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A novel flavivirus:Makkah Region 1994-1996

Since the identification of Congo-Crimean hemorrhagic fever (CCHF) in the Western region in 1991, surveillance of viral hemorrhagic fevers (VHF) has continued to identify patients for whom neither CCHF or dengue was confirmed. In 1995 a previously unidentified flavivirus was isolated from a specimen from a patient who died from suspected CCHF in 1994. The Division of Vectorborne Infectious Diseases, Fort Collins Laboratory, Centers for Disease Control and Prevention examined the virus serologically and by partial nucleotide sequence analysis of the NS5 gene and confirmed that it was a member of the tick borne encephalitis (TBE) group.
Some of the previously negative serum and blood specimens from 1994 and 1995 from CCHF (4), VHF (17), and dengue (19) surveillance were retested for this virus. A case was defined as any febrile patient from whom the flavivirus was isolated or had seroconversion for the new flavivirus antigen without seroreactivity to dengue or CCHF. In addition to the index case, eight other patients had either virus isolation [5] or seroconversion [3].
Medical records were complete on eight patients and lacked laboratory information for one patient who died shortly after admission. All patients had fever (mean 38.7°C, range 37.1°-40 C°) with a mean duration of 5.6 days. Fever was accompanied with chills in four patients and sweating in two patients. Five patients had hemorrhagic phenomena including epistaxis (2), echymosis at needle puncture sites (3), extensive subcutaneous bleeding (1), bloody diarrhea or rectal bleeding (2), and hematemesis (1). Three patients had a morbilliform rash.
Two patients with hemorrhagic disease also had encephalitis manifested by convulsions semicoma and coma. Both had normal computerized tomography scans of their brains. Six others had either unusual irritability or drowsiness. Two patients died. During the first week after onset of fever all eight patients with laboratory testing had leucopenia, thrombocytopenia and elevated serum transaminases and two had elevated serum urea and creatinine (Table 1). Maximum abnormalities were reached at the end of first week from onset of fever.
Additional exposure and demographic information was obtained by reviewing patients' medical files, interviewing the patients (6), and by interviewing the relatives or coworkers of patients (1) who had either died or left the country and could not be interviewed. All patients were adults with a mean age of 34 years (range 24-55) and eight were males. Four were Egyptian, three came from the Indian subcontinent, and two were Saudis. All non-Saudi patients had been in Saudi Arabia for more than three months before their illness. Onset of illness occurred either in the spring or fall months of 1994 or 1995 (Figure). Three patients lived in Jeddah, five in Makkah and one was a butcher from Bisha. The Bisha butcher developed fever while attending Hajj on 21/5/1994 and died without providing the date that he traveled from Bisha to Makkah Of the seven non-Saudi patients, six were butchers, and one was a zoo worker.
The Saudi patients were a soldier and a housewife.
The six butchers handled raw meat either through slaughtering (2), or butchering in butcher shops (2) or kitchens (2). All had daily exposure to sheep meat. In addition to sheep meat, two handled beef and camel meat, and histories for three were unavailable. Three were interviewed directly and reported that they cut their hand frequently while working. One recalled a deep cut in his foot with a bloody knife one week before onset of illness. The zoo worker o y carried raw meat (beef or camel) in his bare hands to feed the zoo animals. The housewife's servants butchered freshly slaughtered sheep carcasses at her home every week. Once around the time of her onset of illness she assisted the servants in butchering a sheep carcass. However, she could not remember whether she had done this before or after her illness. The Saudi Soldier reported visiting a camel pinfold one week before his illness where he drank a large amount of mw camel milk. He denied slaughtering or butchering meat or having tick bites during the month before onset of illness.
Among the six patients that were interviewed, ticks were reported at the work sites of three patients, but not from their residences. Mosquitoes were reported from both work sites and residences of two patients. Rat infestations at home or work were not reported by any of the patients. No patient reported any history of insect bite, blood transfusion, hospitalization, or contact with patients with a similar disease two weeks prior to their illness.
The Department of Agriculture and the Municipality in the region were informed and participated in control measures. Livestock pinfolds in residential areas were closed. In other legal pinfolds, flooring was scraped, sterilized, sprayed with Diazenon and covered with new treated soil. Pre-slaughtering veterinary checkup was emphasized, and butchers and slaughterhouse workers were instructed to apply precautions such as gloving and booting to reduce skin contact and percutaneous exposure to blood. Hospitals and medical departments were informed to report any suspect VHF or encephalitis.

Editorial note:

Flaviviruses in the TBE group are known to range geographically from Negishi in Japan to Omsk hemorrhagic fever (OHF) and Russian spring summer Encephalitis (RSSE) in west and central Asia to Central European Encephalitis (CEE) in Europe to louping ill in the British Isles and southward as Kyanasur Forest disease (KFD) in India. Individual viruses can produce encephalitis alone (RSSE, CEE, and louping ill), VHF or a combination of VHF, encephalitis, and renal dysfunction (KFD, OHF). In their natural cycles these viruses are transmitted by ticks. The natural vertebrate hosts are small mammals and birds. Livestock become infected by tick bite. Transmission to man has been reported from tick bites, trapping and skinning muskrats (OHF), consuming raw milk or cheese (CEE, RSSE), butchering infected sheep (louping ill), and accidental laboratory infections (CEE, KFD, louping ill). Treatment of disease resulting from TBE flaviviruses is supportive.
The exposure information from the nine patients cases presented here indicates that the principal mode of transmission to humans for this novel flavivirus is percutaneous from slaughtering livestock or butchering fresh meat and from drinking raw camel milk.
Control measures should include the continuous cleaning and spraying of animal markets, trucks, pinfolds , and slaughter houses to eliminate ticks. Veterinary services should be available at these places to identify sick animals. Drinking raw milk or products made from raw milk (cheese, laban, yogurt) should be discouraged.
Physicians and veterinarians should report cases of suspected VHF in humans or animals within 24 hours to the DCD (02-647-9775) in the Makkah region and to the Ministry of Health (01 405 7494) for other areas of Saudi Arabia. VHF is defined as onset of fever followed within one week by hemorrhagic manifestations. These include subcutaneous hemorrhage, a rash with a positive tourniquet test, excessive bleeding at needle puncture sites, any gastrointestinal bleeding, and epistaxis. Encephalitis is also reportable. Since nosocomial transmission via blood from patients to medical staff is documented for CCHF and is possible for TBE viruses, any suspect VHF patient should be placed under strict isolation until fever and hemorrhage have resolved. For diagnosis please submit the following specimen to DCD in Jeddah: 10 ml of clotted venous blood. Postmortem serum, liver, lung, spleen and kidney samples should be submitted on fatal VHF cases. All specimens should be submitted in sealed plastic containers enclosed inside a second sealed plastic container. Specimens should be sent immediately on wet ice or frozen (-70 C) and sent on dry ice.
  1. Monath TP: Flaviviruses in Fields BN, Knipe DM (2nd ed): Fields Virology.Raven Press,