The study was conducted in the city of Najran, which is in the southern part of Saudi Arabia on the border with Yemen. It is the capital of Najran region and has a population of ≈250,000. It is an agricultural city in which residents commonly raise domestic animals in their backyards. Cases of ALKHF were found in 6 districts, which were close to each other (within ≈30 km) and rural and in which hygiene was poor.

From 2006 through 2009, laboratory testing for ALKV was performed for Najran residents who sought medical care and whose illnesses met the case definition for suspected ALKHF. Infection with ALKV was suspected if a patient had acute febrile illness for at least 2 days; negative Rift Valley fever, Crimean-Congo hemorrhagic fever, and dengue confirmatory test results; and >2 of the following: 1) at least 3-fold elevation of alanine transferase or aspartate transferase or clinical jaundice; 2) signs of encephalitis such as confusion, disorientation, drowsiness, coma, neck stiffness, hemiparesis, paraparesis, or convulsions; 3) signs of hemorrhage such as ecchymosis, purpura, petechiae, gastrointestinal bleeding (hematemesis, melena, hematochesia), epistaxis, bleeding from puncture sites, or menorrhagia; and 4) platelet count <100 × 10⁹/L, or lactate dehydrogenase or creatine phosphokinase 2× upper reference level.

In addition, as part of public health surveillance, blood samples were collected from household contacts of patients with laboratory-confirmed ALKHF. Samples from persons seeking medical care were tested by ELISA for ALKV-specific immunoglobulin (Ig) M and IgG by using ALKV antigen as described (7,8) and for viral-specific sequence by reverse transcription–PCR (TiBMolbiol, LightMix kit; Roche Applied Science, Basel, Switzerland). Samples from follow-up testing of household contacts were tested by ELISA for ALKV-specific IgG. A total of 11 cases were identified through persons seeking medical care whose illnesses met the case definition for ALKHF, and another 17 cases were identified through follow-up testing of household contacts.

A case of ALKHF was defined as illness in any person who lived in the catchment area of Najran General Directorate of Health Affairs and who had serologic evidence of ALKV infection during January 1, 2006–April 30, 2009. All 28 case-patients identified were included in the study. For each case-patient, 2 controls selected from the same house or the nearest neighboring house. A total of 65 controls were enrolled, each of whom was serologically negative for ALKV-specific antibodies.

A structured questionnaire was based on information collected during the initial review of the outbreak and asked for demographic data (name, age, gender, nationality, educational status, occupation, marital status, and place of residency), clinical features, and possible risk factors such as exposure to domestic animals. Exposure history for case-patients was limited to the 30 days before onset of illness and for controls to the past 30 days. If the case-patient or control was a child and unable to respond, the child’s mother, father, or an older family member helped answer the questions.

After the samples (frequency and percentage distributions, means, and standard deviations) were described, cross-tabulations were constructed to compare risk factors. To estimate the strength of association, we calculated odds ratios (ORs) with 95% confidence intervals (CIs). For the multivariate analysis, the most significant variables from the bivariate analysis (at p<0.05) and relevant variables thought to be associated with ALKHF from other studies were selected for backward stepwise inclusion in the model.

Of 28 case-patients, 11 (39%) were seeking medical advice and hospitalized for ALKHF, and the others were identified through surveillance among household contacts. Among the 11 hospitalized case-patients, 7 diagnoses of ALKHF were made by PCR and 4 by serologic testing. Among the hospitalized case-patients, only 1 had severe symptoms and was admitted to the intensive care unit. The remaining 10 stayed in the hospital for 5–15 days (mean duration 9.3 ± 3.3 days) and received supportive care, including intravenous fluid administration and antimicrobial drugs when indicated.

Although only 11 case-patients sought medical care, 4 reported having had an illness during the study period with symptoms consistent with those of ALKV infection, and 13 seropositive persons reported having had no illness. Among all seropositive persons, fever was found for 15 (54%), bleeding (epistaxis) for 8 (29%), rash for 7 (25%), change in urine color for 6 (21%), gum bleeding for 5 (18%), neurologic signs (e.g., neck rigidity) for 3 (11%), and change in feces color for 1 (4%) (Table 1). No case-patient died. Timing of seeking care for the 11 case-patients was December 2006 (n = 1), January 2007 (n = 1), 2008 (n = 4), and the first 4 months of 2009 (n = 5) (Figure); most cases occurred during March–July. Among the 28 persons with positive serologic test results, 5 clusters were identified in which multiple persons within a single family were infected (these family clusters involved 7, 5, 3, 3, and 2 persons in the respective families).

The 28 case-patients were 4–55 years of age (mean 22 ± 11.2 years), and most (14 [50%]) were 20–39 years of age. Most case-patients were male (18 [64%]) and single (15 [54%]). Case-patients were of 3 nationalities: Yemeni (24 [86%]), Saudi (3 [11%]), and Bangladeshi (1 [4%]). Regarding educational level, 1 (4%) was in preschool, 4 (14%) were illiterate, 13 (46%) had primary or intermediate degree, 8 (29%) had a high school degree, and 2 (7%) had a university degree. Most (12 [43%]) case-patients were students, 4 (14%) had livestock-related jobs, 5 (18%) were housewives, and 7 (25%) had other jobs. Most (20 [71%]) case-patients lived in modern houses (Table 2).

Cases were identified within 6 different districts; most were in the city of Najran. They were in agricultural areas with livestock, some of which lived with the people in the houses.

The mean age of case-patients was 22.3 years ± 11.2 years, and mean age of controls was 25.2 years ± 15.4 years; the difference was not significant (t test, p = 0.657). The age group 20–39 years contained 14 (50%) case-patients and 31 (48%) controls; the age group <20 years contained 13 (46%) case-patients and 24 (37%) controls. No significant difference was noted between case-patients and controls in terms of gender, nationality, education level, marital status, type of home (modern or not), occupation, or district of residence (Table 2).

Among the case-patients, 14 (50%) gave a history of owning or raising domestic animals, compared with 17 (26%) controls (OR 2.82, 95% CI 1.02–7.91). Among those who reported owning or raising domestic animals, all case-patients and controls had sheep on their farms; thus, owning sheep was a significant risk factor (OR 2.82, 95% CI 1.02–7.91). Owning cows and camels was less common; no significant association was found (OR 1.37, 95% CI 0.30–5.86 and OR 10.29, 0.84–279.2, respectively). Risk for infection was significantly higher for those who lived <100 meters from farms (OR 4.00, 95% CI 1.40–11.75) than for those who lived farther from farms (Table 3).

A significantly higher proportion of case-patients (46%) than controls (14%) had direct contact with animals (OR 5.39, 95% CI 1.74–17.3). Furthermore, 9 (32%) case-patients and 3 (5%) controls fed animals (OR 9.79, 95% CI 21.1–51.48); 10 (36%) case-patients and 6 (9%) controls slaughtered animals (OR 5.46, 95% CI 1.54–20.02); and 9 (32%) case-patients and 7 (11%) controls handled raw meat products (OR 3.92, 95% CI 1.14–13.84). A borderline significant association with disease was found for milking animals (OR 4.00, 95% CI 0.99–16.64). Risk was higher for those who dealt with animals in multiple ways (e.g., feeding, slaughtering, milking, handling raw meat products) (χ² for trend 15.53; p<0.001). Unpasteurized milk was consumed by 8 (29%) case-patients and 6 (9%) controls (OR 3.93, 95% CI 1.06–14.88). A statistically significant association was found for tick bites and disease; a higher proportion of case-patients (36%) than controls (5%) reported a history of tick bites (OR 11.48, 95% CI 2.51–59.73). No statistically significant difference between case-patients and controls was found for exposure to mosquitoes (OR 2.72, 95% CI 0.65–13.03) (Table 2).

Multivariate analysis, conducted with variables that were significant (p<0.05) in bivariate analysis and with variables previously reported to be associated with ALKHF (contact with animals, tick bites, close proximity of neighboring farms, consumption of unpasteurized milk, and mosquitoes bites) was conducted by backward stepwise regression analysis. Among these variables, contact with animals, tick bites, and neighboring farms remained predictors for ALKHF (adjusted ORs 3.17, 95% CI 0.96–10.43; 6.20, 95% CI 1.34–28.70; and 3.63, 95% CI 1.25–10.4, respectively) (Table 4).