistent with the recent introduction of RVFV into the Arabian Peninsula from East Africa.

Woods CW, Karpati AM, Grein T, McCarthy N, Gaturuku P, Muchiri E, Dunster L, Henderson A, Khan AS, Swanepoel R, Bonmarin I, Martin L, Mann P, Smoak BL, Ryan M, Ksiazek TG, Arthur RR, Ndikuyeze A, Agata NN, Peters CJ, Anonymous00297. · Centers for Disease Control and Prevention, Atlanta, Georgia, USA. · Emerg Infect Dis. · Pubmed #11897064 links to  free full text

Abstract: In December 1997, 170 hemorrhagic fever-associated deaths were reported in Garissa District, Kenya. Laboratory testing identified evidence of acute Rift Valley fever virus (RVFV). Of the 171 persons enrolled in a cross-sectional study, 31(18%) were anti-RVFV immunoglobulin (Ig) M positive. An age-adjusted IgM antibody prevalence of 14% was estimated for the district. We estimate approximately 27,500 infections occurred in Garissa District, making this the largest recorded outbreak of RVFV in East Africa. In multivariable analysis, contact with sheep body fluids and sheltering livestock in one s home were significantly associated with infection. Direct contact with animals, particularly contact with sheep body fluids, was the most important modifiable risk factor for RVFV infection. Public education during epizootics may reduce human illness and deaths associated with future outbreaks.