A guide to vaccinology: from basic principles to new developments

Deadly Diseases

In the world of human afflictions, the general public often overlooks influenza, considering it an unwanted guest that must be endured during the winter months. But few diseases match the year-in, year-out power of this deadly viral infection. Each year it takes the lives of about 37,000 people in the United States and between 250,000 and 500,000 worldwide. While that toll is significant enough, influenza always has the potential to turn far more lethal, because the viruses can mutate rapidly into new strains. To public health officials, flu tops the list of diseases that could cause a pandemic — a global epidemic.

Influenza got its name in the 1700s from an Italian folk word that attributed colds, cough, and fever to the influence of the stars. Highly contagious, the flu virus passes through the air via water droplets from coughing and sneezing. The organism can survive for hours outside the body. A person infected with flu remains contagious for about a week, beginning one day before symptoms show up.

With its generalized symptoms, the flu mimics the initial stages of many diseases, including the common cold. Flu can be clinically determined by a throat culture and blood test, but by the time results arrive, symptoms may have already run their course. Antiviral drugs can be effective if taken within two days of the start of symptoms.

The flu usually causes fever, body aches, and intestinal problems, as well as upper respiratory tract infections in about 5 percent to 15 percent of the population. Up to 50 million Americans get the flu each year. On average, adults lose three workdays a year as a result. The flu can turn deadly in combination with bacterial pneumonia, an opportunistic infection that attacks flu-weakened lungs. Severe illness affects between three million and five million people each year. The flu is particularly hard on the elderly, who account for 90 percent of the deaths.

Historians believe it was influenza that plagued Greece in 430 B.C.E. During the Peloponnesian War, and that it also ravaged Charlemagne's army in 876 C.E. The first recorded appearance, though, came in New England in 1647, where residents colorfully dubbed the unknown affliction as the "jolly rant," the "new acquaintance," and the "grippe."

New strains of flu arise early each year, and world health officials hurry to identify them in order to develop an effective vaccine. Because the virus mutates so often, immunity doesn't carry over from one year to the next. A flu pandemic sparked by a particularly virulent strain has typically occurred a few times each century, and no one can predict which strain in which year might have global impact. Constant vigilance and early action by global public health authorities is essential because vaccines take six months to produce, test, and distribute — too long to ward off a pandemic once it has taken hold. Another constraint is that at present, vaccines are grown in fertilized eggs, and at any given moment, the number of eggs available in the world is limited. New methods of vaccine production not dependent on eggs are crucial.

Experts agree that another flu epidemic is not only inevitable, but also likely to happen soon. Three times during the 1900s a sub-strain of flu underwent a major genetic change, leading to pandemics: The worse occured in 1918, and there were serious but less dangeours pandemic strains in 1957 (The Asian Flu) and in the 1968 (The Hong Kong Flu). Health officials fear a repeat of the Great Spanish Influenza of 1918, in which an estimated one billion people came down with the disease. Between 21 million and 50 million died — several times the total number of deaths in all of World War I, which ended the year the epidemic began. In the United States alone, 550,000 lost their lives to the disease. Busy gravediggers sang as they worked: "I had a little bird/ Its name was Enza/ I opened the window/ And In-Flu-Enza." As mysteriously as the Spanish flu appeared, it disappeared, leaving health workers to wonder if and when it might return.

A more severe form of human influenza, one that attacks not just the respiratory system but every tissue of the body, can originate in birds, chickens, and pigs. Until 1997, this so-called avian flu hadn't been known to strike humans. But that year in Hong Kong, 18 people came down with severe respiratory disease at the same time a widespread avian flu outbreak hit poultry. Investigations showed that the virus had jumped from birds to humans — the first known instance of that happening.

Within days, Hong Kong authorities destroyed the entire poultry population — about 1.5 million birds — a response that may have averted a pandemic. This avian-to-human transmission of the flu alarmed health officials, and subsequent years have seen minor outbreaks of avian flu in humans elsewhere, including the Netherlands and Vietnam. The real danger is if the avian flu strain evolves from a disease that humans catch from animals to a disease that humans can spread to other humans. The antiviral drug Tamiflu™ may be helpful in fighting symptoms for human victims, and many nations are trying to secure supplies in the event of a large-scale outbreak.

Meanwhile, a new vaccine against the avian flu virus, made by the pharmaceutical company Sanofi Pasteur, has proved effective in 115 volunteer subjects when given in two large doses. While this is hopeful news, critics point out that the large amounts needed mean that the hundreds of millions of doses required to fight a pandemic could never be produced with existing production methods. Vaccines that work at much lower doses are still urgently needed.

Whether the next pandemic originates in humans or birds, its effects will likely be dramatic. An estimated two million to seven million people could die, with tens of millions requiring medical attention. One nightmare scenario: A single person becomes infected with both common and avian flu, allowing the genetic material to mix. The resulting strain would doubtlessly be as lethal as it is contagious.

The key to containing all pandemics is fast action by global health authorities. Western nations stockpile antiviral drugs to protect their own citizens. But rather than combating a virus already spreading globally, health officials suggest rushing drugs and vaccines to the source of the infection and quarantining the area. The goal is to keep the disease from spreading beyond these areas where it breaks out.

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WHO Expresses Concern Over Bird Flu's Potential Human Transmission

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What's the story

The World Health Organization (WHO), on Thursday, raised serious concerns about the escalating transmission of the H5N1 bird flu virus to other species, including humans. During a press briefing in Geneva, WHO's chief scientist, Jeremy Farrar, described the situation as "an enormous concern." The highly virulent H5N1 strain is now impacting new species within the United States (US). Meanwhile, at least two areas under Kerala's Alappuzha district have reported bird flu outbreaks in ducks.

Bird flu epidemic extends to cows and goats

The ongoing bird flu epidemic, which originated in 2020, has now extended to cows and goats. This development led the UN health agency to categorize it as "a global zoonotic animal pandemic." Addressing media, Farrar expressed fear about the virus mutating and gaining the ability to infect humans, then crucially spreading from person to person.

High fatality rate of H5N1 in humans raises concern

While there is no evidence that the influenza A(H5N1) virus is spreading among humans yet, its "extraordinarily high" fatality rate in instances where humans have contracted it through animal contact is alarming. The UN agency has reported 463 fatalities from 889 human cases across 23 states over the past 15 months, indicating a troubling fatality rate of 52%. Farrar emphasized that "this virus is just looking for new, novel hosts."

Bird flu detected in US dairy herd and Indian ducks

WHO data revealed that H5N1 bird flu variant has been detected in numerous mammals over recent years, resulting in millions of wild bird fatalities. However, this marks its first detection in cattle, with eight US states reporting the highly pathogenic avian influenza in a dairy herd. In India, instances of bird flu have been identified in two areas of the Alappuzha district of Kerala, confirmed after samples from symptomatic ducks were tested.

Indian Government response to bird flu outbreak 

To check the spread of the disease, in a meeting—led by the district collector—it was decided to cull domestic birds within a 1km radius of the outbreak's epicenter. This measure aligns with the US government's standard protocol for such incidents. A Rapid Action Force is being assembled by the Animal Welfare Department to manage this situation. The district administration has reassured residents that there is no risk of human transmission and urged them not to panic.

2 cases of avian influenza detected in US 

Recently, two cases of avian influenza in humans were reported in the US. The first case was reported in Colorado, where a person contracted the H5N1 virus following direct contact with infected poultry. In the second case, a person in Texas contracted the virus after exposure to cattle believed to be carriers. Despite the recent case, the Center for Disease Control and Prevention (CDC) maintains that the risk to the general public remains minimal.

No, We Can't Trust Warm Weather To Stop Coronavirus: Here's Why

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Will warm weather and high humidity stop the coronavirus pandemic as some public officials have claimed? While research results haven't been consistent, a new report from the National Academies of Science, Engineering, and Medicine (NAS) suggests that the scientific data is increasingly leaning toward a conclusion — warm weather will not stop the virus from spreading. In fact, this coronavirus will likely still "spread exponentially at higher temperatures and humidity."

The report, which analyzes a variety of studies, was authored by David A. Relman, MD, a member of the NAS' Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats, in a "rapid expert consultation letter" to the White House Office of Science and Technology Policy (that's correct, it's a data analysis prepared specifically for the White House).

Evidence in favor of the virus slowing in warm weather comes, in part, from observing seasonal patterns of viruses like influenza that build in intensity during the fall and winter and wane in the spring. Even a few other coronaviruses follow this pattern. But Relman says data suggesting that SARS-CoV-2, the virus that causes COVID-19, will follow this same pattern is inconclusive at best.

"Some limited data support a potential waning of cases in warmer and more humid seasons, yet none are without major limitations," he writes in the report.

In fact, some of the places where the virus has already spread are experiencing warm weather right now.

"Given that countries currently in 'summer' climates, such as Australia and Iran, are experiencing rapid virus spread, a decrease in cases with increases in humidity and temperature elsewhere should not be assumed."  

In addition, two of the most notorious coronaviruses, SARS-CoV and MERS-CoV, "have not demonstrated any evidence of seasonality following their emergence."

Drawing a reliable answer from research to-date is challenging because many of the studies were conducted in labs with inconsistent conditions, and others are "natural history studies"—many from China— that don't line up well with the particulars of this pandemic. In addition, studies that expose viral particles to a light source in a lab are of little or no value when making determinations about real-world conditions.

"There are significant caveats in all of the studies presented, mostly related to data quality and the limitation in time and location," Relman writes. "There are also important confounding factors associated with geography and, hence, with temperature and humidity."

Even in recent research that suggests higher temperatures and humidity will decrease viral "infectivity," the rate of infection (known as the average R0 or R naught) "was still close to 2 [each infected person infects two additional people] at maximum temperatures and humidity in their data set, suggesting that the virus will still spread exponentially at higher temperatures and humidity."

The report adds that relying on research focused on epidemic influenza strains, which are typically seasonal, is also inadequate because "pandemic influenza strains have not exhibited the typical seasonal pattern."

"There have been 10 influenza pandemics in the past 250-plus years—two started in the northern hemisphere in winter, two in the summer and three in the fall," Relman writes. "All had a peak second wave approximately six months after the emergence in the human population, regardless of when the initial introduction occurred."

Relman's analysis also touches on topics related to indoor temperature, including the troubling persistence of the virus on personal protective equipment (PPE), like masks.

"The persistence of infectious virus on PPE is concerning and warrants additional study to inform guidance for healthcare workers," he writes, noting that a high concentration of viral particles have been found inside masks after a full seven days. This result underscores the need for healthcare workers to use new masks throughout the day to avoid infecting themselves and others.

"Additional studies as the SARs-CoV-2 pandemic unfolds could shed more light on the effects of climate on transmission," the report concludes.

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