Infection three reassortirovannymi swine influenza in the U.S., epidesiologicheskoe investigation and clinical picture.

Thrice reassortirovanny, ie containing genes from swine, avian and human influenza viruses circulating in the population of pigs in the United States since 1998, people are rarely infected with this flu. In April 2009, California identified new influenza A virus of swine origin, c since new influenza in the U.S. only hurt a million people, and WHO has officially declared pandemic. May 18, 2009 on the site New England Journal of Medicine published two articles summarizing information on the infection caused by new influenza of swine origin.

The authors of the first article - Scientists from the Center for Disease Control (CDB), the members of the research team for a new influenza A swine origin, headed by Dr. Dawood FS. They describe a clinical case of influenza in the 10 year old boys with asthma (patient number 1) . March 30, 2009, the boy living in the San Diego (California), there were fever, cough and vomiting. The first of April he went to the doctor, was assigned to symptomatic treatment and the patient recovered well. This child in order of clinical trials of new diagnostic techniques have taken swabs from the nasopharynx to detect influenza viruses A, but to determine its subtype was impossible. The sample is sent to a reference laboratory, where the method of reverse-transcriptase polymerase chain reaction (real-time RT-PCR) confirmed the presence of influenza virus A, but the human subtypes, H1 and H3 were found. 04/15/2009 CDB has identified it as a new influenza virus A (H1N1) swine origin. The same day, CCB has informed the health department of California and began an epidemiological investigation as health authorities, local and state, and the department of veterinary medicine. Virus isolates contained three genes reassortirovannogo swine influenza tsirkuliruyuschegos among pigs in North America and two genes coding for neuraminidase and matrix protein is closer related genes of viruses obtained from patients with fever in Eurasia. March 28, 2009 at nine years old (patient number 2) in the area of Imperial County, California, began coughing and fever. Epidemiological link with a patient she was not. Two days later she took an outpatient swabs from the nasopharynx. Patient number 2 received amoxicillin / clavulanate and recovered without complications. CDB 17/4/2009 confirmed that the patient is a new influenza virus A (H1N1), swine origin, with the same genotype as the patient number 1. According to international laws on 17/04/2009 both cases reported to WHO. Contact with pigs, none of the patients were not identified. For rapid diagnosis of CDB modified sets of diagnostic kits for RT-PCR have been applied since December 2008 to identify seasonal influenza A, B, H1, H3, avian influenza H5, respectively, the new virus.

From 15 April to 5 May 2009 identified 642 cases of infection with a novel influenza A. Numerous cases of human infection reported from Mexico, Canada and other countries. Researchers were available data on 381 patients in the U.S... 18% of them were traveling within seven days prior to the disease in Mexico, seven were hospitalized. At the beginning of the epidemiological investigation identified four focuses the novel: in schools and universities in South Carolina (seven students), Delaware (22), Texas (5) and New York (70 - students, school personnel, contacts, students). In addition to confirmed cases in these four schools, there were cases of acute respiratory disease in family members and school contacts who have the material on the study did not take the scope of patients' age - from three months until 1981, 40% - from 10 to 18, years, 5% - 1951 and older. Among patients for whom clinical data are known, the most common symptoms were: fever (94%), cough (92%), sore throat (66%). In addition, 25% had been vomiting, and even 25% of diarrhea. Information on hospitalization is known in 399 patients, including inpatient treatment were 36 patients (9%). Age of 19 months hospitalized to 51 years. Detailed data are known for 22 of them 4 (18%) of 22 - children under 5 years old. Chronic diseases were present in nine (41%): asthma, autoimmune destruction from taking immunosuppressive drugs, myasthenia gravis with congenital heart disease, a pregnant woman with rheumatoid arthritis and psoriasis. Seven (32%) traveled for seven days prior to the disease in Mexico in 11 patients (50%) on the x-ray revealed pneumonia, including necrotizing one, and on one occasion pneumomediastinum and empyema. Empyema drained, the growth of microbes from the fluid was not. Eight (36%) were in the intensive care unit, four (18%) required mechanical ventilation. Oseltamivir received 14 (74%) patients. By 5 May, recovered 18 of 22 patients (82%) and two previously healthy child is 23 months. And the 30 year-old women remained in serious condition with respiratory failure. It died 22 months children with myasthenia and 33-year-old pregnant woman. New influenza A virus detected by RT-PCR for all 642 patients. In 49 isolates of the virus from 13 states, sequences tsirovannyh to CDB to 5 May 2009, genotype identical to 99-100%.

Sequence analysis of genes A/California/04/2009 (virus isolated from a patient number 1), showed that six gene segments (PB2, PB1, PA, HA, NP, NS) did not differ from previously observed in the swine flu virus with the triple reassortment is already circulating in North America. Neuraminidase genes and M-protein were closer to those of influenza A, circulating in pigs in Eurasia hence the resistance of a new influenza A virus to inhibitors of M2-channel (amantadine, rimantadine). This combination of genes previously not in the U.S. or in other, countries are not met. The remaining genes are 99% homologous to the genes of swine influenza viruses circulating in recent decades in North America.

In the second paper, researchers from the CDB in Atlanta, headed by Dr. Vivek Shinde, generalize the results of surveillance by another group of swine influenza viruses in humans. In the 1990s in North America emerged and became the dominant new, thrice reassortirovannye strains (H1N1, H3N2, and H1N2), causing epizootics in pigs and isolated cases of infection in humans from December 2005 to February 2009. Described 11 such cases the median age of patients - 10 years (range 16 months - 48 years, eight patients younger than 18 years). Male 7 / 11 (64%), two cases - a father and daughter, another one was suspicious of the disease among family members, but without laboratory confirmation. All lived in the Midwest and Southern United States. Four of 11 (36%) became ill in August, 1 (9%) - in October, 2 (18%) in November, 1 (9%) in December, 2 (18%) in January and 1 (9%) in February.

Three contacts with pigs on a farm, one on the market and another on the massacre. In 8 / 11 cases (73%) noted symptoms of respiratory infection in pigs, which were observed contacts. Touched to the pigs 5 / 11 (45%) 3 (27%) approached nearer 6 feet (1.83 meters) to animals, one was at the fair, but did not visit the place where the exposed pigs. In one patient contact is not known, but one could get from a person with suspected infection were in direct contact with sick pigs. The median incubation period (counting was possible in seven patients) was 3.5 days in a big 3 - 9 days. 4 / 11 (36%) suffered from chronic diseases: asthma in two, one on unspecified immunodeficiency and eczema. Influenza vaccine received at least three of them two of hospitalization was not required. Clinical data are known in 10 patients: fever in 9, all the - cough, six patients - a headache and sore throat in three had diarrhea. On two, patients complained of muscle pain, vomiting, shortness of breath. Temperature is known in six patients: median - 39,7 ° C (range 38,5-40,4).

Four were hospitalized; two in the disease went without treatment. Two children, four years and 16 months. Oseltamivir in the hospital did not get to a hospital due to dehydration and the need for medical supervision. A patient of 48 years, smoking, with hormone-dependent bronchial asthma, required endotracheal intubation and mechanical ventilation of the lower respiratory tract infection in her isolated influenza, A virus and Pseudomonas aeruginosa. She received broad-spectrum antibiotics, with 11 days in the hospital added oseltamivir, was discharged on Day 19. 26-year-old previously healthy patient was in the hospital on the third day of fever, pneumonia and sepsis with leukopenia and thrombocytopenia.

In a subsequent pneumonia has spread to other shares lungs; the patient was on mechanical ventilation; a short time received vasopressors, broad-spectrum antibiotics, with 19-day oseltamivir. It was discharged with improvement on the thirtieth day. In addition to these patients received oseltamivir two more. Common blood test performed four patients, three had revealed leukopenia, one had lymphopenia and thrombocytopenia in one. A quick test done eight patients, 7 it was positive. In one patient, a rapid test result is negative, but the virus has been detected in classical viral culture. CDB has confirmed in a subsequent swine influenza in all patients, ten - H1N1, and one - H1N2. From the human virus hemagglutinin gene of this virus differed more than one hundred amino acids. All the isolated cultures are sensitive to inhibitors and M2 (amantadine, rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir).

Thus, in anticipation of this pandemic influenza virus of swine origin in the United States recorded sporadic cases of human infection of swine influenza caused severe damage to the lower respiratory tract, often accompanied by vomiting and diarrhea. Since April 2009, identified three new assortirovanny influenza virus of swine origin, malozarazny for pigs, but caused the current pandemic in humans.

In the accompanying editorial, Dr. Robert B. Belshe from the Department of Infectious Diseases of universities in St. Louis Appreciating the rapid progress in learning a new influenza virus A, indicates that yet unknown, will take place if a new virus pathogen of seasonal influenza, as will change its virulence and how soon will produce a vaccine for mass vaccination. One thing is clear: a new influenza A virus does not last, but only once.

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