Viral Disease

Viral Disease-

-Cytomegalovirus Infection-

-Cytomegalovirus (CMV) infections are of varying severity and is dependent on the host.

-CMV infections in immunocompetent patients are generally asymptomatic or present as a mononucleosis syndrome

-CMV infections in immunocompetent patients can cause significant morbidity and mortality in organ transplant or organ transplant patients

-CMV is a member of the herpesvirus family

-CMV establishes a latent infection after the resolution of the acute infection

-Productive infection leads to the synthesis of intermediate early, early, and late viral proteins.  Viral DNA is detected in monocytes, dendritic cells, and myeloid progenitor cells in the bone marrow

-Secondary, symptomatic disease may present later in life of the host.  This comes from reactivation of latent CMV or reinfection with an exogenous novel strain

-High risk for reactivation of CMV may occur in the following conditions:  systemic immunosuppression, iatrogenic immunosuppression, and AIDS

-CMV has been cultured from multiple sites including urine, throat, blood, semen, stool, tears and breast milk.

-Transmission of CMV can occur from sexual exposure:  contact, blood or tissue, perinatal exposure, and occupational exposure

-CMV can be localized to a single organ or present as a multi-system disorder in a fulminate state

-CMV affects other organs differently

-GI manifestations include colitis, diarrhea, fever, abdominal pain, GI hemorrhage or inflammatory colitis

-Hepatic manifestations of CMV include elevated alkaline phosphatase, and total bilirubin.  Portal vein thrombosis can also occur

-CMV can cause neurologic manifestations such as encephalitis, guillian barre syndrome, brachial plexus neuropathy, transverse myelitis, diffuse axonal neuropathy, Horner's syndrome and cranial nerve palsies

-CMV pneumonia can usually only occur in immunocompromised hosts

-CMV retinitis can occur with advance immunosuppression and AIDS

CMV can cause pericarditis, myocarditis, and atherosclerosis

-Enzyme immunoassays and indirect and anti-complement immunofluorescence assays are most commonly used.  They measure the presence of anti CMV IgM and IgG

-The detection of CMV specific IgM antibodies are useful in newborns

-Most cases of primary CMV infection in immunocompetent hosts occur and pass with no or minimal symptoms.

-Agents available for systemic treatment are usually used only on immunocompromised patients. Antivirals for CMV include:  ganciclovir, valganciclovir, fosacarnet, and ciodfovir


-Epstein Barr Virus-

-Epstein Barr Virus (EBV) is a herpes virus that is spread by contact with susceptible persons and asymptomatic carriers of EBV

-EBV is the infectious agent of infectious mononucleosis

-EBV is associated with the development of B cell lymphomas, T cell lymphomas, Hodgkin lymphoma, and nasopharyngeal carcinomas

-EBV has a latency phase as well as an infectious phase

-Infectious Mononucleosis presents with malaise, headache, low grade fever, sore throat, lymphadenopathy(usually anterior and posterior cervical) and moderate to high fever

-With infectious mononucleosis there is a large percentage of atypical lymphocytes

-Fatigue can be the predominant symptom.  Other less common physical exam findings include:  palate petechiae, periorbital or palpebral edema, and maculopapular rashes

-Nausea, vomiting, and elevated transaminases are found in a good percentage of patients from associated hepatitis.  Splenomegaly is common

-EBV can affect virtually any organ system and can be associated with pneumonia, myocarditis, pancreatitis, mesenteric adenitis, myositis, glomerulonephritis, Guillain Barre syndrome

-There is a specific drug disease specific interaction between mononucleosis and ampicillin

-Oral hair leukoplakia development can happen as a mucocutaneous manifestation of EBV

-Splenic rupture is a rare but fatal complication of infectious mononucleosis. Contact sports athletes need to be kept out of sports until splenomegaly resolves

-Burkitt Lymphoma is the most common childhood malignancy in Africa.  It is associated with EBV and is usually localized to the jaw.

-Diagnosis can be confirmed by the monospot test which assesses heterophile antibodies

-IgG antibodies to early antigen are present at the onset of the clinical illness.

-The treatment of mononucleosis is supportive.  Analgesics, anti-pyretics, and fluid hydration are supportive measures


-Erythema Infectiosum-

-caused by the Human Parvovirus B19

-get diffuse erythema rash and edema to the cheeks

-get a "slapped cheek" appearance

-prodrome of fever, malaise, headache, coryza, itching, myalgias and sore throat

-several syndromes associated with parvovirus B19 include:  Fifth's Disease, Arthropathy, Transient Aplastic crisis with chronic hemolytic disorders, non immune hydrops fetalis, intrauterine death, and hemolytic disorders

-Parvovirus B19 is also associated with myocarditis, dilated cardiomyopathy and left ventricular dysfunction

-pathogenesis of rash is not clear but correlates to serum antibody levels

-management is symptomatic

-Herpes Simplex-

-Herpes simplex virus has two major types HSV type 1 and type 2

-HSV 1 is also known as herpes labialis often referred to as cold sores

-HSV type 1 can also occur at other locations than the lips.  HSV type 1 can be found in the genitalia, liver, eyes, and the central nervous system.

-HSV type 2 is usually specific to genitalia

-When HSV type 1 is in other locations that the lips, it is usually severe infections in the setting of immunosuppression

-HSV type 1 is transmitted at mucosal surfaces or skin sites that permits entry to the epidermis, dermis, and the sensory and autonomic nerve endings

-The cutaneous lesions of HSV present as grouped vesicles on an erythematous base

-When an HSV infection has occurred, the virus lives in the nerve cell bodies in a latent phase until it reactivates

-Precipitating factors for HSV 1 reactivation include:  fever, sunburn, trauma, and menstruation

-HSV infection of a finger is known as a herpetic whitlow

-HSV Type 1 is associated with onset of erythema multiforme

-Ocular HSV infections cans cause keratitis and acute retinal necrosis

-HSV type 1 can also cause encephalitis or aseptic meningitis

-Fulminant hepatitis is rare but a complication of an HSV infection.  Occurs with immunocompromised patients

-Immunocompromised patients  also can get HSV esophagitis and HSV pneumonitis

-Diagnosis can be confirmed by viral culture and Tzanck smear

-Acyclovir, famciclovir, and valacyclovir all interfere with viral replication of the virus.   Famciclovir and valacyclovir have higher oral availability.

-Topical anti-viral agents have marginal benefit and should really not be used

-Parenteral therapy should be used for more severe infections such as:  CNS infections, transverse myelitis, end organ disease (hepatitis or pneumonia), and disseminated HSV

-Anti-viral therapy is most helpful if initiated in the first 72 hours

-Patients can also be offered daily suppressive therapy who have frequent outbreaks


-HIV Infection-

-Human Immunodeficiency Virus (HIV) infection has several stages:
1. Viral Transmission
2.  Primary HIV infection
3.  Seroconversion
4.  Early symptomatic HIV infection
5.  AIDS (CD4 count less than 200/mm3)
6.  Advanced AIDS (CD4 count less than 50/mm3)

-Initial testing should include forth generation HIV 1/2 immunoassay, if negative no further testing is required.

If positive should have HIV 1 and 2 antibodies evaluated.  If indeterminate, check for RNA to see if acute HIV1 infection or not

-Viral transmission comes from sexual intercourse, exposure to contaminated blood, or perinatal transmission

-Heterosexual transmission is the most common reported mode of viral transmission in women

-Risk factors for HIV transmission include:  viral load, lack of circumcision, sexual risk, nitrate inhalant use, and ulcerative genital STD's present at time of intercourse

-Most patients seroconversion occurs to positive HIV serology within 4-10 weeks

-The period of early HIV disease extends from seroconversion to six months following HIV transmission

-During asymptomatic infection, patients may have no findings except possible generalized lymphadenopathy

-Signs and symptoms of acute symptomatic HIV infection include:  fever, fatigue, myalgias, adenopathy, oropharyngeal edema, tonsillar enlargement, painful mucocutaneous ulcerations, rashes, nausea, diarrhea, anorexia, headache and retroorbital pain, and dry cough

-Conditions that define AIDS diagnosed P. Carinii, Esophageal Candidiasis, Wasting, Kaposi Sarcoma, HIV associated dementia, CMV, Toxoplasmosis, Immunoblastic lymphoma, chronic cryptosporidiosis, Burkitt Lymphoma, Disseminated Histoplasmosis, Chronic Herpes simplex

-Once the decision is made to treat an acute or early HIV infection, the choice of treatment should be guided by drug resistance testing

-Common antiretrovirals include ritonavir, atazanavir, darunavir with tenofovir emtricitabine

-Once treatment is initiated, it should be continued indefinitely


-Human Papilloma Virus Infections-

-Human Papilloma Virus (HPV) is a DNA virus

-HPV is the most common sexually transmitted infection in the US

-HPV is associated with condyloma acuminata, cervical cancer, vaginal cancer, vulval cancer, anal cancer, squamous intraepithelial lesions and malignancy, and head and neck malignancy

-High Risk HPV Genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68)

-Low Risk HPV Genotypes (6, 11, 40, 42, 43, 44, 53, 54, 61, 72, 73, and 81)

-Genotypes 16 and 18 of HPV are the most common types found in cervical cancer

-HPV is also implicated in oral cancers and pre-cancer lesions

-Risk factors for HPV infection include unprotected penetrative intercourse or close skin contact of the involved area.  Digital/anal and digital/vaginal contact can cause spread of the virus

-Detecting HPV can be done by HPV DNA and RNA testing.  Can also detect cellular markers

-Prevention of spread of the virus is the best treatment.  Patients that test positive for HPV need closer surveillance (ex pap smears)


-Influenza-

-Influenza is an acute respiratory illness caused by the Influenza A and B viruses

-Transmission of the virus is by respiratory secretions

-Generally speaking, viral shedding can be detected 24-48 hours before the onset of symptoms, but much lower during the symptomatic period of the illness

-Uncomplicated influenza presents with fever, headache, myalgias, nasal congestion, non productive cough, and sore throat.  Physical exam is usually unremarkable

-Pneumonia is the most common complication of influenza

-Myositis and rhabdomyolysis are also complications of influenza

-CNS complications of influenza include:  encephalopathy, encephalitis, transverse myelitis, aseptic meningitis, and Guillain Bare Syndrome

-Two classes of antiviral drugs available for treatment of influenza-
1.  Neuraminidase inhibitors such as zanamivir and oseltamivir are active against influenza A and B
2.  The adamantanes such as amantadine and rimantadine that are active against influenza A

-These agents can shorten the duration of the illness 12 hours to 3 days.  Most studies have shown benefit when instituted 24-48 hours from the onset of symptoms

-Institution of any antivirals is recommended when:  illness requiring hospitalization, age over 65, pregnant women or post partum less than 2 weeks, or progressive, severe or complicated illnesses-High priority age groups for influenza vaccine:  pregnancy, immunocompromised patients, healthcare workers and household contacts

-Measles-

-Measles (Rubeola) virus is a member of the Paramyxovirdae family

-highly contagious childhood viral infection

-Stages of infection include:  incubation, prodrome and then exanthem

-Individuals are asymptomatic usually during incubation period 

-Prodrome presents with fever, coryza, cough, congestion, conjunctivitis, and Koplik spots

-Koplik spots are 1-3 mm whitish, gray, or blue elevation with an erythematous base, usually seen on buccal mucosa opposite molar teeth

-see in patients that are not immunized

-caused by measles virus and paramyxovirus

-Exanthem is erythematous papules appear on the face and neck where they spread to the trunk and arms

-Measles in pregnancy appears to be a risk for serious maternal and fetal complications

-Diagnosis is made by anti-measles IgM which can be detectable 3 days after the appearance of the rash

-Treatment is symptomatic

-Mumps-

-Mumps is a RNA virus that is from the Paramyxovirus family

-Mumps is a self limited viral syndrome

-Mumps has a nonspecific prodrome consists of low grade fever, malaise, headache, myalgias, and anorexia

-The prodrome is proceeded by parotitis which is characteristic of mumps infection

-More serious complications of mumps include meningitis, encephalitis, and orchitis

-Less frequent complications arthritis, pancreatitis, and myocarditis

-Diagnosis is made by positive IgM mumps antibody, significant rise in IgG titers, and isolation of mumps virus in a specimen

-Treatment is symptomatic


-Rabies-

-Rabies has the highest case fatality rate of any infectious disease

-Most rabies is spread by exposure to saliva from the anima bite

-In developed countries, dogs account for spread of 90 percent of rabies cases.  This was essentially eliminated as a source in the 1970's

-There are 4 major reservoirs for rabies in US:  bats, skunks, raccoons, and foxes

-As a general rule small rodents such s rats., mice, squirrels, gerbils, and chipmunks are susceptible but are uncommon in these animals

-Incubation period on average is 1-3 months, but can range from several days to several years after exposure

-Prodrome symptoms of rabies can include:  low grade fever, chills, malaise, weakness, fatigue, anorexia, sore throat, nausea, vomiting, headache, and photophobia

-Clinical rabies may involve two forms of the disease including:  encephalitis (furious) or paralytic (dumb) rabies

-Encephalitis rabies is the most common form of rabies

-Encephalitis (Furious) rabies symptoms include hydrophobia, pharyngeal spasms, fever, and hyperactivity leading to paralysis, coma and then death

-Paralytic (Dumb) rabies presents with ascending paralysis and can mimic Guillian Barre Syndrome

-Most patients with rabies die within two weeks after then onset of coma.  Most patients die because of asphyxiation and respiratory arrest from muscle spasms or uncontrolled seizures in encephalitic rabies and paralysis from paralytic rabies

-The diagnosis of rabies can be made by skin biopsy before death by virus specific immunofluorescent staining or detection of anti-rabies antibodies in the serum or CSF

-Post mortem testing involves brainstem and neural tissues directly of infecting animal or patient

-In general, rabies cannot be effectively treated so needs to be prevented

-There is no proven antiviral therapy for rabies but Ribavirin and Amantadine have showed in vitro activity.  Neither have been studies in clinical trials

-There is no proven role for the rabies vaccine or immune globulin in patients with established rabies

-Rabies immunoglobulin is known as passive immunization and rabies vaccine is active immunization

-Rabies vaccine alone should be given for preexposure prophylaxis

Post-exposure rabies prophylaxis should include the rabies vaccine and immunoglobulin

-Half of the injection in given around the wound and the other half is given intramuscularly as an injection

-Thorough washing of wound and non bite exposures with soap and water is recommended.  A virucidal agent such as povidone and iodine should be used


-Roseola-

-Roseola infantum (sixth disease, pseudorubella,  and 3 day fever) is a viral clinical syndrome characterized by 3-5 days of high fever that resolves abruptly and is followed by development of a rash

-Roseola usually is caused by human herpesvirus

-The fever or Roseola may have a fever that exceeds 40 degrees C (104 degrees F)

-Clinical manifestations of Roseola include:  malaise, palpebral conjunctivitis, edematous eyelids, inflammation of the tympanic membrane, oropharyngeal junctional macules or ulcers, upper and lower respiratory symptoms, vomiting, diarrhea, sterile pyuria, and bulging fontanelle, cervical post auricular occipital lymphadenopathy

-Roseola is usually diagnosed on clinical features and laboratory evaluation is seldom necessary

-Roseola is self limiting and treatment is symptomatic


-Rubella-

-Rubella virus is a member of the Togavirus family.  Rubella is a RNA virus

-Rubella has an incubation period of 14-18 days

-Rubella is acquired via inhalation of infectious large particles aerosols and is augmented by close and prolonged contact with infected individuals

-Infected individuals are contagious 1-2 weeks before the infection becomes clinically apparent

-Many infections of rubella are generally mild and many are subclinical or asymptomatic

- Clinical manifestations of post-natal rubella can include maculopapular rash, low grade fever, lymphadenopathy (posterior cervical, posterior auricular, and sub occipital).  Arthralgias may persist for up to one month

-Congenital rubella syndrome has defects such as hearing loss, mental retardation, cardiovascular defects, and ocular defects

-Specific IgM antibody can be detected as early as 4 days after the onset of the rash and can be detectable for 6-8 weeks after the infection

-Viral isolation from nasopharyngeal secretions can be used to confirm an acute rubella infection during pregnancy

-Treatment is supportive


-Varicella-Zoster Virus Infections-

-Varicella Zoster Virus (VZV) causes two distinct forms of the disease

-Primary VZV infection causes varicella (chickenpox) characterized by vesicular lesions in different stages of development on the face, trunk, and extremities.

-Herpes zoster (shingles) results in reactivation of the endogenous latent VZV infection within sensory ganglia

-The clinical form of shingles is painful unilateral vesicles erupted in a dermatomal distribution

-The clinical form of herpes zoster is characterized by the rash and neuritis

-Recurrent zoster in an immunocompetent host is uncommon

-Complications of zoster include post herpetic neuralgia, bacterial skin infection, ocular uveitis and keratitis, motor neuropathy, meningitis, and herpes zoster oticus (Ramsay Hunt Syndrome)

-Diagnosis is usually clinical but techniques for lab confirmation include viral culture and direct immunofluorescence testing, and PCR assay

-Treatment for VZV includes symptomatic treatment and antiviral therapy

-Acyclovir is the only antiviral therapy available for primary varicella in both healthy and immunosuppressed patients.  There is no clinical data for famciclovir or valacyclovir

Spirochetal Disease

Spirochetal Disease-

-Lyme Disease-

-Lyme disease is a tick borne illness caused by Borrelia burgdorferi

-Lyme disease was first described as "Lyme Arthritis" which was a cluster of children who developed juvenile rheumatoid arthritis is a community in Connecticut

-Three Phases of Lyme Disease:
1.  Early Localized Disease:  characterized by appearance of skin lesion (Erythema Migrans), with or without constitutional symptoms

2.  Early Disseminated Disease:  characterized by multiple erythema migrans lesions and/or neurologic and cardiac findings that can occur weeks to months after inoculation.  Many patients will have no history prior early localized disease

3.  Late Lyme Disease:  involves intermittent or persistent arthritis involving one or a few larger joints.  The knee is most commonly affected.  May have other neurologic problems such as mild encephalopathy or polyneuropathy.  May develop months to years after initial inoculation of the organism.

-Arthritis maybe the only manifestation of the disease

-Other symptoms with Lyme disease include:  fatigue, headache, anorexia, neck stiffness, fever, regional lymphadenopathy, arthralgias, and myalgias

-Typically will not have respiratory or GI symptoms.  Should consider lyme disease if not present

-Serologic testing for antibodies to B. burgdorferi should be used as an adjunct for diagnosis.  This just means that they have the antibodies and may have been exposed.

-In terms of Lyme disease antibiotic prophylaxis following a tick bite, amoxicillin is ineffective and doxycycline is effective

-Oral doxycycline, amoxicillin and cefuroxime have equal efficacy in treating lyme disease

-Most treatment regimens should be 21 days in length


-Rocky Mountain Spotted Fever-

-Rocky Mountain Spotted Fever (RMSF) is a rickettsial disease that is potentially lethal

-RMSF is a tick born disease

-RMSF can vary from mild disease to fulminant disease

-RMSF is caused by the organism Rickettsia rickettsii, which is a gram negative bacteria that is obligate

-Rickettsial infection leads to direct vascular injury which caused prostaglandin production and contributes to increased vascular permeability

-Rickettsial infection then can lead to activation of clotting factors, but true DIC is rare

-Hyponatremia comes from increased ADH from hypovolemia and decreased tissue perfusion

-Rickettsial infections can lead to interstitial pneumonitis, myocarditis, and encephalitis

-RSMF occurs in the US, Canada, Mexico, Central America and parts of South America

-The highest incidence of RMSF is in children less than 10, but has been seen in persons aged as high as 64

-Clinical manifestations of RMSF include:  fever, headache, malaise, myalgias, and joint pain with rash.  The headache is often the worst symptom and fever is present in almost all cases

-Physical exam can reveal the rash, pedal edema, confusion, conjunctival erythema, and retinal abnormalities.  Neck stiffness may be present with CNS involvement

-The diagnosis of RMSF is initially made clinically on symptoms and the right area of the world.  There is no reliable diagnostic test in the early phases of the disease when therapy should be started

-Clinical confirmation must be confirmed by skin biopsy or through serologic testing.  Indirect fluorescent antibody test is the standard method for serology for RMSF

-Doxycycline is the drug of choice for both adults in children except pregnant women for RMSF

-Chloramphenicol is the preferred treatment for most pregnant women

-Treatment should be continued for at least 72 hours after the patient does not have a fever


-Syphillis-

-Syphillis is an infection caused by the bacteria Treponema Pallidum

-Early syphillis has 3 stages primary, secondary, and early latent syphillis

-These occur usually within a year of acquiring the infection

-Latent syphillis is characterized by an asymptomatic infection with a normal physical exam and positive serology

-Studies have shown that the majority of case of syphillis occur in homosexual men

-Infection of Treponema Pallidum occurs only via direct contact with the infected lesion during sexual intercourse

-The early lesions of primary and secondary syphillis are very contagious.  Up to one third of patients exposed to these lesions will acquire the disease

-Syphillis can be also spread through touching or kissing a person who have active lesions on the lips, oral cavity, breast or genitals

-Primary syphillis presents usually as a painless lesion at the site of inoculation about 2-3 weeks of incubation.

-The typical chancre is 1-2 cm ulcer that is raised with an indurated margin.  These are usually on the genitalia.

-Chancre can occur at other sites of inoculation including vagina, posterior pharynx, and anus

-Chancres typically heal within 3-6 weeks without treatment

-Secondary syphillis occurs weeks to a few months later and rash can take any form except vesicular lesions.

-The classic rash of secondary syphillis is diffuse, symmetric macular or papular eruption on the extremities including the palms and soles of feet.

-Systemic symptoms of secondary syphillis can include fever, headache, anorexia, sore throat, myalgias, and weight loss.  Lymphadenopathy can sometimes be appreciated in the posterior cervical, axillary, femoral and inguinal regions

-Other complications of secondary syphillis include alopecia, hepatitis, GI ulcerations, synovitis, albuminuria, invasion of CSF, and posterior uveitis

-Neurosyphillis is an infection in the CNS by Treponema Pallidum

-The chancre of primary syphillis is best diagnosed with dark field microscopy

-Secondary syphillis is best diagnosed by serology (non Treponemal VDRL, RPR, and TURST  tests)
(Treponemal tests include FTA-ABS, MHA-TP, TP-TA, and TP-EIA)

-Penicillin G 2.4 million units is the treatment of choice for all stages of syphillis

Parasitic Disease

Parasitic Disease-

-Helminth Infestations-

-Helminths are multicellular parasites that have complex life cycles within and outside human hosts

-Anti-helminth drugs are used for treatment of symptomatic patients and deworming in regions with a higher prevalence of disease

-There are 3 man in groups of helminths:  flatworms (platyhelminths), thorny headed worms (acanthocephalins), and round worms (nematodes)

-Flatworms include flukes (trematodes) and tapeworms

-Thorny headed worms reside in the GI tract

-Round worms can reside in the GI tract, blood, lymphatic system, and subcutaneous tissue.  These organisms are not typically considered parasites

-Most intestinal flukes are asymptomatic.  When symptoms occur can include inflammation, ulceration, and small abscesses in the intestine.  Can get anorexia, nausea, vomiting, diarrhea and abdominal pain.  Malabsorption can sometimes occur

-Diagnosis is made by observation of worms or eggs in stool or body fluids

-Treatment of intestinal flukes are Praziquantel

-Intestinal tapeworms when cause symptoms and patients note segments in their stool or movement through their anus.  Patients may have nausea, anorexia, and epigastric abdominal pain.

-Diagnosis of intestinal tapeworms is made by visualization of the eggs or segments in their stool.

-Praziquantel is the treatment of choice for intestinal tapeworms

-Mebendazole is indicated for eosinophil colitis, anisakiasis, acariasis, capillarasis, larval tissue, pinworms, and hookworms


-Malaria-

-Malaria is caused by the plasmodia species (five different types)

-Most deaths that occur from malaria are from the plasmodia falciparum species

-Incubation period can be 12-35 days depending on the species

-The next step is the erythrocytic stage where there is a release of merozoites from the infected red cells when they rupture that causes fever and other manifestations

-Malaria should be suspected in any patient with a fever who has had an exposure to a region where malaria is prevalent

-Symptoms are non specific and may include fever, chills, tachycardia, tachypnea, malaise, diaphoresis, headache, cough, anorexia, nausea, vomiting, abdominal pain, and myalgias

-Physical exam may reveal anemia with splenomegaly

-Patients with complicated malaria may have altered LOC, seizures, ARDS, shock, metabolic acidosis, renal failure, liver failure, DIC, severe anemia, hypoglycemia, and massive intravascular hemolysis

-Diagnosis is made by blood smear or rapid diagnostic test.

-Treatment for uncomplicated malaria includes:
1.  Artermisinin derivative combinations
2.  Malarone
3.  Quinine in combination with doxycycline or clindamycin
4.  Lariam in combination with artesunate or doxycycline

-Two major classes available for parenteral treatment for severe malaria quinine and artemisinin derivatives


-Pinworms-

-Enterobius vermicularis (pinworms) is one of the most common nematode infections worldwide

-The cycle beings when female worms deposit themselves on perianal folds

-Autoinfection occurs by scratching the perianal area and transferring infective eggs to the mouth and contaminated hands

-Person to person spreading is done by contact

-After ingestion, eggs hatch and release larvae in the small intestine.  Gravid females migrate to rectum and and deposit eggs usually at night

-Most of the time infection is asymptomatic, may get peri-rectal itching and excoriation

-Diagnosis is made by the scotch tape test where clear tape is applied against the perennial skin allowing the eggs to adhere to the tape.  May see via gross examination

-Treatment is with albendazole or mebendazole once and repeated in 2 weeks


-Toxoplasmosis-

-Toxoplasmosis is an infection caused by an intracellular parasite

-Toxoplasma gondii is the organism that causes toxoplasmosis

-Immunocompetent patients typically are asymptomatic with primary infection

-If those patients become immunocompromised, they may exhibit only mild symptoms initially

-Felines are the only animals Toxoplasma gondii can complete its reproductive cycle

-When humans ingest T. Gondii eggs the organisms invade the intestinal epithelium and disseminate throughout the body

-There are many ways of acquiring toxoplasmosis in humans:
1.  Ingestion of infected oocytes from the environment
2.  Ingestion of tissue cysts in meat form an infected animal or contaminated fruits and vegetables
3.  Can be based from an infected mother to fetus
4.  Can be transmitted by blood or organ transplantation from donor

-When immunocompetent patients are infected with toxoplasmosis patients usually have bilateral symmetrical non tender cervical lymphadenopathy.  May also have generalized lymphadenopathy, fever, chills, sweats, myalgias, pharyngitis, non pruritic maculopapular rash, or hepatosplenomegaly

-Most immunocompetent patients have benign self limiting course lasting weeks to months

-T. gondii is the most common pathogens to cause chorioretinitis (posterior uveitis)

-ELISA serology is the most common diagnostic test employed for diagnosing toxoplasmosis

-Immunocompetent, non pregnant people do not require treatment unless symptomatic for over a month.

-Patients with AIDS with low CD4 counts can have reactivation of the disease easier and become quite ill.

-When Toxoplasmosis reactivates in AIDS patients it most commonly does so causing CNS encephalitis, and leads to cerebral abscesses

-Other areas of the body affected with toxoplasmosis is immunodeficient patients include pneumonitis and chorioretinitis

-Pregnant women who experience a mono like illness and have a negative test should be screened for toxoplasmosis

-The risk of fetal infection increases steeply with advancing gestational age at the time of maternal seroconversion

-A prenatal diagnosis requires an amniocentesis.  Risks versus benefits have to be outweighed

-Treatment of Toxoplasmosis is accomplished with pyrimethamine plus sulfadiazine or clindamycin

-Leucovorin should be given to all patients with pyrimethamine (for the folic acid)

-Treatment is typically at least 6 weeks for those who respond to treatment

Mycobacterial Disease

Mycobacterial Disease-

-Atypical Mycobacterial Disease-

-Non tuberculous mycobacteria (NTM) species are those other than those belonging to the mycobacterium tuberculosis complex

-These organisms are free living that are in a ubiquitous environment

-NTM bacteria cause 4 different clinical syndromes in patients:  pulmonary disease, superficial lymphadenitis, disseminated disease in immunocompromised patients, skin and soft tissue infection

-The most common NTM causing pulmonary disease is the mycobacterium avium complex (MAC)

-Disseminated NTM infections can enter the pulmonary system and then enter into the blood stream and seed in other organs.

-Disseminated NTM presents with fever, night sweats, and weight loss, fatigue, malaise, and anorexia

-Disseminated NTM may have organ specific symptoms and signs of major sites of involvement; adenopathy, or hepatosplenomegaly.  Diagnosis is made through blood cultures

-Mycobacterium Kansasii has never been found in natural water or soil supplies.  It is uncovered where it is endemic from tap water.   Presents as lung disease almost identical to tuberculosis

-Rapidly Growing Mycobacteria (RGM) are environmental organisms and may cause pulmonary disease

-Indications for treatment of NTM include:  respiratory symptoms, constitutional symptoms with abnormal x ray, plus consistent isolation of one specimen in pulmonary secretions

-Most studies support use of the newer macrolides against MAC (zithromax and biaxin)

-Currently the recommended regimen for MAC is Biaxin plus Rifampin, plus Ethambutol

-Treatment should be continued until sputum cultures are negative for at least 1 year



-Tuberculosis-

-Tuberculosis (TB) is caused by the organism Mycobacterium Tuberculosis

-Signs and symptoms of TB include fever, productive cough, retrosternal pain, pleuritic pain, arthralgias, pharyngitis, and enlarged bronchial lymph nodes.

-90 percent of patients with normal immunity control further replication and enter a latent phase of TB

-The other 10 percent of patients develop TB pneumonia seeding near hilum, get hilar lymphadenopathy, may get cervical lymphadenopathy, meningitis, pericarditis, or get miliary dissemination

-Symptoms of reactivated TB include cough, hemoptysis, weight loss, fatigue, chest pain, dyspnea, and night sweats

-Findings on chest x ray with reactivation of disease include upper lobe cavitary lesions, hilar lymphadenopathy, and solitary nodules

-CT scans of the Chest is more sensitive for diagnosis the chest x-rays for TB

-Complications of TB include hemoptysis, pneumothorax, sepsis, bronchiectasis, extensive pulmonary destruction including gangrene, malignancy, and chronic pulmonary aspergilliosis

-Two tests available to for diagnosing latent TB infection:  tuberculin skin test (TST) and interferon gamma release assay

-Indications for testing for latent TB include:  close contacts of patients with active TB, casual contact of patients with highly contagious active TB, and healthcare workers and other occupations where there is a high risk of exposure with untreated contagious active TB (prisoners and homeless shelters)

-TST is used to show those that have been sensitized to mycobacterial antigens

-Induration for TST should be reassessed in 48-72 hours because is mediated by T Lymphocytes from a delayed hypersensitivity

-Interpretation of the test is as follows:  greater than 5 mm induration is positive in HIV patients, close contact with an active case, abnormal chest x ray with findings of old TB, and immunosuppressed patients.  Greater than 10 mm of induration is positive in patients with increase risk of reactivation, children less than 4 years, foreign born patients, residents and employees of high risk settings.  Greater than 15 mm of induration is considered positive in healthy people with a truly low likelihood of true TB infection

-To diagnose active TB, clinical manifestations must be present.  Generally a cough greater than 2-3 weeks, night sweats, weight loss, and lymphadenopathy.  History of prior positive TST, and radiographic features and labs consistent with TB.  It is recommended that the patient have at least three sputum specimens for acid fast bacillus (AFB)

-Patient should be respiratory isolation while being ruled out.  Positive patients need to be reported to the local health department.

-Four drugs are used in the initial treatment o f active TB because of concern INH resistance.  The 4 drugs are INH, rifampin, ethambutol, and pyrazinamide

-Duration of initial treatment lasts usually for 8 weeks.  If culture and sensitive implicate sensitivity to one of the 4 agents, then ethambutol can usually be discontinued

-The continuation phases is administered for 4-7 months and usually consists of INH and Rifampin

-Hepatotoxicity needs to be monitored

-Need to reassess sputum culture after treatment to determine if there is treatment failure

Bacterial Disease

Bacterial Disease-

-Acute Rheumatic Fever-

-Acute Rheumatic Fever is a sequelae that occurs two to four weeks after Group A Strep Pharyngitis

-Acute Rheumatic Fever may consist of arthritis, carditis, chorea, erythema marginatum and subcutaneous nodules

-Acute Rheumatic Fever may also cause damage to cardiac valves that may lead to cardiac problems

-Acute Rheumatic Fever occurs most commonly between the ages of 5-15 years, rarely in the first 3 years of life as well as adults

-Jones Criteria defines the diagnosis of Acute Rheumatic Fever (ARF) via major criteria and minor criteria

-Major Criteria for ARF-

1.  Migratory Arthritis (mainly large joints)

2.  Carditis and Valvulitis

3.  CNS Involvement (Sydenham Chorea)

4.  Erythema Marginatum

5.  Subcutaneous Nodules

-Minor Criteria for ARF-

1.  Fever

2.  Prolonged PR interval

3.  Elevated ESR or CRP

4.  Arthralgia

-Two major criteria, or one major and two minor criteria is considered diagnostic for ARF

-Usually occurs 2-4 weeks follow a Group A Strep infection

-Rheumatic heart disease is the most severe sequelae of ARF.  It usually occurs 10-20 years following the illness

-ARF is the most common cause of acquired valvular heart disease in the world

-Mitral valve is usually more involved than the aortic valve

-The treatment of ARF involves anti-inflammatory management, heart failure management,  and anti-mircobials

-Patients should be treated for strep pharyngitis rather or not pharyngitis is present.  Patients can be treated with amoxicillin, penicillin, penicillin G, cephalexin, or azithromycin, or biaxin

-Patients with cardiomegaly, CHF, or third degree heart block should be treated with therapy for heart failure.  Patients with third degree heart block require pacing

-ASA 80-100 mg/kg per day in children and 4-8 grams per day in adults in the major anti-inflammaotry agent used

-Botulism-

-Botulism is caused by the bacteria Clostridium Botulinum

-Botulism is a rare life threatening infection that causes a neurologic paralysis syndrome from a neurotoxic the bacteria secretes

-There are subtypes of botulism A-H

-G and H types of botulism cause human disease

- C and D types of botulism cause disease in cattle, ducks, and chickens

-The botulinum bacteria when it is in the body releases a neurotoxin that spreads widely to the vascular system and binds to receptors on the synapses at the neuromuscular junction

-Once the toxin makes it into the cytoplasm it disrupts the stimulation of acetylcholine release

-Botulism toxin is the most potent bacterial toxin and the most potent poison

-The botulism toxin is inactivated by chlorinated water after about 20 minutes of exposure and fresh water after 3-6 days

-The botulism toxin is resistant to inactivation by gastric acidity and the gastrointestinal digestive enzymes

-The botulism toxin has no smell or taste

-Clinical features of botulism are:  absence of fever, symmetric neurologic deficits, the patient remains responsive, normal slow heart rate and normal blood pressure, no sensory deficits except blurred vision

-Patients with suspected botulism should be hospitalized and monitored for signs of respiratory failure

-Equine serum heptavalent botulism toxin is used to treat children greater than 1 year of age and adults

-Human derived botulism immune globulin is used for infants less than one year of age

-Penicillin G or Flagyl is IV recommended for those who have wound botulism


-Chlamydia-

-Chlamydia and Chlamydophilia species are obligate intracellular bacteria

-Chlamydia trachomatis is the most common cause of genital tract and ocular infections in the world

-Chlamydophilia psittaci causes atypical pneumonia

-Chlamydia pneumonia presents similar to other pneumonias.  Usually gradual onset of symptoms, pharyngitis, sinusitis, cough and fever.  Chest x ray usually reveals one patchy area of subsegmental infiltrate

-Antibiotic choices for chlamydia pneumonia include azithromycin, clarithromycin, and doxycycline

-Chlamydia trachomatis is the most common cause of sexually transmitted infections

-The majority of affected persons are symptomatic and an ongoing reservoir for the infection

-For infants born via vaginal delivery, chlamydia pneumonia or chlamydia conjunctivitis can occur

-Up to 85 percent of women infected at the cervix with chlamydia have no signs of symptoms

-Routine annual screening is recommended for sexually active women

-Untreated cervical infection can ascend to causes PID and lead to infertility and chronic pain

-Symptoms of chlamydia include dysuria, purulent vaginal discharge and pelvic pain

-Fitzhugh Curtis syndrome is when a chlamydia infection develops into perihepatitis and liver capsule and adjacent peritoneal surfaces

-Complete treatment should be targeted gonorrhea and chlamydia both.  Chlamydia can be treated with 1000 mg of zithromax or doxycycline 100 mg BID for 10 days.  Gonorrhea is treated with rocephin 250 mg IM.

-The patient should be counseled on HIV testing and treatment of sexual partners.  Should also abstain from intercourse for 14 days after partner (s) treated


-Cholera-

-Cholera presents as a secretory diarrhea illness caused by a toxin of strains of gram negative Vibrio cholera

-Cholera presents as profound fluid and electrolyte losses in the stool and rapid development of hypovolemic shock.

-Aggressive fluid replacement reduces the mortality from cholera dramatically

-This organism thrives in brackish aquatic environments that serves as media for human infection

-Cholera can be cultured in stool and rectal swabs using selective media and biochemical tests

-Cholera primarily effects resource limited countries where this inadequate access to clean viable water sources

-Transmission of Cholera is ingestion of food or water of contaminated water sources usually

-The spectrum of cholera severity of illness ranges from asymptomatic colonization to severe diarrhea and hypovolemic loss

-The characteristic diarrhea is profuse "rice water" stool

-Antibiotics are considered adjunctive with treatment and may be of particular use in epidemic settings.  Doxycycline, zithromax, erythromycin, or cipro are recommended

-The WHO recommends oral cholera vaccines for those in endemic areas



-Diphtheria-

-Diphtheria is caused by Corynebacteria Diphtheriae which is a gram positive bacillus

-Diphtheria can manifest itself as a respiratory illness, skin pathology, or just an asymptomatic carrier

-Diphtheria means leather that refers to a tough pharyngeal membrane which is the hallmark of the disease

-Symptoms of diphtheria are sore throat, malaise, cervical lymphadenopathy, and low grade fever

-With diphtheria you can see mild pharyngeal erythema and white exudate that coalesce to form a gray pseudomonas that bleeds with scraping

-With diphtheria can also see adherent pharyngeal, palate, and nasal membranes, systemic toxicity, hoarseness, stridor, and serosanguineous nasal discharge

-Confirmation of diagnosis comes from a culture of respiratory tract secretions or cutaneous lesions, and a positive toxic assay

-Treatment includes the diphtheria anti-toxin and antibiotics such as erythromycin or penicillin G


-Gonococcal Infections-

-Gonococcal infections can include urethra, cervix, epididymis, conjunctiva, pharynx, and rectum

-If infections are not considered from ascending spread of the pathogen to other organs or the patient is not septic it is considered an uncomplicated infection

-Studies have demonstrated that is a confection with chlamydia up to 50 percent of the time

-Rocephin 250 mg IM times one dose is the treatment of choice

-Alternative regimen for gonorrhea is ceftizoxime 500 mg IM or cefoxitin 2 grams times one dose

-Alternative regimen for those with a cephalosporin intolerance is zithromax 2 grams PO.  This is not recommended because of high incidence of GI upset

-Gonococcal pharyngitis should be treated with with rocephin 250 mg IM

-Gonococcal conjunctivitis can be treated with 1 gram of Rocephin IM

-Epididymitis is most likely caused by gonorrhea or chlamydia if the patient is less than 35.  Rocephin 250 mg IM times one dose with Doxycycline 100 mg BID for 10 days for these patients.

-Gonococcal proctitis should be treated with rocephin 250 mg IM times one dose with doxycycline 100 mg BID for 7 days

-Sexual activity should be avoided for 7 days after partner(s) are treated

-Exposed partners should also be treated

-Patients with disseminated gonococcal infection present with one of two syndromes.  Purulent arthritis without associated skin lesions or a triad of tenosynovitis, dermatitis, and polyarthritis without purulent arthritis

-Purulent arthritis needs to have the joint aspirated and cultured.  No studies have been done.  In general cefixime should be started 400 mg BID after parenteral therapy for 7 days

-alternatively isolates of gonorrhea have been susceptible to cipro 500 BID, doxycycline 100 mg BID, or amoxicillin 500 mg four times a day.


-Salmonellosis-

-Salmonella consists of two species:  Salmonella enterica, and Salmonella bongori

-In the clinical setting, gastroenteritis from Salmonella may be clinically similar to gastroenteritis caused by similar organisms

-The cardinal symptoms of Salmonella are nausea, vomiting, fever, diarrhea and abdominal cramping approximately 8-72 hours after eating contaminated food or water

-Salmonella may be mild or even no symptoms

-A small percentage of individuals with Salmonella will develop sepsis as a result of Salmonella infection.

-Sepsis from Salmonella can lead to endocarditis, osteomyelitis, or mycotic aneurysm

-Most cases of Salmonella gastroenteritis resolve without treatment.  Fever usually resolves within 48 hours and diarrhea lasts 4-10 days.

-Diarrhea over 10 days should provoke a workup for other diagnoses

-Positive stool cultures should be treated in symptomatic patients, preemptive treatment in immunosuppressed hosts, food handlers and healthcare workers, and asymptomatic carriage of nontyphoidal Salmonella

-Replacement of electrolytes is essential in symptomatic patients

-Treatment should be considered in patients with more than 9-10 stools per day, high fever, or a need for hospitalization

-The presence of blood in diarrhea does not mean the patient needs antibiotics

-As a rule of thumb, the potential for improvement of severe illness and prevention of complications  appear to outright the small risks of antibiotic treatment

-Appropriate treatment for Salmonella include Cipro, Levaquin, Bactrim Rocephin, Amoxicillin, or  Tetracycline

-Preemptive treatment is indicated for patients with organ transplants, cancer, AIDS, sickle cell, or patients receiving corticosteroids or immunosuppressants

-Antibiotic treatment is appropriate for pregnant women when they have fever, severe disease, sepsis, or they are near term


-Shigellosis-

-Shigella is a non motile, aerobic gram negative bacilli

-The four species of Shigella include:  Shigella dysenteriae, Shigella flexneri, Shigella boydii, and Shigella sonnei

-Shigella survives transit through stomach acid and multiply in the small intestine.  Shigella subsequently pass into the colon where they invade the colonic cells

-Shigella transmission predominately occurs via contaminated food and water and person to person contact

-Symptoms of shigella include fever, abdominal cramping, mucoid diarrhea, bloody diarrhea, watery diarrhea, and vomiting.

-It is important to emphasize, shigella is a disease of lower GI tract

-Incubation range for Shigella is 1-7 days, with a mean of 3 days

-Stool frequency is 8-10 stools per day, but can be up to 100 per day

-Intestinal complications of Shigella infection include:  proctitis, rectal prolapse, toxic megacolon, intestinal obstruction, and colonic perforation

-Systemic complications of Shigella infection include:  dehydration, electrolyte disturbance, sepsis, seizures, reactive arthritis, hemolytic uremic syndrome, and leukamoid reaction (WBC of 50,000 or more)

-Diagnosis should be suspect with frequent small volume, blood stools, abdominal cramping, and tenesmus

-Definitive diagnosis requires a stool culture

-For public health reasons, most clinicians favor antibiotic therapy.

-Empiric antibiotics are indicated in severely ill patients with diarrhea when hospitalization is required

-Other indications of empiric therapy pending cultures include malnourished individuals, HIV patients, food preparers, health care workers and day care workers

-The treatment of choice for Shigella in descending order includes levaquin, cipro, zithromax, bactrim, and rocephin for 3-5 days

-Duration of therapy is short due to low count of organism necessary to cause disease


-Tetanus-

-Tetanus is a nervous system disorder that causes muscle spasms because of toxin produced by an anaerobic bacteria called Clostridium tetani

-The term "lockjaw" now referred to a trismus is one of the cardinal features of tetanus  which is painful, intense spasms of the masseter muscles

-Tetanus can present in one of four clinical patterns:  neonatal, localized, generalized, and cephalic

-Tetanus is rare in the developed worlds because of vaccination

-Predisposing factors include a penetrating injury resulting from inoculation of spores,  or infection with other bacteria, devitalized tissue, a foreign body, and localized ischemia

-Tetanus can develop in different clinical situations such as:  neonates from infection of the umbilical stump, obstetrical patients after septic abortions, post surgical patients, patients with dental infections, diabetic patients with infected extremity ulcers, and patients who inject illicit or contaminated drugs

-Incubation periods can be one day to several months

-The most common and severe clinical form of tetanus is generalized tetanus

-Classic clinical findings of tetanus include:  stiff neck, opisthotonus, risus sardonicus (smile), a board like rigid abdomen, periods of apnea and upper airway obstruction due to vise like contraction of the thoracic muscles

-During generalized tetany spasms, patients clench their fists, arch their back, and flex and abduct their arms while extending their legs

-Localized tetanus occur with spastic muscle contractions in one extremity or body region

-Cephalic tetanus only involves the cranial nerves after injuries to head and neck

Neonatal tetanus occurs in infants 3-21 days old.  It is manifested by rigidity spasms, trismus, inability to suck, and seizures.  Can result from aseptic techniques in managing the umbilical stump of mothers that are poorly immunized

-The goals of treatment of tetanus include:  halting toxin production, airway management, neutralization of the unbound toxin, control of muscle spasm, management of dysautonomia, and generalized supportive management

-Wound management is essential for debridement of contaminated tissue and necrotic tissue.  Antibiotics should include flagyl, but penicillin G is an effective alternative

-Since tetanus toxin is irreversibly bound to tissues, the unbound toxin is the only available for neutralization

-The human tetanus immunoglobulin (HTIG) should be given and infiltrated around the wound and administered at different sites than tetanus toxoid

-All patients with an acute illness should receive tetanus toxoid in 3 doses spaced two weeks apart

-Several medications have been used to produce adrenergic blockade and suppress autonomic hyperactivity.  Magnesium sulfate and labetolol have been used

-Tetanus Prophylaxis-
1.  Patients who received less than 3 doses of tetanus toxoid should be given the tetanus toxoid and tetanus immunoglobulin

2.  Patients who have received 3 doses should just receive tetanus toxoid (recommended in 10 year intervals)

Fungal Disease

Infectious Disease Blueprint-

Fungal Disease-

-Candidiasis-

-Candidia infections can vary from minor localized mucocutaneous infectious to widespread candidia dissemination

-Candidia is considered normal flora in the gastrointestinal and genitourinary tract, candidia can cause disease when there is an imbalance in the body's ecosystem

-Candidia can cause numerous infections:  oral candidia, esophagitis, vulvovaginitis, balanitis, chronic mucocutaneous candidia, mastitis, candidemia, hepatosplenic or chronic disseminated candidiasis, urinary tract infection, endophthalmmitis, osteoarticular infections, meningitis, endocarditis, peritonitis, pneumonia, mediastinitis, pericarditis, and gastrointestinal tract colonization.  

-Oral candidia is common in young infants and older adults with dentures, treated with antibiotics, chemotherapy, radiation therapy to head and neck, inhaled glucocorticoids, or patients with cellular immune problems such as HIV.  

-Oral candidia presents with white plaques on the buccal mucosa, palate, tongue or oropharynx.  

-Oral candidia is treated with nystatin oral suspension

-Candidia Esophagitis is most common in HIV infected patients.  It is considered an AIDS defining illness.  Candidia Esophagitis can also be seen in hematologic malignancies.  

-Symptoms of candidia esophagitis include:  odynophagia and localize their pain to the retrosternal area.  Diagnosis is made by endoscopy

-Candidia vulvovaginitis is the most common form of candida.  It occurs with high estrogen levels, oral contraception use, pregnancy, antibiotics, glucocorticoids, diabetes, HIV infection, IUD, and diaphragm use are risk factors

-Candidia vulvovaginitis can be diagnosed clinically but confirmed with wet mount or KOH prep.  Can be treated with antifungal vaginal suppositories or diflucan

-Balanitis presents with white patches on the penis associated with burning and itching

-Mastitis-lactating women with injured nipples are at risk for developing cellulitis and also can get fungal infections also

-Invasive focal or system infection are associated with candidemia that occurs with immunosuppressed patients

-Fungal UTI usually come with hospitalized patients   Can also get from a disseminated infection from the kidney

-Endophthalmitis can develop from direct eye trauma or eye surgery.  Can get hematogenous spread to the retina but unusual

-Candidia Osteoarticular infections come from result from hematogenous spread or inoculation during trauma or injections

-Candidia Meningitis and endocarditis can present from hematogenous spread.  Both are unusual

-Peritonitis fungal infections can occur following GI tract perforation, anastomosis leaks after bowel surgery, and necrotizing pancreatitis

-Candidia empyema occurs commonly in patients with malignancy

-Candidia mediastinitis occurs after thoracic surgery procedures.  Uncommon


-Cryptococcosis-

-Cryptococcus is a fungal infection caused by cryptococcus gattii

-Cryptococcus manifests itself usually as meningoencephalitis and/or pulmonary infection

-Systemic features include fever, chills, and weight loss.  Other signs and symptoms include papilledema and will have a cough with pulmonary infections

-Cryptococcus may lead to increased ICP, severe headache, hydrocephalus, ataxia, vision and hearing loss

-Workup should include CT scan of chest (for pulmonary) and head for neurologic.  Also need CSF examination, funduscopic exam, and serum cryptococcal antigen

-Most patients with cryptococcal meningitis are immunocompromised.  Forms of immunosuppression seen in include HIV, glucocorticoid therapy, solid organ transplantation, cancer, and hepatic failure

-Treatment for cryptococcus include antifungal agents such as amphotericin B, oral flucytosine, or oral fluconazole

-Persons with AIDS related cryptococcal meningitis need to be on maintenance therapy to prevent relapse


-Histoplasmosis-

-Histoplasmosis is a common fungal infection that is usually asymptomatic but occasionally will result in severe illness

-Histoplasmosis is usually endemic to North and Central America

-The most common areas affected by histoplasmosis is Ohio and Mississippi River valleys.

-Histoplasmosis should be considered during any of the following clinical situations:  pneumonia with hilar and mediastinal lymphadenopathy, mediastinal or hilar masses, pulmonary nodules, cavitary lung disease, pericarditis with mediastinal lymphadenopathy, pulmonary manifestations with arthritis plus erythema nodosum, dysphagia with esophageal narrowing, and superior vena cava syndrome or obstruction of other mediastinal structures

-Stains for fungi, cultures, antigen detection, and serologic tests for Histoplasmosis specific antibodies can help make the diagnosis

-Can also make the diagnosis from biopsy of pulmonary tissue

-Cultures are most useful in patients with chronic pulmonary histoplasmosis

-Patients with acute diffuse pulmonary disease serologic antigen provides the highest sensitivity

-Patients with localized pulmonary disease have a lower yield on serologic or urine antigen and pulmonary cultures maybe higher yield

-Acute pulmonary histoplasmosis moderate to severe should be treated with Amphotericin B IV then followed by Itraconazole.  Solumedrol should also be given

-Acute pulmonary mild to moderate histoplasmosis with symptoms greater than 4 weeks, chronic cavitary pulmonary histoplasmosis, and symptomatic mediastinal granuloma should be treated with Itraconazole

-Histoplasmosis can cause extra pulmonary syndromes including pericarditis and rheumatology syndromes


-Pneumocystis-

-Pneumocystis Jirovecii (Pneumocystis Carinii) is the organism that leads to pneumocystis carinii pneumonia (PCP)

-The incidence of PCP has decreased because of effective antiviral therapy with HIV

-PCP is one of the leading causes of opportunistic infections in the HIV infected patients with low CD4 counts or those not HIV infected patients unaware of the infection or those non compliant with therapy

-The transmission of pneumocystis is the airborne route.  Primary infection occurs early in life, with 75 percent of humans infected by 4 years of age.  It was believed that pneumocystis remained latent unless immunosuppressed.

-Phagocytosis, respiratory burst, and inflammatory activation of alveolar macrophages are impaired in HIV infected patients and contribute to the pathogenies of the infection

-PCP presents with fever, cough, and dyspnea presenting over days to weeks

-As CD4 counts decreases the infection rates of PCP increases

-Chest X Rays can be normal in 25 percent of patients with PCP.  If negative consider CT scan of chest.

-If patient cannot have a CT scan of the chest, Gallium 67 Citrate scanning is sometimes used to screen for PCP

-Definitive diagnosis of PCP requires visualization of the cystic or trophic forms in respiratory secretions

-Pneumocystis cannot be cultured

-Immunofluorescent staining with fluorescein labeled monoclonal antibodies is the gold standard for PCP

-It is recommended to treat PCP with bactrim in non HIV infected patients

-Alternative therapies include pentamidine, atovaquone, bactrim plus dapsone, and primaquine plus clindamycin

-Patients should be treated for 21 days