In 2000, the Naval Medical Research Center Detachment (NMRCD) and the Ministry of Health of Peru established a passive surveillance study to determine arboviral causes of febrile illness (protocol NMRCD.2000.0006). Patients with acute, undifferentiated febrile illness of <7 days were invited to enroll, and demographic and clinical information was obtained at the time of enrollment. Blood samples were obtained and assayed by virus isolation, and convalescent-phase samples were obtained 10 days to 4 weeks later for serologic studies.

Figure 1

Figure 1. Selected sites in Peru of passive surveillance study to determine arboviral causes of febrile illness in Peru, established in 2000 by Naval Medical Research Center Detachment and the Ministry of Health...

Patient 1 was a 7-year-old girl from San Benito, a rural community near Yurimaguas city (Figure 1), who on June 19, 2006, was noted to have nasal congestion, sneezing, chills, malaise, myalgia, abdominal pain, and fever followed by several episodes of watery, nonbloody feces, and vomiting. Her condition rapidly worsened, and she began having tonic–clonic seizures. The next day the involuntary movement and vomiting stopped; however, other signs worsened and she became somnolent and prostrate. Later that day she was admitted to the Hospital Santa Gema of Yurimaguas with fever, dehydration, stupor, and signs of respiratory distress along with tonic–clonic seizures. Temperature was 40°C (104°F), blood pressure 90/50 mm Hg, respiratory rate markedly increased, and heart rate 132 beats/min. Distal cyanosis, nasal flaring, rhonchi without crackles, and supraclavicular and intercostal retractions were noted, but no jaundice, lymphadenopathy or conjunctival hemorrhage were observed. Hepatomegaly (liver 4 cm under the costal border), stupor, and neck stiffness were also noted. Laboratory test results showed a left shift in the leukocyte count and renal failure (Table 1). Blood smears were negative for malaria parasites. Preliminary diagnoses were sepsis, convulsive status, and respiratory distress. Later that day the patient was considered to have a complicated, febrile, neurologic illness, and a blood sample was sent for advanced analysis at the NMRCD in Lima, Peru, and the National Institute of Health of Peru.

The girl was given supportive therapy with broad spectrum antibiotics, intravenous hydration, oxygen, and anticonvulsive medications (diazepam, phenytoin). On June 21, seizures persisted, and the patient became comatose and later died of respiratory arrest. Arterial blood gasses and electrolytes could not be measured because of the limited capacity of the hospital laboratory. The girl’s parents did not consent to lumbar puncture or autopsy.

Figure 2

Figure 2. Neighbor-joining phylogenetic tree of Venezuelan equine encephalitis virus (VEEV) complex based on partial sequence of the PE2 segment (nucleotide positions ≈8385–9190 of the VEEV genome). The tree was rooted by using...

Examination of the girl’s serum in Vero cells identified VEEV, and sequencing and phylogenetic analyses using previously described methods further identified it as subtype ID Panama/Peru genotype (Figure 2) (15). On the day the serum was collected (1 day after onset of signs), viremia titer was 1.8 ×10⁴ PFU/mL, similar to titers from other VEEV-infected study patients who did not have neurologic complications (Table 2). The National Institute of Health reported the sample to be negative for leptospiral and rickettsial organisms, according to ELISA immunoglobulin (Ig) M and indirect immunofluorescent assays, respectively. Blood and cerebrospinal fluid cultures for bacteria were not attempted.

Patient 2 was a 25-year-old man from Puerto Maldonado, a city in the department of Madre de Dios (Figure 1). On February 24, 2005, he reported fever, headache, myalgia, nausea, vomiting, and diarrhea. Because he was from an outlying rural area, he was taken to the local health center where he received intravenous rehydration and partially recovered. The patient stayed at home, but his signs and symptoms persisted. On February 27, jaundice and epistaxis developed, and the local health center referred him to the Santa Rosa Hospital in Puerto Maldonado, where he was admitted on February 28. The patient’s status deteriorated quickly; hematuria and hematemesis were followed by liver and renal failure (Table 1), and the patient died on March 1. Postmortem examination found multiple hemorrhages in his lungs, kidneys, and stomach. A serum sample collected at the time of admission was positive for VEEV antibodies, according to ELISA IgM (titer 6,400) (2,3). The case was presumed to be VEE, although virus isolation attempts were unsuccessful. Serologic assays produced negative results for leptospiral and arboviral diseases, including dengue, Mayaro, yellow fever, Oropouche, and Eastern equine encephalitis.

Patient 1 had no previous history of neurologic disease or poor health. VEEV subtype ID infection (Panama/Peru genotype) was confirmed. Because her viremia titer was similar to titers of other patients who did not have neurologic complications and survived VEEV infection, viremia levels alone may not account for the difference in disease outcome. Although VEEV was isolated from the patient’s serum and she met the Centers for Disease Control and Prevention’s diagnostic criteria for confirmed VEE (www.cdc.gov/ncphi/disss/nndss/casedef/arboviral_current.htm), we cannot rule out concomitant bacterial meningitis in this patient, who had meningismus and leukocytosis. The limited extent of our diagnostic procedures prevent us from concluding with certainty that VEEV infection was the main cause of death.

Patient 2 had severe hemorrhagic complications. Although an uncommon manifestation of VEEV infection, these complications have been reported elsewhere (6,8,14). To date, only VEEV subtype ID has been isolated in and around Puerto Maldonado (5); thus, this patient was probably also infected with this subtype. However, we cannot unequivocally state that the patient died from VEEV infection.

Both fatal cases described in this report were clinically similar to previously reported enzootic and epidemic VEE cases (1,6,8,9,11,14). Initially, both patients had fever, body aches, vomiting, and diarrhea (Table 1) (1, 6,8,9,11), which are also caused by other tropical diseases like dengue. Only some patients, such as patient 1 from Yurimaguas, had neurologic complications (Table 1), which are more commonly observed in children<15 years of age (6,8,9,11).

Our surveillance activities were limited to only 8 surveillance sites in Peru (Figure 1), so VEE cases in other areas may remain undiagnosed. Because of the lack of surveillance activities and proper diagnostic capabilities, fatal VEEV infection in Peru is likely; many cases may remain underreported in isolated rural locations where the disease is most common. Additional studies are needed to fully measure the extent and effects of VEE in Peru.