Approach to illness associated with travel to North Africa

INTRODUCTION — 

The evaluation of illness in returned travelers should focus on the possible infections, given the patient's clinical findings, travel geography, administration (if any) of vaccinations, the nature and timeframe of potential exposure(s), and the incubation period(s) of the relevant possible infections (table 1) [1].

Good resources that provide current information about the infections that occur in various geographic areas are essential [2-4]. The United States Centers for Disease Control and Prevention website includes an online version of Health Information for International Travel under Travelers' Health and updates on travel-related infections [4,5]. The World Health Organization website also has regularly updated information about outbreaks.

The approach to evaluation of illness associated with travel to North Africa will be reviewed here.

Issues related to travel to other regions are discussed separately:

●(See "Approach to illness associated with travel to East Africa".)

●(See "Approach to illness associated with travel to Central Africa".)

●(See "Approach to illness associated with travel to West Africa".)

●(See "Diseases potentially acquired by travel to Southern Africa".)

●(See "Approach to illness associated with travel to Latin America and the Caribbean".)

●(See "Approach to illness associated with travel to East Asia".)

●(See "Approach to illness associated with travel to Southeast Asia".)

●(See "Approach to illness associated with travel to South Asia".)

GEOGRAPHY — 

North Africa refers to the region of the continent of Africa north of the Sahara Desert. For the purposes of this discussion, the countries within this region are Algeria, the Canary Islands (Spain), Egypt, Libya, Morocco, and Tunisia.

This region is characterized by fertile coastal areas and a desert hinterland.

INITIAL EVALUATION — 

The focus of the initial evaluation should be on diagnosis of infections that are treatable, transmissible, and/or have serious sequelae (table 2).

History and physical examination — The clinical history should establish a number of clinical details and include a review of the preceding 12 months prior to presentation (table 3) [6-8]:

●Careful documentation of signs and symptoms and their time of onset – Understanding the clinical timeline is important for establishing the likely incubation period, which is useful for narrowing the differential diagnosis. The causes of travel-associated fever based on the interval since exposure are summarized in the table and figure (table 4 and figure 1).

●The nature of travel (including geographic region, travel dates, type of transportation, and nature of accommodations) – The patient should be asked specifically about travel to areas with malaria transmission (figure 2 and figure 3) and/or areas with ongoing outbreaks (such as viral hemorrhagic fevers or meningitis) [5]. In some circumstances, infection control precautions may be warranted based on clinical and exposure history before diagnostic results are available (table 5).

●Relevant activities and exposures (such as consumption of unsafe water or undercooked food, insect bites, animal exposure, sexual contact). (See 'Consider the exposure history' below.)

●General medical information (including vaccination history, past medical history, and medications).

Physical findings that signal severe illness warranting prompt intervention include hemodynamic instability, respiratory distress, hemorrhagic manifestations, and neurologic findings such as confusion, lethargy, stiff neck, or focal deficits. The physical examination should also include evaluation for skin lesions, lymphadenopathy, retinal or conjunctival changes, enlargement of liver or spleen, genital lesions, and neurologic findings.

Laboratory tests — The initial laboratory evaluation for travelers with fever should include complete blood count and differential, liver enzymes, blood cultures and blood smears, rapid diagnostic test for malaria (if there was exposure to an area with malaria transmission), and/or rapid diagnostic testing for respiratory viruses. Additional studies depend upon exposures and other factors (table 6).

SUBSEQUENT CLINICAL APPROACH

Consider the presenting syndrome — The clinical manifestations should be considered in conjunction with the patient's geographic exposure, the timing of clinical presentation relative to the incubation periods of relevant infections, and the patient's activities while traveling that may represent potential pathogen exposure. Some important syndromic presentations are summarized below with respect to these factors.

Systemic febrile illness

Incubation period ≤10 days — The differential diagnosis of fever with an incubation period ≤10 days since exposure in a returning traveler includes:

●Dengue (see 'Jaundice' below)

●Zika virus infection (see 'Rash' below)

●Leptospirosis (see 'Jaundice' below)

●Rickettsial infection (see 'Rash' below)

●Enteric fever – "Enteric fever" refers to both typhoid fever (caused by Salmonella enterica serotype Typhi [formerly S. Typhi]) and paratyphoid fever (caused by S. enterica serotypes Paratyphi A, B, and C worldwide). Enteric fever is characterized by abdominal pain, fever, and chills. Classic manifestations include relative bradycardia, pulse-temperature dissociation, and "rose spots" (faint salmon-colored macules on the trunk and abdomen). Hepatosplenomegaly, intestinal bleeding, and perforation may occur, leading to secondary bacteremia and peritonitis. The disease occurs worldwide; regions of highest incidence include South Asia, Southeast Asia, and Southern Africa. Transmission is fecal-oral; the incubation period is 6 to 30 days. The diagnosis is established via culture. (See 'Rash' below and "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)

●Viral hemorrhagic fever

•Rift valley fever – Rift valley fever is transmitted via bites from infected mosquitoes or through close contact with infected mammals. Localized outbreaks of Rift Valley fever have occurred in the Nile River valley of Egypt. Symptoms include fever, headache, bleeding, malaise, muscle pain, back pain, vomiting, and joint pain. The diagnosis is established by serology or polymerase chain reaction (PCR).

•Crimean-Congo hemorrhagic fever – Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease transmitted by ticks or by contact with body fluids from infected patients. North Africa is not regarded as a risk area for CCHF; however, there is evidence for transmission in animals [9]. The incubation period following a tick bite is typically one to three days; the incubation period following contact with body fluids is typically three to seven days. Clinical manifestations include sudden onset of fever, headache, malaise, myalgia, sore throat, dizziness, conjunctivitis, photophobia, abdominal pain, nausea, and vomiting. In severe cases, hemorrhagic manifestations (petechiae, ecchymoses, epistaxis, and gum bleeding) are observed. The diagnosis is established by PCR or serology. (See "Crimean-Congo hemorrhagic fever".)

●Relapsing fever – Relapsing fever is characterized by recurring febrile episodes that last approximately three days and are separated by afebrile periods. Transmission is via a tick or louse bearing Borrelia spirochetes. Relapsing fever occurs on every continent except Australia and Antarctica. The incubation period is typically 4 to 14 days; the diagnosis is established via blood smear or serologic testing. (See "Clinical features, diagnosis, and management of relapsing fever".)

There is no risk of malaria in North Africa.

The differential diagnosis of acute fever also includes etiologies that may not be specific to international travel, such as urinary tract infection, influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or infectious mononucleosis.

Incubation period >10 days — The differential diagnosis of fever with an incubation period >10 days since exposure in a returning traveler includes:

●Enteric fever (see 'Incubation period ≤10 days' above)

●Acute human immunodeficiency (HIV) infection (see 'Rash' below)

●Q fever (see 'Respiratory symptoms' below)

●Tuberculosis (see 'Respiratory symptoms' below)

●Viral hemorrhagic fever – Forms of viral hemorrhagic fever in North Africa include Rift Valley fever and CCHF. (See 'Incubation period ≤10 days' above.)

●Visceral leishmaniasis (rare) – Visceral leishmaniasis is characterized by subacute progression of malaise, fever, weight loss, and splenomegaly (with or without hepatomegaly) over a period of months. Transmission occurs via sand fly bites. In North Africa, Leishmania infantum is the principal cause of visceral leishmaniasis. The incubation period is usually two to six months; the diagnosis is established by histopathology or culture. (See "Visceral leishmaniasis: Clinical manifestations and diagnosis".)

●Brucellosis (rare) – Brucellosis is characterized by fever, night sweats, anorexia, arthralgia, fatigue, and weight loss. Transmission occurs via contact with fluids from infected animals (sheep, cattle, goats, pigs, or other animals) or is derived from food products such as unpasteurized milk and cheese. Major endemic areas include the Mediterranean basin, the Persian Gulf, the Indian subcontinent, and parts of Mexico and Central and South America; Africa sustains a large proportion of global risk, including parts of North Africa [10]. The incubation is usually one to four weeks but may be several months. The diagnosis is established by culture or serologic testing. (See "Brucellosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Schistosomiasis (see 'Rash' below)

The differential diagnosis of prolonged fever also includes etiologies that may be nonspecific to travel, such as endocarditis or occult abscess. Noninfectious etiologies, such as malignancy, should also be considered.

Gastrointestinal symptoms

●Travelers' diarrhea – Travelers' diarrhea is classically caused by enterotoxigenic Escherichia coli and other bacterial and viral pathogens; it is characterized by watery diarrhea, malaise, anorexia, and abdominal cramps. Transmission is fecal-oral and most commonly occurs via ingestion of contaminated food or water. The incubation period depends on the pathogen and can range from <1 day to several days. Travel-associated diarrhea is usually self-limited. Patients with severe, prolonged, or bloody diarrhea warrant diagnostic evaluation. (See "Travelers' diarrhea: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Invasive enteropathies

•Campylobacter infection – Campylobacter infection is characterized by acute onset of watery or bloody diarrhea, abdominal pain and cramping, and nausea and vomiting. Fever frequently precedes onset of diarrhea and may be high grade. Campylobacter is a zoonotic bacterial infection acquired by ingesting contaminated food or water. Incubation is usually two to five days (range 1 to 10 days). Diagnosis is made by stool culture or PCR. (See "Campylobacter infection: Clinical manifestations, diagnosis, and treatment".)

•Shigellosis – Shigellosis is a bacterial infection of the distal small intestine and colon characterized by fever, diarrhea (sometimes bloody), nausea, and sometimes cramps and vomiting. Infection occurs worldwide and is acquired by ingestion of food or water that has been contaminated by an infected person. The incubation period is usually one to three days (up to a week). The diagnosis is established via stool culture or PCR. (See "Shigella infection: Epidemiology, clinical manifestations, and diagnosis".)

•Nontyphoidal salmonellosis – Nontyphoidal salmonellosis infection is characterized by diarrhea, nausea, vomiting, fever, and abdominal cramping. Infection occurs worldwide; transmission is fecal-oral. The incubation period is 6 to 72 hours, and diagnosis is established via culture or PCR of stool or blood culture. (See "Nontyphoidal Salmonella: Gastrointestinal infection and asymptomatic carriage".)

●Giardiasis – Giardiasis is characterized by diarrhea, malaise, abdominal cramps, and weight loss. Fever is not prominent. It occurs worldwide and is transmitted by waterborne, foodborne, or fecal-oral routes; the incubation period is typically 7 to 10 days (range 3 to 25 days). The diagnosis may be established by stool microscopy, antigen detection, or PCR. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis".)

●Cyclosporiasis – Cyclosporiasis is characterized by anorexia, nausea, flatulence, fatigue, abdominal cramping, diarrhea, low-grade fever, and weight loss. Transmission is via ingestion of contaminated food or water. The incubation period is approximately one week. The diagnosis is established via stool microscopy or PCR. (See "Cyclospora infection".)

●Cryptosporidiosis – Cryptosporidiosis is characterized by voluminous watery diarrhea and low-grade fever. Fever may precede onset of diarrhea. Infection occurs worldwide, and transmission occurs via waterborne, foodborne, or fecal-oral routes. The incubation period is 3 to 28 days, and the diagnosis is established via stool microscopy, PCR, or enzyme immunoassay. (See "Cryptosporidiosis: Epidemiology, clinical manifestations, and diagnosis".)

●Intestinal amebiasis – Intestinal amebiasis is characterized by loose stools that may be bloody; fever occurs in less than half of patients. Infection occurs worldwide, and transmission is fecal-oral. The incubation period is one to three weeks, and the diagnosis is established via serology or antigen testing together with detection of the parasite in stool or extraintestinal sites (such as liver abscess pus). (See "Intestinal Entamoeba histolytica amebiasis".)

●Liver abscess (rare) – Liver abscess occurs worldwide and may be pyogenic or amebic. It is characterized by fever and right upper quadrant pain, nausea, vomiting, anorexia, weight loss, and malaise. Some patients with amebic liver abscess report history of dysentery within the previous few months; the incubation period is 8 to 20 weeks (median 12 weeks). The diagnosis of liver abscess is made via radiographic imaging. Entamoeba histolytica infection may be established via serology, stool parasite examination, or PCR. Aspiration (for Gram stain, culture, and parasite examination) may be pursued in the setting of high suspicion for bacterial infection (older adults, prior history of gallstones, presence of fever). (See "Pyogenic liver abscess" and "Extraintestinal Entamoeba histolytica amebiasis", section on 'Amebic liver abscess'.)

●Strongyloidiasis – Most patients with Strongyloides infection do not experience prominent symptoms. When manifestations do occur, they may include abdominal pain with diarrhea, cough, or rash. Some patients have eosinophilia in the absence of symptoms. The disease is transmitted via penetration of larvae into the skin, and it is endemic in rural areas of tropical and subtropical regions. The incubation period is weeks to decades; the diagnosis is usually made by detecting rhabditiform larvae in concentrated stool or via serology. (See 'Respiratory symptoms' below and "Strongyloidiasis".)

●Echinococcosis (rare) – Clinical manifestations of Echinococcus multilocularis infection include right upper quadrant discomfort, malaise, and weight loss. The infection is transmitted via ingestion of a tapeworm whose life cycle includes a definitive host (usually dogs) and an intermediate host (such as sheep). Echinococcosis is endemic in Algeria, Morocco, Libya, Tunisia, and Egypt [11]. Onset of clinical manifestations typically occurs decades following infection. The diagnosis is typically established by ultrasound imaging in combination with serologic testing.

The differential diagnosis of gastrointestinal symptoms also includes cosmopolitan etiologies unrelated to travel, such as appendicitis, cholecystitis, pancreatitis, cholangitis due to stones, or new-onset inflammatory bowel disease.

Jaundice — Travel-related infections associated with jaundice include:

●Acute viral hepatitis

•Hepatitis A and E are acute infections transmitted by the fecal-oral route; the incubation period ranges from 15 to 60 days. Hepatitis A is characterized by nausea, vomiting, anorexia, fever, malaise, and abdominal pain; the infection is usually self-limited and occurs worldwide. The average incubation period is 28 days (range 15 to 50 days). Hepatitis E is usually asymptomatic; symptoms occur in up to 5 percent of cases and resemble those of hepatitis A. Hepatitis E occurs worldwide; the prevalence is highest in Asia and Africa. The infections are diagnosed by serology or PCR. (See "Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis" and "Hepatitis E virus infection".)

•Hepatitis B and C can present acutely or chronically and are transmitted by body fluids. Hepatitis D infection always occurs in association with hepatitis B infection. The incubation periods of hepatitis B and C are 4 to 16 weeks and 2 to 26 weeks, respectively. Hepatitis B and C occur worldwide. The infections are diagnosed by serology or PCR. (See "Hepatitis B virus: Clinical manifestations and natural history" and "Hepatitis B virus: Screening and diagnosis in adults" and "Epidemiology, clinical manifestations and diagnosis of hepatitis D virus infection" and "Clinical manifestations and natural history of chronic hepatitis C virus infection" and "Screening and diagnosis of chronic hepatitis C virus infection".)

●Leptospirosis – Leptospirosis is characterized by fever, rigors, myalgia, conjunctival suffusion, and headache; respiratory involvement can develop as a complication. Less common symptoms and signs include cough, nausea, vomiting, diarrhea, abdominal pain, and jaundice. It is transmitted via exposure to animal urine, contaminated water or soil, or infected animal tissue; outbreaks in endemic areas are associated with increased rainfall or flooding. The incubation is 2 to 29 days. The diagnosis is established via serology or culture of blood or urine. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Severe dengue fever – The cardinal features of dengue hemorrhagic fever include fever, increased vascular permeability, hemorrhagic manifestations, and marked thrombocytopenia (≤100,000 cells/mm³). The virus is transmitted by Aedes aegypti mosquitoes, which have broad epidemiologic distribution (figure 4); the incubation period is four to seven days (range 3 to 10 days). The diagnosis is established via PCR, antigen, or serologic testing. (See 'Rash' below and "Dengue virus infection: Clinical manifestations and diagnosis".)

There is no risk of yellow fever in North Africa.

The differential diagnosis of fever with jaundice also includes etiologies that may be nonspecific to travel, such as cytomegalovirus infection and Epstein-Barr virus infection. (See "Infectious mononucleosis" and "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults" and "Overview of diagnostic tests for cytomegalovirus infection".)

Rash — Localized dermatologic conditions that occur in association with travel to Africa include cutaneous larva migrans (CLM), cutaneous leishmaniasis, and phytophotodermatitis. These and other issues related to skin lesions in the returning traveler are discussed separately. (See "Skin lesions in the returning traveler" and "Hookworm-related cutaneous larva migrans" and "Cutaneous leishmaniasis: Clinical manifestations and diagnosis" and "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment".)

Systemic travel-related infections associated with rash include (table 7):

●Meningococcal infection – Meningococcal infection is characterized by acute onset of fever, nausea, vomiting, headache, confusion, and myalgia. Nonblanching purpuric or petechial rash may be observed. (See 'Neurologic symptoms' below.)

●Rickettsial infection – Many tick-borne rickettsial infections present with fever and rash; some are also associated with eschar and/or enlarged nodes (table 8). Rickettsial infections can present along a continuum from spotted fevers, to an eschar, to a systemic typhus illness. The incubation period is typically 2 to 14 days (table 9). Rickettsial diseases endemic in North Africa include epidemic typhus (caused by Rickettsia prowazekii) [12,13], murine typhus (caused by Rickettsia typhi) [14,15], and Mediterranean spotted fever (caused by Rickettsia conorii) [16]. The diagnosis of rickettsial infection may be established via serology or PCR. (See "Epidemic typhus" and "Murine typhus" and "Other spotted fever group rickettsial infections", section on 'R. conorii (Mediterranean spotted fever)'.)

●Measles – Measles is characterized by fever, rash, cough, coryza, and conjunctivitis; pneumonia can develop as a complication of measles. Transmission is human to human and infection occurs worldwide. The incubation period is 6 to 21 days (median 13 days). The diagnosis is usually established via serologic testing. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention".)

●Dengue fever – Classic dengue fever is an acute febrile illness accompanied by headache, retro-orbital pain, and marked muscle and bone pains. Fever typically lasts for five to seven days. Hemorrhagic manifestations and thrombocytopenia can also occur. A macular or maculopapular rash occurs in approximately half of cases. The virus is transmitted by Ae. aegypti or Aedes albopictus mosquitoes, which have broad epidemiologic distribution; the incubation period is four to seven days (range 3 to 10 days). The diagnosis is established via serologic testing, antigen testing, or PCR. (See 'Jaundice' above and "Dengue virus infection: Clinical manifestations and diagnosis".)

●Zika virus – Zika virus infection is characterized by fever, rash, headache, arthralgia, myalgia, and conjunctivitis [17]. The primary mode of transmission is via Aedes mosquito bites; sexual transmission can also occur. Zika virus infection occurs in Africa, Southeast Asia, the Pacific Islands, the Americas, and the Caribbean. The incubation period is 2 to 14 days. The diagnosis of Zika virus infection is established by PCR or serology. (See "Zika virus infection: An overview".)

●Acute schistosomiasis – Transmission of schistosomiasis occurs via exposure to fresh water (lakes and slow-moving rivers). Skin penetration by cercariae usually goes unnoticed; some individuals develop an itchy rash ("swimmer's itch") soon after swimming; this is a localized dermatitis that can result in a pruritic papular or urticarial rash at the site of larval entry.

Acute schistosomiasis syndrome (Katayama fever) is a systemic hypersensitivity reaction to schistosome antigens and circulating immune complexes that occurs three to eight weeks after infection. It is characterized by fever, urticaria and angioedema, chills, myalgias, arthralgias, dry cough, diarrhea, abdominal pain, and headache, and is accompanied by eosinophilia, resolving over days to weeks. Schistosomiasis due to Schistosoma haematobium and Schistosoma mansoni is widespread in North Africa. Transmission occurs through exposure to fresh water (lakes and slow-moving rivers). (See "Schistosomiasis: Epidemiology and clinical manifestations".)

●Enteric fever – Enteric fever (S. enterica serotype Typhi [formerly S. Typhi] and S. enterica serovar Paratyphi A, B, and C) is characterized by abdominal pain, fever, chills, and headache. It may be associated with "rose spots" (faint salmon-colored macules on the trunk and abdomen), though these lesions may be sparse or absent. (See 'Gastrointestinal symptoms' above.)

●Acute HIV infection – Acute HIV infection is commonly characterized by fever, lymphadenopathy, sore throat, rash, myalgia/arthralgia, and headache. The infection is transmitted sexually and occurs worldwide. The incubation period is two to four weeks. The diagnosis is established via immunoassay and viral load. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)

●Cutaneous larva migrans – CLM occurs most commonly as a result of human infection with the larvae of the dog or cat hookworm. It occurs at sites of skin exposure to contaminated soil, most frequently on the lower extremities. Initially, a pruritic erythematous papule develops at the site of each larval penetration. Days, weeks, or months later, intensely pruritic, elevated, serpiginous, reddish-brown lesions appear as the larvae migrate at a rate of several millimeters per day. The diagnosis is based on clinical history and physical findings. (See "Hookworm-related cutaneous larva migrans".)

●Syphilis – Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. Primary syphilis typically consists of a single painless chancre at the site of inoculation, accompanied by regional adenopathy. Secondary syphilis often includes a rash (disseminated and/or involving the palms and soles), fever, malaise, and other symptoms such as pharyngitis, hepatitis, mucous patches, condyloma lata, and alopecia. Neurosyphilis can occur at any time during the course of infection; manifestations may include eye or ear involvement, meningitis, or stroke. The diagnosis is established via serologic testing. (See "Syphilis: Screening and diagnostic testing".)

●Strongyloidiasis (rare) – Strongyloides infection may produce cutaneous reactions when larvae penetrate the skin. These reactions include inflammation, edema, petechiae, serpiginous or urticarial tracts, and pruritus. As larvae migrate, a raised, evanescent pink track develops; these lesions are known as larva currens ("running" larva) and are pathognomonic of strongyloidiasis. (See 'Gastrointestinal symptoms' above and 'Respiratory symptoms' below and "Strongyloidiasis".)

●Anthrax (rare) – Cutaneous anthrax is characterized by a painless papule that enlarges, develops a central vesicle, and subsequently erodes, leaving a necrotic ulcer with a black depressed eschar. Extensive surrounding edema, regional lymphadenopathy, and fever may be present. Anthrax is transmitted by contact with animals or animal materials (eg, skin) contaminated with anthrax spores; it occurs in agricultural regions in Central and South America, Sub-Saharan Africa, Central and Southwestern Asia, and Southern and Eastern Europe. The incubation period is one to seven days; the diagnosis is established via culture or by two supportive nonculture methods. (See "Clinical manifestations and diagnosis of anthrax".)

Respiratory symptoms

Absence of eosinophilia — Travel-related infections associated with fever and respiratory symptoms (in the absence of eosinophilia) include:

●Influenza – Influenza (including seasonal and avian influenza) should be suspected in patients with fever and respiratory symptoms returning from a region where influenza was circulating. The incubation period is two to four days. The diagnosis is established via rapid antigen test or nucleic acid test of nasopharyngeal aspirates, washings, or swabs. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis" and "Avian influenza: Clinical manifestations and diagnosis".)

●Coronavirus disease 2019 (COVID-19) – Symptoms of COVID-19 include cough, myalgias, headache, nasal congestion, sore throat, and diarrhea. Most symptoms occur approximately four to five days after exposure. Direct person-to-person respiratory transmission is the primary means of transmission. The diagnosis is established via nucleic acid amplification test. (See "COVID-19: Clinical features" and "COVID-19: Diagnosis".)

●Middle East respiratory syndrome coronavirus (MERS-CoV) – A novel coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), emerged in 2012 in Saudi Arabia. Subsequently, many cases, clusters, and outbreaks of MERS-CoV infection have been detected in the Arabian Peninsula. Most reported patients have been adults with severe pneumonia and acute respiratory distress syndrome. The diagnosis is established via PCR of lower respiratory tract specimens. (See "Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis".)

●Tuberculosis – Tuberculosis is characterized by cough >2 to 3 weeks in duration, lymphadenopathy, fevers, night sweats, and weight loss. Transmission is human-to-human, and infection occurs worldwide. The incubation period is at least three months. Diagnostic evaluation begins with chest radiography, followed by sputum acid-fast bacilli smear and nucleic acid amplification testing. (See "Diagnosis of pulmonary tuberculosis in adults".)

The differential diagnosis of fever with respiratory symptoms also includes etiologies nonspecific to travel, such as upper respiratory tract infection and community-acquired pneumonia (due to bacterial or viral pathogens). (See "The common cold in adults: Treatment and prevention" and "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults" and "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults".)

Less common travel-related infections with fever and respiratory symptoms include:

●Legionnaires' disease – Legionnaires' disease is characterized by fever, myalgia, headache, and nonproductive cough; abdominal pain and diarrhea may be present. It is transmitted via inhalation of aerosols containing the organism; among travelers, the most common source has been contaminated water in hotels or cruise ships. Infection also occurs in nontravelers. The incubation period is 2 to 10 days (usually five to six days). Special media is needed to culture the organism; the diagnosis can also be established by specific rapid tests, urine antigen, and serologic testing. (See "Clinical manifestations and diagnosis of Legionella infection".)

●Q fever – Q fever (Coxiella burnetii infection) may present with a broad spectrum of manifestations. Respiratory infection consists of fever, nonproductive cough, fatigue, headache, and myalgia. Infection may also be associated with hepatitis, endocarditis, and bone and joint disease. The illness occurs worldwide and is most commonly transmitted by contact with infected animals, materials contaminated with animal manure, contaminated aerosols, or by ingestion of unpasteurized milk. The incubation period for acute infection is usually two to three weeks (range few to 30 days). The diagnosis is established via serologic testing. (See "Q fever: Epidemiology, microbiology, and diagnostic tests".)

●Measles – Measles may include respiratory symptoms but typically presents with rash as the prominent feature. (See 'Rash' above.)

●Anthrax (rare) – Transmission of inhalational anthrax occurs when spores reach the terminal bronchioles and alveoli. Early symptoms are nonspecific and include myalgia, fever, and malaise. After four to five days, illness becomes more severe with progressive respiratory symptoms including dyspnea, hypoxemia, and shock. Diagnostic testing includes culture and PCR testing of blood and specimens from affected clinical sites, acute and convalescent serologic testing, and testing for lethal factor toxin on plasma. Anthrax more frequently presents with rash as the prominent feature. (See 'Rash' above and "Clinical manifestations and diagnosis of anthrax".)

Presence of eosinophilia — Travel-related infections associated with fever, respiratory symptoms, and eosinophilia are rare; they include:

●Loeffler syndrome – Loeffler syndrome is a transient condition associated with transpulmonary passage of larvae (Ascaris, hookworm, or Strongyloides); it is characterized by respiratory symptoms (dry cough, dyspnea, fever, wheezing), characteristic radiographic findings (migratory bilateral round infiltrates), and peripheral eosinophilia. Loeffler syndrome may be observed during acute infection and resolves once larvae migrate to the intestinal lumen. (See "Ascariasis".)

●Strongyloidiasis – Most patients with Strongyloides infection do not experience prominent symptoms. Uncommonly, transpulmonary migration of Strongyloides larvae is associated with dry cough, throat irritation, dyspnea, wheezing, and hemoptysis. Eosinophilia may occur in the presence or the absence of symptoms. (See 'Respiratory symptoms' above and 'Gastrointestinal symptoms' above and "Strongyloidiasis".)

Issues related to the approach to patients with eosinophilia are discussed further separately. (See "Approach to the patient with unexplained eosinophilia".)

Neurologic symptoms — Travel-related infections associated with fever and neurologic symptoms include:

●Meningococcal infection – Meningococcal infection is characterized by acute onset of fever, nausea, vomiting, headache, confusion, and myalgia. Nonblanching purpuric rash may be observed. The infection is transmitted by person-to-person contact via nasopharyngeal carriers. The incubation period is 2 to 10 days, and the diagnosis is established via culture of blood or spinal fluid, agglutination tests, or PCR. (See "Clinical manifestations of meningococcal infection" and "Diagnosis of meningococcal infection".)

●West Nile virus – West Nile virus infection is characterized by fever, headache, malaise, back pain, myalgia, and anorexia; neuroinvasive illness can present as encephalitis, meningitis, or an acute asymmetric flaccid paralysis. It is transmitted by mosquitoes and occurs in Africa, the Middle East, parts of Europe and the former Soviet Union, South and Southeast Asia, Australia, and the Americas. The incubation period is 2 to 14 days. The diagnosis is established via serologic testing in serum and spinal fluid. (See "Clinical manifestations and diagnosis of West Nile virus infection".)

●Rabies (rare) – Rabies is characterized by fever, hydrophobia, and pharyngeal spasms. It is transmitted by animal bite (dogs, bats, and other animals) and is distributed worldwide. The average incubation period is one to three months. The diagnosis can be established by virus-specific immunofluorescent staining of skin biopsy specimens, isolation of virus from the saliva, or detection of anti-rabies antibodies in serum or cerebrospinal fluid. (See "Clinical manifestations and diagnosis of rabies".)

●Guillain-Barré syndrome – Guillain-Barré syndrome (GBS) can be precipitated by infection due to Campylobacter jejuni (within one to two weeks), Zika virus (within one month), and other infections. The cardinal clinical features are progressive, symmetric muscle weakness and diminished deep tendon reflexes. The diagnosis is based upon the clinical presentation. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis".)

The differential diagnosis of fever with neurologic symptoms also includes etiologies unrelated to travel, such as meningitis, encephalitis, brain abscess, and subdural empyema. Travelers with onset of neurologic and/or gastrointestinal symptoms following ingestion of seafood should also be considered for ciguatera fish poisoning and shellfish poisoning. (See "Ciguatera fish poisoning" and "Overview of shellfish, pufferfish, and other marine toxin poisoning".)

Consider the incubation period — The incubation periods for common infections associated with travel are summarized in the table and figure (table 4 and figure 1).

Consider the exposure history — Some important exposures for transmission of infection are summarized below (table 10).

Arthropod bites — Insects serve as vectors for a large number of infectious diseases, as follows:

●Mosquitoes – Infections transmitted by mosquitoes in North Africa include dengue fever, chikungunya, Zika virus infection, and West Nile virus infection. (See related topics.)

●Flies – Infections transmitted by flies include leishmaniasis (sand fly). (See "Visceral leishmaniasis: Clinical manifestations and diagnosis" and "Cutaneous leishmaniasis: Clinical manifestations and diagnosis".)

●Ticks – Infections transmitted by ticks include rickettsial infections and tick-borne relapsing fever. (See related topics.)

●Fleas – Infections transmitted by fleas include murine typhus (R. typhi) and plague. (See "Murine typhus", section on 'Diagnosis' and "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)".)

●Lice – Infections transmitted by lice include epidemic typhus (R. prowazekii) and louse-borne relapsing fever. (See "Epidemic typhus" and "Clinical features, diagnosis, and management of relapsing fever".)

Unsafe water or undercooked food — Consumption of unsafe water or undercooked food may be associated with travelers' diarrhea, giardiasis, enteric fever, salmonellosis, shigellosis, Campylobacter infection, hepatitis A and E, or amebic dysentery.

Consumption of unpasteurized milk and milk products from infected livestock may be associated with listeriosis, brucellosis, Q fever, or tick-borne encephalitis.

Animal exposures — Animal bites may be associated with transmission of rabies (via dogs, bats, and other mammals), cat-scratch fever (Bartonella henselae), rat-bite fever (Spirillum minus or Streptobacillus moniliformis), and simian herpesvirus B infection (via Old World monkeys, especially the macaque family). (See "Zoonoses: Dogs" and "Zoonoses: Cats" and "Zoonoses: Animals other than dogs and cats".)

Contact with animals may be associated with transmission of toxoplasmosis (cats), anthrax (cattle, sheep, goats), Q fever (cattle, sheep, goats), hantavirus infection (rodents), plague (rodents), psittacosis (birds), avian influenza (birds), and rabies (dogs, bats, and other animals).

Sexual contact — Sexual contact with new partners is common among certain subgroups of travelers and visitors to certain locations [18,19]. The clinical history should include a sexual history, including the number of partners, types of sexual activities, and whether barrier protection was used. The physical examination should include a careful genital examination in individuals who have had sexual contact with a new partner while traveling.

Unprotected sex with a new partner or partners or a commercial sex worker may be associated with a number of sexually transmitted infections; these include herpes, syphilis, gonorrhea, chlamydia, HIV, hepatitis (A, B, or C), Zika virus infection, mpox, or viral hemorrhagic fevers.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Travel medicine".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: General travel advice (Beyond the Basics)")

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Travel medicine".)

SUMMARY AND RECOMMENDATIONS

●Geography – Countries in North Africa include Algeria, the Canary Islands (Spain), Egypt, Libya, Morocco, and Tunisia. (See 'Geography' above.)

●History and physical examination (see 'History and physical examination' above)

•The clinical history should include careful documentation of signs and symptoms and their time of onset, the nature of travel, relevant activities and exposures, and general medical information (table 3).

•The physical examination should include evaluation for skin lesions, lymphadenopathy, retinal or conjunctival changes, enlargement of liver or spleen, genital lesions, and neurologic findings. The approach to the initial laboratory evaluation is summarized in the table (table 6).

●Consider the presenting syndrome – The clinician should consider the patient's presenting syndrome in conjunction with the incubation period, relevant epidemiologic exposures, and geographic region of travel. The differential diagnoses for a number of clinical syndromes are summarized above. (See 'Consider the presenting syndrome' above.)

●Consider the incubation period – The incubation periods for common infections associated with travel are summarized in the table and figure (table 4 and figure 1). (See 'Consider the incubation period' above.)

●Consider the exposure history – Relevant exposures for transmission of infection include consumption of unsafe water or undercooked food, arthropod bites, animal exposures, and sexual contact (table 10). (See 'Consider the exposure history' above.)