Medical Microbiology - Parasitology: Lecture 3 PDF

Medical Microbiology - 1 Parasitology Lecture 3 – Protozology Helminthology Prof. Reham ElKased  Trypanosoma brucei Disease: African Trypanosomiasis (Sleeping sickness) T. b. gambiense West African Trypanosomiasis T. b. rhodesiense...

Medical Microbiology - 1 Parasitology Lecture 3 – Protozology Helminthology Prof. Reham ElKased  Trypanosoma brucei Disease: African Trypanosomiasis (Sleeping sickness) T. b. gambiense West African Trypanosomiasis T. b. rhodesiense East African Trypanosomiasis Geographical distribution: T. gambiense is found in West and Central Africa. T. rhodesiense is much more limited, found in East and Southeast Africa. Habitat: transmitted by Tsetse fly Trypanosoma gambiense & T. rhodesiense  metacyclic trypomastigotes are inoculated to human during the bite. multiplication at site of bite and then in the blood and body fluids (lymph & spinal fluids). Infective stage: metacyclic trypomastigotes Diagnostic stage: trypomastigotes in blood Transmission: Tsetse fly less common: Mother-to-child infection Laboratories: accidental infections Blood transfusion Localisation: tsetse fly (host and vector) Midgut (procyclic trypomastigotes) Salivary glands (epimastigotes) man (host) blood stream and body fluids (lymph and spinal fluids) as trypomastigotes Incubation Period: acute trypanosomiasis 6 - 28 days chronic trypanosomiasis may not cause symptoms until months to years Pathogenicity (occurs in 3 stages): 1. Trypanosomal primary lesion (chancre): at the site of bite the parasite develops and multiply (first sign of infection) 2. Haemolymphatic early stage: in blood fever, sweating, headache, anemia, increased pulse rate, joint and muscle pain and enlarged regional lymph nodes (lymphadenopathy). 3. Cerebral late stage (meningoencephalitic stage ): in C.N.S. chronic inflammation with ischaemia and haemorrhage leading to meningoencephalitis, with sever headache, mental dullness and excessive sleeping, finally coma and death.  T. b. rhodesiense T. b. gambiense Distribution East Africa West Africa Disease progression rapid, often fatal Slow (1yr) acute, then chronic Parasitemia High parasitemia Low parasitemia Asymptomatic carriers rare common Laboratory diagnosis: Microscopic examination of chancre fluid, blood film, lymph node aspirate, or CSF (in late stage) for demonstration of motile trypomastigotes. Trypanosoma brucei in a thin blood smear stained with Giemsa Treatment : as soon as possible ◼ Suramin or pentamidine for haemolymphatic stage ◼ melarsoprol for late cerebral stage. Prevention and control: - Avoid heavily infested areas and bushes - Wear long-sleeved shirts - Use insect repellent. - active case-finding through population screening, followed by treatment of the infected persons that are identified. - Use Tsetse fly traps  Trypanosoma cruzi Disease: American trypanosomiasis (Chagas disease) Geographical distribution: Mexico and Central & South America (Latin America) Habitat: transmitted by blood-sucking triatomine bugs e.g. Triatoma Infestans. In bug: gut In man: intracellular or in blood stream Trypanosoma cruzi Infective stage: metacyclic trypomastigotes Diagnostic stage: trypomastigotes in blood Transmission: blood-sucking triatomine bugs e.g. Triatoma Infestans contaminated blood products (transfusions) organ transplantation trans-placental (congenital) laboratory accidents Localisation: triatomine bugs (host and vector) Midgut (epimastigotes) Hindgut (metacyclic trypomastigotes) man (host) Blood stream (trypomastigotes) Intracellular (amastigotes) Incubation period: 5 – 14 days many people; 5 – 40 years Pathogenicity: ❖ A local lesion (chagoma) can appear at the site of inoculation. ❖The acute phase (parasite in blood) is usually asymptomatic, but some patients might present with fever, anorexia, lymphadenopathy, mild hepatosplenomegaly and myocarditis. ❖ Most acute cases resolve over a period of 2 to 3 months into an asymptomatic chronic stage (parasite inside tissues). Romana’s sign, clinical manifestation typically observed in the acute phase of some Chagas disease patients  The symptomatic chronic stage may not occur for years. Its manifestations include cardiomyopathy (the most serious manifestation); pathologies of the digestive tract (megacolon) and weight loss. Chronic Chagas disease and its complications can be fatal chest radiograph showing enlarged heart due to T. cruzi infection. X-ray showing megacolon in Chagas disease Laboratory diagnosis: Microscopic examination of fresh blood for motile trypomastigotes. ELISA for detection of specific antibody in chronic Chagas disease. Isolation of the agent: a) inoculation in culture with specialized media e.g. NNN (diphasic Novy- Nicholle-MacNeal’s) b) xenodiagnosis, where uninfected triatomine bugs are fed on the patient's blood, and their gut contents examined for parasites 4 weeks later. Treatment: As soon as possible The drug of choice is benznidazole but once the disease has progressed to later stages, no medication has been proven to be effective. Sporozoa Plasmodium Toxoplasma gondii no special apparatus for locomotion sexual & asexual reproduction  Plasmodium Disease: Malaria P. vivax (Benign tertian malaria) P. ovale (ovale tertian malaria) P. malariae (Quartan malaria) P. falciparum (Malignant tertian malaria) Tertian (two-day cycle) Quartan cycle (three-day cycle) Geographical distribution:  Infects over 200 million people annually, mostly in poor tropical and subtropical countries of Africa. The deadliest parasitic disease killing over one million people each year. 90 % of the deaths occur south of the Sahara desert and most are under five-year-old children. In addition to Africa, malaria occurs in South and Southeast Asia, Central and South America, the Caribbean and the Middle East. In 2023: there were an estimated 263 million malaria cases and 597 000 malaria deaths in 83 countries. the WHO African Region registered 94% of malaria cases (246 million) and 95% (569 000) of malaria deaths. Children under 5 accounted for about 76% of all malaria deaths in the Region (432,000 African children died from malaria in 2023). Habitat: female Anopheles mosquito (definitive host) Human (intermediate host) Plasmodium are obligate intracellular parasites female Anopheles mosquito. The resting position of the adult is characteristic, head and abdomen in a straight line at an angle of about 45° with the surface on which they rest. Plasmodium Liver cell Mosquito 21 midgut merozoites stomach RBC zygote merozoites Infective stage: sporozoites Transmission: transmitted by blood-sucking female Anopheles mosquito Localisation: female Anopheles mosquito (host and vector): stomach (Macrogametocyte & Microgametocyte) midgut (Oocyst) man (host): Mosquito Stages (Sporogonic Cycle): A mosquito takes a blood meal and ingests liver (Schizont) gametocytes (sexual stage of Plasmodium) blood (Immature trophozoite, mature 21 trophozoite, Schizont, gametocyte). These gametocytes develop in the mosquito's midgut into ookinetes, which then form oocysts Incubation period: 7 – 30 days after mosquito 21 bite. The oocysts release sporozoites 21. Human Stages (Exo-erythrocytic and Erythrocytic Cycles): A mosquito injects sporozoites into a human during a blood meal 21. Sporozoites infect liver cells, developing into schizonts Pathogenicity: vary substantially depending on the infecting species, the level of parasitemia, and the immune status of the patient 1- Symptoms are associated with the release of merozoites and their toxin from ruptured RBCS in the end of each erythrocytic cycle (every 72h in P. malariae and every 48 h in other species): it consists of a) Cold stage or rigor stage (10 min to one hour), the patient suffers from cold sensation and teeth chattering while temp is above normal. b) Hot or fever stage (1-4 hours), due to release of most merozoites. The skin becomes hot and dry and patient suffers from fever, headache and vomiting. c) Sweating stage (1-4 hours), due to rapid drop of temp and is accompanied by reinfection of RBCs. 2- Anaemia due to destruction of RBCs, splenomegaly and hepatomegaly due to engulfed pigment by R.E.S (reticuloendothelial) 3- Adhesion and clumping of infected RBCs in capillaries cause their occlusion headache, myalgia (muscle pain), convulsions, coma, diarrhea or dysentery and dehydration. - In P. falciparum, it is called malignant because it is misleading since the symptoms resembles many other diseases and if not treated early it is fatal. Malaria & Pregnancy: During pregnancy malaria can lead to premature baby delivery or delivery of a low-birth-weight baby. The infant can get the parasite from the mother and develop the disease. Central nervous system involvement (cerebral malaria) can cause blindness, deafness, speech difficulty, paralyses and trouble with movements.  Laboratory diagnosis: always consider malaria in patients who have a history of exposure (mostly: past travel or residence in disease-endemic areas) Microscopic identification is the method most frequently used to demonstrate an active infection - Blood film for comparison of Plasmodium species Microgametocyte of P. vivax Macrogametocyte of P. vivax Mature gametocyte of P. falciparum Differences between strains: POC P. falciparum P. vivax and ovale P. malariae Dormant phase in liver No dormant phase Dormant phase No dormant phase (hypnozoites) Ring trophozoites per Multiple ring Single ring trophozoites Single ring trophozoites cell trophozoites per cell per cell per cell Parasitemia High Low Very low  Treatment: 1. Quinine and chloroquine for blood forms. 2. Primaquine & pyrimethamine for hepatic forms (hypnozoites). 3. Combination for all forms or fansidar or maloprim. Prevention and control: Bed nets Indoor Spraying Number of mosquitoes may be controlled (by eliminating mosquito larvae before they reach adulthood, chemical insecticides) Personal protection methods (glass windows,a well-constructed house), use insect-repellent, wear white or light-colored clothes covering most of the body) Vaccination  Malaria vaccinations RTS,S vaccine R21/Matrix-M vaccine RTS,S vaccine ▪ is the first malaria vaccine recommended by WHO (2021) ▪ trade name Mosquirix ▪ October 2021, the vaccine was recommended by the (WHO) for "broad use" in children ▪ April 2022, 1 million children in Ghana, Kenya and Malawi have received at least one shot ▪ August 2022, UNICEF awarded a contract to GSK to purchase 18 million doses over three years. ▪ requires at least three doses in infants by age 2, with a fourth dose extending the protection for another 1-2 years  R21/Matrix-M: In October 2023, WHO recommended a second safe and effective malaria vaccine. Vaccines are now being implemented in routine childhood immunization programmes across Africa.  Toxoplasma gondii Disease: Toxoplasmosis infects most species of warm-blooded animals, including humans Congenital toxoplasmosis being the most serious form of human infection. Geographical distribution: Worldwide Millions of men, women, and children carry theToxoplasma parasite, but very few have symptoms because the immune system usually keeps the parasite from causing illness. However, women newly infected with Toxoplasma during pregnancy and anyone with a compromised immune system should be aware that toxoplasmosis can have severe consequences. Habitat: cats and warm blooded animals (human, bird, mice) Morphology : 1.Trophozoite (tachyzoite): Intracellular, crescent shaped with central nucleus Motile, and quickly multiplying, and responsible for expanding the population of the parasite in the host 2. Pseudocysts: Intracellular collection of trophozoites in macrophages and RES (reticuloendothelial system) cells 3. Bradyzoites (Cysts): collection of trophozoites enclosed in a tissue cyst formed in chronic stage or latent infection when immunity develops. 4. Oocysts: Oval, contain 2 sporocysts each containing four sporozoites and found in stool of infected cats.  Toxoplasma gondii Both oocyst and tissue cysts transform into tachyzoites shortly after ingestion. Tachyzoites localize in neural and muscle tissue and develop into tissue cyst bradyzoites. If a pregnant woman becomes infected, tachyzoites can infect the fetus via the blood stream. Infective stage: Fecal Oocysts Tissue cysts Diagnostic stage: tachyzoites tissue cysts Transmission: eating undercooked meat of animals harboring tissue cysts consuming food or water contaminated with cat feces contaminated environmental samples (such as fecal-contaminated soil) blood transfusion or organ transplantation transplacentally from mother to fetus (congenital) Localisation: obligate intracellular parasite that invade all cells except RBCs (non nucleated) cats (definitive host- sexual stage) small intestine (oocysts) warm-blooded animals (mice, humans, and birds) (intermediate host – asexual stage) Skeletal muscle, myocardium, and brain (tissue cysts) Incubation period: 10 - 23 days after eating contaminated meat 5 - 20 days after exposure to infected cats Pathogenicity : Infection is usually mild, may be chronic or acute. Severe infection is being seen increasingly often in the immuno-compromised host undergoing immunosuppressive therapy for malignancies or organ transplants. Acquired toxoplasmosis : – in immunocompetent persons is generally an asymptomatic infection. – 10% to 20% of patients with acute infection may develop lymphadenopathy and/or a flu-like illness. Serious or fatal infection occurs in immunodeficiency as in AIDS. – toxoplasmic encephalitis is the most common cause of intracerebral mass lesions and is thought to be caused by reactivation of chronic infection. – Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection. Congenital toxoplasmosis: In early pregnancy it cause severe, often fatal cerebral damage leading to abortion or stillbirth In late pregnancy symptoms occur in the infant 2 - 3 months after birth (mental defects). Laboratory diagnosis: 1. Microscopic examination of aspirates and fluids. 2. ELISA. 3. Animal inoculation (e.g. lymph node biopsy material in mice). 4. Detection of parasite genetic material by PCR Treatment: Treatment is not needed for a healthy person who is not pregnant, as the infection is usually self limiting. Treatment with sulphadiazine and pyrimethamine or trimethoprime, may be recommended for pregnant women or persons who have weakened immune systems.  Helminths = Worms Helminths are parasitic worms that cause a wide variety of infectious diseases multi-cellular parasites (cells are differentiated into organs each having a special function) an outer protective covering, the cuticle or tegument (resist intestinal digestion) do not possess organs of locomotion (muscular contraction and relaxation) may be monoecious (male and female sex organs in the same individual, self- fertilization as well as cross-fertilization) or diecious (the two sexes are separate) All helminths lack vascular and respiratory systems Unlike other pathogens (viruses, bacteria, protozoa and fungi), helminths do not proliferate within their hosts. Worms grow, moult, mature and then produce offspring which are voided from the host to infect new hosts. Worm burdens in individual hosts (and often the severity of infection) are therefore dependent on intake (number of infective stages taken up) Worms develop slowly compared to other infectious pathogens so any resultant diseases are slow in onset and chronic in nature  Helminths form three main life-cycle stages: eggs, larvae and adults. Adult worms infect definitive hosts (those in which sexual development occurs) larval stages may be free-living or parasitize vectors, intermediate or paratenic hosts. adult egg larvae (L1-L4)  Helminths I. Phylum Nemathelminths (round worms) – class Nematoda (nematodes or roundworms) II. Phylum Platyhelminths (flat worms) – i. class Trematoda (trematodes or flukes) – ii. class Cestoda (cestodes or tapeworms) Oral suckers and buccal capsule with sometimes hooks teeth or cutting plates- no suckers, no hooks  Helminths (Multicellular) Helminthology Nemathelminths Platyhelminths (Round worms) (Flat worms) Nematoda A. Intestinal Nematodes 1. Trichinella spiralis 2. Enterobius vermicularis Trematoda Cestoda 3. Ascaris lumbricoides 1. Schistosoma sp. 1. Taenia sp. 4. Hookworms S. haematobium T. solium Ancylostoma duodenale S. mansoni T. saginata Necator americanus S. japonicum 2. Echinococcus granulosus 5. Trichuris trichiuria 2. Fasciola sp. 3. Hymenolepis sp. B. Tissue Nematodes F. hepatica H. nana 1. Wuchereria bancrofti F. gigentica H. diminuta 2. Brugia malayi 3. Fasciolopsis buski 3. Dracunculus medinensis 4. Heterophyes heterophyes 4. Loa loa 5. Onchocerca volvulus