Infectious Disease and Microbiology – Cat-Scratch Disease (Bartonella Infections)


Cat-scratch disease is typically a self-limited acute illness characterized by regional lymphadenopathy with or without fever and constitutional symptoms. It is most commonly caused by Bartonella henselae. In addition to classic lymphadenitis, B. henselae infection may present as fever of unknown origin, hepatosplenic granulomatous disease, neuroretinitis, or encephalopathy. Other medically important Bartonella species include Bartonella quintana, the historical cause of trench fever and a cause of persistent bacteremia, endocarditis, and bacillary angiomatosis, and Bartonella bacilliformis, which causes Oroya fever.


In the United States, the incidence of cat-scratch disease is approximately 10 cases per 100,000 person-years, with an estimated 24,000 recognized cases annually. The disease occurs worldwide and shows seasonal variation in temperate climates, with most cases occurring between August and January. It primarily affects immunocompetent individuals, and about 80% of cases occur in persons younger than 21 years. Most cases are self-limited and present with regional adenopathy. Bartonella quintana is globally endemic and associated with body louse transmission, while Bartonella bacilliformis is transmitted by sand flies and occurs at altitudes above 1 km in the Andes.


Cats, particularly kittens and those infested with fleas, are the natural reservoir of B. henselae. A history of cat exposure is reported in approximately 90% of patients, and about 60% recall a scratch. B. quintana outbreaks are associated with homelessness and poor socioeconomic conditions, where infestation with the human body louse (Pediculus humanus) facilitates transmission. Immunocompromised patients, especially those with advanced HIV infection, are at increased risk of chronic Bartonella infections such as bacillary angiomatosis and bacillary peliosis.


Prevention includes limiting exposure to cat scratches, bites, and licks, especially in immunocompromised individuals. Control of cat fleas may reduce transmission risk.


Bartonella species are fastidious, gram-negative, aerobic rod-shaped bacteria capable of intracellular survival. Infection leads to an inflammatory response and granuloma formation, particularly in lymph nodes. B. henselae accounts for the vast majority of cat-scratch disease cases.


The illness often begins with a small erythematous papule or pustule at the site of inoculation that may persist for weeks. Regional lymph nodes draining the affected area enlarge and become tender. Fever and malaise occur in approximately 30% of patients. Neuroretinitis may present with decreased visual acuity, and encephalopathy may manifest as mental status changes. In HIV-infected individuals, B. henselae bacteremia may cause progressive fatigue, weight loss, recurrent fevers, and hepatomegaly.


Trench fever due to B. quintana typically presents after an incubation period of 3–38 days with sudden onset of chills and fever. Symptoms such as headache, retro-orbital pain, and conjunctival injection are nonspecific. Bacillary angiomatosis presents with red-to-purple papules or nodules that may ulcerate or bleed. Bacillary peliosis involves blood-filled cystic lesions within visceral organs such as the liver or spleen.


On physical examination, regional lymphadenopathy is the most common finding. A primary inoculation lesion may be visible. Parinaud’s oculoglandular syndrome, characterized by conjunctivitis, conjunctival granuloma, and preauricular lymphadenopathy, occurs in approximately 5% of patients. Visceral involvement may produce hepatosplenomegaly.


Laboratory findings may show mild leukocytosis with occasional eosinophilia. Bartonella species can be isolated from blood using specialized culture techniques. Serologic testing with indirect fluorescence assays is widely used; titers greater than 1:256 strongly suggest active infection. If results are equivocal, repeat serology after two weeks may assist diagnosis. Ultrasound of enlarged lymph nodes may help evaluate suppuration and guide aspiration. Histopathology typically shows granuloma formation, and special stains such as Warthin–Starry or tissue PCR may support the diagnosis.


Diagnosis is suggested by compatible clinical findings, history of cat exposure, positive serology, characteristic histopathology, and exclusion of other causes of lymphadenopathy, particularly mycobacterial infections and suppurative adenitis.


Although cat-scratch disease is usually self-limited, antibiotics may hasten resolution. Azithromycin (500 mg orally once, then 250 mg daily for four additional days) is commonly used in adults. Neuroretinitis has been treated with doxycycline plus rifampin, although evidence is limited. Bacillary angiomatosis limited to the skin is treated with erythromycin (500 mg four times daily) or doxycycline (100 mg twice daily) for 8–12 weeks. Bacteremia requires at least four weeks of therapy, and longer courses (2–3 months) are recommended in HIV-infected patients, persistent fever, or endocarditis. Alternative agents include rifampin, ciprofloxacin, and trimethoprim-sulfamethoxazole.


If lymph node suppuration occurs, needle aspiration is preferred over incision and drainage to relieve pain and promote recovery. Valve replacement may be required in Bartonella endocarditis.


Lymphadenopathy usually resolves over several months. One episode appears to confer lifelong immunity. In immunocompetent individuals, fever resolves promptly with or without therapy. In HIV-infected patients, resolution of fever may take longer, although bacteremia typically clears within a week of treatment.


Uncomplicated cat-scratch disease has an excellent prognosis. Complications, including retinitis, encephalopathy, or severe systemic disease, occur in 5–14% of cases. Encephalopathy typically develops weeks after the acute illness and may present with seizures; recovery is usually rapid. Inflammatory organ involvement without angiomatosis or peliosis has been reported in patients with AIDS, affecting the liver, spleen, lymph nodes, heart, and bone marrow.

Infectious Disease and Microbiology – Cervicitis


Cervicitis is a sexually transmitted infection characterized by inflammation of the endocervix and/or ectocervix. It is frequently encountered in sexually active adolescents and young adults, particularly women under 25 years of age.


Cervicitis is common among sexually active adolescent girls under 20 years and young adults aged 20–24 years. In a large U.S. cohort study of individuals aged 18–26 years, the prevalence of chlamydial infection was approximately 4.2%, with higher rates among women than men. Gonorrhea was less common, with a prevalence of 0.4%, and coinfection with both pathogens was rare.


Major risk factors include a new sexual partner within the past 3 months, multiple sexual partners within 6 months, a partner with multiple partners, and inconsistent use of barrier contraception. Preventive strategies emphasize safe sex practices, evaluation and treatment of sexual partners, and annual screening for Chlamydia trachomatis in sexually active women aged 25 years or younger and older women with risk factors. Presumptive treatment is recommended when local prevalence of chlamydia or gonorrhea is high or when follow-up is uncertain.


The most common etiologic agents are Chlamydia trachomatis and Neisseria gonorrhoeae. Other organisms include Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, and herpes simplex virus. In many cases, no pathogen is identified. Vaginal infections such as Trichomonas vaginalis or Candida albicans may extend to involve the ectocervix. Rarely, cytomegalovirus is implicated.


Cervicitis is frequently asymptomatic. When present, symptoms include abnormal vaginal discharge, postcoital bleeding, dysuria, urinary frequency, and dyspareunia. On physical examination, a yellow mucopurulent discharge may be visible in the endocervical canal, and the cervix may be friable and bleed easily on contact.


Diagnostic evaluation includes culture of cervical discharge and nucleic acid amplification testing (NAAT) for C. trachomatis and N. gonorrhoeae, which can be performed on endocervical swabs, vaginal swabs, or urine samples. Gram stain may detect gram-negative intracellular diplococci, which are highly specific for gonococcal infection but less sensitive in cervicitis than in male urethritis. Microscopic examination of vaginal fluid may show leukorrhea (>10 white blood cells per high-power field), which is associated with chlamydial and gonococcal infection. Women with cervicitis should also be evaluated for bacterial vaginosis, trichomoniasis, and pelvic inflammatory disease. If cervical ulcers are present, testing for herpes simplex virus is indicated.


Management includes appropriate treatment of the patient and sexual partners. Patients and partners should abstain from sexual activity until therapy is completed (7 days after single-dose therapy or after completion of a 7-day regimen). In HIV-infected women, treatment reduces cervical viral shedding and transmission risk. In pre-adolescent children, sexually transmitted pathogens warrant evaluation for possible sexual abuse.


Empiric therapy is appropriate when follow-up is uncertain or prevalence of infection is high. For chlamydial infection, first-line treatment includes azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days. For gonococcal infection, ceftriaxone 250 mg intramuscularly as a single dose is recommended. Alternative regimens for chlamydia include ofloxacin, levofloxacin, or erythromycin. For gonorrhea, oral cephalosporins such as cefixime or cefpodoxime may be used, although they may be less effective than ceftriaxone. Fluoroquinolones are not recommended because of increasing resistance.


In pregnancy, azithromycin or amoxicillin is recommended for chlamydial infection. Doxycycline and fluoroquinolones are contraindicated. Gonorrhea in pregnancy is treated with ceftriaxone. Erythromycin formulations may be used as alternatives, though erythromycin estolate is contraindicated due to risk of hepatotoxicity.


Test-of-cure for chlamydia is recommended only when adherence is uncertain, symptoms persist, reinfection is suspected, or in pregnancy. NAAT testing should not be performed within 3 weeks of treatment due to possible false-positive results from nonviable organisms. Routine test-of-cure is not required for uncomplicated gonorrhea treated appropriately unless symptoms persist. Repeat screening within 3–4 months is recommended due to high reinfection rates, especially in adolescents.


Complications of untreated cervicitis include pelvic inflammatory disease, infertility, ectopic pregnancy, chorioamnionitis, premature rupture of membranes, and puerperal infections. Early detection, treatment, and partner management are essential to reduce long-term reproductive morbidity.

Infectious Disease and Microbiology – Chancroid


Chancroid is a sexually transmitted infection characterized by painful genital lesions that may progress to ulceration. The primary lesion typically begins as a tender papule or pustule measuring 2–20 mm in diameter, which rapidly becomes an excavated ulcer with undermined, ragged, or irregular edges.


In the United States, chancroid is rare and usually occurs in localized outbreaks. Only a small number of cases are reported annually, although underdiagnosis is possible. Globally, the disease remains prevalent in parts of Africa, Asia, and Latin America, and in lower socioeconomic populations in the United States.


Risk factors include multiple sexual partners, sexual contact with an infected partner, and travel to or sexual contact with persons from endemic regions. Chancroid increases both transmission of and susceptibility to HIV infection. Approximately 10% of individuals with chancroid acquired in the United States are coinfected with Treponema pallidum (syphilis) or herpes simplex virus (HSV).


The causative agent is Haemophilus ducreyi, a small, fastidious gram-negative rod. The incubation period ranges from 1 to 14 days.


Clinically, tender papules develop at the site of inoculation and become pustular, eroded, and ulcerated within 1–2 days. Multiple lesions may coalesce to form a large ulcer exceeding 2 cm in diameter. Approximately 40% of patients develop tender inguinal lymphadenopathy (“buboes”), which may suppurate and rupture spontaneously. The combination of painful genital ulcers and suppurative inguinal lymphadenopathy is characteristic.


Diagnosis is often based on clinical and epidemiologic features, but misdiagnosis is common; laboratory confirmation is important. Definitive diagnosis requires isolation of H. ducreyi on specialized culture media, which are not widely available. Culture has approximately 80% sensitivity. Polymerase chain reaction (PCR) testing has higher sensitivity (about 95%) but is not widely available and is not FDA approved in many settings. Diagnosis also requires exclusion of syphilis (negative dark-field examination or serology performed more than 7 days after ulcer onset) and genital herpes (negative clinical and laboratory findings). All patients should be tested for HIV at diagnosis.


For specimen collection, the lesion may be gently abraded to obtain exudate, which can be applied to slides for microscopy when indicated. Histopathologic examination typically shows superficial purulent exudate and mononuclear cell infiltrates in the dermis; neutrophil infiltration may be reduced in HIV-infected patients.


The differential diagnosis includes genital herpes, syphilis, acute HIV infection, lymphogranuloma venereum, granuloma inguinale (donovanosis), mycobacterial or fungal infections, parasitic infections, venereal warts, scabies, molluscum contagiosum, folliculitis, and plague. Noninfectious causes such as malignancy, trauma, fixed drug eruptions, Behçet syndrome, and dermatitis herpetiformis should also be considered.


First-line treatment options include azithromycin 1 g orally as a single dose or ceftriaxone 250 mg intramuscularly as a single dose. Alternative regimens include ciprofloxacin 500 mg orally twice daily for 3 days or erythromycin base 500 mg orally four times daily for 7 days. Ciprofloxacin is contraindicated in pregnancy and lactation. Some isolates with intermediate resistance to ciprofloxacin or erythromycin have been reported. Sexual partners within 10 days preceding symptom onset should be evaluated and treated with the same regimen.


Fluctuant buboes may require needle aspiration through intact skin or incision and drainage; incision and drainage may reduce the need for repeated procedures.


Patients should be reexamined within 3–7 days to assess clinical improvement. Complete healing depends on ulcer size; larger ulcers may require more than two weeks to resolve. Healing may be slower in uncircumcised men with subpreputial ulcers. Failure to improve may indicate incorrect diagnosis, coinfection (e.g., syphilis), reinfection, antimicrobial resistance, noncompliance, or HIV infection. Patients with initial negative HIV or syphilis tests should be retested approximately three months later.


Complications include secondary ulcers, draining fistulas following lymph node rupture, and increased risk of HIV transmission. Education on safe-sex practices is essential to prevent recurrence and transmission.

Infectious Disease and Microbiology – Chickenpox (Varicella)


Chickenpox is a highly contagious febrile illness of childhood caused by primary infection with the varicella zoster virus (VZV). It is characterized by a generalized pruritic rash in which lesions at different stages of development—macules, papules, vesicles, pustules, and crusts—are present simultaneously.


The disease occurs worldwide and shows seasonal peaks in late winter and early spring. Before widespread vaccination, the primary attack rate in susceptible individuals was approximately 90%, with household secondary attack rates of 70–90%. Since implementation of routine vaccination programs, incidence, hospitalizations, complications, and deaths have declined dramatically. Both sexes are equally affected. Most cases occur in young children, although an increasing proportion of cases now occur in adolescents and adults in partially vaccinated populations.


Risk factors include close contact with an infected individual (varicella or herpes zoster), lack of immunity, and increasing age at exposure. Approximately 90% of individuals aged 15 years or older are immune, but 10% remain susceptible. Adults, pregnant women, and immunocompromised individuals are at higher risk for severe disease and complications.


Varicella zoster virus is a DNA virus (human herpesvirus 3) in the Herpesviridae family. Humans are the only known reservoir. Transmission occurs via respiratory droplets or direct contact with vesicular fluid. The virus enters through the respiratory mucosa, replicates in regional lymph nodes, and spreads through primary viremia. A secondary viremia disseminates the virus to the skin and other organs. After primary infection, the virus remains latent in sensory ganglia and may reactivate later in life as herpes zoster.


The incubation period is typically 10–14 days (range 10–21 days). Patients are infectious from approximately 48 hours before rash onset until all lesions have crusted. In immunocompetent children, mild prodromal symptoms such as malaise and low-grade fever may precede the rash by 1–2 days. The rash begins on the face and trunk and spreads centrifugally, sometimes involving mucous membranes. Lesions evolve rapidly from macules to papules and then to clear vesicles on an erythematous base. Vesicular fluid becomes turbid, crusting follows, and new crops of lesions appear over 2–4 days. Crusts fall off within 1–2 weeks and usually do not scar unless secondarily infected.


In immunocompromised patients, lesions are more numerous, may have hemorrhagic bases, and heal more slowly. Visceral complications occur in 30–50% of severe cases and can be fatal. Adults typically experience more severe illness and have a higher risk of complications. Pregnant women are at increased risk of varicella pneumonia and may transmit infection to the fetus. Perinatal varicella (maternal infection 5 days before to 2 days after delivery) can result in severe neonatal disease with high mortality. Congenital varicella syndrome, occurring when infection develops in the first two trimesters, may cause limb hypoplasia, skin scarring, ocular abnormalities, and central nervous system impairment.


Diagnosis is primarily clinical, based on the characteristic rash. Laboratory confirmation can be obtained by PCR detection of VZV DNA from lesion specimens, which is the most reliable method. Viral culture, direct immunofluorescence staining, Tzanck smear (showing multinucleated giant cells), and serologic testing may also be used. Chest radiographs may show nodular or interstitial infiltrates in cases of varicella pneumonia.


Differential diagnosis includes disseminated herpes simplex infection, enteroviral rashes, scabies, dermatitis herpetiformis, folliculitis, atypical measles, and rickettsialpox.


Oral acyclovir is recommended within 24 hours of rash onset to reduce disease severity. In immunocompetent children aged ≥2 years and weighing ≤40 kg, the dose is 80 mg/kg/day divided into four doses (maximum 3200 mg/day) for 5 days. Older children and adults may receive 3200 mg/day in four divided doses for 5 days. Adequate hydration is important. Valacyclovir and famciclovir are alternatives for older children and adults. Supportive care includes bathing, antipruritic agents, trimmed fingernails to prevent excoriation, and acetaminophen for fever. Aspirin should be avoided due to the risk of Reye’s syndrome.


Passive immunization with varicella zoster immunoglobulin is recommended for high-risk susceptible individuals after exposure, including immunocompromised persons, pregnant women, certain premature infants, and newborns exposed perinatally. It should be administered ideally within 72 hours and no later than 96 hours after exposure.


Active immunization with the live attenuated varicella vaccine is part of routine childhood vaccination schedules. Two doses are recommended, beginning at 12–15 months of age, with a second dose at 4–6 years. Unvaccinated adolescents and adults without evidence of immunity should receive two doses separated by at least 28 days. Vaccination is contraindicated during pregnancy.


Prognosis in healthy children is excellent, and infection usually confers lifelong immunity. However, severe disease may occur in adults, immunocompromised patients, pregnant women, and neonates. The virus remains latent and may later reactivate as herpes zoster.


Complications include secondary bacterial skin infections (commonly due to staphylococci or group A streptococci), varicella pneumonia (particularly in adults and pregnant women), cerebellar ataxia, encephalitis, meningitis, transverse myelitis, myocarditis, nephritis, hepatitis, bleeding disorders, and Reye’s syndrome. Mortality is low in the post-vaccination era but remains significant in high-risk groups.

Infectious Disease and Microbiology – Cholecystitis and Cholangitis




Cholecystitis refers to acute or chronic inflammation of the gallbladder. Cholangitis is a clinical syndrome characterized by systemic infection originating in the biliary tract, usually due to obstruction. Emphysematous cholecystitis is a severe form of gallbladder inflammation in which gas forms within the gallbladder lumen, wall, or surrounding tissues.


Acute cholecystitis accounts for 3–10% of patients presenting with abdominal pain, increasing to approximately 20% among individuals older than 50 years. Among patients with gallstones (cholelithiasis), 1–4% annually develop biliary colic, and if untreated, about 20% of symptomatic individuals may later develop acute cholecystitis.


In 90–95% of cases, acute cholecystitis results from gallstone obstruction. Risk factors for gallstone formation include obesity, rapid weight loss, hemolytic diseases (such as sickle cell disease and G6PD deficiency), and certain ethnic backgrounds (e.g., Pima Indians). Gallstones are more than twice as common in women as in men, although cholecystitis tends to be more severe in men.


Acalculous cholecystitis occurs without gallstones and is associated with serious medical conditions such as diabetes mellitus, sepsis, ischemia, trauma, burns, prolonged total parenteral nutrition, vasculitis, collagen vascular diseases, sarcoidosis, HIV/AIDS, and certain infections (e.g., tuberculosis and parasitic infections). It is slightly more common in men and is associated with higher complication rates. Emphysematous cholecystitis is more frequent in elderly patients and those with diabetes.


Acute calculous cholecystitis results from obstruction of the cystic duct by gallstones. Acalculous cholecystitis develops due to gallbladder stasis and bile stagnation. Acute cholangitis occurs when obstruction of the common bile duct leads to increased biliary pressure, facilitating bacterial translocation into the bloodstream and resulting in systemic infection.


Common pathogens in biliary infections are polymicrobial and include Escherichia coli, Klebsiella species, Enterococcus species, Enterobacter species, and Pseudomonas species. Anaerobes are more common in elderly patients, diabetics, and those with prior biliary surgery. Obstructive causes of cholangitis include choledocholithiasis, malignant strictures, iatrogenic bile duct injury, primary sclerosing cholangitis, congenital biliary abnormalities, and parasitic infections such as Clonorchis, Opisthorchis, and Ascaris.


Clinically, biliary disease often presents with right upper quadrant abdominal pain that may radiate to the right scapular or infrascapular area. Acute cholecystitis typically begins with biliary colic and fever that progressively worsen. Unlike biliary colic, the pain is continuous. Approximately 60–70% of patients report prior self-limited episodes. Acalculous cholecystitis may present with unexplained fever or vague abdominal discomfort, particularly in critically ill patients.


Acute cholangitis classically presents with Charcot’s triad: fever with chills, jaundice, and right upper quadrant pain. However, only 50–70% of patients exhibit all three features. Severe cases may present with Reynolds’ pentad, which includes hypotension and altered mental status in addition to Charcot’s triad, indicating sepsis and possible organ failure.


On physical examination, right upper quadrant tenderness is highly sensitive for biliary tract disease. A positive Murphy’s sign—pain during inspiration while palpating the right upper quadrant—is suggestive of acute cholecystitis.


Laboratory findings in acute cholecystitis often include fever and leukocytosis. A temperature above 38.5°C or white blood cell count greater than 12,500/mm³ suggests infection. Mild elevations in serum bilirubin and aminotransferases are common. Elevated amylase may indicate concomitant gallstone pancreatitis. Abnormal renal function, thrombocytopenia, or coagulopathy suggest more severe disease. Bile cultures are frequently positive in cases of obstruction and jaundice.


Ultrasonography is the primary imaging modality for diagnosing cholecystitis. Findings include gallbladder wall thickening (>2 mm), pericholecystic fluid, intramural gas, ductal dilation, and a sonographic Murphy’s sign. Hepatobiliary scintigraphy may be used if ultrasound is inconclusive; failure of gallbladder filling suggests cystic duct obstruction. CT scanning can identify bile duct dilation, pneumobilia, or complications and may assist in diagnosing cholangitis.


Management includes prompt administration of antibiotics targeting Enterobacteriaceae. For mild-to-moderate community-acquired acute cholecystitis, recommended regimens include cefazolin, cefuroxime, or ceftriaxone. In severe cases, elderly or immunocompromised patients, or in acute cholangitis, broad-spectrum therapy such as piperacillin–tazobactam, carbapenems, cefepime plus metronidazole, or fluoroquinolones plus metronidazole is indicated. Vancomycin may be added in healthcare-associated infections. Anti-enterococcal coverage is generally not required in uncomplicated community-acquired infections.


Supportive care includes bowel rest, intravenous fluids, correction of electrolyte imbalances, and analgesia. Antibiotics are typically initiated within one hour before cholecystectomy and discontinued within 24 hours postoperatively if infection is confined to the gallbladder.


Early laparoscopic cholecystectomy is preferred over delayed surgery due to lower complication rates and shorter recovery. In severe cases or when surgery is contraindicated, biliary decompression may be achieved through percutaneous drainage or endoscopic retrograde cholangiopancreatography (ERCP). Acute cholangitis often requires urgent biliary drainage in addition to antibiotics.


Prognosis for acute cholecystitis is generally favorable with timely treatment, although recurrence is common if the gallbladder is not removed. Acute cholangitis carries a mortality rate of 10–30%, especially in elderly patients or those with severe sepsis.


Complications include chronic cholecystitis, empyema of the gallbladder, perforation, fistula formation, hepatic abscess, sepsis, and recurrent biliary obstruction. Severe acute cholangitis may result in shock, organ failure, and disseminated infection if not promptly treated.

Infectious Disease and Microbiology – Common Cold




The common cold is an acute, self-limiting viral infection of the upper respiratory tract. It is one of the most frequent infectious illnesses worldwide and primarily affects the nose and throat.


Adults typically experience 2–4 colds per year, while children average 6–10 episodes annually. In the United States alone, approximately 1 billion cases occur each year. The higher incidence in children is partly due to immature immune systems and close contact in school or daycare settings.


Risk factors include close contact with infected individuals, especially in enclosed environments, and direct hand contact with contaminated secretions. Cold transmission increases during winter months when people cluster indoors. Smoking, psychological stress, and immunocompromised states also increase susceptibility.


The common cold is caused by several respiratory viruses. Rhinoviruses account for 30–50% of cases, followed by coronaviruses (10–15%) and influenza viruses (5–15%). Less common causes include parainfluenza virus, respiratory syncytial virus (RSV), adenovirus, enterovirus, and metapneumovirus. Transmission occurs through respiratory droplets, aerosols, and contaminated hands contacting the nose, mouth, or eyes.


Symptoms typically include rhinorrhea, sneezing, nasal congestion, throat irritation, cough, and mild chilliness. Some patients may experience conjunctivitis, muscle aches, fatigue, headache, shivering, and decreased appetite. Fever is uncommon in adults but may occur in children. The illness is usually mild and resolves spontaneously within 7–10 days.


Physical examination generally shows signs of upper respiratory tract infection, such as nasal congestion and mild pharyngeal erythema. Laboratory tests and imaging are not required unless complications or alternative diagnoses are suspected.


The differential diagnosis includes pneumonia, pertussis (whooping cough), sinusitis, influenza, and allergic rhinitis. Persistent or worsening symptoms may warrant further evaluation.


There are no antiviral medications with established benefit for routine treatment of the common cold. Management is symptomatic. Analgesics and antipyretics such as acetaminophen or ibuprofen can relieve aches and fever. Aspirin should be avoided in children and adolescents due to the risk of Reye’s syndrome. Nasal decongestants may provide short-term relief, but topical nasal sprays should not be used for more than three days due to rebound congestion. Ipratropium bromide nasal spray may help reduce nasal discharge. Dextromethorphan can be used for cough in adults, and first-generation antihistamines may relieve symptoms. In children, codeine, dextromethorphan, and antihistamines are generally not recommended.


Complementary therapies such as echinacea, vitamin C, and zinc have not consistently demonstrated clear benefit for active treatment.


Prevention focuses on frequent handwashing, avoiding hand-to-face contact, minimizing exposure to infected individuals, and covering the mouth and nose with the elbow when coughing or sneezing. Sharing towels or utensils should be avoided. Patients should be educated that antibiotics are not effective against viral infections and are not indicated for uncomplicated colds.


The prognosis is excellent, as the disease is generally mild and self-limiting. However, complications can occur, including otitis media, sinusitis, pneumonia, pharyngitis, acute bronchitis, and exacerbations of asthma, chronic bronchitis, or obstructive sleep apnea. A cough persisting longer than three weeks should prompt evaluation for pneumonia or pertussis.

Infectious Disease and Microbiology – Coccidioidomycosis




Coccidioidomycosis is a pulmonary and/or extrapulmonary infection caused by the dimorphic fungus Coccidioides immitis. The disease is commonly referred to as “Valley fever” and may range from a mild respiratory illness to severe disseminated infection.


In the United States, the incidence is approximately 91 cases per 100,000 people. C. immitis is endemic to the southwestern United States, particularly California, Arizona, and Texas, as well as parts of Mexico and Central and South America. Increasingly, cases are recognized outside endemic areas, typically in travelers or due to reactivation of latent infection. Periodic outbreaks with sharp increases in case numbers occur.


Risk is increased in individuals with immunosuppressive conditions or therapies, including AIDS, solid-organ transplantation, lymphoma, and glucocorticoid or other immunosuppressive treatments. Among patients with AIDS, infection is especially likely when CD4 counts are below 250 cells/mm³. Even distant past exposure to endemic regions is important, as latent infection may reactivate during immunosuppression. Pregnancy, particularly in late stages, and diabetes mellitus are also associated with increased risk of severe disease.


The fungus resides in soil and grows optimally at approximately 30°C but also proliferates at body temperature (37°C). Infection occurs through inhalation of airborne arthroconidia. In most cases, acute pulmonary infection resolves spontaneously. However, some patients develop progressive pneumonia or chronic pulmonary infection. Approximately 5% of infected individuals develop asymptomatic residual lung nodules or thin-walled cavities. Disseminated disease occurs in roughly 1 in 200 infected individuals and most commonly involves the meninges, bones, joints, skin, and soft tissues. Extrapulmonary disease usually develops within one year of primary infection but may occur later if immunity declines.


Symptoms typically appear 1–3 weeks after exposure. The most common presentation is a lower respiratory tract infection accompanied by systemic symptoms such as fever, cough, sputum production, chest pain, weakness, anorexia, sweating, and arthralgias. Erythema nodosum or erythema multiforme may occur. Extrapulmonary disease presents with focal symptoms depending on the organ involved. Skin lesions often appear as wart-like nodules. Joint involvement is usually unilateral. Meningitis often affects the basilar meninges and may present with headache as the most prominent symptom.


Physical examination should include careful evaluation of the skin and neurologic system to identify extrapulmonary involvement. Coccidioidal lesions are typically focal and produce localized symptoms such as swelling, ulceration, or discomfort.


Diagnosis relies on culture, serologic testing, and coccidioidal skin testing. Accurate travel history is essential, particularly outside endemic areas. Serum IgM antibodies are detectable in approximately 75% of primary infections early in the course of illness. IgG antibodies develop later and usually decline if the infection resolves. False-positive serologic results are uncommon. Skin testing becomes positive soon after symptom onset in primary infection and rarely cross-reacts with other infections. Cerebrospinal fluid in meningitis typically shows mononuclear pleocytosis, elevated protein, and low glucose. Chest radiographs may demonstrate infiltrates, pleural effusion, or hilar adenopathy.


The role of antifungal therapy in mild or moderate primary pulmonary infection remains uncertain. Treatment decisions are individualized. Oral fluconazole (400 mg daily) or itraconazole (200 mg twice daily) may be given for 3–6 months, particularly in patients with severe symptoms, high antibody titers, extensive lung involvement, significant weight loss, persistent symptoms, or increased host susceptibility. Disseminated disease always requires prolonged antifungal therapy.


Fluconazole and itraconazole are the drugs of choice for meningeal disease. Lifelong suppressive therapy may be required in some cases. Amphotericin B is reserved for patients who fail azole therapy or have severe disseminated infection. Surgical intervention may be necessary for complications such as severe hemoptysis, enlarging cavities, empyema, bronchopleural fistula, or restricted lung expansion.


Approximately 5–10% of infections result in residual sequelae. Early diagnosis of meningitis is critical, as untreated cases carry a 90% mortality within 12 months. Chronic pulmonary disease may develop, particularly in diabetic or immunocompromised patients.


Complications are more common and severe in immunocompromised individuals, especially those with extrapulmonary disease. Organ transplant recipients are at highest risk during the first year after transplantation. Meningitis may occur within six months of primary infection and may lack classic meningeal signs seen in bacterial meningitis. Symptoms can include headache, fever, confusion, seizures, diplopia, ataxia, vomiting, and focal neurologic deficits.

Infectious Disease and Microbiology – Chronic Fatigue Syndrome




Chronic Fatigue Syndrome (CFS) is a heterogeneous disorder characterized by severe, persistent, and debilitating fatigue lasting at least six months. The fatigue is not relieved by rest and significantly interferes with daily functioning. In children, CFS is rare, but school absenteeism or withdrawal from normal activities should be monitored as indicators of functional impairment similar to adult disability.


The estimated prevalence in the United States ranges from 4.0 to 8.7 per 100,000 people, with a worldwide prevalence of approximately 0.6–1%. CFS is two to three times more common in women than in men. Ongoing research is evaluating potential genetic predispositions, but no specific genetic markers have been definitively linked to the disorder.


The pathophysiology of CFS remains uncertain. The etiology is unknown, although infectious triggers have been proposed. Associations with Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpesviruses, hepatitis C virus (HCV), Borrelia burgdorferi (Lyme disease), and Brucella species have been suggested but not conclusively proven. Immune dysfunction and abnormalities of the hypothalamic–pituitary–adrenal axis or autonomic nervous system have also been hypothesized. Depression and fibromyalgia are commonly associated conditions.


Diagnosis is clinical and remains one of exclusion. According to the 1994 CDC criteria, patients must have unexplained, persistent fatigue lasting more than six months, along with at least four of the following symptoms: post-exertional malaise; unrefreshing sleep; impaired memory or concentration; muscle pain; multi-joint pain without swelling or redness; tender cervical or axillary lymph nodes; sore throat; or headache. Physical examination is often unremarkable, although tender lymphadenopathy may be present. There are no specific laboratory or imaging findings; testing is performed primarily to exclude alternative causes of fatigue.


The differential diagnosis is broad and includes depression, CMV infection, EBV infection, brucellosis, post-influenza fatigue, Lyme disease, HIV infection, collagen-vascular disorders, malignancies with paraneoplastic syndromes, and brain tumors.


Treatment is supportive and multidisciplinary, aiming for gradual functional improvement rather than immediate resolution of symptoms. Antidepressants may be used when mood disorders coexist. Cognitive behavioral therapy (CBT) has demonstrated benefit in improving coping strategies and functional outcomes. Graded exercise therapy involves carefully structured and progressive increases in physical activity to avoid the “push-crash” cycle of overexertion followed by post-exertional malaise. Activity pacing combines controlled activity scheduling with behavioral strategies. Sleep hygiene and, when indicated, sleep studies may also be helpful.


Complementary therapies such as massage, relaxation techniques, yoga, tai chi, and healing touch may provide symptomatic relief for some patients. Frequent follow-up with a multidisciplinary healthcare team is recommended.


Prognosis varies widely. Time to diagnosis is often prolonged, averaging approximately five years. Symptomatic improvement occurs in 6–63% of patients, while complete resolution is reported in 0–37% of cases.

Infectious Disease and Microbiology – Cholera




Cholera is a severe watery diarrheal illness caused by Vibrio cholerae. It is characterized by rapid fluid loss that can lead to life-threatening dehydration if untreated.


Globally, cholera remains a major public health problem, with an estimated 3–5 million cases and 100,000–120,000 deaths annually. It is one of the leading causes of death in children under five years of age worldwide. The disease is most common in areas with poor sanitation, contaminated water supplies, and during humanitarian crises or natural disasters.


Risk factors include exposure in endemic or epidemic settings, malnutrition, and immunosuppression, which may lead to a more severe clinical course. Individuals with blood group O are at increased risk of severe disease, particularly with the El Tor subtype. In pregnancy, cholera increases the risk of miscarriage or premature delivery, especially in the third trimester.


Transmission occurs through the fecal–oral route, typically via contaminated water, food, or undercooked seafood. The incubation period ranges from 12 hours to 5 days but may be as short as a few hours in cases of high bacterial inoculum or reduced gastric acidity. The organism produces cholera toxin, which consists of one A subunit and five B subunits. The toxin binds to enterocytes in the small intestine and stimulates chloride ion secretion, resulting in massive water loss into the intestinal lumen.


Vibrio cholerae is a gram-negative rod with over 190 serotypes based on the O antigen. Only serogroups O1 (El Tor and classical biotypes) and O139 are responsible for epidemic cholera. Non-O strains typically cause milder diarrheal illness.


Clinically, cholera presents with sudden onset of profuse watery diarrhea, often described as “rice water stools” with a fishy odor. Stool output can exceed one liter per hour in severe cases (cholera gravis). Patients may experience abdominal cramping but typically do not have fever. Vomiting may occur. Signs of dehydration include poor skin turgor, dry mucous membranes, tachycardia, hypotension, and in severe cases, shock.


Initial laboratory evaluation includes assessment of electrolytes, glucose, and renal function. Severe dehydration may lead to metabolic acidosis, hypokalemia, and acute kidney injury. Diagnosis can be confirmed by stool culture using selective media such as thiosulfate citrate bile sucrose (TCBS) agar. Gram stain may reveal motile gram-negative rods. However, treatment should not be delayed while awaiting confirmation.


The cornerstone of therapy is prompt and aggressive rehydration. Oral rehydration solution (ORS) is highly effective because sodium and glucose absorption remain intact despite toxin activity. Approximately 80% of patients recover with oral hydration alone. Intravenous fluids, preferably isotonic solutions such as lactated Ringer’s, are indicated in patients with severe dehydration or inability to tolerate oral intake.


Antibiotics are adjunctive to rehydration and reduce stool volume by approximately 50% and shorten the duration of bacterial shedding. First-line options include tetracycline (500 mg orally four times daily for 3 days) or a single 300 mg dose of doxycycline. Alternative agents include azithromycin, ciprofloxacin, or norfloxacin. In children and pregnant women, erythromycin or azithromycin is preferred; quinolones and tetracyclines should be avoided in these groups.


Zinc supplementation (30 mg daily) has been shown to decrease stool output and duration of illness, particularly in children. Close monitoring of electrolyte status, acid–base balance, glucose levels, and volume status is essential. Hospital admission is indicated for severe dehydration, inability to tolerate oral fluids, or signs of shock.


Preventive measures include safe water practices such as boiling, chlorination, filtration, and strict hand hygiene. Vaccination with killed whole-cell oral vaccines is recommended by the World Health Organization in endemic areas and provides approximately 78% protection for up to two years. Herd immunity significantly reduces transmission, and partial population vaccination can substantially lower case numbers.


Prognosis is excellent with timely rehydration. However, untreated cholera carries a mortality rate of up to 50%. Complications include arrhythmias due to electrolyte disturbances and acute renal failure secondary to severe dehydration.


Rapid recognition of acute watery diarrhea and immediate initiation of rehydration are critical. Management should focus on fluid and electrolyte replacement first, with antimicrobial therapy administered once the patient is stabilized. Suspected cases should be reported promptly to public health authorities to prevent outbreaks.