Travel and Tropical MedicineRoger Thomas, MD, Ph.D, CCFP. MRCGP

RISKS of Travel to Developing CountriesDiarrhea 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%

Mortality from travel in developing world

50% is cardiovascular (older travelers with pre-existing cardiac condition), but rates are not increased by travelIn 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 20041.7 million deaths, single major cause of death in males 15-45> 750 US citizens die, > 25,000 injured annually on foreign roads, some are permanent residents abroad, (implying > 75 Canadians and > 2,500 accidents) 30 million injuriesEgypt, Kenya, India, S. Korea, Turkey, Morocco most dangerousAdvise do not drive at night, especially rural areas; do not drive motorbike or bike

OUTLINETake a history past medical history, medications, vaccinations planned travel unplanned excursions and sportsBring childhood vaccinations up to date (MMR, polio, tetanus)Vaccinations and medications needed for tripAsk their understanding of risks; your advicePrint off CDC data and have them read and underline itMalaria: prevention; diagnosis; treatmentTravellers diarrhea: prevention; diagnosis; treatmentHelminths 9. Other

Lets begin with a 60 year old going to Peru and EcuadorPMH: HTN, hyperlipidemia, well controlled; never smokerWhat are his/her travel plans?Review CDC website cdc.gov Identify risks and prescribe

60 year old visiting Peru and EcuadorUpdate childhood vaccinationsCheck for egg allergy if plan MMR, influenza, Yellow Fever vaccinesGI 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)

60 year old visiting Peru and Ecuador: Other risks?Helminths such as Amebiasis, echinococcusAmerican trypanosomiasis (Chagas disease)Cutaneous and mucocutaneous LeishmaniasisParagonimiasis (oriental lung fluke)BrucellosisBartonellosis (Oroya fever) on western slopes of Andes up to 3000 mLouseborne typhus in mountainous areas of Peru

28 year old veterinarian, visiting Malawi, South Africa, advising for WHOPMH: LMP 6 weeks ago, rising HcG titres, planning to be in Africa during 1st and 2nd trimestersGI risks?Malaria risks?Rabies risks?Risks to pregnancy?

Live-attenuated vaccines in pregnancyMMR and varicella are live-attenuated and contrandicated in pregnancy because of theoretical risk to fetusHowever, 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

Live-attenuated vaccines in pregnancyNo evidence of harm from inadvertent varicella vaccination in 362 women vaccinated during pregnancy, no cases of congenital varicella

Vaccines in pregnancyNo evidence of increased risk of adverse reactions, teratogenic or embryotoxic effects in pregnancyAll classes of maternal IgG transported across placenta, mostly in 3rd trimestermaternal 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 Advice for pregnancySafe 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

Canadian Immunization Guide Advice for pregnancyNo apparent risk, recommended in women at risk Hepatitis BNo 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)

MalariaIncubation: 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 areaClinical 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.

MalariaCold 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

MalariaHot 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

WHO criteria for Severe malariaIdentify patients with severe malaria for special treatment with one or more of:Cerebral malariaRespiratory distressSevere normocytic anemiaRenal failureHyperparasitemiaPulmonary edemaHypoglycemiaCirculatory collapseSpontaneous bleedingGeneralised convulsions

Cerebral malaria (encephalitis)impairment of consciousness or generalised convulsion followed by comahigh 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: 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)

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)

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 malariaJaundice 1/3 of adults; associated with cerebral malaria, acute pulmonary edemaHypoglycemia Anxiety, breathlessness, lightheadedness, tachycardia, impairment of consciousness, seizures, abnormal posturing can be misinterpreted as due only to the malariaPregnant 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

Chemoprophylaxis of malariaCausal prophylaxis: atovaquone and primaquin act on exo-erythrocytic cycle in liverSchizontocides: atovaquone, mefloquine, chloroquine, doxycycline, proguanil act on intra-erythrocytic parasitesTerminal prophyaxis: Primaquine acts on latent hypnozoites in liver to prevent relapses in P Ovale and P vivax

Chemoprophylaxis of malariaMefloquine 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

Chemoprophylaxis of malariaDoxycycline PO 1.5mg/kg daily. Do not use children < 12 years and pregnant or lactating women; can begin 2 days before enter malarious areaPyrimethamine-dapsone (Malaquine) PO 1 tablet = 12.5 mg pyrimethamine + 100 mg dapsone tablet weekly children 1-5 years 1/2 tablet weekly children 6-11 years 1 tablet weekly children >11 years and adults

Prevention of malariaBednets & 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 95%CI 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

Treatment of MalariaARTEMISINS (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)

Treatment of MalariaSevere 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]

Treatment of MalariaQUININEUncomplicated 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 dailySevere 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 arrhythmiasPregnant women: quinine is the drug of choice.

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 pressureZongo (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%

Large family going to Mexico for daughters wedding. They are worried about getting travellers diarrheaAdvise on risks, precautions and treatment

TRAVELERS DIARRHEA: PREVENTIONHand washing: 30 seconds with soapBoil, 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.

TRAVELERS DIARRHEA: PREVENTION3. Take a micropore filter. Cryptosporidium can pass through a 1 micropore filter, so needs subsequent halogenationChlorine 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 larvaePotassium Permanganate to wash fruit and vegKettle to boil water (boiling for 1 minute kills even Cryptosporidium

TRAVELERS DIARRHEA: PREVENTION6. 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: PREVENTION7. 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

DIAGNOSIS of TRAVELLERs DIARRHEAOn a 3 week trip the indiscreet traveler is most likely to get diarrhea in the first week, and will need guidance about self-treatment.>60% is bacterial: Most common is E. Coli, then Shigella, Salmonella, CampylobacterAttack rate remains same in long-term travelers and expatriates for several years

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.

Diagnosis of Travellers Diarrhea by Clinical Presentation: Dysentery (15%): Usually Shigella. Other causes: Salmonella, Campylobacter, Yersinia, E. Coli serotype 0157:H7, 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.

Diagnosis of Travellers Diarrhea by Clinical Presentation: Chronic diarrhea, lasting > 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.

Treatment of Diarrhea while Travelling

1. Oral rehydrationSevere 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 dairyMild: infants - continue usual breast feeding/formula/ fluids

Treatment of Diarrhea while Travelling2. 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 < 2 years. 3. Pepto-bismol (do not exceed 16 tablets/day): reduces diarrhea by 50% because of anti-peristaltic and anti-secretary effects.

Treatment of Diarrhea while Travelling4. 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.

Treatment of Diarrhea while TravellingTreat all bloody diarrhea with antibiotics.Treat pregnant women with ciprofloxacin, best alternative is azithromycin.Consider whether the rapid diarrhea is limiting antibiotic absorption.

Returning travellers:how many will have symptoms?Which symptoms are most frequent?

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

Returned travellers: basic approach to diagnosisDetailed history of symptomsif persistent fever malaria thick and thin films and repeat in 12-24 hoursDetailed history of itinerary and exposuresCareful physical examCBC, LFTs, creatinine, electrolytes (if had diarrhea) (hepatitis Ags and Abs as appropriate)2 fresh stools

Investigation of prolonged diarrhea (> 14 days) 2 fresh stools for Parasites: Giardia, Cyclospora, Cryptosporidium, Microsporidum, Entamoeba histolyticaBacteria: Enteropathogenic E. Coli, Shigella, Salmonella, Aeromonas, enteroaggreagative E. Coli, noncholera VibriosIf all tests negative, consider ciprofloxacin 500 mg tid x 5 days if not yet given, then flagyl 250 mg tid x 7 daysIf diarrhea continues, sigmoidoscopy or upper GI endoscopy A few patients progress to IBS after Campylobacter

Investigation of persistent fever without focal disease: Blood culturesBacterial endocarditisBacterial sepsisBartonellosisBrucellosisLeptospirosisListeriosisMeliodosisMeningococcemiatyphoid

Investigation of persistent fever without focal disease: blood or CSF for parasitesBabesiosisborreliaeAfrican and American trypanosomiasismalaria microfilariaevisceral leishmaniasisloiasis

Investigation of persistent fever without focal disease: serologyCytomegalovirusEpstein-Barrviral hepatitisLeptospirosisRickettsiaeviral hemorrhagic feversDenguesyphilisrelapsing fevertoxoplasmosis

You are going to work as a physician in a SubSaharan country (Sudan) for 2 years; What can you contribute?Train health professionalsBe able to do and teach a safe C-section and vacuum deliveryReduce infectious disease risks by public health interventionsInvolve other experts in increasing food production in each householdEncourage an organisation to come in and start small loans to households to start businesses (Gramin banks)

Sudan: Infectious Diseases: Arthropod borne diseasesmalaria (except above 2600 m)filariasisonchocerciasis (river blindness)cutaneous and mucocutaeous leishmaniasisvisceral leishmaniasistrypanosomiasis (sleeping sickness)relapsing feverlouse- flea- and tick-borns typhusTungiasisviral hemorrhagic fevers (from mosquitoes, ticks, sand flies)Yellow Fever

Sudan: Food and water-borne infectionshelminthsbacterial diarrhea; typhoidhepatitis A and Ehepatitis Bcholera

Sudan: Food and water-borne infections: Helminths Metazoa

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

Sudan: Food and water-borne infections: Helminths: nematodes (round worms)Ascaris lumbricoidesTrichuris trichiuraEnterobius vermicularisStronglyoidesAncyclostoma duodenaleNecator americanusTrichinella spiralisWucheria bancroftiLoa loaOnchocerca volvulus

Sudan: Food and water-borne infections: Helminths: Cestodes (tape worms)Taenia soliumTaenia saginataEchinococcus granulosusEchinococcus multilocularis

Sudan: Food and water-borne infections: Helminths: Trematodes (flukes)Schistosoma haematobium, mansoni and japonicum