Outbreak of Swine-Origin Influenza A (H1N1) Virus Infection - Mexico, March - April 2009

In March and early April 2009, Mexico experienced outbreaks of respiratory illness and increased reports of patients with influenza-like illness (ILI) in several areas of the country. On April 12, the General Directorate of Epidemiology (DGE) reported an outbreak of ILI in a small community in the state of Veracruz to the Pan American Health Organization (PAHO) in accordance with International Health Regulations. On April 17, a case of atypical pneumonia in Oaxaca State prompted enhanced surveillance throughout Mexico. On April 23, several cases of severe respiratory illness laboratory confirmed as swine-origin influenza A (H1N1) virus (S-OIV) infection were communicated to the PAHO. Sequence analysis revealed that the patients were infected with the same S-OIV strain detected in two children residing in California (1). This report describes the initial and ongoing investigation of the S-OIV outbreak in Mexico.

Enhanced Surveillance
On April 17, in response to the increase in reports of respiratory illness, DGE issued a national epidemiologic alert to all influenza-monitoring units and hospitals (Table 1). The alert asked hospitals to report all patients with severe respiratory illness and recommended collection of diagnostic respiratory specimens from these patients within 72 hours of illness onset. On April 18, DGE staff visited 21 hospitals throughout the country to confirm the apparent increase in illness incidence.

After laboratory confirmation of S-OIV infection on April 23, DGE developed case definitions. A suspected case was defined as severe respiratory illness with fever, cough, and difficulty breathing. A probable case was defined as a suspected case in a patient from whom a specimen had been collected and tested positive for influenza A. A confirmed case was defined as a probable case that tested positive for S-OIV by real-time reverse--transcription polymerase chain reaction (RT-PCR). Health-care officials were contacted and asked to provide retrospective and ongoing data for persons having illness consistent with these case definitions and seeking care on or after March 1.

During March 1-April 30, a total of 1,918 suspected* cases were reported, including 286 probable and 97 confirmed cases (Figure). A total of 84 deaths were reported. A majority of case-reports were for hospitalized patients, reflecting the concentration of surveillance efforts within hospitals. However, DGE also received reports from sites conducting routine seasonal influenza surveillance of patients with ILI. Of 1,069 patients with suspected and probable cases for whom information was available, 755 were hospitalized, and the remaining 314 were examined in outpatient settings or emergency departments. Suspected or probable cases were reported from all 31 states and from the Federal District of Mexico. The four areas with the most cases were Federal District (213 cases), Guanajuato (141), Aguascalientes (93), and Durango (77). In other states, the number of suspected or probable cases ranged from two to 46. Suspected and probable cases were identified in all age groups. Mexico routinely monitors seasonal influenza in a network of outpatient facilities throughout the country. Fifty-one influenza A positive specimens from six states were collected during January 4--March 11 in this surveillance network. All of these specimens tested negative for S-OIV at CDC.

Confirmed Cases of S-OIV Infection
As of April 30, DGE surveillance activities, focusing on patients with severe respiratory disease, had identified 97 patients with laboratory-confirmed S-OIV infection, including seven persons who had died. The first of the 97 patients reported onset of illness (any symptom) on March 17, and the most recent patients reported onset on April 26. Laboratory confirmation of S-OIV infection for the most recent 73 of these 97 cases was reported on the evening of April 29. Collection of additional information on these 73 cases is ongoing. Of the 24 patients for whom demographic and clinical information is available, 20 (83%) were hospitalized, three were examined in outpatient settings, and one had illness that was not medically attended. Patients ranged in age from <1 style="font-weight: bold;">Reported by: General Directorate of Epidemiology, Ministry of Health, Mexico; Pan American Health Organization; World Health Organization; Public Health Agency of Canada; CDC (United States).

Editorial Note:
Understanding the epidemiology and clinical profiles of recent cases of S-OIV infection in Mexico can help inform regional, national, and global control measures in response to the emergence of S-OIV infection. Important areas for investigation worldwide include evidence of person-to-person transmission, the geographic distribution of disease, the clinical spectrum of disease, and the effectiveness of mitigation strategies.

Previous instances of human-to-human transmission of other swine viruses have been reported to result in small clusters of disease and limited generations of disease transmission (2,3). Several findings indicate that transmission in Mexico involves person-to-person spread with multiple generations of transmission. Patients with probable and laboratory-confirmed disease have presented over a period of 4 weeks. Limited contact tracing of patients with laboratory-confirmed disease also has identified secondary cases of ILI.

The clinical spectrum of S-OIV illness is not yet well characterized in Mexico. However, evidence suggests that S-OIV transmission is widespread and that less severe (uncomplicated) illness is common. Patients with confirmed disease have been identified in several states, and suspected cases have been identified in all states, which suggests that S-OIV transmission is widespread. In addition, several countries are reporting S-OIV infection among persons who have travel histories involving different parts of Mexico in the 7 days before illness onset. To date, case-finding in Mexico has focused on patients seeking care in hospitals, and the selection of cases for laboratory testing has focused on patients with more severe disease. Therefore, a large number of undetected cases of illness might exist in persons seeking care in primary-care settings or not seeking care at all. Additional investigations are needed urgently to evaluate the full clinical spectrum of disease in Mexico, the proportion of patients who have severe illness, and the extent of disease transmission.

To expedite confirmation of disease in additional patients, the World Health Organization (WHO) Influenza Collaborating Center in Atlanta, Georgia, has placed the genetic sequence of S-OIV from California in GenBank.† Specific primers for S-OIV have been developed and will be distributed through the WHO Global Influenza Surveillance Network to reference laboratories throughout the world. As of April 26, the National Laboratory for Public Health in Mexico has capacity to perform PCR for S-OIV.

The epidemiologic characteristics of this outbreak underscore the importance of monitoring the effectiveness of community mitigation efforts, nonpharmaceutical interventions, and clinical management practices in anticipation of a possible pandemic.