Browse the corpus

Travel Medicine I(EY POI I{T o Patients with tularemia experience abrupt onset of fever Recommended According to Destination, ltinerary and and respiratory symptoms, and chest radiographs dem- Purpose of Travel onstrate infiltrates, hilar lymphadenopathy, and pleural Hepatitis Ab: 1 month before travel, booster at 6-18 months effusions. Hepatitis Bb: 0, 1 month,6 months (Engerix-B, Recombivax-HB); accelerated schedule: 0, 1 week,3 weeks, and 12 months (combination vaccine with hepatitis A available); or 0, 1 month (Heplisav-B) Viral Hemorrhagic Fever Typhoid': Live-attenuated oralvaccine $y21a);0, 2 days,4 days, The Ebola and Marburg hemorrhagic viruses are the most 6 days; capsularVi polysaccharide intramuscular vaccine; one likely to be used as biologic weapons. In endemic areas, they dose ( p referred fo r i m m u nocom prom ised persons) are spread by vectors, contact with bodily fluids, or fomites. Cholera: Live oral, 10 days before travel; killed oral, whole- Aerosolization is a likely mode of terrorist dissemination. cell-B subunit; O, 1 week (available outside the United States) Symptoms appear 2to 2l days after exposure (see Table 38). Rabies: lnactivated; 0, 7 days, 21-28 days Mortality rates can reach 90%. Ja pa nese encepha litis: I nactivate d; 0, 28 days ( booster Depending on the stage of infection, diagnosis may be recommended )11 months with ongoing risk) confirmed by antigen and antibody assays and PCR. Exposed Poliod: inactivated; single dose (lM or SO) if primary series persons are monitored during the incubation period, with completed;two doses 4-8 weeks apartfollowed bythird dose 6-12 months after second if previously unvaccinated prompt isolation if symptoms develop. Treatment is support- ive (see Table 38). Antiviral medications are under develop- Measles": live-attenuated, two doses separated by 28 days (born after 1956 and no documentation of vaccination or ment. An effective, preventative vaccine is now available. evidence of immunity) rEY POIilT Dengue: three doses given 6 months apart; only in seropositive persons aged 9-45 years (not available in the . Symptoms of viral hemorrhagic fever include fever, United States) headache, myalgia, abdominal pain, diarrhea, and Tick-borne encepha itis: nactivated; th ree doses over I I

I(EY POI I{T o Patients with tularemia experience abrupt onset of fever Recommended According to Destination, ltinerary and and respiratory symptoms, and chest radiographs dem- Purpose of Travel onstrate infiltrates, hilar lymphadenopathy, and pleural Hepatitis Ab: 1 month before travel, booster at 6-18 months effusions. Hepatitis Bb: 0, 1 month,6 months (Engerix-B, Recombivax-HB); accelerated schedule: 0, 1 week,3 weeks, and 12 months (combination vaccine with hepatitis A available); or 0, 1 month (Heplisav-B) Viral Hemorrhagic Fever Typhoid': Live-attenuated oralvaccine $y21a);0, 2 days,4 days, The Ebola and Marburg hemorrhagic viruses are the most 6 days; capsularVi polysaccharide intramuscular vaccine; one likely to be used as biologic weapons. In endemic areas, they dose ( p referred fo r i m m u nocom prom ised persons) are spread by vectors, contact with bodily fluids, or fomites. Cholera: Live oral, 10 days before travel; killed oral, whole- Aerosolization is a likely mode of terrorist dissemination. cell-B subunit; O, 1 week (available outside the United States) Symptoms appear 2to 2l days after exposure (see Table 38). Rabies: lnactivated; 0, 7 days, 21-28 days Mortality rates can reach 90%. Ja pa nese encepha litis: I nactivate d; 0, 28 days ( booster Depending on the stage of infection, diagnosis may be recommended )11 months with ongoing risk) confirmed by antigen and antibody assays and PCR. Exposed Poliod: inactivated; single dose (lM or SO) if primary series persons are monitored during the incubation period, with completed;two doses 4-8 weeks apartfollowed bythird dose 6-12 months after second if previously unvaccinated prompt isolation if symptoms develop. Treatment is support- ive (see Table 38). Antiviral medications are under develop- Measles": live-attenuated, two doses separated by 28 days (born after 1956 and no documentation of vaccination or ment. An effective, preventative vaccine is now available. evidence of immunity) rEY POIilT Dengue: three doses given 6 months apart; only in seropositive persons aged 9-45 years (not available in the . Symptoms of viral hemorrhagic fever include fever, United States) headache, myalgia, abdominal pain, diarrhea, and Tick-borne encepha itis: nactivated; th ree doses over I I unexplained bleeding and bruising appearing 2 to 21 days 6-1 5 months, second dose >2 weeks after first if rapid immune after exposure; disease progression results in hemorrhagic response required (not available in the United States) diathesis, shock, and multiorgan failure. Required for Certain Destinations Yellow feve/: Live attenuated; one dose (no booster required) Men i ngococca : Ouad riva lent conjugate ( MenACWY) or I

unexplained bleeding and bruising appearing 2 to 21 days 6-1 5 months, second dose >2 weeks after first if rapid immune after exposure; disease progression results in hemorrhagic response required (not available in the United States) diathesis, shock, and multiorgan failure. Required for Certain Destinations Yellow feve/: Live attenuated; one dose (no booster required) Men i ngococca : Ouad riva lent conjugate ( MenACWY) or I Travel Medicine polysaccharide (MPSV4); one dose; travel to Saudi Arabia during the Hajj lntrodustion Meningococcal B (MenB); two or three doses; high-risk groups Pretravel consultation should occur at least 4 lo 6 weeks lM = intramusculal SO = subcutaneous.

Travel Medicine polysaccharide (MPSV4); one dose; travel to Saudi Arabia during the Hajj lntrodustion Meningococcal B (MenB); two or three doses; high-risk groups Pretravel consultation should occur at least 4 lo 6 weeks lM = intramusculal SO = subcutaneous. before departure. Regularly updated information by coun- "All patients being evaluated for travel should receive or be up to date with all scheduled immunizations, including COVID-19, influenza, pneumococcal, tetanus- try is available on the CDC and World Health Organization diphtheria-pertussis, polio, varicella, and zoster vaccines. See MKSAP 19 General (WHO) websites (http://www.cdc.gov/travel and http:// lnternal Medicine 2 for routine adult immunization recommendations. blf not received as part of routine scheduled immunizations. www.who.int/ith). Travel-related illnesses (mostly febrile, lf the vaccine series was completed as part of scheduled immunization, repeat immunization is not required. diarrheal, respiratory, and cutaneous infections) are cOral vaccine should not be administered within 24 hours of the antimalarial drug reported in20% to 60% of returning travelers; many of these mefloquine because of the potential to decrease the vaccine's immunogenicity; patients must not take any antibiotic for at least 72 hours before receiving the vaccine. are vaccine preventable. Pretravel immunizations are listed dlf traveling to countries with wild or vaccine-derived poliovirus circulation. in Table 39. Potentially severe travel-associated infections are listed in Table 40, the most significant of which are "Additional dose if documented to have had one dose but no proof of immunity. See Viral lnfections for further information. reviewed here. lThe approved, live-attenuated yellow fever vaccine is currently unavailable in the United States; another live yellow fever vaccine used in Europe is available as an alternative option in the United States under the FDAs investigational new drug Malaria program.

before departure. Regularly updated information by coun- "All patients being evaluated for travel should receive or be up to date with all scheduled immunizations, including COVID-19, influenza, pneumococcal, tetanus- try is available on the CDC and World Health Organization diphtheria-pertussis, polio, varicella, and zoster vaccines. See MKSAP 19 General (WHO) websites (http://www.cdc.gov/travel and http:// lnternal Medicine 2 for routine adult immunization recommendations. blf not received as part of routine scheduled immunizations. www.who.int/ith). Travel-related illnesses (mostly febrile, lf the vaccine series was completed as part of scheduled immunization, repeat immunization is not required. diarrheal, respiratory, and cutaneous infections) are cOral vaccine should not be administered within 24 hours of the antimalarial drug reported in20% to 60% of returning travelers; many of these mefloquine because of the potential to decrease the vaccine's immunogenicity; patients must not take any antibiotic for at least 72 hours before receiving the vaccine. are vaccine preventable. Pretravel immunizations are listed dlf traveling to countries with wild or vaccine-derived poliovirus circulation. in Table 39. Potentially severe travel-associated infections are listed in Table 40, the most significant of which are "Additional dose if documented to have had one dose but no proof of immunity. See Viral lnfections for further information. reviewed here. lThe approved, live-attenuated yellow fever vaccine is currently unavailable in the United States; another live yellow fever vaccine used in Europe is available as an alternative option in the United States under the FDAs investigational new drug Malaria program. Recommendations from the Centers for Disease Control and Prevention. CDC Malaria is the most common cause of febrile illness in return- Yellow Book 2020: Health lnformation for lnternational Travel. New York: Oxford ing travelers, particularly from sub-Saharan Africa and large University Press; 20 1 9. Available on line at https://wwwnc.cdc.gov/travel/ ye llowboo k/2020/travel-related- infectio us-d iseases/ma la ria. parts of Asia, and less frequently from Latin America and some Caribbean countries. Preventive measures include limiting Incubation periods range from 1 week to 3 months. outdoor exposure between dusk and dawn, using insecticide Symptoms include fever, headache, myalgia, and gastrointesti- impregnated bed nets and insect repellents containing 20% nal symptoms. More severe disease occurs with hyperpara- N- diethyl, 3 -methylbenzamide (DEET), and using antimalarial sitemia (5%-107" parasitized erythrocytes). Serious disease chemoprophylaxis. primarily occurs with Plosmodium falciparum, including

Recommendations from the Centers for Disease Control and Prevention. CDC Malaria is the most common cause of febrile illness in return- Yellow Book 2020: Health lnformation for lnternational Travel. New York: Oxford ing travelers, particularly from sub-Saharan Africa and large University Press; 20 1 9. Available on line at https://wwwnc.cdc.gov/travel/ ye llowboo k/2020/travel-related- infectio us-d iseases/ma la ria. parts of Asia, and less frequently from Latin America and some Caribbean countries. Preventive measures include limiting Incubation periods range from 1 week to 3 months. outdoor exposure between dusk and dawn, using insecticide Symptoms include fever, headache, myalgia, and gastrointesti- impregnated bed nets and insect repellents containing 20% nal symptoms. More severe disease occurs with hyperpara- N- diethyl, 3 -methylbenzamide (DEET), and using antimalarial sitemia (5%-107" parasitized erythrocytes). Serious disease chemoprophylaxis. primarily occurs with Plosmodium falciparum, including 60

Travel Medicine TABLE 41 . Characteristics of Plasmodium Species Characteristics P.vivax P ovale P. malariae P.falciparum P. knowlesi lncubation period 10-30 days 10-20 days 1 5-35 days 8-25 days lndeterminate Geographic Tropicaland WestAfrica and Tropicalzones Tropicaland South and distribution temperate zones Southeast Asia temperate zones Southeast Asia Parasitemia Low Low Very low High Can be high Risk for disease Low risk Low risk Very low risk High risk High risk severity Disease relapse risk Yes Yes Yes No No Chloroquine Yes No Rare Yes No resistance

Parasitemia Low Low Very low High Can be high Risk for disease Low risk Low risk Very low risk High risk High risk severity Disease relapse risk Yes Yes Yes No No Chloroquine Yes No Rare Yes No resistance mental status alterations, seizures, hepatic failure, dissemi- food or water contaminated by organisms shed in the stool of nated intravascular coagulation, intravascular hemolysis, infected humans. Travel to South, East, and Southeast Asia metabolic acidosis, kidney disease, hemoglobinuria, and hypo- (lndian subcontinent) and portions of sub-Saharan Africa glycemia. Subsequently, anemia, thrombocytopenia, spleno- pose the greatest risk of infection. Oral and parenteral vaccines megaly, and elevated aminotransferase levels may develop. See (see Table 39) provide temporary immunity in 50% to B0% of Table 4lfor specific Plasmodium species features. recipients. Identification of malarial parasites on the peripheral Fever with headache, arthralgia, myalgia, pharyngitis, and blood smear is diagnostic. Morphologic features help deter- anorexia follows a 1- to 2-week incubation period. Abdominal mine the specific species. Rapid tests that detect malaria anti- pain can be accompanied by early-onset diarrhea, which may gens may lack sensitivity and specificity. Polymerase chain spontaneously resolve or become severe late in disease. One reaction (PCR) and serologic assays exist, although each has fifth of patients have constipation at diagnosis. In untreated ill- limitations. ness, temperature progressively increases and may remain ele- Because of their potential for severe infection, identiffing vated (up to 40'C [tO+'p]) for 4 to 8 weeks. A pulse temperature P falciparum and P. knowlesi is critical. Malarial symptom dissociation (relative bradycardia) and prostration are common. onset shortly after returning from travel to endemic zones, a About 20% of patients develop discrete, blanching, 1- to 4-mm high level of parasitemia, and distinctive morphologic charac- salmon-colored macules (rose spots, Figure 3O, on page 65) on teristics should raise suspicion for P. falciparum infection. the chest and abdomen during the second week of illness. Malarial chemoprophylaxis and treatment depend on pos, Moderate hepatosplenomegaly, leukopenia, anemia, throm- sible drug resistance and individual contraindications to spe- boqtopenia, and elevated aminotransferase levels are common. cific medications (Table 42, Thble 43). A full treatment regimen Secondary bacteremia may cause complications such as empy- should be considered for travelers to remote areas where access ema, muscle abscess, and endovascular infections. Intestinal to medical care may not be readily available. Additional detailed hemorrhage or perforation may occur 2 to 3 weeks after infec- information about malaria is provided in the CDC Yellow Book tion onset. Encephalopathy occurs in more severe cases. (https' //wwwnc. cdc. gov i travel /yellowbook / 2 0 2 0 /travel- Gallbladder invasion by typhoid bacilli may result in a related infectious diseases/malaria) or by calling the CDC carrier state with organisms being shed in the stool for more malaria hotline (ll o - +eaJl sa\ . than 1 year. Those with gallstones and chronic biliary disease are at greatest risk. rtv Po ltT5r Isolation of S. typhi or S. paratyphi from blood, stool, . Malaria is the most common cause of febrile illness in urine, or bone marrow is diagnostic; isolation success declines returning travelers; symptoms include fever, headache, after the first week of illness. Rapid serologic tests are available myalgia, and gastrointestinal symptoms. to distinguish S. entericaserotype Typhi antibodies. o Malarial symptom onset shortly after returning from Antibiotic treatment decreases mortality and shortens the travel to endemic zones and a high level of parasitemia duration of fever. Because of antibiotic resistance, all isolates should raise suspicion for Plasmodium falciparum should undergo susceptibility testing. Ceftriaxone or fluoro- infection. quinolones (for 14 days) or azithromycin (t g aay 1, then 500 mg/day for 6 days) are preferred treatments. Dexamethasone decreases mortality in severe illness, such as associated shock Typhoid (Enteric) Fever and encephalopathy. A 4- to 6-week course of ciprofloxacin Salmonella enterica serotype Typhi and Solmonella enterica effectively eradicates chronic carriage, although cholecystec- serotype Paratyphi (A, B, and C) cause prolonged febrile and tomy may be needed in cases of cholelithiasis. often serious infection (typhoid fever) acquired by consuming (Text continued on page 6 5)

mental status alterations, seizures, hepatic failure, dissemi- food or water contaminated by organisms shed in the stool of nated intravascular coagulation, intravascular hemolysis, infected humans. Travel to South, East, and Southeast Asia metabolic acidosis, kidney disease, hemoglobinuria, and hypo- (lndian subcontinent) and portions of sub-Saharan Africa glycemia. Subsequently, anemia, thrombocytopenia, spleno- pose the greatest risk of infection. Oral and parenteral vaccines megaly, and elevated aminotransferase levels may develop. See (see Table 39) provide temporary immunity in 50% to B0% of Table 4lfor specific Plasmodium species features. recipients. Identification of malarial parasites on the peripheral Fever with headache, arthralgia, myalgia, pharyngitis, and blood smear is diagnostic. Morphologic features help deter- anorexia follows a 1- to 2-week incubation period. Abdominal mine the specific species. Rapid tests that detect malaria anti- pain can be accompanied by early-onset diarrhea, which may gens may lack sensitivity and specificity. Polymerase chain spontaneously resolve or become severe late in disease. One reaction (PCR) and serologic assays exist, although each has fifth of patients have constipation at diagnosis. In untreated ill- limitations. ness, temperature progressively increases and may remain ele- Because of their potential for severe infection, identiffing vated (up to 40'C [tO+'p]) for 4 to 8 weeks. A pulse temperature P falciparum and P. knowlesi is critical. Malarial symptom dissociation (relative bradycardia) and prostration are common. onset shortly after returning from travel to endemic zones, a About 20% of patients develop discrete, blanching, 1- to 4-mm high level of parasitemia, and distinctive morphologic charac- salmon-colored macules (rose spots, Figure 3O, on page 65) on teristics should raise suspicion for P. falciparum infection. the chest and abdomen during the second week of illness. Malarial chemoprophylaxis and treatment depend on pos, Moderate hepatosplenomegaly, leukopenia, anemia, throm- sible drug resistance and individual contraindications to spe- boqtopenia, and elevated aminotransferase levels are common. cific medications (Table 42, Thble 43). A full treatment regimen Secondary bacteremia may cause complications such as empy- should be considered for travelers to remote areas where access ema, muscle abscess, and endovascular infections. Intestinal to medical care may not be readily available. Additional detailed hemorrhage or perforation may occur 2 to 3 weeks after infec- information about malaria is provided in the CDC Yellow Book tion onset. Encephalopathy occurs in more severe cases. (https' //wwwnc. cdc. gov i travel /yellowbook / 2 0 2 0 /travel- Gallbladder invasion by typhoid bacilli may result in a related infectious diseases/malaria) or by calling the CDC carrier state with organisms being shed in the stool for more malaria hotline (ll o - +eaJl sa\ . than 1 year. Those with gallstones and chronic biliary disease are at greatest risk. rtv Po ltT5r Isolation of S. typhi or S. paratyphi from blood, stool, . Malaria is the most common cause of febrile illness in urine, or bone marrow is diagnostic; isolation success declines returning travelers; symptoms include fever, headache, after the first week of illness. Rapid serologic tests are available myalgia, and gastrointestinal symptoms. to distinguish S. entericaserotype Typhi antibodies. o Malarial symptom onset shortly after returning from Antibiotic treatment decreases mortality and shortens the travel to endemic zones and a high level of parasitemia duration of fever. Because of antibiotic resistance, all isolates should raise suspicion for Plasmodium falciparum should undergo susceptibility testing. Ceftriaxone or fluoro- infection. quinolones (for 14 days) or azithromycin (t g aay 1, then 500 mg/day for 6 days) are preferred treatments. Dexamethasone decreases mortality in severe illness, such as associated shock Typhoid (Enteric) Fever and encephalopathy. A 4- to 6-week course of ciprofloxacin Salmonella enterica serotype Typhi and Solmonella enterica effectively eradicates chronic carriage, although cholecystec- serotype Paratyphi (A, B, and C) cause prolonged febrile and tomy may be needed in cases of cholelithiasis. often serious infection (typhoid fever) acquired by consuming (Text continued on page 6 5) 62

Travel Medicine T,ABtE 44. Antimalarial Chemoprophylaxis Regimens Drug Dose Time of Prophylaxis Time of Prophylaxis lnitiation (before Travel) Discontinuation (after Returning) For endemic areas with chloroquine-resistant Plasmodium falciparum Atovaq uone/proguanil' 250 mg/100 mg once daily 1-2 days 7 days Mefloquine 250 mg once weekly >2 weeks 4 weeks Doxycyclineb 100 mg once daily 1-2 days 4 weeks Tafenoquineb,' 200 mg once daily for 3 days; 3 days 1 week then 200 mg once weekly (begin 7 days after loading dose) For endemic areas with chloroquine and mefloquine-resistant P. falciparumd Atovaquone/progua nil" 250 mg/100 mg once daily 1-2 days 7 days Doxycyclineb 100 mg once daily 1-2 days 4 weeks Tafenoquineb,' 200 mg once daily for 3 days; 3 days l week then 200 mg once weekly (begin 7 days after loading dose) For endemic areas with chloroquine-sensitive P. falciparum Chloroquine 500 mg once weekly 1-2 weeks 4 weeks Hydroxychloroquine 400 mg once weekly 1-2 weeks 4 weeks Atovaquone/prog ua nilu 250/100 mg once daily 1-2 days 7 days

For endemic areas with chloroquine-sensitive P. falciparum Chloroquine 500 mg once weekly 1-2 weeks 4 weeks Hydroxychloroquine 400 mg once weekly 1-2 weeks 4 weeks Atovaquone/prog ua nilu 250/100 mg once daily 1-2 days 7 days Mefloquine 250 mg once weekly >2 weeks 4 weeks Doxycyclineb 100 mg once daily 1-2 days 4 weeks Primaquineb,' 30 mg base once daily 1-2 days 7 days Tafenoquineb,' 200 mg once daily for 3 days; 3 days 1 week then 200 mg once weekly (begin 7 days after loading dose) For endemic areas with Plasmodium vivax Primaquineb,' 30 mg base once daily 1-2 days 7 days Chloroquine 500 mg once weekly 1-2 weeks 4 weeks Hydroxychloroquine 400 mg once weekly 1-2 weeks 4 weeks Atovaquone/prog uani lu 250/100 mg once daily 1-2 days 7 days Mefloquine 250 mg once weekly 2 weeks 4 weeks Doxycyclineb 100 mg once daily 1-2 days 4 weeks Tafenoquineb,' 200 mg once daily for 3 days; 3 days 1 week then 200 mg once weekly (begin 7 days after loading dose)

Tafenoquineb,' 200 mg once daily for 3 days; 3 days 1 week then 200 mg once weekly (begin 7 days after loading dose) Prophylaxis for relapse due to P.vivax ot Plasmodium ovale Primaquineb,',", 30 mg base once daily 1-2 days 1-2 weeksr Tafenoquineb,',' 300 mg once 1-2 days 1 week (single dose) "Not indicated in pregnant women; can be used if other options not available or tolerated. bShould not be used in pregnant women. cContraindicated in persons with severe forms of glucose-6-phosphate dehydrogenase deficiency. dBorders of Thailand with Cambodia and Myanmar (Burma). 'ln pregnant women, continue chloroquine 500 mg once weekly for the duration of their pregnancy; after delivery use primaquine or tafenoquine if not breastfeeding' Two weeks after leaving malarious zone if prolonged exposure to P. vivax and P. ovale. Recommendations from the Centers for Disease Control and Prevention. CDC Yellow Book2O2O: Health lnformation for lnternational Travel' New York: Oxford University Press; 201 9. Available online at https://wwwnc.cdc.gov/travel/yellowbook/2O2Oltravel-related-infectious-diseases/malaria. 63

Travel Medicine Drug Dose and Duration Non-falcip arum Speciesb Chloroquine phosphate (500 mg) 1000 mg,then 500 mg at 6,24,and48h Hyd roxychloroq ui ne (400 mg) 800 mg, then 400 mg at 6,24, and 48h Plasmodium falciparum or Species Not ldentified Acquircd in chloroquine-sensitive area Chloroquine phosphate (500 mg) Same as for non-falciparum species or Hydroxychloroquine (400 mg) Acquired in chloroquine-resistant area Atovaquone-proguanil (250 mg/1 00 mg) 4 tabs daily (or 2 tabs twice/d)for 3 d Artemether-lumefantrine' (20 mg/1 20 mg) 4 tabs at 0, 8, 24,36,48, and 60 h Ouinine sulfate (325 mg) plus one of the following 2 tabs (650 mg)three times /d{or 3 or 7 dd Doxycycline (100 mg) 100 mg twice/d forT d Tetracycline (250 mg) 250 mg four times/d for 7 d Clindamycin (300 mg) 20 mg base/kg/d divided three times /d f or 7 d Mefloquine" (250 mg) 3 tabs (750 mg), then 2 tabs (500 mg)in 6-12h Acquired in mefl oquine-resistant arear Atovaquone-proguanil Same as above or Ouinine sulfate plus do4yrycline ortetrarycline or clindamycin Relapse prevention (infection with Plasmodium vivax ot Plasmodium ovalel Primaquine phosphateo (15 mg) 2 tabs daily for 14 d Tafenoquinss (300 mg) 1 tab once Treatment in pregnant women .

Acquired in mefl oquine-resistant arear Atovaquone-proguanil Same as above or Ouinine sulfate plus do4yrycline ortetrarycline or clindamycin Relapse prevention (infection with Plasmodium vivax ot Plasmodium ovalel Primaquine phosphateo (15 mg) 2 tabs daily for 14 d Tafenoquinss (300 mg) 1 tab once Treatment in pregnant women . Chloroquine-sensitive species: Ch loroqui ne phosphate (500 mg) Same as above P vivax and P ovale relapse prevention: Chloroquine Once weekly until after delivery phosphate (500 mg) Ch loroqu i ne-resista nt P falci p a ru mh: Ou i ni ne su lfate pl us Same as above clindamycin or mefloquine Arte mether-l u m efa ntri n e (second a nd th i rd tri mesters) Same as above Mefloquine (all trimesters) Same as above

Chloroquine-sensitive species: Ch loroqui ne phosphate (500 mg) Same as above P vivax and P ovale relapse prevention: Chloroquine Once weekly until after delivery phosphate (500 mg) Ch loroqu i ne-resista nt P falci p a ru mh: Ou i ni ne su lfate pl us Same as above clindamycin or mefloquine Arte mether-l u m efa ntri n e (second a nd th i rd tri mesters) Same as above Mefloquine (all trimesters) Same as above Treatment of severe disease (acquired in all malarial areas) Artesunatei (parenteral) 2.4m1/kg lVat 0, 12,24, and 48 h AND (follow artesunate with either) Artemether-lumefantrine Dose as above Atovaquone-proguanil Dose as above Doxyrycline Dose as above (can give 100 mg lV every 12 hr >urs until able to take oral) Clindamycin Dose as above (can give 10 mg base/kg loadir rg dose lV then 5 mg/kg lV every 8 hours until able to take oral) Ouinine sulfate Dose as above lV = intravenous. aPatients who develop malaria while receiving prophylaxis should be treated with a different drug regimen. 6P. vivax acquired in Papua New Guinea or lndonesia should be considered chloroquine resistant. ACT in the United States. dSeven-day duration is indicated if infection was acquired in Southeast Asia.

Treatment of severe disease (acquired in all malarial areas) Artesunatei (parenteral) 2.4m1/kg lVat 0, 12,24, and 48 h AND (follow artesunate with either) Artemether-lumefantrine Dose as above Atovaquone-proguanil Dose as above Doxyrycline Dose as above (can give 100 mg lV every 12 hr >urs until able to take oral) Clindamycin Dose as above (can give 10 mg base/kg loadir rg dose lV then 5 mg/kg lV every 8 hours until able to take oral) Ouinine sulfate Dose as above lV = intravenous. aPatients who develop malaria while receiving prophylaxis should be treated with a different drug regimen. 6P. vivax acquired in Papua New Guinea or lndonesia should be considered chloroquine resistant. ACT in the United States. dSeven-day duration is indicated if infection was acquired in Southeast Asia. "lncreased risk of neuropsychiatric reactions; not recommended for P falciparum infection acquired in Southeast Asia because of drug resistance. rFound on the eastern border of Myanmar (Burma) and adjacent parts of China, Laos, and Thailand; western border of Thailand and adjacent parts of Cambodia and Laos; and southern Vietnam. sConfirm absence of glucose-6-phosphate dehydrogenase deficiency in patient. Not indicated in pregnant women. hAtovaquone-proguanil and artemether-lumefantrine are generally not recommended for use in pregnant women. Doxycycline and tetracyclin not indicated in pregnancy. iApproved for commercial use in the United States as of May 26,2020.|f unable to obtain, call the CDC malaria hotline (770-448-7788). 64

Travel Medicine inflammatory bowel disease, immunocompromised states (including advanced HIV), and comorbidities that would be adversely affected by significant dehydration. Bismuth subsal- icylate can be used to prevent diarrhea, but the doses required are inconvenient and can lead to salicylate toxicity. probiotics are not recommended. Fluid replacement is the mainstay of treatment. Antimicrobials are recommended only in severe disease (Table a4). Self-treatment with azithromycin (preferred in South and Southeast Asia) or a fluoroquinolone (increasing concern for resistance and adverse reactions) is usually suf- J ficient. Rifaximin and rifamycin are minimally absorbed tu s oral antibiotic alternatives but are not recommended if fever and/or bloody diarrhea is present. Bismuth subsal tIGURE 30. Rosespots on the chestofa patientwith typhoid fevercaused by icylate in large doses can be beneficial in milder cases. the bacterium Salmonella typhi. Antimotility medications (e.g., loperamide and diphenoxy Reproduced from the CDC Public Health Image Library. https://phil.cdc.gov/Details.aspx?pid=2215 late) should only be given with antimicrobial therapy but should not be used in patients with dysentery or bloody diarrhea because of increased risk of colitis and colonic I( EY PO I1{TS perforation. . Typhoid fever commonly presents with fever, headache, arthralgia, myalgia, pharyngitis, anorexia, abdominal TABLE 44. Oral Treatment and Prophylaxis for Travelers' pain with early-onset diarrhea, pulse-temperature dis- Diarrhea sociation, and prostration. Agent Regimen o Ceftriaxone, fluoroquinolones, and azithromycin are Treatmenta preferred treatments for typhoid fever; dexamethasone Azithromycinb 1000 mg single dose or 500 mg daily decreases mortality in severe disease (shock and for3d encephalopathy). Norfloxacin 400 mg twice daily for 3 d Ciprofloxacin 750 mg single dose or 500 mg twice daily for 3 d' Travelers' Diarrhea Ofloxacin 400 mg single dose or once daily for The most common travel-associated infection is diarrhea, 3d. defined by the sudden onset of three or more loose or watery Levofloxacin 500 mg single dose or once daily for stools per day with at least one of the following: fever, cramps, 3d. nausea, abdominal pain, or blood in the stools. Risk is greatest Rifamycind 388 mg (two 1 94-mg tablets)twice for travelers to South and Southeast Asia, sub-Saharan Africa, daily for 3 d the Middle East, and Latin America. Rifaximind 200 mg three times daily for 3 d Travelers' diarrhea usually occurs within the first 2 weeks Prophylaxis" of travel and is usually self-limited; however, life-threatening Rifaximin 200 mg once ortwice daily volume depletion or severe colitis with systemic manifesta- tions can occur. Some travelers develop chronic diarrhea or a Bismuth subsalicylate 30 mL or two tablets chewed 4 times daily postinfective irritable bowel syndrome. Enterotoxigenic Escherichia coli is the most common "Antimotility medications (loperamide or diphenoxylate) can be used alone along with oral hydration {or mild-to-moderate diarrhea but must be taken with cause (see Table 40). antibiotics with severe diarrhea. They should not be used if fever or bloody diarrhea is present. Pretravel advice includes avoiding consumption of tap bPreferred for travelers from Southeast Asia, pregnant women, and with fever or water (through drinks, ice, or when brushing teeth), bloody diarrhea. undercooked meats, unpasteurized dairy products, and 'lf symptoms persist after 24 hours. fruits that are not peeled just before eating. Water disinfec- dNot for use with fever or bloody diarrhea. tion can be accomplished by boiling for 3 minutes or by "Chemoprophylaxis is recommended for no more than 2-3 weeks (the duration using chlorine and iodine. Commercial water filters are not studied in trials and a period short enough to minimize the risk for antimicrobial- associated adverse effects); fluoroquinolone antibiotics are no longer as dependable. recommended and should be avoided. Antimicrobial prophylaxis is effective but is generally not Recommendations from Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for recommended because of the potential for adverse effects. the prevention and treatment of travelers' diarrhea: a graded expert panel report J Trav Med. 2017;24:s63-s80. IPMID: 285210041doi: 10.1 093/ jtm/tax026 Prophylaxis should be considered in persons with coexisting

inflammatory bowel disease, immunocompromised states (including advanced HIV), and comorbidities that would be adversely affected by significant dehydration. Bismuth subsal- icylate can be used to prevent diarrhea, but the doses required are inconvenient and can lead to salicylate toxicity. probiotics are not recommended. Fluid replacement is the mainstay of treatment. Antimicrobials are recommended only in severe disease (Table a4). Self-treatment with azithromycin (preferred in South and Southeast Asia) or a fluoroquinolone (increasing concern for resistance and adverse reactions) is usually suf- J ficient. Rifaximin and rifamycin are minimally absorbed tu s oral antibiotic alternatives but are not recommended if fever and/or bloody diarrhea is present. Bismuth subsal tIGURE 30. Rosespots on the chestofa patientwith typhoid fevercaused by icylate in large doses can be beneficial in milder cases. the bacterium Salmonella typhi. Antimotility medications (e.g., loperamide and diphenoxy Reproduced from the CDC Public Health Image Library. https://phil.cdc.gov/Details.aspx?pid=2215 late) should only be given with antimicrobial therapy but should not be used in patients with dysentery or bloody diarrhea because of increased risk of colitis and colonic I( EY PO I1{TS perforation. . Typhoid fever commonly presents with fever, headache, arthralgia, myalgia, pharyngitis, anorexia, abdominal TABLE 44. Oral Treatment and Prophylaxis for Travelers' pain with early-onset diarrhea, pulse-temperature dis- Diarrhea sociation, and prostration. Agent Regimen o Ceftriaxone, fluoroquinolones, and azithromycin are Treatmenta preferred treatments for typhoid fever; dexamethasone Azithromycinb 1000 mg single dose or 500 mg daily decreases mortality in severe disease (shock and for3d encephalopathy). Norfloxacin 400 mg twice daily for 3 d Ciprofloxacin 750 mg single dose or 500 mg twice daily for 3 d' Travelers' Diarrhea Ofloxacin 400 mg single dose or once daily for The most common travel-associated infection is diarrhea, 3d. defined by the sudden onset of three or more loose or watery Levofloxacin 500 mg single dose or once daily for stools per day with at least one of the following: fever, cramps, 3d. nausea, abdominal pain, or blood in the stools. Risk is greatest Rifamycind 388 mg (two 1 94-mg tablets)twice for travelers to South and Southeast Asia, sub-Saharan Africa, daily for 3 d the Middle East, and Latin America. Rifaximind 200 mg three times daily for 3 d Travelers' diarrhea usually occurs within the first 2 weeks Prophylaxis" of travel and is usually self-limited; however, life-threatening Rifaximin 200 mg once ortwice daily volume depletion or severe colitis with systemic manifesta- tions can occur. Some travelers develop chronic diarrhea or a Bismuth subsalicylate 30 mL or two tablets chewed 4 times daily postinfective irritable bowel syndrome. Enterotoxigenic Escherichia coli is the most common "Antimotility medications (loperamide or diphenoxylate) can be used alone along with oral hydration {or mild-to-moderate diarrhea but must be taken with cause (see Table 40). antibiotics with severe diarrhea. They should not be used if fever or bloody diarrhea is present. Pretravel advice includes avoiding consumption of tap bPreferred for travelers from Southeast Asia, pregnant women, and with fever or water (through drinks, ice, or when brushing teeth), bloody diarrhea. undercooked meats, unpasteurized dairy products, and 'lf symptoms persist after 24 hours. fruits that are not peeled just before eating. Water disinfec- dNot for use with fever or bloody diarrhea. tion can be accomplished by boiling for 3 minutes or by "Chemoprophylaxis is recommended for no more than 2-3 weeks (the duration using chlorine and iodine. Commercial water filters are not studied in trials and a period short enough to minimize the risk for antimicrobial- associated adverse effects); fluoroquinolone antibiotics are no longer as dependable. recommended and should be avoided. Antimicrobial prophylaxis is effective but is generally not Recommendations from Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for recommended because of the potential for adverse effects. the prevention and treatment of travelers' diarrhea: a graded expert panel report J Trav Med. 2017;24:s63-s80. IPMID: 285210041doi: 10.1 093/ jtm/tax026 Prophylaxis should be considered in persons with coexisting 65

Travel Medicine #lti't+,,i rrY P0l l{Ts HVC . Fluid replacement is the mainstay of treatment for travelers' diarrhea; azithromycin and fluoroquinolones are recommended only in severe disease. o Antimicrobial prophylaxis for travelers' diarrhea is generally not recommended; however, prophylaxis should be considered in persons with inflammatory bowel disease, immunocompromised states, and comorbidities that would be adversely affected by significant dehydration.

#lti't+,,i rrY P0l l{Ts HVC . Fluid replacement is the mainstay of treatment for travelers' diarrhea; azithromycin and fluoroquinolones are recommended only in severe disease. o Antimicrobial prophylaxis for travelers' diarrhea is generally not recommended; however, prophylaxis should be considered in persons with inflammatory bowel disease, immunocompromised states, and comorbidities that would be adversely affected by significant dehydration. Dengue Fever, Chikungunyd, and Zika tIGURE 31. Petechialrash following application of blood pressure cuff constituting a positive "tourniquet test" that supports the presence of microvascular The dengue fever, chikungunya, and Zika arboviruses are fragility compatible with dengue fever. spread by daytime-feeding Aedes species mosquitoes, and their presentations are similar (Table a5). Diagnosis is confirmed by serologz (lgM and IgG) or Dengue fever is the most prevalent arthropod-borne reverse transcriptase PCR. Therapy is supportive. A live attenu viral infection in the world and the most frequent cause of ated dengue vaccine is approved for use only in persons aged 9 acute febrile illness among returning travelers from endemic areas, including Southeast Asia, the South Pacific, to 16 years. South and Central America, and the Caribbean. The incu- Beginning in 2013, chikungunya virus emerged in the bation period is 4 to 7 days. Patients may be asymptomatic Americas, with outbreaks in Central and South America and or present with an acute febrile illness associated with the Caribbean. No vaccine is available. Symptoms resemble frontal headache, retro-orbital pain, and myalgia; severe dengue fever, including fever and severe bilateral and sym- lumbosacral pain is characteristic (see Table 40). As the metrical polyarthralgia, often involving the hands and feet (see fever abates, a scarlatiniform rash, which spares the palms Table 40). Laboratory findings include lymphopenia, throm and soles, may evolve into areas of petechiae on extensor bocytopenia, and elevated aminotransferase levels. Definitive surfaces (Figure 31). Fever resolves after 5 to 7 days; how- diagnosis relies on serologic assays or viral RNA detection by ever, some patients experience a second febrile period (sad- reverse transcriptase PCR testing. Illness typically resolves dleback pattern). In patients with severe infection, spontaneously in 7 to 10 days. However, some patients experi life-threatening hemorrhage and shock may ensue, with ence rheumatologic symptoms for months or years. liver failure, encephalopathy, and myocardial damage. This Symptomatic treatment includes NSAIDs and aspirin avoid syndrome appears to be related to previous infection of a ance (risk of bleeding complications and potential risk of Reye different serotype and is unlikely in travelers who have not syndrome in children). had dengue fever previously. Laboratory findings include Thousands of Zika virus infections were reported in leukopenia, thrombocytopenia, and elevated serum ami- the United States between 2015 and 2016, of which several notransferase levels. were presumed to be from local transmission. In 2018 and 2079, no Zika virus transmission by mosquitoes was reported in the continental United States. Sexual transmis TABLE 45. Important Clinical Distinguishing Features of sion from an infected male partner can occur. Most patients Arbovirus lnfection recover uneventfully after a mild illness. Fetal development ClinicalFinding Dengue Chikungunya Zika risks in pregnant women infected with Zika are a concern. Fever # # # Pregnant women must be advised against travel to areas Myalgia H + + where Zika outbreaks exist. Women who are pregnant and Arthralgia + # # those who are planning to conceive should consult the CDC website for current information when considering travel. Headache + # + Reverse transcriptase PCR testing on serum and urine is Conjunctivitis # used for diagnostic evaluation during the initial 2 weeks Rash + # # after illness onset. Thereafter, IgM antibody detection Bleeding # is used. Virus-specific plaque reduction neutralization tests Shock + can discriminate between Zika virus and cross-reacting antibodies against related flaviviruses. Treatment is I +++ = always; ++ = common; + = rare; - = almost never supportive.

Dengue Fever, Chikungunyd, and Zika tIGURE 31. Petechialrash following application of blood pressure cuff constituting a positive "tourniquet test" that supports the presence of microvascular The dengue fever, chikungunya, and Zika arboviruses are fragility compatible with dengue fever. spread by daytime-feeding Aedes species mosquitoes, and their presentations are similar (Table a5). Diagnosis is confirmed by serologz (lgM and IgG) or Dengue fever is the most prevalent arthropod-borne reverse transcriptase PCR. Therapy is supportive. A live attenu viral infection in the world and the most frequent cause of ated dengue vaccine is approved for use only in persons aged 9 acute febrile illness among returning travelers from endemic areas, including Southeast Asia, the South Pacific, to 16 years. South and Central America, and the Caribbean. The incu- Beginning in 2013, chikungunya virus emerged in the bation period is 4 to 7 days. Patients may be asymptomatic Americas, with outbreaks in Central and South America and or present with an acute febrile illness associated with the Caribbean. No vaccine is available. Symptoms resemble frontal headache, retro-orbital pain, and myalgia; severe dengue fever, including fever and severe bilateral and sym- lumbosacral pain is characteristic (see Table 40). As the metrical polyarthralgia, often involving the hands and feet (see fever abates, a scarlatiniform rash, which spares the palms Table 40). Laboratory findings include lymphopenia, throm and soles, may evolve into areas of petechiae on extensor bocytopenia, and elevated aminotransferase levels. Definitive surfaces (Figure 31). Fever resolves after 5 to 7 days; how- diagnosis relies on serologic assays or viral RNA detection by ever, some patients experience a second febrile period (sad- reverse transcriptase PCR testing. Illness typically resolves dleback pattern). In patients with severe infection, spontaneously in 7 to 10 days. However, some patients experi life-threatening hemorrhage and shock may ensue, with ence rheumatologic symptoms for months or years. liver failure, encephalopathy, and myocardial damage. This Symptomatic treatment includes NSAIDs and aspirin avoid syndrome appears to be related to previous infection of a ance (risk of bleeding complications and potential risk of Reye different serotype and is unlikely in travelers who have not syndrome in children). had dengue fever previously. Laboratory findings include Thousands of Zika virus infections were reported in leukopenia, thrombocytopenia, and elevated serum ami- the United States between 2015 and 2016, of which several notransferase levels. were presumed to be from local transmission. In 2018 and 2079, no Zika virus transmission by mosquitoes was reported in the continental United States. Sexual transmis TABLE 45. Important Clinical Distinguishing Features of sion from an infected male partner can occur. Most patients Arbovirus lnfection recover uneventfully after a mild illness. Fetal development ClinicalFinding Dengue Chikungunya Zika risks in pregnant women infected with Zika are a concern. Fever # # # Pregnant women must be advised against travel to areas Myalgia H + + where Zika outbreaks exist. Women who are pregnant and Arthralgia + # # those who are planning to conceive should consult the CDC website for current information when considering travel. Headache + # + Reverse transcriptase PCR testing on serum and urine is Conjunctivitis # used for diagnostic evaluation during the initial 2 weeks Rash + # # after illness onset. Thereafter, IgM antibody detection Bleeding # is used. Virus-specific plaque reduction neutralization tests Shock + can discriminate between Zika virus and cross-reacting antibodies against related flaviviruses. Treatment is I +++ = always; ++ = common; + = rare; - = almost never supportive. 66

Travel Medicine KEY POIilTS Rickettsial lnfection o Dengue fever typically presents with acute febrile ill- Rickettsial infections occur worldwide and are transmitted by ness, frontal headache, retro-orbital pain, myalgia, and fleas, lice, mites, and ticks. Rickettsio typhi (murine typhus) is arthralgia, with or without minor spontaneous bleed- prevalent in tropical and subtropical areas, but it can also ing; gastrointestinal or respiratory symptoms may pre- occur in Texas, California, and Hawaii. Rickettsiaprowazekiis dominate, and severe lumbosacral pain is characteristic. the only rickettsial species transmitted by human body lice . Symptoms of chikungunya resemble dengue fever, and has a worldwide distribution. including abrupt fever and severe bilateral and symmet African tick-bite fever (Rickettsio africae) is second rical polyarthralgia, often involving the hands and feet; a only to malaria as the cause of febrile illness in those who maculopapular rash on the limbs and trunk is common. have journeyed to Africa, especially South Africa. Symptoms o Of most concern inZikavirus infection is the risk to include fever, headache, malaise, conjunctivitis, and phar fetal development in infected pregnant women. yngitis often accompanied by a maculopapular, vesicular, or petechial rash. Following the bite of an infected tick or mite, an eschar with regional lymphadenopathy develops at the site of inoculation with R. africae, Rickettsia conorii Hepatitis Virus lnfestions (lt4editerranean spotted fever) , and Orientia tsutsugamushi Hepatitis A virus (UaV) infection is acquired through ingestion (scrub typhus). Microvascular permeability is the hallmark of of food and water contaminated with human feces. Travel to rickettsial infections, with extensive vasculitic-appearing skin Central and South America, Mexico, South Asia, and Africa lesions. Severe complications may include shock, meningoen- poses the greatest risk of infection. cephalitis, and organ damage. Recrudescent attacks are known Hepatitis A vaccination is recommended for persons to occur months and even years later. traveling to developing countries who are not already immune Diagnosis is conflrmed by PCR, immunohistochemical (see Table 39). Protective antibody titers develop within 2 to analysis of tissue samples, or culture during the acute stage of 4 weeks in almost 100% of healthy recipients after the initial illness before antibiotic initiation. Confirmatory serologic dose. A second dose is given 6 to 18 months after the initial assays often do not detect antibodies until the convalescent injection. Serum immune globulin is indicated for those who phase of illness. When clinical suspicion is high, empiric ther- decline vaccination or are allergic to its components. Immune apy is warranted. The treatment of choice for all rickettsial globulin should also be considered in addition to vaccination infections is doxycycline for 7 to 10 days. if travel is scheduled within 2 weeks for adults older than t(EV POtr{T3 40 years, immunocompromised persons, and persons with chronic liver disease and other chronic medical conditions (for o Rickettsial infections occur worldwide, with clinical further information, see MKSAP 19 Gastroenterologz and presentation including fever, headache, malaise, con- Hepatologr). junctivitis, and pharyngitis often accompanied by a Previously unvaccinated persons traveling to areas where maculopapular, vesicular, or petechial rash. hepatitis B virus is prevalent (sub-Sahara Africa and Western . The treatment of choice for all rickettsial infections is Pacific) warrant pretravel vaccination. Health care workers, doxycycline for 7 to 10 days. persons seeking medical or dental care, or those likely to engage in sexual activity with local residents or undergoing tattooing have an increased risk of transmission and should be Brucellosis vaccinated regardless of destination before all international Human brucellosis may follow ingestion of unpasteurized travel (see Table 39). dairy products or undercooked meat, by direct contact with See MKSAP 19 Gastroenterology and Hepatologz for dis- fluids from infected animals, or by inhalation of contaminated cussion of hepatitis C virus. aerosols. The highest prevalence is found in the Mediterranean KEY POIilTS countries, Balkans, Persian Gult Middle East, and Central and . Hepatitis A immunity develops within 2to 4 weeks of South America. vaccination; vaccination and immune globulin are rec- Symptoms include fever, myalgia, arthralgia, fatigue, ommended if travel is scheduled within 2 weeks for headache, and night sweats. Focal infection may involve the adults older than 40 years and those with chronic central nervous system and osteoarticular, cardiovascular, and medical conditions. genitourinary systems. Disease relapse and chronic infection may occur. . An accelerated vaccination schedule (0, 7, and 21-30 days) Diagnosis relies on cultures of blood, bone marrow other is available in a combined hepatitis A/B vaccine; a booster body fluids, or tissue. An initial elevated titer of 1:160 or greater dose is required at 12 months to ensure long-term on the serum agglutination test or demonstration of a fourfold protection. increase from acute to convalescent titers is diagnostic.

KEY POIilTS Rickettsial lnfection o Dengue fever typically presents with acute febrile ill- Rickettsial infections occur worldwide and are transmitted by ness, frontal headache, retro-orbital pain, myalgia, and fleas, lice, mites, and ticks. Rickettsio typhi (murine typhus) is arthralgia, with or without minor spontaneous bleed- prevalent in tropical and subtropical areas, but it can also ing; gastrointestinal or respiratory symptoms may pre- occur in Texas, California, and Hawaii. Rickettsiaprowazekiis dominate, and severe lumbosacral pain is characteristic. the only rickettsial species transmitted by human body lice . Symptoms of chikungunya resemble dengue fever, and has a worldwide distribution. including abrupt fever and severe bilateral and symmet African tick-bite fever (Rickettsio africae) is second rical polyarthralgia, often involving the hands and feet; a only to malaria as the cause of febrile illness in those who maculopapular rash on the limbs and trunk is common. have journeyed to Africa, especially South Africa. Symptoms o Of most concern inZikavirus infection is the risk to include fever, headache, malaise, conjunctivitis, and phar fetal development in infected pregnant women. yngitis often accompanied by a maculopapular, vesicular, or petechial rash. Following the bite of an infected tick or mite, an eschar with regional lymphadenopathy develops at the site of inoculation with R. africae, Rickettsia conorii Hepatitis Virus lnfestions (lt4editerranean spotted fever) , and Orientia tsutsugamushi Hepatitis A virus (UaV) infection is acquired through ingestion (scrub typhus). Microvascular permeability is the hallmark of of food and water contaminated with human feces. Travel to rickettsial infections, with extensive vasculitic-appearing skin Central and South America, Mexico, South Asia, and Africa lesions. Severe complications may include shock, meningoen- poses the greatest risk of infection. cephalitis, and organ damage. Recrudescent attacks are known Hepatitis A vaccination is recommended for persons to occur months and even years later. traveling to developing countries who are not already immune Diagnosis is conflrmed by PCR, immunohistochemical (see Table 39). Protective antibody titers develop within 2 to analysis of tissue samples, or culture during the acute stage of 4 weeks in almost 100% of healthy recipients after the initial illness before antibiotic initiation. Confirmatory serologic dose. A second dose is given 6 to 18 months after the initial assays often do not detect antibodies until the convalescent injection. Serum immune globulin is indicated for those who phase of illness. When clinical suspicion is high, empiric ther- decline vaccination or are allergic to its components. Immune apy is warranted. The treatment of choice for all rickettsial globulin should also be considered in addition to vaccination infections is doxycycline for 7 to 10 days. if travel is scheduled within 2 weeks for adults older than t(EV POtr{T3 40 years, immunocompromised persons, and persons with chronic liver disease and other chronic medical conditions (for o Rickettsial infections occur worldwide, with clinical further information, see MKSAP 19 Gastroenterologz and presentation including fever, headache, malaise, con- Hepatologr). junctivitis, and pharyngitis often accompanied by a Previously unvaccinated persons traveling to areas where maculopapular, vesicular, or petechial rash. hepatitis B virus is prevalent (sub-Sahara Africa and Western . The treatment of choice for all rickettsial infections is Pacific) warrant pretravel vaccination. Health care workers, doxycycline for 7 to 10 days. persons seeking medical or dental care, or those likely to engage in sexual activity with local residents or undergoing tattooing have an increased risk of transmission and should be Brucellosis vaccinated regardless of destination before all international Human brucellosis may follow ingestion of unpasteurized travel (see Table 39). dairy products or undercooked meat, by direct contact with See MKSAP 19 Gastroenterology and Hepatologz for dis- fluids from infected animals, or by inhalation of contaminated cussion of hepatitis C virus. aerosols. The highest prevalence is found in the Mediterranean KEY POIilTS countries, Balkans, Persian Gult Middle East, and Central and . Hepatitis A immunity develops within 2to 4 weeks of South America. vaccination; vaccination and immune globulin are rec- Symptoms include fever, myalgia, arthralgia, fatigue, ommended if travel is scheduled within 2 weeks for headache, and night sweats. Focal infection may involve the adults older than 40 years and those with chronic central nervous system and osteoarticular, cardiovascular, and medical conditions. genitourinary systems. Disease relapse and chronic infection may occur. . An accelerated vaccination schedule (0, 7, and 21-30 days) Diagnosis relies on cultures of blood, bone marrow other is available in a combined hepatitis A/B vaccine; a booster body fluids, or tissue. An initial elevated titer of 1:160 or greater dose is required at 12 months to ensure long-term on the serum agglutination test or demonstration of a fourfold protection. increase from acute to convalescent titers is diagnostic. 67

lnfectious Gastrointestinal Syndromes The treatment of choice for uncomplicated brucellosis is America. Clinical manifestations range from mild to severe extended therapy with doxycycline plus either rifampin or life-threatening disease with a 30% to 60% mortality rate. gentamicin. Neurobrucellosis requires several months of com- Diagnosis is confirmed by detection of viral RNA by reverse bined ceftriaxone, doxycycline, and rifampin. transcriptase PCR or virus isolation performed ear$ in the course of disease or by the presence of IgM antibodies. I(EY POIl{T Treatment is supportive. Vaccination with the approved, live- . The treatment of choice for uncomplicated brucellosis attenuated yellow fever vaccine is recommended for travelers is doxycycline plus either rifampin or gentamicin; neu- to endemic areas of Africa and South America. A certificate of robrucellosis requires several months of combined cef- proof of vaccination is required for entry into several endemic triaxone, doxycycline, and rifampin. countries, and travelers who have recently visited yellow fever zones are prohibited entrance to some nonendemic countries without similar documentation (www.cdc.gov/travel). The Japanese Encephalitis yellow fever vaccine in the United States is currently unavail- Japanese encephalitis virus is a flavivirus transmitted by mos- able. Authorization from the FDA to use an alternate European quitos. It is the most prevalent cause of vaccine-preventable vaccine can be obtained. infectious encephalitis throughout most of Asia and parts of the western Pacific. The risk of infection for most travelers is low and most infected persons remain asymptomatic. A few persons (<l%) who develop clinical disease present with I nfectious Gastroi ntesti na I encephalitis. The mortality rate is 20"/. to 30%. Syndromes Diagnosis is confirmed by the detection of virus-specific IgM antibodies in the cerebrospinal fluid. Viral RNA detection Overview is definitive but insensitive. Treatment is supportive. In the Diarrhea is defined as three or more unformed stools daily. United States, a two-dose inactivated vaccine is available and Diarrhea lasting less than 14 days is considered acute, 14 to recommended for travelers to endemic areas based on risk 30 days is persistent, and longer than 30 days is chronic. Acute stratification. infectious diarrheal presentations include acute gastroenteri- tis, with associated fever, nausea, vomiting, flatulence, tenes- mus, and crampy abdominal pain. Chronic infectious diarrhea Tick-Borne Encepha I itis is most likely caused by parasites. Not all diarrheal presenta- Tick-borne encephalitis is caused by three related subtypes of tions are infectious, such as inflammatory bowel disease, flaviviruses classified by their endemic geographic areas endocrine disorders, celiac disease, irritable bowel syndrome (European, Siberian, and Far Eastern). Most infections occur (lBS), and medication-induced diarrhea. between early spring and late fall. Those older than 50 years Generally, patients with mucoid or bloody diarrhea (i.e., have the greatest incidence of clinical infection. A biphasic i11- dysentery), fever, significant abdominal cramping, or sus- ness occurs in about one third of infected persons after an pected sepsis and those who are immunocompromised or incubation period (t-Z weeks), beginning with a nonspecific require hospitalization should have diagnostic assessment of phase (fever, headache, malaise, and arthralgia). A second their stool to guide antimicrobial use. Additional areas of con- neuroinvasive phase may develop in the few patients who do cern include persistent symptoms (>t week) or outbreak set- not fully recover, manifested by meningitis, encephalitis, tings where day-care participants, institutional residents, altered mental status, seizures, cranial nerve palsies, and flac- health care providers, or food handlers are involved. cid para$sis. Disease severity, case fatality, and permanent Increasingly available, rapid multiplex molecular gastrointes- neurologic deficits increase with age and vary by geographic tinal assays that identify common bacterial, parasitic, and Iocation (Far Eastern is most severe, followed by Siberian and viral pathogens from a stool sample are generally more sensi- European). tive than stool culture and microscopy with special stains Diagnosis is confirmed by detection of IgM antibodies (Table 46). Isolates from culture, however, can provide antibi- from cerebrospinal fluid or serum. otic susceptibilities and strain-typing information in outbreak Inactivated vaccines based on European and Far Eastern situations that are unavailable from culture-independent diag- strains of virus (two each) are available in Europe and Russia nostic assays. but not licensed in the United Sates. Treatment is supportive. Most healthy patients with watery diarrhea of less than 3 days' duration can be treated with supportive care without diagnostic assessment. When acute diarrhea is debilitating Yellow Fever and associated with travel, antibiotic therapy with a fluoro- The yellow fever flavivirus belongs to the viral hemorrhagic quinolone, azithromycin, or rifaximin is recommended; if not fever group. Infection is transmitted by mosquitoes in endemic travel associated and fever of38.3 'C (101'F) or greater persists areas of sub-Saharan Africa and tropical regions of South for 3 or more days, then microbiologic assessment should be

The treatment of choice for uncomplicated brucellosis is America. Clinical manifestations range from mild to severe extended therapy with doxycycline plus either rifampin or life-threatening disease with a 30% to 60% mortality rate. gentamicin. Neurobrucellosis requires several months of com- Diagnosis is confirmed by detection of viral RNA by reverse bined ceftriaxone, doxycycline, and rifampin. transcriptase PCR or virus isolation performed ear$ in the course of disease or by the presence of IgM antibodies. I(EY POIl{T Treatment is supportive. Vaccination with the approved, live- . The treatment of choice for uncomplicated brucellosis attenuated yellow fever vaccine is recommended for travelers is doxycycline plus either rifampin or gentamicin; neu- to endemic areas of Africa and South America. A certificate of robrucellosis requires several months of combined cef- proof of vaccination is required for entry into several endemic triaxone, doxycycline, and rifampin. countries, and travelers who have recently visited yellow fever zones are prohibited entrance to some nonendemic countries without similar documentation (www.cdc.gov/travel). The Japanese Encephalitis yellow fever vaccine in the United States is currently unavail- Japanese encephalitis virus is a flavivirus transmitted by mos- able. Authorization from the FDA to use an alternate European quitos. It is the most prevalent cause of vaccine-preventable vaccine can be obtained. infectious encephalitis throughout most of Asia and parts of the western Pacific. The risk of infection for most travelers is low and most infected persons remain asymptomatic. A few persons (<l%) who develop clinical disease present with I nfectious Gastroi ntesti na I encephalitis. The mortality rate is 20"/. to 30%. Syndromes Diagnosis is confirmed by the detection of virus-specific IgM antibodies in the cerebrospinal fluid. Viral RNA detection Overview is definitive but insensitive. Treatment is supportive. In the Diarrhea is defined as three or more unformed stools daily. United States, a two-dose inactivated vaccine is available and Diarrhea lasting less than 14 days is considered acute, 14 to recommended for travelers to endemic areas based on risk 30 days is persistent, and longer than 30 days is chronic. Acute stratification. infectious diarrheal presentations include acute gastroenteri- tis, with associated fever, nausea, vomiting, flatulence, tenes- mus, and crampy abdominal pain. Chronic infectious diarrhea Tick-Borne Encepha I itis is most likely caused by parasites. Not all diarrheal presenta- Tick-borne encephalitis is caused by three related subtypes of tions are infectious, such as inflammatory bowel disease, flaviviruses classified by their endemic geographic areas endocrine disorders, celiac disease, irritable bowel syndrome (European, Siberian, and Far Eastern). Most infections occur (lBS), and medication-induced diarrhea. between early spring and late fall. Those older than 50 years Generally, patients with mucoid or bloody diarrhea (i.e., have the greatest incidence of clinical infection. A biphasic i11- dysentery), fever, significant abdominal cramping, or sus- ness occurs in about one third of infected persons after an pected sepsis and those who are immunocompromised or incubation period (t-Z weeks), beginning with a nonspecific require hospitalization should have diagnostic assessment of phase (fever, headache, malaise, and arthralgia). A second their stool to guide antimicrobial use. Additional areas of con- neuroinvasive phase may develop in the few patients who do cern include persistent symptoms (>t week) or outbreak set- not fully recover, manifested by meningitis, encephalitis, tings where day-care participants, institutional residents, altered mental status, seizures, cranial nerve palsies, and flac- health care providers, or food handlers are involved. cid para$sis. Disease severity, case fatality, and permanent Increasingly available, rapid multiplex molecular gastrointes- neurologic deficits increase with age and vary by geographic tinal assays that identify common bacterial, parasitic, and Iocation (Far Eastern is most severe, followed by Siberian and viral pathogens from a stool sample are generally more sensi- European). tive than stool culture and microscopy with special stains Diagnosis is confirmed by detection of IgM antibodies (Table 46). Isolates from culture, however, can provide antibi- from cerebrospinal fluid or serum. otic susceptibilities and strain-typing information in outbreak Inactivated vaccines based on European and Far Eastern situations that are unavailable from culture-independent diag- strains of virus (two each) are available in Europe and Russia nostic assays. but not licensed in the United Sates. Treatment is supportive. Most healthy patients with watery diarrhea of less than 3 days' duration can be treated with supportive care without diagnostic assessment. When acute diarrhea is debilitating Yellow Fever and associated with travel, antibiotic therapy with a fluoro- The yellow fever flavivirus belongs to the viral hemorrhagic quinolone, azithromycin, or rifaximin is recommended; if not fever group. Infection is transmitted by mosquitoes in endemic travel associated and fever of38.3 'C (101'F) or greater persists areas of sub-Saharan Africa and tropical regions of South for 3 or more days, then microbiologic assessment should be 68