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Fever Acute, Chronic, Recurring, With Exanthum, With Hemorrhage or Shock

Acute Fever

Bartonellosis (Oroya fever) (South America/Andes Mountains): Bartonellosis is a gram negative bacterial systemic infection with Bartonella bacilliformis, which is transmitted by sandflies. Infection is characterized by insidious onset of fever, malaise, headache, myalgia; or in other cases, acute onset high fever, chills, drenching sweats, lymphadenopathy, hemolytic anemia, liver involvement and altered consciousness. Essential features are fever, progressive hemolytic anemia, generalized lymphadenopathy, and exposure to sandflies. Salmonellosis is a common complication of bartonellosis. Nodular (and often ulcerated) lesions occur one to three months after the onset of illness. Treatment is with penicillin, tetracycline, streptomycin, or chloramphenicol.

Chikungunya (Topical areas, especially urban, of Asia, India, and East Africa): Chikungunya is an arboviral infection transmitted by the Aedes aegypti mosquito. Incubation is 2-4 days and the illness is self-limiting with acute symptoms (abrupt onset fever, headache, arthralgias, nausea, vomiting, abdominal pain, sore throat, lymphadenopathy, rash at defervescence, and malaise) lasting 3-10 days. Arthralgias remain a problem for weeks to several months after the acute phase. Febrile convulsions may occur in young children. Treatment is supportive for fever and pain.

Dengue Fever: See full discussion (East and West Africa, Southeast and East Asia, Pacific Islands, Eastern Australia, Central and South America, Mexico, South Texas, Caribbean Islands - with distribution increasing, especially in urban areas): Dengue Fever is a flavivirus (several serotypes) infection transmitted by mosquitos. There is increasing incidence and prevalence of cocirculation of multiple serotypes. Dengue is usually a self-limited illness characterized by abrupt onset high (biphasic) fever, chills, headache, rash, signs of bleeding, changes in taste, sore throat, nausea, vomiting, diarrhea, anorexia, severe aching myalgia and arthralgia (hence "bone-break" fever), and depression. Complications include meningoencephalitis, dengue hemorrhagic fever (DHF), and dengue shock syndrom (DSS). Treatment is supportive and convalescence tends to be lengthy.

Diphtheria (Worldwide): Diphtheria is an acute upper respiratory infection caused by virulent strains of the toxin-producing gram positive bacillus, Cornybacterium diphtheriae. Symptoms include fever, serosanguinous nasal discharge, sore throat, and gray pseudomembrane in the pharynx, nasopharynx, and/or trachea. Complications include respiratory tract obstruction, pneumonia, peripheral neuritis, and/or myocarditis. Immunization is essentially universal among younger people in the U.S., but some refugees and immigrants may not be immunized. Treatment includes (1) diptheria antitoxin within 48 hours of onset (after testing for sensitivity to antitoxin); (2) procaine penicillin G 600,000 units IM bid for 14 days (150,000 units/kg/day IV for 10 days for pediatric patients) or erythromycin 500 mg parenterally or po qid; (3) bedrest and supportive care; and (4) isolation until secretions are noncontagious. With some differences in regime, carriers are also treated.

Encephalitis: Causes of encephalitis among refugees and immigrants include arborvirus infections (mosquito or tick-borne - especially cerebral malaria), trypanosomiasis, relapsing fever, trichinosis, cysticerosis, toxocariasis, and angiostrongyliasis. Arbovirus encephalitis (Worldwide - according to specific disease): The most important (highest case- fatality rates) arbovirus or arthropod-borne encephalitides are (1) Japanese encephalitis (JE), which is found throughout Asia and the Pacific; (2) Murray Valley (MV), which is found in Australia and New Guinea; and (3) eastern equine encephalomyelitis (EEE), which is found in the Americas and Caribbean. Severe infections are usually characterized by acute onset of fever, meningeal signs (headache, stiff neck, irritability, nausea and vomiting, delirium, >vital signs), tremors, convulsions, and stupor progressing to coma. Treatment is primarily supportive.

Familial Mediterranean fever (Mediterranean area, primarily among persons of Sephardic Jewish, Armenian, and Arab ancestry): Familial Mediterranean fever (FMF) is an inherited disorder whose etiology is unknown. FMF is characterized by recurrent episodes of fever, abdominal pain, peritonitis and/or pleuritis or other chest pain; and in some cases, amyloidoses, arthritis, and skin lesions (especially on lower extremities). Onset is usually between the ages of 5 and 15 years. Treatment of acute attacks is supportive. Prophylactic treatment with colchicine 0.6 mg po tid or bid is effective. Fascioliasis: See trematodes, liver-dwelling.

Hemorrhagic fevers (HFs): See full discussion of HFs. The major HFs include hemorrhagic fever with renal syndrome, hantavirus pulmonary syndrome, South American HFs, Lassa HF, Marburg and Ebola HFs, Kyasanur Forest HF, Omsk HF, Crimean-Congo HF, Chikungunya fever, dengue fever and HF, and Rift Valley fever (distribution is noted in the full discussion). The viral hemorrhagic syndrome (VHS) results from widespread increased permeability of microvasculature. Depending on the severity of vascular instability and decrease in platelet function, presentation may range from mild to severe illness; and hemorrhagic manifestations are not always apparent. A common course of illness begins with an abrupt onset of fever, myalgia, cutaneous flushing, and conjunctival suffusion. Within several days, the patient's condition worsens to include syncope, photophobia, headache, hyperesthesia, abdominal pain, nausea/vomiting, anorexia, and prostration. Treatment is primarily supportive, except that Lassa fever, South American HFs, and possibly Crimean-Congo HF and Rift Valley HF may be treated with a slow infusion of IV ribavirin.

Leptospirosis: See full discussion (Worldwide, especially tropical areas of Latin America and Southeast Asia): Leptospirosis is a spirochette (Leptospira interrogans) infection transmitted primarily through exposure to water contaminated with urine from infected animals. Leptospirosis varies from asymptomatic to a severe or fatal illness. There are two common forms (anicteric and icteric or Weil's syndrome). Anicteric leptospirosis is the more common and milder form, and often is biphasic, with the first phase characterized by sudden onset high fever with chills, headache, conjunctival suffusion, cough and pulmonary chest pain, abdominal pain, nausea and vomiting, and myalgia. The illness may resolve after about one week with no further manifestations; or, after one to three days, recur with milder and more varied symptoms than in the first phase - except that aseptic meningitis may occur. Icteric leptospirosis or Weil's syndrome is the more severe form and is characterized by symptoms as described above (except not usually biphasic); and after about one week, the development of decreased renal function, pulmonary complications, jaundice, and/or hemorrhagic manifestations. Treatment includes antibiotics (doxycycline, penicillin, or others) and support.

Malaria: See full discussion (Tropical Africa, Asia, South and Central Americas; East China, Middle East): Malaria is caused by the protozoas Plasmodium falciporum, P. vivax, P. ovale, and P. malariae and is transmitted by mosquito bite, parenteral injection, or congenitally. Malaria is usually characterized by sudden onset of high fever, sweating, chills, uncontrollable shaking, headache, and splenomegaly. Fever tends to wax and wane in 48-72 hour cycles, though cycles may be irregular, especially with infection by P. falciporum. Onset may also be insidious, with less dramatic symptoms such as fever, headache, dyspnea, abdominal pain, nausea, diarrhea, myalgias, and splenomegaly. P. falciporum may cause parasitemia resulting in a life-threatening condition characterized by hemolysis, jaundice, anemia, acute renal failure, and hemoglobinuria. Cerebral malaria, also life-threatening, is characterized by gradual onset of severe headache, drowsiness, delerium, and coma. Seizures may also occur and are most common in children. P. faciporum causes death in as many as 25% of untreated cases. Treatment depends on the organism, immune status of the patient, and severity of the attack. Oral chloroquine is a mainstay of treatment except for infection with chloroquine-resistant P. falciporum. P. falciporum presents the greatest challenge because of severity of attacks as well as the existence of multidrug (especially chloroquine)-resistant strains. Combination drug treatment is common, e.g., mefloquine combined with artesunate for multidrug-resistant strains as described in the full discussion.

Melioidosis (Southeast Asia): Melioidosis is infection by Pseudomonas pseudomallei (gram negative bacillus) with symptoms of fever, pulmonary infection that may range from bronchitis to necrotizing pneumonia. Acute septicemic melioidosis is most common among debilitated persons. Focal suppuration (nodule, lymphangitis, lymphadenopathy) results from inoculation through a break in the skin. Chronic suppurative disease may involve virtually any body system. Recrudescence may occur many years after the initial infection. Treatment is according to susceptibility. Common antibiotics used are TMP-SMX (not in Thailand), Augmentin, doxycycline, and cephalosporins.

Meningitis, chronic and recurrent, is common worldwide, often as a complication of communicable diseases caused by a variety of pathogens as follows: (1) Bacterial causes include incompletely treated suppurative meningitis, parameningeal infection, Lyme disease, mycobacterium tuberculosis, syphilis; and less commonly actinomycosis brucellosis, leptospirosis, nocardial infection, and Whipple's disease. (2) Fungal infections with the potential to cause meningitis include aspergillosis, blastomycosis, cryptococcus, coccidiomycosis, candidiasis, histoplasma, and sporotrichosis. (3) Protozoal causes include toxoplasmosis and trypanosomiasis. (4) Helminthic causes include angiostrongyliasis, cysticercosis, gnathostomiasis, and trichinosis. (5) Viral causes include echoviral infections, herpes, HIV, lymphocytic choriomeningitis, and mumps. Viral or aseptic meningitis is characterized by sudden onset of fever and signs and symptoms of meningeal involvement (headache, neck stiffness, irritability/malaise, and sometimes rash and nausea and vomiting (from Chin, 2000; Koroshetz & Swartz, 1998).

Meningoencephalitis is relatively common worldwide and in some cases occurs as a complication of communicable diseases. Viruses are the most common pathogen, especially enteroviruses, but also arboviruses, herpesviruses, and other pathogens in illnesses including African trypanosomiasis, amebiasis, angiostrongyliasis, candidiasis, Chagas' disease, cryptococcosis, cytomegalovirus, dengue fever, hemorrhagic fevers, herpes, listeria, toxoplasmosis, and others. Young age and immunocompromise increase the risk of meningoencephalitis.

Pertussis or whooping cough (Worldwide): Most refugees and immigrants arrive in the U.S. with at least the first series of immunizations. However, not all records are accurate and some small risk exists for pertussis and other such illnesses. The infectious agent is Bordetella pertussis. Pertussis occurs in three stages: (1) The catarrhal stage is manifested by gradual onset of slight fever, dry cough, coryza, sneezing, malaise, and anorexia. (2) The paroxysmal stage begins 10-14 days after onset of symptoms and lasts 4-6 weeks. This stage includes the characteristic whooping cough (paroxysmal violent coughing spells with respiratory distress and without intervening inhalation and then a high-pitched inspiratory crowing whoop). Mucous is copious, clear, and tenacious; and vomiting may follow coughing. Coughing is most severe for the first 10-14 days of the paroxysmal stage and then severity gradually decreases. Paroxysms of coughing and the whoop are not always present in older children or adults. (3) The convalescent stage is marked by a chronic cough lasting as long as two years. Treatment includes respiratory isolation until the patient has received at least five days of a 14 day course of antibiotics; erythromycin (estolate form preferred) 50 mg/kg/day in 2-4 divided doses with a maximum of 2 gm/day for 14 days; supportive care is given in the hospital for younger and older patients. Cough suppressants are ineffective.

Plague (Worldwide, but primarily rural and lightly populated areas in undeveloped countries): Plague is an acute febrile zoonotic disease caused by Yersinia pestis, a microaerophilic coccobacillus of the family Enterobacteriaceae. Plague is transmitted primarily by flea (from rodents) bite, but also from direct inoculation through handling infected mammal carcasses or via the respiratory route from infected droplets from a patient with pneumonic plague. The most recent pandemic was in the late 19th and early 20th centuries and resulted in estimated 12,000,000 deaths. In recent years (1970s-1990s), most cases have been reported in Africa, Asia, and the Americas. There are three common forms of plague: bubonic (most common), pneumonic (most rapid and most frequently fatal), and septicemic - with the latter two either primary or secondary to metastatic spread. Plague is manifested by abrupt onset of high fever, severe headache, severe myalgias, prostration, and in some cases, delirium. The incubation period is 2-10 days. An ulcer may develop at the inoculation site. Lymphadenitis is followed by painful, draining bubo(s). Pneumonic plague produces fulminant pneumonitis with frothy bloody sputum and sepsis. Hematogenous spread or septicemic plague is characterized by rapid decline, coma, and purpura - hence the term "black plague." Treatment must be quickly instituted in all cases. IM streptomycin is the first line treatment, though IM or IV gentamicin is frequently used. IV or po tetracycline or doxycycline are also used.

Pneumonia: See anthrax, ascariasis, blastomycosis, coccidioidomycosis, histoplasmosis, HIV/AIDS, legionellosis, paragonimiasis, plague, psittacosis, Q fever, typhus, strongyloidiasis, tuberculosis. Note other, more common causes.

Psittacosis (Worldwide): Psittacosis is Chlamydia psittaci infection contracted from infected birds. Psittacosis is characterized by rapid onset of fever, chills, headache, dry cough, myalgia; and later development of dyspnea and atypical pneumonia. Complications include endocarditis, hepatitis, or neurologic complications. Except for contact with birds, psittacosis is indistinguishable from viral, mycoplasmic, or other atypical pneumonias. Treatment is with tetracycline or erythromycin.

Q fever (Worldwide): Q fever is a rickettsial zoonosis (infection with gram negative Coxiella burnetii) contracted primarily from inhalation of dust contaminated by infected animals, especially sheep, cattle, and goats; and also other mammals. Other routes of infection include contact with milk and tissue from infected animals. Manifestations of acute Q fever include fever, fatigue, headache, cough, abdominal pain, nausea, diarrhea, and myalgia. Pneumonia develops in a small number of patients. Other complications are hepatitis, pericarditis, myocarditis, and meningoencephalitis. Hepato/splenomegaly and endocarditis are common in chronic Q fever. Endocarditis is frequently associated with purpuric rash, renal insufficiency, stroke, and heart failure. Treatment of acute Q fever is with doxycycline or a quinolone. Chronic Q fever requires combination therapy such as rifampin and doxycycline.

Relapsing fevers (Louse-borne relapsing fever [LBRF] is a public health problem primarily in the highlands of Ethiopia; while tick-borne relapsing fever [TBRF] has a much wider distribution): RFs are spirochetal infections with Borrelia sp. (gram negative helical bacteria) and are characterized by recurrent episodes of fever and apyrexia. Manifestations of both LBRF and TBRF are sudden-onset of fever, chills, headache, tachycardia, nausea and vomiting, arthralgia, myalgias, and petechial rashes. Hepatosplenomegaly is common and confusion may occur. Conjunctival injection, epistaxis, cough, and slight hemoptysis may also occur. Symptoms last for 3-10 days, when there is a crisis (>fever and severity of other symptoms), followed by recovery and relapse in about 7-14 days. There are one to two relapses in untreated LBRF and three to ten relapses in untreated TBRF. LBRF is treated with a single dose of oral erythromycin, tetracycline, doxycycline or chloramphenicol; or single parenteral dose of the preceding medications or penicillin G. TBRF is treated with a seven day course of the same medications. Jarisch-Herxheimer reactions to treatment are common (acute febrile reaction with headache and myalgia).

Rickettsioses (Worldwide): The rickettsioses are febrile exanthematous illnesses caused by arthropod carried rickettsiae. Rickettsioses include the typhus group, spotted fever group, Q fever, trench fever, and erlichiosis. See Boutonneuse fever, Q fever, spotted fevers, trench fever, and typhus.

Trench fever (Worldwide, decreasing incidence): Trench fever is thought to occur after bites from ectoparasites infected with Bartonella sp. (as in cat scratch fever). Trench fever is characterized by abrupt onset of fever, headache, myalgia, malaise, and often aseptic meningitis. Treatment is with prolonged antibiotic therapy, including erythromycin or azithromycin.

Trichinosis (trichinella) (Worldwide): Trichinosis is a nematode (roundworm) infection with Trichinella sp. from ingestion of meat that contains cysts, especially undercooked pork or meat from a carnivore. Infection ranges from light and asymptomatic to heavy and life-threatening. Manifestations vary according to the life cycle of the worms: Initially there is malaise, nausea, cramping abdominal pain, and diarrhea. Gastrointestinal symptoms are followed in 1-6 weeks by fever, eosinophilia, periorbital and facial edema, conjunctivitis, dysphagia, dyspnea, cough, myalgia, and muscle spasms. Complications include meningitis and other neurological disorders, myocarditis, pneumonia, and nephritis. The current treatment of choice is mebendazole 300 mg po tid for 10 days (sometimes with prednisone to control symptoms).

Typhoid and paratyphoid fever (sometimes termed enteric fever) (Most of the developing world, especially Africa, Asia, and Latin America, including Mexico): Typhoid fever is an acute systemic febrile illness caused by Salmonella typhi and other anaerobic gram-negative Salmonella serovars, e.g., S. paratyphi, which causes the less severe paratyphoid fever. Typhoid is usually spread by feces-contaminated food or water. Note that vaccination is not completely effective. Incubation is highly variable, ranging from 3-60 days. The hallmark sign is the gradual onset of steadily increasing and then persistently high fever (though children may experience abrupt onset). Early manifestations are fever, chills, malaise, headache, sore throat, cough, and sometimes abdominal pain and constipation or diarrhea. As the illness progresses, prostration, abdominal distension, hepatosplenomegaly, anorexia, and weight loss are common. Untreated typhoid may result in complications in any of the body systems. The severity of illness varies according to immunocompetence, infectious dose of microorganisms, and other factors. Treatment is with chloramphenicol 3-4 g/d po for adults and 50-75 mg/kg/d po for children. When the patient becomes afebrile, the dose may be decreased to 2 g/d for adults and 30 mg/kg/d for children. The total duration of treatment is two weeks. In the U.S., the more common treatment is amoxicillin 4-6 g/d po in four divided (1-1.5 g) daily doses for adults and 100 mg/kg po in four divided daily doses for children. Trimethoprim-sulfamethoxazole, ciprofloxacin, or ofloxacin are also used. Early effective treatment results in increased frequency of (usually mild) relapse.

Typhus: See full discussion (numerous areas of the world as noted in discussion below): The typhus group of illnesses are one of several rickettsioses or febrile exanthematous illnesses caused by bites of rickettsial-infected arthropods or exposure to their feces. The three most important typhus group diseases are: epidemic louse-borne typhus, scrub typhus, and endemic (murine) typhus. (1) Epidemic louse-borne typhus is caused by Rickettsia prowazekii, with infection favored by crowded, unsanitary living conditions such as in concentration or the more primitive refugee camps - especially those in cold areas. Epidemic louse-borne typhus is currently most prevalent in mountainous areas of Africa, Asia, and Latin America. It is characterized by a prodrome of headache and constitutional symptoms; then the abrupt onset of high fever, chills, and prostration; then a macular rash progressing to maculopapular and petechial. Other common manifestations are delirium, conjunctival injection, photophobia, eye pain, flushed facies, hearing loss, hypotension, pulmonary involvement, renal insufficiency, and splenomegaly. Recovery may be spontaneous, or complications, including pneumonia, circulatory collapse, myocarditis, and uremia may lead to death. Treatment is with doxycycline 200 mg in a single dose or until the patient is afebrile for 24 hours. (2) Scrub typhus is transmitted by the bite of infected mites or chiggers, and is found in most areas of Asia. Scrub typhus illness ranges from mild to severe, and is characterized by gradual onset of fever, chills, headache, myalgia (backache), cough, nausea and abdominal pain, eschar at the site of the infecting bite, regional lymphadenopathy and a maculopapular rash. Severe scrub typhus is characterized by encephalitis and pneumonia. Scrub typhus is treated with doxycycline 100 mg bid po for 7-14 days; or chloramphenicol 500 mg qid po for 7-14 days. Azithromycin is also effective. (3) Endemic (murine) typhus is transmitted by the bite of infected fleas and is found worldwide. Endemic typhus is characterized by several days of prodromal constitutional symptoms, followed by the abrupt onset of fever, chills, and nausea and vomiting. Pulmonary involvement is common and may include interstitial pneumonia, pleural effusion, and/or pulmonary edema. Treatment is with doxycycline 100 mg bid po for 7-14 days; or chloramphenicol 500 mg qid po for 7-14 days.

Yellow fever (most of tropical and subtropical South America and Africa): Yellow fever (YF) is caused by an arbovirus transmitted by the Aedes aegypti mosquito from one human to another (the urban form of YF) or from monkeys to humans (the jungle or sylvan form of YF). YF is characterized by sudden onset flu-like (non-specific) symptoms occurring in two stages with a short intervening remission. The first stage of severe YF has a sudden onset of fever, chills, intense headache, lumbosacral back pain, myalgia, nausea and vomiting, conjunctival injection, dark urine, and bradycardia in relation to fever. After a 12-24 hour remission, there is an "intoxication" or hepatorenal stage that features reemergence of generalized symptoms including increased temperature, increased nausea and vomiting, abdominal pain, jaundice, and prostration. Complications of severe YF include jaundice, dehydration, decreased renal function, delirium, and hemorrhagic symptoms. Terminal signs include progressive tachycardia, intractable hiccups, and shock. Lab findings include albuminuria, leukopenia, abnormal liver function, increased prothrombin times. Treatment is supportive, i.e, control of fever, vomiting, dehydration, and pain.

Viral diseases not discussed here.

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Chronic Fever

Actinomycosis (Worldwide): Actinomycosis is an anaerobic gram positive bacterial infection that features abscesses, fever, and usually follows trauma. Primarily affects cervicofacial area; and also respiratory system/thorax and/or gastrointestinal system (ileocecal region). Treatment is with penicillin, tetracycline, or erythromycin.

Brucellosis or undulant fever: See full discussion (Worldwide, especially Africa, Asia, and the Middle East). Brucellosis is caused by gram negative coccobacilli (Brucella abortus and other B. biovars) transmitted through contaminated milk, animal products, and related. Fever, chills, sweats, aches, fatigue, and joint pain are the most common manifestations. The most commonly affected systems (with a variety of manifestations) are cardiac, respiratory, gastrointestinal, genitourinary, and central nervous system. Long-term treatment 3-8 or more weeks) with medication combination is necessary. Doxycycline + rifampin or TMP/SMX DS tablets + rifampin are commonly used.

Chagas' Disease or American trypanosomiais: See full discussion (Most of Latin America): Chagas' disease is a protozoan infection with Trypanosoma cruzi transmitted by insect bite. Patients may be asymptomatic or have a lesion at the site of the bite; and symptoms of prolonged fever, tachycardia, fatigue, weakness, splenomegaly, and lymphadenopathy. Myocarditis or meningoencephalitis may also occur. Most patients experience spontaneous remission of symptoms, followed by a lifelong low-grade parasitemia. There is not currently a satisfactory treatment for any stage of Chagas' disease. Current treatment includes nifurtimox 8-10 mg/kg/day po qid for 90-120 days or benznidazole 5 mg/kg/day po for 60 days. These long-term therapies are toxic to some patients. In the United States, nifurtimox is available only from the Centers for Disease Control and benznidazole is not available in the U.S.

Familial Mediterranean fever (Mediterranean area, primarily among persons of Sephardic Jewish, Armenian, and Arab ancestry): Familial Mediterranean fever (FMF) is an inherited disorder whose etiology is unknown. FMF is characterized by recurrent episodes of fever, abdominal pain, peritonitis and/or pleuritis or other chest pain; and in some cases, amyloidoses, arthritis, and skin lesions (especially on lower extremities). Onset is usually between the ages of 5 and 15 years. Treatment of acute attacks is supportive. Prophylactic treatment with colchicine 0.6 mg po tid or bid is effective. Fascioliasis: See trematodes, liver-dwelling.

Filariasis: See full discussion (Distribution given below). The filarial parasites are tissue-dwelling roundworms whose microfilarial (mf) larvae are transmitted by several species of mosquitos or flies. The most problematic forms of filariasis are (1) Bancroftian filariasis and Malayan filariasis (much of the tropical and subtropical world between the Tropics of Cancer and Capricorn) which involve the lymphatic system and result in elephantiasisis; (2) loiasis or loa loa (tropical Africa) in which worms live in subcutaneous tissue; and (3) Onchocerciasis (tropical Africa and to a lesser extent Central and South America) which causes river blindness and skin disorders. Treatment in most cases is effective only against the mf, hence the infection continues and repeated treatment (with ivermectin and/or DEC) may be necessary.

Histoplasmosis (Africa, Americas, East Asia, Australia): Best known in the West as an opportunistic infection of HIV, histoplasmosis is found among immigrants as the classic small-form histoplasmosis (primarily pulmonary) and as African histoplasmosis (primarily bone and cutaneous). Treatment is with amphotericin B initially, and itraconazole or fluconazole are used for maintenance therapy.

HIV/AIDS: HIV/AIDS is found world-wide, and is especially common in sub-Saharan Africa, Southeast Asia, and India. Heterosexual transmission is common in these areas. Readers are referred to the CDC and other current sources of information (See links).

Relapsing fevers (Louse-borne relapsing fever [LBRF] is a public health problem primarily in the highlands of Ethiopia; while tick-borne relapsing fever [TBRF] has a much wider distribution): RFs are spirochetal infections with Borrelia sp. (gram negative helical bacteria) and are characterized by recurrent episodes of fever and apyrexia. Manifestations of both LBRF and TBRF are sudden-onset of fever, chills, headache, tachycardia, nausea and vomiting, arthralgia, myalgias, and petechial rashes. Hepatosplenomegaly is common and confusion may occur. Conjunctival injection, epistaxis, cough, and slight hemoptysis may also occur. Symptoms last for 3-10 days, when there is a crisis (>fever and severity of other symptoms), followed by recovery and relapse in about 7-14 days. There are one to two relapses in untreated LBRF and three to ten relapses in untreated TBRF. LBRF is treated with a single dose of oral erythromycin, tetracycline, doxycycline or chloramphenicol; or single parenteral dose of the preceding medications or penicillin G. TBRF is treated with a seven day course of the same medications. Jarisch-Herxheimer reactions to treatment are common (acute febrile reaction with headache and myalgia).

Tuberculosis (Worldwide): Tuberculosis (TB) is a chronic infection - most commonly pulmonary - caused by the acid-fast bacillus, Mycobacterium tuberculosis. Infection is usually acquired through inhalation of infected droplets expelled by cough from a person with active disease. Most cases (85%) of TB are pulmonary. Pulmonary symptoms include cough, chest pain, and hemoptysis. Constitutional symptoms are often present in pulmonary disease, and include fever, chills, night sweats, fatigue, decreased appetite, and weight loss. Symptoms of extrapulmonary TB depend on the site(s) of infection. Tuberculosis should always be ruled out in any person at-risk or with the above symptoms. Medical evaluation includes complete medical and family/close contacts/travel history, physical examination, Mantoux tuberculin skin test, chest x-ray, and appropriate bacteriologic or histologic examinations, e.g., smear and culture of sputum. Treatment is according to (1) classification of disease, e.g., exposure without infection, infection without disease, current TB disease, previous TB disease, or TB suspected; (2) whether disease is drug-resistant; (3) immune status of the patient; and (4) other factors. The treatment of TB is complex and is evolving at a rapid pace. Readers are referred to the U.S. Centers for Disease Control and Prevention: http://www.cdc.gov/ for current standards of testing and treatment.

Typhoid and paratyphoid fever (sometimes termed enteric fever) (Most of the developing world, especially Africa, Asia, and Latin America, including Mexico): Typhoid fever is an acute systemic febrile illness caused by Salmonella typhi and other anaerobic gram-negative Salmonella serovars, e.g., S. paratyphi, which causes the less severe paratyphoid fever. Typhoid is usually spread by feces-contaminated food or water. Note that vaccination is not completely effective. Incubation is highly variable, ranging from 3-60 days. The hallmark sign is the gradual onset of steadily increasing and then persistently high fever (though children may experience abrupt onset). Early manifestations are fever, chills, malaise, headache, sore throat, cough, and sometimes abdominal pain and constipation or diarrhea. As the illness progresses, prostration, abdominal distension, hepatosplenomegaly, anorexia, and weight loss are common. Untreated typhoid may result in complications in any of the body systems. The severity of illness varies according to immunocompetence, infectious dose of microorganisms, and other factors. Treatment is with chloramphenicol 3-4 g/d po for adults and 50-75 mg/kg/d po for children. When the patient becomes afebrile, the dose may be decreased to 2 g/d for adults and 30 mg/kg/d for children. The total duration of treatment is two weeks. In the U.S., the more common treatment is amoxicillin 4-6 g/d po in four divided (1-1.5 g) daily doses for adults and 100 mg/kg po in four divided daily doses for children. Trimethoprim-sulfamethoxazole, ciprofloxacin, or ofloxacin are also used. Early effective treatment results in increased frequency of (usually mild) relapse.

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Recurring Fever

HIV/AIDS: HIV/AIDS is found world-wide, and is especially common in sub-Saharan Africa, Southeast Asia, and India. Heterosexual transmission is common in these areas. Readers are referred to the CDC and other current sources of information (See links).

Malaria: See full discussion (Tropical Africa, Asia, South and Central Americas; East China, Middle East): Malaria is caused by the protozoas Plasmodium falciporum, P. vivax, P. ovale, and P. malariae and is transmitted by mosquito bite, parenteral injection, or congenitally. Malaria is usually characterized by sudden onset of high fever, sweating, chills, uncontrollable shaking, headache, and splenomegaly. Fever tends to wax and wane in 48-72 hour cycles, though cycles may be irregular, especially with infection by P. falciporum. Onset may also be insidious, with less dramatic symptoms such as fever, headache, dyspnea, abdominal pain, nausea, diarrhea, myalgias, and splenomegaly. P. falciporum may cause parasitemia resulting in a life-threatening condition characterized by hemolysis, jaundice, anemia, acute renal failure, and hemoglobinuria. Cerebral malaria, also life-threatening, is characterized by gradual onset of severe headache, drowsiness, delerium, and coma. Seizures may also occur and are most common in children. P. faciporum causes death in as many as 25% of untreated cases. Treatment depends on the organism, immune status of the patient, and severity of the attack. Oral chloroquine is a mainstay of treatment except for infection with chloroquine-resistant P. falciporum. P. falciporum presents the greatest challenge because of severity of attacks as well as the existence of multidrug (especially chloroquine)-resistant strains. Combination drug treatment is common, e.g., mefloquine combined with artesunate for multidrug-resistant strains as described in the full discussion.

Relapsing fevers (Louse-borne relapsing fever [LBRF] is a public health problem primarily in the highlands of Ethiopia; while tick-borne relapsing fever [TBRF] has a much wider distribution): RFs are spirochetal infections with Borrelia sp. (gram negative helical bacteria) and are characterized by recurrent episodes of fever and apyrexia. Manifestations of both LBRF and TBRF are sudden-onset of fever, chills, headache, tachycardia, nausea and vomiting, arthralgia, myalgias, and petechial rashes. Hepatosplenomegaly is common and confusion may occur. Conjunctival injection, epistaxis, cough, and slight hemoptysis may also occur. Symptoms last for 3-10 days, when there is a crisis (>fever and severity of other symptoms), followed by recovery and relapse in about 7-14 days. There are one to two relapses in untreated LBRF and three to ten relapses in untreated TBRF. LBRF is treated with a single dose of oral erythromycin, tetracycline, doxycycline or chloramphenicol; or single parenteral dose of the preceding medications or penicillin G. TBRF is treated with a seven day course of the same medications. Jarisch-Herxheimer reactions to treatment are common (acute febrile reaction with headache and myalgia).

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Fever with Exanthum

Chikungunya (Topical areas, especially urban, of Asia, India, and East Africa): Chikungunya is an arboviral infection transmitted by the Aedes aegypti mosquito. Incubation is 2-4 days and the illness is self-limiting with acute symptoms (abrupt onset fever, headache, arthralgias, nausea, vomiting, abdominal pain, sore throat, lymphadenopathy, rash at defervescence, and malaise) lasting 3-10 days. Arthralgias remain a problem for weeks to several months after the acute phase. Febrile convulsions may occur in young children. Treatment is supportive for fever and pain.

Dengue Fever: See full discussion (East and West Africa, Southeast and East Asia, Pacific Islands, Eastern Australia, Central and South America, Mexico, South Texas, Caribbean Islands - with distribution increasing, especially in urban areas): Dengue Fever is a flavivirus (several serotypes) infection transmitted by mosquitos. There is increasing incidence and prevalence of cocirculation of multiple serotypes. Dengue is usually a self-limited illness characterized by abrupt onset high (biphasic) fever, chills, headache, rash, signs of bleeding, changes in taste, sore throat, nausea, vomiting, diarrhea, anorexia, severe aching myalgia and arthralgia (hence "bone-break" fever), and depression. Complications include meningoencephalitis, dengue hemorrhagic fever (DHF), and dengue shock syndrom (DSS). Treatment is supportive and convalescence tends to be lengthy.

Enterovirus exanthems: Enterovirus exanthems are rashes secondary to gastrointestinal tract infection by picornaviruses, including poliovirus, coxsackieviruses, and echoviruses.

Rickettsioses (Worldwide): The rickettsioses are febrile exanthematous illnesses caused by arthropod carried rickettsiae. Rickettsioses include the typhus group, spotted fever group, Q fever, trench fever, and erlichiosis. See Boutonneuse fever, Q fever, spotted fevers, trench fever, and typhus.

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Fever with Hemorrhage or Shock

Dengue Fever: See full discussion (East and West Africa, Southeast and East Asia, Pacific Islands, Eastern Australia, Central and South America, Mexico, South Texas, Caribbean Islands - with distribution increasing, especially in urban areas): Dengue Fever is a flavivirus (several serotypes) infection transmitted by mosquitos. There is increasing incidence and prevalence of cocirculation of multiple serotypes. Dengue is usually a self-limited illness characterized by abrupt onset high (biphasic) fever, chills, headache, rash, signs of bleeding, changes in taste, sore throat, nausea, vomiting, diarrhea, anorexia, severe aching myalgia and arthralgia (hence "bone-break" fever), and depression. Complications include meningoencephalitis, dengue hemorrhagic fever (DHF), and dengue shock syndrom (DSS). Treatment is supportive and convalescence tends to be lengthy.

Hemorrhagic fevers (HFs): See full discussion of HFs. The major HFs include hemorrhagic fever with renal syndrome, hantavirus pulmonary syndrome, South American HFs, Lassa HF, Marburg and Ebola HFs, Kyasanur Forest HF, Omsk HF, Crimean-Congo HF, Chikungunya fever, dengue fever and HF, and Rift Valley fever (distribution is noted in the full discussion). The viral hemorrhagic syndrome (VHS) results from widespread increased permeability of microvasculature. Depending on the severity of vascular instability and decrease in platelet function, presentation may range from mild to severe illness; and hemorrhagic manifestations are not always apparent. A common course of illness begins with an abrupt onset of fever, myalgia, cutaneous flushing, and conjunctival suffusion. Within several days, the patient's condition worsens to include syncope, photophobia, headache, hyperesthesia, abdominal pain, nausea/vomiting, anorexia, and prostration. Treatment is primarily supportive, except that Lassa fever, South American HFs, and possibly Crimean-Congo HF and Rift Valley HF may be treated with a slow infusion of IV ribavirin.

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