Extra intestinal protozoa
|Extraintestinal Protozoa: life cycles||often more complex than for the intestinal protozoa, with different stages of the life cycle occurring in different hosts.|
|Extraintestinal Protozoa: importance of public health measures||The vetoer-human life cycle is complex and delicate, though clearly successful for many infectious agents. However, it is susceptible to interdiction through public health measures - primarily vector control through sanitation, draining of insect breeding grounds, insecticide spraying. These measures are far more effective than chemotherapy either pre or post infection|
|Toxoplasma gondii: life cycle||the domestic cat is the definitive host. Many mammals and birds, including humans are intermediate hosts. IN the intermediate host, the organisms divide intracellularly in any host tissue. Sexual reproduction occurs only in the intestines of cats, producing oocysts stable for extended periods. Transmission is by ingestion of oocysts from material contaminated by cat feces.|
|Toxoplasma gondii: Diseases|| Acute toxoplasmosis|
Acute congenital toxoplasmosis
|Acute toxoplasmosis||Exposure to T. gondii is asypmtomatic in 80-90% of immunocompetent hosts|
Symptoms: arise ~1 week after exposure and include cervical lymphadenopathy, headaches, night sweats, chorioretinitis. These symptoms reflect a preference of the organism for cels of the CNS, eye, lungs, and lymphoid system. Tissue cysts can persist indefinitely
|Toxoplasmic encephalitis||Primarily an AIDS related infection, the AIDS defining illness in 1/6 of AIDS patients.|
Symptoms: include altered mental status, chorioretinitis, seizures, sensory abnormalities, hemiparesis, and coma
potentially fatal due to neurological involvement; also can cause a pneumonia-like infection. Toxoplasmosis in AIDS patients often results from reactivation of latent infections rather than new exposure
|Acute congenital Toxoplasmosis||Affects infants born to toxoplasmosis-infected mothers. If disease is acquired in the first trimester ~17% of fetuses are affected, in the third ~65% are.|
SYMPTOMS: severe neurological abnormalities, including cerebral calcifications, hydrocephaly or microcephaly, chorioretinitis, and neuromuscular defects. Spontaeous abortion or miscarriage can occur.
EXPOSURE at earlier gestational ages means more sever symptoms including abortion or death in the first few months postpartum. Later gestational ages has a range of effects from mild to severe including death. Children can born apparently normal and develop symptoms later
|Toxoplasma gondii: pathology||Dstrcution of host cells doing acute infection can cause necrotic lesions. In immunosuppressed patients, there is often brain involvement with potentially large necrotic abscesses. Congenital infections frequently manifest retinal foci that an impair vision. Exposure during gestation can lead to sever neurological abnormalities.|
|Toxoplasma gondii: Diagnosis||Serology is most common initial clue. Since many people have been exposed, rising IgG titers from a series of tests over a few days-weeks is diagnostic. Eleveated IgM titers is also indicative of acute infection. IgM Abs are not present during reactivation and this is less useful in AIDS patients.|
Examination of tissue samples after Wright or Giemsa staining can ID parasites, but routine histology often misses them. Inoculation of tissue culture or mice can also ID T. gondii, but this can take several weeks.
Detection of parasite DNA by PCR is useful in diagnosing in utero infections.
|Toxoplasma gondii: treatment||often not required for immunocompetent individuals.|
Treatment is indicated for severe disease or in pregnant women, AIDS patients, and newborns. Combination therapy with pyrimethamine and sulfadiazine is usually effective. Pyrimethanmine should not be given to women in the first trimester; spramycin in s an alternative but less effective. Treatment should be continued indefinitely in AIDS patients to prevent relapse.
|Free living amoebae|| Naegleria fowerli|
They are free living because they do not have a definitive host. They live as amoeba in aquatic environments, including fresh water, wet soil, sewage and swimming pools
|Naegleria fowerli: life cycle||Forms a cyst trophozoite and flagellated forms. The flagellated form is usually transient.|
|Acanthamoeba: life cycle||found as cysts and trophozoites in the environment|
|Naegleria fowerli and Acanthamoeba: transmission||N. fowerli - trophozoites are the infectious form via the olfactory neuroepithelium|
Acanthamoeba - enter body via the lower respiratory tract or broken skin. both the cysts and trophozoites are infective.
These parasites are usually acquired while swimming in fresh water contaminated by the parasites
|Primary Amebic Meningoencephalitis||Rare but extremely serious ~95% mortality, usually within 72 hours. Symptoms include headaches mental-status changes, alterations in taste/smell, sensitivity to light. Both N. fowler and Acanthamoeba can cause PAM; progression is slower with Acanthamoeba|
|Amebic Keratitis||Caused by Acanthamoeba. Corneal ulcers resulting from trauma or contact lens use. Granulomatous skin lesions are also seen|
|Naegleria fowerli and Acanthamoeba: Pathology||diffuse hemorrhage and necrosis of brain tissue is common with PAM|
|Naegleria fowerli and Acanthamoeba: diagnosis||DIFFICULT. trophozoites can occasionally be seen in wet mount microscopic examination of CSF or brain biopsies. Amoeba will not be seen in gram stained CSF because they are destroyed during staining. PAM should be considered in patients with meningitis where CSF stains do not ID bacterial or fungal agents. Keratitis can be diagnosed by corneal or skin scrapings from lesions.|
|Naegleria fowerli and Acanthamoeba: Treatment||Few cases of PAM are treated successfully. Amphotericin B, miconazole and rifampicin have occasionally been successful. Keratitis can be treated with topical .1% propamidine isethionate or miconazole. can be combined with oral itraconazole. Keratoplasty or corneal grafts may be necessary.|
|Plasmodium: causes|| malaria|
Most deaths are in kids <5
one of the 3 leading causes of death from infectious disease
|Plasmodium: species infecting humans|| P. facliparum - causes malignant tertian malaria|
P. vivax - causes tertian malaira
P. malariae - causes quartan malaria
P. ovale - rarest form
|Plasmodium: transmission||people are infected through the bite of a female Anopheles mosquito carrying Plasmodium. can also occur due to transfusion|
|Plasmodium: life cycle||The mosquito is the definitive host, where sexual reproduction occurs. Differentiation into sexually competent forms occurs in the human, so mosquito-human transition is required for the completion of the life cycle.|
|Plasmodium: epidemiological and genetic issues|| Most blacks of african origin are resistant to vivax malaria because they genetically lack the Duffy antigens on RBCs that are required for P. vivax entry.|
Individuals heterozygous for the sickle-cell anemia mutation - again mostly blacks from african origin - are resistant to all forms of malaria
|Plasmodium: symptoms|| Fever|
Myalgia, malaise, fatigue
|Plasmodium: Symptoms: Fever|| Usually cyclical. the periodicity is an inexact indactor of the infectious species. Paroxisms and chills are common.|
P. falciparum - 24 hours (but can be absent in severe cases)
p. vivax - 48 hours
P. malariae - 72 hours
P. ovale - irregular
|Plasmodium: Symptoms: anemia||Caused by lysis of the RBCs during parasite replication. This PANYTOPENIA usually includes drops in all drops in all blood cellular components.|
|Plasmodium: Symptoms: hepatomegaly/splenomegally||results from increased activity of phagocytes removing cell debris and bloodborne parasites|
|Plasmodium: symptoms: Neurological symptoms/ altered mental status||mostly P. falciparium rarely P.vivax. Headaches confusion lethargy, coma|
|Plasmodium: symptoms: organ failure||Caused by anemia, reduced O2 delivery, occlusion of capillary beds. Blackwater fever, dark urine from exertion of hemoglobin, is caused by kidney malfunctions|
|Plasmodium: pregnancy associated malaria||Most adults in endemic areas develop resistance to malaria. However this resistance does not carry through pregnancy, with pregnant women, particularly in the first pregnancy, susceptible. Parasite attachment to capillaries in the placenta can restrict blood flow to the fetus and lead to spontaneous miscarriage/abortion. resistance returns postpartum and increases during pregnancy as a function of parity.|
|Plasmodium: drug resistance||An increasingly serious problem. P. falciparium in africa is now almost completely resistant to chloroquine. P. falciparum is commonly resistant in central/south america and southeast asia as well. Reports of P. vivax resistant to chloroquine have emerged recently|
|Plasmodium: Diagnosis||Almost exclusively diagnosed by microscopic examination of thin blood smears. Morphology of RBCs and parasites are diagnostic for species ID as well.|
IDing the infectious Plasmodium species is important for proper treatment decisions
In endemic areas with limited tools diagnosis can be made by recent history of fever in combination with epidemiological criteria
ELISA for parasite antigen exist, but are expensive, can be preformed by technicians with limited expertise.
In endemic areas malaria can be assumed in kids <5 with a fever, then immediate treatment for malaria can begin with the benefits out weighing the potential risks
|Plasmodium: treatment of uncomplicated P. falciparum malaria||Defined as symptomatic malaria from P. falciparum w/o evidence of rogan dysfunction or neurological involvement|
Endemic areas: combination therapies with artesiminin-based drugs (artemether or aretsunate) are indicated in most cases. DRUG 1-artemesinins DRUG 2-non-artemesinin antimalarials: mefloquine, lumefaantrin, amodiaquine, and sulfadoxin-pyrimethamine
Oral administration is most common, but rectal suppositories or IV are also available
non endemica areas: 1 of these 4 drugs:
1. atovaquone-proguanil (malarone)
2. artemaether-lumefantrin (coartem)
3. quinine sulfate plus clindamycin, tetracycline or doxycycline
4. Mefloquine (if others are not available)
|Plasmodium: treatment of severe P. falciparum malaria||if symptomatic malaria occurs with any of the following symptoms it is severe|
Pulmonary edema, respiratory distress, Impaired consciousness, Hemoglobulinuria, Multiple convulsions, Severe anemia, Jaundice, Renal impairment
Primary concern is keep patient alive, prevention of relapse, development of disabilities and or drug resistance is secondary.
IT IS A MEDICAL EMERGENCY
|Plasmodium: treatment of uncomplicated P. falciparum malaria initial treatment||One of 3 drugs. |
quinidine, this one has some toxicity particularly in renal function and should be avoided if possible
In the US: Quinidine gluconate is the front lineantimalarial for severe falciparum malaria. Parenteral administration is recommended. After initial treatment, a combination with doxycycline, tetracycline or other oral antifungals should be initiated.
Continuing treatment: follow with oral antimalarials once the patient can tolerate them
|Vivax, Malariae, Ovale infections||These infections are less severe than falciparum malaria though occasional cerebral involvement is seen with vivax. These are generally sensitive to chloroquine; reports are emerging of increasing chloroquine resisitance in vivax infections. Primary treatments include chloroquine, mefloquine, amodiaquine. |
P. vivax and P. ovale have "hypnozoite" liver stages that are persistent for months to years in the liver. Relapses long after the initial infection are common. THESE DORMANT TAGES ARE UNRESPONSIVE TO MOST DRUGS; PRIMAQUINE IS EFFECTIVE AND SHOULD BE COMBINED WITH THE PRIMARY ANTIMALARIAL
severe vivax malarial should be treated as severe falciparum malaria, with the addition of primaquine
|Vivax, Malariae, Ovale infections: mixed infections||it should be recognized that some patients may have infections from multiple species|
|Vivax, Malariae, Ovale infections: supportive care||antimalarials can be given alongside treatments to mitigate symptoms - antipyretics for fever, antimetics for nausea, fluid replacement|
|Vivax, Malariae, Ovale infections: special populations||because of limited efficacy and safety data, some treatment options are preferred for pregnant women, infants, and patients with AIDS|
|Trypanosomes - African Trypanosomiasis: general|| Trypanosomes are vector-borne flagellated bloodstream pathogens. They are classified as kinetoplastids based on the presence of a unique, darkly staining organelle (the kinetoplast)|
african sleeping sickness is the common name for this disease, the vector is the Tsetse fly
|Trypanosomes - African Trypanosomiasis: species|| Trypanosoma brucei subspecies gambiensis (west african Trypanosomes)|
Trypanosoma brucei subspecies rhodensiensis (east african Trypanosomes)
|Trypanosomes - African Trypanosomiasis: life cycle|| similar for both species|
|Trypanosomes - African Trypanosomiasis: symptoms||Acute phase: a few days to weeks after exposure. an early indication may be ulceration at the bite site called a TRYPANOSOMAL CHANCRE|
Systemic phase: Fever often intermittent but unresponsive to antimalarials, lymph node enlargement, myalgia, and arthralgia are common. Winterbottom's sign an enlargement of posterior cervical lymph nodes is characteristic of West african disease. A more generalized lymphadenopathy is seen with east african disease.
CNS involvement: lethargy, tremors, headaches, wasting syndrome. meningoencephalitis, atazia or personality changes. these become increasingly pronounced extending to coma and death withing a few months for the East african form and a few years for West african
|Trypanosomes - African Trypanosomiasis: diagnosis||Parasites can be found in the blood and lymph during the acute phase. Blood diagnosis is usually by thin or thick films; blood concentration may be helpful. Latertrypanosomes can be seen mostly in CSF; CSF also shows elevated lymphocyte numbers and IgM|
immunological diagnosis is not commonly used. T. brucei has a very complex antigenic variation system that complicates use of ELISA
|Trypanosomes - African Trypanosomiasis: treatment|| Suramin and pentamidine are effective against the bloodstream forms, but not the CNS disease. For chronic disease, melarsoprol is indicated. None of these have high efficacy|
Eflornithine has been recently shown to be effective
|Trypanosomes - American Trypanosomiasis (Chagas' disease): general||Caused by Trypanosoma cruzi, related to T. brucei. The vector is the Reduviid, or "kissing bug". Transmitted when feces from infected bugs contaminate bite sites|
|Trypanosomes - American Trypanosomiasis (Chagas' disease): disease||Endemic to central and south america. infection can be acute, chronic, or asymptomatic and many people in endemic areas show no pathology|
|Trypanosomes - American Trypanosomiasis (Chagas' disease): life cycle||One notable difference from T. brucei - the presence of an "amastigote" phase which penetrates tissues and divides intracellularly bu fission. this stange can be a source of reinfection|
|Trypanosomes - American Trypanosomiasis (Chagas' disease): symptoms||An inflamed lesion (chagoma) may occur at the bite site, though this is not universal. There are 3 stages:|
1. Acute phase - arises 7-20 days post-infection, and includes fever, lymphadenopathy, hepato/splenomegaly, subcutaneous edema and rash. A few may develop acute myocarditis or meningoencephalitis
2. Indeterminant/Asymptomatic chronic phase: - potential symptoms include cardiac enlargement (chronic chagasic cardiomyopathy) with heart enlargement and defects in conduction. Arrythmias, blockages and thromboembolisms can occur. Involvement of the esophagus or colon is also possible
most deaths due to chagas disease occur due to cardiac damage during the chronic phase. Death from acute chagas is rare
|Trypanosomes - American Trypanosomiasis (Chagas' disease): Diagnosis||Microscopy - parasites can be seen in thick or thin blood films, but can be hard to detect, particularly in later stages. Concentration of blood samples may be neccessary.|
Xenodiagnosis, infecting experimentalanimals with blood samples from suspected cases is frequently used.
Immunological diagnosis using enzyme-linked assays or immunofluorescence is becoming more common
Imaging studies to examine heart function and morphology can indicate symptoms, bt are not diagnostic for Chagas
|Trypanosomes - American Trypanosomiasis (Chagas' disease): treatment||Only the acute phase can be treated, but not efficaciously. Benznidazole or nifurtimox are the drugs of choice. Since the acute phase is rarely diagnosed, chemotherapy is not often used|
|Leishmania: general||a flagellated parasite similar to trypanosomes. Occurs worldwide in temperate and tropical climates. The vector is the sandfly and several rodent species are thought to be reservoirs.|
|Leishmania: species||21 different species can infect humans. The major species are L. donovani, L. tropica, L. braziliensis, and L. major|
|Leishmania: life cycle||Primarily intracellular in the human host|
|Cutaneous Leishmaniasis aka oriental sore, Delhi or aleppo boil, uta or chiclero ulcer||Caused by L. major, L. braziliensis, L. meicanii and tropica|
Symptoms begin with a red papule at the bite sites 2 weeks to 2 months after infection. The lesion ulcerates and becomes crusted and hyperpigmented. The ulcers are painless, but may itch intensely
Diagnosis is via microscopic examination of Giemsa-stained scraptins from the lesions. Serological tests are not effective until late in the infection, but senstitive DNA-based tests are becoming available.
Treatment options include sodium stibogluconate, miltefosine or meglumine antimonate. Some reports of success with azole antifunglas exist. Without treatment, lesions will heal in a few months, generally leaving a scar.
| Mucocutaneous leishmaniasis|
|Caused by the L. viannia braziliensis subspecies and closely resembles the|
cutaneous disease. However, it can metastasize to mucosal surfaces,
including the nasopharynx. Severe disease can cause substantial damage
to these tissues, necessitating reconstructive surgery. Diagnosis and
treatment are as for the cutaneous disease; amphotericin B has also been
reported to be effective.
| Visceral Leishmaniasis|
aka Kala-azar or Dumdum fever
|Caused mostly by species related to L. donovani. ~500,000 cases per year, mostly in South Asia, Brazil, and Sudan.Infected bites are usually unapparent. Primary symptoms develop after a few weeks to a year or more and include fever and chills, hepatosplenomegaly, pancytopenia, renal dysfunction, and hypergammaglobulinemia. 80-90% of untreated symptomatic infections progress to death within 2 years. Diagnosis is generally made by detecting parasites in Giemsa stained blood smears or by culturing from blood or aspirates from liver or spleen.|
Serological tests are available for Leishmania antigens; the K39 antigen appears specific to visceral disease. A skin test exists, but patients do not become skin test positive until late in the infection. Treatment options are limited but a new agent, miltefosine, has been used successfully. It is available only via the CDC as an investigational drug, where sodium stibogluconate is the preferred drug. Sodium stibogluconate has significant toxicity issues (particularly in pregnant
women). Other drugs include Amphotericin B and paromomycin.
|Babesia species||Babesiosis is transmitted by tick bites and caused by multiple species of Babesia.|
In the U.S., B. microti is the most common species with the northeastern seaboard as the most endemic area. Voles and other small mammals are reservoirs.
Symptoms arise 1-4 weeks following infection and include malaise, fever and
chills, and weakness. Severe cases may also develop hepatosplenomegaly, anemia and renal failure. Splenectomy significant raises susceptibility and likelihood of severe disease.
Diagnosis is by blood film. Babesia is related to Plasmodium and has a similar
erythrocytic cycle and morphology within red blood cells. Babesia is generally larger and darker, and sometimes forms an x-shape called the Maltese cross. Travel history should be useful to differentiate malaria and
Treatment is often unnecessary as most mild cases resolve spontaneously. A combination of clindamycin and quinine is usually indicated.