Infectious Disease and Microbiology – Relapsing Fever
Relapsing fever is a spirochetal infection characterized by recurrent episodes of fever separated by periods of normal temperature. The disease occurs in two major forms: louse-borne (epidemic) relapsing fever and tick-borne (endemic) relapsing fever.
The epidemiology of relapsing fever varies according to the mode of transmission. Louse-borne relapsing fever, caused by Borrelia recurrentis, is strongly associated with poor socioeconomic conditions, overcrowding, war, famine, and natural disasters, which facilitate the spread of body lice. Although uncommon worldwide today, endemic areas persist in parts of Central and East Africa and the Andes region of South America.
Tick-borne relapsing fever has a worldwide distribution but is particularly common in tropical Africa. In the United States, cases occur mainly west of the Mississippi River. In mountainous regions such as California, Utah, Arizona, New Mexico, Colorado, Oregon, and Washington, Borrelia hermsii is the predominant species, whereas Borrelia turicatae is more common in nonmountainous areas of the Southwest.
Risk factors for louse-borne relapsing fever include homelessness and overcrowding. Tick-borne relapsing fever is associated with recreational or occupational exposure to tick-infested environments. B. hermsii infection is frequently linked to exposure to cabins in pine forests, while B. turicatae infection may follow entry into caves or crawling under houses.
Preventive measures focus on control of lice and ticks. In high-risk settings for tick-borne relapsing fever, postexposure prophylaxis with doxycycline may be recommended. A suggested regimen is doxycycline 200 mg orally on the first day followed by 100 mg daily for four additional days.
The pathophysiology differs according to the vector. In louse-borne disease, crushing infected lice releases Borrelia recurrentis, which enters the body through skin breaks or mucous membranes. Tick-borne disease is transmitted through the saliva of soft-bodied ticks during feeding. Because argasid ticks feed rapidly at night and produce painless bites, many individuals are unaware they were bitten.
Fever corresponds to periods of spirochetemia. During afebrile intervals, spirochetes are sequestered within internal organs. Under immune pressure, the organisms undergo antigenic variation and reappear in the bloodstream, producing recurrent febrile episodes.
Relapsing fever is caused by spirochetes of the genus Borrelia. The human body louse (Pediculus humanus corporis) transmits B. recurrentis, causing epidemic relapsing fever. Tick-borne disease is transmitted by soft-bodied ticks of the genus Ornithodoros, which can carry more than 15 pathogenic Borrelia species.
The incubation period is usually around 8 days, ranging from 5–15 days. Illness begins abruptly with fever accompanied by chills, rigors, headache, malaise, arthralgias, diffuse myalgias, lethargy, cough, jaundice, and photophobia. Some patients develop petechial, macular, or papular rashes. Cardiac and neurologic manifestations may occur, particularly in tick-borne disease.
The febrile episode typically ends suddenly after 3–6 days. After an afebrile period lasting approximately 7–9 days, symptoms recur. Louse-borne relapsing fever usually produces one or two relapses, whereas multiple relapses are common in tick-borne disease.
Physical examination may reveal conjunctival injection and edema, hepatomegaly, splenomegaly, diffuse abdominal tenderness, lymphadenopathy, rales, rhonchi, and neurologic abnormalities. Neurologic complications are more common in tick-borne relapsing fever.
The definitive diagnosis is made by demonstrating Borrelia organisms in peripheral blood obtained during febrile episodes. Thick and thin blood smears stained with Giemsa or Wright stain should be carefully examined. Organisms are rarely detectable during afebrile periods. Dark-field microscopy can also identify spirochetes. Polymerase chain reaction testing may be performed on blood samples. Serologic tests may support the diagnosis but have limited sensitivity and specificity.
The differential diagnosis includes malaria, leptospirosis, dengue fever, babesiosis, tularemia, ehrlichiosis/anaplasmosis, rat-bite fever, and typhus, especially during epidemics of louse-borne relapsing fever.
Treatment depends on the type of disease. Louse-borne relapsing fever is treated with a single oral dose of tetracycline 500 mg or doxycycline 100 mg. Tick-borne relapsing fever requires a longer course, typically tetracycline 500 mg orally every 6 hours or doxycycline 100 mg orally twice daily for 7 days.
Patients with meningitis or encephalitis should receive parenteral antibiotics such as penicillin G or ceftriaxone for 10–14 days. Erythromycin may serve as an alternative regimen, particularly for patients unable to take tetracyclines.
A Jarisch-Herxheimer reaction may occur shortly after initiation of antibiotic therapy, especially with penicillin treatment. This reaction results from rapid destruction of spirochetes and may present with fever, hypotension, chills, and worsening symptoms.
Careful follow-up is necessary because relapses are common. Untreated louse-borne relapsing fever has a mortality rate ranging from 4–40%, while untreated tick-borne disease carries a mortality rate of 2–5%.
Major complications include myocarditis with arrhythmias, liver damage, cerebral hemorrhage, acute respiratory distress syndrome, meningitis, meningoencephalitis, cranial neuritis, aphasia, hemiplegia, iridocyclitis, and panophthalmitis.

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Infectious Disease and Microbiology – Rabies
Rabies is a fatal viral infection caused by a bullet-shaped, single-stranded RNA virus belonging to the family Rhabdoviridae. The disease primarily affects the central nervous system and is almost universally fatal once clinical symptoms develop.
Rabies remains a major global public health problem. Approximately 15 million people receive postexposure prophylaxis annually worldwide. According to the World Health Organization, many cases are underreported, and annual deaths may exceed 55,000. The disease is more common in developing countries and occurs worldwide except in Antarctica and a few isolated island nations. In developing nations, dog bites are the most common mode of transmission, whereas in developed countries transmission more commonly occurs through raccoons, bats, foxes, and skunks.
Individuals at increased risk include laboratory workers involved in rabies research or vaccine production, veterinarians, wildlife officers, and people frequently exposed to wild animals. Exposure in caves may result from inhalation of aerosolized bat excreta. There is no known genetic predisposition.
The most effective preventive measure is mass vaccination of animals, especially dogs. Individuals with occupational or travel-related risk should receive preexposure vaccination. Preexposure prophylaxis consists of rabies vaccine administered intramuscularly on days 0, 7, and 21 or 28. Antibody titers should be periodically checked in high-risk individuals such as laboratory workers and wildlife officers.
The rabies virus enters the body through broken skin or mucous membranes, most commonly after an animal bite. The incubation period usually ranges from 20–90 days but may vary considerably. After entry, the virus travels centripetally through peripheral nerves by axonal transport to the central nervous system, where viral replication occurs with formation of characteristic Negri bodies. The virus then spreads centrifugally to tissues including the salivary and lacrimal glands.
Human infection usually results from bites of rabid animals, especially dogs. Because the virus is present in high concentrations in saliva, scratches or licks on broken skin may also transmit infection.
History is crucial for diagnosis. Multiple bites, bites involving the face, and deep penetrating injuries carry greater risk than superficial bites through clothing or bites to extremities. Early symptoms include paresthesias or pain at the bite site, fever, malaise, sore throat, nausea, and vomiting. This prodromal phase generally lasts 2–10 days.
Following the prodrome, encephalitis develops. Patients may exhibit fever, personality changes, agitation, hyperactivity, hallucinations, biting behavior, and autonomic instability. Characteristic findings of furious rabies include hydrophobia, in which attempts to drink or even the sight of water provoke painful pharyngeal spasms, and aerophobia, in which airflow or sensory stimuli trigger spasms. Seizures may occur, sometimes precipitated by tactile stimuli. Periods of agitation alternate with intervals of lucidity. Rapid progression to coma commonly follows. Paralysis may develop later in the disease.
Paralytic rabies presents differently and may resemble Guillain-Barré syndrome, with progressive weakness and paralysis.
Laboratory diagnosis is difficult and often secondary to clinical suspicion and exposure history. Direct fluorescent antibody testing of a skin biopsy taken from the nape of the neck remains the standard diagnostic method. RT-PCR testing of saliva, cerebrospinal fluid, or tissue specimens may also be used. Cerebrospinal fluid findings are nonspecific and may show pleocytosis. MRI may demonstrate increased T2 signal intensity in the hippocampi, hypothalamus, or brainstem, although imaging findings are not specific.
Pathologic examination reveals Negri bodies, especially in hippocampal pyramidal cells. Paralytic rabies may also show segmental demyelination resembling Guillain-Barré syndrome.
The differential diagnosis includes tetanus, viral encephalitis, acute disseminated encephalomyelitis, poliomyelitis, Guillain-Barré syndrome, and acute demyelinating polyneuropathy.
Management after exposure is critical because established rabies is almost universally fatal. Immediate wound cleansing with soap and water and irrigation with iodine-containing solutions can reduce transmission risk by approximately 90%.
For previously unvaccinated individuals, postexposure prophylaxis includes human rabies immunoglobulin at 20 units/kg administered once on day 0. As much of the dose as possible should be infiltrated around the wound, with the remainder injected intramuscularly at a site distant from vaccine administration. Rabies vaccine is administered intramuscularly in the deltoid region on days 0, 3, 7, 14, and 28.
Previously vaccinated individuals do not require rabies immunoglobulin and instead receive booster vaccine doses on days 0 and 3.
Immunocompromised patients may have inadequate vaccine responses and should undergo antibody testing 2–4 weeks after vaccination.
Hospital admission is recommended for patients with deep or multiple wounds, altered behavior, or neurologic symptoms. Supportive care, including intravenous fluids and careful nursing management, is essential in symptomatic rabies. Environmental stimuli should be minimized to reduce provocation of spasms and seizures.
Patients should be advised to observe the biting dog or animal for 10 days if possible. If the animal dies, disappears, or develops abnormal behavior during this period, health authorities should be notified immediately.
The prognosis of clinical rabies is extremely poor, with nearly 100% mortality in unvaccinated individuals once symptoms develop. In contrast, individuals who receive prompt postexposure prophylaxis after exposure generally have an excellent prognosis.
Complications include encephalomyelitis, intractable seizures, Guillain-Barré syndrome, myocarditis, arrhythmias, respiratory failure, vascular collapse, and death.

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Infectious Disease and Microbiology – Pyelonephritis
Pyelonephritis is a common infection of the upper urinary tract that causes inflammation of the renal pelvis, calyces, and renal parenchyma. It may occur as acute uncomplicated pyelonephritis, acute complicated pyelonephritis, chronic pyelonephritis, or xanthogranulomatous pyelonephritis. Chronic pyelonephritis is characterized by uneven renal scarring and chronic inflammatory changes affecting the renal interstitium and tubules.
The disease is much more common in females than males. Young women, infants, and elderly individuals are the groups most commonly affected. In the United States, more than 250,000 cases occur annually.
Risk factors include pregnancy, urinary tract obstruction caused by prostate disease or urethral narrowing, renal calculi, diabetes mellitus, and recurrent urinary tract infections. In young women, frequent sexual intercourse, spermicide use, stress incontinence, a new sexual partner, and a personal or maternal history of urinary tract infection significantly increase the likelihood of infection. Prevention focuses on prompt recognition and treatment of lower urinary tract infections and reduction of modifiable risk factors.
Most infections occur by ascending spread of organisms from the urethra to the bladder and then through the ureters to the kidneys. Less commonly, hematogenous spread occurs, particularly with gram-positive organisms or fungal infections.
The most common pathogen is Escherichia coli, responsible for approximately 80% of cases. Other important organisms include Proteus species and Klebsiella species. Less common causes include Pseudomonas aeruginosa, enterococci, and Staphylococcus saprophyticus. Isolation of Staphylococcus aureus from urine usually suggests bacteremia. Emphysematous pyelonephritis, a severe gas-forming necrotizing infection of the kidney, is commonly caused by E. coli and Klebsiella species and rarely by Candida species.
Symptoms may develop over several hours or days and commonly include fever, chills, malaise, headache, nausea, vomiting, flank pain, back pain, abdominal pain, dysuria, urgency, and hematuria. Elderly patients may have only minimal symptoms, while children often present with nonspecific findings.
Physical examination frequently demonstrates fever, tachycardia, flank tenderness, dehydration, or signs of sepsis in severe disease.
Diagnosis begins with urinalysis showing pyuria and bacteriuria, although absence of bacteria does not exclude pyelonephritis. Pretreatment urine cultures are essential. Laboratory studies may demonstrate leukocytosis with left shift, elevated inflammatory markers such as ESR and CRP, and abnormalities in renal function tests. Blood cultures may be helpful in severe infections.
Imaging is indicated in recurrent disease, atypical presentations, persistent hematuria, suspected obstruction, or failure to improve after 72 hours of treatment. Plain abdominal radiographs may identify calculi or gas formation. Ultrasonography is preferred initially in recurrent or atypical cases. Contrast-enhanced CT scanning is useful for identifying obstruction, renal or perinephric abscesses, and complicated anatomy. Repeat imaging may be required if clinical deterioration occurs despite treatment.
The differential diagnosis includes cystitis, urethritis, vaginitis, appendicitis, pelvic inflammatory disease, and renal or bladder tumors.
Treatment depends on disease severity and local antimicrobial susceptibility patterns. Outpatient treatment for uncomplicated pyelonephritis may include oral amoxicillin, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, ciprofloxacin, levofloxacin, norfloxacin, or cefpodoxime. Fluoroquinolones are commonly used because of excellent renal penetration. Therapy usually lasts 10–14 days, although short-course high-dose levofloxacin may be used for 5 days.
Hospitalized patients require intravenous antibiotics such as ciprofloxacin, levofloxacin, ceftriaxone, gentamicin, ampicillin, aztreonam, imipenem-cilastatin, ertapenem, or ticarcillin-clavulanic acid. After clinical improvement and resolution of fever, patients are transitioned to oral therapy to complete treatment.
Supportive care includes rest, analgesics, antiemetics, and adequate hydration. Intravenous fluids are essential in septic or dehydrated patients.
Consultation with a urologist is recommended when obstruction or structural abnormalities are present, since surgical correction may be necessary. Infectious disease consultation is helpful for resistant or unusual organisms such as Pseudomonas aeruginosa or extended-spectrum beta-lactamase–producing bacteria.
Surgical management may be required in emphysematous pyelonephritis, renal or perinephric abscess, renal stones, or xanthogranulomatous pyelonephritis.
Hospital admission is indicated for severe illness, dehydration, inability to tolerate oral medications, pregnancy, or concern for sepsis. Patients can generally be discharged after 24–48 hours of clinical improvement and defervescence.
Follow-up includes post-treatment urine cultures and further imaging or laboratory evaluation in patients with persistent symptoms. Patients should be advised to complete antibiotic therapy exactly as prescribed and maintain adequate hydration.
Acute uncomplicated pyelonephritis generally has an excellent prognosis, with overall in-hospital mortality below 1–2%. Complications include bacteremia, septic shock, renal abscess, perinephric abscess, and struvite stone formation, particularly in infections caused by Proteus species.
ICD-9 Codes

• 590.00 – Chronic pyelonephritis without lesion of renal medullary necrosis
• 590.10 – Acute pyelonephritis without lesion of renal medullary necrosis
• 590.80 – Pyelonephritis, unspecified

Clinical Pearls
Escherichia coli and Klebsiella pneumoniae have developed significant resistance to many antibiotic classes. Extended-spectrum beta-lactamase production, often associated with quinolone resistance, presents a major therapeutic challenge. Carbapenems or fosfomycin disodium may be necessary for treatment in resistant infections. Treatment should always be guided by local susceptibility patterns of urinary pathogens. Quinolones and sulfonamides should be avoided during pregnancy and in patients with glucose-6-phosphate dehydrogenase deficiency.
Infectious Disease and Microbiology – Q Fever
Q fever is a globally distributed zoonotic infection caused by Coxiella burnetii. The disease was named “Q” for “query” because its cause was unknown when first described in 1935. It usually presents as an acute febrile illness, atypical pneumonia, or hepatitis, although chronic infection can occur, most commonly as endocarditis.
The primary reservoirs of C. burnetii are cattle, sheep, and goats, though many animals including rodents and cats may be infected. The organism is shed in milk, urine, feces, and particularly amniotic fluid of infected animals. Humans usually acquire infection by inhaling contaminated aerosols. Very few organisms are needed to cause infection, making the bacterium highly infectious. Transmission through blood transfusion is rare.
The disease is often underdiagnosed and underreported worldwide. Many infections are asymptomatic. Cases tend to occur more commonly during lambing and calving seasons, particularly between February and May in some regions. Men are affected more frequently than women.
Prevention includes avoiding unpasteurized milk, proper disposal of infected animal products, isolation of affected animals, and vaccination of high-risk workers in countries where vaccines are available, such as Australia.
Coxiella burnetii is a gram-negative intracellular coccobacillus capable of surviving within host phagolysosomes. Acute infection is characterized by antibodies directed against phase II antigens, while chronic infection is associated with elevated phase I antibody titers. Host immune response, especially T-cell–mediated immunity, plays a major role in determining disease progression.
Approximately half of infected individuals remain asymptomatic. Symptomatic acute Q fever commonly presents as a self-limited febrile illness, influenza-like syndrome, atypical pneumonia, or hepatitis. Symptoms include fever, chills, headache, sweats, nausea, vomiting, diarrhea, and malaise. Pneumonia and hepatitis frequently coexist. Severe infection during pregnancy may result in abortion or neonatal death.
Headache is the most common neurologic symptom. Rare manifestations include epididymitis, erythema nodosum, Guillain-Barré syndrome, hemolytic anemia, optic neuritis, pancreatitis, orchitis, myocarditis, pericarditis, osteomyelitis, meningoencephalitis, and prolonged fever.
Chronic Q fever most commonly manifests as endocarditis, particularly involving the aortic valve. Fever may be absent or low grade. Infection of vascular grafts, aneurysms, and prosthetic material has become increasingly recognized.
Physical examination in acute disease often reveals high fever, occasionally reaching 40°C, with relative bradycardia. Hepatomegaly and splenomegaly may occur. Rash is uncommon compared with other rickettsial diseases.
Diagnosis is primarily serologic. Indirect immunofluorescence is the preferred test. Acute infection is suggested by a fourfold rise in antibody titers between acute and convalescent samples or elevated IgM titers. PCR testing may detect bacterial DNA in blood or tissue specimens. Laboratory abnormalities may include elevated ESR and CRP, thrombocytopenia or thrombocytosis, monocytosis, elevated alkaline phosphatase, and abnormal liver function tests.
Chest imaging in Q fever pneumonia may reveal pleural effusions or infiltrates, and radiographic resolution can take several weeks. Chronic infection should be considered in cases of culture-negative endocarditis.
The differential diagnosis includes other causes of atypical pneumonia, hepatitis of unknown origin, culture-negative endocarditis, and central nervous system infections.
Early treatment improves outcomes. Acute Q fever is usually treated successfully with doxycycline 100 mg twice daily for 14 days. Chronic Q fever, especially endocarditis, is treated with prolonged doxycycline plus hydroxychloroquine therapy, often for 3–4 years or longer. Treatment duration is guided by serial antibody titers. Rifampin or fluoroquinolones may also be used in selected chronic cases.
Most acute infections resolve spontaneously, but chronic Q fever carries significant morbidity and mortality. Mortality from acute disease is approximately 2%, whereas mortality from Q fever endocarditis may reach 25–60%, with frequent relapse.

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Infectious Disease and Microbiology – Pyelonephritis
Pyelonephritis is a common infection of the upper urinary tract that causes inflammation of the renal pelvis, calyces, and renal parenchyma. It may present as acute uncomplicated pyelonephritis, acute complicated pyelonephritis, chronic pyelonephritis, or xanthogranulomatous pyelonephritis. Chronic pyelonephritis is characterized by uneven renal scarring and chronic inflammatory changes involving the renal interstitium and tubules.
The disease is much more common in females than males. Young women, infants, and elderly individuals are the most commonly affected groups. In the United States, more than 250,000 cases occur annually.
Risk factors include pregnancy, urinary obstruction due to prostate disease or urethral narrowing, renal stones, diabetes mellitus, and recurrent lower urinary tract infections. In young women, frequent sexual intercourse, spermicide use, stress incontinence, a new sexual partner, and a personal or maternal history of urinary tract infection significantly increase risk. Prevention focuses on early diagnosis and treatment of lower urinary tract infections and reduction of modifiable risk factors such as spermicide use.
Most infections occur by ascending spread of pathogens from the urethra to the bladder and then through the ureters to the kidneys. Less commonly, hematogenous spread occurs, especially with gram-positive organisms or fungal infections.
The most common causative organism is Escherichia coli, responsible for approximately 80% of cases. Other pathogens include Proteus species and Klebsiella species. Less common causes include Pseudomonas aeruginosa, enterococci, and Staphylococcus saprophyticus. Isolation of Staphylococcus aureus from urine often suggests bacteremia. Emphysematous pyelonephritis, a severe gas-forming necrotizing infection, is commonly caused by E. coli and Klebsiella species and occasionally by Candida species.
Symptoms may develop over several hours or days. Patients commonly experience fever, chills, nausea, vomiting, malaise, headache, flank pain, back pain, abdominal pain, and symptoms of lower urinary tract infection such as dysuria, urgency, and hematuria. Elderly patients may present with few symptoms, while children often present nonspecifically.
Physical examination commonly reveals fever, tachycardia, flank tenderness, and sometimes signs of sepsis or dehydration. Toxic appearance may indicate severe infection.
Diagnosis begins with urinalysis demonstrating pyuria and bacteriuria, although absence of bacteria does not exclude pyelonephritis. Pretreatment urine cultures are essential. Laboratory studies may show leukocytosis with left shift, elevated ESR and CRP, and abnormal renal function tests. Blood cultures may be helpful in severe cases.
Imaging is reserved for atypical presentations, recurrent disease, suspected obstruction, or failure to improve within 72 hours of therapy. Plain abdominal radiographs may identify calculi or gas formation in emphysematous pyelonephritis. Ultrasonography is preferred initially for recurrent or atypical disease. Contrast-enhanced CT scanning provides better evaluation of obstruction, abscesses, or complicated anatomy. Repeat ultrasonography may be necessary if deterioration occurs despite treatment.
The differential diagnosis includes cystitis, urethritis, vaginitis, appendicitis, pelvic inflammatory disease, and tumors of the kidney or bladder.
Treatment depends on disease severity and whether the infection is complicated. Outpatient therapy for uncomplicated acute pyelonephritis may include oral amoxicillin, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, ciprofloxacin, levofloxacin, norfloxacin, or cefpodoxime. Fluoroquinolones are commonly used because of their excellent renal tissue penetration. Treatment generally lasts 10–14 days, although high-dose levofloxacin may be given for 5 days.
Hospitalized patients require intravenous therapy with agents such as ciprofloxacin, levofloxacin, ceftriaxone, gentamicin, ampicillin, aztreonam, imipenem-cilastatin, ertapenem, or ticarcillin-clavulanic acid. Once fever resolves and clinical improvement occurs, patients are transitioned to oral therapy to complete the course.
Supportive care includes rest, analgesics, antiemetics, and adequate hydration. Intravenous fluids are especially important in septic or dehydrated patients.
Consultation with a urologist is indicated when urinary obstruction or structural abnormalities are present, as surgical correction may be necessary. Infectious disease consultation is helpful for unusual or resistant organisms such as Pseudomonas aeruginosa or extended-spectrum beta-lactamase–producing bacteria.
Surgical intervention may be necessary in emphysematous pyelonephritis, renal or perinephric abscess, renal calculi, or xanthogranulomatous pyelonephritis.
Hospital admission is recommended for severe illness, high fever, significant pain, dehydration, inability to tolerate oral medications, poor compliance, or pregnancy. Patients may be discharged after 24–48 hours of clinical improvement and defervescence.
Follow-up includes post-treatment urine cultures and further imaging or laboratory testing in patients with persistent symptoms. Patients should be advised to complete prescribed antibiotic courses and maintain adequate fluid intake.
Acute uncomplicated pyelonephritis generally carries an excellent prognosis, with overall in-hospital mortality below 1–2%. Complications include bacteremia, septic shock, renal abscess, perinephric abscess, and formation of struvite stones, particularly with Proteus infections.

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Infectious Disease and Microbiology – Psittacosis
Psittacosis, also called parrot fever or ornithosis, is a systemic zoonotic infection caused by Chlamydophila psittaci. It is transmitted from infected birds to humans and most often affects the lungs, producing an atypical pneumonia. Although the name comes from the Greek word for parrot, almost any bird can act as a source of infection.
The disease is uncommon in the United States, with only a small number of reported cases each year, but it is likely underdiagnosed because many infections are mild or self-limited. C. psittaci is estimated to cause a small percentage of community-acquired pneumonia cases. People at higher risk include bird owners, pet shop workers, poultry workers, veterinarians, pigeon fanciers, taxidermists, zoo workers, and people who handle birds or bird tissues.
Transmission occurs mainly through inhalation of contaminated bird secretions, dried feces, feathers, or tissues. Infected birds may appear healthy or may show signs such as ruffled feathers, respiratory symptoms, conjunctivitis, or diarrhea. Shedding increases when birds are stressed. Prevention includes proper bird quarantine, treatment of infected birds by veterinarians, protective clothing, gloves, eye protection, and fitted respirators when handling potentially infected birds or cleaning cages.
After an incubation period of about 5–21 days, psittacosis usually begins suddenly with fever, chills, headache, muscle aches, sweating, and a dry cough. Respiratory symptoms may be mild early in illness. Severe headache is common, and some patients develop confusion, agitation, lethargy, or meningoencephalitis. Gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea may occur. Rarely, psittacosis can involve the heart, kidneys, liver, eyes, joints, blood, or central nervous system. Severe cases can progress to respiratory failure, septic shock, kidney failure, liver failure, disseminated intravascular coagulation, or hemophagocytic syndrome.
On examination, patients may have fever, pharyngitis, hepatomegaly, and abnormal lung findings such as fine rales, rhonchi, egophony, or bronchial breath sounds. Neck stiffness, photophobia, altered mental status, and splenomegaly may occur in some cases.
Diagnosis can be difficult because laboratory findings are nonspecific. Testing may include complete blood count, electrolytes, kidney and liver function tests, coagulation studies, urinalysis, blood cultures, and specific testing for psittacosis. White blood cell counts may be low, normal, or elevated, and inflammatory markers may rise. Mild liver enzyme elevation is common. Diagnosis is usually made by serology, showing a fourfold rise in IgG titers between acute and convalescent samples. PCR testing of respiratory specimens may also help, although culture is rarely performed because it requires specialized facilities.
Chest radiographs are abnormal in most patients and may show interstitial infiltrates, nodules, a miliary pattern, or lobar consolidation. Radiographic findings may appear more severe than the physical examination suggests. Bronchoscopy with bronchoalveolar lavage may be useful when PCR testing is needed.
The differential diagnosis includes other causes of atypical or community-acquired pneumonia, such as Chlamydia pneumoniae, Mycoplasma pneumoniae, Coxiella burnetii, Legionella pneumophila, viral pneumonia, influenza, histoplasmosis, coccidioidomycosis, and obstructive lung cancer.
Doxycycline is the first-line treatment. Mild to moderate disease is treated with doxycycline 100 mg orally twice daily, while severe cases may require intravenous doxycycline. Tetracycline is an alternative. Symptoms and fever usually improve within 24–48 hours after treatment begins. Therapy should continue for at least 10 days and generally for 10–14 days after fever resolves. Macrolides such as azithromycin or erythromycin may be used in children, pregnancy, or patients unable to tolerate doxycycline.
Severe cases may require hospitalization, respiratory support, and intensive care. Patients with altered mental status, hypoxemia, cardiac dysfunction, or kidney impairment should be admitted. Droplet precautions and standard infection control practices should be used.
Follow-up includes completion of antimicrobial therapy and public health reporting. Health departments may investigate possible bird sources and additional cases. Patients should be educated about symptoms in birds and humans, transmission routes, and prevention strategies.
With appropriate doxycycline therapy, prognosis is usually excellent and death is rare. Complications can include fulminant multisystem disease, hepatitis, anemia, reactive arthritis, meningoencephalitis, keratoconjunctivitis, myocarditis, pericarditis, nephritis, thrombophlebitis, and pulmonary infarction.

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Infectious Disease and Microbiology – Pseudomonas Infections, Melioidosis, and Glanders
Members of the genus Pseudomonas are motile, gram-negative, aerobic bacteria associated with a broad range of infections. Burkholderia pseudomallei (formerly Pseudomonas pseudomallei) causes melioidosis, also known as Whitmore’s disease or Nightcliff gardener’s disease. Burkholderia mallei (formerly Pseudomonas mallei) causes glanders, a zoonotic disease primarily affecting horses, mules, and donkeys but also capable of infecting humans. Both B. pseudomallei and B. mallei are considered potential bioterrorism agents.

Pseudomonas aeruginosa is one of the leading causes of hospital-acquired urinary tract infections, pneumonia, and bacteremia. It accounts for approximately 10% of all nosocomial infections and is especially common among patients hospitalized for more than one week. Melioidosis is endemic in tropical regions, particularly Southeast Asia, while glanders remains endemic in parts of Africa, Asia, the Middle East, Central America, and South America. Person-to-person transmission of melioidosis is rare.

Risk factors for P. aeruginosa infection include disruption of normal host barriers through endotracheal intubation or urinary catheterization, immunosuppression, and prior broad-spectrum antibiotic therapy. Patients with cystic fibrosis are especially susceptible to chronic lower respiratory tract colonization and infection. P. aeruginosa is also a major cause of ventilator-associated pneumonia. Central nervous system infections are associated with neurosurgical procedures, indwelling devices, cerebrospinal fluid leaks, penetrating trauma, and bacteremia. Bone and joint infections may occur after surgery, intravenous drug use, or penetrating trauma. Malignant external otitis is a severe invasive infection seen primarily in diabetic or immunocompromised patients and may extend into the central nervous system. Ocular infections, gastrointestinal infections in neutropenic patients, and burn wound infections are also common manifestations.

Risk factors for melioidosis include diabetes mellitus, thalassemia, chronic kidney disease, and occupational or environmental exposure to contaminated soil or water. There is no available vaccine against Pseudomonas infections, and prevention mainly relies on minimizing risk factors and limiting healthcare-associated exposures.

The pathogenesis of Pseudomonas infections begins with bacterial attachment and colonization of surfaces such as catheters, respirators, and damaged tissue. This may lead to localized infection followed by hematogenous dissemination and systemic disease.

P. aeruginosa is the most important human pathogen within this group. Other clinically relevant species include Burkholderia cepacia, associated with respiratory infections in cystic fibrosis patients and various nosocomial infections; Burkholderia pickettii, implicated in hospital outbreaks; Comamonas acidovorans, a rare cause of endocarditis; Pseudomonas fluorescens, linked to contaminated blood products; Pseudomonas putida, which may cause sepsis in immunocompromised hosts; and Stenotrophomonas maltophilia, associated with pneumonia, bacteremia, endocarditis, meningitis, urinary tract infections, and wound infections.

Clinical manifestations depend on the organ system involved. In early cystic fibrosis, P. aeruginosa causes recurrent upper respiratory symptoms, while advanced disease leads to chronic productive cough, recurrent pneumonia, respiratory compromise, weakness, and weight loss. Corneal ulcers due to P. aeruginosa may progress rapidly and threaten vision. Malignant external otitis presents with severe otalgia and otorrhea, and physical examination typically reveals erythema, swelling, purulent discharge, granulation tissue, and debris in the external auditory canal.

Characteristic skin lesions known as ecthyma gangrenosum may occur in P. aeruginosa bacteremia. These lesions begin as hemorrhagic vesicles with surrounding erythema and progress to central necrosis and ulceration. Exposure to contaminated hot tubs or pools may result in diffuse pruritic maculopapular or vesiculopustular eruptions. Osteomyelitis of the foot often follows penetrating injury, while sternoclavicular septic arthritis is associated with intravenous drug use.
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Melioidosis most commonly involves the lungs and presents with fever, productive cough, and tachypnea. It may also produce acute or chronic suppurative infections of the skin and internal organs. Glanders may manifest as chronic suppurative abscesses, mucopurulent infection of mucous membranes with granulomatous ulcers, or systemic disease with fever, pleuritic chest pain, diarrhea, headache, and myalgia. Lymphadenopathy and splenomegaly may also occur.
Diagnosis requires appropriate cultures from blood, urine, sputum, bronchoalveolar lavage fluid, wounds, or other affected sites, followed by antimicrobial susceptibility testing. Imaging studies depend on the site of infection. In malignant external otitis, CT and MRI often demonstrate bony erosion and new bone formation. Melioidosis may produce upper lobe infiltrates or thin-walled cavities resembling tuberculosis on chest imaging. MRI is useful in suspected osteomyelitis, while echocardiography is indicated when endocarditis is suspected in bacteremic patients. Bronchoalveolar lavage or endotracheal aspirates are useful for confirming respiratory infections in intubated patients.
Differential diagnosis varies according to the clinical presentation. In cases of pneumonia, alternatives include bacterial pneumonias, viral infections, and Pneumocystis jiroveci pneumonia.
Most P. aeruginosa infections are treated with one or two antibiotics to which the organism is susceptible. Common antipseudomonal agents include aminoglycosides, carbapenems, extended-spectrum penicillins such as piperacillin, third-generation cephalosporins such as ceftazidime, fluoroquinolones such as ciprofloxacin, and monobactams. Increasing resistance to ciprofloxacin necessitates caution when selecting empiric therapy.
Bacteremia is commonly treated with agents such as ceftazidime, cefepime, meropenem, imipenem-cilastatin, piperacillin-tazobactam, or aztreonam in beta-lactam-allergic patients. Addition of an aminoglycoside may be appropriate in settings with high resistance rates. Pneumonia is managed similarly, though inhaled tobramycin may also be used. Osteomyelitis requires prolonged high-dose antipseudomonal beta-lactam or fluoroquinolone therapy, often combined with surgical intervention. Central nervous system infections are treated primarily with ceftazidime, cefepime, or meropenem, while imipenem is generally avoided because of neurotoxicity and rapid resistance development.
Ocular infections require topical, subconjunctival, intravitreal, and sometimes systemic antibiotics depending on severity. Malignant external otitis is treated with beta-lactam antibiotics or ciprofloxacin, although relapse may occur even after prolonged therapy. Urinary tract infections are managed with antipseudomonal beta-lactams, fluoroquinolones, or aminoglycosides. Burn wound infections often require topical therapy and careful antibiotic selection because resistance can develop rapidly.
Treatment of melioidosis depends on disease severity and often requires prolonged therapy. Glanders is initially treated with agents such as imipenem, ceftazidime, or meropenem combined with ciprofloxacin and doxycycline, followed by extended oral therapy to reduce relapse risk.
Surgical intervention is frequently necessary in osteomyelitis and may be required in malignant otitis externa for debridement. Infectious disease consultation is strongly recommended, particularly in cases of melioidosis or glanders.
Close follow-up is essential because of the risk of relapse and emergence of multidrug-resistant organisms. Resistance mechanisms include chromosomal beta-lactamases and extended-spectrum beta-lactamases. Prognosis depends on the site of infection, severity of illness, host immune status, and timeliness of therapy. Complications include septic shock, respiratory failure, metastatic infection, brain abscesses, septic emboli, cranial nerve involvement, meningitis, and death.

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​Infectious Disease and Microbiology – Prostatitis


The term prostatitis encompasses several infectious and noninfectious disorders affecting the prostate gland. These include acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis with inflammatory and noninflammatory subtypes, asymptomatic inflammatory prostatitis, and granulomatous prostatitis. The most common form is chronic prostatitis/chronic pelvic pain syndrome, accounting for approximately 90% of cases. Overall prevalence of prostatitis ranges from 2–16% in the general population.


Genitourinary procedures are an important risk factor for acute bacterial prostatitis. Effective management of acute prostatitis reduces the risk of recurrent or chronic bacterial prostatitis. Bacterial prostatitis is associated with secretory dysfunction of the prostate. Prostatic secretions become more alkaline, affecting local antibiotic penetration, and there is a reduction in prostatic antibacterial factor, a zinc-containing antimicrobial polypeptide normally present in prostatic fluid.


Acute bacterial prostatitis is most commonly caused by typical uropathogens including Escherichia coli, other Enterobacteriaceae, Pseudomonas aeruginosa, and enterococci. Chronic bacterial prostatitis is usually caused by the same organisms. The inflammatory subtype of chronic prostatitis has an uncertain etiology, although some cases are associated with Chlamydia or Mycoplasma species. Leukocytes are present in expressed prostatic secretions. The noninflammatory subtype also has an unclear cause, though some patients demonstrate voiding dysfunction related to dyssynergy between bladder detrusor and internal sphincter muscles. Granulomatous prostatitis is rare and may follow acute bacterial prostatitis or result from infections such as tuberculosis, nontuberculous mycobacteria, cryptococcosis, blastomycosis, coccidioidomycosis, or histoplasmosis. In patients with AIDS, the prostate may serve as a persistent focus of cryptococcal infection.


Acute bacterial prostatitis should be suspected in any man presenting with symptoms consistent with urinary tract infection accompanied by perineal, pelvic, or lower back pain. Urinary frequency, dysuria, urgency, fever, and chills are common. Chronic bacterial prostatitis often presents with recurrent urinary tract infections caused by the same organism. Patients are frequently asymptomatic between episodes, although some report symptoms similar to chronic nonbacterial prostatitis.


Chronic prostatitis commonly presents with persistent or intermittent perineal, pelvic, lower back, scrotal, or inguinal pain. Urinary symptoms such as frequency, hesitancy, dribbling, urgency, and dysuria may occur. Erectile dysfunction and ejaculatory complaints are also common. Patients with asymptomatic inflammatory prostatitis have no genitourinary pain and are usually diagnosed incidentally during evaluation for infertility or elevated prostate-specific antigen levels.


Physical examination findings vary according to the type of prostatitis. In acute bacterial prostatitis, digital rectal examination performed gently may reveal an enlarged, tender prostate; vigorous examination should be avoided to prevent bacteremia. In chronic prostatitis, the prostate is generally normal on examination. Granulomatous prostatitis produces a firm, indurated prostate.


Laboratory evaluation includes urinalysis, urine culture, blood urea nitrogen, and creatinine measurements before initiating antibiotics. The classic diagnostic method is the four-glass Meares-Stamey test, which compares cultures from urethral urine (VB1), bladder urine (VB2), expressed prostatic secretions (EPS), and postmassage urine (VB3). Elevated bacterial colony counts in EPS or VB3 compared with VB1 suggest bacterial prostatitis. Presence of leukocytes in EPS or VB3 indicates prostatic inflammation. A simplified two-glass pre- and post-prostatic massage test is also commonly used. Imaging studies such as transrectal ultrasonography and CT scanning are useful for detecting prostatic stones and abscesses. Elderly patients with chronic prostatitis symptoms but no infection should undergo evaluation for bladder cancer with urine cytology, bladder ultrasonography, and cystoscopy if indicated.


Granulomatous prostatitis demonstrates granulomas with lipid-laden histiocytes, plasma cells, and multinucleated giant cells on histopathology. The differential diagnosis of prostatitis includes benign prostatic hyperplasia, bladder neck dysfunction, urethral stricture, prostatic calculi, and prostate cancer.


Treatment depends on the specific subtype. Mild acute bacterial prostatitis without nausea or vomiting is treated with oral fluoroquinolones such as levofloxacin or ciprofloxacin, or with trimethoprim-sulfamethoxazole (TMP-SMX), generally for 2–4 weeks. Moderate or severe illness requires parenteral antibiotics such as ampicillin plus gentamicin or intravenous fluoroquinolones until fever resolves, followed by oral therapy to complete a four-week course. Persistent infection may require retreatment for up to 12 weeks.


Chronic bacterial prostatitis requires antibiotics with good prostatic penetration. Preferred regimens include oral fluoroquinolones for four weeks or TMP-SMX for six weeks. Approximately one-third of patients achieve complete response, while others experience partial or no response. Extended antibiotic courses up to 12 weeks may be required. Suppressive therapy with daily TMP-SMX may be necessary in patients with recurrent infections.


There is no consistently effective therapy for chronic inflammatory prostatitis because the etiology is uncertain. A short trial of doxycycline or a macrolide is reasonable to target possible Chlamydia or Mycoplasma infection. If improvement occurs, treatment may continue for an additional 2–4 weeks. In noninflammatory prostatitis associated with voiding dysfunction, alpha-blockers such as tamsulosin, terazosin, or alfuzosin may provide benefit. Antibiotic therapy is not indicated for asymptomatic inflammatory prostatitis.


Supportive management of acute bacterial prostatitis includes stool softeners, analgesics, and antipyretics. Transurethral catheterization should be avoided because it may obstruct drainage of prostatic secretions; suprapubic catheterization is preferred if urinary retention occurs. In chronic prostatitis, hot sitz baths, anti-inflammatory medications, reassurance, and encouragement of sexual activity may improve symptoms. Some patients with pelvic floor tension myalgia benefit from pelvic floor exercises, diathermy, or diazepam. Prostatic massage, oral zinc, and vitamin supplements have unproven benefit.


Surgical intervention may be necessary in chronic bacterial prostatitis complicated by recurrent urinary tract infections despite suppressive therapy or by infected prostatic calculi. Transurethral or open prostate resection may be considered in selected patients.


Follow-up urine cultures should be obtained approximately 14 days after completing treatment for acute bacterial prostatitis. Complications of acute bacterial prostatitis include prostatic abscess, prostatic infarction, bacteremia, progression to chronic bacterial prostatitis, and granulomatous prostatitis.

Infectious Disease and Microbiology – Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) is a rare, subacute demyelinating disease of the brain white matter caused by primary infection or reactivation of JC virus (JCV). First identified in 1958, PML primarily affects patients with AIDS or other forms of impaired cell-mediated immunity. The disease is characterized by rapidly progressive focal neurologic deficits and is often fatal. PML is considered an AIDS-defining illness.
The incidence of PML increased significantly during the HIV/AIDS epidemic but declined after the widespread introduction of highly active antiretroviral therapy (HAART). Before the HIV era, reported deaths due to PML were approximately 1.5 per 10 million persons in 1974, increasing to 6.1 per 10 million by 1987. Among untreated HIV-positive individuals, 1–4% may develop PML. In 1992, approximately 2% of HIV-related deaths were attributed to PML. A Danish study demonstrated declining incidence rates following the introduction of HAART: 3.3 cases per 1000 patient-years during the pre-HAART era (1995–1996), 1.8 cases per 1000 patient-years during early HAART (1997–1999), and 1.3 cases per 1000 patient-years during late HAART (2000–2006).

JC virus infection is extremely common in the general population. Seroprevalence among adults in the United States and Europe ranges from 60–80%. Primary infection usually occurs during childhood between 10 and 14 years of age and is generally asymptomatic. Although most individuals remain asymptomatic carriers, active viral replication is more commonly observed in immunocompromised patients, particularly those infected with HIV. Asymptomatic urinary shedding of JCV and BK virus has been documented in immunosuppressed individuals, pregnant women, and the elderly.

The most important risk factor for PML is advanced HIV infection, especially with CD4 counts below 100/mm³. More than 60% of PML cases occur in this setting. Other risk factors include congenital or acquired immunodeficiency, organ transplantation, hematologic malignancies, chronic corticosteroid therapy, and immunosuppressive treatment for autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and sarcoidosis. Rare cases have occurred without identifiable immunodeficiency. Cases have also been reported in patients with multiple sclerosis or Crohn’s disease receiving natalizumab therapy, with risk increasing with prolonged treatment duration.

The exact mode of transmission and incubation period of JCV are not fully understood. Primary infection has been documented in renal transplant recipients receiving organs from seropositive donors. In PML, the virus infects oligodendrocytes within the central nervous system, leading to widespread demyelination. Neurologic deterioration progresses rapidly over weeks and typically occurs without signs of increased intracranial pressure. In some HIV-positive patients, initiation of HAART may paradoxically trigger inflammatory PML as part of immune reconstitution inflammatory syndrome (IRIS).

JC virus is a DNA virus belonging to the family Papovaviridae and genus Polyomavirus. Although BK virus is another known human polyomavirus, it is not associated with PML.

Patients with PML typically present without constitutional symptoms such as fever. Common manifestations at presentation include hemiparesis, visual field deficits such as homonymous hemianopia, cognitive impairment, aphasia, ataxia, cranial nerve deficits, sensory abnormalities, seizures, confusion, personality changes, and dementia. The spinal cord is usually spared. As the disease progresses, patients may develop profound neurologic deficits including cortical blindness, quadriparesis, severe dementia, coma, and marked motor weakness. Clinical manifestations are often more severe than expected from imaging or pathological findings. The presentation is similar in both HIV-positive and HIV-negative individuals.

The diagnostic gold standard is demonstration of JC virus antigen or genomic DNA within brain tissue combined with characteristic pathological findings. Detection methods include immunocytochemistry, in situ hybridization, and polymerase chain reaction (PCR). Because brain biopsy carries substantial risk, PCR detection of JCV DNA in cerebrospinal fluid is the preferred diagnostic test. In patients not receiving HAART, PCR sensitivity ranges from 72–92% and specificity from 92–100%. Sensitivity decreases after initiation of HAART because viral replication declines. Cerebrospinal fluid findings are nonspecific and may include pleocytosis, elevated IgG, and oligoclonal bands. Serologic testing is generally not useful. Viral culture is impractical because JCV grows very slowly and susceptible cell lines are difficult to obtain.
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Imaging studies play a central role in diagnosis. CT scans typically demonstrate hypodense, non-enhancing subcortical white matter lesions without edema or mass effect, often involving the periventricular regions, centrum semiovale, parieto-occipital areas, and cerebellum. MRI is more sensitive and usually reveals multiple asymmetric subcortical white matter lesions with high T2 signal intensity. Inflammatory PML is characterized by contrast-enhancing lesions. Electroencephalography may show focal or diffuse slowing, and abnormalities may occasionally precede CT changes.

Pathologically, PML results from direct JCV infection and destruction of oligodendrocytes, leading to multifocal demyelination throughout the central nervous system with minimal inflammatory response. Reactive gliosis, bizarre astrocytes with lobulated nuclei, and lipid-laden macrophages are commonly observed. The cerebral hemispheres, cerebellum, and brainstem may all be affected, while spinal cord involvement is uncommon. Electron microscopy reveals polyomavirus inclusions within enlarged oligodendrocyte nuclei.

The differential diagnosis includes HIV encephalopathy, opportunistic CNS infections such as cytomegalovirus, neurosyphilis, cryptococcosis, tuberculous meningitis, and toxoplasmosis, as well as primary CNS lymphoma and Kaposi’s sarcoma. Other considerations include acute multiple sclerosis, acute hemorrhagic leukoencephalitis, herpes simplex encephalitis, multifocal varicella-zoster leukoencephalitis, postinfectious encephalomyelitis, and cyclosporine-induced neurotoxicity.

There is currently no specific antiviral therapy for PML. In HIV-positive patients, the primary treatment strategy is aggressive antiretroviral therapy to restore immune function. Patients with dementia may require supervised medication administration to ensure adherence. In individuals with PML related to immunosuppressive therapy, reduction or discontinuation of immunosuppressive agents is recommended whenever possible. Intravenous or intrathecal cytarabine may provide some benefit in patients with hematologic malignancies, although evidence is limited. Cidofovir has not demonstrated clinical benefit. Corticosteroids may be useful in inflammatory PML associated with immune reconstitution. In cases associated with natalizumab therapy, plasma exchange combined with discontinuation of natalizumab has been attempted.

Patients require frequent neurologic and clinical follow-up to monitor for disease progression or recurrence. HIV-positive patients also require ongoing monitoring of HIV disease activity and immune status.
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The prognosis of PML remains poor. Death typically occurs within approximately six months of diagnosis. However, some HIV-positive patients may experience spontaneous fluctuations or prolonged survival over several years, particularly if immune function improves substantially with aggressive antiretroviral therapy.

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Infectious Disease and Microbiology – Poliomyelitis
Poliomyelitis is an acute viral infection caused by a small RNA enterovirus known as poliovirus. Most infections are asymptomatic or inapparent. However, in approximately 1% of infected individuals, the virus invades the central nervous system and causes varying degrees of paralysis. Poliomyelitis was once a major global cause of disability and death, but widespread vaccination has dramatically reduced disease incidence worldwide.

No cases of wild-type poliovirus infection have been reported in the United States since 1979. Before eradication efforts intensified, vaccine-derived polioviruses were reported at an average rate of 8–10 cases annually until 1998. Humans are the only known reservoir, and there are no chronic carriers or animal reservoirs. Wild-type polioviruses, vaccine strains from oral poliovirus vaccine (OPV), and vaccine-derived polioviruses may circulate in susceptible populations. By 2005, indigenous transmission of wild-type poliovirus types 1 and 3 had been eliminated from all but four countries: Afghanistan, India, Nigeria, and Pakistan. Wild-type poliovirus type 2 transmission has been globally interrupted. Despite major eradication efforts, outbreaks continue to occur after importation of wild-type virus into previously polio-free countries.

Risk factors for poliovirus infection include overcrowding and poor sanitation, both of which facilitate fecal–oral transmission. Factors associated with increased risk of paralytic disease include B-cell immunodeficiency, strenuous exercise during the early phase of illness, intramuscular injections into affected limbs, and recent tonsillectomy.

Two vaccines are available for prevention: the inactivated poliomyelitis vaccine (IPV) and the live attenuated oral poliomyelitis vaccine (OPV). IPV is administered parenterally and contains all three poliovirus serotypes. It produces excellent systemic immunity, with nearly 100% seroconversion after the third dose, but induces limited intestinal immunity, allowing asymptomatic infection and viral shedding. OPV, used mainly in developing countries, is inexpensive and easy to administer. It induces strong intestinal immunity and enhances herd immunity because vaccinated individuals shed attenuated virus in stool. However, OPV carries a rare risk of vaccine-derived paralytic poliomyelitis, especially in immunocompromised individuals. For this reason, all-IPV schedules are now recommended in the United States and Europe. The routine childhood IPV schedule includes four doses administered at 2 months, 4 months, 6–18 months, and 4–6 years of age.
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Humans are the only known reservoir for poliovirus. In developing countries, the fecal–oral route is the principal mode of transmission, while respiratory droplet spread is relatively more important in developed countries. After entering the body, the virus initially infects intestinal epithelial cells and replicates within local lymphatic tissue, causing minor viremia. Infection may terminate at this stage or progress to major viremia involving reticuloendothelial tissues. Central nervous system invasion occurs by retrograde axonal transport from muscle to nerve and spinal cord. Poliovirus preferentially destroys anterior horn cells and motor nuclei within the spinal cord, pons, and medulla, leading to flaccid paralysis affecting the axial muscles, limbs, cranial nerves, or brainstem.
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Poliovirus belongs to the family Picornaviridae and genus Enterovirus. Three serotypes exist: types 1, 2, and 3. Infection with one serotype confers immunity only to that serotype, with little cross-protection against the others. Prior to widespread vaccination, serotype 1 caused most paralytic cases.

The incubation period from exposure to the onset of minor illness is approximately 9–12 days, while paralysis generally develops after 11–17 days. Approximately 95% of infections are asymptomatic and detectable only by serology or viral isolation. Abortive poliomyelitis, also known as minor illness, occurs in 4–8% of infected individuals and presents as a nonspecific upper respiratory tract infection with sore throat, low-grade fever, abdominal pain, and diarrhea. Recovery is rapid and complete.

Nonparalytic poliomyelitis occurs in about 1% of infections and is characterized by signs of aseptic meningitis, including neck and back stiffness and pain, following a nonspecific febrile illness. Symptoms usually resolve within 2–10 days.

Spinal paralytic poliomyelitis represents the major form of disease and occurs in approximately 0.1% of infections. Patients develop localized muscle pain and fasciculations several days after the minor illness stage. Fever returns, followed by the rapid onset of asymmetric flaccid paralysis, predominantly involving proximal muscles. Lower extremities are more commonly affected than upper extremities. Sensory loss is typically absent, but deep tendon reflexes are lost. Severe cases may progress to quadriplegia and bulbar involvement.

Bulbar paralytic poliomyelitis involves cranial nerve nuclei, particularly cranial nerves IX and X, leading to dysphagia, nasal speech, and respiratory compromise. Bulbar involvement occurs in 5–35% of paralytic cases and may progress rapidly over several days or even hours. Mixed spinal and bulbar involvement is common. A rare form, polioencephalitis, occurs primarily in children and may present with seizures.

Laboratory evaluation commonly demonstrates cerebrospinal fluid pleocytosis similar to other causes of aseptic meningitis. Poliovirus can be isolated from pharyngeal secretions during the first week of illness and from stool specimens for several weeks. Isolation from cerebrospinal fluid is uncommon. Serologic testing with acute and convalescent sera can confirm infection through neutralizing antibody responses against all three serotypes. Molecular genotyping is important in distinguishing wild-type from vaccine-derived strains.

Neuroimaging studies such as CT or MRI are mainly used to exclude alternative causes of paralysis. MRI may reveal T2-weighted hyperintensities involving the bilateral anterior horn cells. Pathological examination demonstrates neuronal destruction and inflammatory lesions affecting the gray matter of the anterior horns and motor nuclei of the brainstem.

The differential diagnosis includes other enteroviral infections, botulism, West Nile virus infection, transverse myelitis, epidural spinal lesions, tick paralysis, Guillain-Barré syndrome, neuropathies, and stroke. Guillain-Barré syndrome is distinguished by its symmetric ascending paralysis.

There is no specific antiviral therapy for poliomyelitis. Management is primarily supportive. During the acute phase, hospitalization is required for monitoring and supportive care. Strict bed rest is essential to minimize progression of paralysis. Positive pressure ventilation may be necessary when respiratory muscle weakness causes reduced vital capacity. Physical therapy should begin promptly once progression of paralysis has stopped in order to preserve muscle function and prevent contractures. Patients should consume a diet rich in fiber because constipation is common.
The prognosis varies according to disease severity. Bulbar poliomyelitis carries the highest mortality rate, approaching 60%. Approximately two-thirds of patients with paralytic disease are left with some degree of permanent weakness. Complete recovery is uncommon in patients with severe paralysis. Survivors of bulbar paralysis often show substantial improvement within 10 days, and long-term outcome can usually be estimated after one month.
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Complications of paralytic poliomyelitis include respiratory failure, gastric dilatation, and paralytic ileus. Years after recovery, some patients develop post-poliomyelitis syndrome, characterized by gradual onset of muscle weakness, pain, fatigue, and muscle atrophy affecting previously involved muscles. This syndrome typically appears 25–35 years after the initial infection.

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Infectious Disease and Microbiology – Pneumonia
Pneumonia is defined as inflammation of the pulmonary parenchyma caused by an infectious agent. Pneumonia can be categorized according to the clinical setting in which it occurs. These categories include community-acquired pneumonia (CAP), which may be typical or atypical; pneumonia occurring in nursing-home residents; nosocomial pneumonia, including hospital-acquired and ventilator-associated pneumonia; pneumonia in immunocompromised hosts; and aspiration pneumonia.

Pneumonia is a major cause of morbidity and mortality worldwide. Approximately 4 million patients develop pneumonia annually in the United States. Community-acquired pneumonia affects about 12 per 1,000 inhabitants each year, with the highest incidence occurring at the extremes of age. Nosocomial pneumonia develops in approximately 0.5–1.5% of hospitalized patients and is particularly common among mechanically ventilated patients, especially those ventilated for prolonged periods. CAP is more common in children and adults older than 60 years.

Several important risk factors predispose individuals to pneumonia. These include alcoholism, aspiration, endotracheal intubation, immunosuppression, age greater than 65 years, hospitalization or nursing-home residence, particularly ICU stay, and underlying pulmonary diseases such as COPD and cystic fibrosis. Preventive measures include influenza and pneumococcal vaccination and minimizing the duration of endotracheal intubation whenever possible.

The pathophysiology of pneumonia involves activation of the host inflammatory response. Inflammatory mediators and chemokines released by macrophages and recruited neutrophils increase alveolar-capillary permeability, leading to alveolar filling with fluid and inflammatory cells. This results in infiltrates, rales, hemoptysis, hypoxemia, decreased lung compliance, and dyspnea. Increased respiratory drive, airway secretions, and infection-related bronchospasm further contribute to respiratory symptoms.

The etiology of pneumonia varies depending on the clinical setting. In community-acquired pneumonia, Streptococcus pneumoniae remains the most common pathogen. Other important organisms include Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, and Staphylococcus aureus, particularly following influenza infection. Community-acquired MRSA strains may cause necrotizing or cavitary pneumonia. Viral pathogens such as hantaviruses, metapneumoviruses, and coronaviruses including SARS are also implicated. Polymicrobial infections are common, and Coxiella burnetii is an important atypical pathogen.

Nosocomial pneumonia is usually caused by gram-negative bacilli such as multidrug-resistant Pseudomonas, Klebsiella, Acinetobacter, and Xanthomonas species. MRSA is also common. Anaerobic bacteria and Legionella species may occasionally be involved, particularly in outbreaks related to contaminated water supplies.

In immunocompromised hosts, the responsible pathogens depend on the nature of the immune defect. Patients with humoral immune deficiencies are susceptible to S. pneumoniae, H. influenzae, S. aureus, and Neisseria species. Granulocyte dysfunction predisposes to gram-negative bacilli and Aspergillus infections. Cellular immune deficiencies increase susceptibility to fungal infections such as Pneumocystis jiroveci, Candida, and Cryptococcus; parasitic infections such as Toxoplasma and Strongyloides; mycobacterial infections; and viral infections including CMV and herpesviruses.

Patients with community-acquired pneumonia often report a recent upper respiratory tract infection. Symptoms commonly include fever, cough, sputum production, pleuritic chest pain, dyspnea, chills, sweats, fatigue, headache, myalgias, and arthralgias. Elderly patients may present atypically with confusion or altered mental status. Nosocomial pneumonia should be suspected in hospitalized patients after more than 48 hours of admission.

Physical examination commonly reveals tachypnea and tachycardia. Tactile fremitus may be increased or decreased. Percussion may demonstrate dullness due to consolidation or pleural fluid. Crackles, bronchial breath sounds, and pleural friction rubs may be present. Severe disease may manifest with hypotension or evidence of organ failure.

Initial laboratory evaluation includes complete blood count, pulse oximetry or arterial blood gas measurements, inflammatory markers such as C-reactive protein, and microbiologic cultures obtained from uncontaminated respiratory specimens. Chest radiography is the primary imaging study. If the initial chest radiograph is negative despite strong clinical suspicion, repeat imaging or chest CT may be necessary. Pneumatoceles suggest S. aureus infection, while upper-lobe cavitary lesions raise suspicion for tuberculosis. CT scanning may help identify post-obstructive pneumonia due to tumors or foreign bodies.

Additional diagnostic procedures may be required in severely ill or diagnostically challenging cases. These include bronchoscopy with bronchoalveolar lavage, transbronchial biopsy, lung biopsy, PCR testing, urinary antigen testing for S. pneumoniae and Legionella, and quantitative cultures. Concurrent endocarditis or meningitis should be excluded when clinically suspected.
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The differential diagnosis includes infectious conditions such as bronchitis, empyema, lung abscess, and acute exacerbations of chronic bronchitis, as well as noninfectious conditions such as congestive heart failure, pulmonary embolism, lung cancer, and lymphoma.

Empiric antimicrobial therapy depends on the severity and setting of pneumonia. Outpatients with community-acquired pneumonia who are previously healthy and have not received recent antibiotics may be treated with azithromycin, clarithromycin, or doxycycline. Patients with comorbidities or recent antibiotic exposure should receive either a respiratory fluoroquinolone or a beta-lactam combined with a macrolide. Hospitalized non-ICU patients are generally treated with a respiratory fluoroquinolone or a beta-lactam plus macrolide. ICU patients require broader therapy with a beta-lactam plus azithromycin or a fluoroquinolone. If Pseudomonas is suspected, antipseudomonal agents are required, and linezolid should be added when CA-MRSA is suspected.

Treatment duration for CAP is generally at least 5 days, although many patients require 7–10 days of therapy. Longer treatment courses are necessary for infections due to Legionella, Coxiella burnetii, or S. aureus. Nosocomial pneumonia without MDR risk factors may be treated with ceftriaxone, respiratory fluoroquinolones, ampicillin-sulbactam, or ertapenem. Patients at risk for multidrug-resistant organisms require broad-spectrum antipseudomonal beta-lactams combined with aminoglycosides or fluoroquinolones and MRSA coverage with vancomycin or linezolid.

Supportive management includes adequate hydration, oxygen therapy, and assisted ventilation when necessary. Early administration of empiric antibiotics is critical and should ideally occur within 4 hours of hospital arrival. Severity assessment tools such as CURB-65 and the Pneumonia Severity Index help determine the need for hospitalization.

Patients should be monitored closely for oxygen saturation and clinical response. Discharge is appropriate once the patient is clinically improved, afebrile for at least 72 hours, hemodynamically stable, and able to tolerate oral antibiotics.
Radiographic abnormalities may take 4–12 weeks to resolve. Persistent or recurrent pneumonia should prompt evaluation for underlying malignancy or structural lung disease. Prognosis is generally excellent in outpatients with CAP, with mortality rates below 1%. Mortality rises to approximately 10% among hospitalized patients and is significantly higher in ventilator-associated pneumonia.
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Complications include treatment failure due to resistant organisms, inadequate therapy, or noninfectious mimics; metastatic infection; complicated pleural effusions; and lung abscess formation.

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