The preventive medicine department of the General Health Directorate in Najran reported an unusually large number of patients suffering from hemorrhagic fever since 2003. The first cases appearing in this outbreak were reported from Alkhurma, near Taif city, so the investigators used the name Alkhurma hemorrhagic fever (AHFV). This case control study aims to describe the epidemiologic characteristics of the outbreak, associated risk factors, and to provide evidence-based recommendations for control and prevention of its recurrence.
The study was conducted in Najran City. A case was defined as any person who lived in the catchment area of Najran General Health Directorate and laboratory confirmed as suffering from AHFV, during the period from 1st of January 2006 to 30th of April 2009. Controls were defined as any household or neighborhood person who had not suffered from AHFV during the same period, confirmed by serological examination. A total of 28 cases and 65 controls were included in the study.
Out of 28 AHFV cases, 11 (39.3%) had sought medical advice and been hospitalized. The rest were diagnosed by surveillance of household contacts. Clinical features reported were fever (53.6%), epistaxis (28.6%), rash (25.0%), gum bleeding (17.9%), change in urine color (21.4%) and neck rigidity (10.7%).
The first case appeared in December 2006 followed by two cases the following month in 2007, 20 cases appeared in 2008, and 5 over the first four months of 2009. The majority of the cases occurred during the period from March to July (Figure 1). Half the cases (50.0%) were 20-39 years of age, 46.4% were under 20, and 3.6% over 40. Males constituted 64.3% and 53.6% were single. The highest proportion was Yemenis (85.7%), followed by Saudis (10.7%), and Bangladeshis (3.6%). Regarding occupations, 14.3% had livestock-related occupations (shepherds and butchers), 42.9% were students, 17.9% were housewives, and 25.0% other occupations. Half of the cases (50.0%) gave history of owning or raising domestic animals compared to 26.2% of controls (Odds Ratio OR 2.82, CI: 1.02-7.91), which was statistically significant. Furthermore, individuals living closer than 100 meters to farms had a significantly higher risk of acquiring infection (OR 4.00, CI: 1.4-11.8).
Dealing with domestic animals and related behaviors, such as feeding animals,slaughtering, milking, and handling raw meat products, was also statistically significant. Those who practiced multiple behaviors had a significantly higher risk (p value <0.001).
A higher proportion of cases reported history of tick bites than controls (35.7% compared to 4.6% respectively; OR 11.48, CI 2.51-59.73), showing a statistically significant association between tick bites and disease. There was no association between mosquito bites and acquiring the disease.
Variables that were significant in the bivariate analysis (at P<0.05) or believed to be associated with AHFV, namely dealing with animals, tick bites, neighboring farms, drinking unpasteurized milk and mosquitoes bites, were entered in backward stepwise regression analysis. Dealing with animals, tick bites and neighboring farms remained significant predictors for infection. These variables were entered in the final model for controlling for each other as well as for age, gender, nationality and occupation. Dealing with animals and tick bites remained significantly associated with the disease (adjusted OR 7.72, CI: 1.16-51.23 and OR 9.67, CI: 1.41-66.18, respectively). Neighboring farms did not show an association with the disease (adjusted OR=2.85; CI: 0.83-9.76) (Table1).
Editorial note:
Alkhurma hemorrhagic virus is a member of the family Flaviviridae, discovered in Saudi Arabia for the first time in 1995. It was unknown before that time until one patient, suspected to have Congo-Crimean hemorrhagic fever, died in 1994. Specimens from that patient, sent to the Center for Disease Control and Prevention (CDC) confirmed the diagnosis of a new virus “flavivirus”, which was closely related to the Kyasanur Forest disease virus that exists in India.1,2 That patient reportedly developed fever after slaughtering a sheep imported from Alkhurma city (near Taif).
Active surveillance of hemorrhagic diseases during Hajj season of 2001 detected four cases of acute febrile illness. They were hospitalized and blood specimens were sent to the CDC for further investigations and the result showed their positivity for the new flavivirus.3 Between 2001 to 2003, another 20 cases were detected and laboratory confirmed. These cases were reported from Alkhumra district, south of Jeddah and the virus was given the name Alkhumra virus.3
Several routes of transmission have been suggested, including contamination of a skin wound with the blood of an infected vertebrate, bites of an infected tick, or by drinking unpasteurized contaminated milk.4
To our knowledge, this is the first study to assess risk factors associated with AHFV. Unlike previous studies; patients with subclinical illness discovered accidently during the past three years were also included. In this study, the seasonal pattern of the disease (Mar-Jul) is similar to that found in the western province (Jeddah and Makkah) among 11 cases recovered during the period from 1994-1999, which may support the evidence of its relation with the activity peak of ticks (feeding) occurring at the beginning of March.5,6
Risk factors for human infection identified in this study included a broad array of activities associated with animal exposures, most significantly direct contact. Close farms to houses was associated with an increased risk of disease, but was not significant with multivariate analysis, which may reflect that closeness to farms in itself is not associated with disease, but rather the direct contact with neighboring animals.
Although livestock related occupations, such as butchering, showed no significance association with disease, a history of slaughtering livestock was highly associated, which agrees with results of previous studies.1,3
Ingestion of unpasteurized milk has been noted as a risk factor in previous studies. The mode of transmission is unclear, but was suggested to be due to contamination of milk.4,7 Although bivariate analysis in this study showed a significant association between unpasteurized milk ingestion and disease, adjusting for other risk and demographic factors showed no significant association.
Only 10 of the 28 interviewed cases had a history of ticks’ bite within a month before getting the disease. However, this was found to be highly significant even after adjusting for other variables. The association of tick bites and AHFV is supported by the study of Charrel et al, where Alkhurma hemorrhagic virus was isolated from ticks (Ornithodoros spp) collected from camels and camel resting places in western Saudi Arabia.8 The role of ticks might explain the relationship of some behaviors, such as direct contact with animals and milking, as well as neighboring farms, with disease since the exact mode of transmission is not yet known.
Seroprevalence studies to establish endemicity of the disease should be conducted along with studies on animals and possible vectors, such as ticks
and mosquitoes, should be encouraged. Health education and the safety measures and precautions to prevent infection should also be conducted.
References
1.Zaki AM. Isolation of a flavivirus related to the tick-borne encephalitis complex from human cases in Saudi Arabia. Trans R Soc Trop Med Hyg 1997 Mar;91(2):179-81.
2.Qattan I, Akbar N, Afif H, Azmah SA, Khateeb T, Zaki A, et al. A novel flavivirus: Makkah Region 1994-1996. Saudi Epidemiology Bulletin 1996;1(3):2-3.
3.Madani TA. Alkhumra virus infection, a new viral hemorrhagic fever in Saudi Arabia. J Infect 2005 Aug;51(2):91-7.
4.Charrel RN, de L, X. [The Alkhurma virus (family Flaviviridae, genus Flavivirus): an emerging pathogen responsible for hemorrhage fever in the Middle East]. Med Trop (Mars) 2003;63(3):296-9.
5.Charrel RN, Zaki AM, Fakeeh M, Yousef AI, de CR, Attoui H, et al. Low diversity of Alkhurma hemorrhagic fever virus, Saudi Arabia, 1994-1999. Emerg Infect Dis 2005 May;11(5):683-8.
6.Hrklova' G, Nova'kova' M, Chytra' M, Kostova' C, Petko B. Monitoring the distribution and abundance of Ixodes ricinus ticks in relevance of climate change and prevalence of Borrelia burgdorferi sensu lato in Northern Slovakia (Liptovsk valley). Folia veterinaria 2008;52(2):62-3.
7.Kerbo N, Donchenko I, Kutsar K, Vasilenko V. Tickborne encephalitis outbreak in Estonia linked to raw goat milk, May-June 2005. Euro Surveill 2005;10(6):E050623.
8.Charrel RN, Fagbo S, Moureau G, Alqahtani MH, Temmam S, de L, X. Alkhurma hemorrhagic fever virus in Ornithodoros savignyi ticks. Emerg Infect Dis 2007 Jan;13(1):153-5.
Table 1: Multivariate logistic regression results of risk factors of Alkhurma hemorrhagic fever, Najran, 2006-2009
| |
Crude OR
|
Model 1
|
Model 2
|
|
OR
|
CI
|
aOR*
|
CI
|
aOR**
|
CI
|
|
Dealing with domestic animals
|
5.39
|
1.74-17.3
|
3.17
|
0.96-10.43
|
7.72
|
1.16-51.23
|
|
Ticks bites
|
11.48
|
2.51-59.73
|
6.20
|
1.34-28.70
|
9.67
|
1.41-66.18
|
|
Adjacent farms distance
|
4.00
|
1.40-11.75
|
3.63
|
1.25-10.49
|
2.85
|
0.83-9.76
|
Adjusted OR for the risk factors (dealing with domestic animals, tick bites, adjacent farms distance) after elimination of non-significant variables (drinking unpasteurized milk and owning or raising domestic animals) using backward stepwise strategy.
** adjusted for the risk factors (dealing with domestic animals, tick bites, adjacent farms distance) as well as for age group, gender, nationality, and occupation.