Diarrhea in Child Travelers - Eyal Leshem Viral Gastroenteritis Team CISTM14, Quebec City - International Society of Travel Medicine

Diarrhea in Child Travelers

                Eyal Leshem
         Viral Gastroenteritis Team

               CISTM14, Quebec City

  National Center for Immunization & Respiratory Diseases
  Division of Viral Diseases

Liu et al Lancet 2014

Liu et al Lancet 2014

Kotloff et al Lancet 2013

Steffen et al JAMA 2015

Kendell et al CID 2012

Pediatric Traveler’s Diarrhea
    We know what causes
     pediatric diarrhea in
     developing countries

    We know what causes
     travelers diarrhea

Kean, Annals of Intern Med 1963

Pediatric Traveler’s Diarrhea
    We know what causes
     pediatric diarrhea in
     developing countries

    We know what causes
     travelers diarrhea

    What do we know about
     pediatric travelers
     diarrhea??

Kean, Annals of Intern Med 1963

Parents of child seeking advice treatment of traveler’s diarrhea :
• 2-year-old
• Thailand or Mexico (VFR, some visits to rural areas)
• 2 months trip
                         Regimen               Thailand    Mexico
    A       Rehydration, ORS only
    B       Fluids and loperamide
    C       Fluids and bismuth subsalicylate
    D       Fluids and rifaximin
    E       Fluids and co-trimoxazole
    F       Fluids and ciprofloxacin
    G       Fluids and azithromycin

Hagmann et al JTM 2014

Parents of child seeking advice treatment of traveler’s diarrhea :
• 2-year-old
• Thailand or Mexico (VFR, some visits to rural areas)
• 2 months trip
                         Regimen               Thailand    Mexico
    A       Rehydration, ORS only               29%         34%
    B       Fluids and loperamide                2%          2%
    C       Fluids and bismuth subsalicylate      0          3%
    D       Fluids and rifaximin                  0           0
    E       Fluids and co-trimoxazole            2%          2%
    F       Fluids and ciprofloxacin              0           0
    G       Fluids and azithromycin             74%         58%

Hagmann et al JTM 2014

Parents of child seeking advice treatment of traveler’s diarrhea :
• 2-year-old
• Thailand or Mexico (VFR, some visits to rural areas)
• 2 months trip
                         Regimen               Thailand    Mexico
    A       Rehydration, ORS only               29%         34%
    B       Fluids and loperamide                2%          2%
    C       Fluids and bismuth subsalicylate      0          3%
    D       Fluids and rifaximin                  0           0
    E       Fluids and co-trimoxazole            2%          2%
    F       Fluids and ciprofloxacin              0           0
    G       Fluids and azithromycin             74%         58%

Hagmann et al JTM 2014

Parents of child seeking advice treatment of traveler’s diarrhea :
• 2-year-old
• Thailand or Mexico (VFR, some visits to rural areas)
• 2 months trip
                         Regimen               Thailand    Mexico
    A       Rehydration, ORS only               29%         34%
    B       Fluids and loperamide                2%          2%
    C       Fluids and bismuth subsalicylate      0          3%
    D       Fluids and rifaximin                  0           0
    E       Fluids and co-trimoxazole            2%          2%
    F       Fluids and ciprofloxacin              0           0
    G       Fluids and azithromycin             74%         58%
    H       Az Allergic – ciprofloxacin?
Hagmann et al JTM 2014

Parents of child seeking advice treatment of traveler’s diarrhea :
• 2-year-old
• Thailand or Mexico (VFR, some visits to rural areas)
• 2 months trip
                         Regimen               Thailand    Mexico
    A       Rehydration, ORS only               29%         34%
    B       Fluids and loperamide                2%          2%
    C       Fluids and bismuth subsalicylate      0          3%
    D       Fluids and rifaximin                  0           0
    E       Fluids and co-trimoxazole            2%          2%
    F       Fluids and ciprofloxacin              0           0
    G       Fluids and azithromycin             74%         58%
    H       Az Allergic – ciprofloxacin?        28%         38%
Hagmann et al JTM 2014

Objectives
   To present what we know about the epidemiology of
    diarrhea in child travelers

   To discuss treatment options and the role of empiric
    antibiotic use

Traveler’s Diarrhea Definition
    Adults
        ≥3 unformed stools / day

    Children
        ≥2 fold increase in the frequency of unformed stools

NIH consensus report 1985

EPIDEMIOLOGY

What is the incidence of travelers diarrhea in
                children aged

What is the incidence of travelers diarrhea in
                children aged

Incidence of Traveler’s Diarrhea - Children
    Pitzinger 1991

    Zurich University Vaccination Center
           Retrospective survey
           Pretravel visitors of vaccine center
           Questionnaire 2 weeks after return
           Age 0-20 years old

    N=363 Travelers

Pitzinger, PIDJ 1991

Incidence of Traveler’s Diarrhea by Age
                         / 2 Weeks of Travel

Pitzinger, PIDJ 1991

Incidence of Traveler’s Diarrhea by Age
                         / 2 Weeks of Travel

Pitzinger, PIDJ 1991

Incidence of Traveler’s Diarrhea by Age
                         / 2 Weeks of Travel

Pitzinger, PIDJ 1991

Are children at higher risk than adults
                 accompanying them?
A. Yes
B. No

7 episodes / 100 person weeks

Newman-Klee, AJTMH 2007

ETIOLOGY

Etiology of Traveler’s Diarrhea - Children
     University of Bern, Switzerland
         Children aged 5 weeks – 15 years
         Admitted due to acute diarrhea

     History of stay in hot climate, poorly industrialized
      country during the last 10 days prior to disease onset

Essers, Clin Infect Dis 2000

Etiology of Traveler’s Diarrhea - Children
     In children hospitalized due to diarrhea
     Rotavirus most common cause of diarrhea (24%)
     Bacterial causes
         Salmonella spp.
         Campylobacter spp.
         Aeromonas spp.

Essers, Clin Infect Dis 2000

Etiology of Traveler’s Diarrhea - Children
     Travel history by etiology of diarrhea

                                   Recent travel to hot climate
                                             country
Shigella spp. and ETEC                         60%
Other bacterial causes                         16-29%
Rotavirus                                        4%

Essers, Clin Infect Dis 2000

CLINICAL FEATURES AND SEVERITY

What is the median duration of travelers diarrhea
             in children aged7 days

Duration of Traveler’s Diarrhea by Age Group

      Age (years)      Mean Duration      Median
                          (days)       Duration (days)
      0-2                   29               17
      3-6                    8                4
      7-14                   3                3
      15-20                  5                5
      Total                 11                3

Pitzinger, PIDJ 1991

Duration of Traveler’s Diarrhea by Age Group

      Age (years)      Mean Duration      Median
                          (days)       Duration (days)
      0-2                   29               17
      3-6                    8                4
      7-14                   3                3
      15-20                  5                5
      Total                 11                3

Pitzinger, PIDJ 1991

What proportion of children aged 35%

Traveler’s Diarrhea Severity in Children
       Characteristics of traveler’s diarrhea among a cohort of
       American travelers to developing countries

                               10 Years old and
                                                    adults
 Use of medical                    39%                4%
 care
 Vomiting                          46%                 17%
 Alteration of                     46%                 26%
 activities*

Hill et al, AJTMH 2000 ; *NS

Fever and/or Bloody Stool in Children with
                     Traveler’s Diarrhea
35%                    33%
30%
25%
20%                                        16%
15%
10%
 5%
 0%
                       0-2                 3-20
                             Age (Years)

Pitzinger, PIDJ 1991

Why is Acute Gastroenteritis a Severe Disease in
               Young Children?
   Severe dehydration
     Hypovolemic shock
   Replacement with fluids lacking electrolytes
     Normovolemic hyponatremia
   Severe dysentery
     Intestinal perforation
     Sepsis

Are There Severe Outcomes of Traveler’s Diarrhea
                 in Children??
   Literature review
     No reports of child deaths due to traveler’s diarrhea

   Travel medicine professionals (Leshem, personal
    survey)
     Not aware of a single case

PREVENTION

Prevention of Travelers Diarrhea in Children
    Breastfeeding in very young
     children
       Alternatively use of formula + safe
        water
    Adherence to food and water
     precautions:

Newman-Klee, AJTMH 2007 ,Steffen JAMA 2015

Prevention of Travelers Diarrhea in Children
    Breastfeeding in very young
     children
       Alternatively use of formula + safe
        water
    Adherence to food and water
     precautions:
       32% in children
       17% in accompanying adults

Newman-Klee, AJTMH 2007 ,Steffen JAMA 2015

Prevention of Travelers Diarrhea in Children
    Antibiotic chemoprophylaxis
          Rarely used
          Consider use in high-risk
          Immune compromised
          IgA deficiency

    Rotavirus vaccines

Steffen JAMA 2015

TREATMENT

Treatment of Child Traveler's Diarrhea
   Prevention of dehydration
     Oral rehydration salts (ORS)
     Initiated immediately with recognition
      of diarrhea by parents
   Use a teaspoon / syringe
   Give 5mL every 2-4 minutes
     Do not stop if child vomits
   Continue breastfeeding / resume
    regular diet

Antibiotic Treatment of Child Diarrhea
   ISTM Pediatric interest group survey
     ORS only 29-34%

Antibiotic Treatment of Child Diarrhea
   ISTM Pediatric interest group survey
     ORS only 29-34%
   Why are travel health professionals hesitant about
    prescribing empiric antibiotics for traveler’s diarrhea in
    children?

Rational for considering the use of empiric
       antibiotics for traveler’s diarrhea in children
                  Child with Travelers Diarrhea   Child with Diarrhea in
                                                  Developed Countries

Etiology          Bacterial?                      Viral

Clinical course   Prolonged severe                Self limited, mild

Benefit           Reeducation of disease:         Marginal
                  • duration
                  • severity
                  • need for medical assistance
                  Emergency ABx

Risk              Marginal?                       • HUS (Ecoli O157:H7)
                                                  • Abx resistance
                                                  • SAEs

When Should Antibiotics be Started
   Judgment call:
   Any case of diarrhea
     Initiate ORS
     Consider antibiotics
   Consider use antibiotics
       Younger age
       Remoteness / limited availability of healthcare
       Signs of dehydration
       Any signs of severe disease (fever, vomiting, dysentery)

Antibiotic Treatment of Child Traveler's Diarrhea
   Azithromycin
   Dose: 10mg/kg QD up to 3 days
   Travel >2 weeks
     Unreconstituted powder – mix with water
   Recommended for SE Asia (FQ resistance)

Parents of child seeking advice treatment of traveler’s diarrhea :
• 2-year-old
• Thailand or Mexico (VFR, some visits to rural areas)
• 2 months trip
                         Regimen               Thailand    Mexico
    A       Rehydration, ORS only                29%        34%
    B       Fluids and loperamide                2%          2%
    C       Fluids and bismuth subsalicylate      0          3%
    D       Fluids and rifaximin                  0           0
    E       Fluids and co-trimoxazole            2%          2%
    F       Fluids and ciprofloxacin              0           0
    G       Fluids and azithromycin              74%        58%
    H       Az Allergic – ciprofloxacin?         28%        38%
Hagmann et al JTM 2014

Antibiotic Treatment of Child Traveler's Diarrhea
   Ciprofloxacin
   Dose: 20mg/kg/day divided BID for 3 days
   Not approved by many countries for use in children
     “To date no child treated with FQs has developed physician drug
      attributed bone or joint toxicity. This is based on experience with
      extensive use of ciprofloxacin and levofloxacin in children and
      adolescents.” (Red book 2012)
   Not for SE Asia (FQ resistance)

Antibiotic Treatment of Child Traveler's Diarrhea
   Second line antibiotics
       Furazolidone
       Nalidixic acid
       Cefixime
       Rifaximin (non-invasive disease, pt. age>12 years)

   No place for use of TMP / SMX
     Widespread resistance

Treatment of Child Traveler's Diarrhea
   Bismuth subsalicylate
     Not recommended by AAP
     Concerns regarding salicylate intoxication

   Loperamide
     Not recommended by AAP
     Concerns severe adverse events
     Extrapyramidal adverse events

Conclusions

Conclusions

Thank You

For more information please contact Centers for Disease Control and Prevention

1600 Clifton Road NE, Atlanta, GA 30333
Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
E-mail: cdcinfo@cdc.gov Web: http://www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the
Centers for Disease Control and Prevention.

                    National Center for Immunization & Respiratory Diseases
                    Division of Viral Diseases

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FUTURE RESEARCH

Antibiotic Treatment of Child Diarrhea
   Use of antibiotic for treatment of children with diarrhea
    is discouraged
       Antibiotic resistance
       Risk of hemolytic uremic syndrome (E. coli 0157:H7)
       Allergic reactions
       Adverse events

Evidence Based Child Traveler’s Diarrhea
   Burden of child traveler’s diarrhea
     Risk for severe disease
     Mortality?
   Etiology
   Prevention
     Targeting high risk populations (VFRs, travel to remote
      destinations)
   Treatment
     Effectiveness
     Safety
   ISTM Pediatric Interest Group Survey (PO23.01)

Incidence of Traveler’s Diarrhea - Children
    Pitzinger 1991

    Zurich University Vaccination Center
           Retrospective survey
           Pretravel visitors of vaccine center
           Questionnaire 2 weeks after return
           Age 0-20 years old

    N=363 Travelers

Pitzinger, PIDJ 1991

Incidence of Traveler’s Diarrhea - Children
   Newman-Klee 2007
         Pretravel clinic University hospital in Lausanne
         Retrospective survey of traveling families
         Post travel questionnaire of common travel related symptoms
         Age 0-16 years
         157 Child – adult pairs

   Incidence of diarrhea was similar in adults and children
       7 episodes / 100 person weeks

Newman-Klee, AJTMH 2007

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For more information please contact Centers for Disease Control and Prevention

1600 Clifton Road NE, Atlanta, GA 30333
Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
E-mail: cdcinfo@cdc.gov Web: http://www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the
Centers for Disease Control and Prevention.

                    National Center for Immunization & Respiratory Diseases

Epidemiology of Child Traveler’s Diarrhea
   Diarrhea occurred on average on the 8th day

   28% had a second episode
     Adventurous travel style

Antibiotic Treatment of Child Traveler's Diarrhea
Rational for use of empiric antibiotics for traveler’s
diarrhea in children:
 Etiology – predominantly bacterial

 Clinical course – prolonged, severe

 In adults, antibiotics reduce duration and severity of
  diarrhea

Etiology of Traveler’s Diarrhea - Adults
   Adult travelers etiology identified 60-80% of cases
   Mostly bacterial (50-80%)
   Viruses
   Parasites