Travel and Tropical Medicine

1
Travel and Tropical Medicine

• Roger Thomas, MD, Ph.D, CCFP. MRCGP

2
RISKS of Travel to Developing Countries

• Diarrhea 34
• (ETEC causes 30-60 of these cases)
• Respiratory 26
• Skin disorder 8
• Acute mountain sickness 6
• Accident and injury 5
• Illness with fever 3

3
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)

4
Traffic accidents worldwide 2004

• 1.7 million deaths, single major cause of death
  in males 15-45
• gt 750 US citizens die, gt 25,000 injured annually
  on foreign roads, some are permanent residents
  abroad, (implying gt 75 Canadians and gt 2,500
  accidents)
• 30 million injuries
• Egypt, Kenya, India, S. Korea, Turkey, Morocco
  most dangerous
• Advise do not drive at night, especially rural
  areas do not drive motorbike or bike

5
OUTLINE

• Take a history
• past medical history, medications,
  vaccinations
• planned travel
• unplanned excursions and sports
• Bring childhood vaccinations up to date (MMR,
  polio, tetanus)
• Vaccinations and medications needed for trip
• Ask their understanding of risks your advice
• Print off CDC data and have them read and
  underline it
• Malaria prevention diagnosis treatment
• Travellers diarrhea prevention diagnosis
  treatment
• Helminths 9. Other

6
Lets begin with a 60 year old going to Peru and
Ecuador

• PMH HTN, hyperlipidemia, well controlled never
  smoker
• What are his/her travel plans?
• Review CDC website cdc.gov
• Identify risks and prescribe

7
60 year old visiting Peru and Ecuador

• Update childhood vaccinations
• Check for egg allergy if plan MMR, influenza,
  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
  3,600 meters rapidly by plane, no slow ascent
  risks begin above 2,400 meters)
• PE from air travel (5/million)

8
60 year old visiting Peru and Ecuador Other
risks?

• Helminths such as Amebiasis, echinococcus
• American trypanosomiasis (Chagas disease)
• Cutaneous and mucocutaneous Leishmaniasis
• Paragonimiasis (oriental lung fluke)
• Brucellosis
• Bartonellosis (Oroya fever) on western slopes of
  Andes up to 3000 m
• Louseborne typhus in mountainous areas of Peru

9
28 year old veterinarian, visiting Malawi, South
Africa, advising for WHO

• PMH LMP 6 weeks ago, rising ?HcG titres,
  planning to be in Africa during 1st and 2nd
  trimesters
• GI risks?
• Malaria risks?
• Rabies risks?
• Risks to pregnancy?

10
Live-attenuated vaccines in pregnancy

• MMR and varicella are live-attenuated and
  contrandicated in pregnancy because of
  theoretical risk to fetus
• However, no evidence of harm from inadvertent
  rubella vaccination
• ?226 pregnant females 1971- 1989 in US
• caused subclinical infection in 1-2 of
  fetuses,
• no evidence of congenital rubella
• ?Motherisk found no evidence of increased
  
• rate of fetal malformations in 94 women
• vaccinated with rubella 3 months before
• conception or during pregnancy

11
Live-attenuated vaccines in pregnancy

• No evidence of harm from inadvertent varicella
  vaccination
• ? in 362 women vaccinated during pregnancy, no
  cases of congenital varicella

12
Vaccines in pregnancy

• No evidence of increased risk of adverse
  reactions, teratogenic or embryotoxic effects 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

13
Canadian Immunization Guide Advice for pregnancy

• Safe
• ? Influenza (good idea as pregnant women have
  4 x hospitalisation rate for influenza compared
  to non-pregnant due to increased CVS volume, HR
  and O2 consumption)
• ? Diptheria/tetanus
• ? Polysaccharide meningococal vaccine (no
  evidence for conjugate vaccine)
• ? Salk poliomyelitis vaccine

14
Canadian Immunization Guide Advice for pregnancy

• No apparent risk, recommended in women at risk
• ? Hepatitis B
• No apparent risk, consider in high-risk
  situations
• ? Hepatitis A
• ? Pneumococcal polysaccharide
• ?Cholera (no data)
• ?Typhoid (no data)
• ?Pertussis (no data)
• ? Live Japanese encephalitis (no data)
• Contraindicated (unless high risk travel
  unavoidable)
• ? Yellow fever (6/million risk of visceral
  and 6/million risk of cerebral complications for
  all vaccinees)

15
Malaria

• Incubation for Plasmodium falciparum 7-14 days
  (up to 6 weeks)
• 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.

16
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
  goose-
• pimpled

17
Malaria

• Hot stage up to 104F (2-6 hours) (Ague
  attack 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

18
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

19
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

20
Cerebral malaria (encephalitis)

• brainstem signs
• ? dolls 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)

21
Cerebral malaria (encephalitis)

• children may have subtle convulsions (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)

22
Malarial Anemia (defined as lt 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

23
Jaundice and hypoglycemia in malaria

• Jaundice
• 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

24
Chemoprophylaxis of malaria

• Causal prophylaxis atovaquone and primaquin act
  on exo-erythrocytic cycle in liver
• Schizontocides 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

25
Chemoprophylaxis of malaria

• Mefloquine PO (Begin 1 week before departure,
  continue 4 weeks after return)
• 62.5 mg weekly children 3 months 5
• years
• 125 mg weekly 6-8 years
• 187.5 mg 9-14 years
• 250 mg weekly adults

26
Chemoprophylaxis of malaria

• Doxycycline PO 1.5mg/kg daily. Do not use
  children lt 12 years and pregnant or lactating
  women can begin 2 days before enter malarious
  area
• 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 gt11 years and
  adults

27
Prevention of malaria

• Bednets clothes impregnated with pyrethroids.
• Cochrane review by Gamble (2006) found for 4 RCTs
  of treated nets vs. no nets a reduction in
  relative risks
• RR
  95CI
• ?placental malaria 0.79 0.63 to 0.98
• ?low birth weight 0.77 0.61 to 0.98
  
• Avoid going out at night, wear long sleeves and
  long trousers (80 of bites on ankles)
• Compliance with medication

28
Treatment of Malaria

• ARTEMISINS (halve parasite clearance time
  compared to quinine, but RCTs do not show
  reduction in mortality compared to quinine)
• Uncomplicated disease artesunate or artemether
  by mouth 4mg/kg x 3 days. Give each day in
  divided doses. Artesunate suppositories are easy
  to use. Use with second drug (e.g. mefloquine) to
  prevent recrudescence)

29
Treatment of Malaria

• Severe disease
• ? Artesunate 2.4 mg/kg IV or IM then 1.2
  mg/kg IM daily.
• To make artesunate dissolve 60 g in 0.6
  ml of 5 NaHCO3,
• dilute to 5 ml with 5 dextrose and give
  IV or IM.
• ? Artemether Loading dose 3.2 mg/kg IM then
  maintenance 1.6
• mg/kg IM. Do not give artemether IV,
  only orally, by suppository
• or IM. Complete the therapy with oral
• sulfadoxine/pyrimethamine

30
Treatment of Malaria

• QUININE
• Uncomplicated disease 10m/kg quinine SALT by
  mouth three times daily x 7 days. Once parasites
  eradicated, change to tetracycline 4mg/kg PO four
  times daily OR doxycycline 3mg/kg PO once daily
• Severe disease starting dose 20mg/kg quinine
  SALT IV over 2-4 hours THEN 10mg/kg infused over
  2 hours every 8 hours until tolerates oral
  medication (sulfadxine/pyrimethamine). If given
  IM, dilute to 60mg/ml and split between sites if
  volume exceeds 5ml
• Give IV doses in 500ml of 5 glucose
  over 4 hours
• Reduce rate if cardiac arrhythmias
• Pregnant women quinine is the drug of choice.

31
Falciparum strains adjust to antibiotic pressure

• Treatment of malaria must take into account local
  sensitivity to medications and shifts in parasite
  genome due to antibiotic pressure
• Zongo (Lancet 2007) showed in children older than
  6 months in a 28 day RCT in Burkina Faso that
  risk of recurrent malaria was
• amodiaquine sulfadoxine-pyrimethamine 1.7
  artemether-holofantrine
  10.2

32
Large family going to Mexico for daughters
wedding. They are worried about getting
travellers diarrhea

• Advise on risks, precautions and treatment

33
TRAVELERS DIARRHEA PREVENTION

• Hand washing 30 seconds with soap
• Boil, cook or peel, eat when piping hot. Avoid
  salads, ice cubes, food vendors, cans cooled in
  water (probably from a stream), 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.

34
TRAVELERS DIARRHEA PREVENTION

• 3. Take a micropore filter. Cryptosporidium can
  pass through a 1 micropore filter, so needs
  subsequent halogenation
• 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
• Potassium Permanganate to wash fruit and veg
• Kettle to boil water (boiling for 1 minute kills
  even Cryptosporidium

35
TRAVELERS DIARRHEA PREVENTION

• 6. Pepto-bismol 2 tablets qid reduces risk by
  65 (children gt 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).

36
TRAVELERS DIARRHEA PREVENTION

• 7. Dukoral cholera vaccine provides 60
  cross-over protection against ETEC.
• 8. Antibiotics considering side-effects, best to
  use antibiotics for treatment in the case of
  diarrhea rather than prophylaxis

37
DIAGNOSIS of TRAVELLERs DIARRHEA

• On a 3 week trip the indiscreet traveler is most
  likely to get diarrhea in the first week, and
  will need guidance about self-treatment.
• gt60 is bacterial Most common is E. Coli, then
  Shigella, Salmonella, Campylobacter
• Attack rate remains same in long-term travelers
  and expatriates for several years

38
Diagnosis of Travellers Diarrhea by Clinical
Presentation Watery diarrhea (60)

• Mostly enterotoxigenic E. Coli also Salmonella,
  Campylobacter, Vibrios. Parasites such as
  Giardia, Cryptosporidium, Cyclospora and Isospora
  can cause watery diarrhea. 10 is viruses.
• Symptoms last 3-5 days and range from several
  watery stools per day to more explosive profuse
  but non-bloody diarrhea. Some may have nausea,
  cramps, vomiting, low grade fever.

39
Diagnosis of Travellers Diarrhea by Clinical
Presentation Dysentery (15)

• Usually Shigella. Other causes Salmonella,
  Campylobacter, Yersinia, E. Coli serotype
  0157H7, more rarely amebiasis.
• 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.

40
Diagnosis of Travellers Diarrhea by Clinical
Presentation Chronic diarrhea, lasting gt 1 month
(3-5)

• Usually Giardia or Campylobacter. 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.

41
Treatment of Diarrhea while Travelling

• 1. Oral rehydration
• Severe dehydration. WHO is glucose based,
  CeraLyte is rice based. If not available, make
  your own with 1 teaspoon salt and 2 tablespoons
  sugar or honey in 1 L water. Continue to drink
  even if vomiting.
• Moderate drink 3 L water/day, add soup salty
  crackers, avoid dairy
• Mild infants - continue usual breast
  feeding/formula/ fluids

42
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
  anti-secretory actions.
• Young children are more susceptible to side
  effects drowsiness, vomiting and paralytic
  ileus. Not approved for children lt 2 years.
• 3. Pepto-bismol (do not exceed 16 tablets/day)
  reduces diarrhea by 50 because of
  anti-peristaltic and anti-secretary effects.

43
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.
• Resistance 90 in Thailand, 50 Nepal, 40
  Egypt
• ? Alternatives
• Levaquin 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.
• ? Flagyl 250 mg tid x 5-7 days if you
  consider you may
• have Giardia and cannot get medical
  help. Do not
• use with alcohol.

44
Treatment of Diarrhea while Travelling

• Treat all bloody diarrhea with antibiotics.
• Treat pregnant women with ciprofloxacin, best
  alternative is azithromycin.
• Consider whether the rapid diarrhea is limiting
  antibiotic absorption.

45
Returning travellers

• how many will have symptoms?
• Which symptoms are most frequent?

46
Returned travellers

• Freedmans (NEJM 2006) study of 17,353 ill
  returned travellers from 30 GeoSentinel sites in
  developing countries
• per 1000
  travellers
• Systemic febrile illness 226
• Acute diarrhea 222
• Dermatologic disorder 170
• Chronic diarrhea 113
• Nondiarrheal GI disorder 82
• Respiratory disorder 77
• Death 1

47
Returned travellers basic approach to diagnosis

• Detailed history of symptoms
• if persistent fever malaria thick and thin films
  and repeat in 12-24 hours
• Detailed history of itinerary and exposures
• Careful physical exam
• CBC, LFTs, creatinine, electrolytes (if had
  diarrhea) (hepatitis Ags and Abs as appropriate)
• 2 fresh stools

48
Investigation of prolonged diarrhea (gt 14 days)

• 2 fresh stools for
• Parasites Giardia, Cyclospora, Cryptosporidium,
  Microsporidum, Entamoeba histolytica
• Bacteria Enteropathogenic E. Coli, Shigella,
  Salmonella, Aeromonas, enteroaggreagative E.
  Coli, noncholera Vibrios
• If all tests negative, consider ciprofloxacin 500
  mg tid x 5 days if not yet given, then flagyl 250
  mg tid x 7 days
• If diarrhea continues, sigmoidoscopy or upper GI
  endoscopy
• A few patients progress to IBS after Campylobacter

49
Investigation of persistent fever without focal
disease Blood cultures

• Bacterial endocarditis
• Bacterial sepsis
• Bartonellosis
• Brucellosis
• Leptospirosis
• Listeriosis
• Meliodosis
• Meningococcemia
• typhoid

50
Investigation of persistent fever without focal
disease blood or CSF for parasites

• Babesiosis
• borreliae
• African and American trypanosomiasis
• malaria
• microfilariae
• visceral leishmaniasis
• loiasis

51
Investigation of persistent fever without focal
disease serology

• Cytomegalovirus
• Epstein-Barr
• viral hepatitis
• Leptospirosis
• Rickettsiae
• viral hemorrhagic fevers
• Dengue
• syphilis
• relapsing fever
• toxoplasmosis

52
You are going to work as a physician in a
SubSaharan country (Sudan) for 2 years What can
you contribute?

• Train health professionals
• Be able to do and teach a safe C-section and
  vacuum delivery
• Reduce infectious disease risks by public health
  interventions
• Involve other experts in increasing food
  production in each household
• Encourage an organisation to come in and start
  small loans to households to start businesses
  (Gramin banks)

53
Sudan Infectious Diseases Arthropod borne
diseases

• malaria (except above 2600 m)
• filariasis
• onchocerciasis (river blindness)
• cutaneous and mucocutaeous leishmaniasis
• visceral leishmaniasis
• trypanosomiasis (sleeping sickness)
• relapsing fever
• louse- flea- and tick-borns typhus
• Tungiasis
• viral hemorrhagic fevers (from mosquitoes,
• ticks, sand flies)
• Yellow Fever

54
Sudan Food and water-borne infections

• helminths
• bacterial diarrhea typhoid
• hepatitis A and E
• hepatitis B
• cholera

55
Sudan Food and water-borne infections Helminths

• Metazoa
• Flat worms Round worms
• 
  (nematodes)
• Cestodes Trematodes
• (tape worms) (flukes)

56
Sudan Food and water-borne infections
Helminths nematodes (round worms)

• Ascaris lumbricoides
• Trichuris trichiura
• Enterobius vermicularis
• Stronglyoides
• Ancyclostoma duodenale
• Necator americanus
• Trichinella spiralis
• Wucheria bancrofti
• Loa loa
• Onchocerca volvulus

57
Sudan Food and water-borne infections
Helminths Cestodes (tape worms)

• Taenia solium
• Taenia saginata
• Echinococcus granulosus
• Echinococcus multilocularis

58
Sudan Food and water-borne infections
Helminths Trematodes (flukes)

• Schistosoma haematobium, mansoni and japonicum