Bugs Without Borders: View from the Americas

Bacterial and viral pathogens travel the globe passport-free; where human travel is monitored, microorganisms are free to spread worldwide. The perspective from the Americas was provided in a symposium at the annual meeting of Infectious Diseases Society of America, which was held in New Orleans, Louisiana.

The appearance and epidemic spread of the Zika and chikungunya viruses in the Americas, in general, and Venezuala in particular, should have come as no surprise, according to Jaime Torres, MD, Tropical Medicine Institute, Universidad Central de Venezuala, Caracas, Venezuala. Both of the aforementioned viruses are spread by arthropods, which range widely. However, for good reasons, both epidemics took health authorities by surprise.

“This was the first simultaneous occurrence of three large viral epidemics transmitted by the same vector. For the first time, a mosquito-borne virus infection has been shown to cause congenital malformations. Zika was the first arbovirus to be sexually transmitted,” said Dr. Torres in his session.

Complicating the issue is the geography of the outbreaks. Medical knowledge generated south of the equator can face hurdles when it comes to acceptance in the north. The reported link between Zika virus infection and microcephaly was initially viewed with some reserve, despite prior knowledge from the outbreak in French Polynesia. Preliminary data suggesting that the involvement of the genitourinary, cardiac, and digestive systems has yet to gain traction.

The real risk of congenital Zika virus syndrome may be greater than presently perceived. “Up to 6% of Zika virus-infected pregnant women will miscarry or have stillborn deliveries. Actual rates might be even higher. Surviving infants have as much as a 13% chance of Zika-related microcephaly and associated mental, ocular, and hearing impairments. Many could be impaired in less obvious ways, with disabilities appearing later in a child’s development,” Dr. Torres explained.

There are many unanswered question regarding the effect of Zika infection later in pregnancy and long-term sequelae of intrauterne infection, as two examples. A critical question concerns the scope of the most recent Zika outbreak.

“Is the substantial size, severity, and unexpected complications of the Zika virus outbreak in the Americas compared with what has been seen in the past in other areas due to immunological enhancement from prior dengue virus exposure or key sequence changes in the virus genome making it more virulent?” Dr. Torres questioned.

Another pathogen that has spread extensively in the Americas is carbapenem-resistant Enterobacteriaceae (CRE). Maria Virginia Villegas, MD, International Center for Medical Research & Training, Cali, Columbia, discussed the situation in Latin America.

CREs, especially Klebsiella pneumoniae carbapenemases (KPCs), are global pathogens; this is reflected in their widespread occurrence throughout Latin America. KPC was first reported in Latin America in 2005 in Columbia. The following year, cases were reported in Argentina and Brazil, with subsequent cases in Venezuela, Chile, Ecuador, Peru, Uruguay, Mexico, and the Caribbean.

New Delhi metallo-β-lactamase (NDM-1) was first described in 2008. By 2012, it had spread from the Indian subcontinent to Latin America, first in Guatemala, and then more extensively throughout the continent.

The pattern of appearance and geographical expansion has been repeated for other pathogens. “The increasing incidence of CRE is an important threat to public health. CRE cause a variety of diseases, ranging from pneumonia to urinary tract infections, to serious bloodstream or wound infections. Few clinical studies have reported the clinical impact of carbapenemases in Latin America,” Dr. Villegas said in her session.

“The lack of surveillance due to limited resources in Latin America is contributing to under-reporting of a probable epidemic situation. Clinical studies are needed and joint efforts should be made between countries,” she added.

Another pathogen of concern has been multi-drug resistant tuberculosis (MDR-TB) followed more recently by extremely-drug resistant TB (XDR-TB). Eduardo Gotuzzo, MD, FACP, FIDSA, Director of the Institute of Tropical Medicine, Universidad Peruana Caryetano Heredia, Lima, Peru, addressed the problem in Peru.

“Resistant TB is not a new phenomenon. In the 1950s there was no effective treatment against TB. MDR-TB is an emerging problem due to globalization. There are significant epidemiological differences between countries,” Dr. Gotuzzo said in his session.

TB is not new to Peru; examination of mummified remains indicates an epidemic occurred some 1500 years ago. By 2000, the situation in Peru was dire; the nation was considered a global hot spot of TB. Eradication efforts paid off; in 2002 the World Health Organization (WHO) recognized Peru’s success. However, by 2014 Peru reported more cases of MDR-TB than any other country in the Americas.

Factors contributing to the failure of control included delayed treatment, the increased prevalence of the important co-morbidities of diabetes and HIV, and a public health system in which subjects are lost to follow-up.

XDR-TB has reared its head in the Americas, as elsewhere, with South Africa as the most recognized country. Linezolid produced promising results in one study. 15 of 19 (79%) patients had negative sputum culture after 4 months of treatment, with the rate climbing to 87% (34 of 39 patients) at 6 months, and 27 of 38 (71%) patients being considered cured after 1 year. Other promising drugs include clofazimine and thioderazine. The latter is not yet in the WHO guidelines.

Another reason for some optimism in Peru is the adoption of rapid testing. From 2008-2015, 455 of all rapid testing were done in the country. Timelier testing can translate to swifter start of treatment.

DISCLOSURES

Jaime Torres: None

Maria Virginia Villegas: Grant support and/or honoraria from AstraZeneca, Merck, MSD, Roche, and Pfizer

Eduardo Gotuzzo: Stockholder in Amgen, Biogen, and Eli Lilly; Former grant funding from Astellas Pharma Inc., and Clintrex/Astra Zeneca; Honoraria from SHEA (supported by Merck)

SOURCES

• Photos and tape of IDSA presentations
• Rodrigues N et al. Science 2016 352:345-349
• Dos Santos T et al. N Engl J Med 2016 375:1598-1601
• Perez F et al. Clin J Med 2013 80:225-233
• WHO Global Tuberculosis Report 2015
• Lee M et al. N Engl J Med 2015 373:290-291

PRESENTATIONS

Infectious Diseases in the Americas: Bugs Without Borders

• Zika and Chikungunya in the Americas: What we have learned; Jaime Torres, MD, Tropical Medicine Institute, Universidad Central de Venezuala, Caracas, Venezuala
• Antimicrobial resistance: Spread of carbapenem-resistant Enterobacteriaceae in Latin America; Maria Virginia Villegas, MD, MSC, International Center for Medical Research & Training, CIDEM, Cali, Columbia
• Changes in immunocompromised hosts: A South American experience; Edson Abdala, MD, PHD, Universidade de Sao Paulo, Sao Paulo, Brazil
• XDR tuberculosis in Peru; Eduardo Gotuzzo, MD, Universidad Peruana Caryetano Heredi, Lima, Peru

Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at hoyle@square-rainbow.com.