Swine Influenza


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In 1743, when disease was presumed to be astral in origin, European newspapers reported on a contagious influence (influenza in Italian) that was being visited on the citizens of Rome. Two hundred years later, Wilson Smith and colleagues would isolate an influenza A virus, one of the members of the orthomyxovirus family. Swine influenza virus (SIV) or S-OIV (swine-origin influenza virus) is any strain of the influenza family of viruses that is endemic in pigs. As of 2009, the known SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2, H3N1, H3N2, and H2N3. Swine influenza (also called Pig influenza, swine flu, hog flu and pig flu) is an infection by any one of several types of swine influenza virus. In all, 50 cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia, one had Hodgkin disease and two were known to be previously healthy. Despite these apparently low numbers of infections, the true rate of infection may be higher, since most cases only cause a very mild disease, and will probably never be reported or diagnosed. This article presents the scenario of the 2009 H1N1 influenza, popularly known as “swine flu” and the data from inpatient admissions in Indraprastha Apollo Hospitals, Delhi, for the duration October 2009 to January 2010.

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Swine Influenza

  1. 1.                                                                                                                                              SWINEE INFLUEN      NZA
  2. 2. Review Article THE PRESENT SCENARIO-2009 H1N1 INFLUENZA (“SWINE FLU”) 2009 H1N1influenza, (sometimes called “swine flu”) is a new influenza virus causing illness in people. This new virus was first detected in people in the United States in April 2009. This virus is spreading from person-to-person worldwide, probably in much the same way that regular seasonal influenza viruses spread. On June 11, 2009, the World Health Organization (WHO) signaled that a pandemic of 2009 H1N1 flu was underway. This virus was originally referred to as “swine flu” because laboratory testing showed that many of the genes in this new virus were very similar to influenza viruses that normally occur in pigs (swine) in North America [1]. But further study has shown that this new virus is very different from what normally circulates in North American pigs [2- 4]. It has two genes from flu viruses that normally circulate in pigs in Europe and Asia and bird (avian) genes and human genes [5]. Scientists call this a “quadruple reassortant” virus [6] (Fig. 1). Illness with 2009 H1N1 virus has ranged from mild to severe. While most people who have been sick have recovered without needing medical treatment, hospitalizations and deaths from infection with this virus have occurred.The information analyzed by CDC supports the conclusion that 2009 H1N1 flu has caused greater disease burden in people younger than 25 years of age than older people [7]. At this time, there are relatively fewer cases and deaths reported in people 65 years and older, 21 Apollo Medicine, Vol. 7, No. 1, March 2010 SWINE INFLUENZA Suresh Chandra*and Neelam Bisht** *Senior Consultant,**Associate Consultant, Department of Internal Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110076, India. Correspondence to: Dr Suresh Chandra, Senior Consultant, Department of Internal Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. In 1743, when disease was presumed to be astral in origin, Europeannewspapers reported on a contagious influence (influenza inItalian) that was being visited on the citizens of Rome. Twohundred years later, Wilson Smith and colleagues would isolate an influenza A virus, one of the members of the orthomyxovirus family. Swine influenza virus (SIV) or S-OIV (swine-origin influenza virus) is any strain of the influenza family of viruses that is endemic in pigs. As of 2009, the known SIV strains include influenza C and the subtypes of influenzaAknown as H1N1, H1N2, H3N1, H3N2, and H2N3. Swine influenza (also called Pig influenza, swine flu, hog flu and pig flu) is an infection by any one of several types of swine influenza virus. In all, 50 cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia, one had Hodgkin disease and two were known to be previously healthy. Despite these apparently low numbers of infections, the true rate of infection may be higher, since most cases only cause a very mild disease, and will probably never be reported or diagnosed. This article presents the scenario of the 2009 H1N1 influenza, popularly known as “swine flu” and the data from inpatient admissions in Indraprastha Apollo Hospitals, Delhi, for the duration October 2009 to January 2010. Key words: Swine flu, H1N1 influenza, Apollo experience. Fig.1. Electron microscope image of the reassorted H1N1 influenza virus
  3. 3. Apollo Medicine, Vol. 7, No. 1, March 2010 22 Review Article getting sick to 5 to 7 days after. This can be longer in some people, especially children and people with weakened immune systems [10,11]. SIGNS AND SYMPTOMS Mild or uncomplicated illness is characterized by typical symptoms like fever (although not everyone with influenza will have a fever), cough, sore throat, rhinorrhea, muscle pain, headache, chills, malaise, sometimes diarrhea and vomiting, but no shortness of breath and little change in chronic health conditions [12]. Progressive illness is characterized by typical symptoms plus signs or symptoms suggesting more than mild illness: chest pain, poor oxygenation (e.g., tachypnea, hypoxia, labored breathing in children), cardiopulmonary insufficiency (e.g., low blood pressure), CNS impairment (e.g., confusion, altered mental status), severe dehydration, or exacerbations of chronic conditions (e.g., asthma, chronic obstructive pulmonary disease, chronic renal failure, diabetes or other cardiovascular conditions) [13]. Severe or complicated illness is characterized by signs of lower respiratory tract disease (e.g., hypoxia requiring supplemental oxygen, abnormal chest radiograph, mechanical ventilation) (Fig. 2), CNS findings (encephalitis, encephalopathy), complications of low blood pressure (shock, organ failure), myocarditis or rhabdomyolysis, or invasive secondary bacterial infection which is unusual when compared with seasonal flu (Table 1). However, pregnancy and other previously recognized high risk medical conditions from seasonal influenza appear to be associated with increased risk of complications from this 2009 H1N1. These underlying conditions include asthma, diabetes, suppressed immune systems, heart disease, kidney disease, neurocognitive and neuromuscular disorders. CDC laboratory studies have shown that no children and very few adults younger than 60 years old have existing antibody to 2009 H1N1 flu virus; however, about one-third of adults older than 60 may have antibodies against this virus. It is unknown how much, if any, protection may be afforded against 2009 H1N1 flu by any existing antibody. EPIDEMIOLOGY Spread of 2009 H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza [8]. Sometimes people may become infected by touching something – such as a surface or object – with flu viruses on it and then touching their mouth or nose [9]. The 2009 H1N1 virus is not zoonotic swine flu, as it is not transmitted from pigs to humans, but from person to person. People infected with seasonal and 2009 H1N1 flu shed virus and may be able to infect others from 1 day before Table 1. CDC estimates of 2009 H1N1 cases and related hospitalizations and deaths fromApril-November 14, 2009, by age group 2009 H1N1 Mid-level range* Estimated range * Cases 0-17 years ~16 million ~12 million to ~23 million 18-64 years ~27 million ~19 million to ~38 million 65 years and older ~4 million ~3 million to ~6 million Cases Total ~47 million ~34 million to ~67 million Hospitalizations 0-17 years ~71,000 ~51,000 to ~101,000 18-64 years ~121,000 ~87,000 to ~172,000 65 years and older ~21,000 ~15,000 to ~29,000 Hospitalizations Total ~213,000 ~154,000 to ~303,000 Deaths 0-17 years ~1,090 ~790 to ~1,550 18-64 years ~7,450 ~5,360 to ~10,570 65 years and older ~1,280 ~920 to ~1,810 Deaths Total ~9,820 ~7,070 to ~13,930
  4. 4. Review Article 23 Apollo Medicine, Vol. 7, No. 1, March 2010 based on laboratory testing or clinical signs (e.g. persistent high fever and other symptoms beyond three days) [14]. People at high risk for developing flu-related complications • Children younger than 5, but especially children younger than 2 years old • Adults 65 years of age and older • Pregnant women • People who have medical conditions including: • Asthma • Neurological and neurodevelopmental conditions [including disorders of the brain, spinal cord, peripheral nerve, and muscle such as cerebral palsy, epilepsy (seizure disorders), stroke, intellectual disability (mental retardation), moderatetoseveredevelopmentaldelay,muscular dystrophy, or spinal cord injury]. • Chronic lung disease (such as chronic obstructive pulmonary disease [COPD] and cystic fibrosis) • Heart disease (such as congenital heart disease, congestive heart failure and coronary artery disease) • Blood disorders (such as sickle cell disease) • Endocrine disorders (such as diabetes mellitus) • Kidney disorders • Liverdisorders • Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders) • Weakened immune system due to disease or medication (such as people with HIV or AIDS, or cancer, or those on chronic steroids) • People younger than 19 years of age who are receiving long-term aspirin therapy. DIAGNOSIS Case definition of H1N1 influenza Suspected case A suspected case of swine influenza A (H1N1) virus infection is defined as: a person with acute febrile respiratory illness (fever = 38ºC) with onset: within 7 days of close contact with a person who is a confirmed case of Swine influenzaA(H1N1) virus infection, or within 7 days of travel to areas where there is one or more confirmed Swine influenzaA(H1N1) cases, orresides in a community where there is one or more confirmed swine influenza cases. Probable case A probable case of swine influenza A (H1N1) virus infection is defined as: a person with an acute febrile respiratory illness who is positive for influenza A, but unsubtypable for H1 and H3 by influenza RTPCR or reagents used to detect seasonal influenza virus infection, or is positive for influenza A by an influenza rapid test or influenza immunofluorescence assay (IFA) plus meets criteria for a suspected case, or an 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. Fig.2. The radiograph (A) shows bilateral alveolar opacities in the base of both lungs that progressed and became confluent. The specimen (B, hematoxylin and eosin) shows necrosis of bronchiolar walls (top arrow), a neutrophilic infiltrate (middle arrow), and diffuse alveolar damage with prominent hyaline membranes (bottom arrow).
  5. 5. Apollo Medicine, Vol. 7, No. 1, March 2010 24 Review Article Confirmed case A confirmed case of swine influenza A (H1N1) virus infection is defined as: a person with an acute febrile respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at WHO approved laboratories by one or more of the following tests:Real time PCR,,Viral culture,Four-fold rise in swine influenza A (H1N1) virus specific neutralizing antibodies. DIAGNOSTIC TESTS This season CDC recommends that influenza diagnostic testing be prioritized for (i) hospitalized patients with suspected influenza, (ii) patients for whom a diagnosis of influenza will inform decisions regarding clinical care, infection control, or management of close contacts; and (iii) patients who died of an acute illness in which influenza was suspected. Most patients with a clinical illness consistent with uncomplicated influenza who reside in an area where influenza viruses are circulating do not require diagnostic influenza testing for clinical management [15,16]. Rapid influenza diagnostic tests (RIDTs) Rapid influenza diagnostic tests (RIDTs) are widely available, commercial diagnostic tests that can detect influenza viruses in 30 minutes or less. Depending on which commercially available RIDT is used, the test can either (i) detect and distinguish between influenza Aand B viruses; or (ii) detect both influenza A and B but not distinguish between influenza A and B viruses. Rapid influenza diagnostic tests (RIDTs) are widely available but have variable sensitivity (range 10-70%) for detecting 2009 H1N1 influenza when compared with real-time reverse transcriptase polymerase chain reaction (rRT-PCR), and a negative RIDT result does not rule out influenza virus infection. RIDTs have a high specificity (>95%). Viral culture Viral culture is available in certain laboratories but often does not provide results in time to help with clinical decisions. However, viral culture is an important source of public health virologic data on influenza antigenic characteristics and antiviral susceptibilities. Viral culture is highly sensitive and specific. Direct immunofluorescence assays (DFAs) and Indirect immunofluorescence assays (IFAs) Immunofluorescence (fluorescent antibody staining) is available at many hospital laboratories and can generally yield test results in 2 to 4 hours, and sensitivities are generally higher than rapid tests, but lower than viral culture or real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Like RIDTs, direct immunofluore- scence assays (DFAs) are widely available and have variable sensitivity for detecting 2009 H1N1 virus (range 47-93%). DFAs detect and distinguish between influenzaA and B viruses but do not distinguish among different influenzaAsubtypes. Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) Nucleic acid amplification tests, including rRT-PCR, are the most sensitive and specific influenza diagnostic tests, but they may not be readily available, obtaining test results may take one to several days, and test performance depends on the individual rRT-PCR assay. As with any assay, false negatives can occur. Table 2 summarises the diagnostic tests for influenza. Hospitalized patients with suspected influenza should be considered for testing with an available influenza diagnostic test. Since a negative RIDT or DFA test result does not exclude influenza virus infection, hospitalized patients with a negative RIDT or DFA result should have priority for further testing with rRT-PCR, if influenza infection is clinically suspected. Specimens The following specimens are generally appropriate for influenza virus diagnostic testing: nasopharyngeal swab; nasal aspirate, wash or swab; endotracheal aspirate; bronchoalveolar lavage (BAL); and combined nasopharyngeal or nasal swab with oropharyngeal swab. The performance of rRT-PCR assays specific for 2009 H1N1 influenza has not been established for bronchoalveolar lavage and tracheal aspirates. If testing these specimens for 2009 H1N1 influenza, consider testing in parallel with a nasopharyngeal, nasal, or oropharyngeal swabs or a nasal aspirate. TREATMENT Antiviral drugs for treatment of influenza The neuraminidase inhibitors are the drugs of choice for treatment of 2009 H1N1 influenza and influenza-like illness in both children and adults [17]. Oseltamivir: The neuraminidase inhibitor oseltamivir formulated as capsules or oral suspension (Tamiflu®) is FDA-approved for the treatment of uncomplicated acute influenza in patients 1 year and older who have been symptomatic for no more than 2 days.
  6. 6. Review Article 25 Apollo Medicine, Vol. 7, No. 1, March 2010 Definitive testing for 2009 H1N1 requires real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) or viral culture. These tests should be prioritized for persons with suspected or confirmed influenza requiring hospitalization and based on guidelines from local and state health departments. Rapid influenza diagnostic tests (RIDTs) should not be used to rule out influenza because false negative results are common. The sensitivity of rapid tests in detecting 2009 H1N1 has ranged from 10% to 70%. Clinicians should not withhold treatment based on a negative rapid test result. Zanamivir: The neuraminidase inhibitor zanamivir formulated for oral inhalation (Relenza®) is FDA- approved for the treatment of influenza in patients 7 years of age and older who, similar to approved uses for oseltamivir, have uncomplicated illness and have been symptomatic for no more than 2 days. Peramivir: A third neuraminidase inhibitor peramivir formulated for intravenous (IV) administration is an investigational product currently being evaluated in clinical trials.As of October, 2009, safety and/or efficacy data from 1,891 patients with acute uncomplicated seasonal influenza A has been submitted to the FDA. Efficacy and safety have not been evaluated in hospitalized patients [18]. Even though the data are insufficient to allow FDA approval,under the EUA, treatment of adult patients with IV peramivir is approved only if: (i) the patient has not responded to either oral or inhaled antiviral therapy; (ii) drug delivery by a route other than IV is not expected to be dependable or is not feasible; or (iii) the clinician judges IV therapy is appropriate due to other circumstances. Initiation of treatment Uncomplicated influenza illness The algorithm for treating uncomplicated influenza illness is as follows (Fig.3). Treatment should be started empirically based on clinical judgment as early as possible even before definitive diagnostic test results become available, i.e., treatment should not wait for laboratory confirmation of influenza. Treatment is most effective when started in the first 48 hours of illness.As noted above, however, evidence suggests treatment may benefit patients with prolonged or severe illness even when started more than 48 hours after the onset of illness (Table 3). Fig.3. Algorithm for treating uncomplicated influenza illness Table 2. Diagnostic tests for influenza Influenza diagnostic Method Availability Typical Sensitivity for Distinguishes 2009 tests processing 2009 H1N1 H1N1 influenza time influenza from other influenzaA viruses? Rapid influenza diagnostic Antigen detection Wide 0.5 hour 10-70% No tests (RIDT) Direct and indirect immuno- Antigen detection Wide 2-4 hours 47-93% No fluorescence assays (DFA and IFA) Viral isolation in tissue cell Virus isolation Limited 2-10 days – Yes culture Nucleic acid amplification tests RNA detection Limited 48-96 hours 86-100% Yes (including rRT-PCR) (6-8 hours to perform test)
  7. 7. Apollo Medicine, Vol. 7, No. 1, March 2010 26 Review Article Treatment of influenza when oseltamivir-resistant viruses are circulating Oseltamivir resistance is common among seasonal influenzaA(H1N1) viruses.These viruses typically remain susceptible to zanamivir, rimantadine, and amantadine. However, since April 2009, very few seasonal H1N1 viruses have circulated in the United States. Therefore, treatment, when indicated, with either oseltamivir or zanamivir is appropriate. However, if viral surveillance data indicate that oseltamivir-resistant seasonal H1N1 viruses have become more common or are associated with identified community outbreaks, zanamivir or a combination of oseltamivir and rimantadine or amantadine should be considered for use as empiric treatment for patients who might have oseltamivir-resistant seasonal human influenzaA(H1N1) virus infection (Table 4) [19]. Oseltamivir-resistant infection with the 2009 pandemic influenzaA(H1N1) virus has so far been described only in a cluster in Vietnam and is conferred by the H275Y substitution in the neuraminidase enzyme. The resistant 2009 H1N1 are transmissible and can replicate and cause illness in healthy people in the absence of selective drug pressure. Although data are limited, it is likely that the detected levels of oseltamivir resistance are clinically relevant [20]. The risk of resistance is considered higher in patients with severely compromised or suppressed immune systems who have prolonged illness, have received oseltamivir treatment (especially for an extended duration), but still have evidence of persistent viral replication. The risk of resistance is also considered higher in people who receive oseltamivir for so-called “post- exposure prophylaxis” following exposure to another person with influenza, and who then develop illness despite taking oseltamivir [21]. The loss of oseltamivir as a treatment option for severe 2009 H1N1 infection could have profound consequences. To minimize this risk, the use of oseltamivir should be restricted to prophylaxis and treatment in high-risk persons or the treatment of people with severe or deteriorating illness, antiviral stockpiles should be diversified, and optimal dosages and combination therapies should be urgently studied. Close monitoring and reporting of resistance to neuraminidase inhibitors are essential [22]. Table 3. Antiviral medication dosing recommendations for treatment or chemoprophylaxis of 2009 H1N1 infection Medication Treatment(5 days) Chemoprophylaxis(10 days) Oseltamivir Adults 75 mg twice daily 75 mg once daily Children 12 months Body weight (kg) Body weight (lbs) 15 kg 33lbs 30 mg twice daily 30 mg once daily > 15 kg to 23 kg >33 lbs to 51 lbs 45 mg twice daily 45 mg once daily >23 kg to 40 kg >51 lbs to 88 lbs 60 mg twice daily 60 mg once daily >40 kg >88 lbs 75 mg twice daily 75 mg once daily Children 3 months to < 12 months 3 mg/kg/dose twice daily 3 mg/kg/dose once per day Children 0 to < 3 months 3 mg/kg/dose twice daily Not recommended unless situation judged critical due to limited data on use in this age group Zanamivir Adults 10 mg (two 5 mg 10 mg (two 5 mg inhalations) once daily inhalations) twice daily Children ( 7 years or older for treatment, 5 years for chemoprophylaxis) 10 mg (two 5 mg inhalations) 10 mg (two 5 mg inhalations) once daily twice daily
  8. 8. Review Article 27 Apollo Medicine, Vol. 7, No. 1, March 2010 Antiviral chemoprophylaxis of exposed individuals Infectious period One day before fever begins until 24 hours after fever ends. Who may be considered for antiviral chemoprophylaxis The following persons who are a close contact of a person with suspected or confirmed 2009 H1N1 influenza during the infectious period: Persons at high risk for complications of influenza, health care workers and emergency medical personnel, pregnant women. Whom not to treat chemoprophylactically Groups of healthy children or adults based on potential exposures in the community, workplace, school, camp or other settings, if >48 hours have elapsed since the last close contact, the close contact did not occur during the infectious period . PREVENTION Everyday steps to protect your health • Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it. • Wash your hands often with soap and water. If soap and water are not available, use an alcohol-based hand rub.Avoid touching your eyes, nose or mouth. Germs spread this way. • Avoid close contact (i.e., being within about 6 feet) with persons with influenza like illness. • If you are sick with flu-like illness, CDC recommends that you stay home for at least 24 hours after your fever is gone except to get medical care or for other necessities. (Your fever should be gone without the use of a fever-reducing medicine.) Keep away from others as much as possible to keep from making others sick • Chance of transmission is also reduced by disinfecting household surfaces, which can be done effectively with a diluted chlorine bleach solution. Studies have shown that influenza virus can survive on environmental surfaces and can infect a person for 2 to 8 hours after being deposited on the surface. Interim recommendations for facemask and respirator use to reduce 2009 influenza A (H1N1) virus transmission Use of N95 respirators or facemasks generally is not recommended for workers in non-healthcare occupational settings for general work activities. For specific work activities that involve contact with people who have ILI(influenza like illness), such as escorting a person with ILI, interviewing a person with ILI, providing assistance to Table 4.When to consider the use of antibiotics in the treatment of 2009 H1N1 influenza–associated pneumonia Indication Primary influenzal Secondary bacterial pneumonia lower respiratory disease following influenza Identification of influenza +++ ++; lower rate of recovery because later in illness Fever +++ +++; secondary fever after a period of defervescence Diagnostic specimen from lower Normal flora Gram's stain or culture shows pre- respiratory tract (sputum speci- dominant organism (Streptococcus men, tracheal aspirate, specimen pneumoniae, Staphylococcus aureus, obtained on bronchoscopy of Streptococcus pyogenes, Hemophilus intubation) influenzae, Moraxella catarrhalis) X-ray Diffuse process Lobar consolidation White-cell count Normal to low Increased Onset of respiratory compromise 1-2 days after initial symptoms 4-7 days after initial symptoms ill contacts in family +++ +++ Underlying risk factors (particularly ++ ++ neuromuscular, immunologic ++ denotes often found, and +++ usually found.
  9. 9. Apollo Medicine, Vol. 7, No. 1, March 2010 28 Review Article an individual with ILI, the following are recommended: • workers should try to maintain a distance of 6 feet or more from the person with ILI; • workers should keep their interactions with ill persons as brief as possible; • the ill person should be asked to follow good cough etiquette and hand hygiene and to wear a facemask, if able, and one is available; • workers at increased risk of severe illness from influenza infection should avoid people with ILI (possibly by temporary reassignment); and, • where workers cannot avoid close contact with persons with ILI, some workers may choose to wear a facemask or N95 respirator on a voluntary basis. • In the occupational healthcare setting, respiratory protection is recommended. VACCINES Vaccination is the best way to prevent influenza infection and its complications. Seasonal influenza vaccines are highly effective in preventing influenza disease [23]. The vaccines against 2009 H1N1 influenza are expected to work in a similar fashion to the seasonal influenza vaccines. CDC and FDA believe that the benefits of vaccination with the 2009 H1N1 influenza vaccine far outweigh the risks. • Killed, inactivated vaccines – Manufacturers are using WHO recommended recombinant/re-assortant vaccine seed strains. This is most accepted type of strategy and is being followed by three Indian manufacturers (Serum Institute of India, Bharat Biotech and Panacea Biotech). • Live attenuated nasal vaccines (LAIV)– These vaccines are based on the principle of production of seasonal influenza vaccine originally manufactured by Russians but now marketed in USA also. (Proposed by Serum Institute of India Ltd). • Vaccines using virus like particles (VLP)– These are genetically engineered vaccines in which only the proteins are expressed which form non-infectious virus-like-particles. So far only one vaccine developed this technology has been approved by the FDA (USA) – a vaccine for prevention of cervical cancer. Cadila Pharmaceutical India Ltd. has proposed production of an H1N1 vaccine using this technology in technical collaboration with a US based company Novavax , in which Cadila has a majority share. The technology has been licensed to Cadila in India and it will set up a plant to manufacture the vaccine in India. This has already been assessed and approved by Review Committee for genetically and Engineered Modified Organisms (RCGEM) of DBT. The merits of this technology are to be debated by a high-powered committee. • Recombinant fusion protein subunit vaccine using toll like receptors (TLR) in E coli expression vector– Biological E Ltd. Hyderabad, has proposed production of an H1N1 vaccine using this technology platform in technical collaboration with Vaccinate (a US based biotech company). The technology is being transferred to Biological E and the vaccine would be manufactured at Hyderabad. Approval of the RCGEM is being sought. Further details of the time- lines of preclinical and human studies are awaited. 2009 H1N1 ACIP vaccination recommendations CDC’sAdvisory Committee on Immunization Practices (ACIP), a panel made up of medical and public health experts, met July 29, 2009, to make recommendations on who should receive the 2009 H1N1 vaccine [24]. The groups recommended to receive the 2009 H1N1 influenza vaccine include: • Pregnant women because they are at higher risk of complications and can potentially provide protection to infants who cannot be vaccinated; • Household contacts and caregivers for children younger than 6 months of age because younger infants are at higher risk of influenza-related complications and cannot be vaccinated. Vaccination of those in close contact with infants younger than 6 months old might help protect infants by “cocooning” them from the virus; • Healthcare and emergency medical services personnel because infections among healthcare workers have been reported and this can be a potential source of infection for vulnerable patients. Also, increased absenteeism in this population could reduce healthcare system capacity; • All people from 6 months through 24 years of age; • Children from 6 months through 18 years of age because cases of 2009 H1N1 influenza have been seen in children who are in close contact with each other in school and day care settings, which increases the likelihood of disease spread;
  10. 10. Review Article 29 Apollo Medicine, Vol. 7, No. 1, March 2010 • Young adults 19 through 24 years of age because many cases of 2009 H1N1 influenza have been seen in these healthy young adults and they often live, work, and study in close proximity, and they are a frequently mobile population; and, • Persons aged 25 through 64 years who have health conditions associated with higher risk of medical complications from influenza. The 2009 H1N1 vaccine is not intended to replace the seasonal flu vaccine. It is an additional influenza vaccine for this influenza season. Many people will be recommended to get both vaccines. So the best advice is, get the seasonal flu vaccine as soon as it is available in your community, and if you are in one of the recommended groups, get the 2009 H1N1 vaccine when it becomes available . The 2009 H1N1 influenza vaccine is showing a similar safety profile to seasonal flu vaccines, which have a very good safety track record [24]. The most common side effects following flu vaccinations are mild, such as soreness, redness, tenderness or swelling where the shot was given. In 1976, there was a small risk of GBS following influenza (swine flu) vaccination (approximately 1 additional case per 100,000 people who received the swine flu vaccine).That number of GBS cases was slightly higher than what is normally seen in the population, whether or not people were vaccinated. Since then, numerous studies have been done to evaluate if other flu vaccines were associated with GBS. In most studies, no association was found, but two studies suggested that approximately 1 additional person out of 1 million vaccinated people may be at risk for GBS associated with the seasonal influenza vaccine [25- 26]. FDA and CDC are closely monitoring reports of serious problems following the 2009 H1N1 influenza vaccines, including GBS. Flu antiviral drugs taken from 48 hours before through 2 weeks after getting LAIV can lower or prevent the vaccinated person from responding to the vaccine and the person may not get immune protection from the vaccine. Contraindication for vaccination People who have a severe (life-threatening) allergy to chicken eggs or to any other substance in the vaccine should not be vaccinated. APOLLO EXPERIENCE OF 2009 H1N1 DISEASE Starting from October 2009 till January 2010,there were 94 admissions for suspected H1N1 disease. Of these,72 were confirmed to be H1N1 influenza by throat swab RTPCR test. The mean age of presentation was 32 yrs, and 21% of patients were less than 18 years of age. The male and female ratio was 1:1, and the median time of presentation to our hospital was 6 days. Symptomatology Fever was present in all the patients, while the occurrence of other symptoms were as follows-cough 88%, sore throat 55.6%, shortness of breath 58.3%, diarrhea 22.2% and vomiting 13.9% (Fig. 4). Coexisting illnesses Coexisting illness were present in 75% patients- hypertension (9), diabetes mellitus (11), allergic bronchitis (3), COPD (2), bronchial asthma (6), dyslipidemia (2), pulmonary tuberculosis (1), coronaryartery disease(4), hypothyroidism (2), pregnancy (2), obesity (1), psoriasis (1), post op meningioma (1), old splenic infarct (1), post AVR (1), Wegener’s disease (1), polycystic ovarian disease (1), post renal transplant (2), CLL (1), CVA(1) (Fig.5). Laboratory abnormalities Laboratory abnormalities observed in the patients were- leucopenia 19.4%, leucocytosis 16.7%, deranged liver function tests 38.9%, deranged renal profile 27.8% and thrombocytopenia 8.3%. Two patients had positive dengue serology, and the coinfection of H1N1 influenza and dengue fever has not been reported elsewhere till now. Fig. 4. Symptomatology of patients (A-fever, B-cough, C-shortness of breath, D-sore throat, E-diarrhea, F-vomiting).
  11. 11. Apollo Medicine, Vol. 7, No. 1, March 2010 30 Review Article Chest X ray revealed varied findings like few infiltrates, bronchopneumonia and ARDS in 56.9% patients and 44.4% patients required non invasive ventilation.33.3% patients required invasive ventilation and mortality was high in this group 23.6% (Fig. 6). During the period October 2009 to January 2010,there were 94 admissions with suspected swine flu,however,72 of them were confirmed with RTPCR assay.Majority of the patients presented within 6 days of illness and fever,cough and shortness of breath were the most common complaints.An overwhelming 75% of these patients had varied preexisting medical or surgical illnesses. Patients with an abnormal Chest X Ray were more likely to receive ventilatory support.Multiorgan dysfunction was common in patients with ARDS and this group carried a high mortality as expected.There were two patients with a coinfection with Dengue virus,a phenomenon which has not been reported yet. Swine flu’s lesson for the medical professionals Other than humility and a familiar lesson about the dangers of hubris, what can we learn from the sobering realities presented by these latest developments? First, preparation is an important and necessary activity, but in no way is it protective. One might even argue that it can have the negative consequence of lulling us into thinking we have a problem covered, when clearly we never do. In defense of this panic-driven approach, the product may not be entirely useless: preparation, albeit for the wrong invader, sharpens reflexes and can have at least some minimal practical yield, such as stockpiles of protective gear for health care workers. Second, we should marvel at the raw, restless power of microbes. They have the numbers – trillions and quadrillions and more that replicate wildly, inaccurately, and disinterestedly. Nothing microbes do, whether under the duress imposed by antimicrobials or from some less evident pressure, should surprise us. It’s their world; we only live in it. In this regard, it is perhaps fitting that our most successful incursion against them – Fleming’s discovery of penicillin on a nearly discarded culture plate – is immortalized as a fluke, an accident, the product of sloppy laboratory hygiene, anything but a headlong Manhattan Project–like assault against the enemy. Finally, and perhaps most important, doctors should be reminded against profligate use of antimicrobial agents. Once again, it seems that our message against profligate use of antimicrobial agents has crept over into the realm of morality, that comic-book world of good guys and bad guys. Yes, over prescribing of antibiotics is an enormous problem that must be curtailed. It causes predictable problems, and its interruption results in predictable relief of drug resistance. Just as we must watch our waistlines and our bottom lines and not drink to excess and never exceed the speed limit, in the same spirit we must control runaway antibiotic use because it will help people’s health and save money–but not because such restraint is holy or somehow separates good people from bad. In the future, we must resolve to keep fire and brimstone out of public health decisions. Otherwise, good judgment, necessary alertness, and scientific doubt also may go up in smoke. Fig. 5. Coexisting illnesses in the patients (A-hypertension, B-diabetes mellitus, C- allergic bronchitis, D-COPD, E- bronchial asthma, F-dyslipidemia, G-pulmonary tuberculosis, H-coronary artery disease, I- hypothyroidism, J-pregnancy, K-obesity, L-psoriasis, M- post op meningioma, N-old splenic infarct, O-post AVR, P-Wegener’s disease, Q-polycystic ovarian disease, R- post renal transplant, S-CLL, T-CVA ). Fig. 6. Laboratory abnormalities in the patients (A-leucopenia B-leucocytosis, C-deranged liver function tests, D-deranged renal profile, E-thrombocytopenia, F-abnormal Chest X-ray).
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