Transcript Travel and Tropical Medicine

Travel and Tropical Medicine
Roger Thomas, MD, Ph.D, CCFP,
MRCGP
OUTLINE: 6 KEY TASKS
1. Past medical history, medications, vaccinations,
planned travel, unplanned excursions and sports
2. Update childhood vaccinations (MMR, polio, tetanus)
3. Print off CDC data: ask patient read and underline
4. Ask their understanding of risks
5. Vaccinations and medications needed for trip
6. Specific situations: (a) Mountain sickness (slide 10)
(b) Vaccines in pregnancy (14-18)
(c) Malaria: life cycle 19-20; prevention 21-23;
chemoprophylaxis 24-31; treatment 32; clinical 33-40
(d) Traveller’s diarrhea: prevention; diagnosis; treatment
42-58
(e) Cholera 59; (f) Ebola 61; (g) Yellow Fever 62-65; (h)
Typhoid 66 (g) Dengue 66-69 (h) Schistosomiasis 70-1
Global, regional, and national incidence and mortality for
HIV, tuberculosis, and malaria during 1990-2013: a
systematic analysis for the Global Burden of Disease Study
2013. Lancet 2014
HIV
• 18 million new HIV infections (95% uncertainty interval
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17 to 21 million)
292 million prevalent cases (281 to 317)
13 million HIV deaths (13 to 15)
Due to interventions including PMTCT and ART, 191
million life-years (166 to 215 million) saved, 703%
(654% to 761%) in developing countries
101 countries (74 of which are developing) still have
increasing HIV incidence
Global disease burden 2013
TB (HIV-negative)
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incidence 71 million (69 million to 73 million)
prevalence 112 million (108 million to 116 million)
deaths 13 million (12 million to 14 million).
Annualised rates of change (ARC) for incidence,
prevalence, and death negative after 2000.
TB in HIV-negative individuals disproportionately occurs
in men and boys 640% of cases (636 to 643) and 647%
of deaths (608 to 703).
Global disease burden 2013
Malaria
• Cases rapidly increased 1990 to peak 232
million (143 to 387 million) in 2003
• 12 million deaths (11 to 14 million) 2004
• Since 2004, child deaths from malaria in
sub-Saharan Africa decreased by 315%
(157% to 441%).
• Outside of Africa, malaria mortality
steadily decreased since 1990.
Mortality from travel in
developing world
• 50% is cardiovascular (older travelers with
pre-existing cardiac condition), but rates
are not increased by travel
• In younger travelers injuries are main
cause of death: accidental death rate in
15-44 year olds is 2-3 times domestic rate
(MVA, scooters, drowning)
Traffic accidents worldwide
• 1.7 million deaths, major cause of death in
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males 15-45 (mostly urban pedestrians in
developing countries)
Of 309 Canadian travellers who died abroad,
25% accidents (mostly MVA)
1 death/million km in USA, 23 Sri Lanka, 44
Turkey; also high rates Egypt, Kenya, India, S.
Korea, Morocco
30 million injuries; in Ghana <10% pedestrian
injuries reported
Do not drive at night, rural areas; motorbike or
bike
Let’s begin with a 60 year old going
to Peru
• PMH: HTN, echocardiogram < 40%
ejection fraction
• What are his/her travel plans? (3 months
at agricultural research stations in
Amazonas and Madre de Dios regions,
then archaelogical dig at high altitude)
• Review CDC website cdc.gov
• For the 6 basic planning tasks (slide 2)
identify risks and prescribe
60 year old visiting Peru: Plan
• Update childhood vaccinations
• Check for egg allergy if plan MMR, influenza,
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Yellow Fever vaccines
GI risk: cholera? typhoid? Bacterial diarrhea?
Hepatitis? (Twinrix) Helminths?
Yellow Fever?
Malaria risks?
High altitude sickness risks? (he/she is going to
Cuzco 3,500 meters rapidly by plane, no slow
ascent; risks begin above 2,400 meters)
PE from air travel to Peru (5/million?)
Acute Mountain Sickness, HACE, HAPE
• Acute Mountain Sickness: 22% adults
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ascending to 7000-9000 feet; 42% to 10,000;
75% to 15,000
High Altitude Cerebral Edema: brain edema
and increased intracranial pressure > Ataxia,
confusion, disorientation, irrationality, lethargy,
severe nausea and vomiting. Time to coma < 12
hours.
High Altitude Pulmonary Edema: hypoxia
causes increased PA pressure and fluid leaks,
and a low hypoxic ventilatory response permits
extreme hypoxemia, especially when sleeping
60 year old visiting Peru: CDC lists these risks
• At the country level CDC usually lists all risks
and you need to be cautious and use other
sources to assess relative risk
• Also you need to know if risks for travelers differ
from locals with prolonged exposure
1. Dengue fever (avoid daytime bites from Aedes
aegyptii) Northern coastal and lowland urban
areas. Peru not listed as dengue epidemic area
2. Malaria in certain regions
3. Yellow Fever. CDC recommends vaccination.
60 year old visiting Peru: CDC lists these risks
4. Filariasis (daytime bites from urban Culex fatigans and
rural Anopheles mosquitoes transmitting Wucheria
bancroftii) However, need chronic exposure to develop
disease.
5. American trypanosomiasis (Reduviid (assassin) bug feces
on skin transmitting American trypanosomiasis =
Chagas’ disease). However, need chronic exposure to
develop disease. No cases in returning travelers
6. Bartonellosis (Oroya fever) on western slopes of Andes
up to 3000 m. Very rare
7. Louseborne typhus in mountainous areas of Peru. Very
rare.
Prevention of Acute Mountain Sickness
Kayser B. High Altitude Medicine and Biology 2012;13(2)
Acetazolamide
N RCTs
Relative risk
95%CI
250 mg/day
5
0.55
0.42, 0.74
500 mg/day
14
0.50
0.40, 0.63
750 mg/day
6
0.45
0.34, 0.61
Acetazolamide
NNT to prevent AMS if
climbing (AMS rate in
controls 34%)
NNT to prevent AMS
if transport then
climbing (AMS rate in
controls 61%)
250 mg/day
6.5
3.7
500 mg/day
5.9
3.3
750 mg/day
5.3
3.0
28 year old veterinarian, visiting Malawi,
South Africa, advising for WHO
• PMH: LMP 6 weeks ago, rising ΒHcG titres,
planning to be in Africa during 1st and 2nd
trimesters
• Risks to pregnancy?
• Malaria risks?
• GI risks?
• Rabies risks?
Vaccines in pregnancy
• All classes of maternal IgG transported
across placenta, mostly in 3rd trimester
• maternal IgG has half life of 3-4 weeks in
infant, waning after 6-12 months of life.
• Strong evidence of benefits of vaccines
Canadian Immunization Guide
(2013) Recommended in pregnancy
Influenza inactivated vaccine
► High priority as increased risk of influenzarelated morbidity & adverse neonatal outcomes.
► No adverse events after H1N1 vaccine in
100,000 pregnant women in Canada and
500,000 in Europe.
►Pregnant women have 4 x hospitalisation rate
for influenza compared to non-pregnant due to
increased CVS volume, HR and O2
consumption).
► Avoid live vaccines, e.g. nasal
Canadian Immunization Guide (2013)
Recommended in pregnancy
Hepatitis B
► Test all pregnant women for HBsAg
► If no markers of Hep B infection and at
high risk of Hep B during pregnancy, give
complete series
Canadian Immunization Guide (2013) May
be indicated in in pregnancy
• Hepatitis A, if travel to endemic area, as
can cause severe disease in pregnancy.
No RCTs in pregnancy. No theoretical
reason to suspect increased risk.
• Td. No increased adverse events
• Tdap. (acellular pertussis) If have not
received as adult, give post-partum
• IPV (inactivated polio). May give if at
increased risk of wild polio virus. Limited
data.
Canadian Immunization Guide (2013) May
be indicated in in pregnancy
• Pneumococcal. Review says is safe. Give if at
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high risk of invasive pneumococcal disease. To
improve antibody response can given Pneu-C-13
vaccine then Pneu-P-23 8 weeks later. Cochrane
review found insufficient evidence for protection of
infant as an indication for maternal vaccination
Meningococcal. Not studied in pregnancy.
Consider if high risk.
Rabies. If exposed, give post-exposure prophylaxis
Cholera & Japanese encephalitis vaccines not
studied in pregnancy. Consider inactivated
parenteral typhoid vaccine in high risk situations
Your 28 year old patient going to Malaŵi
• Assess risks using the 6 tasks on slide 2
• Provide vaccination advice
Malaria life cycle
• Hepatic stage: Sporozoites enter liver cells. Each
P. falciparum sporozoite asexually reproduces
30,000 merozoites; each P. vivax 10,000
• Erythrocytic stage: Hepatocytes burst and release
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merozoites into blood stream. Ring form matures
and asexually reproduces 6-32 merozoites, which
then invade other RBCs
After 2 weeks some merozoites develop into
gametocytes. If female mosquito bites a human
and ingests them the gametocytes develop in her
gut and 10 days later sporozoites can be injected
into another human, the obligate host.
Malaria
• Incubation: for Plasmodium falciparum: hepatic
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stage (5-7 days) from bite to symptoms 8-25 (avg
12 days); erythrocytic stage (2 days)
Partial immunity from long-term residence is
against erythrocytic stages and diminishes within
6-12 months of leaving endemic area
Clinical presentation: (clinical diagnosis is
inaccurate as malaria is a great imitator; must do
thick and thin films)
Prodrome of tiredness, malaise and aching in the
back, joints and abdomen, anorexia and nausea
and vomiting. Tender splenomegaly. Conjunctivae
suffused. Patient febrile for 2-3 hours before
paroxysm.
Prevention of malaria
• Bednets & clothes impregnated with pyrethroids.
• Cochrane review by Gamble 2007 found for 4
RCTs of treated nets vs. no nets relative risks:
RR
95%CI
►placental malaria
0.79 0.66 to 0.90
►low birth weight
0.77 0.61 to 0.98
►miscarriages/stillbirths 0.67 0.47 to 0.97
• Avoid going out at night, wear long sleeves and
long trousers (80% of bites on ankles)
• Compliance with medication
Bednets (average use 42%) +
chemoprevention, Uganda, 0-24 month olds
Bigira P. et al. Protective Efficacy and Safety of Three Antimalarial Regimens for the Prevention of Malaria in Young Ugandan Children: A
Randomized Controlled Trial. PLoS Med 11(8): e1001689. doi:10.1371/journal.pmed.1001689.
Intervention
No of episodes of malaria
per infant per year
Control
6.95
monthly sulfadoxine-pyrimethamine
6.73
Daily trimethoprimsulfamethoxazole
5.21
monthly dihydroartemisininpiperaquine (Protective efficacy 58% (95%
CI 45%–67%; p = 0.001)
3.02
Malaria prevention: Domestic spraying
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13 heterogeneous studies
Relative risk for reducing malaria prevalence
0.38 (95% CI 0.31 to 0.46)
More effective if:
► high initial prevalence
► multiple rounds of spraying
► DDT
► regions with a combination of Plasmodium
falciparum and P. vivax malaria.
Kim D, et al. Reduction of malaria prevalence by indoor residual spraying: a meta-regression analysis.
Am J Trop Medicine Hyg 2012;87(1):117-24.
Chemoprophylaxis of malaria
• Causal prophylaxis: atovaquone and
primaquine act on exo-erythrocytic cycle
in liver
• Schizonticides: atovaquone, mefloquine,
chloroquine, doxycycline, proguanil act on
intra-erythrocytic parasites
• Terminal prophyaxis: Primaquine acts
on latent hypnozoites in liver to prevent
relapses in P.Ovale and P. vivax
Chemoprophylaxis
Medication
Adult dose
Regimen
Begin
before
exposure
End after
exposure
Atovaquoneproguanil
250/100mg
Daily
1 day
7 days
Mefloquine
250mg
Weekly
1-3 weeks
4 weeks
Doxycycline
100mg
Daily
1-2 days
4 weeks
Primaquine *
30mg (base)
Daily
1 day
3-7 days
*G6PD testing mandatory
Chemoprophylaxis of malaria: Mefloquine
62.5 mg weekly children 3 months – 5 years
125 mg weekly 6-8 years
187.5 mg 9-14 years
• 50% resistance Thai-Cambodian and ThaiBurmese borders
• Questionnaires about adverse events:
1:6000 British soldiers, 1:10,000 European
and 1:20,000 Canadian travellers
Mefloquine
• Side-effects: Headache, dizziness,
confusion, vertigo, seizures, peripheral
neuropathy, insomnia, dreams, anxiety,
psychosis
• Only drug approved for 2nd & 3rd
trimesters of pregnancy in chloroquineresistant areas. Limited data suggest safe
for 1st trimester
• Do not prescribe for persons with major
psychiatric disorders even if currently
stable
Chemoprophylaxis of malaria:
Doxycycline
• Do not use children < 8 years and
pregnant or lactating women
• 95% effective against P. falciparum
• Adverse effects; abdominal pain, nausea,
vomiting, diarrhea, photosensitivity (~
20%?), vaginal candidiasis (2.8%)
• Advantages: preventive for leptospirosis,
rickettsial disases and traveler’s diarrhea
Chemoprophylaxis of malaria: Doxycycline
Atovaquone-Proguanil (Malarone)
• Acts on both liver and erythrocyte stages
• Efficacy 95-100%
• Adverse effects: Lowest withdrawal rate
(2%) for adverse effects compared to
mefloquine and doxycyline
• Can be used in children > 5 kg
• Do not use if creatinine clearance
<30mL/min
Chemoprophylaxis of malaria: Primaquine
• Intended for radical cure of P. vivax
• Efficacy against P. falciparum Kenya 85%,
Irian Jaya (NE Indonesoia) 94.5%,
Colombian soldiers 94%
• Must test for G6PD deficiency; otherwise ˂
2% adverse effects
Pyrimethamine-dapsone
(Malaquine)
• PO 1 tablet = 12.5 mg pyrimethamine +
100 mg dapsone
¼ tablet weekly children 1-5 years
1/2 tablet weekly children 6-11 years
1 tablet weekly children >11 years and
adults
Plasmodium falciparum malaria Treatment:
Artemisinin combination therapy
• Recommended 1st line therapy worldwide but decreased
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artemisinin susceptibility (slower parasite clearance time)
reported in SE Asia.
27 clinical trials vs. comparators 1999-2009, intention-totreat analysis
15,017 (77% children < 6 years of age) patients treated
for uncomplicated P. falciparum malaria, 44 sites in subSaharan Africa
Average parasite load before treatment = 27,125/muL
Results:
Persistent parasitaemia Day 2 8.6%, 1.5% Day 3
Parasite clearance 31 hours (p=0.001 all comparisons)
Zwang J, et al. Plasmodium falciparum clearance in clinical studies of artesunate-amodiaquine and
comparator treatments in sub-Saharan Africa, 1999-2009. Malaria Journal 2014;13:114.
Malaria
• “Cold stage” of rigors (15-60 minutes):
► sudden feeling of cold and apprehension
► pulse rapid and low volume
► mild shivering turns into violent teeth
chattering and shaking of the whole body.
Patients try to cover themselves with
bedclothes
► core temperature is high but peripheral
vasoconstriction with skin cold and goosepimpled
Malaria
• “Hot stage” up to 104F (2-6 hours): (“Ague attack”
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resembles the “endotoxin reactions” of lobar pneumonia
or pyelonephritis)
► restless, unbearably hot, throws off all the
bedclothes, excited
► severe throbbing headache, palpitations,
tachypnea, postural syncope
► may vomit
► may become confused, convulse
► skin dry flushed and burning
► splenomegaly may be detected first the first time in
this stage
“sweating stage” (2-4 hours): temperature returns to
normal and patient sleeps
WHO criteria for Severe malaria
Identify patients with severe malaria for
special treatment with one or more of:
• Cerebral malaria
• Respiratory distress
• Severe normocytic anemia
• Renal failure
• Hyperparasitemia
• Pulmonary edema
• Hypoglycemia
• Circulatory collapse
• Spontaneous bleeding
• Generalised convulsions
Cerebral malaria (encephalitis)
• impairment of consciousness or
generalised convulsion followed by coma
• high fever can cause irritability,
obtundation, psychosis, and febrile
convulsions (children) so urgently treat
impairment of consciousness
• may thrash or lie immobile with eyes open
or have dysconjugate gaze
Cerebral malaria (encephalitis)
• brainstem signs:
► doll’s eyes (in children)
► may be decorticate (flexion of elbows
and wrists, supination of the arm)
suggests severe bilateral damage to the
midbrain
► may be decerebrate (extension of
wrists and elbows with pronation of the
arms suggests damage to the midbrain or
the caudal diencephalon)
Cerebral malaria (encephalitis)
• children may have subtle convulsions
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(nystagmoid eye movements, salivation, shallow
irregular respirations, clonic movements of an
eyebrow, finger, toe or mouth)
with excellent care mortality is 15-20%; death
within hours for children
respiratory distress (compensation for metabolic
acidosis), laboured breathing, intercostal
recession, nasal flaring, accessory muscles of
respiration)
Malarial Anemia (defined as < 5 g/dl):
• children with severe anemia usually have
acidosis (deep Kussmaul breathing);
• malarial anemia kills as many children as
cerebral malaria (mortality = 5-15%;
mortality from acidosis = 24%; mortality
from severe anemia + acidosis = 35%)
• also common in pregnant women
Jaundice and hypoglycemia in malaria
• Jaundice
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1/3 of adults; associated with cerebral malaria, acute
pulmonary edema
Hypoglycemia
Anxiety, breathlessness, lightheadedness, tachycardia,
impairment of consciousness, seizures, abnormal
posturing can be misinterpreted as due only to the
malaria
Pregnant women:
► cell-mediated immunity is altered to favour survival of
the fetus (more so in primigravidae), the placenta is
heavily parasitized (the parasites adhere to chondriotin
sulphate on the syncytiotrophoblast) The peripheral
blood film may show no parasites
►risk is greatest for primigravidae in areas of unstable
malaria
Provide advice to your 28 year old patient
and her two children aged 2 and 4 going to
Malaŵi
• How to reduce the risk of malaria
• The symptoms of malaria
• Prescribe to reduce the risk of malaria
Large family going to a tropical country for
wedding. They are worried about getting
traveler’s diarrhea
• Advise on risks, precautions and
treatment
• Risk of travellers’ diarrhea = 40% in high
risk countries of Latin America, Africa and
S. Asia (unchanged over past 50 years)
Diarrhea in children in Asia and Africa (GEMS
study, unpublished data first 2 years)
EPEC = : E coli enteropathogenic; ETEC = E coli enterotoxigenic.
Erlich P et al. Infections intestinales aiguës: vaccins actuels et futurs. Presse Med 2013;42:93-101.
Age 0-11 months
12-23 months
24-59 months
1st
Rotavirus
Rotavirus/Shigella
Shigella
2nd
Cryptosporidium
Cryptosporidium/
Rotavirus
Rotavirus
3rd
EPEC
ETEC
ETEC/Vibrio cholerae
4rd
ETEC/Campylobacter
jejuni
Shigella/Vibrio
cholerae
Vibrio Cholerae/
campylobacter jejuni
5th
Shigella
Norovirus/Entamoeba
histolytica
Norovirus
Handwashing worldwide
Freeman MC. Hygiene and health: systematic review of handwashing practice worldwide
and update on health. Trop Med Int Health 2013 19(8):906-916
• 42 studies; 19% of world population wash
hands with soap and water after touching
excreta
Studies
RR diarrheal disease
after handwashing
95%CI
All studies
0.60
0.53, 0.68
Excluding unblinded
studies
0.77
0.32, 1.86
TRAVELERS’ DIARRHEA: PREVENTION
1. Hand washing: 30 seconds with soap
2. Boil, cook or peel, eat when piping hot.
Avoid salads, ice cubes, food vendors,
cans cooled in water, shellfish,
undercooked seafood
► However, most travelers commit a food
indiscretion within the first 72 hours due to
being tempted by the sight of snacks, pre-paid
buffets and the unavailability of hot food
►Studies of US naval ships abroad showed the
more indiscretions ashore (salads, ice in drinks,
food vendors … ) the more were on sick parade
the next day with diarrhea.
TRAVELERS’ DIARRHEA: PREVENTION
3. Take a micropore filter. Cryptosporidium can
pass through a 1 micropore filter, so needs
subsequent halogenation
4. Chlorine is less effective in acid or alkaline or
cool water, so lengthen contact time (2 hours
for Giardia, 10 minutes for bacteria).
Resistance to halogenation increases from
bacteria, viruses, protozoan cysts, bacterial
spores to parasitic ova and larvae
5. Potassium Permanganate to wash fruit and
veg
6. Kettle to boil water (boiling for 1 minute kills
even Cryptosporidium)
TRAVELERS’ DIARRHEA: PREVENTION
7. Pepto-bismol: 2 tablets qid reduces risk by 65%
(children > 3 years: 1 tablet qid)
► Indications: Prophylactic Pepto-bismol for a
short trip: Consider if immunocompromised, HIV+,
severe inflammatory bowel disease, renal failure, poorly
controlled insulin dependent diabetes. Or of you are a
conference speaker or a musical performer who must be
well at a specific time.
► Contraindications:
(a) 2 tablets have the salicylate content of one
325 mg aspirin, so contraindicated if allergy to aspirin,
bleeding disorder, taking warfarin, history of GI bleed.
(b) If taking doxycycline: Pepto-bismol inhibits
absorption of doxycycline (an important anti-malarial).
TRAVELERS’ DIARRHEA: PREVENTION
8. Dukoral cholera vaccine: 3 RCTs show provides no
cross protection against ETEC.
9. Antibiotics: considering side-effects, best to use
antibiotics for treatment in the case of diarrhea rather
than prophylaxis
10. Rotavirus vaccines:
• Rotarix (contains G1 serotype and P8), two doses at 2
and 4 months, 80% to 96 % effective in industrialised
countries, 50% to 70% in developing countries
• Rotateq (contains G1, G2, G3, G4 serotypes and P)
three doses at 2, 4, and 6 months. 98% effective in in
industrialised countries, 51% to 64 % in Asia and Africa.
Erlich P et al. Infections intestinales aiguës : vaccins actuels et futurs. Presse Med 2013;42:93101.
Inactivated cholera vaccine: Dukoral
Erlich P et al. Infections intestinales aiguës : vaccins actuels et futurs. Presse Med
2013;42:93-101.
• 67% effective against O1, not effective
against O139 and other vibrios
• whole cell V. Cholerae O1 Inawa and
Ogaba strains + recombinant B subunit of
cholera toxin
• 2 doses 1-6 weeks apart, lasts 2 years (for
children 2-5 years 3 doses, lasts months)
Typhoid vaccines
Route
Dosing
Minimum age
Typhoid O live
attenuated (oral)
(Vivotif (Berna)
Oral
1 Capsule days 1,3,5,7 in 4 oz
warm water. 1 hour before or 2
hours after meal. Swallow not
chew. Population of antibodysecreting cells peaks between 7 to
10 days after first dose. Each
dose replicates 3-5 times then
lyses over 48 hours. Maximum
interval between doses must be <
72 hours and all capsules taken
within 10 days.
3 years
Typhoid I
(Typhim Vi,
Typherix)
IM
1
5 years
Vaccines for rotavirus, cholera, ETEC,
shigella
DAS JK. Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC
and rotavirus. BMC Public Health 2013;13 Suppl 3
• 24 studies
• Rotavirus 74% mortality reduction
• Cholera incidence 52% reduction
• Mortality reductions for cholera, ETEC &
shigella in children < 5 years: insufficient
evidence
Your family going to a tropical
country
• Advise them how to minimise risks of
diarrhea
DIAGNOSIS of TRAVELLER’s DIARRHEA
• On a 3 week trip the indiscreet traveler is
most likely to get diarrhea in the first
week, and will need guidance about selftreatment.
• >60% is bacterial: Most common is E.
Coli, then Shigella, Salmonella,
Campylobacter (undercooked poultry)
• Attack rate remains same in long-term
travelers and expatriates for several years
5 clinical syndromes of Traveller’s Diarrhea:
1. Watery diarrhea (60%)
• Mostly enterotoxigenic E. Coli; also Salmonella,
Campylobacter, Vibrio parahemolyticus and
vulnificus (seafood).
• Parasites: Giardia, Cryptosporidium, Cyclospora &
Isospora
• 10% viruses (norovirus, rotavirus)
• Cause usually not identified
• Symptoms last 3-5 days and range from several
watery stools/day to more explosive profuse but
non-bloody diarrhea. Some may have nausea,
cramps, vomiting, mild fever.
5 Clinical syndromes of Traveller’s Diarrhea
2. Dysentery (15%)
• Usually Shigella. Other causes: Salmonella,
Campylobacter, Yersinia, E. Coli serotype
0157:H7, more rarely non-colera vibrios and
Aeromonas
• Symptoms: small volume stools with mucous,
•
high fever, abdominal pain and tenderness,
prostration, feeling of incomplete evacuation.
Blood seen in only 50% of patients.
Treatment: Treat all bloody diarrhea with
antibiotics; fluids to prevent dehydration.
5 Clinical syndromes of Traveller’s Diarrhea
3. Acute gastroenteritis
• Vomiting, little diarrhea
• Staph aureus Incubation 2-7 hours,
recovery in 12-18 hours
• C. perfringens Incubation 8-14 hours
• Bacillus cereus produces two toxins. One
toxin produces symptoms like Staph aureus
and the other like C. perfringens
•
4. Typhoid fever
Febrile illness and systemic toxicity. May or
may not have diarrhea.
5 Clinical syndromes of Traveller’s Diarrhea
5. Chronic diarrhea, lasting > 14 days (3-5%)
• Usually Giardia or Campylobacter.
Also enteroaggregative E. Coli,
Aeromonas, Plesiomonas. In many
cases tests are negative and is attributed
to postinfectious lactose intolerance and
IBS.
• Symptoms: vague abdominal pain,
bloating, nausea, weight loss, low grade
fever.
Diagnosing the type of diarrhea
• Check out your family’s diarrhea
symptoms and diagnose
Treatment of Diarrhea while Travelling
1. Oral rehydration: Severe: WHO per L purified water
• sodium chloride 3.5 g
• Potassium chloride 1.5 g
• Sodium bicardonate 2.5 g
• Glucose 20g
• CeraLyte is rice based. If not available, make your own
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with 1 teaspoon salt and 2 tablespoons sugar or honey
in 1 L water. Continue to drink even if vomiting.
Moderate dehydration: drink 3 L water/day, add soup
+ salty crackers, avoid dairy
Mild: infants - continue usual breast feeding/formula/
fluids
Treatment of Diarrhea while Travelling
2. Loperamide: 2 mg. capsules: two STAT then 1
capsule for every loose stool, max 16 mg/day
reduces frequency of stools and duration of
illness by 80% due to anti-motility and antisecretory actions.
• Young children are more susceptible to side
effects: drowsiness, vomiting and paralytic ileus.
Not approved for children < 2 years.
3. Pepto-bismol (do not exceed 16 tablets/day):
reduces diarrhea by 50% because of antiperistaltic and anti-secretary effects.
Treatment of Diarrhea while Travelling
• Need calories to repair gut cells so eat
• Steamed or baked fish, chicken,
vegetables, toast, bananas applesauce,
soup, soft drinks, dilute fruit juice, saltine
crackers. Avoid dairy.
Treatment of Diarrhea while Travelling
• 4. Antibiotics: If copious or bloody stools, or fever.
► ciprofloxacin 750 mg once or 500 mg bid. If unwell
continue for a total of three days.
HOWEVER: Resistance: 90% in Thailand, 50% Nepal,
40% Egypt
► Alternatives:
levofloxacin 500 mg once or 500 mg daily x 3 days
azithromycin 1000 mg once or 500 mg daily for 3
days (also effective against Shigella, Salmonella, E.
Coli, Campylobacter and typhoid fever. In Thailand
more effective against Campylobacter than
ciprofloxacin.
► metronidazole 250 mg tid x 5-7 days if you consider
you may have Giardia and cannot get medical help.
Do not use with alcohol.
Treatment of Diarrhea while Travelling
• Reseve antibiotics for invasive enterocolitis
with fever and dysentery, profuse diarrhea
with more than three liquid stools within
12 hours. Duration of antibiotherapy 1 to
5 days.
• Treat pregnant women with ciprofloxacin,
best alternative is azithromycin.
• Consider whether the rapid diarrhea is
limiting antibiotic absorption.
•
Marchou B. Diarrhées du voyageur: épidémiologie, prévention et conduite à tenir. Presse Med.
2013; 42:76–81.
Problems with fluoroquinolones
• High resistance to fluoroquinolones in MRSA, P.
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aeruginosa, anaerobes, and pathogens isolated from
ICUs
Increasing resistance in community-acquired E.coli and
N. gonorrhea.
10-30% of community acquired respiratory tract
infections (CARTIs), H. influenzae and S. pneumoniae
harbour 1st step mutations in quinolone resistance
determining region. These mutants pass susceptibility
testing unnoticed and are primed to acquire high-level
fluoroquinolone resistance rapidly, especially in elderly
and immunocompromised patients
Dalhoff A. Global Fluoroquinolone Resistance Epidemiology and Implications for
Clinical Use. Interdisciplinary Perspectives on Infectious Diseases 2012; Article ID
976273, 37 pages doi:10.1155/2012/976273
Problems with fluoroquinolones
• 1/3 to 2/3 of Enterobacteriaceae producing extended
spectrum β-lactamases (ESBL) are also fluoroquinolone
resistant, and others are primed to acquire high-level
resistance during treatment.
• Fluoroquinolones select for methicillin resistance in
staphylococci, limiting use in skin infections
• Co-selection of fluoroquinolone resistance by βlactams or aminoglycosides, and vice versa β-lactam- or
aminoglycoside resistance by fluoroquinolones
demonstrates that chemically unrelated drug classes
select for drug resistant mutants and even multidrug
resistant strains
Antiemetics for diarrhea
DAS JK The effect of antiemetics in childhood gastroenteritis. BMC Public Health 2013
Suppl 3
• 750,000 children < 5 die annually from
gastroenteritis
Medication
RR vomiting
95%CI
Rectal dimenhydrinate
0.60
0.44, 0.82
IV ondansetron
0.50
0.24, 1.04
Oral ondansetron
0.35
0.26, 0.46
IV metoclopramide
0.80
0.50, 1.28
Total
0.46
0.35, 0.61
Please treat your family’s
diarrhea
• Discuss with your family their options and
prescribe
Ebola
Schieffelin JS, et al. Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone. NEJM
October 29, 2014DOI: 10.1056/NEJMoa1411680
• 10,100 cases reported in Guinea, Sierra Leone, Liberia, Senegal,
Nigeria, and Mali to October 25, 2014
• Kenema Government Hospital, Sierra Leone: 213 patients
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symptoms of Lassa hemorrhagic fever or Ebola (106 Ebola)
Incubation: 6-12 days, symptoms to hospitalisation 6 days
Symptoms: fever (89%), headache (80%), weakness (66%),
dizziness (60%), diarrhea (51%), abdominal pain (40%), sore throat
(34%), vomiting (34%), conjunctivitis (31%)
Rx: Fluids, 55% antimalarials, 93% antibacterials (ceftriaxone)
Prognostic factors associated with death: > 45 years, 38°C,
weakness, dizziness, diarrhea on presentation
Death: 33% if < 100,000 Ebola copies/ml of serum; 94% if >10
million copies/ml (P=0.003)
Yellow Fever
• Marked underreporting of cases
• 45 endemic countries in Africa and Latin America (900
million)
• < 550 million doses of yellow fever vaccine given
worldwide. Planned vaccination of additional 174 million
in Africa and Latin America 2011-2020 estimated will
avoid 34,849 deaths
Brighton Collaboration definitions of serious adverse
events after yellow fever vaccination:
• Viscerotropic disease: “Multiple organ system
dysfunction following vaccination, with spectrum from
relatively mild multi-system disease to severe multiple
system organ failure and death involving hypotension,
hemorrhage, and acute renal and respiratory failure.”
Yellow Fever Vaccine is very safe
• Encephalitis: “demonstration of acute inflammation of
•
•
•
central nervous system parenchyma (± meninges) by
histopathology.”
Anaphylaxis: “an acute hypersensitivity reaction with
multi-organ-system involvement that can present as, or
rapidly progress to, a severe life-threatening reaction.”1
Published cases which meet Brighton
Collaboration criteria: neurologic criteria (1 death);
42 Viscerotropic Disease criteria (24 deaths) (includes 2
with both viscerotropic and neurologic criteria); 33
Anaphylaxis; 2 Wild Virus
Published cases with insufficient detail to be
assessed with Brighton Collaboration criteria: 108
additional neurological cases, 58 viscerotropic cases
Yellow Fever
• Unvaccinated traveler: the risk of disease
during endemic periods = 1/267; death = 1/1,333
in an endemic African country (levels 10 times
lower in South America)
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•
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•
•
•
Thomas RE, Lorenzetti D, Spragins W, Jackson D, Williamson T. A systematic review of yellow fever vaccineassociated serious adverse events. World Health Organization. 1 December 2010
Thomas RE, et al. Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious
adverse events: Systematic review. Vaccine. 2011; 29(28):4544-4555.
Thomas RE, et al. Reporting Rates of Yellow Fever Vaccine 17D or 17DD-Associated Serious Adverse Events in
Pharmacovigilance Data Bases: Systematic Review. Current Drug Safety 2011;6(3): 145-154.
Thomas RE, et al. The Safety of Yellow Fever Vaccine 17D or 17DD in Children, Pregnant Women, HIV+
Individuals, and Older Persons: Systematic Review. J. Trop. Med. Hyg. 2012;86(2):359–372.
doi:10.4269/ajtmh.2012.11-0525.
Thomas RE, et al.Mortality and Morbidity Among Military Personnel and Civilians During the 1930s and World
War II From Transmission of Hepatitis During Yellow Fever Vaccination: Systematic Review. Am J Pub Health.
2013;103(3):e16-29. doi:10.2105/AJPH.2012. 301158)
Dengue
• Flavivirus with 4 serotypes DEN-1, DEN-2, DEN•
•
•
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3, DEN-4. Infection confers long-term immunity
only to that serotype
Transmitted by Aedes aegyptii and Aedes
albopticus, worldwide in tropics & subtropics
2.5 billion at risk
100 million/year. Most common Asia (esp
Thailand). Also Caribbean, Pacific islands,
Americas, 19,000 deaths/year
No vaccine or medications available
Dengue Control
• Due to impure water supply many houses in
•
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developing countries have open water containers.
Mosquitoes like to breed in water containers in or
near houses
Integrated vector management most effective to
reduce number of immature parasites per water
container (relative effectiveness 0.12 (95% CI
0.02 to 0.62) [lower numbers show more effective]
Best to provide pure piped water
Erlanger TE, et al. Effect of dengue vector control interventions on entomological parameters in developing countries:
a systematic review and meta-analysis. Medical and Veterinary Entomology (2008) 22, 203–221
• No evidence peridomestic spraying effective.
Esu E, et al.
Effectiveness of peridomestic space spraying with insecticide on dengue transmission; systematic review. Tropical
Medicine & International Health 2010;15(5):619-31.
Dengue Hemorrhagic fever (DHF) and shock
syndrome (DSS)
• 250,000/year
• DHF grades 1 and 2 = plasma leakage
• DSS grades 3 and 4 = life-threatening shock (mortality
•
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50x no shock)
Sudden onset high fever (5-7 days), headache, fatigue,
severe myalgia, arthralgias, 50% maculopapular rash
Platelets < 100,000/mm3
Capillary leakage: ascites, pleural effusion. US
demonstrates 10x more cases than clinical exam
Tourniquet test for capillary fragility: ≥ 20
petechiae/inch2 after Bp cuff deflated
Mortality 10-20% but 0.2% in experienced hospitals;
Decreased mortality in Thailand over past 40 years
Dengue Shock Syndrome
•
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DSS more likely if:
serotype 2 in Thailand
younger (children, immature immune system)
female gender (differences in seeking care?)
neurological signs
nausea/vomiting, abdominal pain, gastrointestinal
bleeding, hepatomegaly, increased ALT or AST
Increased hemoconcentration, ascites, pleural effusion,
hypoalbuminemia, hypoproteinemia,, thrombocytopenia,
coagulation dysregulation
secondary infection
Huy NT, et al. Factors Associated with Dengue Shock Syndrome A Systematic Review and Meta-Analysis. PLoS
Negl Trop Dis 7(9): e2412. doi:10.1371/journal.pntd.0002412.
Dengue diagnosis
• immunochromatographic test (ICT)
manufactured by Panbio. (Results in < 60
minutes)
• Sensitivity
0.45 to 1.0
• Specificity
0.57 to 1.0
• Diagnostic odds ratio
4.5 to 1287
• Positive likelihood ratio 2.3 to 59
• Negative likelihood ratio 0.01 to 0.56
•
Blacksell SD, et al. A systematic review and meta-analysis of the diagnostic accuracy of rapid
immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans
Royal Soc Trop Med Hyg 2006;100(8):775-84.
Schistosoma haematobium (trematode)
• Africa and Egypt
• A human urinates eggs into fresh water, snails
ingest eggs, replicate in snail, released into fresh
water as cercariae, which then penetrate human
skin (swimmer’s itch)
• Cercariae change to schistomules and migrate to
lungs, causing Katayama syndrome 2-8 weeks
after exposure
► high fever, cough, SOB, wheezing, headache,
splenomegaly, urticarial rash
• Flukes then migrate to genitourinary venules
and cause granulomas and calcification
S. mansoni and S. japonicum
• S. mansoni Africa and Brazil; S. japonicum
Asia (Laos)
• Humans excrete eggs in stool, and
another human ingests them by mouth
• Final destination of schistosmules is
mesenteric venules, causing granulomas
and calcification
Resources
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www.cdc.gov go to travelers, then destinations (best on line source)
Canadian Immunization Guide, 8th edition 2013. www.phac-aspc.gc.ca
or www.naci.gc.ca
Public Health Agency of Canada http://www.travelhealth.gc.ca Includes
official EBM statements from CATMAT (Committee to Advise on Tropical
Medicine and Travel), which are a bit wordy
World Health Organisation www.who.int/ith
Schwartz E. Tropical Diseases in Travelers. Oxford: Wiley-Blackwell, 2009.
(good for specific diseases).
Rose SR, Keystone JS. International Travel Health Guide. (Philadelphia:
Mosby. (For patients, updated annually, chapter on each country, patients
can buy this).
Jong EC, McMullen R. (Eds.)The Travel & Tropical Medicine Manual. (4TH
ed.) Philadelphia: W.B. Saunders, 2008 (best short book).
Keystone JS (ed.). Travel Medicine (2nd ed). Mosby Elsevier, 2011. Also
online
JeffreyHC, Leach RM. Atlas of Medical Helminthology and Protozoology.
Edinburgh & New York: Churchill Livingstone. (Outstanding, comprehensive,
colour plates).