If I have diarrhea after vacation…

I may want to remember this reference: “Enteropathogens and Chronic Illness in Returning Travelers” NEJM 2013; 368: 1817-25.

Some “fun facts:”

  • In 2007, more than 30 million Americans traveled to developing regions. ~8% traveling to these regions needed medical care during or after travel.  Gastrointestinal symptoms were present in more than 25% who sought medical care.
  • According to the GeoSentinel Surveillance Network (42 travel medicine sites), between 1996-2005, 65% of enteric infections were due to parasites, 31% bacteria, and 3% viral. (J Infect 2009; 59: 19-27) (Parasites typically have more long-lasting infections which should be considered in interpreting this data; in addition, some pathogens are more difficult to isolate.)
  • Six pathogens were most prevalent: Giardia, Campylobacter, Entamoeba histolytica, Shigella, Stronglyoides, and Salmonella.

In addition to an enteric pathogen color-coded prevalence map, the article has a useful table identifying areas at high risk, mode of transmission, incubation period, common symptoms, recommended diagnostic tests and treatments.

To minimize the impact of these enteropathogens, physicians can help prepare travelers with appropriate vaccinations, malaria chemoprophylaxis (if needed), and effective anti-bacterial drugs for self-treatment should symptoms develop.

Related blog posts:

Norovirus Impact on Young Children

As noted in a previous blog (Norovirus -now more important than rotavirus | gutsandgrowth), Norovirus has become the most important cause of gastroenteritis in children younger than 5 years.  More data to back up that claim has been published (NEJM 2013; 368: 1121-30).

The authors examined laboratory-confirmed cases of norovirus in children younger than 5 years with acute gastroenteritis in hospitals, emergency departments, and outpatient clinical settings during the years 2009 and 2010.  Using the New Vaccine Surveillance Network (NVSN), the authors undertook a 2-year prospective population-based survey with a catchment population of more than 141,000.  The specific sites included county populations around the University of Rochester, Vanderbilt University, and Cincinnati Children’s.

Results:

  • Norovirus was detected in 21% of children with acute gastroenteritis (2009-2010); it was also detected in 4% of healthy controls.
  • The age group with the highest rates of norovirus infection in this study were 6-18 months of age.
  • The GII.4 Minerva strain was most predominant strain in 2009 and GII.4 New Orleans in 2010. (In 2012, a novel GII.4 Sydney variant has emerged).
  • Rotavirus was identified in 12% of children with acute gastroenteritis (2009-2010).
  • Using this data, the authors extrapolated national estimates (for norovirus) of 14,000  hospitalizations per year (in this age group), 281,000 emergency room visits, and 627,000 outpatient visits.
  • The estimated costs exceed more than $273 million.

Related blog entry:

Closer to Star Trek Medicine

In Star Trek, Dr. Leonard McCoy used a medical tricorder to effortlessly diagnose a lot of conditions (Tricorder – Wikipedia, the free encyclopediaMedical tricorder – Wikipedia, the free encyclopedia).  While many of the newest diagnostic tests are not as portable, they share a feature of being able to diagnose a wide range of conditions quickly.  These tests include imaging studies like MRI and CT, genetic microarrays, and now PCR panels to diagnose a broad array of respiratory and gastrointestinal ailments.

One of the newest is the “xTAG GPP.”  With one stool sample, this Gastrointestinal Pathogen Panel (GPP) can detect at least 11 common bacteria, viral, and parasitic pathogens in about five hours.  Thus, all patients with identifiable gastroenteritis illnesses can be diagnosed more quickly.  The test relies on a “multiplex nucleic acid test.”

FDA News Release Jan 15, 2013  (Press Announcements > FDA permits marketing of first test that can ):

“Infectious gastroenteritis is an inflammation of the stomach and intestines caused by certain viruses, bacteria, or parasites. Common symptoms include vomiting and diarrhea, which can be more severe in infants, the elderly, and people with suppressed immune systems. Gastroenteritis can be spread easily through person-to-person contact and contaminated food, water, and surfaces. 
 
The Centers for Disease Control and Prevention reports that between 1999 and 2007 gastroenteritis-associated deaths in the United States increased from nearly 7,000 to more than 17,000 per year. Norovirus and Clostridium difficile accounted for two-thirds of the deaths. 
 
The xTAG Gastrointestinal Pathogen Panel (GPP), a multiplexed nucleic acid test, detects the following causes of gastroenteritis:
 
Bacteria
  • Campylobacter
  • Clostridium difficile (C. difficile) toxin A/B
  • Escherichia coli (E. coli) O157
  • Enterotoxigenic Escherichia coli (ETEC) LT/ST
  • Salmonella
  • Shigella
  • Shiga‐like Toxin producing E. coli (STEC) stx 1/stx 2
 
Virus
  • Norovirus
  • Rotavirus A
 
Parasite
  • Cryptosporidium
  • Giardia
 
“Tests such as the XTag GPP that can detect viruses, bacteria, and parasites from one sample at the same time can help clinicians more quickly identify and treat what’s causing gastroenteritis,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiology at the FDA’s Center for Devices and Radiological Health. “The test could also allow clinicians and public health professionals to more quickly identify and investigate the source of potential gastroenteritis outbreaks.”
The manufacturer demonstrated the performance of the xTAG GPP by collecting samples from 1,407 patients with suspected infectious gastroenteritis and comparing the xTAG GPP results to individual tests that are known to separately and reliably detect the 11 viruses, bacteria, or parasites associated with the xTAG GPP. The manufacturer also ran the test on 203 samples from patients with previously confirmed infectious gastroenteritis, and 313 additional specimens from pediatric patients with suspected infectious gastroenteritis. Results were comparable to the individual tests. Due to the risk of false positives, all positive results from the xTAG GPP need to be confirmed by additional testing (blog entry underlined for emphasis, not in original FDA release).
 
Luminex, Inc., of Austin, Texas, manufactures the xTAG.”
According to manufacter’s website, the test also detects Yersinia, Entamoeba histolytica, and adenovirus.  It reports sensitivity of of >94% for almost all pathogens (except Salmonella which was 84%) and specificity of >94% for all of the pathogens.

Norovirus -now more important than rotavirus

Norovirus has become more important than rotavirus.  This is evident based on a recent review (NEJM 2012; 367: 2126-32).

Key points:

  • Noroviruses are the most common cause of acute gastroenteritis requiring hospital ER evaluation in U.S. adults.  It is predicted to become the most common cause of diarrhea in all age groups worldwide once rotavirus infection is controlled through vaccination.
  • Noroviruses are small nonenveloped single-stranded RNA viruses from the Calciviridae family.  There are six major genogroups.
  • Exposure can occur from other individuals, contaminated food/water, and environment sources, including nosocomial.
  • Chronic infection is common in immunocompromised hosts, perhaps 15-20% of some immunocompromised populations.  Evolution of the norovirus genome in patients infected for extended periods is relatively rapid (3.3% amino acid substitutions per year).
  • In normal hosts, viral shedding lasts 20-40 days; in the immunocompromised, shedding can occur for years.
  • Can be detected readily with RT-PCR assays.
  • There are no vaccines or specific viral agents available that have proven efficacy.  Passive antibody therapies have been given in individual cases.
  • Hand-washing is crucial, especially in the hospital.  In one study, 80% of hospital surfaces were contaminated with multiple norovirus strains—this study was done in a unit for children with immunodeficiencies.

Additional References:

Related blog entry:

Salmonella by mail-order

Sometimes patients are amazed that hemoccult cards can be sent by mail.  Now, I learned something new: you can mail-order live poultry and thereby spread salmonella far and wide (NEJM 2012; 366: 2065-73).  This study identified 316 cases in 43 states.

Key findings:

  • 36 hospitalized (23%)
  • 38 had chicks as pets (42%); of these, 22 (69%) said the pet owner was a child <5 years
  • Salmonella enterica serotype Montevideo subtype
  • 81% of infections identified as coming from a hatchery in Western U.S.
  • After identification of problem, owners implemented recommendations which lowered salmonella contamination.  After these measures, outbreak strain still detected in 7% of samples
  • Hatcheries mail live poultry to all 50 states –4 million birds are produced annually for this purpose. Approximately 250,000 birds are shipped each week, usually within 24 hours of hatching; each costing about $5 each.

Because only a portion of salmonella infections are identified with laboratory tests, there are likely thousands more infections associated with this outbreak.  Overall, nontyphoidal salmonella infections are estimated to cause 1 million illnesses, 19,000 hospitalizations, and 370 deaths annually.  Most infections are acquired as foodborne illnesses.  Though contact with animals, as this report indicates, is another mechanism.  These birds can appear healthy and intermittently shed salmonella.

Individuals wishing to reduce their risk of illness should practice careful hand hygiene around animals.  See link for helpful advice:

http://www.cdc.gov/healthypets/resources/salmonella-baby-poultry.pdf

The poultry business can help by adhering to sanitary practices, by avoiding artificially coloring chicks (which targets children), and by warning recipients of the danger of salmonella infection.

A drug that makes a difference: ondansetron

Ondansetron (Zofran ®) use has become more common and is making a difference (JPGN 2012; 54: 381-86).  This drug has been a terrific advance for so many individuals with disorders that provoke vomiting and nausea.  Not only does it have a high degree of effectiveness, but side effects are also quite uncommon.

The cited study documents ondansetron’s increasing use in Toronto.  This retrospective cohort study of children younger than 18 years with gastroenteritis examined emergency room visits between 2003 and 2008.  20% of 22,125 charts were selected randomly for review (n=3508 patients in final analysis).  During the study period, intravenous rehydration decreased from 27% to 13% and ondansetron use increased from 1% to 18%.  Associated with ondansetron use, mean length of stay decreased from 8.6 to 5.9 hours.  Also, the week following the index visit, there was a reduction in return visits from 18% to 13% as well as decreased need for intravenous rehydration (7% to 4%).

The authors state that analysis elsewhere has indicated that appropriate usage of ondansetron for this indication could result in savings of more than $65 million each year in the U.S.  The main limitation of this study is that other factors could have changed during the study period and resulted in some of these improvements; though, this institution did not have any major changes which could be identified.

Of course, ondansetron is used in many other clinical settings besides the emergency room.  Though the drug is expensive, it is worth the cost.

Additional references:

  • -Arch Pediatr Adolesc Med 2008; 162: 858-65.  Use of antiemetic agents in AGE.
  • -Ann Emerg Med 2008; 52: 22e6-9e6.  Use of oral ondansetron in children with AGE who failed oral rehydration.
  • -NEJM 2006; 354: 1698. Use of zofran did not decrease hospitalization but did decrease need for IV fluids and decreased vomiting.