Emerging and reemerging infectious diseases

Definition

First introduced by Nobel laureate Joshua Lederberg, the phrase “emerging infectious diseases” applies to 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.

Another major challenge to the global health community is drug resistance, particularly to antibiotics, of certain diseases such as tuberculosis (TB), typhoid, malaria, and sexually transmitted diseases such as HIV (human immunodeficiency virus) infection. There has been a renewed commitment in the twenty-first century 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 diseases include the bubonic plague, or 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 US President George W. Bush decreed that members of the US 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 50 million persons—more than the war itself. In 2010, emerging viral scourges include H1N1 influenza, 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 multidrug 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 sixty and younger; only 1 percent of those sixty-five years and older and 50 percent of those twenty-five to forty-nine years were infected. Usually, the flu causes the greatest morbidity and mortality in those sixty-five years and older. H1N1 infected about 22 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 1980s, 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 39.9 million persons globally living with HIV and AIDS in 2023.

Although HIV infection is 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. The world awaits the first cure and vaccine to prevent the dreaded disease in 2023. 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, US President Barack Obama announced the implementation of a new strategy to prevent HIV infection and to better serve those living with HIV/AIDS. President Obama 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 would focus on gay and bisexual men, on Black people and other persons of color, and on substance abusers. Program goals included reducing new HIV infections by 25 percent and increasing the number of those who know their HIV status from 79 percent to 90 percent.

Targets to end the AIDS epidemic by 2030 were outlined in the Sustainable Development Goal 3. The 2020 target was missed, and in 2023, the new interim target was to reduce HIV and AIDS by 95 percent by 2025. In 2022, the President’s Emergency Plan for AIDS Relief (PEPFAR) remained the largest donor to international air efforts aimed at eliminating AIDS, TB, and malaria. In 2022, 30.7 million people were receiving treatment for HIV, but there were also 1.3 million new infections that year, and 630,000 people died of AIDS in 2023.

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 the WHO, the disease killed 597,000 persons in 2023, of whom 95 percent were African. Seventy-six percent of those who died of malaria were younger than five years of age.

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.

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 a result, educating health workers and entire communities about malaria prevention, diagnosis, and treatment remains vital to effective case management and to forestalling 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 remained the world’s leading causes of death. HIV/AIDS, malaria, and TB remained among the world’s leading causes of death in 2022 and were becoming more difficult to treat because of resistance to drug therapies and, in the case of malaria, resistance to insecticides. HIV was the leading global cause of death among women of child-bearing age and, though AIDS deaths declined between 2015 and 2021 because of antiretroviral treatment (ART), it remained a global health concern.

Most prevalent in developing countries, TB and malaria further retard economic and social development. Malaria killed 619,000 in 2021, and it was shown to decrease a country’s gross domestic product by 1.3 percent and reduce foreign business investment. The WHO reported a cost of $15 billion to diagnose, treat, and prevent TB, which killed 1.3 million persons in 2022. 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 thousands of persons each year, and though the WHO reports that the number of persons who had newly contracted HIV infection declined from 1.4 million in 2010 to 650,000 in 2021, there were 38.4 million persons living with HIV and AIDS worldwide by 2021; 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 more than 90 percent of cases.

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 $350 billion worldwide by 2022. In 2023, an outbreak of bird flu cost the US alone $2.5 billion to $3 billion.

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. Between 1999 and 2021, 55,443 cases were reported to the CDC along with 2,683 deaths.

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.

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