Sunday, May 25, 2008

Microbial Threats to Health: The Threat of Pandemic Influenza

Microbial Threats to Health: The Threat of Pandemic Influenza

By Mark S. Smolinski, Margaret A. Hamburg, and Joshua Lederberg, Editors, Committee on Emerging Microbial Threats to Health in the 21st Century.

Microbes live in every conceivable ecological niche on the planet and have inhabited the earth for many hundreds of millions of years. Indeed, microbes may be the most abundant life form by mass, and they are highly adaptable to external forces. The vast majority of microbes are essential to human, animal, and plant life. Occasionally, however, a microbe is identified as a pathogen because it causes an acute infectious disease or triggers a pathway to chronic diseases, including some cancers. Certainly, humankind remains ignorant of the full scope of diseases caused by microbial threats, as only a small portion of all microbes have been identified by currently available technologies.

Microbial threats continue to emerge, reemerge, and persist. Some microbes cause newly recognized diseases in humans; others are previously known pathogens that are infecting new or larger population groups or spreading into new geographic areas. Within the last 10 years, newly discovered infectious diseases have emerged in the United States (e.g., hantavirus pulmonary syndrome from Sin Nombre virus) and abroad (e.g., viral encephalitis from Nipah virus). During the same time, the worldwide resurgence of long-recognized infectious diseases (e.g., tuberculosis, malaria, cholera, and dengue) has gained in force. The United States has seen the importation of infectious diseases, such as West Nile encephalitis, measles, multidrug-resistant tuberculosis, malaria, and cyclosporiasis, from immigrants, U.S. residents returning from foreign destinations, and products of international commerce.

The realization of just how quickly newly discovered infectious diseases can spread has generated a heightened appreciation of the inherent dangers of microbial pathogens. Acquired immunodeficiency syndrome (AIDS) has become the fourth-leading cause of death worldwide in a mere 20 years since its discovery. Today, more than 40 million people are living with infection from the human immunodeficiency virus (HIV), and 20 million people have died from AIDS. In just 3 years since West Nile virus was discovered in the Western Hemisphere, the virus has spread from its epicenter in New York to 39 states (including California), infecting thousands and killing hundreds.

Can a focus on naturally occurring microbial threats be maintained in the face of expanded efforts to contain the threat of intentional biological attacks? Some may ask which is the greater risk—the intentional use of a microbial agent to cause sudden, massive, and devastating epidemics of disease, or the continued emergence and spread of natural diseases such as tuberculosis, AIDS, malaria, influenza, and multidrug-resistant bacterial infections. It is a tragic reality that hundreds of people die from naturally occurring infections every hour, whereas until now, intentional biological attacks on a major scale have remained a theoretical risk, rife with political as well as technical uncertainties. HIV/AIDS has taught us the importance of remaining vigilant to the devastation of naturally arising epidemics, which can have profound effects not only on individuals, but also on whole nations and regions. The economic and social disruption that often follows an infectious disease outbreak and typically accompanies the persistent burden due to endemic infectious diseases can be a major destabilizing force for any nation. The challenge is to keep our concerns and responses in reasonable balance.

Throughout history, humans have struggled to control both the causes and the consequences of infectious diseases, and we will continue to do so into the foreseeable future. Disease control for many pathogens includes vaccines and pharmaceuticals, but how long these controls will remain effective or even available is uncertain. We appear less able (or willing) to develop new antimicrobials and vaccines than once was the case, especially for infectious diseases that affect developing countries disproportionately.

A variety of technical, political, social, and economic issues challenge our ability to develop and deploy new antimicrobials and vaccines. The burden of infectious diseases has become further compounded as resistance to vector-control agents and antimicrobials has grown pervasive not only in the United States, but also worldwide.

Factors in Emergence

The convergence of any number of factors can create an environment in which infectious diseases can emerge and become rooted in society. A model was developed to illustrate how the convergence of factors in four domains impacts on the human–microbe interaction and results in infectious disease.

The Convergence Model. At the center of the model is a box representing the convergence of factors leading to the emergence of an infectious disease. The interior of the box is a gradient flowing from white to black; the white outer edges represent what is known about the factors in emergence, and the black center represents the unknown (similar to the theoretical construct of the “black box” with its unknown constituents and means of operation). Interlocking with the center box are the two focal players in a microbial threat to health—the human and the microbe. The microbe–host interaction is influenced by the interlocking domains of the determinants of the emergence of infection: genetic and biological factors; physical environmental factors; ecological factors; and social, political, and economic factors.

Ultimately, the emergence of a microbial threat derives from the convergence of (1) genetic and biological factors; (2) physical environmental factors; (3) ecological factors; and (4) social, political, and economic factors. As individual factors are examined, each can be envisioned as belonging to one or more of these four domains.

Microbial adaptation and change.
Microbes are continually undergoing adaptive evolution under selective pressures for perpetuation. Through structural and functional genetic changes, they can bypass the human immune system and infect human cells. The tremendous evolutionary potential of microbes makes them adept at developing resistance to even the most potent drug therapies and complicates attempts at creating effective vaccines.

Human susceptibility to infection.
The human body has evolved with an abundance of physical, cellular, and molecular barriers that protect it from microbial infection. Susceptibility to infection can result when normal defense mechanisms are altered or when host immunity is otherwise impaired by such factors as genetically inherited traits and malnutrition.

Climate and weather.
Many infectious diseases either are strongly influenced by short-term weather conditions or display a seasonality indicating the possible influence of longer-term climatic changes. Climate can directly impact disease transmission through its effects on the replication and movement (perhaps evolution) of pathogens and vectors; climate can also operate indirectly through its impacts on ecology and/or human behavior.

Changing ecosystems.
In general, changes in the environment tend to have the greatest influence on the transmission of microbial agents that are waterborne, airborne, foodborne, or vector-borne, or that have an animal reservoir. Given today’s rapid pace of ecological change, understanding how environmental factors are affecting the emergence of infectious diseases has assumed an added urgency.

Economic development and land use.
Economic development activities can have intended or unintended impacts on the environment, resulting in ecological changes that can alter the replication and transmission patterns of pathogens. A growing number of emerging infectious diseases arise from increased human contact with animal reservoirs as a result of changing land use patterns.

Human demographics and behavior.
An infectious disease can result from a behavior that increases an individual’s risk of exposure to a pathogen, or from the increased probability of exchange of a communicable infectious disease between humans as the world’s population increases in absolute number. Additional factors include demographic changes such as urbanization and the growth of megacities; the aging of the world’s population and the associated increased risk of infection; and the growing number of individuals immunocompromised by cancer chemotherapy, chronic diseases, or infection with HIV.

Technology and industry.
Infectious diseases have emerged as a direct result of changes in technology and industry. Advances in medical technologies, such as blood transfusions, human organ and tissue transplants, and xenotransplantation (using an animal source), have created new pathways for the spread of certain infections. Even the manner in which animals are raised as food products, such as the use of antimicrobials for growth production, has abetted the rise in infectious diseases by contributing to antimicrobial resistance.

International travel and commerce.
The rapid transport of humans, animals, foods, and other goods through international travel and commerce can lead to the broad dissemination of pathogens and their vectors throughout the world. Microbes that can colonize without causing symptoms (e.g., Neisseria meningitidis) or can infect and be transmissible at a time when infection is asymptomatic (e.g., HIV, hepatitis B, and hepatitis C) can spread easily in the absence of recognition in traveling or migrant hosts. Pathogens in meat and poultry, such as the agents of “mad cow disease,” can also be delivered unintentionally across borders, while the vectors of tropical diseases can be transported in cargo holds or in the wheel wells of international aircraft.

Breakdown of public health measures.
A breakdown or absence of public health measures—especially a lack of potable water, unsanitary conditions, and poor hygiene—has had a dramatic effect on the emergence and persistence of infectious diseases throughout the world. The breakdown of public health measures in the United States has resulted in an increase in nosocomial infections, difficulties in maintaining adequate supplies of vaccines in recent years, immunization rates that are far below national targets for many population groups (e.g., influenza and pneumococcal immunizations in adults), and a paucity of needed expertise in vector control for diseases such as West Nile encephalitis.

Poverty and social inequality.
At the same time that infectious diseases have significant and far-reaching economic implications, social inequality, driven in large part by poverty, is a major factor in emergence. Mortality from infectious diseases is closely correlated with transnational inequalities in income. Global economic trends affect not only the personal circumstances of those at risk for infection, but also the structure and availability of public health institutions necessary to reduce risks.

War and famine.
War and famine are closely linked to each other and to the spread of infectious diseases. Displacement due to war and the fairly consistent sequelae of malnutrition due to famine can contribute significantly to the emergence and spread of infectious diseases such as malaria, cholera, and tuberculosis.

Lack of political will.
If progress is to be made toward the control of infectious diseases, the political will to do so must encompass not only governments in the regions of highest disease prevalence, but also corporations, officials, health professionals, and citizens of affluent regions who ultimately share the same global microbial landscape. The complacency toward the threat of infectious diseases that has become somewhat entrenched in developed countries must reverse in direction if we are to avoid losing windows of opportunity to reduce the global burden of infection.

Intent to harm.
The world today is vulnerable to the threat of intentional biological attacks, and the likelihood of such an event is high. The U.S. public health system and health care providers should be prepared to address various biological agents that pose a risk to national security because of their potential to cause large numbers of deaths and widespread social disruption.

Recognizing and addressing the ways in which the factors in emergence converge to change vulnerability to infectious diseases is essential to the development and implementation of effective prevention and control strategies.

Detecting and responding to global infectious disease threats is in the economic, humanitarian, and national security interests of the United States and essential to the health of its people.

~ ~ ~

Excerpt from: Microbial Threats to Health: The Threat of Pandemic Influenza. ISBN: 978-0-309-09717-8, 48 pages, 6 x 9, paperback (2005). Available through The National Academies Press.


Dipl.-Ing. Wilfried Soddemann said...

Spread of avian flu by drinking water:

Proved awareness to ecology and transmission is necessary to understand the spread of avian flu. For this it is insufficient exclusive to test samples from wild birds, poultry and humans for avian flu viruses. Samples from the known abiotic vehicles also have to be analysed. There are plain links between the cold, rainy seasons as well as floods and the spread of avian flu. That is just why abiotic vehicles have to be analysed. The direct biotic transmission from birds, poultry or humans to humans can not depend on the cold, rainy seasons or floods. Water is a very efficient abiotic vehicle for the spread of viruses - in particular of fecal as well as by mouth, nose and eyes excreted viruses.

Infected birds and poultry can everywhere contaminate the drinking water. All humans have very intensive contact to drinking water. Spread of avian flu by drinking water can explain small clusters in households too. Proving viruses in water is difficult because of dilution. If you find no viruses you can not be sure that there are not any. On the other hand in water viruses remain viable for a long time. Water has to be tested for influenza viruses by cell culture and in particular by the more sensitive molecular biology method PCR.

There is a widespread link between avian flu and water, e.g. in Egypt to the Nile delta or Indonesia to residential districts of less prosperous humans with backyard flocks and without central water supply as in Vietnam: See also the WHO web side: .

Transmission of avian flu by direct contact to infected poultry is an unproved assumption from the WHO. There is no evidence that influenza primarily is transmitted by saliva droplets: “Transmission of influenza A in human beings” .

Avian flu infections may increase in consequence to increase of virus circulation. In hot climates/the tropics flood-related influenza is typical after extreme weather and floods. Virulence of influenza viruses depends on temperature and time. Special in cases of local water supplies with “young” and fresh H5N1 contaminated water from low local wells, cisterns, tanks, rain barrels, ponds, rivers or rice paddies this pathway can explain small clusters in households. At 24°C e.g. in the tropics the virulence of influenza viruses in water amount to 2 days. In temperate climates for “older” water from central water supplies cold water is decisive to virulence of viruses. At 7°C the virulence of influenza viruses in water amount to 14 days.

Human to human and contact transmission of influenza occur - but are overvalued immense. In the course of influenza epidemics in Germany, recognized clusters are rare, accounting for just 9 percent of cases e.g. in the 2005 season. In temperate climates the lethal H5N1 virus will be transferred to humans via cold drinking water, as with the birds in February and March 2006, strong seasonal at the time when drinking water has its temperature minimum.

The performance to eliminate viruses from the drinking water processing plants regularly does not meet the requirements of the WHO and the USA/USEPA. Conventional disinfection procedures are poor, because microorganisms in the water are not in suspension, but embedded in particles. Even ground water used for drinking water is not free from viruses.
Ducks and rice [paddies = flooded by water] major factors in bird flu outbreaks, says UN agency
Ducks and rice fields may be a critical factor in spreading H5N1
26 March 2008 – Ducks, rice [fields, paddies = flooded by water! Farmers on work drink the water from rice paddies!] and people – and not chickens – have emerged as the most significant factors in the spread of avian influenza in Thailand and Viet Nam, according to a study carried out by a group of experts from the United Nations Food and Agriculture Organization (FAO) and associated research centres.

“Mapping H5N1 highly pathogenic avian influenza risk in Southeast Asia: ducks, rice and people” also finds that these factors are probably behind persistent outbreaks in other countries such as Cambodia and Laos.
The study, which examined a series of waves of H5N1 highly pathogenic avian influenza in Thailand and Viet Nam between early 2004 and late 2005, was initiated and coordinated by FAO senior veterinary officer Jan Slingenbergh and just published in the latest issue of the Proceedings of the National Academy of Sciences of the United States.
Through the use of satellite mapping, researchers looked at a number of different factors, including the numbers of ducks, geese and chickens, human population size, rice cultivation and geography, and found a strong link between duck grazing patterns and rice cropping intensity.

In Thailand, for example, the proportion of young ducks in flocks was found to peak in September-October; these rapidly growing young ducks can therefore benefit from the peak of the rice harvest in November-December [at the beginning of the cold: Thailand, Viet Nam, Cambodia, Laos are situated – different from Indonesia – in the northern hemisphere].

“These peaks in congregation of ducks indicate periods in which there is an increase in the chances for virus release and exposure, and rice paddies often become a temporary habitat for wild bird species,” the agency said in a news release.

“We now know much better where and when to expect H5N1 flare-ups, and this helps to target prevention and control,” said Mr. Slingenbergh. “In addition, with virus persistence becoming increasingly confined to areas with intensive rice-duck agriculture in eastern and south-eastern Asia, evolution of the H5N1 virus may become easier to predict.”

He said the findings can help better target control efforts and replace indiscriminate mass vaccination.
FAO estimates that approximately 90 per cent of the world’s more than 1 billion domestic ducks are in Asia, with about 75 per cent of that in China and Viet Nam. Thailand has about 11 million ducks.

Dipl.-Ing. Wilfried Soddemann - Epidemiologist - Free Science Journalist

"Δημήτριος ο Ταξιδευτής" said...

nice post!
very informative...

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