Rift Valley fever: still an emerging infection after 3500 years
Authors: Ali S Khan, Carl V Smith
Journal: The Lancet Global Health (2016)

In the Book of Exodus, the description of the fifth plague of Egypt evokes a high mortality epizootic disease affecting livestock such as camels, goats, and sheep. It is debatable whether Rift Valley fever was that biblical plague but it is undeniably an ancient zoonosis and its modern history is no less dramatic.1Davies FG The historical and recent impact of Rift Valley fever in Africa.Am J Trop Med Hyg. 2010; 83: 73-74Crossref PubMed Scopus (50) Google Scholar The virus was first isolated in 1930 after a heavy mortality of newborn lambs was reported on a Merino sheep farm in Naivasha, Rift Valley, Kenya following unusually heavy rainfall.2Daubney R Hudson JR Garnham PC Enzootic hepatitis or Rift Valley fever. An undescribed virus disease of sheep cattle and man from east Africa.J Pathol. 1931; 34: 545-579Crossref Google Scholar The associated human disease was identified 20 years later in South Africa and the relevant microbiology, clinical disease, ecology, and epidemiology seemed to be well established. This dominant disease narrative continues to be punctuated by multiple novel revelations including those reported in The Lancet Global Health by Maria Baudin and colleagues.3Baudin M Jumaa AM Jomma HJE et al.Association of Rift Valley fever virus infection with miscarriage in Sudanese women: a cross-sectional study.Lancet Glob Health. 2016; (published online Sept 27.)http://dx.doi.org/10.1016/S2214-109X(16)30176-0Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar Rift Valley fever is mainly a disease of animals with enzootic and epizoonotic mosquito-borne transmission cycles associated with corresponding endemic and epidemic disease in human beings based on a complex set of relationships between domesticated animals, the vectors, human behaviours, local ecology, and climate. The disease has long been characterised by waves of spontaneous abortions among domesticated animals and severe illness of pregnant animals and newborns that often heralds human infections. Human infections are generally subclinical or self-limited although it can be associated with a severe febrile illness and jaundice. Less than 5% develop the three major complications: encephalitis, retinitis and other ocular lesions, and a haemorrhagic fever. Transmission to human beings is mainly from direct or indirect contact with infected animals and their organs but disease has also been transmitted by mosquitoes and by aerosols generated in the laboratory. Vaccines are available for animals to limit the substantial economic impact of the disease. Rift Valley fever was considered to be limited to sub-Saharan Africa until it caused an epidemic in Egypt in 1977. It was then considered confined to Africa until an outbreak in Saudi Arabia and Yemen in 2000. Now it is recognised as an agricultural threat to the rest of the Middle East and other countries with competent mosquito vectors. Similarly, the disease has never been associated with person-to-person transmission including the reassuring lack of nosocomial infections even among health-care workers tending to patients with haemorrhagic fever. This dogma was altered in this century by two case reports of vertical transmission.4Adam I Karsany MS Case report: Rift Valley fever with vertical transmission in a pregnant Sudanese woman.J Med Virol. 2008; 80: 929Crossref PubMed Scopus (53) Google Scholar, 5Arishi HM Aqeel AY Al Hazmi MM Vertical transmission of fatal Rift Valley fever in a newborn.Ann Trop Paediatr. 2006; 26: 251-253Crossref PubMed Scopus (53) Google Scholar Baudin and colleagues3Baudin M Jumaa AM Jomma HJE et al.Association of Rift Valley fever virus infection with miscarriage in Sudanese women: a cross-sectional study.Lancet Glob Health. 2016; (published online Sept 27.)http://dx.doi.org/10.1016/S2214-109X(16)30176-0Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar extend these case reports with a large study that presents the unique observation of spontaneous abortions among febrile patients in Port Sudan infected with Rift Valley fever. The authors are explicit about all the challenges of this study, including the lack of placental and fetal tissue or virus isolation for a definitive diagnosis, but also the limited samples and clinical data; the discrepancy between the physician's record of universal jaundice among these febrile patients and the lack of corresponding laboratory evidence; the lack of corresponding public health data from the community; and the high rate of miscarriages in the fever of unproven origin group in whom Rift Valley fever was also excluded.6Kline J Stein Z Susser M Warburton D Fever during pregnancy and spontaneous abortion.Am J Epidemiol. 1985; 21: 832-842Crossref Scopus (42) Google Scholar Although enviable, it might be premature to simply accept this association based on the keen observation of astute clinicians who suspected Rift Valley fever after noting the simultaneous outbreaks of fever of unproven origin associated with haemorrhagic disease admitted to the general hospital and of miscarriages among febrile patients on the obstetrics ward. Additional explanations might be some unique features of the implicated virus for which no isolates or full-length sequence is available, some characteristic of these pregnant patients, or another co-factor. However, none of these limitations undermines the observed association: we have the first report of an outbreak of human miscarriages associated with an ancient disease of animals that is itself associated with outbreaks of abortions. The observation of spontaneous abortion due to Rift Valley fever is timely given the experience with two other emerging infections: Zika in the Americas and Ebola in west Africa. Zika is a sister arthropod-borne (arbo) virus initially isolated in Uganda and recognised as a minor human pathogen in the mid-1900s. Thanks again to a series of astute clinicians in this decade, Zika is associated with a severe clinical form with meningoencephalitis and Guillian-Barré syndrome.7Oehler E Watrin L Larre P et al.Zika virus infection complicated by Guillain-Barre syndrome—case report, French Polynesia, December 2013.Euro Surveill. 2014; 19: 1-3Crossref Google Scholar It is also a recognised teratogen during pregnancy with a range of adverse pregnancy outcome and birth defects.8Calvet G Aguiar RS Melo ASO et al.Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study.Lancet Infect Dis. 2016; 16: 653-660Summary Full Text Full Text PDF PubMed Scopus (807) Google Scholar Ebola is a haemorrhagic fever virus that is almost universally fatal to pregnant women and their offspring with the highest risk of person-to-person transmission during parturition. Sexual transmission has also been reported for both, and transmission from blood transfusions and organ transplantation should be expected. Adverse birth outcomes have been associated with a number of other arboviruses and haemorrhagic fever viruses: Dengue, West Nile virus, Japanese encephalitis virus, Venezuelan encephalitis virus, and Lassa.9Theiler RN Rasmussen SA Treadwell TT Jamieson DJ Emerging and zoonotic infections in women.Infect Dis Clin North Am. 2008; 22: 755-772Summary Full Text Full Text PDF PubMed Scopus (33) Google Scholar Astute clinicians play a crucial role in identifying emerging and re-emerging infectious diseases. The current pattern of identification of new microbes will likely continue or might even accelerate with climate disruption, weakened health systems, and more rapid and robust transportation networks for people, animals, and goods. It is incumbent on public health practitioners to improve the prediction and detection system for emerging infections to alert the health system and community to take preventive measures. Clinicians should be open to the possibility of adverse birth outcomes associated with emerging pathogens, new clinical manifestations, and alternate means of transmission. Women should be counselled about the potential risks of pregnancy loss and other adverse pregnancy outcomes associated with travel to areas with endemic viral diseases. It is tempting to use these data to alert pregnant patients who live in or travel to these areas to be concerned about Rift Valley fever. The lack of viral isolation from fetal tissue and plausible other alternative causes of pregnancy loss make this a bit premature. However, it would seem prudent to routinely recommend the use of an effective mosquito repellent, wearing long-sleeved shirts and pants, and use of mosquito netting in areas with endemic and epidemic disease. Additional investigation and viral isolation could add Rift Valley fever to the list of viral illnesses that cause adverse pregnancy outcomes. We declare no competing interests. Association of Rift Valley fever virus infection with miscarriage in Sudanese women: a cross-sectional studyThis study is the first to show an association between infection with Rift Valley fever virus and miscarriage in pregnant women. Further studies are warranted to investigate the possible mechanisms. Our findings have implications for implementation of preventive measures, and evidence-based information to the public in endemic countries should be strongly recommended during Rift Valley fever outbreaks. Full-Text PDF Open Access