health problems during travel - ucsf cme · • health problems during travel: 64% – diarrhea:...

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5/14/10 1 Health Problems During Travel Health problems during travel: 64% – Diarrhea: 46% – Respiratory infections: 26% – Skin problems: 8% – Injuries: 5% Highest risk travel: Indian subcontinent Hill, DR: J Travel Med. 7:259, 2000 Health Problems After Travel Illnesses after travel: 26% – Illness began after return home: 70% – Falciparum malaria: 3 patients (0.4% patients; 1.5% illnesses after travel) Hill, DR: J Travel Med. 7:259, 2000

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5/14/10

1

Health Problems During Travel

•  Health problems during travel: 64% – Diarrhea: 46% – Respiratory infections: 26% – Skin problems: 8% –  Injuries: 5%

•  Highest risk travel: Indian subcontinent

Hill, DR: J Travel Med. 7:259, 2000

Health Problems After Travel

•  Illnesses after travel: 26% –  Illness began after return home: 70% – Falciparum malaria: 3 patients (0.4% patients;

1.5% illnesses after travel)

Hill, DR: J Travel Med. 7:259, 2000

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General travel advice

•  Don’t drink the water •  Avoid unpeeled, uncooked fruits and

vegetables •  Food should be well-cooked •  Avoid insect bites •  Don’t swim in fresh water in the tropics •  Be careful about STDs

Vectors and their diseases Mosquitoes: Malaria, Dengue, Yellow fever, Viral

encephalitis, Lymphatic filariasis Blackflies: Onchocerciasis Sand flies: Leishmaniasis, Bartonellosis Tsetse flies: African trypanosomiasis Kissing bugs: Chagas’ disease Fleas: Plague, Typhus Lice: Typhus, Bartonellosis Midges: Visceral filariasis Mites: Rickettsialpox, Tsutsugamushi fever Ticks: Lyme disease, RMSF, Other rickettsiae,

Babesiosis, Ehrlichiosis, Relapsing fever

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Immunizations

•  Advised for some or all adults regardless of travel

•  Required in some countries •  Advised in certain travel circumstances

Immunizations Advised for some or all adults regardless

of travel

Tetanus Mumps Influenza Diphtheria Rubella Pneumococcus Measles Polio Hepatitis B

Immunizations Required in some countries

(need certificate of vaccination)

•  Yellow fever •  Not: Cholera •  Not: Small pox

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Immunizations Advised in certain travel circumstances

•  Hepatitis A •  Typhoid •  Meningococcal •  Rabies •  Japanese encephalitis •  Plague

Hepatitis A

•  Developing world: nearly all adults have been infected

•  U.S. – Seroprevalence in adults much lower –  ~100,000 cases / year –  ~70 deaths / year from fulminant hepatitis

•  Travelers to high-risk areas – Risk of infection high (3.6% / year)

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Hepatitis A Vaccine

•  Two formalin-inactivated killed virus vaccines available in U.S.

•  Seroconversion >95% after 2 doses •  Protection high

What about immune globulin?

•  Passive vaccination against hepatitis A •  No longer needed in anyone receiving the newer

hepatitis A vaccines •  Consider use only for those in need of immediate

protection – the newer vaccines should offer adequate protection after ~ 2 weeks

•  It is OK to give the two vaccines simultaneously

Typhoid

•  Systemic febrile illness due to infection with Salmonella typhi

•  Initially relatively mild illness •  Can progress to serious complications

(intestinal perforation, death) •  Endemic in developing countries •  U.S.: ~400 reported cases / year; most

acquired during foreign travel

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Typhoid vaccines

•  Two vaccines released in 1990’s – Efficacy of each good (~50-80%) – Both well tolerated

•  Ty21a: Live, attenuated, oral vaccine •  Typhim Vi: Injectable polysaccharide

vaccine

Who should get which vaccine?

•  Tetanus booster (q 10 yrs), Hepatitis A: Just about everyone traveling anywhere

•  Polio: Once as an adult; risk is remote •  Yellow fever: When required; Travel to rural areas

S. America and Africa •  Typhoid: Long-term travel; Those not following

food and drink precautions •  Meningococcal: Travelers to Mecca on Haj; Long-

term travelers

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Traveler’s Diarrhea

Delhi belly La turista Rome runs Casablanca crud Greek gallop Malta dog Turkey trots Montezuma’s revenge Aztec two-step Poona poohs Basra belly Aden gut

Traveler’s Diarrhea Causes

•  Enterotoxigenic E. coli •  Shigella •  Salmonella •  Other bacteria: Campylobacter, Vibrio, etc. •  Viruses: Rotavirus, Norwalk, Enteroviruses, etc. •  Parasites: Giardia, Amoeba, Cryptosporidium

Traveler’s Diarrhea Clinical Presentation

•  Onset usually during first week of travel •  Secretory, watery diarrhea •  Fever in only 10-20% •  Bloody stools in < 10% •  Duration usually 2-4 days

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Traveler’s Diarrhea Treatment

•  Fluid replacement •  Antimotility agents: Imodium, Lomotil •  Pepto Bismol •  Antibiotics: Usually quinolones

Traveler’s Diarrhea Prevention

•  Food and drink precautions •  Pepto Bismol •  Antibiotics (usually quinolones)

Traveler’s Diarrhea New Drug: Rifaximin (Xifaxan)

•  Non-absorbed antibiotic •  Related to Rifampin •  As effective as Cipro against mild

traveler’s diarrhea •  Do not use for complicated disease

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Drugs for treatment of traveler’s diarrhea

Drug Dosing Cost1

Ciprofloxacin 500 mg BID x 3d $30

Azithromycin 1000 mg x 1 or 500 mg qD x 3d

$31 or $47

Rifaximin 200 mg TID x 3d $33

Doxycycline 100 mg BID x 3d <$5

1Med. Lett. 46:74, 2004

Traveler’s Diarrhea Consensus

•  Treatment: An antibiotic plus an antimotility agent, beginning soon after symptoms start.

•  Chemoprophylaxis: Not recommended routinely, but daily antibiotic therapy is effective.

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Malaria

•  Hundreds of millions of cases per year •  Over one million deaths per year •  U.S.:

– About 1500 cases per year –  5-10 deaths per year

Human malaria parasites •  Plasmodium falciparum •  Plasmodium vivax •  Plasmodium ovale •  Plasmodium malariae •  Plasmodium knowlesi

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Incidence of malaria in the USA

CDC, Malaria surveillance, 2005

Region of acquisition of malaria for episodes diagnosed in the USA

CDC, Malaria surveillance, 2005

Purpose of travel in those diagnosed with malaria in the USA

CDC, Malaria surveillance, 2005

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Under-appreciated malaria risk: those returning to their country of origin

Species in malaria infections diagnosed in the USA

CDC, Malaria surveillance, 2005

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Malaria Clinical presentation

•  Febrile paroxysm •  Respiratory and GI symptoms are common •  Uncommon findings: rash, lymphadenopathy •  Fever pattern usually not regular •  Severe disease: falciparum malaria

Falciparum malaria

•  Cerebral malaria •  Renal failure •  Noncardiogenic pulmonary edema •  Anemia •  Hypoglycemia •  Shock •  Death

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Malaria diagnosis

Interval between return from travel and onset of malarial illness P. falciparum occurs early

CDC, Malaria surveillance, 2005

New method for malaria diagnosis- RDTs

•  BinaxNOW malaria test FDA approved 2007 •  Detects:

–  P. falciparum-specific antigen (HRP2) –  Antigen all human plasmodia (aldolase)

•  Approved for hospital and commercial labs; under consideration as point-of-care test

•  How good is the test? P. falciparum P. vivax –  Sensitivity 99.7% 93.5% –  Specificity 94.2% 99.8%

(tested at parasite density > 5,000/µl)

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Antimalarial drugs

•  4-aminoquinolines: Chloroquine, Amodiaquine •  Quinine, Mefloquine, Halofantrine •  Antifolates: Sulfadoxine/Pyrimethamine, LapDap •  Artemisinins: Artesunate, Artemether, etc. •  Antibiotics: Doxycycline, Clindamycin •  Malarone •  Primaquine

Artemisinin-based combination therapy

•  Artemisinins very potent •  Short half-life of artemisinins helps to prevent

selection resistant parasites •  Partner drugs have longer half-lives, and

eliminate small numbers of remaining parasites

Parasite Density

Partner Drug

Artemisinin New Infections

• Artemether/lumefantrine • Artesunate/amodiaquine • Artesunate/mefloquine • DHA/piperaquine

Treatment of malaria in the U.S. (2008)

•  Nonfalciparum malaria –  Chloroquine –  Also Primaquine for vivax and ovale (after G6PD

shown to be normal)

•  Falciparum malaria –  Quinine plus Doxycycline (adults) –  Quinine plus Clindamycin (children) –  Malarone (atovaquone/proguanil) –  Mefloquine –  Severe disease: IV Quinidine

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Treatment of malaria in the U.S. •  Nonfalciparum malaria

–  Chloroquine –  Also Primaquine for vivax and ovale (after G6PD

shown to be normal)

•  Falciparum malaria –  Coartem –  Quinine plus Doxycycline (adults) –  Quinine plus Clindamycin (children) –  Malarone (atovaquone/proguanil) –  Mefloquine –  Severe disease

•  IV Quinidine •  IV Artesunate

Artemisinins for the treatment of severe malaria

•  IM artemether equivalent to IM quinine •  IV artesunate superior to IV quinine

–  1461 patients in Asia: mortality 15% vs. 11% (34.7% risk reduction)

–  Systematic review → similar risk reduction

•  Drugs may also be administered rectally •  Not yet widely used for severe malaria in most

developing countries

Dondorp, et al, Lancet 2005, 366, 717-25 Rosenthal, NEJM 2008, 358:1829-36

IV Artesunate for the treatment of severe malaria in the USA

•  Available only through CDC –  Requires dx malaria and either severe disease or

inability to take oral medications –  Must call CDC (770-488-7788 or 770-488-7100) –  Drug released from CDC quarantine stations

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Coartem (Riamet) for uncomplicated falciparum malaria •  Artemether (20 mg) + Lumefantrine (120 mg) •  Standard therapy for uncomplicated

falciparum malaria in > 20 countries •  Rapidly clears parasitemia and symptoms •  Well-tolerated •  Efficacy in non-immune population little-

studied •  4 tablets BID x 3 days •  Approved by FDA April, 2009

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Chemoprophylaxis of malaria •  Chloroquine •  Mefloquine •  Doxycycline •  Malarone

Chemoprophylaxis of malaria Drug Dosing Toxicity Cost1

Chloroquine Weekly Very safe Cheap

Mefloquine Weekly CNS $63

Doxycycline Daily GI & Skin $4

Malarone Daily GI $103

1Wholesale cost for a 2-week trip

Antimalarial chemoprophylaxis Summary

•  Is prophylaxis really needed? –  Many cities in endemic countries are not a risk –  Cities in Africa and Indian subcontinent are high risk –  Detailed information available from CDC (www.cdc.gov)

•  Areas without chloroquine resistance: Chloroquine •  Areas with chloroquine resistant falciparum malaria

–  Mefloquine – usually first choice, but contraindicated with psych disease or seizure disorder

–  Malarone – adequate replacement for mefloquine, but expensive, especially for a long trip

–  Doxycycline – particularly for areas with multidrug resistance (esp. rural SE Asia)

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Health Problems After International Travel

Diarrhea •  Prolonged traveler’s diarrhea •  Protozoan parasites •  Tropical sprue •  Noninfectious

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Diarrhea After Return From Travel

•  Reasonable to manage as traveler’s diarrhea –  For simple diarrhea, presumptive therapy with a

quinolone and antimotility agent is OK •  Inflammatory diarrhea

–  Stool culture and O&P –  Presumptive therapy with a quinolone

•  Persistent diarrhea –  Repeat O&P to rule out giardiasis, other parasites –  Consider presumptive therapy with Flagyl –  Consider GI consultation for endoscopy

Health Problems After International Travel

Febrile Illness Malaria Acute schistosomiasis Typhoid Amebiasis Hepatitis prodrome Rickettsial illnesses Dengue Leptosporosis Other viral illnesses Brucellosis Acute HIV Other protozoa TB Chikungunya virus

Fever in returned travelers •  195 patients admitted to a London hospital •  Most common diagnoses

–  Malaria: 82 (42%) –  No dx: 49 (25%) –  Gastroenteritis: 14 (7%) –  Dengue fever: 12 (6%) –  Bacterial pneumonia: 8 (4%) –  Upper respiratory tract infection: 6 (3%) –  Hepatitis A: 6 (3%) –  Typhoid: 6 (3%)

Doherty, et al.: QJM 88:271, 1995

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Fever in returned travelers •  232 patients admitted to an Australian referral hospital

over a 3 year period •  Most common diagnoses

–  Malaria: 62 (27%) –  Gastroenteritis: 33 (14%) –  Upper respiratory tract infection: 28 (12%) –  No dx: 22 (9%) –  Dengue fever: 18 (8%) –  Bacterial pneumonia: 14 (6%) –  Typhoid: 8 (3%) –  Hepatitis A: 6 (3%)

O’Brien, et al., CID 33:603, 2001

Dengue fever

•  Endemic in many areas and spreading •  Transmitted by Aedes mosquitoes •  Incubation period: 4-7 days •  Major clinical features: fever, headache,

musculoskeletal pain, diffuse rash, minor bleeding problems

•  Dengue hemmorhagic fever

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Fever after return from travel Workup

•  Physical exam •  Blood smears •  Blood cultures •  Consider serologies •  Other tests based on presentation

Health Problems After International Travel

Eosinophilia •  Acute schistosomiasis •  Strongyloidiasis •  Filariasis •  Ascariasis •  Hookworms •  Other helminths

Travel Advice Summary •  General

–  Food and drink precautions –  Avoid insect bites

•  Immunizations –  Tetanus –  Yellow fever –  Hepatitis A, Typhoid, Meningococcus

•  Diarrhea –  Food and drink precautions –  Antibiotics and antimotility agents

•  Malaria –  Avoid mosquito bites –  Prophylaxis: Usually Mefloquine or Malarone –  Prompt evaluation of febrile returned travelers