Notes on H1N1 in Chile

I recently made rounds in the adult and pediatric ICUs of one of the university hospitals in Chile, Hospital Clínico UC. The staff there confirmed that about one-third of non-ICU patients that are admitted have no fever. Even more interesting, half of the outpatients with confirmed H1N1 also exhibit no fever.

Physicians from both ICUs described screening patients with no other symptoms than rhinorrhea (runny nose), that turned out to have confirmed cases of H1N1.

The lesson here is that the clinical expression of H1N1 is extremely broad. Screening only the patients who exhibit a high fever will result in many overlooked cases. Further, when counting infected patients, if fever is part of the case definition, the denominator will be greatly underestimated.

It is surprising to see how differently H1N1 is being managed throughout Latin America, especially between Chile and Brazil. In Chile, clinicians make a clinical diagnosis—confirmation is not essential—and Oseltamivir is administered. The drug is given to patients free of charge.

H1N1 and Pregnancy

During my travels to Latin American countries contending with the disease in their winter season, I learned that pregnancy has been recognized as a risk factor for serious disease outcome with influenza strains in general. Pregnant women who contract the current version of pandemic H1N1 influenza risk being in an ICU and dying of the infection. H1N1 targets young adults - not the very young children and elderly as past circulating strains of seasonal influenza do. As a result, more young woman are at risk.

Two risk factors- morbid obesity and pregnancy - both conditions overrepresented among dying patients with H1N1, share a degree of insulin resistance. This is a metabolic condition which can predispose to infection. It is also possible that pregnancy and obesity have low lung volumes in common that may be contributing to severity. While this is based on speculation, it is my hope that scientific studies will examine why H1N1 causes such severe disease in pregnancy.

The key public health implications are that pregnant women should be a high priority to receive a future safe H1N1 vaccine. In the meantime they should avoid contact with any patients who might have the pandemic strain.

During my time in Latin America, I uncovered the following supporting evidence:

• In Brazil, I learned that pregnancy was a risk factor for needing intensive care treatment after infection with H1N1.

• In Columbia, one of seven reported deaths in adults with H1N1 was in a pregnant woman.

• In Argentina, of 85 deaths after H1N1 in the region of Buenos Aires, one fourth were in pregnant women. Obesity, which was recognized as a likely risk factor for dying in Mexico and more recently in the United States, was a close second to pregnancy among those dying of H1N1 in the same region.

Notes on H1N1 in Brazil

In Brazil I had dinner with two former fellows and their colleagues, where I gained new insights into the H1N1 situation in Latin America. Here there has been an upsurge of reported cases. This increase appears to correlate with vacationers returning from Argentina and Chile with the virus.

The Brazilian government is managing the outbreak in a way unlike any other country I have examined. Patients with influenza-like illness (ILI) (i.e. fever with either cough or sore throat) in São Paulo, a mega-city of approximately 15 million, can be screened—by law—at only seven hospital emergency rooms.

Here, patients are screened using an immunoblot procedure with a sensitivity of 70 percent. The Oseltamivir drug is administered if (and only if) a patient with a positive screen also has some defined high-risk factors. A confirmation polymerase chain reaction (PCR) test is then done and sent to a single lab, responsible for the entire city’s PCR evaluation. It takes more than ten days for the PCR results to become available.

To me, the most troubling issue is that infectious disease specialists here cannot write a prescription for Oseltamivir or screen for flu. The government grants this authority only to the physicians at the seven designated emergency departments.

Notes on H1N1 in Argentina

I recently visited Argentina. This country’s population is one-third the size of Mexico’s, though they have reported even more deaths from the virus. The government here is taking strict steps to try to limit the spread of H1N1 among its population.

Schools here are currently closed, and the government has ordered them to remain closed for a full month. Large gatherings and meetings have been prohibited throughout the country. Pregnant women and other high-risk young adults are not allowed to go to work.

As soon as an Argentinean experiences symptoms, they are sent directly to the hospital for testing. However, Oseltamivir—an anti-influenza antibiotic—is given only to young adults here.

It is interesting to observe such major differences in the way H1N1 is being managed in Latin America. I will report back more of what I’ve learned in the coming days.

New Outbreak in Mexico

In recent discussions with the director of the Institute for Respiratory Diseases and other physicians, I learned more about a new surge in H1N1 in Mexico. The most severe cases are occurring in the state of Chiapas. Patients there who are on respirators currently have a 50 percent mortality rate. This is very similar to the rate for patients who were initially on respirators at the Institute for Respiratory Diseases. The Institute recently sent some faculty and medical residents to Chiapas to add greatly needed expertise to their efforts there.

By December of this year, Mexico will have 20 million doses of a vaccine for H1N1 available. In the meantime, they are wrestling with how to choose the population that will receive the vaccine. Should it be administered to the high-risk young adults? Children, who most frequently transmit the virus? Or pregnant adult women? The next difficult decision will be choosing which people in that targeted group will receive the vaccine.

This is indeed a complex situation for Mexico, which they are dealing with in a very thoughtful and organized manner. I have traveled to other countries in Latin America contending with the disease in their winter season. It appears there is a clear contrast in response to H1N1, and I gained first-person insights on the situation there, which I will write posts on soon.

Changing the Way We Think About a Pandemic

WHO has recently declared a flu pandemic – the first since 1968. So we might ask ourselves, “what is different?” Moving from a phase 5 pandemic alert to a level 6 alert currently only implies that there is a sustained spread in different continents.

But such a move is confusing since each year the seasonal flu – which bears similar characteristics – kills 500,000 people globally, yet no pandemic level 6 has ever been declared. In contrast, the current H1N1 Swine flu has killed fewer than 150 people. Shouldn’t the pandemic scale be more focused on severity and the resources needed to control epidemics?

To me, a pandemic implies a response to an infectious threat that requires an international surge in capacity for resources, communication and cooperation. Thus, the two key elements determining the pandemic alert level and necessary response are efficiency of transmission and disease severity.

One could insist that sustained transmission of a totally new infectious agent should be considered for a level 6 pandemic scale. But what do we do if H1N1 stays around for three years? When does “new” end? To avoid confusion, I think the requirement for surge capacity is key. Thus, a global outbreak of a common cold virus would not reach a high level on the pandemic scale, since few new resources would be needed and severity is not an issue.

For resources, I would include the types (food, water, medical equipment, drugs, vaccines, etc.), the quantity, and the effective delivery systems. One might also include the estimate of the country’s GDP that will be needed to support the control measures. In Mexico, it has been estimated that over 4.5% of its GDP will be needed to cover the costs of managing H1N1. For communication, I would include the measures of the pandemic transmission and severity as mentioned above, and the rate of resource utilization for a region or country. For cooperation, I mean the legal, administrative, medical and other types of required sharing across regions and countries.

Once we have the definitions, we could construct a hierarchy of levels of Pandemic Threat based on the increasing need for resources, communication and cooperation across regions and countries, and these would be paralleled by increasing rates of transmission and severity.

Progressing from the bottom end of the Pandemic Threat Scale to the top would imply increasing transmission and severity as well as increasing surge capacity for resources, international communication and cooperation.

An implication of such a system is that we need international agreements before and not after a pandemic. The World Bank for example might reward a country for early reporting of a new disease as an incentive to the country worried about the economic consequences of transparency. Countries would have to accept help when it is needed and not be constrained by their own national laws. A new Pandemic Threat Scale will require unprecedented international cooperation that does not exist today. But surely it is needed, and H1N1 has shown our lack of clarity in 2009.

H1N1 in Mexico – Lessons Learned

The Mexicans have taught the world that transparency and full disclosure was brave and admirable and saved countless lives but came at the price of severe economic consequences. The argument made by me and others after SARS that the World Bank should provide incentives to countries for rapid reporting of novel pathogens causing epidemics seems to still be valid today.

A week or so after the outbreak, a flight to Mexico from Atlanta was only 15% occupied, and on arrival the airport was nearly deserted. I had been asked to Mexico City by my colleagues at the National Institutes of Respiratory Infection and planned to make rounds with them in the wards and ICU’s.

The city was awakening from the infection control measure called social distancing. The traffic on this mega city of 20 million was only half of its usual density compared to my experiences in 25 prior trips. Cabbies still wore masks as did the staff in all restaurants, most of the police officers, and perhaps 10-20% of the citizens walking around. On that day the swimming pools and restaurants were opening for business; football (soccer) was about to resume, and schools were opening on Monday, May 11^th.

Almost two weeks earlier Mexican health authorities announced to the world the increasing number of cases and deaths from the new strain of influenza virus fully cognizant of the economic consequences. In a brief 10 day interval they made a critical decision for transparency, in bold contrast to the 110 day interval before the world learned about SARS in China. Because there was no vaccine and no certainty that the available drugs to treat influenza would be effective, the only option left was social distancing.

On Friday and Saturday I made rounds on the wards and ICUs of the National Institute of Respiratory Infection and National Institute of Nutrition. Patients in their 20s, 30s, and 40s were on respirators, and so the inhuman statistics now had meaning. In the last few weeks, those in ICUs intubated and on mechanical ventilators included a bus driver, a housekeeper from one of the hospitals, an anesthesiologist and a mechanic. H1N1 appears to be an equal opportunity virus.

Outside the hospital, medical residents in training and wearing masks were screening all people entering the hospital. At another table nurses and physicians had set up a center for health care workers and their families to answer any questions, to give the 24/7 hotline and instructions. They were essentially managing fear and offering psychological support. Their creative implementation of triage outside of the hospital entrances is wise.

On Saturday rounds in the ICU at the Nutrition Institute, a young man had just died and a second had relapsed and returned from the ward to be intubated. Influenza has the ability to cause severe illness and kill healthy young people. We have been fortunate in the U.S. with mild cases, but complacency would be a foolish path ahead.

Influenza H1N1 may rear its dark side yet in the U.S. It may soon advance to South America where the winter is approaching, and may resurface with a new face in the Northern Hemisphere in the fall and winter 2009-2010. We have time to prepare for a vaccine if needed, and we certainly can applaud the Mexican health authorities and learn from their remarkable encounters with H1N1.

The Return of Swine Flu – A Death in the U.S. and Uncertainty

Sadly, the U.S. reported its first death in a 23 month old Mexican toddler visiting in Texas.

Cases have developed in countries on at least five continents over a brief time period. The first death in the U.S. among 64 cases, which is also the first death globally outside of Mexico among 100 or more cases, is difficult to put into perspective with any confidence – especially since the baby came from Mexico. The death of a baby in the U.S. is tragic, but each year we see 36,000 deaths from influenza in our country. Influenza is always serious – even without an exotic strain from another country. We cannot at this time predict the mortality of the Swine flu outbreak, but only put in a range of 0.1% of cases to something higher such as 0.5% (seen in the 1957 “Asian” flu and 1968 “Hong Kong” flu pandemics). A 1% mortality may be worst case scenario and seems unlikely.

If more deaths are occurring in Mexico than the rest of the world, why would this happen? In both the U.S. and Mexico the same virus is attacking the same age cohort – young adults. Then any big differences would be ascribed to differences in patients. Is it possible that patients in Mexico have co-infection with a second virus? Do they have high rates of secondary bacterial pneumonia with Staphylococcus aureus or Pneumococcus? Is the particulate air pollution in Mexico City damaging airways and lungs causing more disease? Do patients have an unusually robust immune response to the virus – the so-called cytokine storm? We do not know the answers to any of these questions, but the key point is this: CDC in concert with health authorities in Mexico should perform sophisticated viral and bacterial studies, and pathology analyses on patients with severe disease and on patients who have died. Our understanding of how to manage this viral infection will be enhanced with such information.

As we prepare ourselves in the U.S. for more illnesses and more deaths from the new Swine flu, it is the uncertainty that is especially challenging. Knowing the cause of severe illnesses and deaths and the true mortality will be of critical importance.

The Return of Swine Flu: Mexico vs. U.S.

Those who boldly predict the outcome of influenza do so at their own peril.

The 2009 Swine Flu outbreak in the U.S. and Mexico is different than previous outbreaks. The key issue today is why deaths have been reported in Mexico and not elsewhere. The same virus is attacking the same age group - healthy young adults - in the affected countries. So, the difference in outcome must be differences among the patients. This is likely due to one of three things: in Mexico, the patients have more secondary bacterial pneumonia (e.g. with Staph or Pneumococcus), or co-infected with flu virus and another virus, or there is more damage to the lungs given the high level of pollution in Mexico City.

Since the cases in the U.S. are mild, it cannot be the rapid access to ICUs here that is saving lives - as some have speculated. Furthermore, the antivirals are weak therapeutic agents, which disproves that our access to therapy is saving patients with the disease.

The good news is that we have two antivirals that are effective against the circulating strain of Swine Flu. The key point, however, is that each offers excellent protection as a prophylactic agent- from recent studies of the antivirals about 70% of exposed but not ill people can be spared infection. Yet both drugs are marginal as therapeutic agents, and neither has been rigorously tested in life-threatening cases of flu. That is the reason to seek a safe and effective vaccine.

There are important lessons from prior influenza and Severe Acute Respiratory Syndrome (SARS) pandemics:

* Accurate and early reporting of all cases globally is essential for control. The delays in reporting the initial cases of SARS in China contributed to its early dissemination.

* Infection Control in hospitals must be assiduous to avoid spread to health care workers and other patients. This was noted early in Canada with the SARS pandemic, and rapid interventions led to its control there. Specifically, handwashing and prudent use of masks are helpful and effective. If the new Swine Flu strain shows occasional ability to be airborne within microscopic droplets, the use of negative air pressure rooms - if available to keep the air currents going only in the direction of the patient's room- may help.

* Lastly, the need for psychological support of health care workers was not fully appreciated early in the SARS outbreaks. These dedicated men and women are overepresented by young adults- susceptible to Swine Flu. Careful attention to their needs and support for their families would be essential.

In 1976, when my colleagues and I reported two patients in Virginia with Swine Flu, it added some concern that the original cluster at Fort Dix had spread beyond New Jersey. President Ford received impassioned advice from health policy experts at that time and strongly advocated a national vaccine program. Subsequently, there were two unexpected outcomes: The Swine Flu epidemic never materialized, and the vaccine unexpectedly caused a 7-fold increase in a neurological side effect leading to weakness and paralysis, the Guillian Barre Syndrome. A shakeup at CDC followed, and for years the public's willingness to accept vaccines was diminished.

It is unclear if Swine flu will act more like the devastating avian flu pandemic of 1918-19 or the fizzled Swine flu outbreak of 1976. However, the latest "influence" to visit itself upon the citizens of the world reminds us that epidemics are part of the natural interaction of people and microbes throughout civilization. Yet each time we react as though we have discovered something new. The only really new things are our surprise and consistent inability to recall all of the lessons from prior visitations.

KEEP THOSE HANDS TO YOURSELF TO REDUCE SPREAD OF DISEASE

The handshake is deeply ingrained in our culture. Other than the kiss, it’s the way we are taught to say hello, goodbye, or to “seal a deal.”

It is thought to be an ancient custom whereby strangers encountering each other could show that no weapon was being held, but the handshake may have outlived its usefulness. In fact, the Japanese and Europeans could have a better idea. Rather than shaking hands when they meet each other, the Japanese clasp their own hands and bow, and the Europeans peck each other on both cheeks.

No hands meet. And that may be a very good thing to think about when it comes to preventing the spread of infectious diseases, like the common cold, the norovirus (the flu), and the deadly MRSA bacteria.

It turns out that shaking hands is among the best ways to spread germs. According to a recent study by the London School of Hygiene, hands are a critical link in the chain of illness as they transmit infections from surfaces to people and person to person.

Actually, it turns out this warning is really nothing new. As far back as 1919, The New York Times reported on a Montclair, New Jersey health officer, John Gaub, who issued a warning about the dangers of “indiscriminate hand shaking” in his community.

Of course, you can always wash your hands after shaking with someone, which is the most effective way to stop the spread of viruses. A study of Detroit school children found that those who regularly washed their hands had 24 percent fewer sick days due to respiratory illness and 51 percent fewer due to stomach illness.

But unless handwashing is done perfectly, some germs may linger.

While most people think that viruses, particularly the flu, are spread through the air - the truth is they are most often passed from one person to another when the sick person rubs his nose and touches something like the handle you are about to use to open the bathroom door, or the keyboard you touch or the telephone you pick up. If you then touch your own eye or nose or mouth, you may initiate an infection from your newly contaminated hands.

While the flu season is still raging – and cities like Boston feel its worst effects with the tragic death of 12-year-old boy from the flu -- the potential for infection spreading continues to loom, it just makes sense to reinforce the simple and obvious ways that we can avoid getting sick

Wash your hands frequently. And stop shaking hands.
It’s not rude. It is a lesson in good health.

Fighting the Flu

While there has been a lot of news about the flu vaccine this season, today's New York Times includes a story about a very hopeful breakthrough in flu vaccine development.

Full article: www.nytimes.com/2009/02/23/health/

This year's flu season has left many anxious over the most common vaccine's effectiveness due to evolving strains of the disease. Yet now scientists may have found a way to develop a vaccine that wouldn't have to change every year because it would stay ahead of the virus.

While, if proven effective, this is a wonderful development, for the remainder of the flu season I encourage people to be smart about their health and protect themselves from contracting the virus in the first place. Next season may bring a better vaccine, but for now: always wash your hands, avoid sharing water bottles, and always keep a little antibacterial handy.