What are emerging and reemerging infectious diseases?

Definition

First introduced by Nobel laureate Joshua Lederberg, the phrase “emerging
infectious diseases” applies to those infectious diseases that newly appear in a
populace, have been in existence for some time but are rapidly increasing in
incidence or geographic range, or appear as new drug-resistant strains of viruses,
bacteria, fungi, or parasitic species. Most emerging diseases are zoonotic in
origin and are disseminated through a range of vectors, from insects such as
mosquitoes to nonhuman primates.

While new infectious diseases continue to emerge, many of the old plagues remain, often appearing in more virulent and drug-resistant forms. While many outbreaks inexplicably appear, often there are specific identifiable ecological factors, such as climate change; agricultural development, such as land clearing; or demographic changes that may place people at increased risk through exposure to unfamiliar microbes or their natural zoonotic hosts.

Still another major challenge to the global health community is the growing
drug
resistance, particularly to antibiotics,
of certain diseases. These diseases include tuberculosis
(TB), typhoid, malaria, and sexually transmitted diseases
such as HIV (human immunodeficiency virus) infection. There has been a
renewed commitment to vaccine research to prevent and treat these infections and
other preventable infectious diseases.

Often to blame for emerging diseases are megacities, with their increased urban crowding, general lack of potable water, and ability, through its populations, to rapidly spread contagious diseases around the world through air travel. Mostly, these are global problems and are viewed as global infectious disease threats.

Background

Throughout history, populations have been afflicted by major outbreaks of
emerging
infectious diseases. These disease include the
bubonic
plague (also known as the Black Death), caused by the
bacterium Yersinia pestis and spread by fleas that feed on rats.
The plague emerged in the fourteenth century and decimated populations in Europe
and Asia.

Even more deadly than Y. pestis, however, was the variola
virus, the etiologic agent responsible for smallpox,
which evolved from poxviruses in cattle and emerged into human populations
thousands of years ago; from the fourteenth to sixteenth centuries, Spanish
conquistadors vanquished Central America by causing a smallpox epidemic through
introduction of the smallpox virus into indigenous populations, thereby disabling
their armies. More than four hundred years later, in 1980, the World Health
Organization (WHO) declared that smallpox had been eradicated
worldwide. In 2003, however, the United States entered into war with Iraq, and
U.S. president George W. Bush decreed that members of the U.S. Armed Forces be
vaccinated against smallpox in anticipation of a biological attack. This order
came on the heels of several acts of bioterrorism in 2001 in the United
States, wherein anthrax infection caused by Bacillus
anthracis emerged in Florida and New York.

The United States was also at war (World War I) in 1918 when the
influenza pandemic of that year killed up to fifty million
persons, more than the war itself. In 2010, emerging viral scourges include
H1N1
influenza, or swine flu, which exhibited drug-resistant
strains, and HIV, which was isolated in 1981 and continues to mutate in persons
with HIV infection and AIDS (acquired immunodeficiency syndrome), mandating the
need for new therapies and combinations. Emerging bacterial scourges include
methicillin-resistant Staphylococcus A (MRSA), multi-drug
resistant tuberculosis (MDR-TB), and extensively multi-drug resistant TB
(XMDR-TB). In addition, malaria, a parasitic disease, has demonstrated resistant
strains of its most lethal species, Plasmodium falciparum.

Emerging Viruses

Swine flu is a zoonotic disease resulting from a mix of swine, avian, and
human flu viruses. Between 2006 and 2009, investigators in China isolated H1N1,
H1N2, and H3N2 from pigs, observing a novel reassortment between contemporary
swine and avian influenza viruses and hypothesizing that swine may serve as hosts
for genetic reassortment between humans and avian panzoonotic viruses.

H1N1 first emerged in the Northern Hemisphere in Mexico, where the index case
was isolated. Following the regular flu season of April, 2009, H1N1 appeared in
the United States; during the 2008-2009 flu season, influenza A (H1), A (H3), and
B viruses had cocirculated. In mid-April, the Centers for Disease Control and
Prevention (CDC) documented the first two cases of novel
influenza A pandemic (H1N1) in the United States. Beginning in September, the CDC
had antigenically characterized flu viruses; one seasonal influenza A (H1N1),
three influenza A (H3N2), four influenza B, and 412 influenza A (H1N1) 2009
viruses, the latter spread rapidly in the Northern Hemisphere and producing
unprecedented morbidity and mortality in infants, young children, and pregnant
women. Most cases were found in persons age sixty and younger; only 1 percent of
those age sixty-five years and older and 50 percent of those age twenty-five to
forty-nine years were infected. Usually, the flu causes the greatest morbidity and
mortality in those age sixty-five years and older. H1N1 infected about twenty-two
million people in the United States and killed almost four thousand persons
between April and October, 2009.

Emerging Retroviridae

HIV/AIDS is of zoonotic origin and was first observed in nonhuman primates who came in close contact with hunters and with persons clearing land in the African plains. Since the time that HIV, the virus that causes AIDS, was isolated in the early 1980’s, the virus has continued to emerge in new populations and new geographic locations and has continued to morph into new strains and variants, becoming resistant to available antiretroviral therapies (ART); new drugs and combinations of old and new therapies must be produced to help keep alive the more than 1.3 million persons in North America living with HIV and AIDS in 2008.

Although HIV infection is now treated as a chronic disease in many developed
countries, developing nations continue to struggle to facilitate prevention
programs and to obtain enough drugs to treat all those infected with the virus.
The world awaits the first cure and vaccine to prevent the dreaded disease.
Moreover, despite the advent of highly active antiretroviral therapy (HAART) in 1996, a range of
comorbidities continues to affect those living with HIV and AIDS. These
comorbidities include liver disease (hepatitis B and C),
non-Hodgkin’s
lymphoma, neurological illnesses, malignancy, malnutrition,
and increased susceptibility to TB and MDR-TB. In addition, socioeconomic factors
such as poverty, unemployment, stigmatization, drug and alcohol addiction, and
undocumented immigration status are often by-products of those infected with the
disease.

In 2010, the CDC presented one of the first large-scale studies to demonstrate a strong association between poverty and HIV infection; poverty was shown to be a powerful driver of the AIDS pandemic. Of note, the study was conducted by surveying nine thousand heterosexual persons living in cities of the United States, a population not considered to be of high risk of contracting HIV infection. The results of the study revealed a 2.1 percent incidence of HIV infection, twice the expected number.

Also, in 2010, U.S. president Barack Obama announced the implementation of a new strategy to prevent HIV infection and to better serve those living with HIV/AIDS. The president declared his commitment to continue the fight against HIV and AIDS in the United States and across the globe with an emphasis on prevention, and he allocated $30 million in funding in addition to an earlier pledge, in 2009, of $45 million over five years; the new strategy will focus on gay and bisexual men, on blacks and other persons of color, and on substance abusers. Program goals include reducing new HIV infections by 25 percent and increasing the number of those who know their HIV status from 79 to 90 percent.

Emerging Mycobacterial Diseases

The emergence and spread of Mycobacterium tuberculosis strains
that are resistant to multiple drugs represent an emerging threat for global
control of both TB and HIV; TB often coinfects patients with HIV and AIDS, whose
weakened immune systems are more vulnerable to bacterial
infections, especially TB, MDR-TB, and XMR-TB. WHO estimates
that almost one-half million cases of MDR-TB emerged in 2006; MDR-TB is defined as
resistance to a minimum of the anti-TB drugs, isoniazid and rifampin, and in
certain regions of the world, prevalence of MDR-TB may be greater than 20 percent.
Although HIV may or may not be directly associated with the risk of developing
MDR-TB, nosocomial outbreaks of MDR-TB in persons with HIV/AIDS have been noted.
HIV/AIDS has also been linked to an increased risk for rifampin-monoresistant
TB.

In addition, new cases of XMR-TB that are defined as MDR-TB resistant to a
fluoroquinolone and to a (minimum of one) second-line injectable anti-TB agent,
have been reported in forty-five countries and on all continents. Treatment of
MDR-TB is complex and may result in the use of less effective and more toxic drugs
that require treatment over longer periods of time, thereby threatening success;
this is a serious problem for developing countries, especially countries (such as
those in sub-Saharan Africa) with a high prevalence of HIV-1 infection. MDR-TB and
XMR-TB also are of concern in developed countries because of mass immigration and
global travel; even long-term visitors appear to significantly contribute to the
burden of TB among foreign-born persons in the United States.

Emerging Parasitic Diseases

Malaria continues to wreak havoc across the developing
world. According to WHO, the disease killed 881,000 persons in 2008, 89 percent of
whom were African; 88 percent of these persons were younger than age five
years.

Malaria is spread through mosquito bites. While significant progress in malaria
control has been made in some of the highly endemic nations, such as Zambia,
Zanzibar, and Rwanda, where control relies on a combination of interventions that
include the use of insecticides and sleeping nets, the
number of patients treated for malaria with a confirmed diagnosis of malaria
remains low in Africa. This can lead to the inappropriate administration of
antimalarial medications, a practice that could foster the spread of
resistance.

Of note, parasite resistance to almost all commonly used antimalarials has been observed in the most lethal parasite species, P. falciparum, presenting a huge barrier to successful disease management. Although artemisinin-based combination therapy (ACT) has made a significant contribution to malaria control by reducing transmission, its administration to infants and small children may be especially problematic. As such, educating health workers and entire communities about malaria prevention, diagnosis, and treatment remains vital to effective case management and to the forestalling of the emergence of resistance to both ACT and insecticides used in vector control.

Global Impact

The impact of emerging infectious diseases on global health is far reaching; new and reemerging infectious diseases that were once unknown or thought to have disappeared have reappeared, and diseases that were once treatable have become resistant to drug therapies that once worked. In addition, socioeconomic determinants and environmental factors have been shown to play a significant role in morbidity and mortality from emerging infectious diseases, which remain the world’s leading cause of death (killing 34 percent of persons who succumb each year across the globe, 9 percent of whom are children). HIV/AIDS, malaria, and TB are the three leading threats to global health and are becoming more difficult to treat because of resistance to drug therapies and, in the case of malaria, resistance to insecticides.

Most prevalent in developing countries, TB and malaria are further retarding
economic and social development. Malaria kills almost one million persons each
year, and it can decrease a country’s gross domestic product by 1.3 percent; for
example, malaria costs African countries more than $12 billion per year. TB kills
more than 1.7 million persons per year, costing affected countries more than $3.1
billion in 2008 (up from $2.3 billion in 2007). MDR-TB should be given high
priority in global public health and biomedical research, and greater efforts
should be made to furnish appropriate resources to economically disadvantaged
areas for fighting MDR-TB and preventing XMR-TB.

HIV/AIDS kills 2 million persons each year, and though the number of persons
who contracted HIV infection declined from 3.2 million in 2001 to 2.7 million in
2008, there are 33.4 million persons living with HIV and AIDS worldwide; they are
able to survive because of antiretroviral therapy (ART) and preventive measures.
Sub-Saharan Africa is the global epicenter of the AIDS
pandemic, with 71 percent of cases. According to the journal
Health Affairs, if the pandemic continues unabated, more than
1 million persons will become infected each year through 2031, the fiftieth
anniversary of the beginning of the HIV/AIDS pandemic, at a total cost of $722
billion.

Many other infectious diseases of zoonotic origin have emerged at considerable
cost to human and animal life, with attendant economic losses when livestock are
removed from the food chain: Emerging zoonotic infectious diseases, including
bovine spongiform encephalitis (BSE, or mad cow disease) and avian
influenza (or bird flu), cost an estimated $120 billion
worldwide from 1995 to 2008.

Another zoonotic disease emerged in 2009 and soon became a pandemic. According to WHO, as of November, 2009, there were more than 40,600 cumulative confirmed and probable cases of H1N1 influenza and 7,826 deaths worldwide, though this may be an underestimate because the statistics are based on just 20 percent of the countries and communities that were able to provide confirmed laboratory data. In 2010, the Global Influenza Surveillance Network (GISN) reported that H1N1 continued to circulate in Malaysia, Singapore, India, Bangladesh, Bhutan, Chile, and Uruguay. During the height of the pandemic, many countries culled swine, resulting in economic hardship and adding to the losses incurred by human morbidity, mortality, and other related expenses.

Environmental factors such as climate change have influenced the emergence of
disease, as was demonstrated with the appearance of vector-borne West Nile
virus infection, which is endemic to the Near East and
Africa. West Nile was observed in the Western Hemisphere for the first time in the
northeastern United States in 1999, and it continues to return each summer to the
same region as mosquitoes return to feed on the viral reservoir of infected birds;
in July, 2010, the New York City Department of Health and Mental Hygiene issued an
alert for the virus, which can sicken and kill humans. From 2004 through 2007,
hospitalization costs for waterborne pathogens such as Legionnaires’
disease (caused by a bacterium), cryptosporidiosis (caused by a fungus), and giardiasis
(caused by a protozoan) were $154 million to $539 million.

Despite the foregoing statistics, there is growing worldwide recognition that science and public policy based on historical experience, international law, and ethics must intersect more effectively if the global community is to conquer the multitude of problems resulting from new and reemerging infectious diseases.

Bibliography

Drexler, Madeline. Emerging Epidemics: The Menace of New Infections. New York: Penguin Books, 2010. A comprehensive book that includes the history of a range of emerging diseases, including H1N1 and West Nile virus infection.

Fischback, M. A., and C. T. Walsh. “Antibiotics for Emerging Pathogens.” Science 325, no. 5944 (August 28, 2009): 1089-1093. Discusses options for developing new antibiotics to circumvent existing bacterial resistance mechanisms.

Garrett, Laurie. Betrayal of Trust: The Collapse of Global Public Health. New York: Hyperion Books, 2001. Focuses on biopreparedness, bioterrorism, and public health preparedness.

Giles-Vernick, Tamara, and Susan Craddock, eds. Influenza and Public Health: Learning from Past Pandemics. London: Earthscan, 2010. Discusses lessons learned from past flu pandemics about transmission patterns and successful (and not so successful) interventions.

Hill, Stuart. Emerging Infectious Diseases. San Francisco: Benjamin Cummings, 2005. Includes historical data and updates on emerging diseases of the twenty-first century.

Leslie, T., et al. “Epidemic of Plasmodium falciparum Malaria Involving Substandard Antimalarial Drugs, Pakistan, 2003.” Emerging Infectious Diseases 15 (2009): 1753-1759. Describes the role of substandard treatment of malaria in the formation of resistant malarial strains.

MacPherson, D. W., et al. “Population Mobility, Globalization, and Antimicrobial Drug Resistance.” Emerging Infectious Diseases 15 (2009): 1727-1732. A timely assessment of the root causes of drug resistance.

Strickland, Thomas, et al., eds. Hunter’s Tropical Medicine and Emerging Infectious Diseases. 8th ed. Philadelphia: W. B. Saunders, 2000. This is a classic textbook written by internationally known experts in the field. Although it uses some technical words, most readers should find the text understandable.