PARASITIC DISEASES 1. Toxoplasmosis a) cerebral toxoplasmosis b) extracerebral toxoplasmosis 2. Leishmaniosis a) Cutaneous and mucocutaneous leishmaniosis b) Visceral leishmaniosis 3. Trypanosomiasis a) The American trypanosomiasis b) The African trypanospmiasis West African trypanosomiasis East African trypanosomiasis Svatava Snopková, 4/2020 TOXOPLASMOSIS DEFINITION •An acute or chronic infection caused ¨ by the obligate intracellular protozoan ¨ Toxoplasma gongii ¨ ¨In immunocompetent human •Infection is usually asymptomatic ¤ ¨In immunocompromised patient •symptoms occur, they range from a mild, self-limited ¤ to a fulminant disseminated disease SYMPTOMS ¨Usually involve the following: •Central nervous system, eyes •Skeletal or cardiac muscles •Lymph nodes, Liver, Lungs ¨ ¨Severe diseminated diseases (infections) •In an immunocompromised patients •By the transplcental passage of parasite ¤ from an infected mother to the fetus ¤ (congenital toxoplasmosis) • ¨ toxo 2.jpg Life cycle of toxo - cats are the definitive hosts for T. gondii 1.Oocysts in the cat´s intestine are created •they are excreted in the cat feces 2. Oocysts are ingested by an intermediate host (e.g. a human) 3. Tachyzoites (grough stage) migrate to tissues and can infect any organ toxo.jpg bradyzoit-cysta ve tkáni.jpg Tachyzoites •grouwth stage of toxoplasma •migrate and form cysts in various tissues Epidemiology The seroprevalence of toxo depends on geografic location: US – between 3-67% tropical countries – up to 90% toxo-maso.jpg images (1).jpg ¨Risk for toxoplasmosis ¨- eating undercooked meat ¨Risk – steak tartare Epidemiology ovoce a zelenina.jpg ¤Risk ¤- contaminated vegetables ¨ ¤Ingestion of oocysts ¤from contaminated soil ¨ toxo-kontaminace na podlaze.jpg TOXOPLASMOSIS •Immune responses are able to eliminate most of the tachyzoites when immune systém is sufficient and competent •Therefore 80 – 90% of cases in immunocompetent persons are asymptomatic ¨ •the greatest incidence of toxo is seen among patients with a low CD4 count n <100 cells/mm3 due to immunoderficiency •In areas with high seroprevalence for toxoplasmosis, 25% to 50% of all AIDS patients, who are not receiving antiretroviral therapy, will develop CNS toxoplasmosis Toxo in immunocompromised patients ¨The infection usually involves the CNS ¨Clinical manifestations of cerebral toxoplasmosis infection include the following: •Headache, seizures,weakness •Cranial nerve abnormalities, Visual field defects •Mental status changes •Cerebellar signs •Speech abnormalities, Meningism •Sensory or motor disorders, Disorientation, Hemiparesis •Convulsions, Coma and death n EXTRACEREBRAL TOXO •Less common among patients with immunodeficiency •The prevalence is estimated ¨ at 1,5% to 2,0% •lungs (pneumonitis) •eye (chorioretinitis) •heart ¨Cases of gastrointestinal, liver, skin, or multiorgan involvement also have been reported Extracerebral toxoplasmosis •Involving other organs among patients is rare •Dg. is usually based on biopsy ¨ ¨OCULAR TOXOPLASMOSIS •Is usually based on a suggestive ophthalmoscopic picture •Histopathologic identification of T.gondii ¨ in the eye can establish the diagnosis ¨ Severe,_active_retinochoroiditis_by_Toxoplasma_gondii.jpg retinochoroiditis DIAGNOSIS ¨Is based on: •Compatible clinical picture •Neuroimaging findings •Serology • ¨Definitive diagnosis is based on pathology. Neuroimaging (CT, MRI) ¨The abscesses of cerebral toxoplasmosis are typically •Multiple •Located in the cortex or deep nuclei (thalamus and basal ganglia) •Surrounded by edema •Enhance in a ringlike pattern with contrast 26 toxo absces 2.jpg SEROLOGY •Approx. 20% of patients ¨ have no detectable antibodies •Titer of antibodies does not always rise during infection •Negative serology does not rule out infection •But a rising titer may be of diagnostic significance OTHER LABORATORY METHODS ¨PCR (polymerase chain reaction) ¨ in blood samples suggest that •This modality has limited diagnostic value in cases of cerebral toxoplasmosis ¨ ¨CSF (cerebrospinal fluid) •Is also nonpathognomonic and reveals elevated protein and mild pleocytosis • MAIN TREATMENT ¨The regimen of choice for acute therapy •Pyrimethamine 50 to 75 mg/d ¨ + sulfadiazine 4 to 8 g/d •Leucovorin – coadministtered to prevent the folinic acid deficiency and ameliorate the hematologic toxicity of pyrimethamine •Duration of treatment ¨ – usually for 6 to 8 weeks ALTERNATIVE TREATMENT •Pyrimethamine + clindamycin •Atovaquone (alone) •Atovaquone + pyrimethamine •Clarithromycin •Clarithromycin + pyrimethamine •Azithromycin + pyrimethamine •Trimethoprim-sulfamethoxazole PATIENT FOLLOW-UP ¨After induction treatmen • •Patients with immunodeficiency schould receive lifelong suppression therapy ¨ pyrimethamine 25-50 mg/d ¨ + sulfadiazine 2-4 g/d PROPFYLAXIS FOR HIV+ INDIVIDUALS ¨Toxoplasma-seropositive •With CD4 counts less than 100 cells/mm3 ¨ should receive ¨ prophylaxis against toxoplasmosis ¨ (the doses of TMP/SMX recommended for P. carinii pneumonia appear to be effective) PREVENTION FOR INDIVIDUALS AT RISK •Not to eat raw or undercooked („pink“) meat •Wash fruits and vegetables •Wash hands after contact with raw meat ¨ and after contact with soil •Wash hands after changing a cat litter box PRIMARY PROPHYLAXIS for HIV-positive people conditions pathogen drug CD4+ any + TB exposure M. tuberculosis isoniazid (+pyridoxin), rifampicin, pyrazinamid, ethambutol CD4+ < 200/mm3 Pn. carinii jiroveci co-trimoxazol, pentamidine (aerosol), dapson CD4+ < 150/mm3 + antibody to Toxoplasma positive Toxoplasma gondii co-trimoxazol, dapson, pyrimethamin(+folinat) CONGENITAL TOXOPLASMOSIS ¨Sabin tetrade •classic tetrade of signs 1. 1.Retinochoroiditis 2.Hydrocephalus 3.Convulsions 4.Intracerebral calcifications congenital toxo.jpg CONGENITAL TOXOPLASMOSIS •Clinical findings are variable •There may be no sequelae, or sequelae may develop at various times after birth • •Premature infants may present with CNS or ocular disease • •Full-term infants usually develop milder disease, with hepatosplenomegaly and lyfadenopathy ¨ congenital toxo.jpg Immunocompromised patients ttoxo 2.jpg images.jpg Intimate contact with cats is risk for acquering of toxo for pregnant woman and for immunocompromised patients LEISHMANIASIS Leishmaniasis ¨ ¨Leishmaniasis refers to the spectrum of diseases caused by the protozoa Leishmania spp. ¨ ¨Protozoa are transmitted by a sandfly vector ¨ ¨Clinically, leishmaniasis is divided into: nCutaneous nMucocutaneous nVisceral n Epidemiology - incidence ¨Leishmania infection is among the most common parasitic diseases ¨ ¨Currently, leishmaniasis occurs in four continents ¨Is considered to be endemic in 88 countries ¨72 of which are developing countries ¨ ¨With about 10 million infected persons ¨400 000 new infections every year are referred globally ¨In Europe, infections L. major and L. tropica are increasingly occuring due to travel and immigration Old World cutaneous leishmaniasis Leishmaniasis_cl_ltropica.jpg > 90% of cases • L. tropica ¨and related species ¨ •L. aethiopica ¨The „oriental sore“ occurs throughout tropical and subtropical regions in Asia, China, ¨the Mediterranean, and Africa Leishmaniasis_cl_major.jpg Old Word cutaneous leishmaniasis >90% of cases • L. major • ¨ ¨90% of cutaneous leishmaniasis cases occur ¨in Afghanistan, Iran, Saudi Arabia and Syria. ¨ Leishmaniasis_mucocutaneous.jpg > 90% of cases 90% of mucocutaneous leishmaniasis occur in Bolivia, Brazil and Peru ¨ ¨New World cutaneous and mucocutaneous leishmaniasis •L. brasiliensis •L.chagasi •L. mexicana ¨Widespread ¨in Latin America Leishmaniasis_vl - Kopie.jpg Geographical distribution of visceral leishmaniasis in the Old and New world 90% of all visceral leishmaniasis cases occur in Bangladesh, Nepal, India, Sudan and Brazil Typical risk factors for Leish. ¨ 1.Children and young adults ¨ are the most frequently affected ¨ 2.Leishmaniasis remains an important problem for military personnel operating in endemic regions ¨ 3.Visceral leishmaniosis is more common among immunocompromised persons, such as thous with HIV infection, or after organ transplantation Transmission of Leishmania spp. ¨ ¨In most areas, ¨the Leishmania spp. are inoculated 1.When the sandfly vector attempts to feed ¨ (person is infected when bitten by mosquitoes) 2.Through contact with infected animals 3.Transmission from human to human is possible ¨ phlebotomus.jpg Sand Fly Phlebotomus is vector of Leishmania spp. Leishmania spp. ¨ ¨Have a dimorphic life cycle ¨ nPromastigotes (flagellum) nInfective stage for humans n nAmastigotes (flagellum-free) nThey live in macrophages of the host n •Leishmania spp. occurs in the body of mosquito as promastigotes (flagella form), In animals, which are a reservoir (canids, rodents, cattle) and human - protozoa proliferate as amastigotes (flagellum-free form) PHIL_3400_lores-schema nákazy.jpg 05-pakmed-net-february-17-2013-medical-education-college-student-y3508dikke.jpg Promastigotes of Leishmania spp. - they are the infective stage for hunans ¨The multiplication of promastigotes by longitudinal fission (arrow) that occurs naturally in the gut of sandfly vectors. ¨ ¨They are characterized by a flagellum and a kinetoplast-DNA (arrow) anterior to the nucleus. promsti-L.tropica.jpg promast..jpg Amastigotes of Leishmania spp. - macrophages are filled with amastigotes ¨The organisms reside in macrophages of the host and can be found throughout the body (in various tissue). ¨They measure 1-5 μm long by 1-2 μm wide. ¨ ¨Amastigotes are formed after the macrophage phagocytizes an infective promastigote and are spherical to ovoid amasti.jpg Leish_amasti_TouchPrep_mn.jpg ¨ Cutaneous leishmaniasis ¨The incubation period varies nFrom a few weeks to several months nIn some cases, up to years n ¨Initial lesion nUsually appears 2 to 8 weeks after the sandfly bite ¨A local lesion that starts as a small, erythematous papule ¨At the side where promastigotes are inoculated ¨The papule gradually increases in size slowly to form a typical leishmaniotic ulcer ¨Become crusted, and finaly ulcerates Cutaneous leishmaniosis images (1) - Kopie.jpg ¨The ulcer is usually •shallow and circular •with well-defined, raised, erythematous borders •and a bed of granulation tissue •Round with raised borders and a granulating base •and covered by exudate •May persist for months to years images (4).jpg ¨Leishmaniotic ulcer •Gradually increases in size •May reach a diameter of 2 cm or more •Satellite lesions that fuse with the original ulcer may be present •There is frequently a serous or seropurulent discharge ¨ ¨A wide variety of skin manifestations, ranging from small, dry, crusted lesions to large, deep, mutilating ulcers, which are seen especially in American cutaneous leishmaniasis MC3.jpg Differential diagnosis of cutaneous leishmaniasis ¨ ¨Includes the following: ¨ nFungal infections nLupus vulgaris (skin tuberculosis) nMycobacterial infections of the skin (due to atypical mycobacteria, toberculosis, or leprosis) nNeoplasms nSyphilis n Visceral leishmaniasis („kala-azar“) ¨ ¨Causative agents include: nLeishmania donovani nLeishmania infantum nLeishmania chagasi n ¨Incubation period nVaries and depends on the type of the infection nCan be up to 8 months or more Visceral leishmaniasis („kala-azar“) ¨Is characterised by: nThe abrupt onset of fever nRigors nMalaise nAnd other nonspecific symptoms nAs early as 2 weeks after infection nFever may be intermittent or continuous nSweating with chills accompanies the temperature spikes „Kala-azar“ stažený soubor (2).jpg ¨ ¨As time passes, ¨the spleen and liver become enlarged ¨and fill the whole abdomen „Kala-azar“ diff. dg. kala-azar.jpg ¨Can present as: •Organomegaly •Fever of unclear etiology •Unexplained chronic anemia •Can mimic other infectious diseases (malaria, typhoid fever, brucellosis, etc.) Laboratory ¨In person with visceral leishmaniasis are present: nAnemia nLeukopenia nHypergamaglobulinemia ¨ ¨A definitive diagnosis depends on the demonstration nOf amastigotes in tissue nOr isolation of the organism in culture n Laboratory ¨Culture which may reveal the parasites are the most often: nBone marrow nLiver, spleen nLymph node nBlood (in some cases) ¨The most common diagnostic procedure for dg: „kala-azar“ nBone marrow aspiration nLiver or spleen biopsy n ¨ELISA (enzyme-linked immunosorbent assay) ¨ and the indirect immunofluorescent antibody assay nCan be used but are nondiagnostic procedures n Main treatment ¨ ¨Most commonly used for treatment are: ¨ ¨Pentavalent antimonial compounds nAre most commonly used ¨Amphotericin B nHas been used to treat patients who fail to respond or relapse with antimonials ¨Liposomal amphotericin B ¨Pentamidine nIs a less commonly used alternative Prevention is non-specific ¨ ¨Includes non-specific measures: ¨ ¨Travelers to endemic areas should be educated about the risk of leishmaniasis and the prevention of bites by sandflies ¨ ¨Leishmaniasis remains an important problem for military personnel operating in endemic regions Geografic distribution 1-s2.0-S1471492209001688-gr1 - Kopie.jpg TRYPANOSOMIASIS Trypanosomiasis ¨ ¨A zoonotic protozoal disease ¨ ¨Transmitted to humans ¨ via blood-sucking insect vectors ¨ ¨It produces various ¨ acute and chronic diseases in humans ¨ ¨Is divided into ¤The American trypanosomiasis ¤The African trypanospmiasis American trypanosomiasis ¨ ¨„Chagas´ disease“ ¨ nCausative agent – Trypanosoma cruzi n (related to Leishmania spp.) n n16 to 18 million people are currently infected in Latin America nIs the most serious parasitic disease n in Latin America n and annually infected 700,000 new victims. ¨ ¨ trypanosomiasis american.jpg T. cruzi is present In South America, Central America, Mexico Epidemiology ¨ ¨Trypanosoma cruzi ¤Is present in many species ¤ of wilde and domestic mammals ¤Most cases in humans occur during childhood ¤Disease is much more common in areas of poverty and rural areas Casa Chagas.jpg Transmission ¨ ¨T. cruzi is transmitted: ¨ nVia blood-sucking insects (kissing bugs) n – Triatoma n nVia blood transfusion n nIn utero, and is associated with fetal demise n and fetal abnormalities Main rout of transmission ¨Via blood-sucking insects (kissing bugs) ¨Triatoma ¤Is In the insects´ feces ¤From there, the infectious trypomastigotes enter ¤ the human body through breaks in the skin ¤Trypomastigotes are transformed into amastigotes (in human body) ImageResizer.jpg Cycles_Chagas_810.jpg Incubation ¨ ¨Acute symptoms of Chagas´ disease ¤occur 1 week after contact with the parasite ¤ ¨Chronic symptoms of Chagas´disease ¤take years to decades to cause significant illness Acute Chagas´ disease images.jpg ¨Chgoma ¨A small, indurated papule with erythema and local lymphadenopathy ¨Chagoma occurs at the site of invasion by the organism - ¨Romaňa sign •when contact is made from the organism to the conjunctiva, periocular edema occurs or swelling and closure of the eye ¨ images (1).jpg Acute Chagas´disease ¨ ¨Fevers, constitutional symptoms, lymphadenopathy, and splenomegaly ¨ can occur and usually resolve within weeks ¨ ¨Central nervous system symptoms ¨ and myocarditis are rare complications ¨ at this stage Diagnosis of acute Ch. disease ¨Finding circulating parasites in the blood is essential ¨The organisms are motile ¨Detection occurs 50% of the time of acute symptoms ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ ¨ Trypomastigotes circulating among erythrocytes in blood during acute phase ¨ cd_18fig2 - Kopie.jpg Chronic Chagas´disease megacolon.jpg ¨Develops years after the initial infection ¨ ¨Megaesophagus and dysphagia ¨Aspiration is common ¤and due to aspiration pneumonia is ¤ a common complication ¤ ¨Colonic dysfunction with megacolon occurs ¨ ¨ megacolon (1).jpg ¨ Chronic Chagas´ disease images (2).jpg ¨X ray - development of megaesophagus ¨Development of cardiomyopathy ¨is associated with heart failure ¨and/or arrhytmias, which are often fatal chagas-disease-6.jpg Diagnosis of chronic Ch. disease ¨ ¨Serology is used to detect antibodies to the organism nMany false-positive tests occur ¨ ¨Histologic examination of affected tissue nEssential for diagnoses of chronic disease The histological changes in the affected tissue cd_18fig2.jpg Treatmen of Chagas´disease ¨ ¨Acute or chronic disease: ¨ ¨Nifurtimox orally over a 90 to 120 days ¤Side effects on CNS and GIT ¨Benzimidazol orally for 60 days ¨Pacemaker insertion is warranted nin patients with arrhythmias and heart block ¨Management of congestive heart failure is important ¨Treatment is insuficient African trypanosomiasis tryps_africa.jpg ¨Occurs in 36 countries in sub-Saharan Africa ¨ - Angola, Sudan, the Democratic Republic of Congo, Central African Republic, Chad, Uganda, Tanzania, Malawi, Coast Ivory… ¨500 000 new infection every year is reported ¨Is a zoonotic protozoal disease (as well as American trypanosimiasis) ¨ Blood-sucking fly Tse-tse tse-tse.jpg ¨Genus Glossina ¨Vector ¨It transmits the parasite between reservoir animals (cattle, pigs, wild mammals, antelope…) ¨ Trypomastigotes are transmitted from the salivary glands of the fly to the human during a blood meal. 350px-AfrTryp_LifeCycle.gif African trypanosomiasis ¨African sleeping sickness ¨ ¨West African trypanosomiasis ¨ ¤Causative agent nTrypanososma brucei gambiense nIt is present in tropical rain forests and rural regions in Central and West Africa ¤Outbreak of disease is greatest in the dry seasons ¨ ¨ West African trypanosomiasis chancre.jpg ¨ ¨Chancre ¨ ¨Initial infection ¨ ¨Develops within 1 to 2 weeks following the tsetse fly bite West African trypanosomiasis ¨Several weeks to several months after the initial infection, patients develop fevers associated with lymphadenopathy ¨Massive enlargement of the cervical lymph nodes is seen ¨ Winterbottom´s sign stažený soubor (3).jpg West African trypanosomiasis ¨ ¨Marked constitutional signs occur at this stage: ¨ nPruritus nArthralgias nTransient edema of the face and extremities nErythematous rashes with internal clearing n… West African trypanosomiasis images (5).jpg 006-R6558.jpg ¨ ¨ ¨Several months to years after the initial infections, patients can develop CNS signs nof lethargy, somnolence, personality changes, ataxia, fasciculations, meningoencephalitis… ¤Progressive slow progression to stupor, coma and death. African trypanosomiasis ¨African sleeping sickness ¨ ¨East African trypanosomiasis ¨ ¨Is caused mostly by nTrypanosoma brucei rhodesiense ¨Reservoir of disease is mostly in wild game such as antelope ¨infection in humans is limited ¨ East African trypanosomiasis ¨It follows that of the East African disease nIt is much more acute in nature ¨Symptoms occure a few days following the insect bite ¨Fever and rash develop within weeks after the tse-tse fly bite, as opposed to months, such is in West African trypanosomiasis ¨Lymphadenopathy is less apparent ¨Patients often die of cardiac failure or arrhythmias due to pancarditis ¨CNS signs may occur at the time that fevers are present ¨ Diagnosis of African trypanosomiasis trypanosoma brucei.jpg ¨Organism of Trypanosoma brucei can be seen in: ¨ ¨Fluid from chancres or aspirate from lymph nodes ¨Blood ¨Cerebrospinal fluid Treatment ¨T. brucei gambiense infection ¤without CNS abnormalities nSuramin nPentamidine ¤With or without CNS involvement nEflornithine nTryparsamide ¨T. brucei rhodesiense infection nSuramin, pentamidine, melarsoprol n ¤ ¤ n ¨ ¨ ¨ ¨ ¨ ¨Thank you for your attention…