Infectious myositis is an acute, subacute, or chronic infection of skeletal muscle. Once considered a tropical disease, it is now seen in temperate climates as well, particularly with the emergence of HIV infection.[1, 2] In addition to HIV, other viruses, bacteria (including mycobacteria), fungi, and parasites can cause myositis. For a detailed discussion of HIV-associated myopathies, refer to HIV-1 Associated Myopathies.
Single or multiple muscle groups in the limbs can be involved, a notable exception being trichinosis, which commonly involves orbital muscles. In most instances, involvement of proximal muscles is predominant. Characteristic myopathic features and findings of polymyositis, including inflammatory infiltrates, may be seen.
Viruses: Viruses implicated in the pathogenesis of myositis include HIV-1, human T lymphotrophic virus 1 (HTLV-1), influenza, coxsackieviruses, and echoviruses. As in the non–HIV-infected population, HIV-associated polymyositis is most likely autoimmune in origin. Influenza myositis could be due to direct viral invasion or autoimmune response.
Pyomyositis: The pathogenesis is unclear, but trauma, viral infection, and malnutrition have been implicated. Although most cases of pyomyositis occur in healthy individuals, other pathogenetic factors include nutritional deficiency and associated parasitic infection in tropical climates. In the temperate climates, pyomyositis is seen most commonly in patients with diabetes, HIV infection, and malignancy.
Lyme borreliosis: Musculoskeletal manifestations are noted frequently in Lyme borreliosis. The disease is transmitted by the bites of ticks of the Ixodes genus that carry the spirochete (see image below). The animal reservoirs are the white-footed mouse in the Eastern United States and the wood rat in California. Human infection results from the bite of infected ticks in the late spring and early summer. Lyme myositis may result from direct invasion of muscle by the spirochete Borrelia burgdorferi or by autoimmune mechanisms.[3]
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Ixodes scapularis (dammini), tick vector for Lyme disease. Courtesy of Centers for Disease Control and Prevention.
American trypanosomiasis: The causative organism is a protozoan, Trypanosoma cruzi. The insect vectors are reduviid bugs such as Rhodnius prolixus ("vinchuca"), Triatoma infestans, and Panstrongylus megistus. The insect defecates on the host's skin as it feeds, contaminating the bite wound with feces containing the parasites. T cruzi occurs in 2 forms in humans, the intracellular amastigote and the trypomastigote form in blood, which is ingested by the insects (see image below). The parasite reproduces asexually and migrates to the hindgut. In humans, the parasite loses its flagellum and transforms into the amastigote form, which may enter muscle and multiply, resulting in myositis.
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Trypanosoma cruzi in blood smear. Courtesy of Centers for Disease Control and Prevention.
Cysticercosis: Myositis also can occur in cysticercosis, which represents an infection by the larval stage of the intestinal tapeworm Taenia solium. Human infection results from ingestion of raw or incompletely cooked pork. Another mode of infection is by contamination of food and water by feces containing the eggs of the tapeworm. The larvae migrate throughout the body and may form fluid-filled cysts in a variety of tissues, including muscle.
Pyomyositis: Approximately 676 cases have been reported in the US literature since 1971.
Lyme disease: Endemic areas include the Northeast, mainly Connecticut, Massachusetts, Maryland, and New York; the North-Central region, mainly Wisconsin and Minnesota; and the West Coast, especially Northern California.
International
In eastern Uganda, 400-900 cases of tropical myositis occur per year; it is rare in western Kenya.
Cysticercosis is most prevalent in India, Eastern Europe, Central America, and Mexico.
In endemic areas of Latin America, 8% of the population is seropositive for American trypanosomiasis.
Mortality/Morbidity
A potentially life-threatening complication of pyomyositis is toxic shock syndrome.
Rhabdomyolysis can complicate influenza and, rarely, coxsackievirus myositis.
Race-, sex-, and age-related demographics
In Hawaii, muscle abscesses were noted to be confined to the Polynesians. In the French Pacific islands, the disease is not seen in the French settlers.
Infectious myositis has a male predominance and is typically seen in young adults.
Risk factors for Staphylococcus aureus pyomyositis - Strenuous activity, muscle trauma, skin infections, infected insect bites, illicit drug injections, connective tissue disorders, and diabetes
Overseas travel
Consumption of poorly cooked meats (especially pork products in the case of trichinosis or cysticercosis)
Tick bites
Pyomyositis
Psoas abscess - Subtle symptoms such as fever and flank and hip pain; may manifest as pyrexia of unknown origin; may be primary (no identifiable source of infection/from occult hematogenous spread) or secondary (spread from infection in the vicinity)
Occur mostly in the immunocompromised
Fever and malaise
Streptococcal myositis
Most common form is group A streptococci (GAS) necrotizing myositis/streptococcal myonecrosis
Usually seen in the men and young adults
Spontaneous occurrence (no history of penetrating trauma) or in the immunocompromised
Trichinosis
Cardinal features - Myalgia, periorbital swelling, and fever (see following image)
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A patient with trichinosis and ocular involvement. Courtesy of Centers for Disease Control and Prevention and Dr. Thomas F. Sellers, Jr.
Depending on site of involvement - Diplopia, dysarthria, dysphagia, dyspnea
Lyme myositis
Pain and weakness of the proximal muscle groups
Symptoms in the vicinity of skin lesions or in limb muscles
Cysticercosis with myositis - Fever, myalgias
Trypanosomiasis with myositis
Acute stage
May be asymptomatic or characterized by fever
Myositis occurring in the early stage of infection - Symptoms such as muscle weakness and myalgias mimicking those of polymyositis
Chronic stage - Myalgias
Toxoplasma myositis - Fever, myalgias, and muscle weakness
Influenza myositis - Childhood and adult forms recognized
Childhood form
Fever, malaise, and rhinorrhea followed 1-7 days later by severe pain, especially in the calves
Muscle pain worse with movement, especially with walking
Symptoms of myositis - Generally last 1-7 days
Adult form
Fever, myalgias, generalized weakness
Muscle swelling in some patients
Acute coxsackievirus myositis
Group A virus infection - Myalgias, weakness
Group B virus infection - Causes epidemic pleurodynia (Bornholm disease or epidemic myalgia), which is considered a form of myositis
This is an acute, febrile disorder with abrupt onset of pain in the abdomen or lower thoracic region.
Pain can be referred to the back and shoulders.
Pain is worse with movement, breathing, or coughing.
Fungal myositis
Most often seen in severely immunosuppressed patients
Clinical presentation is similar to pyomyositis
Cryptococcal myositis
Rare cause of myositis
Most involve immunocompromised patients.
Symptoms overlap those of bacterial myositis.
Often present with lower extremity pain and swelling
Muscles are painful, swollen, tender, and indurated.
Quadriceps muscle is involved most commonly.
The second most common location is the psoas muscle, followed by the upper extremities.
Depending on the site of involvement, it may mimic appendicitis (psoas muscle), septic arthritis of the hip (iliacus muscle), or epidural abscess (piriformis muscle).
This may be difficult to distinguish clinically from inflammatory myopathy.
Findings may be subtle in immunocompromised persons requiring a high index of suspicion for diagnosis.
Streptococcal myositis
Prodrome - Flulike symptoms
Evolves to severe local muscle pain, swelling, and fever
Involvement of orbital muscles can result in diplopia and strabismus.
Dysarthria or dysphagia can result when tongue and pharyngeal muscles are affected.
Limb muscles usually are mildly involved.
Other manifestations include myocarditis and dyspnea from diaphragmatic involvement.
Lyme myositis
Weakness and atrophy of the proximal muscle groups can occur, accompanied by local swelling and tenderness.
Muscle weakness may be a major presenting feature of this disease.
Rarely, late ocular involvement, including orbital myositis[4] , may occur.
Cysticercosis with myositis
The most common sites of involvement are the skeletal and cardiac muscle, brain, and eyes.
When skeletal muscles are involved, palpable cysticerci (mature larvae) appear in subcutaneous tissues.
A notable feature of this type of myositis is muscle pseudohypertrophy, which may be seen in the tongue or calf muscles.
During the acute stage of disease, patients may have fever and muscle tenderness.
Trypanosomiasis with myositis
The acute stage of the disease may be characterized by fever, lymphadenopathy, and hepatosplenomegaly.
At the site of the insect bite, local inflammation (involving subcutaneous tissues and muscle) results in a swelling known as a chagoma.
Contamination of the eyes produces unilateral periocular and palpebral edema with conjunctivitis and preauricular lymphadenopathy (Romaña).
Extraocular involvement is rare. It may present with features of subacute orbital myositis and may mimic an orbital tumor.
During the acute parasitemic stage, intense infection of the myocardium may occur, producing severe myocarditis and disturbances of cardiac conduction.
Clinical manifestations in the early stage of myositis include muscle weakness, tenderness, and erythema mimicking those of polymyositis and dermatomyositis.
Skeletal muscle may be involved in the chronic stage as well and can last for decades.
Toxoplasma myositis
Muscle invasion by Toxoplasma gondii usually is seen in immunocompromised individuals with disseminated toxoplasmosis.
The clinical features are similar to those of polymyositis, with manifestations of fever and muscle weakness.
Polymyositis is a prominent feature even in the congenital form of toxoplasmosis.
Influenza myositis[5, 6]
Muscle weakness, tenderness, and swelling
More severe in adults
Proximal muscles are affected predominantly.
In children, involvement of the gastrocnemius-soleus muscles causes calf pain and difficulties with walking (toe-walking, wide-based gait)
Complications include myocarditis and respiratory dysfunction.
Acute coxsackievirus myositis
Group A virus
These viruses can cause an acute, diffuse inflammatory myopathy.
This may progress to rhabdomyolysis and myoglobinuria, leading to renal failure.
Group B virus infection (epidemic myalgia)
Muscle tenderness and swelling may be noted in some patients.
Relapses can occur 2 weeks to a few months after the initial presentation.
Fungal myositis
Clinically presents with fever, rash, and muscle tenderness
Parasitic -T gondii, Trichinella spiralis, Trichinella nativa (from eating bear meat), T nelsoni, T britovi, T pseudospiralis, Echinococcus granulosus, T solium, T cruzi, microsporidia
Fungal -Cryptococcus neoformans, Candida species (especially Candida tropicalis, Candida krusei, Candida albicans) , Histoplasma capsulatum, Coccidioides species , Aspergillus species , Pneumocystis jiroveci, microsporidia (eg, Anncaliia algerae[8] ), Fusarium species, and Actinomyces species; less common are mucormycosis, Sporothrix schenckii, and Blastomyces dermatitidis
MRI is the imaging modality of choice for the diagnosis of pyomyositis. MRI is helpful in differentiating pyomyositis from osteomyelitis. It is especially useful in differentiating early muscle inflammation from abscess formation. MRI is also the best imaging modality for evaluation of pelvic infections.[9]
CT scanning may show hypertrophy of involved muscle groups and effacement of the fat planes. Contrast enhancement may indicate abscess formation. CT is also useful for distinguishing tumors and hematomas from abscess.
Ultrasound or MRI also may be used to localize involved muscle.
Gallium scan is useful for localization in the early stages of illness.
Streptococcal myositis - CT scan helpful in assessing extent of muscle involvement and necrosis
Tuberculous pyomyositis
MRI: Findings are consistent with an abscess (ie, low signal intensity on T1-weighted images and high signal intensity on T2-weighted images of affected muscles).
Following gadolinium infusion, peripheral rim enhancement is noted. This is indicated by subtle hyperintensity on T1-weighted images and hypointensity on T2-weighted images.
Cysticercosis with orbital involvement: Multiplanar imaging with MRI may be obtained to identify a cyst with a mural nodule. With gadolinium, a nodule shows intense enhancement.
Trichinosis
Imaging of soft tissue or muscles may demonstrate the calcified lesions with classic "puffed rice" or "spindle-shaped" radiographic appearance.
MRI, CT, and ultrasonography may show a clear cyst with a scolex.
MRI is superior at demonstrating the cysts in the soft tissues.
Muscle biopsy is required to confirm diagnosis. Findings in the acute stage of larval invasion of the muscles include segmental necrosis and interstitial infiltrates composed mainly of eosinophils. The Trichinella species larvae sometimes can be seen in the muscle biopsy. However, encapsulated cysts (without larvae), granulomas, and focal calcification are more likely to be encountered.
Pyomyositis
Widespread necrosis of muscle fibers, perimysium, and blood vessels is noted. Pleomorphic inflammatory response consisting of both neutrophils and lymphocytes is noted.
Streptococcal myositis
Muscle necrosis and gram-positive bacteria in chains is noted.
Cysticercosis
The viable larvae produce little or no tissue reaction. However, rupture or death of a cysticercus (mature larva) evokes an acute inflammatory response with a pleomorphic exudate composed of neutrophils and eosinophils. Over time, fibrous tissue encapsulates the cysts. A chronic granulomatous response may surround the cysts.
Lyme myositis
Muscle biopsy shows atrophic fibers and an infiltrate consisting of lymphocytes, plasma cells, and macrophages. Borrelia burgdorferi can be detected in muscle fibers by the modified Dieterle silver stain method.
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Histopathology: Borrelia burgdorferi spirochetes in Lyme disease, with Dieterle silver stain. Courtesy of Centers for Disease Control and Prevention a....
Trypanosomiasis
Sections of infected tissues may reveal clusters of amastigotes in muscle cells surrounded by acute or chronic inflammation.
Influenza myositis
Muscle fiber necrosis without inflammatory change is observed. Influenza viral particles have been identified in muscle fibers under electron microscopy. Muscle fiber regeneration is seen in some, with an inflammatory response consisting of mononuclear and polymorphonuclear leukocytes.
Fungal myositis
Muscle biopsy is needed to confirm diagnosis. Budding yeast and pseudohyphae may be seen.
All medical care should be provided in conjunction with an infectious disease specialist and the primary care physician.
HIV polymyositis: Corticosteroids remain the mainstay of treatment of polymyositis.
Trichinosis
Thiabendazole is effective if administered within 24 hours of infection. It has minimal effect in established infection.
Optimal dosage has not been established.
It can be combined with prednisone 40-60 mg/day in patients with severe pain and weakness.
Trypanosomiasis
Benznidazole is a trypanocidal drug that is quite effective in the acute phase of the illness.
It reduces cardiac complications and parasitemia and has been found to be beneficial in the early chronic phase.
Successful treatment is evinced by serological tests remaining negative for at least 1 year after conclusion of treatment.
Viral myositis
Treatment comprises bed rest, intravenous fluids, and symptomatic management with antipyretics and analgesics.
Antiviral agents such as amantadine could be considered in adults.
Tuberculous and toxoplasmal myositis, cysticercosis: Please refer to the following articles: HIV-1 Associated Myopathies, Neurocysticercosis, and Neuroimaging in Neurocysticercosis.
Pyomyositis
Promptly administer systemic antibiotics. This could eliminate the need for surgical drainage in selected cases.
The choice of antibiotic is determined by identification of the causative organism.
Antibiotics initially are given intravenously until clinical improvement is noted, followed by oral antibiotics for a total course of 3 weeks (eg, cefazolin or ceftriaxone IV followed by cephalexin PO).
Streptococcal myositis
High-dose penicillin G (4 million units) and clindamycin (800-900mg) IV
Intravenous fluids
Fungal myositis: Use an antifungal agent such as amphotericin B or an echinocandin such as caspofungin.
Pyomyositis: During the suppurative phase, abscess aspiration under ultrasonic or CT guidance may be required. Surgical drainage is especially necessary for large abscesses.
Fungal myositis: Focal fungal abscesses may require surgical drainage/debridement.
Treat the underlying cause of infectious myositis. Use appropriate antibiotics for pyomyositis. Prednisone may be effective to treat HIV-1–associated polymyositis.[10]
Clinical Context:
Treats trichinosis infections; inhibits helminth-specific mitochondrial fumarate reductase; alleviates symptoms of trichinosis during invasive phase. Little value in disease that spreads beyond lumen of intestines; absorption from GI tract is poor.
Clinical Context:
May be useful in early stages of trichinosis. Causes worm death by selectively and irreversibly blocking uptake of glucose and other nutrients in susceptible adult intestine where helminths dwell.
Parasite biochemical pathways are sufficiently different from those of the human host to allow selective interference by chemotherapeutic agents in relatively small doses.
Clinical Context:
For treatment of Lyme myositis. Treats gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s).
Clinical Context:
Drug of choice for most neurologic manifestations of Lyme disease; third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to penicillin-binding proteins.
Clinical Context:
Can be used for treatment of pyomyositis. Semisynthetic cephalosporin effective against: S aureus (including penicillinase-producing strains), Staphylococcus epidermidis, group A beta-hemolytic streptococci, and other strains of streptococci.
Clinical Context:
For treatment of severe infections caused by methicillin-resistant (beta-lactam-resistant) staphylococci; and for treatment of staphylococcal infection in individuals allergic to penicillin or cephalosporins.
Prevent trichinosis and cysticercosis by adequately processing pork.
When traveling in endemic areas of Latin America, apply insect repellents such as N -diethyl-meta-toluamide (DEET) to avoid American trypanosomiasis. Pyrethrin insecticides also may be used to kill insect vectors. Using bed nets to keep away insects is advisable.
Influenza, echovirus, Legionella, and, rarely, coxsackievirus myositis can be complicated by rhabdomyolysis.[11, 5, 6]
Pyomyositis: Life-threatening complications include sepsis and toxic shock syndrome.
Gas gangrene usually follows penetrating injuries complicated by clostridial pyomyositis.
In the case of trichinosis, heavy infestation may be fatal because of myocarditis and/or diaphragmatic involvement. Myocarditis can lead to cerebral embolism.
Prompt administration of antibiotics can result in complete resolution of pyomyositis.
Most patients with trichinosis and myopathic involvement recover after several weeks. Infection may be fatal if severe and involving other organs systems (eg, cardiac, pulmonary, CNS).
Travelers visiting area of endemic trichinosis should be educated on the hazards of eating raw or undercooked pork.
Educate traveling diabetic patients concerning the need for prompt treatment of cutaneous infections and infected insect bites and to avoid strenuous activity.
The Myositis Association of America serves as a resource for patients and the medical community.
For patient education resources, see the Bites and Stings Center.
What is infectious myositis?What is the pathophysiology of infectious myositis?What is the prevalence of infectious myositis in the US?What is the global prevalence of infectious myositis?What are complications of infectious myositis?What are the demographic predilections of infectious myositis?What are the risk factors for infectious myositis?What are the signs and symptoms of pyomyositis?Which clinical history findings are characteristic of streptococcal myositis?What are the signs and symptoms of trichinosis?What are the signs and symptoms of lyme myositis?What are the signs and symptoms of cysticercosis with myositis?What are the signs and symptoms of trypanosomiasis?What are the signs and symptoms of toxoplasma myositis?What are the signs and symptoms of influenza myositis?What are the signs and symptoms of acute coxsackievirus myositis?What are the signs and symptoms of fungal myositis?What are the signs and symptoms of cryptococcal myositis?Which physical findings are characteristic of pyomyositis?Which physical findings are characteristic of streptococcal myositis?Which physical findings are characteristic of trichinosis?Which physical findings are characteristic of lyme myositis?Which physical findings are characteristic of cysticercosis with myositis?Which physical findings are characteristic of trypanosomiasis with myositis?Which physical findings are characteristic of toxoplasma myositis?Which physical findings are characteristic of influenza myositis?Which physical findings are characteristic of acute coxsackievirus myositis?Which physical findings are characteristic of fungal myositis?Which pathogens cause infectious myositis?What are the differential diagnoses for Infectious Myositis?Which lab studies are performed in the workup of pyomyositis?Which lab studies are performed in the workup of streptococcal myositis?Which lab studies are performed in the workup of trichinosis?What is the role of serology in the workup of infectious myositis?Which lab studies are performed in the workup of cysticercosis in infectious myositis?Which lab studies are performed in the workup of HTLV-1 infection in infectious myositis?Which lab studies are performed in the workup of trypanosomiasis?Which lab studies are performed in the workup of influenza myositis?Which lab studies are performed in the workup of coxsackievirus myositis?Which lab studies are performed in the workup of cryptococcal myositis?Which lab studies are performed in the workup of fungal myositis?Which imaging studies are performed in the workup of pyomyositis?Which imaging studies are performed in the workup of streptococcal myositis?Which imaging studies are performed in the workup of tuberculous pyomyositis?Which imaging studies are performed in the workup of cysticercosis in infectious myositis?Which imaging studies are performed in the workup of trichinosis?What is the role of skin testing in the workup of infectious myositis?What is the role of electromyography (EMG) in the diagnosis of infectious myositis?What is the role of needle aspiration in the diagnosis of infectious myositis?What are the histologic features of trichinosis?What are the histologic features of pyomyositis?What are the histologic features of streptococcal myositis?What are the histologic features of cysticercosis in infectious myositis?What are the histologic features of lyme myositis?What are the histologic features of trypanosomiasis?What are the histologic features of influenza myositis?What are the histologic features of fungal myositis?Which specialists should be consulted in the treatment of infectious myositis?How is HIV polymyositis treated?How is trichinosis treated?How is trypanosomiasis treated?How is viral myositis treated?How is tuberculous and toxoplasmal myositis treated?How is pyomyositis treated?How is streptococcal myositis treated?How is fungal myositis treated?What is the role of surgery in the treatment of infectious myositis?Which specialist consultations are beneficial in the treatment of infectious myositis?Which medications are used in the treatment of infectious myositis?Which medications in the drug class Antibiotics are used in the treatment of Infectious Myositis?Which medications in the drug class Anthelmintic are used in the treatment of Infectious Myositis?Which medications in the drug class Corticosteroids are used in the treatment of Infectious Myositis?When is inpatient care indicated in the treatment of infectious myositis?How is infectious myositis prevented?What are the complications of infectious myositis?What is the prognosis of infectious myositis?What should be included in patient education for infectious myositis?
Mohammed J Zafar, MD, FAAN, FACP, FASN, Associate Clinical Professor of Medicine, West Michigan University School of Medicine; Neurologist, Clinical Neurophysiologist and Neuroimager, Kalamazoo Nerve Center, PLLC
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Florian P Thomas, MD, PhD, MA, MS, Chair, Neuroscience Institute and Department of Neurology, Director, National MS Society Multiple Sclerosis Center and Hereditary Neuropathy Foundation Center of Excellence, Hackensack University Medical Center; Founding Chair and Professor, Department of Neurology, Hackensack Meridian School of Medicine at Seton Hall University; Professor Emeritus, Department of Neurology, St Louis University School of Medicine; Editor-in-Chief, Journal of Spinal Cord Medicine
Disclosure: Nothing to disclose.
Chief Editor
Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM, Adjunct Associate Professor of Neurology, University of Missouri-Columbia School of Medicine; Medical Director of St Mary's Stroke Program, SSM Neurosciences Institute, SSM Health
Disclosure: Nothing to disclose.
Additional Contributors
Roberta J Seidman, MD, Associate Professor of Clinical Pathology, Stony Brook University School of Medicine; Director of Neuropathology, Department of Pathology, Stony Brook University Medical Center
Tulio AM et al. Strickland TG. American trypanosomiasis. 7th ed. Hunter's Tropical Medicine; 1991. 628-37.
Ixodes scapularis (dammini), tick vector for Lyme disease. Courtesy of Centers for Disease Control and Prevention.
Trypanosoma cruzi in blood smear. Courtesy of Centers for Disease Control and Prevention.
A patient with trichinosis and ocular involvement. Courtesy of Centers for Disease Control and Prevention and Dr. Thomas F. Sellers, Jr.
Histopathology: Borrelia burgdorferi spirochetes in Lyme disease, with Dieterle silver stain. Courtesy of Centers for Disease Control and Prevention and Dr Edwin P. Ewing, Jr.
Ixodes scapularis (dammini), tick vector for Lyme disease. Courtesy of Centers for Disease Control and Prevention.
Trypanosoma cruzi in blood smear. Courtesy of Centers for Disease Control and Prevention.
A patient with trichinosis and ocular involvement. Courtesy of Centers for Disease Control and Prevention and Dr. Thomas F. Sellers, Jr.
Histopathology: Borrelia burgdorferi spirochetes in Lyme disease, with Dieterle silver stain. Courtesy of Centers for Disease Control and Prevention and Dr Edwin P. Ewing, Jr.
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