ID physicians speculate on potential emerging diseases in the next decade

In the past 10 years, outbreaks or new mechanisms of spread have been seen with diseases never seen before in the United States. In some cases, this has occurred in diseases never before recognized anywhere in the world. Examples are the SARS (new disease), West Nile virus, influenza A (H1N1) (new disease) and monkeypox outbreaks, as well as the anthrax attack (new method of spread). For this column, we are speculating on diseases that might emerge or spread in the United States in the next five to 10 years.

We have reviewed the candidate diseases with consideration of the effects of global warming, increasing international travel, vectors already present in the United States, increasing importation of wild life (the United States is the world’s largest importer of wild life) and the potential of bioterrorism.

We will consider dengue, chikungunya, yellow fever, Japanese encephalitis, influenza, multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), MDR-gram negative bacilli, malaria and bioterrorism. Other possibilities for which there is too little space to consider are Trypanosoma cruzi from ingesting contaminated, imported foods, progressive multifocal leukoencephalopathy from immunoactive drugs, prion disease, and vaccine preventable diseases, such as mumps, if vaccination levels fall as they have in some industrialized parts of the world. Of course, there is also the potential of introduction of a currently unknown or rare disease, most likely of animal origin. We must expect the unexpected, as it will surely occur.

Arthropod-borne viruses

Dengue, chikungunya and yellow fever viruses have been on the move in various parts of the world recently. The risk of transmission of these three viruses is related to introduction of these viruses into localities where populations of Aedes aegypti and A. albopictus mosquitoes are high. There have been several chikungunya cases imported into the United States by international travelers, including one case in Louisiana, where there are populations of both A. aegypti and A. albopictus, but without further transmission.

Dengue viruses have also been imported. An outbreak occurred in Maui, Hawaii, in 2001, apparently imported by a traveler from an outbreak on French Polynesia. The virus was transmitted in Maui by A. albopictus. A small dengue outbreak occurred in Key West, Fla., at the end of 2009, transmitted by A. aegypti. From 2001 to 2004, the CDC reported 366 suspected imported dengue cases in 37 states and the District of Columbia, but there was no ongoing transmission.

Yellow fever virus can be transmitted by A. aegypti and by A. albopictus. However, A. albopictus has not been implicated in yellow fever outbreaks in endemic areas in South America, where mosquitoes and the virus occur. Introduction of yellow fever virus into the United States would be more likely coming from an urban outbreak than from isolated jungle cases. The most recent urban yellow fever outbreak was in Paraguay in 2008, where A. aegypti was the vector.

There are established populations of A. aegypti and A. albopictus, mainly in the southeastern United States, where the risk of introduction and subsequent transmission of dengue, chikungunya and yellow fever viruses is highest. However, cultural practices in the United States, such as use of air conditioning and window screens, are significant barriers to transmission, especially for A. aegypti, which breeds in and around buildings.

The risk of Japanese encephalitis virus introduction and establishment throughout North America is real. There are competent mosquito vectors present and avian species that have been shown experimentally to serve as hosts. Introduction of virus-infected mosquitoes via commercial aircraft coming from Japanese encephalitis virus endemic areas is possible, in the same way that West Nile virus came into the United States.

Influenza

Avian H5N1 influenza has spread in water birds over Asia, Africa and parts of Europe. It is likely to eventually be introduced into the United States via wild migrating or imported birds. However, should infection in birds in the United States occur, there are relatively few backyard flocks of poultry (compared with numerous ones in Asia), and commercial poultry are carefully managed and regulated. Thus, there is much less likelihood of transmission to poultry and then to humans. Furthermore, because of the difficult person-to-person transmission (fairly level numbers of cases globally for the past six years), it is unlikely to spread in its current form among humans in the United States. Of course, H5N1 could mutate to a more infectious and contagious form for humans, but it hasn’t happened with six years of opportunity (ie, close contact of infected backyard flocks of poultry with humans and pigs), and it is likely that it won’t.

However, it must be remembered that a new pandemic of influenza will inevitably occur from an entirely different strain, and such new pandemics have occurred within as short an interim period as 11 years.

Antibiotic resistant bacteria

MDR-gram negative bacilli and MDR- and XDR-TB are being reported around the world, including the United States, at ever increasing rates. MDR-TB refers to infection with Mycobacterium tuberculosis resistant to isoniazid and rifampin; XDR-TB refers to a subgroup of MDR-TB, resistant additionally to a fluoroquinolone and at least one of the second-line injectable drugs (capreomycin, amikacin or kanamycin). In the high-income countries of Western Europe and the United States, immigration from countries with high rates of MDR-TB is the single most important factor associated with their TB dynamics. Countries of origin for foreign-born persons with MDR-TB do not have proper TB diagnostic services and quality-assured second-line drugs needed to treat MDR-TB. The inability to detect drug resistance early is one of the major factors responsible for the development of MDR-TB; this invariably results in prolonged exposure to ineffective drugs and promotes development of further drug resistance. Until MDR-TB is controlled in the countries of origin, MDR-TB in the United States will likely continue to increase.

MDR-gram negative bacilli, including extended spectrum beta-lactamase and AmpC-producing pathogens, have been difficult problems for some time in American hospitals. Carbapenem antibiotics (meropenem, imipenem, doripenem and ertapenem) are often used as a last resort for treating serious health care-associated infections due to these organisms because these drugs are not destroyed by extended spectrum beta-lactamase and AmpC beta-lactamases. Resistance to the carbapenem antibiotics has been uncommon until now; but, as would be expected, with expanded use of the carbapenems, nosocomial MDR-gram negative bacilli have acquired carbapenem resistance in addition to resistance to other classes of antibiotics (such as trimethoprim/sulfamethoxazole, fluoroquinolones and aminoglycosides) and are proliferating. They may still be susceptible to the polymyxins and tigecycline. However, emergence of resistance may develop on therapy with these drugs, making these pathogens truly multidrug-resistant to the point of being untreatable.

Two species that have become most problematic in this regard are Klebsiella pneumoniae and Acinetobacter baumannii; MDR-A. baumannii is frequently isolated in nosocomial infections and is especially prevalent in intensive care units, where both sporadic cases, as well as outbreaks, have occurred. In K. pneumoniae, a new class of carbapenemases, known as K. pneumoniae carbapenemases (KPC), encoded by a gene that resides on a highly transferable plasmid, can hydrolyze all penicillins, cephalosporins and carbapenems. KPC-producing K. pneumoniae have caused several extended outbreaks throughout the United States and in several other countries. Very few drugs are active against these MDR-gram negative bacilli; new drugs and new targets for antimicrobial action are urgently needed, as well as enhanced measures to prevent spread of these organisms.

Malaria

Malaria (including Plasmodium knowlesi) is a possibility for outbreaks in the United States. We have the Anopheles mosquito vector in much of the United States, and malaria was at one time endemic in parts of this country. The potential certainly exists for introduction and spread with global warming (more mosquitoes) and increasing travel. Mosquito control measures would probably limit the outbreak.

Bioterrorism

Lastly, we have the ever present threat of bioterrorism with infections or intoxications caused by bacteria such as anthrax, plague, tularemia, and botulism and viruses such as Variola, Ebola, Marburg, Lassa, Hendra, Nipah and tick-borne encephalitis.

Despite all predictions, outbreaks will occur that are absolutely unpredictable in nature.

Dr. Levison is an adjunct professor at Drexel University, College of Medicine in Philadelphia.

Dr. Yuill is professor emeritus, Department of Pathobiological Sciences, Department of Wildlife Ecology, Nelson Institute for Environmental Studies at the University of Wisconsin-Madison in Madison, Wisconsin.

Dr. Kaye is professor of medicine, Drexel University, College of Medicine in Philadelphia.