Journal of Infection and Public Health
Volume 2, Issue 4 , Pages 157-166, 2009

Swine flu

Senior Resident, Department of Neurology, Chhatrapati Shahuji Maharaj Medical University, Lucknow 226003, India

Received 9 June 2009; received in revised form 20 August 2009; accepted 27 August 2009.

Article Outline

Summary 

The recent outbreak of human infection with a novel Swine-Origin Influenza A (H1N1) virus is spreading rapidly through sustained human-to-human transmission in multiple countries. Human-to-human transmission occurs by inhalation of infectious droplets and droplet nuclei, and by direct contact, which is facilitated by air and land travel and social gatherings. The most frequently reported symptoms are fever, cough, myalgia, and sore throat. Detailed contact and travel histories and knowledge of viral activity in community are essential for prompt case detection by the health personnel. Real-time Reverse Transcriptase-Polymerase Chain Reaction analysis of throat swabs or lower respiratory samples is a sensitive means of diagnosis. Use of oral oseltamivir may be warranted for the treatment of severe illness.

Keywords: Swine influenza, H1N1, Swine flu, Oseltamivir

 

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Introduction 

The recent outbreak of a novel Swine-Origin Influenza A (H1N1) virus (S-OIV), which was first detected in April 2009 in California (USA) [1], has now migrated to other parts of the Americas, Europe, Australia, and Asia. S-OIV is a ‘triple-reassortment’ influenza virus, containing genes from human, swine, and avian influenza A viruses [2]. As of 19 August 2009, 210 countries have officially reported over 182,166 cases of S-OIV infection, including 1799 deaths reported by over 40 countries. The United States has reported the majority of fatal cases: 7511 laboratory-confirmed human cases, including 477 deaths. The other countries reporting laboratory-confirmed cases are Mexico, Canada, the United Kingdom, Australia, Thailand, Chile, Spain, Panama, Brazil, India, etc. [3]. On April 29, 2009 the World Health Organization designated the outbreak a pandemic.

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Clinical features 

Transmission 

Transmission of S-OIV is thought to occur in the same way as seasonal flu [4], [5]. Human-to-human transmission occurs by inhalation of large infectious droplets and droplet nuclei as well as by direct contact with secretions or aerosols [6]. Possibly, swine-to-human transmission may occur [7]. At present, there is no evidence of spread of infection by eating pork, or through water. Judging the pandemic potential of S-OIV is difficult with limited data, though recent epidemiological analyses suggest its transmissibility is substantially higher than that of seasonal flu, and comparable with previous influenza pandemics [8].

Infectious period 

Data regarding the estimated duration of S-OIV shedding by patients is limited and based upon seasonal influenza virus infection. In general, persons with S-OIV infection should be considered potentially infectious from 1 day before to 7 days following illness onset or until symptoms resolve. Children, patients with lower respiratory tract infections, elderly and immunocompromised patients might be infectious for up to 10 days or longer [9], [10]. This is due to low cytotoxic T-lymphocyte activity which is responsible for viral clearance and recovery from infection [11]. Cytotoxic T-lymphocyte activity declines in the elderly as well as in immunocompromised individuals so that viral shedding could persist longer in them [12]. However, studies of viral shedding to define the infectious period of S-OIV are needed. The potential for persons with asymptomatic infection to be the source of infection to others is unknown but should be investigated.

Incubation period 

The precise incubation period has not been established for S-OIV infection, it could range from 1 to 7 days, and most likely from 1 to 4 days [13]. This is comparable to the incubation period of avian influenza A (H5N1) which is 1–8 days [14], but longer than that of seasonal human influenza (1–4 days) [15].

Symptoms 

Novel S-OIV Investigation Team of Centers for Disease Control and Prevention, United States of America report a series of 642 cases from United States identified by enhanced surveillance and confirmed by real-time RT-PCR, viral culture, or both. The most frequently reported symptoms in this series are fever (94%), cough (92%), and sore throat (66%); 25% of patients report diarrhoea, and a further 25% report vomiting [16]. Myalgia and joint pains may also be present. Nine percent of patients in this series required hospitalization. Of 22 hospitalized patients, 8 required admission to an intensive care unit, 4 had respiratory failure, and two expired. Eleven patients (50% of hospitalized patients in this series) had radiologically confirmed pneumonia, including one patient each of pneumomediastinum, necrotizing pneumonia, and empyema. Radiographic changes in patents with pneumonia include diffuse, multifocal, or patchy infiltrates, interstitial infiltrates, and segmental or lobular consolidation with air bronchograms [17], [18].

Complications 

People of any age with certain chronic medical conditions, children less than 5 years, persons 65 or older, and pregnant women might be at increased risk for complications from S-OIV infection [19]. Complications like pneumonia and dehydration have required hospitalization in approximately 2–5% of confirmed cases in the United States and 5–6% in Mexico [5], [18]. Few bacterial infections have been detected in patients with S-OIV; these include empyema, necrotizing pneumonia, as well as ventilator-associated pneumonia due to Acinetobacter baumannii, Achromobacter xylosoxidans, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Patients with ventilator-associated pneumonia have serious risk of death (up to 58%) mainly due to multi-organ failure [18]. Neurological complications in form of seizures is reported in four children in Texas with S-OIV developed, though all four recovered fully [20].

There are few characteristics of this pandemic which appear unusual compared with a typical influenza seasonal outbreak. First, the percentage of patients requiring hospitalization (2–6%) appears to be higher than would be expected during a typical influenza season (0.4–1%) [21]. Second, the need for hospitalisations for S-OIV infection has been particularly high among persons aged between the ages of 1.5 and 59 years [22], which is different than that of seasonal influenza, in which severe infection requiring hospitalizations typically occurs in children aged less than 1 year and adults aged more than 65 years [21]. Why only few elderly individuals have been affected during the current pandemic is intriguing. This may be due to some degree of preexisting immunity in older individuals against antigenically similar influenza viruses that circulated prior to 1957 [23]. Of five pregnant women requiring hospitalization for S-OIV infection, one had spontaneous abortion (at 13 weeks of gestation) and one developed premature rupture of membranes (at 35 weeks of gestation) [19].

Mortality 

As of August 19, 2009, there have been 182,166 laboratory-confirmed cases of S-OIV worldwide, including 1799 deaths (0.98%) [3]. Most of the deaths are reported by the Americas (1579 deaths). Asian countries have reported 106 deaths. Europe and Africa have reported fewer deaths.

Most of the deaths are related to respiratory failure resulting from severe pneumonia and acute respiratory distress syndrome [24]. Renal or multi-organ failure occurs in 24% cases. In Mexico, most of the deaths (54%) occurred in previously healthy individuals between the ages of 20 and 59 [24]. In other parts of world, most of the deaths occurred in individuals with underlying health problems [25], [26]. One death in Mexico and one death in the US occurred in women who were in the third trimester of pregnancy when they became ill [19], [24].

The number of deaths in US was highest among people 25–49 years of age (39%), followed by people 50–64 year of age (25%) and people 5–24 year of age (16%) [27]. This pattern is different from what is seen in seasonal influenza, where an estimated 90% of influenza-related deaths occur in people 65 years of age and older [21].

At present, the data seem to imply that this new virus is relatively mild, with case fatality ratios around 1%, similar to or less than that seen for seasonal influenza [28]. However, simple interpretations of these crude figures at the beginning of a pandemic may be misleading in terms of assessing severity. This may occur due to bias in estimates of the case fatality ratio (with time, efforts may become more focused on the most severe cases, leading to an overestimation of the case fatality ratio) and from the inevitable delay between symptom onset and death, which in the early phase of the epidemic can lead to underestimation of the case fatality ratio if it is not adjusted for [29].

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Management 

Case detection 

The possibility of S-OIV infection should be considered in all patients with severe acute respiratory illness in countries or territories with known S-OIV. Clinicians should consult their individual health ministries for information about incidence of the disease in their countries and guidelines for case detection. Recommendations can also be found at the World health organization website (http://www.who.int/csr/resources/publications/swineflu/interim_guidance/en/index.html) and the United States Centers for Disease Control and Prevention website (http://www.cdc.gov/swineflu).

As per United States Centers for Disease Control and Prevention guidelines [13], testing for S-OIV should be considered in individuals with an acute febrile respiratory illness (a measured temperature of 37.8°C or higher and recent onset of at least one of the following: rhinorrhea, nasal congestion, sore throat, or cough) or sepsis-like syndrome. Priority for testing should be given to those who require hospitalization and those who are at high risk for severe complications. In addition, patients having influenza-like illness developing within 7 days of close contact with a person who is a confirmed case of S-OIV infection, or who has travelled to areas with known S-OIV activity in past 7 days, the possibility of S-OIV warrants consideration [30].

Not all individuals with suspected S-OIV infection need to have the diagnosis confirmed, particularly if the illness is mild [13]. Recommendations on whom to test may differ by state or country and clinicians should be aware of them. For countries with limited laboratory capacity, or limited access to laboratory capacity, World Health Organization recommends that they should aim to test a number of samples per week in order to verify that disease activity is still largely due to S-OIV [30].

Specimen collection 

To test for S-OIV, upper respiratory specimens, such as a nasopharyngeal swab or aspirate, nasal wash, or tracheal aspirate should be collected with appropriate personal protective precaution. Specimens should be sent to the nearest laboratory which has been equipped to test S-OIV. Swabs with a synthetic tip (e.g., polyester or Dacron) and aluminum or plastic shaft should be used. Swabs with cotton tips and wooden shafts are not recommended. The collection vial in which the swab is placed should contain 1–3mL of viral transport media. Specimens should be placed in viral transport media and placed on ice (4°C) or refrigerated immediately for transportation to the laboratory. Once the samples arrive in the laboratory, they should be stored either in a refrigerator at 4°C or in a −70°C freezer. If a −70°C freezer is not available, they should be kept refrigerated, preferably for ≤1 week. Specimens should be shipped on dry ice to the state public health laboratory in clearly labeled containers and should include all information requested by the state health laboratory [13], [30].

Virus detection 

Real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) 

The recommended test to confirm the diagnosis of S-OIV is real-time RT-PCR for influenza A, B, H1, and H3 [13], [30]. The strain of H1N1 influenza A virus associated with the 2009 pandemic tests positive for influenza A and negative for H1 and H3 by real-time RT-PCR.

Viral culture 

A virus culture is diagnostic, but culture is usually too slow to help guide clinical management. A negative viral culture does not exclude pandemic S-OIV infection [13], [31].

Rapid antigen tests 

Clinicians may consider using rapid influenza antigen tests as part of rapid evaluation of patients suspected of having S-OIV infection, but results should confirmed by real-time Reverse Transcriptase (RT)-PCR or culture [32]. The sensitivity and specificity of rapid antigen testing for S-OIV infection have not been established. Based on limited data, the sensitivity of rapid antigen testing for detecting S-OIV is probably similar to, or lower than, the sensitivity for detecting seasonal influenza [33]. A negative rapid influenza test does not exclude infection [32].

Immunofluorescent antibody testing 

A patient with a positive Immunofluorescent antibody testing may be considered a probable case if he or she meets the other criteria. A negative test does not exclude S-OIV infection since these tests have unclear sensitivity to detect this virus [34].

Case definition [13] 

A suspected case of S-OIV infection is defined as a person with acute febrile respiratory illness (fever=37.8°C) with onset:

(i)within 7 days of close contact with a person who is a confirmed case of S-OIV infection, or

(ii)within 7 days of travel to areas where there are one or more confirmed S-OIV cases, or

(iii)resides in a community where there are one or more confirmed swine influenza cases.

A probable case of S-OIV infection is defined as a person with an acute febrile respiratory illness who:

(i)is positive for influenza A, but unsubtypable for H1 and H3 by influenza RT-PCR or reagents used to detect seasonal influenza virus infection, or

(ii)is positive for influenza A by an influenza rapid test or an influenza immunofluorescence assay plus meets criteria for a suspected case, or

(iii)individual with a clinically compatible illness who died of an unexplained acute respiratory illness who is considered to be epidemiologically linked to a probable or confirmed case.

A confirmed case of S-OIV infection is defined as a person with an acute febrile respiratory illness with laboratory-confirmed S-OIV infection by one or more of the following tests:

(i)Real-time RT-PCR

(ii)Viral culture

(iii)Four-fold rise in S-OIV specific neutralizing antibodies.

Hospitalization 

Most cases of S-OIV infection tend to be mild and self-limited and do not require visit to a health care provider or hospitalization [16]. Patients with severe illness and those at high risk for complications from influenza should seek medical care. Those with severe illness and complications may require prolong hospitalization, and in some cases ventilatory support [5], [18]. If patients are discharged early, both the patients and their families require education on personal hygiene and infection-control measures.

Antiviral agents 

S-OIV is susceptible to oseltamivir and zanamivir, neuraminidase inhibitor antiviral medications, which target the early phase of the infection. However, this strain is resistant to adamantanes, such as amantadine and rimantadine [35].

Oseltamivir 

Oseltamivir is a prodrug that is hydrolyzed by the liver to its active metabolite, oseltamivir carboxylate, with an elimination half-life of about 6–10h. Oseltamivir is a neuraminidase inhibitor, serving as a competitive inhibitor of sialic acid, found on the surface proteins of normal host cells. By blocking the activity of the neuraminidase, oseltamivir prevents new viral particles from being released by infected cells [36]. The therapeutic oral dosage for S-OIV infection in adults is 75mg taken twice daily for 5 days, starting within 48h of the initial symptoms to capture the early phase of viral replication (Table 1). For chemoprophylaxis, the recommended dosage is 75mg taken once daily for 10 days after exposure. Therapeutic and prophylactic dosing schedules for children are similar (about 2mg/kg twice a day for 5 days for treatment, and 2mg/kg once a day for 10 days for prophylaxis) [13]. Adverse effects of oseltamivir includes nausea, vomiting and transient neuropsychiatric events (self-injury or delirium). These dangerous side effects occur more commonly in children and adolescents [37]. Nausea and vomiting might be less severe if oseltamivir is taken with food.

Table 1. Antiviral medication dosing recommendations for treatment or chemoprophylaxis of S-OIV infection.
Agent, group TreatmentChemoprophylaxis
Oseltamivir
Adults 75mg capsule twice daily for 5 days75mg capsule once daily

Children ≥12 months15kg or less60mg per day divided into 2 doses30mg once daily
15–23kg90mg per day divided into 2 doses45mg once daily
24–40kg120mg per day divided into 2 doses60mg once daily
>40kg150mg per day divided into 2 doses75mg once daily

Zanamivir
Adults Two 5mg inhalations (10mg total) twice dailyTwo 5mg inhalations (10mg total) once daily
Children Two 5mg inhalations (10mg total) twice daily (age, 7 years or older)Two 5mg inhalations (10mg total) once daily (age, 5 years or older)
Zanamivir 

Zanamivir is administered by inhalation with a dry powder inhaler. The bioavailability of the drug is 10–20% by inhalation, compared with 2% by oral administration. About 90% of the absorbed dose is excreted unchanged in the urine. The elimination half-life in serum of zanamivir is about 2–5h [38]. The mechanism of action is similar to oseltamivir. The therapeutic dose is 10mg inhaled twice daily for 5 days starting within 48h of the initial symptoms. For chemoprophylaxis, the dose is 10mg inhaled once daily for 10 days after exposure (Table 1). The recommended doses for children are the same. Because zanamivir therapy requires the patient to voluntarily inhale through the device, oseltamivir may be preferred over zanamivir for young children. Zanamivir is not recommended for treatment for patients with chronic airway disease or asthma as it can induce bronchospasm [38].

Recommendations 

During the current pandemic, patients with mild illness do not require antiviral agents unless they have risk factors for complications [13]. However, the decision of whether to initiate antiviral therapy for each patient should be based upon the clinician's judgment, especially in areas with limited antiviral availability. Clinicians should consult with their ministries of health and/or the World Health Organization for specific recommendations.

The United States Centers for Disease Control and Prevention has released guidelines for the use of antivirals for patients with confirmed or suspected S-OIV infection and close contacts which are as follows [13].

Adults 

Antiviral therapy should be started in all adult hospitalized patients with confirmed, probable, or suspected patients and in those at increased risk for complications. Therapy should be started as soon as possible, since evidence of benefit is strongest when treatment is started within 48h of illness onset. Some studies of hospitalized patients have demonstrated benefit even when therapy for seasonal influenza is started >48h after onset of illness [5], [17], [18]. In patients with severe infection, therapy can be started even past 48h of symptoms. Recommendations for use of antivirals may change as data on antiviral effectiveness, clinical spectrum of illness, adverse events from antiviral use, and antiviral susceptibility data become available.

Pregnancy 

Oseltamivir and zanamivir are Pregnancy Category C drugs, reflecting that clinical studies have not been done to assess the safety of their use during pregnancy [13], [35]. Because of more data about its safety in pregnancy, the use of oseltamaivir is preferred over zanamavir during pregnancy. Both oseltamivir and zanamivir are considered to be compatible with breastfeeding [39]. Pregnant women who meet case definitions for confirmed, probable, or suspected S-OIV infection should receive antiviral therapy with oseltamivir, since the potential benefit outweighs the theoretical risk to the fetus. Treatment should be initiated as early as possible.

In addition to antiviral therapy, use of acetaminophen is important when fever is present, since hyperthermia during the first trimester has been associated with neural tube defects and other birth defects [40]. In addition, fever during labor is a risk factor for neonatal seizures, encephalopathy, cerebral palsy, and neonatal death [41].

Children 

All hospitalized children with confirmed, probable, or suspected S-OIV infection and those at higher risk of complications should receive antiviral agents. In addition, all children younger than 5 years of age, particularly those less than 2 years of age, are at increased risk for complications of influenza. Either oseltamivir or zanamivir can be given in children, when indicated, during the current pandemic [13]. For children less than 1 year of age, oseltamivir is the recommended drug. Children taking oseltamivir should be closely observed for serious neuropsychiatric events as described above.

Children who may have influenza infection should not take aspirin or aspirin-containing products, such as bismuth subsalicyclate due to the increased risk of Reye syndrome [42].

Post-exposure chemoprophylaxis 

Post-exposure chemoprophylaxis should be considered for both close contacts of cases and health care personnel who have had a recognized, unprotected close contact exposure to a confirmed, probable or suspected case during the infectious period of that patient. Close contact is defined as person who has cared for or lived with a person who is a confirmed, probable or suspected case of S-OIV infection, or having been to a setting where there was a high likelihood of contact with respiratory droplets and/or body fluids of such a patient. Examples of close contact include kissing or embracing, sharing eating or drinking utensils, physical examination, or any other contact between persons likely to result in exposure to respiratory droplets. Close contact typically does not include activities such as walking by an infected person or sitting across from a symptomatic patient in a waiting room or office [43].

For antiviral chemoprophylaxis of S-OIV infection, either oseltamivir or zanamivir can be given (Table 1). Antiviral post-exposure chemoprophylaxis should be given for 10 days after the last known exposure to S-OIV.

Antiviral resistance 

As with other antiviral agents, resistance to the agent is expected with widespread use of oseltamivir and zanamivir. At least five isolates of S-OIV with resistance to oseltamivir have been detected from patients in Denmark, Japan, Hong Kong, and Canada [44], [45]. Mutations conferring resistance are single amino acid residue substitutions (His274Tyr) in the neuraminidase enzyme [46].

However, in locations where oseltamivir-resistant virus is circulating, zanamivir may be given. In such a setting, for patients who are unable to take zanamivir, rimantadine, amantadine or ribavarine may be added to oseltamivir [47]. One recent study has reported reduced zanamivir susceptibility in nine influenza A (H1N1) viruses isolated between 2006 and early 2008 from Australasia and South East Asia which contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation [48].

Additional therapy 

Additional therapy such as antibiotics should be used at the discretion of the clinicians if the patient's clinical condition warrants. Patients with pandemic S-OIV infection who develop pneumonia should be treated empirically for community-acquired pneumonia [49]. In patients with severe community-acquired pneumonia requiring intensive care unit admission who also have either necrotizing/cavitary infiltrates or empyema, pathogens like methicillin-resistant S. aureus (MRSA), A. baumannii, A. xylosoxidans and E. coli infection should be suspected and treated aggressively as mortality may be high among them [18].

Role of corticosteroids in the management of severely ill patients with novel S-OIV infection is unclear, and routine corticosteroid use is not recommended. Low doses of corticosteroids may be considered for patients in septic shock who require vasopressors and have suspected adrenal insufficiency. Prolonged use of or high dose corticosteroids can result in serious adverse events in influenza virus-infected patients, including opportunistic infection and possibly prolonged viral replication [50].

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Prevention 

Immunization 

Vaccines are the most powerful public health tool for control of influenza. Seasonal influenza vaccines are not expected to provide protection against S-OIV infection because this novel strain hemagglutinin is different from seasonal influenza A (H1N1) [51]. Around 20 vaccine manufacturers are preparing to make S-OIV vaccine, and it is expected to be available as early as September 2009 [52]. As vaccines available initially will not be sufficient, a step-wise approach to vaccinate particular groups may be considered. The Strategic Advisory Group of Experts of the World Health Organization suggested the following groups for consideration, noting that countries need to determine their order of priority based on country-specific conditions: healthcare providers; pregnant women; those aged above 6 months with one of several chronic medical conditions; healthy young adults of 15–49 years of age; healthy children; healthy adults of 50–64 years of age; and healthy adults of 65 years of age and above. Since the S-OIV vaccine is not intended to replace the seasonal flu vaccine, individuals should be encouraged to get their seasonal flu vaccine along with it [52].

Household and close contacts 

Household contacts of persons with confirmed cases of S-OIV should receive post-exposure prophylaxis as described above. Contacts of a patient with proven or suspected virus should monitor their temperature and symptoms. Medical attention should be sought if they have fever greater than 37.8°C plus one or more of the following: rhinorrhea or nasal congestion; sore throat; cough. All people of patient's family, including patient, should cover their cough and wash hands often. People with influenza-like illness should remain at home until at least 24h after they are free of fever (37.8°C), or signs of a fever without the use of fever-reducing medications [53]. In community and home settings, the use of facemasks and respirators are not recommended, except for persons at increased risk of severe illness from influenza. However, healthcare providers caring for persons with confirmed, probable or suspected S-OIV infection should wear N-95 respirator [54].

Travel 

People with symptoms of flu should not leave home or travel. If symptoms develop during flight or public transport vehicle, the person with illness should protect others by wearing a facemask if tolerable to reduce the number of droplets coughed or sneezed into the air or use a tissue to cover their nose and mouth when coughing or sneezing. The person with illness should sit at least 6 feet apart from others without compromising flight safety. If the person with illness is travelling to a different country, the captain of the plane should report the illness to quarantine officials in the jurisdiction of the airport where the plane is expected to land prior to arrival or as soon as illness is noted. Quarantine officials will work with the airline and local and state health departments to assist with medical transportation of the patient upon arrival, disease control and containment measures, passenger and crew notification and surveillance activities, and airline disinfection procedures [55].

Public gathering 

In public gatherings, it is difficult to maintain physical distance between people. As a result, there may be increased risk for spread of S-OIV. Such gatherings can include school or college classes, church services, sporting events, concerts, social and cultural celebrations, weddings, conferences, and other similar activities attended by relatively large groups of people. It is recommended that persons with influenza-like illness should avoid such gatherings and stay at home for 7 days after the onset of illness or at least 24h after symptoms have resolved, whichever is longer [56]. Persons who are at high risk of complications from S-OIV infection should consider staying away from public gatherings in communities where S-OIV is circulating. All persons should be reminded to use appropriate respiratory and hand hygiene precautions.

Further, large public gatherings offer a good opportunity for public health officials and event organizers to deliver key educational messages about measures attendees can take to help reduce the spread of S-OIV infection. Other measures like hand washing facilities with soap and running water, hand sanitizer, tissues, and on-site medical assessment can be provided by event organizers to help reduce the risk for infection. [57].

School closures are not universally recommended due to ethical concerns, though policies may vary in different countries [58]. However, it is pertinent to mention that the current pandemic spread to United States from Mexico in March–April 2009 after some students of a New York school contracted S-OIV infection during a visit to Mexico over spring break [1].

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Global efforts 

World Health Organization (WHO) is actively monitoring the progress of the pandemic through consultations with its Regional Offices and member states. WHO has teamed up with agencies like United States Centers for Disease Control and Prevention, the Pan-American Health Organization/(PAHO/WHO), Global Outbreak Alert and Response Network, European Centre for Disease Prevention and Control, and the China Centre for Disease Prevention and Control to better understand the outbreak, including clinical illness severity and transmission patterns, and to facilitate the production and distribution of S-OIV vaccine.

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Conclusions 

Although it has been just over four month since the first few cases were identified, the outbreak of human infection with a novel S-OIV is spreading rapidly through sustained human-to-human transmission in multiple countries. The spread of infection has been facilitated by air and land travel and social gatherings. The better understanding of routes of transmission, clinical features, pathogenesis, and perhaps, response to treatment is required to check the spread of infection. Detailed contact and travel histories and knowledge of viral activity in community are essential for prompt case detection by the health personnel. Real-time RT-PCR analysis of throat swabs or lower respiratory samples may offer sensitive means of diagnosis. Use of oral oseltamivir may be warranted for the treatment of severe illness. Above all, there is an urgent need for global coordination in clinical and epidemiologic research to control this outbreak.

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Conflict of interest 

Funding: None.

Competing interests: None declared.

Ethical approval: Not required.

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Acknowledgment 

None.

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PII: S1876-0341(09)00061-6

doi:10.1016/j.jiph.2009.08.006

Journal of Infection and Public Health
Volume 2, Issue 4 , Pages 157-166, 2009

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