Gastrointestinal Infections

Eric J. Stern, MD

Pediatric infectious diseases

2011

WHO <5y mortality

• Diarrhea – 19%

• PNA/URI – 19% (in a/w malnutrition)

• Measles – 7%

• Malaria – 5%

• Malnutrition (direct cause) – 21%

• One or more of these 5 – 71%

Oxford Handbook of Trop Med

Climate Change and

Infectious Diseases• Temps expected to increase 1.8°C - 5.8°C

by end of century

• Will alter hydrologic cycle -->more rainfall, more drought, more severe weather (hurricanes, floods, tsunamis)– Waterborne diseases, diarrheal diseases,

runoff, contamination of water by livestock

– WHO: 10% increase in diarrheal disease by 2030

• Insect vectors more active at higher temperatures

Climate Change and

Infectious Diseases (2)

• Kyoto protocol (2005) - not signed by

US, set to expire in 2012

• Copenhagen (2009) - no binding

resolution

• Developing countries

disproportionately affected

Post-disaster Infections:

Day 3-7• Wound infections

• Diarrheal disease (crowding, DPs)

• Pneumonia

• Vaccine-preventable diseases (crowding, displaced persons camps, disruption of healthcare system)– measles

– Diphtheria

– Tetanus

– Hep A

Post-disaster Infections:

>4 weeks• Gastrointestinal infections

• Wound infections (ie, Vibrio spp.)

• Sepsis

• Mosquito-borne illness - malaria, dengue

• TB (crowding, disrupted med supply, disrupted public health)

• HIV (blood transfusions, disrupted med compliance)

Long-Term Infectious

Disease Concerns

• Local public health concerns remain long after natural disaster…

• Disruption of public health system, chronic care facilities

• Increasing incidence of vaccine-preventable diseases

• Ecological impact on wildlife

• Climate change

Water

• Diarrheal disease

• Contaminated baby

formula

• Where does

purification take

place? Point of origin

vs consumption?

• Bottles

• Tankers

• Filters

• Aluminum, chlorine

• “Bladders,” “onion

tanks”

Port-au-Prince, 2010

Plans for Controlling

Infectious Diseases after

Natural Disasters1. Ensure access to safe drinking water

and sanitation

2. Provide access to primary care facilities

3. Implement surveillance system for potential outbreaks

4. Promote measles vaccination and vitamin A supplementation

5. Prevent epidemics of malaria and dengue

Traveler’s diarrhea

• Affects 20-60% of traveler’s to low-income countries

• So. Asia > Sub-Saharan Africa > Cent. and So. America

• Pathogens: Enterotoxigenic E. coli, Salmonella spp., Shigella, Campylobacter, viral gastro– Emergence of Enterotoxigenic Bacteroides

• Rx: azithromycin due to FQ-R Campylobacter (SE Asia) + metronidazole

Diarrheal Diseases:

Pathogens– Viral gastroenteritis

(Norovirus, Rotavirus, enteric Adeno ST 41, 43)

– V. cholera

– Enterotoxigenic E. coli

– Salmonella

– Shigella

– Campylobacter

– Yersinia

– C. difficile

– Cryptosporidiium, Isospora, Cyclospora

– Giardia

– Parasitic: ascariasis, strongyloides, hookworm, whipworm

– Other: food poisoning (Staph, Bacillus cereus)

Case 1

• 25 year old female migrant worker returned for 2.5 weeks to S.D. after family visit to Nicaragua

• 3 days of fever to 105F (>41C), constipation, vomiting, H/A, abdominal pain, myalgias

• Took no malaria prophylaxis, was bitten by mosquitoes

• Reportedly ate no unpasteurized dairy products

• No known ill contacts

• Helped with family shopping, foods bought in local street markets…

Case 1 (cont.)

• PE ill-appearing

• T103.4 P68 R24 BP112/78 cor, lungs nl abd - RUQ tenderness with mild rebound ext - no rash

• WBC 4.8 36S 34B Hct 36 Plts 170K

• Malaria smear negative x1

Case 1 (cont.)

• Blood culture: positive for S. typhi

• Bone marrow aspirate culture also

positive S. typhi

• Treatment: IV ceftriaxone, fever continued

for 4 days on appropriate therapy

• Stool culture: negative x1, positive x2,

became negative 2 weeks later

Typhoid fever (“Enteric fever”)

• Salmonella typhi

– Enterobacteriaceae

family

• Gram-negative rod

with flagellae

• Paratyphoid

– S. paratyphi A

emerging…no vaccine

– usually milder, but two

not clinically

distinguishable

Typhoid fever

• Fecal-oral transmission in areas with poor hygiene, unsafe water

• Average incubation: 10-20 days (range 3-60)

• Epidemic and endemic foci: India, Southeast Asia ,Philippines, eastern Europe

• Intermediate risk: Mexico, C. America

Typhoid Fever

• Clinical manifestations: fever, headache, malaise, splenomegaly, rash (transient), constipation followed by diarrhea

• Severe outcome due to ileal perforation

– 10% mortality if untreated

• Serologic tests (Widal antibodies, febrile agglutinins) usually not helpful

• Treatment: ceftriaxone/cefixime, azithromycin, ciprofloxacin

– Nalidixic acid/FQ-R in SE Asia

• Vaccine only ~60-75% effective, no coverage for S. paratyphi

• Uncomplicated Salmonella AGE – consider Abx for <1y

Typhoid vaccines

CDCLong. Principles and Practices of Ped Inf Dis

Campylobacter

• Motile, comma-shaped GNR

• Grows @ 42ºC

• Foodborne or waterborne

– Unpasteurized dairy, poultry

• Fever, abd pain, colitis bloody diarrhea

• “pseudoappendicitis” syndrome –

mesenteric lymphadenitis

• C. jejuni Guillaun-Barre Syndrome

Shigella

• Highly infectious (low inoculum – as few as 10 organisms)

• Shigella sonnei most common

• Clinical: watery -> bloody...Seizures

• 2009 – Kansas City outbreak >250 cases

• Treatment recommended for confirmed cases to decrease transmission and decrease duration of illness

• Rx: ceftriaxone, cipro, azithro

• TMP-SMX resistance 47% in 1999-2003 89% in 2006

MMWR 2006;55: 1068-71

Yersinia

• Short GNR

• Y. enterocolitica, Y. pseudotuberculosis

• Y. pestis (plague)– septicemic vs pneumonic vs bubonic

– transmitted by rat fleas, domestic + feral cats

• US SW

• Tropism for intraabdominal lymphoid tissue --> pseudoappendicitis

• Disseminated infection

• increased risk in iron-overload states

• Reactive arthritis late

Case 2

• 16 yo healthy female from Imperial County, CA traveled to Panama for three weeks on a church mission trip

• Took malaria meds, had 2 Hep A doses, typhoid Vi CPS vaccine, and routine immunizations up-to-date

• Stayed with local family; numerous mosquito bites

• Upon return, febrile illness with headaches, muscle/joint/bone pain, mild transient rash

Case 2 (cont)

• WBC 3.2 with mild neutropenia; plt’s 115k

• Malaria screen negative

• Dengue serologies IgM positive

• Continued fatigue, malaise, gradually worsening GI symptoms, 4 kg weight loss (weeks)

• Bloating, decreased appetite, constipation alternating with diarrhea

• Unable to bring stool sample to laboratory

• Thoughts? Next steps?

Case 2 – Giardia lamblia

• Empiric

metronidazole x

10d significant

improvement

over first week of

Rx

Case 2 (cont)

• Dx’s: 1. Dengue 2. Presumed giardiasis

• Principles: “ticks and fleas”

– Immigrants and travelers may present with multiple infections and/or complications, e.g., anemia

– Empiric outpatient therapy sometimes warranted (as in tropics): confirmation ideal but not always practical

Giardia lamblia

• Rx: metronidazole, Nitazoxanide

(Alinia)

• Retreatment occasionally necessary

– Ongoing household reinfection?

– Immune deficiency (CVID)?

– Other? (ie, IBD)

Case 3: Haiti

• 23 yo aide worker, airlifted from rural mountainous Haiti after 6 weeks of non-bloody watery diarrhea

• Cipro/flagyl x 5 days

• Stool fecal leuks neg, Cx neg

• Med-evaced to GUH for severe dehydration

• Cholera???

Haiti: current situation

• 1.2 million DPs

• MSF teams treated >41,000 cholera

patients since start of outbreak

• More than 1,800 deaths

• Under reporting

• Crowding, poor sanitation, malnutrition

• Disrupted water system

• Buckets

Cholera

• Vibrio cholera 01

• Other non-cholera Vibrio sp. (haemolyticus, parahaemolyticus)

• Low infectious dose

• Rapid environmental spread

– Biofilms in environment increase infectivity to human as better passes through stomach

– Sewage-contaminated drinking water, seafood contaminated with water, food/water contaminated with feces

• Cytokine-producing T-cells

• cGMP transport profuse “rice-water” stools

CDC Nov. 2010

Reactive arthritis

• Reiter’s no longer P.C.

(arthritis/urethritis/uveitis)

• SSYC

• Predilection for lower extremities

• 1-4 wks post-infectious diarrhea

(avg: 2 wks)

• HLA-B27?

Clostridium difficile• 1935 – C. difficile discovered

• 1978 – first associated w/ disease

• 2004 – CDC reports new, more virulent strain

• Epidemiology:

– CDC: 15-30,000 deaths/year

– 1-2.5% fatality

– 13 cases/1,000 hospitalized

• Difficult to eradicate

– Alcohol-based hand sanitizers do not kill spores

– Can live in hospital room up to 40 days

– Contact isolation gown, gloves

– Wash hands!

Clostridium difficile• Almost every antibiotic can cause

– PCN, Clinda, Cephs most common

– Can occur weeks after Abx stopped

• Sx: fever, abd pain, profuse diarrhea +/- blood, elevated WBC/CRP leukemoid rxn

• Dx: stool C. diff toxin (A>B)

• Carriage w/o symptoms common in newborns and <1y

– Intestinal colonization as high as 50% in healthy neonates vs <5% in >2y

– Difficult to interpret toxin assay results in <12mo w/o GI sxs, fever, etc. only order if pre-test probability high

Clostridium difficile

• Rx: metronidazole 30mg/kg/day PO div Q8hrs OR Vanco 40mg/kg/day PO if no response to metronidazole x 10d

– Metronidazole resistance reported

– PO Vanc role in VRE

• Up to 40% relapse - retreatment • Contact precautions: duration of clinical

illness while C.diff pos

• Alcohol-based hand cleansers are not effective in removing C.diff spores

Rotavirus• Reoviridae Family

• 11 segments of

dsRNA

• Strain diversity

• 15 ST; G1-G4, G9

cause majority of

disease

• G1 ST 73% No. Amer.

• Surface antigens VP7

(G protein) and VP4 (P

protein) = immune

response

Rotavirus (cont.)

• #1 cause severe diarrhea children <5 in U.S. and

worldwide

– US: 600,000 outpatient visits, 55-70,000

hospitalizations, 20-60 deaths/yr

– Nearly 100% children infected by 5y

• “Wintertime vomiting disease”

• Fever, vomiting, profuse non-bloody diarrhea

(3 - 9 days)

– Vomiting helps dx vs AGE

• Dehydration

PIDJ – Dec 2010

Rotavirus Vaccine

• 1998 Rotashield - safe and effective in prelicensure testing among 18,000

– Pulled from market due to association with intussusception w/i 14d vaccination

– Decision to pull vaccine made early

– CDC, other health agencies involved in surveillance

– Peak incidence intussusception ages 3-9 mo, when vaccine given…Causal vs coincidental?

– Devastating loss of vaccine to developing countries

Rotavirus Vaccine (2)

• 2006 Rotateq - bovine, pentavalent, reassortant live-attenuated oral

• 2008 Rotarix – monovalent, live-attenuated

• Rotateq:– REST Trial - 6 cases intuss. (n=34,837 Rotateq) in 1st

42d vs 5 cases placebo (n=34,788)

– 3 doses, beginning b/w 6-12 weeks

– All 3 doses by 32 weeks

– 71% VE during 1st and 2nd seasons; 88% VE for severe Rota infections

– recent Bangla and Vietnam study 48% effective vs severe Rota

Norwalk agent 1st virus identified to cause gastro

Occurs year round - cold weather, hospitals, cruise ship

Sx: sudden onset vomiting, nonbloody diarrhea

Duration: 1-3 days…longer in immunocompromised

Immunocompromised may shed virus for up to 56 days

Koo - CID 2009

First case series describing Noro as cause of persistent

gastroenteritis in adult HSCT recipients

Previous reports in children

RT-PCR gold standard - best early in illness

Consider Noro esp. in cases of GVHD diarrhea refractory

to prolonged steroid therapy

Conclusion: Contact

precautions• In general, contact precautions until

diarrhea stops

• Little kids bigger concern for

nosocomial transmissionmay not

wash hands well

• Shigella, E. coli 0157:H7 – no

diarrhea and x2 neg stool Cx

• Salmonella – no diarrhea and x3 neg

stool Cx

References

• Ivers, LC and Edward, TR. Infectious disease of severe weather-related and flood-related natural disasters. Curr Opin Infect Dis 2006, 19:408-14.

• Lignon, BL. Infectious diseases that pose specific challenges after natural disasters: a review. Semin Pediatr Infect Dis 2006; 17:36-45.

• MMWR: Vibrio Illnesses After Hurricane Katrina --- Multiple States, Aug-Sept 2005

• Othman, N, Ismail, I, Yip, R, Zainuddin, Z, Kasim, SM, Isa, R, and Noh, LM. Infections in post-tsunami victims. Pediatr Infect Dis J 2007 Oct; 26(10):960-1.

• Watson, JT, Gayer, M, and Connolly, MA. Epidemics after natural disasters. CDC 2007 January. Available at http://www.cdc.gov/ncidod/EID/13/1/1-appt.htm