Strategic Solutions, Inc.

The eruption of the swine flu outbreak in April of 2009 took the world by surprise. Like many other epidemiologists, I was looking the other way at H5N1, wondering if this strain was finally going to peter out or mutate into something more infectious.

However, once reports started coming in from Mexico, worldwide epidemiological networks, and public health agencies in this country (the CDC for example), as well as the WHO started getting a handle on it, and quickly framed the outbreak as potentially alarming because in previous pandemics, influenza viruses had taken at least 6 months to spread as widely as the H1N1 influenza has done in 6 weeks. After much political wrangling from member states, the WHO declared a pandemic level 6 from level 5 on June 11, 2009. Phase 6 is characterized by sustained human-to-human transmission caused by community-level outbreaks in at least 1 country in 2 WHO regions (besides Central and North America, the other region was Europe.

As of June 11, 28,119 laboratory-confirmed cases, including 144 deaths, had been reported to the WHO from Canada (4), Chile (2), Costa Rica (1), the Dominican Republic (1), Mexico (108), Colombia (1) and the United States (27). Although 74 countries in 5 WHO regions have been affected, approximately 90 percent of reported cases have occurred in the Americas.

The H1N1 swine flu is called such because the majority of the RNA in the current strain has been shown to come from swine flu H1N1 viruses. Although we lack detailed data (surveillance in pigs in the last 10 years has been minimal) we can say with some degree of certainty that late last year or in early 2009, swine flu jumped from a pig to a human. This probably occurred in the U.S. or Canada although we will never know for sure. The presumed index case then infected another human and at some point someone in Mexico was infected, and perhaps the R0 increased suddenly; and so it began. Although the media frenzy suggested that the outbreak began in a pig farm in Mexico, and that a boy was the index case, this has been discounted.

Transmission
What made the spread of this pandemic happen so quickly was international travel, in which cases from Mexico and the USA seeded urban centers in other countries, and caused local outbreaks to quickly spread due to high intensity transmission (what we call a high R0, the basic reproduction number). Basically, R0 is defined as the number of people infected by one individual with the disease (the technical definition is more precise, but the basic definition suffices for our purposes). Early estimates of R0 varied from 1.2 to 1.6, but more recent models have placed the value around 2-2.4, compatible with the estimates of the 1918 influenza pandemic. One of the drivers for the high number is probably the explosive outbreaks observed in schools, and some studies have suggested that initial “overreaction” in shutting down many schools actually might have mitigated the transmission dynamics in some urban areas.

Clinical attack rates (CAR; percentage of the population that is infected—symptomatic or assymptomatic) for seasonal flu range from 5% to 15%, whereas CAR for the H1N1 has been estimated at 22%-33%, which suggests that transmission dynamics for the H1N1 strain are more aggressive compared to seasonal flu.

Lesson learned #1: although perceived as overreaction in many instances, shutting down schools for periods of time in affected areas appears to be worthwhile.

Age group affected
Seasonal flu tends to affect older adults (> 50 years of age) as well as the very young. In contrast, the 1918 pandemic had a W-shaped profile in regard to age (and mortality), meaning that children, healthy adults (20-40 years) and the elderly (60-65 years +) were most affected. In the current pandemic, most cases in all countries have occurred among adolescents and young adults. Males and females are similarly affected. (Data compiled by the WHO from Chile, countries of the European Union and the European Free Trade Association, Japan, Panama, and Mexico indicate that approximately 25% of cases were aged 0-9 years, 36% were aged 10-19 years, 17%were aged 20-29 years, 9% were
aged 30-39 years, 7% were aged 40-49 years, and 5% were aged greater than 50 years.)

At this stage we don’t truly know whether this strain of H1N1 has a predilection for children and adolescents, or whether we have some bias in terms of case reporting in regard of age. If the former is true, it would mean that the younger population is immunologically naïve, and older people have some resistance to the strain because of immunological cross-reactivity from exposure to other H1N1 strains.

Morbidity and mortality
The course of most cases has generally been mild, no worse that seasonal influenza. The duration of onset and resolution of fever has been 1-8 days (median, 3 days). Nevertheless, there have been some substantial numbers of hospitalizations. For example, the New York City Department of Health and Mental Hygiene reported 567 hospital admissions and 16 deaths. The hospitalized patients in this geographic area have been typically younger than those seen during seasonal influenza outbreaks; approximately 79% of patients were aged < 50 years; 46% < 18 years and 20% < 5 years; only 5% of hospitalized cases were aged > 65 years.

Due to the lack of clinical data (we hope to see many papers published in the next 2-3 months), we are not sure whether the severity of illness and the majority of deaths are attributable to underlying risks or diseases (what we term comorbidities), which is the typical situation in seasonal flu, or whether we are seeing violent reaction in immunologically naive populations. Anecdotally, many ER physicians have reported that only perhaps a third of all comorbidity and mortality is responsible for the severity of cases and deaths.

Many health centers in the U.S. were overwhelmed in April and May with individuals asking to be treated for flu. This was easily predictable. Had the numbers been twice as high, many hospitals would have been hard pressed to operate normally even if the mortality rate had stayed the same.

We lacked early accurate data regarding the clinical picture and how health centers in different countries were coping with the epidemic. However, it was clear from news media reports that the public did not understand that going to the ER or health care facility was a waste of time unless the individual was showing severe symptoms of the disease (i.e., severe respiratory symptoms, dehydration, fever, etc.). This is understandable; families want to know they are okay, and getting the best treatment. But because there is no truly effective treatment for influenza (antiviral drugs have to be administered within 48 hours to be effective, and even then can only mitigate the course of the disease), the treatment is largely supportive, and so going to a heath care facility for a mild case of influenza is not a good idea.

Lesson learned #2: Widespread multimedia campaigns must be instituted early to educate the public in regard to visiting health care facilities.

Health care facility issues
Although we have few studies on the subject, one report indicated that few health care workers were infected directly from patients. This is good news. At the same time, it was demonstrated that some health care facilities were lax in infection control. Of course, had the CFR been much worse, perhaps better precautions might have been taken. (CFR = case fatality ratio: number of individuals whose death is attributable to influenza/number of individuals infected.)

We are also lacking data on how many health care facilities actually implemented a prior influenza or biopreparedness plan, including triage. There were some suggestions that in the busiest ERs this occurred, but nationwide, we don’t know the whole story. This is a gray area because we don’t know if such plans weren’t activated because the CFR wasn’t any worse than seasonal flu.

Lesson learned #3: Many health care facilities are still too lax in regard to infection control, and some lack sufficient equipment protection for health care workers. Better procedures would also improve nosocomial infection rates of other diseases, too, so there are other benefits to be gained besides influenza-related issues.

Ongoing issues
Because the epidemic started in Central and North America and spread to Europe before further spreading to Asia and the southern hemisphere, containment strategies are still in operation in Australia and Asia, particularly China. What does containment mean? Typically travelers suspected of having H1N1, or unlucky travelers who are deemed to have been too close to individuals suspected of having been infected are quarantined. If you’ve read the headlines, you will have heard of many distressing stories of families being separated and quarantined in dingy hotel rooms. This practice must stop. At this stage of the pandemic, containment is an absolute waste of time, and only hurts individuals. There are plenty of studies showing the futility of quarantine or containment in regard to influenza. My advice? Unless you have an emergency, avoid travel to Hong Kong, China, or Australia.

Lesson learned #4: Containment strategies are futile. Education of public health authorities in countries in which this obnoxious practice continues to take place should be a priority for the WHO. Travel advisories to these countries should be mandatory; perhaps less tourism will wake these morons up.

The Future
There are 3 possible scenarios. First, the pandemic could peter out this summer and then disappear into the “background noise” of seasonal flu. Second, the pandemic could intensify over the summer in the southern hemisphere and continue in the northern hemisphere. This would probably make it equivalent to the 1968-69 influenza pandemic. Third, this H1N1 strain to could reassort with other strains or mutate. If it reassorted with H7N7 or H5N1 strains we could be in for some serious trouble and might expect a second much more lethal wave late this fall or winter (in the northern hemisphere). My bet is on scenario number 2 although the probability for scenario number 3 is not vanishingly small (maybe 5-10%).

Time will tell where we are going; we have much better surveillance apparatus in place compared to earlier years, and it is likely that trends will become quickly known.