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Musculoskeletal System

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.

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.

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.

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.

Lyme disease (North America, Europe, Asia): Lyme borreliosis is a tick-borne spirochete, and though Lyme disease often considered (in the U.S.) as a North American illness, is also found in Europe and Asia. There also are similar tick-borne illnesses. Lyme disease occurs in three stages: (1) Early localized infection is characterized by erythema migrans, i.e., papule or macule expanding to large annular lesion with clearing center or center that becomes indurated or necrotic. (2) Early disseminated infection is characterized by fever with chills, secondary (and smaller) lesions, headache, stiff neck, myalgias, arthralgias, and malaise and fatigue; other neurological signs, and sometimes cardiac problems may also develop. (3) Late persistent infection is characterized by the development of arthritis, chronic synovitis, and other musculoskeletal problems. Central and peripheral nervous system disorders also occur, as well as skin lesions such as acrodermatitis chronicum atrophicans which presents as discoloration and swelling of a distal extremity progressing to a condition resembling localized scleroderma. Diagnosis of Lyme disease is based on exposure and presence of specific symptoms (erythema migrans + at least one late manifestion + laboratory confirmation - usually antibodies by ELISA). Treatment is with oral antibiotics (doxycycline or amoxicillin or cefuroxime axetil or erythromycin for 10-60 days, depending on severity/extent of illness) or, if neurological involvement, with IV antibiotics.

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.

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.

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).

Trematodes (flukes): See schistosomiasis above or full discussion and see trematode infection by affected system below. Trematodes, biliary duct-dwelling cause diseases including clonorchiasis and opisthorchiasis. (1) Clonorchiasis (China, Taiwan, Korea, Japan, Vietnam, and other areas of Asia) is a liver fluke (Clonorchis sinensis) infection of the biliary tract following ingestion of raw or pickled fish. Symptoms include upper abdominal pain, irregular high fever, lymphadenopathy, myalgia, and arthralgia. The condition may be chronic and include intermittent fever, vague abdominal symptoms, anorexia, and fatigue. Eosinophilia is pronounced. Treatment is with praziquantel 25 mg/kg po tid for one day. (2) Opisthorchiasis (Eastern Europe and Russia; Thailand) is a liver fluke infection of the biliary tract following ingestion of raw or pickled fish. Most infected persons have no significant symptoms. If the parasite load is high, symptoms may include upper abdominal pain, feeling that something is moving in the liver, hepatomegaly with tenderness, jaundice, intermittent fever, lymphadenopathy, myalgia, and arthralgia. The condition may be chronic and include intermittent fever, vague abdominal symptoms, anorexia, and fatigue. Eosinophilia is pronounced. Treatment is with praziquantel 25 mg/kg po tid for one day.

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).

Trypanosomiasis (African) or African sleeping sickness (Tropical Africa): Trypanosomiasis is caused by protozoal parasites, Trypanosoma brucei rhodesiene or T b gambiense, transmitted by bite of the tsetse fly. T b rhodesiene infections are more virulent than T b gambiense; and in the former, patients experience three stages of illness (trypanosomal chancre, hemolymphatic, and meningoencephalitic) as opposed to two stages in the latter (trypanosomal chancre and meningoencephalitic) with significantly milder symptoms. The painful trypanosomal chancre (3-10 cm) appears about two days after the bite and lasts 2-4 weeks. The hemolymphatic stage is characterized by high fevers lasting several days, with symptom-free periods of days to weeks. Less common manifestations of this stage are severe headache, malaise, arthralgia, lymphadenopathy, circinate rash, pruritis, and hepatosplenomegaly. Weight loss and debilitation also occur, and myocarditis may develop. The meningoencephalitic stage is characterized by progressive apathy, nighttime insomnia and daytime somnolence, anorexia, retarded speech, extrapyramidal signs (tremors, fasciculations, choreiform movements, and Parkinsonian-like appearance), and finally, coma and death. Treatment is complex and toxic, and depends on the infecting organism and stage of illness. Among the medications currently in use are suramin, melarsoprol, pentamidine, eflornithine, and corticosteroids.

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.

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