Fever in a traveler returning from Ethiopia

Ken Koon Wong

doi:10.3949/ccjm.87a.19017

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Figure 1
Workup of fever in a returning traveler.
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Figure 2
Two Giemsa-stained, thin-film blood smear photomicrographs. Left, a Plasmodium falciparum macrogametocyte; right, a microgametocyte. Image by US Centers for Disease Control and Prevention, Steven Glenn, Laboratory & Consultation Division 1979.

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TABLE 1

Incubation periods of common travel-related infections^a

Short (< 10 days)	Medium (10–21 days)	Long (> 21 days)
Bacteria Typhoid and paratyphoid Bacterial diarrhea Bacterial pneumonia Neisseria meningitidis Brucella species Rickettsia species Spirochetes Relapsing fever (Borrelia recurrentis) Leptospirosis Viruses Hemorrhagic fevers^b Respiratory viruses Influenza, Middle East respiratory syndrome coronavirus (MERS-CoV) Measles Protozoa Malaria African trypanosomiasis Amoebic dysentery Parasite Fascioliasis	Bacteria Typhoid and paratyphoid Brucella species Rickettsia species Spirochete Leptospirosis Viruses Hemorrhagic fevers^b Human immunodeficiency virus (acute) Cytomegalovirus Hepatitis A Rabies Measles Chicken pox (varicella) Protozoa Malaria Giardia Toxoplasma African trypanosomiasis Parasite Babesia	Bacteria Rickettsia species Brucella species Bartonellosis Tuberculosis Spirochetes Leptospirosis Syphilis Viruses HIV (acute) Hepatitis B, hepatitis C Epstein-Barr virus Cytomegalovirus Rabies Measles Protozoa Malaria Leishmaniasis African trypanosomiasis Parasites Filariasis Leishmaniasis Amebic liver abscess Babesia

↵a Bold-face type indicates a serious transmissible infection; isolation precaution is mandatory when such infections are suspected.
↵b Viruses that cause hemorrhagic fevers in humans comprise 5 distinct families:
- Arenaviridae (lymphocytic choriomeningitis virus, Junin virus, Machupo virus, Lassa virus, Guanarito virus, Sabia virus, Chapare virus, Lujo virus)
- Bunyaviridae (orthobunyavirus, phlebovirus [eg, Rift Valley fever virus], nairovirus [eg, Crimean-Congo hemorrhagic fever], hantavirus)
- Flaviviridae (yellow fever, dengue fever, Japanese encephalitis, West Nile virus, Zika virus)
- Filoviridae (cuevavirus, Marburgvirus, Ebolavirus)
- Paramyxoviridae (measles, mumps, Newcastle disease virus, Hendra virus, Nipah virus).

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TABLE 2

Causes of relative bradycardia

Diseases that cause relative bradycardia^a
Infections Legionella Psittacosis Q fever Typhus (Rickettsia typhi, Orientia tsutsugamushi) Typhoid fever (Salmonella typhi) Babesiosis Malaria Leptospirosis Yellow fever Dengue Viral hemorrhagic fevers Rocky Mountain spotted fever
Noninfectious causes Beta-blockers Drug fever Central nervous system lesions Lymphomas Factitious fever
Diseases not associated with relative bradycardia
Infections Mycoplasma pneumoniae Streptococcus pneumoniae Salmonella (nontyphoidal)

↵a A median increase in heart rate of less than 10 beats per minute for every increase of 1ºC in body temperature.

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TABLE 3

Diseases that mosquitoes carry

Anopheles
Malaria (Plasmodium species)
O’nyong’nyong

Aedes
Dengue fever
Yellow fever (Africa)
West Nile fever
Chikungunya
Eastern equine encephalitis
Zika virus

Culex
West Nile virus
Japanese encephalitis
St. Louis encephalitis

Haemogogus
Yellow fever (South America)

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TABLE 4

Severe malaria definition and treatment^a

Definition	Treatment
Positive blood smear and at least one of the following criteria: Impaired consciousness or coma Severe normocytic anemia (hemoglobin < 7 g/dL) Acute kidney injury Acute respiratory distress syndrome Hypotension Disseminated intravascular coagulation Spontaneous bleeding Acidosis Hemoglobinuria Jaundice Repeated generalized convulsions Parasitemia ≥ 5%	Intravenous artesunate is available under an expanded-access investigational new drug protocol (call the US Centers for Disease Control and Prevention) and Artemether-lumefantrine, atovaquone-proguanil, doxycycline (clindamycin in pregnant women); if no other options, mefloquine

↵a Severe malaria is most often caused by Plasmodium falciparum.

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TABLE 5

Treatment of uncomplicated malaria

Plasmodium species	Region	Recommended medication
P falciparum or species not identified	Chloroquine-resistant (all areas except Central America or the Caribbean) or unknown	Atovaquone-proguanil Artemether-lumefantrine Quinine sulfate + doxycyline, clindamycin, or tetracycline Mefloquine^a
P falciparum or species not identified	Chloroquine-sensitive (Central America or the Caribbean)	Chloroquine phosphate Hydroxychloroquine
**P malariae or P knowlesi**	All	Chloroquine phosphate Hydroxychloroquine
**P vivax or P ovale**	Chloroquine-sensitive	Chloroquine phosphate + primaquine phosphate or tafenoquine Hydroxychloroquine + primaquine phosphate or tafenoquine
*P vivax*	Chloroquine-resistant (Papua New Guinea or Indonesia)	Quinine sulfate + doxycyline or tetracycline + primaquine phosphate or tafenoquine Atovaquone-proguanil + primaquine phosphate or tafenoquine Mefloquine + primaquine phosphate or tafenoquine
Alternatives for pregnant women	Chloroquine-sensitive	Chloroquine phosphate Hydroxychloroquine
Alternatives for pregnant women	Chloroquine-resistant P falciparum and P vivax	Artemether-lumefantrine (2nd or 3rd trimester only) Quinine sulfate + clindamycin (all trimesters) Mefloquine (all trimesters)^a

↵a Do not use in mefloquine-resistant areas (eg, Thailand, Myanmar, Cambodia, Vietnam).

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TABLE 6

Risk factors for acquiring malaria

Risk factors	Not risk factors
Rural setting	Urban setting
Camping	Air-conditioned environment
Longer duration of stay	Shorter duration of stay
Altitude of destination (< 2,000 m above sea level)	High altitude (≥ 2,000 m above sea level)
Inappropriate chemoprophylaxis	Appropriate chemoprophylaxis with good adherence
Visiting friends and relatives (eg, immigrants who return to home country to visit friends and relatives)

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TABLE 7

Chemoprophylaxis for malaria

Drug	Adult dosage	Adverse effects and cautions	Price^a
Chloroquine phosphate^b	500 mg (300 mg base) once every week Start 1–2 weeks before travel; stop 4 weeks after leaving malaria-endemic area	Hypoglycemia, potential retinopathy from prolonged use Only in chloroquine-sensitive areas (Central America and Caribbean)	$23.11–$55.60 (7 tablets)
Atovaquone-proguanil	250 mg/100 mg daily Start 1–2 days before travel; stop 1 week after leaving malaria- endemic area	Diarrhea, dreams, oral ulcers, headache Take with food or whole milk Contraindicated in severe renal impairment (creatinine clearance < 30 mL/min)	$64.10–$86.02 (30 tablets)
Doxycycline	100 mg daily Start 1–2 days before travel; stop 4 weeks after leaving malaria-endemic area	Drug-induced esophagitis, photosensitivity Do not use in children < 8 years old or in pregnant women	$13.65–$52.23 (30 tablets)^{^b,^c}
Mefloquine^{^b,^d}	250 mg once every week Start 2 or more weeks before travel; stop 4 weeks after leaving malaria-endemic area	Do not use in individuals with cardiac conduction abnormalities, history of seizures, or serious psychiatric illnesses Do not use in first trimester of pregnancy	$30–$46.97 (8 tablets)
Primaquine phosphate	30 mg daily Start 1–2 days before travel; stop 1 week after leaving malaria-endemic area	Contraindicated in glucose-6 phosphate dehydrogenase (G6PD) deficiency and women who breastfeed G6PD-deficient infants	$37.68–$47.73 (28 tablets)
Tafenoquine	Loading: 200 mg daily starting 3 days before travel Maintenance: 200 mg/week while in malaria-endemic area, starting 7 days after the last loading dose Terminal prophylaxis: 200 mg once, 7 days after the last maintenance dose	Contraindicated in G6PD deficiency and women who breastfeed G6PD-deficient infants Contraindicated in patients with history of psychotic disorders or current psychotic symptoms	$37.52–$42.41 (2 Krintafel 150-mg tablets)

↵a Drug price obtained from www.goodrx.com on 10/25/19 at 11:33 AM.
↵b Can be used in pregnancy.
↵c Doxycyline monohydrate.
↵d Do not use if traveling to mefloquine-resistant areas (eg, Thailand, Myanmar, Cambodia, Vietnam).