Master's Programme in Biomedical Sciences (Infectious & Tropical Diseases) 2024-2025 PDF

Master’s programme in Biomedical Sciences “Infectious and Tropical diseases” Prof. G. Caljon / Prof. em. L. Maes 2024 - 2025 Programme 2024-2025 ITD – specific – Master 1 Human parasites, micro-organisms and zoonoses 6 Caljon Sem1 Molecul...

Master’s programme in Biomedical Sciences “Infectious and Tropical diseases” Prof. G. Caljon / Prof. em. L. Maes 2024 - 2025 Programme 2024-2025 ITD – specific – Master 1 Human parasites, micro-organisms and zoonoses 6 Caljon Sem1 Molecular bacteriology of Infectious Diseases 3 Malhotra Sem1 Ecology, epidemiology and control of infectious 6 Leirs Sem1 diseases Integrated Infectious and tropical disease practicals 3 Caljon Sem1 Immunology of tropical infectious diseases 6 Caljon Sem2 Pathogenesis and clinical aspects of tropical infectious 6 Ariën Sem2 diseases Novel vaccine technologies and applications 3 Delputte Sem2 Molecular virology and infections 3 Delputte Sem2 ITD – specific – Master 2 Molecular epidemiology of Infectious Diseases 3 Dujardin Sem1 Health economics and mathematical models of Sem1 3 Beutels infectious diseases Optional courses 2024-2025 Laboratory Animal Science - Rodents 4 Chris Van Ginneken Sem1 B&B and BMW/BMS Laboratory Animal Science - Fish 4 Dries Knapen Sem1 B&B and BMW/BMS Academic English 4 Tommas Ellender Sem 1&2 BMW/BMS Quality Management and GLP 4 Eva Geuens Sem1 BMW/BMS Summer School - Course at foreign 4 Debby Van Dam Sem2 B&B and BMW/BMS institution Massive Open Online Course(s) 4 Debby Van Dam Sem2 B&B and BMW/BMS Entomology of vector-borne diseases 4 Ruth Müller Sem1 BMS Preparedness and rapid response 4 Nicole Berens-Riha Sem1 BMS  Epidemiology Infections Pathology viruses, bacteria, Immunology parasites, fungi Clinic Human parasites, microorganisms and zoonoses Prof. G. Caljon / Prof. L. Maes (UA) Prof. L. Rigouts (ITG) Parasitology + Mycology Visit to ITM Th: 30 h / Pr: 10 h / Seminar: 12 h English book for PAR PowerPoint slides Blackboard: links, “Monsters inside me” Quiz Written examination All subjects presented and discussed during the lectures, seminars and practical exercises Parasitewonders.com  Partim I Parasitology  Part-1 Definitions & Classification Symbiosis ‘living together’ of >2 different species 50% of all animal species are parasitic 100% of animals and plants become parasitized Several parasites per host species Different hosts for one parasite species Parasitology = study of parasitic symbiosis = protozoa, helminths, arthropods Parasite morphology, biology, diagnosis Relation between host and parasite physiology, biochemistry, cell biology Immunology immune mechanisms: humoral, cellular Epidemiology transmission and distribution: host – parasite – (vector) – environment Clinical disease and treatment pharmacology, clinics, pathology Definitions-1 Definitions-2 Life cycle Some parasites have a complex life cycle: - 1 to 4 successive hosts - inclusion of invertebrate and vertebrate hosts - alternation between ‘terrestrial’ and ‘aquatic’ biotopes - horizontal en vertical transmission options Epidemiology Clinical disease + diagnosis Design of preventive and curative control Adaptations For establishment in the host (infection, survival, reproduction) Parasite – host interactions Anti-parasite immunity See course Immunology H.I. C.I. Anti-parasite immunity See course Immunology Pathogenesis Parasite Host Species / Strain Age Infection pressure Nutritional status Localization Immune status Stage Physiological condition 1. Wasting, spoliation (direct, indirect) 2. Formation of toxic products 3. Immunosuppression 4. Allergy and hypersensitivity 5. Mechanical damage (pressure, obstruction, migration) 6. Irritation (skin, organs) and tissue damage Clinical signs Subclinical (most frequent) Clinical (parasite load, specific immunity, host factors) GI anorexia, diarrhea, constipation, vomiting, anemia, e.a. Respiratory anorexia, sneezing, coughing, dyspnea, tachypnea, e.a. Reproduction sterility, abortion, congenital disorders, e.a. CNS anorexia, convulsions, paralyses, e.a. Vascular anorexia, edema, anemia, e.a. Skin itch, erythema, crusts, alopecia, e.a. Liver fever, anorexia, icterus, edema, e.a. Organs specific organ failure Global health situation Prevalence Particularly in tropics en subtropics !!!! In developing countries !!!! Poor living conditions & hygiene Inadequate disease control and treatment Malnourishment Poor health education Regional or ethnic (dietary) habits Climate conditions Immunosuppression (HIV) and opportunistic infections  Worldwide prevalence Deaths Infection (millions infected) (x1000) Current situation Toxoplasmosis Ascariasis 1000-2000 1000 0 20-60 Hookworm disease 800-900 50-90 Amebiasis 200-400 40-100 Schistosomiasis 200-300 200 Malaria 200-300 2000 Filariasis 250 nd Giardiasis 200 0 Enterobiasis 60-100 0 Strongyloidiasis 50-80 0 Trypanosomiasis 15-20 100 Leishmaniasis 1-2 80 General classification Nomenclature: genus with capital, italic or underlined Schistosoma mansoni S. mansoni Plasmodium falciparum P. falciparum  Part-2 Protozoa Protozoa: general characteristics Kingdom: Protista Subkingdom “Protozoa”: >45.000 species described – 10,000 parasites (remaining are free-living) in plants – invertebrates – vertebrates subdivided in 7 phyla (only 3 with human medical importance) Unicellular eukaryote cell structure with specialized intracellular organelles (metabolism, locomotion, etc..) and autonomous cell function Small organisms with short generation time and high reproduction potential Sexual and/or asexual multiplication Protozoa: classification Protozoa: characteristics Protozoa: characteristics Protozoa: classification Intestinal amoebae Intestinal amoebae general morphology 15 - 60μ 10 - 20μ E.histolytica E.gingivalis E.nana I.butschlii Entamoeba histolytica Prevalence - Global distribution - More frequent in tropics and subtropics (→ developing countries) India, Far East, S- and W-Africa, Latin-America - 3rd most important cause of mortality (after malaria and schistosomiasis) >500 million cases – >100.000 deaths per year Epidemiology - Person-to-person transmission → densely populated areas - Infection via orofaecal route → poor hygiene - Uptake of resistant cysts (via food, drinking water, e.a.) - Amoebiasis less important in ‘travellers diarrhoea’ Important: differentiation from the non-pathogenic species (E. dispar) !! Entamoeba histolytica: life cycle Entamoeba histolytica: symptomatology - non-invasive luminal amoebiasis - asymptomatic carrier state → 90% of cases - self-limiting - occasional resurgences - invasive luminal amoebiasis - amoebic dysentery: acute (incubation 1-4w) → chronic - amoebic colitis - amoebic appendicitis, toxic megacolon - amoeboma (dd. colon cancer) - extra-intestinal amoebiasis (→ organ abscess→ mortality) - mainly in liver (sometimes acute peritonitis upon intestinal rupture) - other complications: abscesses in lung, pericardium, brain, skin, e.a Entamoeba histolytica: diagnosis Coprology (for 3 consecutive days) for trophozoites and/or cysts - trophozoites: trichrome- or HE-stain (direct ‘wet smear’) - cysts: iodine-stain after concentration method (flotation) Serology - PCR using species- and strain-specific primers - ELISA for detection of Ab or Ag (diff. E. dispar !!) Imaging (for organ involvement) - RX, CT-scan, MRI-scan, ultrasound Entamoeba histolytica: control Prevention - filtration or boiling of drinking water (chlorine not effective !!) - well-cooked food, washed fruit and vegetables - good sanitation and hygiene !!! Chemotherapy 1. luminal action (for asymptomatic carriers) - iodoquinol, diiodohydroxyquin - paromomycin 2. systemic action - emetine, dehydroemetine (liver + intestinal wall) - chloroquine (liver) 3. luminal + systemic action - nitro-imidazoles (metronidazole, tinidazole, ornidazole) Opportunistic amoebae Trophozoiten: trichome stain Acanthamoeba keratitis Trophozoite: trichome stain Microsporidians Many different genera and species Parasitize wide range of invertebrates and vertebrates and different organs Human infection relatively rare! * clinical symptoms in AIDS patients Balantidium coli In tropical regions throughout the world Associated with malnutrition Relatively rare infection B. suis Mostly asymptomatic cyste trophozoite Balantidiosis = dysentery colitis with haemorrhagic diarrhoea Muco-flagellates 1 Giardia intestinalis (duodenalis, lamblia) Prevalence global distribution - frequent in ‘temperate’ and ‘tropical’ zones common in children (6-10 y) and homosexual males More frequent in malnutrition, immunosuppressive and crowding conditions Epidemiology animals may function as reservoir, vb. beaver, cattle (Ass-B = zoonotic) infection via oro-faecal route (→ poor hygiene) uptake of resistant cysts (via drinking water) – highly infectious ! important cause of ‘travellers’ diarrhoea (→ malabsorption) Clinic mostly asymptomatic – self-limiting ! incubation period: 1-2 weeks → chronic diarrhoea symptoms: no fever, malaise, cramps, nausea, anorexia, steatorrhea Giardia: cycle, morphology trophozoite cyst Giardiasis Diagnosis Coprology on fresh stool samples or intestinal aspirates 10 x 14 - trophozoites: direct ‘wet smear’ - cysts: iodine staining after flotation (zinc-sulphate) Antigen detection - ELISA, IF, PCR 11 - 12 Prevention – filtration of drinking water (chlorine and iodine variable efficacy), boiling 5’ – boiled food, washed fruits and vegetables – good sanitation (hand washing !!) Chemotherapy - metronidazole, (furazolidone, quinacrine, albendazole) Muco-flagellates 2 Limited clinical importance, except T. vaginalis Global distribution Trichomonas vaginalis pH >5 17 x 7  Trichomonas vaginalis Prevalence global distribution (180 million infected) both in males and females → STD frequent in association with HIV, gonorrhoea, Chlamydia Symptoms asymptomatic -- particularly in males (50%) symptomatic -- more in females → vulvo-vaginitis incubation period: 1-2 w. vaginal discharge (mucoid, purulent), itch, burning sensation Diagnosis demonstration of trophozoites in vaginal mucus (‘wet smear’) Treatment metronidazole (topical or systemic treatment !!) - all partners must be treated! Differentiation table Kinetoplastids Parasites of plants, animals and man Presence of kinetoplast (→ kinetosome) Microtubular cytoskeleton Flagel in flagellar pocket Undulating membrane (in some stages) Glycocalyx (surface coat) One important family: Trypanosomatidae (man / animal pathogen) - genus Trypanosoma - genus Leishmania indirect cycle (via insect vector) haemoflagellates different morphological forms Kinetoplastida: morphology Polymorfism Vertebrate Invertebrate Amastigote 1. Nucleus 2. Kinetoplast 3. Kinetosome 4. Axoneme 5. Flagellum 6. Undulerende membraan Promastigote Trypomastigote Epimastigote Trypanosoma species Trypanosomiasis T.brucei Sleeping sickness T.cruzi Chagas disease Sleeping sickness: disease forms Sleeping sickness: cycle Tsetse- belt 15-35 d Sleeping sickness Prevalence - ~ 900 cases/year (1990: 300.000 – mortality 55.000) - sleeping sickness in animals (‘Nagana’) → economic impact Clinical forms East-African or Rhodesian sleeping sickness vector: Glossina morsitans (savannah type) reservoir: wild and domestic animals (= zoonosis !) acute course of infection (incubation 1 month) – no ‘person-to-person’ transmission West-African or Gambian sleeping sickness vector: Glossina palpalis, G. tachinoides (river type) reservoir: man ! chronic course of infection (incubation several months to one year) – ‘person-to-person’ transmission Sleeping sickness Symptoms chancre 1. Local reaction on inoculum site (‘chancre’) → erythema, swelling, lymphadenopathy 2. Systemic spread in the blood = stage-1 → fever, headache, anorexia → lymphadenopathy, tremor, apathy 3. Cerebral spread = encephalitis = stage-2 → headache, apathy, paralysis, tremor, somnolence, coma, mortality Winterbottom’s sign Diagnosis 1. Clinical: apathy, swollen lymph nodes (Winterbottom’s sign), neurological symptoms 2. Parasitological: demonstration of trypanosomes in lymph node aspirate, blood or cerebrospinal fluid 3. Serological: demonstration of Ab (CATT) or Ag Sleeping sickness Treatment 1. Suramin → T. rhodesiense → IV administration, haemo-lymphatic stages, cidal → polysulfonated napthylamine: inhibition of glycolysis 2. Pentamidine → T. gambiense → IV/IM administration, haemo-lymphatic stages, cidal → diamidine: inhibition of dihydrofolate-reductase 3. Melarsoprol → T. rhodesiense → IV administration, ‘late-stage’  toxicity ! → trivalent arsenical : inhibition of glycolysis 4. Eflornithine / DFMO → T. gambiense → IV administration, ‘late-stage’  high dose / combination Nifurtimox (NECT)! → polyamine: inhibition of ornithine-decarboxylase 5. Fexinidazole → T. gambiense → Oral administration, haemo-lymphatic and late stages → Activation by nitroreductase, DNA damage Chagas disease T. cruzi Triatoma “kissing bug” 1 –2w 8-10 2-4wd Triatoma Rhodnius Panstrongylus Pseudocysts - Heart 1.5-4  - CNS - bone marrow Chagas disease Prevalence Latin-America – 20 million infected, 100 million ‘at risk’ – 50.000 deaths per year Reservoir: dog, cat, rodents, e.a. → zoonosis (sylvatic + domestic cycle) Sources of infection: blood-sucking bugs (80%), blood transfusion (5-20%), congenital (2-10%) Symptoms Dermal swelling at biting site (Chagoma) – peri-orbital oedema + conjunctivitis (Romana’s sign) Acute phase: spread via blood to various organs (1-3w): fever, headache, anorexia, liver- en spleen swelling Chronic phase (> 1j): cardiac insufficiency, GI-symptoms (mega- colon, mega-oesophagus) Chagas disease Diagnosis 1. Parasitological → acute stage - demonstration of trypomastigotes in blood smear - xenodiagnosis (vector) or in vitro blood culture 2. Serological → chronic stage 16-20  - demonstration of Ab or Ag (IHA, IF, ELISA) - PCR of kinetoplast DNA 3. Clinical: ECG, radiography, endoscopy Treatment 1. Etiologic: benznidazole or nifurtimox 2. Symptomatic: analgetics, corticosteroids, beta-blockers, … P112 Leishmania: species Leishmania: life cycle Animal reservoir Leishmaniasis Symptoms variable according to Leishmania species VL: splenomegaly, hepatomegaly, lymphadenopathy, lethality CL: superficial skin ulcers with necrosis and crust formation MCL: deep skin ulcers extending into subcutis and cartilage PKDL: skin manifestation after VL relapse Diagnosis Parasitological: demonstration of amastigotes in biopsies (microscopic, xenodiagnosis, in vitro isolation) Serological: Montenegro skin test, LFT (rK39) Treatment pentavalent antimony (Pentostam®, Stibogluconate®) miltefosine amphotericin-B + liposomal formulation paromomycin, pentamidine, allopurinol Leishmaniasis: clinical forms 2 6 1 3 4 5 1.: visceral leishmaniasis by L. donovani // 2.3: Post kala-azar dermatitis (PKDL) // 4, 5: cutaneous leishmaniasis // 6: mucocutaneous leishmaniasis by L. braziliensis Apicomplexa Obligate intracellular parasites Presence of apical complex in ‘invasive’ stages Reproduction: asexual (schizogony, sporogony) and sexual (gametogony with formation of micro- and macrogametes) Complex life cycles (direct or indirect) Apicomplexa: characteristics Apical complex secretory and cytoskeletal structural elements function in host-specificity and cell penetration present in invasive stages microtubular cytoskeleton Coccidia/Eimerida: general characteristics Important genera: Isospora, Cyclospora and Cryptosporidium Obligate intracellular (mostly in gastrointestinal system) High host-specificity, cycle with site-specific endogenous stages Variable pathogenicity (→ infection dose, immune- and nutritional status of the host) Eimeria Isospora Isospora belli Prevalence - global distribution - oro-faecal route of infection - role in traveller’s diarrhoea Symptoms - transient watery diarrhoea, vomiting - HIV: life-threatening ! Diagnosis - demonstration of oocysts in stools Treatment - symptomatic: fluid therapy - trimethoprim-sulfa or pyrimethamin Cyclospora spp. C.cayetanensis Prevalence - global (Central- en South-America, East-Europe, Asia, India, …) - oro-faecal route of infection - role in traveller’s diarrhoea Symptoms - severe watery diarrhoea, nausea, vomiting Diagnosis - demonstration of oocysts in stools (dd. Cryptosporidium) Treatment - symptomatic: fluid therapy - trimethoprim-sulfa of pyrimethamin  Cryptosporidium Less host-specific - zoonosis 8 Cryptosporidium species known Intestinal or respiratory system (brush border) Relevant in ‘immunocompromized’ conditions (HIV, cancer, transplant, diabetes,..) Cryptosporidiosis Prevalence - global – in man and animals - oro-faecal route of infection - Mostly subclinical Symptoms pp= 3-4 d - Profuse watery diarrhoea, nausea, vomiting, (fever) Diagnosis - Demonstration of oocysts in stools (acid-fast staining) - IFA, ELISA, PCR Treatment - symptomatic: fluid therapy - no drugs available ! Sarcocystidae Indirect cycle → intestinal + tissue stages Asexual multiplication in vertebrate intermediate host Sexual multiplication in carnivorous final host Isospora-type of oocyst 2 genera infect man: Toxoplasma, Sarcocystis Toxoplasma gondii 12x10 tachyzoite Rosette bradyzoite Zoitocyst = tissue cyst Toxoplasmosis Prevalence - global distribution - 13% of world population infected - age-related: 20-30j: 50% - total 70% - infection during pregnancy: 6.7 ‰ -- transmission: 30-40% Pathology - caused by multiplication of tachyzoites in ‘susceptible’ tissues - more severe course of infection in conditions of immunosuppression Symptoms - + acute chronic congenital abnormalities retinitis, blindness Fetus Adult Resorption / abortion fever, muscle pain, headache congenital abnormalities lymph node swelling Chorioretinitis / blindness myocarditis / encephalitis Mental retardation encephalitis Toxoplasmosis: prevention and control Determined by the immune ELISA status of the pregnant woman IgM/IgG Dietary habits geen ‘rood’ vlees (bakken, pekelen) diepvries vlees (-15°C, 3d) Hygiene avoid contact with cat faeces wash vegetables and fruit wear gloves when gardening Cat ?? no feeding of raw meat sero-status ?? PCR Toxoplasma Ag Malaria Prevalence Predominantly but not exclusively in tropics and subtropics Most important tropical disease in man !! - in 90 countries (40% of world population) - 500 million infections. 1-2 million deaths per year (2019: 409K deaths) Plasmodium life cycle SPP’s LPP’s 10d Hypnozoite P.vivax P.ovale Plasmodium spp. characteristics Haemozoin (pigment) formation Plasmodium spp. morphology 2nd intermediate host) // furcocercaria in Schistosoma: active skin penetration 5 6 Standard life cycle Developmental stages Digenea classification Location venous system intestinal liver lung liver intestinal Several other species infect man and animals → zoonoses Visceral flukes Fasciola hepatica 2-3 d Lymnea sp. >6w PP= 10-12w Biotope 3-4w & testes >10°C well developed vitellaria thin-walled eggs Fasciola hepatica Prevalence Global distribution – 2 million cases – more in countries with intensive sheep- and cattle farming - economically important ! Man as accidental host (consumption of watercress) F.hepatica: in temperate zones – [F.gigantica: in (sub)tropics] Cinic Mostly subclinical (>50%) Symptoms related to infection dose (acute – chronic) fever, colic, weight loss, anemia, liver swelling exceptionally gall colic and icterus caused by cholangitis halzoun: consumption of raw infected liver Diagnosis Parasitological: demonstration of eggs in the stools Serological: demonstration of Ab (ELISA) Treatment Triclabendazole Clonorchis sinensis Same cycle O. felineus O. viverrini Migration PP = 1m low pathogenicity Clonorchis sinensis Prevalence South-East Asia (20 million cases) In endemic aeras: 10-80% infection (animal reservoir !) Source of infection: consumption of raw fish Clinic Generally subclinical Symptoms dependent on infection dose acute: fever, eosinophilia, skin rash, anorexia, (diarrhea) chronic: purulent cholangitis (obstruction) and bile duct carcinoma Diagnosis Parasitological: demonstration of eggs in stools Serological: demonstration of Ab or Ag (ELISA), skin test Treatment Praziquantel, bithionol Fasciolopsis buski PP = 1m 1cm Heterophyes, Metagonimus Distribution: Middle- and Far-East 3-4w PP = 1w 2-3w Paragonimus westermani + ectopy !! 3-4w 2-3w PP = 2-3m Schistosoma characteristics S.japonicum - separate sexes (dioecious) - female: roundworm-like, longer than male - male: gynaecoforal canal (copulation), small suckers - parasites of venous system - typical morphology of the eggs (spine, no operculum) - pathology caused by the eggs (inflammatory reaction) - indirect cycle via freshwater snail 1. infection by furcocercaria (skin penetration) 2. via systemic circulation to the lungs 3. to portal venous system (copulatie) 4. further migration to organ bloodvessels 5. eggs migrate through the blood vessel wall 6. excretion (faeces, urine) Schistosoma cycle Schistosoma species Schistosomiasis or bilharziosis 200 – 250 million cases worldwide – worm survival: 10-15y in endemic areas: prevalence up to 80% pathology by (occlusive) fibrotic inflammatory reactions slow development of (partial) protective immunity Schistosomiasis in man Most infections remain subclinical Severe forms (5-10%) dependent of infection dose 1. Cercaria dermatitis - itch, local edema for about 4 days 2. Acute schistosomiasis “Katayama fever” migration phase (1-2 m): fever, nausea, vomiting, cough, lymphadenopathy, myocarditis patent phase (>2m – 1y): haematuria, haemorrhagic diarrhoea 3. Chronic granulomatosis Organ failure (liver, kidney, bladder, intestines) by the extensive fibrotic granuloma formation (also in ectopic places (lungs, CNS) with necrosis and ulceration), – hepatosplenomegaly Schistosomiasis in man 200 million infected 20-200K deaths/year bladder intestine liver (V.porta) Schistosoma haematobium Urinary schistosomiasis PP= 10-12w Katayama fever mostly absent Frequent and painful micturition, haematuria Bladder ulcer, cystitis, association with development of bladder cancer Schistosoma mansoni Intestinal schistosomiasis PP= 7-8w pronounced Katayama fever lesions in large intestine and rectum (abscesses, ulcers, polyps,..) haematemesis, melaena, diarrhoea ectopic lesions: liver, brain, spine, lungs Schistosoma japonicum Oriental schistosomiasis PP= 5-6w most severe form of Katayama fever: myocarditis, acute mortality lesions particularly in small intestine and liver haematemesis, melaena, epilepsy caused by cerebral granuloma’s Schistosoma spp.: control Schistosomiasis in man Diagnosis demonstration of eggs in urine, stools, tissue biopsy haematology: eosinofilia, increase of liver enzymes serology: IgM/IgG Ab (ELISA with ‘soluble egg antigen’) Prevention education: avoid contact with freshwater, sanitation and hygiene Snail control: molluscicides, biological control Treatment praziquantel, (oxamniquine, metrifonate, artemisinins); → community-based treatment programmes Trichobilharzia, Ornithobilharzia Swimmers itch: urticaria, papular dermatitis  Deel-4 Cestoda (tapeworms) Eucestoda General characteristics parasitic (3400 species) in vertebrates – global distribution as adult always in the gastrointestinal system (small intestine) at least 2 hosts (indirect cycle) characteristic larva: hexacanth (3 x 2 hooks) no free-living stages, all stages are endoparasites high specificity for vertebrate final host, low specificity for intermediate hosts ( trematodes) Variable size: few mm to several meters dorso-ventrally flattened segmented ( trematodes) coelome and intestinal system absent Morphology excretion system based on flame cells hermaphrodite (repeating per segment) scolex – neck – strobila (proglottids) General structure bothriate species-specific (identification) Presence of attachment organs: rostrum, acetabula (suckers), bothria, hooks Organs and en structures Proglottid structure Morphology of mature & gravid proglottid species-specific (→ identification) Excretion duct Uterus (longitudinal) Vas deferens Nerve (lateral) Genital porus Testis Ootype Vagina Tegument Ovarium Mehlis’ gland Vitellaria Excretion duct (transversal) Comparative morphology Diphylolobothrium Taenia Dipylidium General classification Class: Cestoda Subclass: 1. Cestodaria: not segmented, in fish and reptiles 2. Eucestoda: segmented, in man and animals Pseudophillidea cycle stages Environment Intestine Extra-intestinal Egg Oncosphere Metacestode-1 Metacestode-2 cercomeer 1st intermediate 2nd intermediate copepod fish Egg sparganum Cyclophyllidea cycle forms Environment Intestine Extra-intestinal Egg Oncosphere Metacestode-1 (bladder worm) Egg cysticercoid cysticerc coenurus hydatid Cyclophyllidea species Diphyllobothrium latum 2-3w cyclops 18-20d >10m PP= 4w 67 x 46 Diphyllobothrium latum Prevalence Global distribution → sub-arctic zones (Scandinavia, Russia, N-America, Japan) Endemic in areas where freshwater fish is consumed or processed raw Clinic Generally asymptomatic Non-specific symptoms: anorexia, weight loss, tiredness Megaloblastic anaemia by lack of Vit B12 in predisposed people Diagnosis Demonstration of segments or eggs (with operculum !) in stools Prevention boiling (56°C for 5’) or freezing (-18°C for 24h) Treatment Niclosamide, praziquantel Spirometra ‘sparganosis’ Infection Contaminated drinking water, raw freshwater fish, traditional wound treatment Clinic Local swelling, oedema (in eye: conjunctivitis) Control Prevention: boiling of food, filtration of drinking water Therapy: chirurgical removal Taenia saginata / solium cycle “beef tapeworm” “pork tapeworm” 10w 2-3 m T. solium C. cellulosae C. bovis 1-4 m T.solium PP= 2-3 m 35 x 40 T.saginata Taenia saginata / solium characteristics T. solium: proglotids excreted in short chains T. saginata: proglotids individually excreted, moving ! NCC C. racemosae C.bovis Taeniasis Prevalence worldwide: endemic in Africa, Asia, China, C- and S-America, Mexico (Europe: Spain, Portugal, East-European countries) 50 million people infected – 50,000 deaths/year due to NCC Clinic taeniasis: mostly asymptomatic, sometimes anorexia, weight loss, tiredness cysticercosis: dependent on organ involvement (sc, muscle, eye, heart) neurocysticercosis (NCC): convulsions, increased intracranial pressure, psychiatric disorders Diagnosis Demonstration of segments (or eggs) in stools – segment differentiation ! NCC: EITB on serum, CF on CSF, ELISA on CSF, radiography, CAT, MRI Control Prevention: Taeniasis: meat quality inspection, freezing/cooking NCC: hygiene, boiling of drinking water, washing of vegetables, fruit Treatment (!) praziquantel, albendazole (+ glucocorticoids in NCC) surgical removal of cysticercs Hymenolepis nana “dwarf tapeworm” Vampyrolepis nana H.nana fraterna H.nana nana 5-6 d 1-4 cm vlooien, kevers Hymenolepis diminuta “rat tapeworm” Tenebrio Tribolium Man is 2-3w accidental host! 20-90 cm PP= 17-25d Dipylidium caninum 3-4 w Human is Ctenocephalides spp. accidental Trichodectes canis host pp= 2 – 3 w Proglottid 25 - 50 cm Egg-capsule Echinococcus granulosus cycle E. multilocularis PP= 6-7 w P= 5m Echinococcus spp. characteristics Adulten in darm 2-8 mm 33 x 28 Species: E.granulosus, E.multilocularis, E.vogeli, E.oligarthrus Hydatidosis E. granulosus: cyst form (CE) E. multilocularis: alveolar form (AE) Hydatidosis Prevalence: global Mediterranean, S-America, S-Africa, Australia, New-Zeeland, Balkan, e.a. Domestic cycle versus sylvatic cycle / AE less frequent than CE Clinic: dependent on the location of the hydatid (90% in liver and lung) Pressure lesions: obstruction of bile ducts, bronchi, increase of intracranial pressure Secondary hydatidosis with anaphylaxis (high mortality) Diagnosis Serology: IHA, ELISA, ID Imaging: Rx, ultrasound, CT-scan, (MRI) Control Prevention: hygiene, diet / deworming of dogs Treatment CE: chirurgical, PAIR-technique AE: (chirurgical) + suppressive medication (ABZ, MBZ)  Part-5 Nematodes (roundworms) General characteristics free-living (small) or parasitic (larger) direct or indirect cycle in plants and animals (invertebrates, vertebrates) >100,000 species in vertebrates (256 families, 2271 genera) most frequent in digestive-, respiratory- and circulation system Morphology Round, elongated with pointed endings Bilateral symmetrical, non-segmented Separated sexes (dimorphic: F > M) Complete digestive system No respiratory or circulatory system Pseudocoelome (‘body cavity’) Body wall = cuticula General morphology Stomodeum Proctodeum External structures 3x2 Internal structures General characteristics Species determination - host - location in the host Worm: size, length Cuticula: alae, papillae, amphids Buccal cavity: size, form, lips – cutting blades - teeth Oesophagus: form, length, bulbus Bursa copulatrix: spicules, gubernaculum Other: excretion pore, vulva flap, papillae, striation,.. Standard life cycle free-living = direct cycle intermediate host = indirect cycle ‘Hatching’ - temperature - humidity Premature - larval factors adult ‘Molting’ Specific host - Synthesis of cuticula factors - exsheatment Infectious larva: free or still in egg Standard life cycle L3 larva is non-feeding Escheatment: host- and site-specific CO2 temp enzymes Arrested development L3-L4 - seasonal - immune status - overcrowding Typical morphology of nematode eggs 3 (4) layers: vitelline – chitin – lipid – (mucopolysaccharide) Embryonation: aerobe process ! Soil-transmitted helminth infections Classification Remark free infectious L3 – cutaneous infection infectious L3 in intermediate host – passive infection or via inoculation shortened exogenous phase – L1 or L2 infectious – in egg Infectious L1 – direct infection or via intermediate host Strongyloides stercoralis “threadworm” Rhabditidae: very small (2 - 5 mm) threadlike worms [M < F] Homogonous (direct) and heterogonous (indirect) cycle Protandrogone female worms (parasitic) Global distribution (mainly tropics, subtropics) Clinical in young and weakened individuals Auto-infection in man (chronic course of infection – HIV !) S. stercoralis cycle PP= 3-4w 50 x 30  Strongyloidiasis Prevalence Endemic in tropics and subtropics – 100 million people infected Associated with situations of poor hygiene and sanitation Clinic Cutaneous: dermal swelling with intense itch (feet and hands) ‘larva currens’ Respiratory: cough, bronchitis, painful chest Intestinal: nausea, vomiting, diarrhoea Severe to fatal outcome: hyperinfection syndrome and disseminated strongyloidiasis Diagnosis Coprology: demonstration of larvae (eggs) in stools (diff.: hookworms) Serology: IF, ELISA for Ab (persistent >1y after cure) Control Prevention: sanitation, avoid contact with contaminated soil Treatment: ABZ, IVM Hookworms haematophagous: buccal capsule with cutting teeth and plates M: pronounced bursa – 2 spicules oviparous – thin-walled eggs (morula at excretion) ‘sheated’ infective L3 larvae –cutaneous infection or via oral uptake / extra-intestinal larval A.caninum N.americanus migration >20°C >15°C Hookworms: cycle A. braziliense – dog A. caninum – dog CLM B. phlebotomum - cattle L3 sheated Oral infection 1w PP= 5-6 w 1-2 d 20-30ºC humid conditions protected from sunlight Ancylostomiasis Prevalence Global distribution (1 billion infected) Clinic dependent on infection pressure Invasion → skin lesions: vesicles, erythema, severe itch (ground itch) Migration → respiratory symptoms: cough, chest pain Intestinal → enteritis: diarrhoea, nausea, vomiting, anorexia, e.a. → anaemia, tiredness, dyspnoea Diagnosis Coprology: demonstration of eggs in stools (larve culture for differentiation) CLM: linear red papular lesions, itch / sec. bacterial infections Control Sanitation, avoid contact with contaminated soil, chemotherapy (ABZ, IVM, PYR)  zoonosis Cutane larva Migrans (CLM) Ascaridida “roundworms” Large worms – host-specific – in small intestine Zoonotic infections possible = larva migrans Direct cycle: resistant thick-walled eggs (with L2 !) Morphology: mouth with 3 lips, no capsule M: no bursa, 2 equal spicules Ascaris lumbricoides L2 2-4w PP= 3m >16ºC PP= 60 d 45 x 62 Ascaris lumbricoides Prevalence Most prevalent (1.4 billion infected) Endemic in developing countries Infection via food and oro-faecal transmission Clinic dependent on infection pressure Mostly asymptomatic (growth retardation) Respiratory: pneumonitis with coughing, fever and dyspnoea Intestinal: abdominal discomfort, intestinal obstruction with colic's Erratic migration: gall duct (colic's, cholangitis), pancreas duct Diagnosis Coprology: demonstration of eggs in stools Control Prevention: sanitation (avoid oro-faecal transmission), health education Treatment: (community-based): ABZ, MBZ, PYR  VLM Visceral larva migrans OLM L2 PP= 19 d L3 Anisakiasis Anisakis simplex “herring worm disease” allergic enteritits surgical removal  Enterobius vermicularis “pinworm” PP= 3 w very low pathogenicity 10 mm host-specific male: 1 spicule female: long pointed tail 3 mm Retro- infectio n L2 50 x 25 Enterobiasis Prevalence Very wide distribution (350-500 million infected worldwide) More in temperate areas – frequent in young children Retro-infection, auto-infection, inhalation and faecal-oral contact Clinic Mostly without symptoms Occasionally: itch, irritation in anal and perineal region, sleeplessness Rarely: ectopic location in vagina, oviduct, peritoneal cavity Diagnosis Demonstration of worms and/or eggs (Scotch-tape test) in anal area Control Prevention: personal hygiene, health education Chemotherapy: ABZ, MBZ, PYR (repeat within 2-3w ! ) – all members of the household Class Adenophorea 1. Trichuridae 70 species - direct cycle – Ad in large intestine mucosa 2. Capillariae 300 species (complex classification) - directe or indirecte cycle – Ad in various organs 3. Trichinellidae 7 species - Ad in small intestine – larvae in muscle Trichuris trichiura L1 >3w T.trichiura Mooth without lips Large oesophagus with stichocytes (stichosoom) 1 spicule with sheat survival: 1-3 year 50 x 22 Trichuris trichiura “whipworm” Prevalence global distribution (800 million cases) mainly in tropics, poor sanitation conditions most frequent in young children mixed infections with roundworms and hookworms Clinic infections day 10): paralysis, myositis, eosinofilia, respiratory problems, e.a. 3. Recovery phase (> 1 month): encystation of the larvae - calcification Larvae inactivated by freezing -15°C for 20 days - except T. nativa by cooking >77 °C Filarial worms Wuchereria bancrofti Bancroftian filariosis 100 million infected nocturnal 4 cm 10 cm 1-3w Aedes, Culex, PP = >6m Mansonia, Anopheles “elephantiasis” Brugia malayi Malayan lymphatic filariosis nocturnal 2 cm 5 cm 20 million infected Aedes, Culex, 2w Mansonia Lymphatic filariasis Clinic → due to host reaction against Mif and Maf → structural and functional abnormalities of the lymph vessels → symptoms only after repeated (years) and intense exposure (→ endemic areas) Incubation: no symptoms – slight fever (lymphangitis) Acute phase: fever, lymphadenopathy (ADL: adenolymphangitis) Chronic phase (obstruction of lymph ducts): hydrocoele, severe swelling of extremities (elephantiasis: arms, legs, scrotum, vulva, breasts), TPR (tropical pulmonary eosinophilia) with cough, dyspnoea, body weight loss Diagnosis demonstration + identification of Mif’s in peripheral blood (but periodicity !!) // demonstration of filaria antigen in peripheral blood // PCR Control Prevention: vector control combined with ‘community treatment’ Therapy: DEC (+) IVM, (ABZ) Onchocerca volvulus Cutaneous filariosis no periodicity 20 million infected 120 million at risk 2w 30 cm 50 cm Cutaneous nodule PP = >1y Rivier blindness Zoonotic species: O. gutturosa, O. cervicalis Onchocerciasis Clinic Onchocercomata: SC-nodules in pelvis area (Africa) or head (Lat. America) Onchodermatitis: caused by Mif’s in skin (immunological damage): 1/ severe itch, scratch lesions, ulcer formation due to sec. bacterial infections 2/ alteration of skin quality and pigmentation: crust formation, oedema, papules, loss of elasticity, scar formation, hypertrophy River blindness: inflammatory reaction on Mif’s in cornea, sclera, iris, retina and development of progressive blindness (after 7-9 year) Diagnosis Demonstration of Mif in skin ‘snips’ Presence of adult worms in skin nodules Control Ivermectine (IVM): 1-2x/year against Mif -- no effect on Maf Di-ethyl-carbamazine (DEC): but side-effects (Mazotti reactie) Suramin: dangerous side-effects !! Tetracyclins → Wolbachia Loa loa diurnaal 3 cm 7 cm 20 million infected PP = >1j 2w Transient migratory angioedema Calabar swellings Other symptoms: local lymphadenitis fever, local oedema Orchitis, e.a. Dracunculus medinensis Clinic Painful skin blister, occasional allergy (fever, sneezing, itch, oedema, …) Frequent secondary infections – ulcer formation Chronic painful swelling by encapsulation and calcification Diagnosis Demonstration of female worm in skin blister Treatment Extraction (stick-method) or excision In combination with metronidazole administration Dracunculus medinensis Guinea (fire) worm 2-3 w 2 cm zoetwater ! 1m PP = >1j  Part 6 Arthropoda a. Arachnida (spiders) b. Insecta (insects) Morphological division antennae Importance of arthropods 85% >1 million species – global distribution Parasitic for plants, animals and man Significant medical and economical importance Arthropoda: role as disease vector Pathogens Transmission Viruses Mechanical Ricketsia Biological Bacteria - propagative Protozoa - cyclo-propagative Nematodes - cyclo-developmental Cestodes - transovarial General morphology 1. Bilateral symmetrical 2. Presence of coelome, complete digestive system 3. Segmented body parts: head – thorax – abdomen 4. Articulating legs (arthro-podos) 5. Separated sexes 6. Chitin exoskelet: sclerites (plates) → ecdysis - dorsal: tergum - ventral: sternum - lateral: pleuron General structure Acari: mites and ticks Standard life cycle Dust mites Ixodidae (hard ticks): 1 nymph stage Mange mites capitulum (gnathosoma) genital opening stigmata Argasidae soft ticks [ E - L – N1 → N5 – Ad ] Argas reflexus Morphology Biology Leather-like integument (wrinkled) several nymph stages (generally 5) No dorsal shield nocturnal blood suckers (not permanent on host) Capitulum dorsally not visible Long survival without feeding (months !) Claws (no pulvillus, except in larvae) Multiple gonotrophic cycles weak sex dimorphism Vectors of ‘tick-borne relapsing fever’ [zoonosis]  Ixodidae hard ticks [ E - L - N – Ad ] Morphology Hard chitin shield [full cover in males] Mouth parts well developed and dorsally visible Sometimes pair of eyes dorsolateral on scutum Tarsus with 2 claws and pulvillus Pronounced sexual dimorphism (M < F) Dermacentor Sometimes coloured scutum (‘ornate’ ticks) Ixodidae cycle 3-host tick tropics 1 year subtropics 20-50d 2 year temperate 3 year ‘spring feeders’ Ixodidae morphology I. ricinus (3 hosts) Lyme TBE nymph larva Ixodidae as disease vector in Europe Lyme disease Cause Borrelia burgdorferi (spirochete) Reservoir rodents, wild animals Vector ticks (Ixodes spp.) – infection after 2 days !!! Symptoms acute → chronic 1. Erythema migrans [within 1-2w] + flu-like symptoms 2. Arthritis (painful knee) [after a couple of months] 3. Nervous symptoms (meningitis, paralyses) [after months or years] 4. Heart problems (arrhythmia’s) [after a couple of weeks] Diagnosis = difficult anamnesis !!!! (tick bite, summer months) Erythema migrans (absent in 25% of cases) serology: ELISA (pos after several weeks) Treatment = antibiotics therapy for 2-4 w PO: doxycyclin, amoxicillin, (cefuroxime)(macrolides) IV: penicillin, ceftriaxone Prevention = removal of the tick (2500 species – mostly in mammals – poor host-specificity !! laterally flattened, 3rd pair of legs = long (jumping), no wings sexual dimorphism, holometabole, temporary ectoparasites, blood suckers presence of ctenidia on the head (genal ctenidium) and 1st thoracal tergite (pronotal ctenidium) – backwards-directed setae on body – pygidium (sensilium) F M Fleas cycle E – L1 – L2 – L3 – P – Ad 1w to >1 year >13°C 50-90% RH 1- 3 w Eggs deposited on host – fall off the body Duration of cycle strongly dependent of environmental factors: hatch: 1-3w / 2 moulds (>2w interval) / pupation (1w – 1y) / adult (can survive 1 year without feeding) Fleas species Medical relevance Biting lesions with secondary infections (dermatitis), Allergy: eczema, asthma Intermediate hosts for tapeworm species Vector for diseases Diptera: general characteristics more than 120 000 species described 1 pair of membranous, functional wings on mesothorax 1 pair of halters on metathorax pro-, meso- and metathorax mostly fused mouthparts adapted to suck/pierce (proboscis) complete metamorphosis (holometabole) sex dimorphism / F: oviparous, larviparous of puppiparous 2 subordes (Nematocera and Brachycera) Medical relevance parasitic as larva or as adult ‘nuissance’ pests: irritation, blood loss most important vectors for pathogens ! (bacteria, viruses, protozoa, e.a.) Diptera general characteristics Culicidae mosquito’s [ E – L1 – L2 – L3 – L4 – P – Ad ] - global, particularly in warmer areas - long antennae – F: without hairs / M: plumy - fine scaled wings – long fine legs - M feeds on nectar, F feeds on blood // oviparous - holometabole // cycle in water Sub-families 1. Culicinae: Culex, Aedes, (Mansonia, Theobaldia) 2. Anophelinae: Anopheles Culicidae: subdivision in subfamilies Anopheles Culex / Aedes Mansonia Aedes: individual eggs Culex – Aedes cycle 0.5 – 1 m 1w Ei L1 1w L2 2w L3 L4 Culicinae as disease vectors 1. Malaria - Plasmodium spp. 2. Filaria - Wuchereria, Brugia, Dirofilaria Anopheles 3. ARBO-viruses - Hemorrhagic fever * yellow fever * dengue fever - Encephalitis Aedes * Japanese B encephalitis, e.a. Blackflies Buffalo gnats Simulium global - problem in warm areas – associated with water small, robust, dark colour, hunchback, hairless 4-12d painful bite M (holoptic) feeds on nectar (reduced mouth parts) F (dichoptic) feeds on nectar and Larva on blood (adapted mouth parts) weaves a 6 moults cocoon Vector for Onchocerca Cause of simulio-toxicosis Sand flies mothflies Psychodidae 1.5 – 2.5 mm 2 sub-families: Psychodinae, Phlebotominae 3 haematophagous genera: Lutzomyia, Phlebotomus, Sergentomyia Brown colour, haired – long antennas Wings in V-position >10d Feeding: M: nectar; F: nectar, blood Nocturnal feeding – painful bite Vector Leishmania Sand fly fever (Bunyovirus) 4 larval instars Carrion’s disease (Bartonella sp) 2-10w Tse-tse flies Glossina Tse-tse fly hatchet cell Glossina cycle [ E - L1 – L2 - L3 – P – Ad ] every 10-12 d 10-tal larvae per fly >35d Tabanids [ E – L1-7 – P – Ad ] - global distribution, robust, good flyers, sometimes strongly coloured - 2 important genera: Tabanus “horse flies” en Chrysops “deer flies” - short antennae, piercing mouth parts, painful bite - M: feeds on nectar – F: also feeds on blood: “pool-feeders” - mechanical transmission of bacteria (anthrax, tularemia), cysts (Giardia, Entamoeba, Cryptosporidium) – vector transmission of Loa loa “horse fly” “deer fly” hexagonal cell Flies - maggots: acephale – hook-like ‘mouth parts’ - puparium (hard) - cycloraphe – circular lid - proboscis: sucking vs piercing - habitat: offal – dung – cadavers – meat [E – L1 – L2 – L3 – P – Ad] piercing sponging - nuissance - mechanical vector: typhus, cholera, dysenterie, e.a. - myiases by larvae * facultative: blowflies * obligate: screwworm Flies Sarcophaga sp. Calliphora sp. Lucilia sp. Chrysomya sp. Cochliomya sp.  Addenda Antiparasitic drugs Overview of zoonoses Parasitological diagnosis Anthelmintics The “ideal” anthelmintic Broad spectrum Activity against mature and immature forms Easy to administer Inhibit re-infection over extended period of time Wide safety margin Compatible with other drugs Not prone for rapid resistance induction Cost effective PK - PD Mode-of-action Pharmacokinetics (PK) Pharmacodynamics (PD) delivery Absorption speed of action Distribution spectrum Metabolism residual effect Excretion withdrawal, (eco-impact) Resistance Mode-of-action Specificity Drug Class Parasite survival Antiparasitic drug Energy supply Protozoa Neuromuscular coordination Helminths Cell integrity - homeostasis Arthropods Anthelmintics: mode-of-action Effect on cell integrity 1. Inhibitors of tubulin polymerization 2. Uncoupling of oxidative phosphorylation 3. Inhibition of glycolysis Effect on neuromuscular coordination 1. Cholinesterase inhibitors 2. Cholinergic agonists 3. Muscle hyperpolarization 4. Potentiating of inhibitory transmitters Effect on cell integrity 1. Inhibitors of tubulin polymerisation Nematocidal > Cestocidal* >> Trematocidal* * Primary: binding affinity for β-tubulin Secondary: inhibition of cellular transport and energy metabolism Thiabendazole - cambendazole Mebendazole - Flubendazole – Parbendazole - Oxibendazole Netobimin - Albendazole* - Albendazole-sulfoxide Febantel - Fenbendazole – Oxfendazole Triclabendazole * * Effect on cell integrity 2. Uncoupling of oxidative phosphorilation Trematocidal > Nematocidal >> Cestocidal* Primary: H+ leakage through inner mitochondrial membrane Secondary: inhibition of energy metabolism Substituted phenols: disophenol, nitroxynil, niclofolan, … Salicylanilides: oxyclozanide, rafoxanide, --------- niclosamide* 3. Inhibition of glycolysis Trematocidal Primary: inhibition of energy metabolism chlorsulon Effect on neuromuscular coordination = feeding, migration, attachment Neuronal control: ganglion → neuron → synapse → muscle Excitatory (depolarizing) → spastic paralysis OP’s, imidazothiazoles, tetrahydropyrines Inhibitory (polarizing) → flaccid paralysis Piperazines, macrocyclic lactones Neuromuscular coordination 1. Cholinergic inhibitors Nematocidal // Insecticidal* Acetylcholine-esterase inhibitors * OP’s: trichlorfon, dichlorvos, coumaphos, haloxon, …. Ganglion stimulants Imidazothiazoles: levamisole Neuromuscular junction stimulants Tetrahydropyrines: morantel, pyrantel Neuromuscular coordination 2. Cholinergic stimulants Nematocidal // Insecticidal* Hyperpolarisation of nerve membrane - piperazine - di-ethyl-carbamazine (DEC) Binding to glutamate-gated chloride channel receptors Macrocyclic lactones * - Avermectins: ivermectin, doramectin, selamectin, eprinomectin,.. - Milbemycins: milbemycin-oxime, moxidectin Other anthelmintics 1. Destruction of tegument Cestocidal // Trematocidal - Praziquantel, Epsiprantel interaction with intracellular Ca2+ concentration [+ spastic paralysis of the suckers] Antiprotozoals Narrow-spectrum, group-specific drugs 1. Amoeba and flagellates (intestinal) 2. Haemoflagellates Trypanosomes Leishmania 3. Intestinal coccidia Isospora, Toxoplasma 4. Haemosporidia Plasmodium Babesia  Amoeba Entamoeba Antiprotozoals Flagellates Trichomonas Non-systemic drugs Quinoleine derivatives Diloxanide furoate Tetracyclins Systemic drugs Emetine derivatives Chloroquine Nitro-imidazoles: metronidazole, tinidazole, carnidazole, … Antiprotozoals Haemoflagellates African trypanosomes (sleeping sickness) Naphtylamines suramin Diamidines diminazene, berenil, pentamidine Arsenicals melarsoprol, trimelarsan Polyamines eflornithine (DFMO) American trypanosomes (Chagas disease) Nitrofurans nifurtimox Nitroimidazoles benznidazol, megazol Leishmaniasis Antimonials stibogluconate, meglumine Alkylphopholips miltefosine Polyenes amphotericin-B Antiprotozoals Haemosporidia → antimalarials Antifolates DHFR-inhibitors: pyrimethamine, proguanil, trimethoprim DHPS-inhibitors: sulfadoxine, sulfamethoxazole, dapsone,.. Quinines 8-aminoquinolines: primaquine 4-aminoquinolines: chloroquine, amodiaquine, mefloquine, … Antibiotics tetracyclins: oxytetracyclin, doxycylin, … macrolides: lincomycin, clindamycin, erythromycin, … Artemisinins natural products: artemisinin, artemether, arteether,.. synthetic trioxanes Ectoparasiticides Insecticides Acaricides 1. Pyrethrins, pyrethroids 2. Organophosphates, carbamates 3. Avermectins 4. Chlorinated hydrocarbons 5. Insect growth regulators 6. Others: rotenone, amitraz 7. Repellents: DEET 8. Synergists: piperonyl-butoxide Pyrethrins, pyrethroids Action Interference with neurotransmission (Na+ - K+ channels) Drugs Pyrethrins Pyrethroids Permethrin, cyalothrin, deltamethrin, cypermethrin, ……. Properties Insecticidal, acaricidal Adulticidal Rapid action: paralysis (knock-down) High safety factor Short withdrawal Resistance development: + Organophosphates, carbamates Action Inhibition of cholinesterase Drugs Organophosphates trichlorphon, dichlorvos fenitrothion, tetrachlorvinphos chlorpyriphos, azametiphos, diazinon, e.a. Carbamates Carbaryl, propoxur Properties Insecticidal, acaricidal Adulticidal + larvicidal Rapid action: paralysis (knock-down) Low safety factor Long withdrawal Resistance development: +++ Organochlorines Action Interference with neurotransmission (Na+ - K+ channels) Drugs DDT Chlordane, lindane, methoxychlor, ……. Properties Insecticidal, acaricidal Adulticidal Slow action: paralysis Low safety factor Long withdrawal + ecotoxicity Resistance development: ++ Avermectins Action Interference with Cl- gated ion channels (GABA potentiation) Drugs Avermectins: ivermectin, doramectin, selamectin, eprinomectin,.. Milbemycins: milbemycin-oxime, moxidectin Properties Insecticidal, acaricidal Adulticidal + larvicidal rapid action: paralysis High safety factor Short withdrawal + ecotoxicity Resistance development: + Overview of parasites in man Overview zoonoses : Dog infantum Overview zoonoses : Cat Overview zoonoses : Cattle Overview zoonoses : Sheep Overview zoonoses : Pig Parasitological diagnosis Indirect methods: serology (Ag, Ab) Direct methods: demonstration of parasietes, eggs, larvae Density parasite eggs: 1.1 – 1.2 g/l Faeces, blood, urine, skin Fresh stools storage in fridge (24 h) 2 to 5 grams needed sedimentation flottation (d: 1.20 – 1.25 g/l) (Scotch tape method) Parasitological diagnosis Collection Basic equipment of stools Parasitological diagnosis Flotation 15-30 min or centrifugation (400-600g) Parasitological diagnosis Quantitative determinations EPG: eggs per gram OPG: oocysts per gram LPG: larvae per gram 2 gram stools in 60 ml flotation solution homogeous mixing filling of counting chamber Allow flotation (5 - 10 min) counting 1 chamber: EPG = n x 200 McMaster counting chamber EPG and OPG are not in relation Volume chamber = 0.15 ml to the worm population !! Parasitological diagnosis Baermann technique Larval culture 20g stools double gauze Filter paper funnel sieve tepid water rubber tube 7 d at room T° clamp Isolation and identification of larvae pipet 24h at room T° Parasitological diagnosis Blood smear Direct smear: filaria mif, trypanosomes (motility) Thin blood smear: intracellular parasites, trypanosomes “Feather region” Giemsa-, Wright staining - too thin - - good - - too thick -