We performed a serologic investigation to determine whether orthobunyaviruses commonly infect humans in the Yucatan Peninsula of Mexico. Orthobunyavirus-specific antibodies were detected by plaque reduction neutralization test in 146 (18%) of 823 persons tested. Further studies are needed to determine health risks for humans from this potentially deadly group of viruses.
We previously reported the isolation of Cache Valley virus (CVV), Kairi virus (KRIV), Cholul virus (CHLV), and South River virus (SOURV) from mosquitoes in the Yucatan Peninsula of Mexico (
CVV is a recognized human pathogen (
Serum samples were obtained from 823 febrile patients at the Secretaria de Salud de Yucatán and other health institutions in Merida during January–October 2007. The patients resided in all 3 states of the Yucatan Peninsula of Mexico: Yucatan (n = 809), Quintana Roo (n = 8) and Campeche (n = 6). The study was approved by the Institutional Biosafety Committees at Iowa State University (Ames, IA, USA) and the Universidad Autónoma de Yucatán (Mérida, Mexico).
All serum samples were examined at a dilution of 1:20 by plaque reduction neutralization test (PRNT) by using CVV (strain CVV-478), and PRNTs were performed as described (
Titers were expressed as the reciprocal of highest serum dilutions yielding
Antibodies that neutralized CVV were detected in 146 (18%) of 823 study participants. The mean ages of patients with and without antibodies that neutralized CVV were 32.0 and 22.3 years, respectively. Logistic regression analysis showed that the risk for infection increased significantly with age (p = 0.0001).
Serum samples from 50 seropositive patients were titrated and analyzed by comparative PRNT to identify the orthobunyaviruses responsible for these infections. Six persons were seropositive for CVV, 5 for CHLV, and 1 for SOURV or a SOURV-like virus; 38 had antibodies to an undetermined orthobunyavirus (
| Patient ID no. | Demographic characteristics | PRNT90 titers | Diagnosis | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Residence | Age, y/sex | CVV | CHLV | KRIV | SOURV | MAGV | WYOV | |||
| 28 | Yucatan | 18/M | 80 | 20 | – | – | 40 | – | UND | |
| 34 | Yucatan | 39/F | 80 | 20 | – | – | 20 | – | CVV | |
| 52 | Quintana Roo | 39/F | 160 | – | – | 40 | 80 | – | UND | |
| 54 | Yucatan | 32/M | 40 | 20 | – | – | 40 | – | UND | |
| 62 | Yucatan | 44/M | 40 | – | – | 20 | 20 | – | UND | |
| 72 | Yucatan | 23/M | 80 | – | – | – | 40 | – | UND | |
| 81 | Yucatan | 60/F | 20 | 20 | – | 20 | – | – | UND | |
| 92 | Yucatan | 13/M | 160 | 20 | – | 20 | 80 | – | UND | |
| 93 | Yucatan | 42/F | 40 | 20 | – | – | 20 | – | UND | |
| 113 | Yucatan | 24/F | 20 | – | – | – | – | – | UND | |
| 114 | Yucatan | 29/F | 40 | – | – | – | 20 | – | UND | |
| 120 | Yucatan | 60/F | 20 | – | – | 320 | – | – | SOURV or SOURV-like virus | |
| 159 | Yucatan | 54/M | 20 | – | – | – | 20 | – | UND | |
| 161 | Yucatan | 53/M | 20 | 20 | – | – | – | – | UND | |
| 163 | Yucatan | 27/F | 160 | 80 | 40 | – | 40 | – | UND | |
| 167 | Yucatan | 16/M | 160 | – | – | – | 40 | – | CVV | |
| 183 | Yucatan | 69/F | 20 | – | – | – | 20 | – | UND | |
| 184 | Yucatan | 34/M | 160 | 40 | – | – | 80 | – | UND | |
| 185 | Yucatan | 25/F | 20 | – | – | – | – | – | UND | |
| 192 | Campeche | 54/F | 80 | 40 | – | – | 20 | – | UND | |
| 193 | Yucatan | 16/F | 80 | – | – | – | 20 | – | CVV | |
| 194 | Yucatan | 69/F | 20 | – | – | 20 | – | – | UND | |
| 200 | Yucatan | 3/F | 40 | – | – | 40 | 40 | – | UND | |
| 205 | Yucatan | 53/M | 40 | – | – | 20 | 20 | – | UND | |
| 208 | Yucatan | 57/F | 20 | 160 | – | – | – | – | CHLV | |
| 210 | Yucatan | 42/M | 20 | – | – | – | 20 | – | UND | |
| 224 | Yucatan | 34/M | 20 | 20 | – | 20 | – | – | UND | |
| 234 | Yucatan | 39/F | 20 | 80 | – | – | 20 | – | CHLV | |
| 236 | Yucatan | 74/F | 20 | – | – | 20 | – | – | UND | |
| 386 | Yucatan | 14/F | 20 | – | – | 20 | – | – | UND | |
| 388 | Yucatan | 60/M | 160 | 1,280 | 160 | – | 40 | – | CHLV | |
| 389 | Yucatan | 5/M | 20 | – | – | 20 | – | – | UND | |
| 390 | Yucatan | 33/M | 40 | 20 | 40 | 20 | 40 | – | UND | |
| 392 | Yucatan | 22/M | 20 | – | – | – | – | – | UND | |
| 393 | Yucatan | 29/M | 40 | 20 | – | – | 40 | – | UND | |
| 396 | Yucatan | 34/F | 80 | – | – | – | 20 | – | CVV | |
| 397 | Yucatan | 32/M | 80 | – | – | – | 40 | – | UND | |
| 399 | Yucatan | 27/M | 320 | 1,280 | 160 | – | 320 | – | CHLV | |
| 400 | Yucatan | 37/F | 20 | – | – | – | – | – | UND | |
| 401 | Yucatan | 30/F | 160 | – | – | – | 40 | – | CVV | |
| 402 | Yucatan | 18/M | 20 | – | – | – | 20 | – | UND | |
| 403 | Yucatan | 50/F | 20 | 20 | – | – | – | – | UND | |
| 407 | Yucatan | 27/M | 80 | 20 | – | – | 40 | – | UND | |
| 408 | Yucatan | 40/F | 20 | – | – | – | – | – | UND | |
| 412 | Yucatan | 60/M | 20 | 320 | 80 | 40 | 40 | – | CHLV | |
| 415 | Yucatan | 17/F | 20 | – | – | 20 | – | – | UND | |
| 420 | Yucatan | 16/F | 160 | – | – | – | 20 | – | CVV | |
| 429 | Yucatan | 37/F | 20 | – | – | – | – | – | UND | |
| 442 | Yucatan | 10/F | 20 | 40 | – | 20 | – | – | UND | |
| 455 | Yucatan | 30/F | 20 | – | – | 20 | 20 | – | UND | |
*PRNT, plaque reduction neutralization test; CVV, Cache Valley virus; CHLV, Cholul virus; KRIV, Kairi virus; SOURV, South River virus; MAGV, Maguari virus, WYOV, Wyeomyia virus; –, titer <20; UND, undetermined orthobunyavirus.
CHLV and POTV share the same medium RNA segment, so antibodies for these viruses cannot be differentiated by PRNT. Furthermore, antibodies to CHLV and POTV cannot be differentiated by complement fixation test (
As already noted, serum samples from 38 (76%) of the study participants analyzed by comparative PRNT had antibodies to an undetermined orthobunyavirus. Most of these persons had low PRNT90 titers; the highest PRNT90 titer for 29 of these persons did not exceed 40. Because neutralizing antibody levels decline over time, these findings may indicate that many of these infections occurred years ago, and the trace amounts of neutralizing antibodies that remained were insufficient to yield a
We found 18% of the 823 Yucatan residents participating in our study had evidence of orthobunyavirus exposure. This number is presumably an underestimate; additional seropositive persons might have been identified if the initial PRNTs had not been restricted to CVV. In particular, additional seropositive persons likely would have been detected if SOURV was used in the initial PRNTs, because a screening algorithm that includes only a BUN serogroup virus would likely miss many CAL serogroup virus infections. Nevertheless, we provide evidence that orthobunyaviruses commonly infect humans in the Yucatan Peninsula.
Previous serosurveys have provided information on the seroprevalence of orthobunyaviruses in humans in the United States. For example, antibodies that neutralized CVV were detected in 42/356 (12%) residents in Maryland and Virginia in 1961–1963 (
All persons in our study cohort initially sought care for unspecified fever; however, we could not determine whether any of these febrile illnesses were a direct consequence of orthobunyavirus infection. The detection of acute orthobunyavirus infections is limited because no IgM-capture ELISA for orthobunyavirus diagnosis exists. PRNTs can be used to identify recent orthobunyavirus infections when paired acute and convalescent serum samples are available, but for our study, only single serum samples were available from each participant. Orthobunyavirus viremias in humans are transient and of low magnitude, which makes reverse transcription PCR ineffective for the detection of orthobunyavirus RNA in serum samples. However, a duplex reverse transcription PCR was recently developed for the detection of CVV RNA in human cerebrospinal fluid (
In conclusion, we provide evidence that orthobunyaviruses commonly infect humans in the Yucatan Peninsula. These viruses are also a common cause of infection of livestock in this region (
We thank Amanda J. Panella for providing labile serum factor; Robert B. Tesh for providing isolates of SOURV, Maguari virus, and Wyeomyia virus; and Nubia Rivero-Cárdenas for technical assistance with the serum sample collections.
This study was supported by the Iowa State University Plant Sciences Institute Virus–Insect Interactions Initiative.
Dr Blitvich is an associate professor in the College of Veterinary Medicine at Iowa State University, Ames, Iowa. His research interests are the mechanisms of vector and host interactions in arbovirus transmission cycles.