COMPLICATIONS OF H1N1 INFECTION

The primary complication with new H1N1 infection is profound primary influenza pneumonia, and deaths are usually related to this problem. Physicians have experienced extreme difficulty in ventilating these patients. As a result, extracorporeal membrane oxygenation—a technique that long fell out of favor in adult medicine—has renewed interest. The pneumonia is particularly a problem in infected people with preexisting cardiovascular disease or lung disease (especially asthma), pregnant women, and obese individuals. Obesity is a remarkably apparent risk with this influenza that has not been recognized in the past.

Secondary bacterial pneumonias can occur with H1N1 influenza, particularly in older people, immunocompromised individuals, and those with preexisting lung disease. Some nonpulmonary complications can be severe or fatal. People infected with H1N1 have developed rhabdomyolysis, myocarditis, and toxic shock syndrome (related to secondary bacterial, especially Group A streptococci, infections). There is concern that neurologic sequelae such as Reye syndrome may occur in children.

Transmission of this virus occurs primarily by large droplet nuclei through coughing and sneezing—some transmission may occur by fomites and respiratory aerosol. It is important to educate people to cough into their sleeve or elbow instead of their hands. Hand washing 10 times a day reduces the risk of getting influenza.¹

The median incubation period is only two days. In adults, the period of infectivity occurs right before or the day before symptoms begin and lasts up to seven days after the onset of clinical illness. Children can shed virus longer and may be infectious before symptoms begin and for a while after they seem to have recovered. Immunocompromised individuals can shed virus for weeks and even months. H1N1 influenza is generally an illness of five to seven days unless a complication develops.

The rapid flu test—a functional assay that is linked in a rapid card test—which many physicians have in their clinics, has been disappointing. In some studies, only 40% of people with new H1N1 infection have a positive rapid flu test result, so physicians should not exclude that diagnosis if the neuraminidase activity assay finding is negative. The best test is the real-time polymerase chain reaction assay if it is available, or another nucleic acid-based assay.

TREATMENT

It has been argued that anyone who has a flu-like illness should be treated for H1N1, but there is concern that the drug supplies will not last. Physicians should especially treat individuals who are at greatest risk—pregnant women, immunocompromised patients, young children, patients with underlying metabolic or cardiopulmonary disease, and probably obese patients as well.

One argument to prescribe oseltamivir or other neuraminidase inhibitors is that it might decrease the period of viral shedding, assuming the virus is susceptible and patients are absorbing the medication. But from an epidemiologic perspective, it may be worthwhile to treat infected individuals to decrease their ability to transmit to others. However, that is only true if the drug is given early on—a substantial virus peak occurs even with treatment.

Two standard medications are on the market—oseltamivir (Tamiflu—Roche Laboratories), an oral preparation, and zanamivir (Relenza—GlaxoSmithKline), an inhaler. Both drugs are effective and H1N1 is susceptible to both, although resistance has been described.² Peramivir (BioCryst Pharmaceuticals) is an intravenous formulation now available on a compassionate-use basis for some severely ill individuals in which an intravenous route is preferred.

These antivirals need to be administered as early in the infection process as possible, and a negative rapid flu test result should not exclude the diagnosis. Infected individuals should not wait to see what happens before filling their prescriptions. These individuals should be socially isolated. If they get sick, they should see their physician again within a couple of days because they may be developing a complication such as primary influenza pneumonia or a secondary bacterial pneumonia, or they may have a neuraminidase-resistant organism. And, in my opinion, physicians should make an assessment from a public health perspective regarding what is occurring with the rest of the family. For example, the infected individual's pregnant wife or 3-month-old baby at home should be of great concern. Physicians should make efforts to treat not only the patient but also their at-risk close contacts to prevent illness in the family.

VACCINATION

Inactivated and live-attenuated vaccines against new H1N1 are available. These vaccines were made by using the same manufacturing system we have been using for the seasonal influenza vaccines for decades—nonadjuvanted, basic chick-embryo-based, safe vaccines.

Physicians should apply the same dos and don'ts regarding who should and should not receive this vaccine as they do with the seasonal influenza vaccine. The only caveat is that if a patient received the live-attenuated seasonal influenza vaccine, physicians must wait at least four weeks to administer the monovalent, inactivated new H1N1 vaccine. Otherwise data suggest the same type of side effect profile as seen with the standard seasonal influenza vaccine can occur.

The priority groups for vaccination are pregnant women, followed by young children, then older children, and then the caregivers of children less than 6 months old (who cannot receive the vaccine). The next priority groups are police officers, firemen, public health authorities, healthcare workers, and, finally, adults with one of the risk factors for severe influenza.

FINAL THOUGHTS

Since this is a current event, we do not know how it will unfold over the winter months. However, we can make a few predictions based on what happened in the southern hemisphere. It has been bad, but it could be a lot worse.

What could be worse? Antiviral resistance could spread, or mutational events could increase the intrinsic virulence of the organism. A hybrid H5N1-new H1N1 virus would be particularly unpleasant. There may be additional delays in vaccine manufacturing, or it may turn out that the vaccine does not work as well as we think it is going to work. Antiviral drug stocks may become depleted (which has not happened). Or we could have a second hit—this pandemic influenza followed in the same year by another respiratory virus.

As healthcare workers, we have to stick together and try to protect as many people as we can and rethink our approach to the next pandemic. The public health response to this outbreak has been disappointing, and we can and should do better in the future.

Speaker: Steven Opal, MD
Division of Biology and Medicine
Alpert Medical School
Brown University
Providence, RI 02912

Dr. Opal presented this information at the physician and veterinarian collaborative seminar "Pets, People, and Pathogens: Emerging Diseases" on November 18, 2009, in Providence, R.I. Coastal Medical (Providence, R.I.) and the Companion Animal Parasite Council jointly sponsored this seminar.

Special thanks to Theresa Entriken, DVM, for writing this lecture summary and sharing this information with Veterinary Medicine readers.

REFERENCES

1. Mitka M. Hand washing, a key anti-flu strategy, often neglected by health care workers. J Am Med Assoc 2009;302(17):1850-1851.

2. Chen H, Cheung CL, Tai H, et al. Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China. Emerg Infect Dis 2009;15(12):1970-1972.