diarrhea in child travelers

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

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

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


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%



• 2-year-old


• 2 months trip









H Az Allergic – ciprofloxacin?



• 2-year-old


• 2 months trip









H Az Allergic – ciprofloxacin? 28% 38%



• 2-year-old


• 2 months trip

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 <2 years

A. 10%

B. 20%

C. 30%

D. 40%

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


Are children at higher risk than adults accompanying them?

A. Yes

B. No

Newman-Klee, AJTMH 2007

7 episodes / 100 person weeks

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


In children hospitalized due to diarrhea

Rotavirus most common cause of diarrhea (24%)

Bacterial causes Salmonella spp.

Campylobacter spp.

Aeromonas spp.



Travel history by etiology of diarrhea


Recent travel to hot climate country

Shigella spp. and ETEC 60%

Other bacterial causes 16-29%

Rotavirus 4%

CLINICAL FEATURES AND SEVERITY

What is the median duration of travelers diarrhea in children aged<2 yeas

A. 1 day

B. 3 days

C. 5 days

D. >7 days

Duration of Traveler’s Diarrhea by Age Group

Age (years) Mean Duration (days)

Median Duration (days)

0-2 29 17

3-6 8 4

7-14 3 3

15-20 5 5

Total 11 3


What proportion of children aged <10 years will need medical care for traveler’s diarrhea

A. 5%

B. 10%

C. 25%

D. >35%

Traveler’s Diarrhea Severity in Children

Characteristics of traveler’s diarrhea among a cohort of American travelers to developing countries

Hill et al, AJTMH 2000 ; *NS

<10 Years old >10 Years old and adults

Use of medical care

39% 4%

Vomiting 46% 17%

Alteration of activities*

46% 26%

Fever and/or Bloody Stool in Children with Traveler’s Diarrhea

33%

16%

0%

5%

10%

15%

20%

25%

30%

35%

0-2 3-20

Age (Years)


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


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


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%


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: • duration • severity • need for medical assistance Emergency ABx

Marginal

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)









H Az Allergic – ciprofloxacin? 28% 38%



• 2-year-old


• 2 months trip


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)


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

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: [email protected] 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.


Division of Viral Diseases

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FUTURE RESEARCH


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)


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



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: [email protected] 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.


Epidemiology of Child Traveler’s Diarrhea

Diarrhea occurred on average on the 8th day

28% had a second episode Adventurous travel style


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

diarrhea in child travelers

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