Protozoa Causative Agent
Entamoeba histolytica Subphylum: Sarcodina Superclass: Rhizopoda Class: Lobosea Order: Amoebida Family: Entamoebidae Genus: Entamoeba
Life Cycle / Transmission / Morphology MOT: MOT: *Oral-fecal, contaminated water & food Common on day care centers, institutions (prisons, mental, home for the aged), use of night soil (vegetables), food & water handlers, mechanical vectors (flies & cockroaches), sexual intimacy (homosexuals through oral & anal sex) venereal transmission through fecal-oral contact direct colonic inoculation through contaminated enema equipment Isoenzymes: Phosphoglucomutase, hexokinase Cystic Stage: >10 um infective stage cyst (1-4 nuclei) quadrinucleate cyst (1-4 – resistant to gastric acidity & dessication & can survive in a moist environment for several weeks central karyosome – “bull’s eye karyosome chromatoidal bodies with rounded ends (cigar-shaped) excystation occurs in the SI or LI, where a cyst undergoes nuclear followed by a cytoplasmic division to form 8 trophozoites Trophozoite Stage: pseudopodium-long finger-like motility cystoplasm with ingested RBCs 1 nucleus with central karyosome
Cyst-cytoplasmic division carrying 1 nucleus on the distal SI »moves to the colon with the undigested food »descending colon (dry env’t: trophozoites do not survive) »starts to vomit out what ingested »precystic stage »trophozoites passed out in stool
Signs & Symptoms / Pathology
Diagnosis
PROTOZOAN INFECTIONS: INTESTINAL AMOEBAE only member of the family to cause colitis Microscopic detection of & liver abscess cysts & trophozoites on stool specimens Amoebiasis Asymptomatic: cyst passers / cyst Consistency / carrier state (but can infect others) appearance: Symptomatic: trophozoites Cyst (solid) Diarrhea/dysentery Trophozoites (solid) – die within 30 mins to Ulceration (intestinal) 1 hour Extraintestinal: liver (common), lungs, brain, pericardium (serious case), skin -examine ASAP Factors: Virulence Factors: Contamination: urine & chlorine water may kill lectin for adherence the trophozoite secretion of proteolytic enzymes DFS – 2mg stool release of cytotoxins contact dependent cytolysis Best method in the recovery of trophozoites phagocytosis & cysts symbiosis of intestinal bacteria Concentration Host Factors: techniques Nutrition: ꜛCHO, ꜛcholesterol diet (more favourable for colonization) FECT (Formaline Ether Concentration Test) Stress Bacterial flora MIFC (Merthiolate Iodine Formaline ꜜ O2 tension (grows at the cecal region) CM: Concentration Test) Diarrhea – mucous Zinc Sulfate Dysentery – mucous & blood More sensitive than DFS in the detection of cysts Loose bloody stools Culture Pain & cramps on abdomen Stained smears Fever, tenesmus, wt loss, nausea, anorexia Gold standard Intestinal ulcer microscopically Wide base with “bottle neck” ulcer H&E, PAS, Trichome staining & Chlokasol Deeper ulcer: intestinal perforation Liver/Amoebic abscess (R abscess (R lobe usu Blackez Staining (?) affected) Charcot Leyden Crystals –by-products of IgE ALA (amoebic liver abscess) Aspirates – liver/ R hypochondriac pain, fever, jaundice, leucocytosis pulmonary (wet-stained smears) ꜛESR, ꜛalkaline phosphates Pleuro-pulmonary amoebiasis Serology Rupture of liver abscess at the R IHAT (Indirect hemidiaphragm, cough, pleuritic pain, Hemagglutination) dyspnea, chills/fever, leucocytosis IFAT (Indirect Pericarditis – rupture of the liver abscess Flourescent Atb Test) at the L lobe. CIE (Counter Rare. If occurs, serious complication Immunoelectrophoresis) Chest pains, CHF-like manifestation Atg detection (Stools): Brain Amoebiasis – hematogenous route ELISA Cutaneous amoebiasis PCR (Polymerase (Polymerase Chain Reaction)
Treatment
Goals: To cure invasive disease at both intestinal & extraintestinal sites To eliminates the passage of cysts from the intestinal lumen
Prevention & Control
Cyst passers Metronidazole Diloxanide furoate Colitis Metronidazole Tiridazole Liver abscess Tiridazole Percutaneous drainage of liver abscess To those who do not respond to metronidazole & for prompt treatment of severe pain
Environmental sanitation Proper waste disposal Safe drinking water & food Proper food handling Hygiene Avoid night soil for fertilizer Health education & promotion
Epidemiology / Demographics Worldwide Prevalent in tropics Risks: Risks: children, pregnant women & women in postpartum period treated with corticosteroids, malignancy & malnutrition
COMMENSAL AMOEBA Causative Agent Entamoeba coli
Life Cycle / Transmission / Morphology Cyst: >10 um bigger than the E. hystolitica 1-8 nuclei Karyosome off center / eccentric Chromatoidal bars: jagged-ends “broomsticks-” or “needle sticks-” or “slinter-” like
Entamoeba hartmanii
Entamoeba dispar Entamoeba polecki
Entamoeba gingivalis
Trophozoites: Blunt / rounded & broader ps eudopodia Slow motility (sluggish) Thick, irregular, peripheral chromatin Nucleus: large eccentric karyosome No RBC on the cytoplasm but with vac uolated filling or granular endoplasm of undigested food, bacteria, etc. Narrower, less differentiated ectoplasm Cyst: <10 um (5-10 um) quadrinucleated coarse cytoplasm Similar to E. hystolitica but is much smaller & does not ingest RBCs More sluggish in movement Immature cysts: Chromatoidal bars-short with tapered ends, or thin & bar-like Similar to E. hystolitica morphology but DNA & rRNA & isoenzyme pattern are different Parasite of pigs & monkeys Cyst: Uninucleated Nuclear membrane & karyosome are very prominent in fecal smears Found in the mouth (gum & teeth surface), gum pockets & tonsillar crypts MOT: Kissing, droplet spray or s haring utensils
Endolimax nana
Trophozoite: 10-20 um Moves quickly & numerous blunt pseudopodia Cyst: 6-10 um in dm Quadrinucleate when mature Trophozoite: 6-15 um Sluggish movement
Iodamoeba butschilii
Nucleus: vesicular, large & irregularly-shaped karyosome anchored to the nucleus by ac hromatic fibrils Cyst: Uninucleated, large glycogen body Trophozoite: 9-14 um long (6-20 um) Nucleus: large vesicular with large endosome surrounded by achromatic granules
Diagnosis Stool examination Liquid to semi-formed stools will show trophozoites Formed stools show cysts DFS Demonstrate trophozoites Concentration techniques ZnSo4 & FECT Recovery of cysts FECT & Iodine stain To differentiate the species Swab between gums & teeth To examine trophozoites for E. gingivalis
Prevention & Control Proper disposal of human waste Good personal hygiene
Epidemiology / Demographics cosmopolitan in distribution harmless inhabitant of the colon OFWs Food handlers
Causative Agent Balantidium coli
Life Cycle / Transmission / Morphology Trophozoite: 30-300 um long & 30100 um wide Nucleus: macronucleus / micronucleus Macronucleus: kidney-shaped, horse-shoe-shaped Cytosome: anterior indentation (mouth) Cytopyge: posterior indentation (anus) Mucocysts: extrusive organelles, beneath the cell membrane Cilia: hair-like projections, spiral, rolling motio Cyst: Infective Stage LC: same with Entamoeba MOT: contaminated food & water containing cysts IP: 4-5 days Ingested cysts excyst in the SI »become trophozoites »inhabit the lumen, mucosa, & submucosa of the LI (cecal region) »multiply binary fission »pathologic changes in the intestinal wall & mucosa Cyst formed as protection for survival outside the host »encyst during intestinal transport or after evacuation of semiformed stools
Causative Agent Gardia lamblia Other names: G. intestinalis, G. duodenalis, Lamblia duodenalis, L. intestinalis
Life Cycle / Transmission / Morphology MOT: ingestion of food contaminated with mature cysts Cyst: 8-12 um long & 7-10 um wide Double-walled usually ovoidal Axostyle-running across the cytoplasm Flagella: retracted into axonemes, the median body & deeply stained curved fibrils surrounded by a tough hyaline cyst wall secreted from condensed cytoplasm Paired parabasal bodies Nucleus-quadrinucleated (mature cysts); binucleated (young cysts)
CILIATES (Ciliophora) Signs & Symptoms / Pathology Diagnosis Balantidiasis/Balantidial dysentery Rare infection in man (occupational hazard) Common on pigs Trophozoite can penetrate & produce necrosis/ulceration at the intestinal lumen (ulcers – irregular, undetermined edges: rounded /narrow base & wide neck) Also invades the appendix S/sx: Intermittent diarrhea/constipation / tenesmus Diarrhea (6-15 episodes/day) Abdominal pains / tenderness / colic Anorexia, NV, wt loss, weakness Dysentery – blood mucoid stools, perforation, haemorrhage & shock Fetid breath Extraintestinal: peritonitis, UTI, inflammatory vaginitis
Stool exam 90% trophozoites 10% cysts (infrequent) DFS & Concentration techniques Demonstration of cysts & trophozoites in feces
Known to cause epidemic & endemic diarrhea Gardiasis/Lambliasis Asymptomatic Symptomatic Habitat: SI Impaired absorption of fat, Dxylose & Vit. B12 Acute: nausea, lassitude, anorexia, diarrhea, abdominal distention, weight loss Flatus-rotten eggs smell (hydrogen sulfite) Chronic: fatty stools (steatorrhea)
Tetracycline adults & older children CI: children <8 y/o & pregnant women Iodoquinol Metronidazole children CI: early prenancy
Prevention & Control Proper sanitation Safe water supply Protection of food from contamination
Culture
FLAGELLATES (Mastigophora) Signs & Symptoms / Pathology Diagnosis
Treatment
Stool exam Demonstration of trophozoites & cysts Duodenal Aspirate Exam Enter- test (String test) May demonstrate trophozoites Swallows a gelatin capsule containing a nylon string DFS Trophozoites: floating leaf-like motility Ag detection test in stools
Treatment Metronidazole / Tinidazole Should not be taken with alcohol AR: nausea, HA, drowsiness, metallic taste Quinacrine Alternative drug SE: yellow staining of skin, pychosis
Prevention & Control Proper sanitary disposal of human excreta to prevent contamination of food & water supply Safe drinking water (Boiling, filtration, 2% iodine)
Epidemiology / Demographics Uncommon in temperate countries Tropics: in association with pigs Associated with poor environmental sanitation Philippines: few & sporadic
Epidemiology / Demographics Associated with poor environmental sanitation Food handlers Increasing prevalence is attributed to homosexual oro-anal practices Outbreaks: waterborne Risk factors: Poor hygiene Poor sanitation Overcrowding Immunodeficiency Bacterial & fungal overgrowth in the SI
Trophozoite: 9-12 um long & 5-15 um wide Pear-shaped / pyriform / tear drop-shaped Axostyle-distinct medial line Parabasal bodies Curved / convex dorsal (pointed) Concave ventral Nucleus-binucleated, ovoidal (one on each side of the midline Organelle of attachment: sucking disc (large adhesive disc) Flagella: 4 pairs, falling leaf-like, kite-like motion (erratic tumblinglike motion) Bilaterally symmetrical organism Reproduction: longitudinal binary fission Found in diarrheic stools
Trichomonas vaginalis
Metabolism: Glucose (Embden-Meyerhof) Acetate, ethanol, alanine Arginine/Alanine – participates in glucose metabolism Cannot synthesize lipid (host gut) General morphology of Trichomonads: Pear-shaped Axostyle: extended beyond the length of the organism 5 Flagella: 4 in the anterior end, 1 trails along the undulating membrane 1 nucleus Cyclostome: less prominent IP: 4-30 days after exposure Lumen flagellate Die at 40C (with dessication under sunlight) Largest among trichomonads Do not produce cysts, only trohozoites Ovoid nucleus Undulating membrane: <1/2 of the axostyle Diagnostic feature: siderophil granules Associated with: Non-specific NSV (vaginitis) NSP (prostatitis) NSU (urethritis)
(ELISA) Monoclonal Atb
Homosexual practices “gay bowel syndrome”
Ab dectection: IFAT/ELISA Direct fluorescent Atb assays
Male: Asymptomatic: self-limiting, less persistent Symptomatic: discharge, pruritus (head of penis), burning sensation of urination Female: Asymptomatic: self-limiting, less persistent Symptomatic: pruritus, vulvovaginitis, vaginal discharge, painful coitus, vaginal odor Cervix-edematous, blisters, petechiae, “strawberry cervix”, punctate hemorrhages
Experimental results: survive in urine 9-20 hours Wash clothL 23 hours
Specimen: discharge Microscopy: fresh, tumbling/twitching motility Staining: Giemsa Pap Smear AO (Aquidine-Orange Stain) Siderophil granules Culture: in pouch system Whiff test: 20% KOH, fishy odor (+)
Simultaneous for sexual partners Nitro-imidazoles: Metronidazole / Imidazole
Associated with venereal transmitted diseases, STIs, gonorrhoea (2430%) Non-venereal: virgins, children/babies, neonatal Worldwide distribution Both sexes affected Incidence correlates with the number of sexual partners Peak in age groups 6-35 y/o Female: 50-75% prostitutes 7-32% social / VD clinics 5% family planning clinics Higher among postmenstrual females
Causative Agent Blastocystis hominis
Life Cycle / Transmission / Morphology Isolates form chicken, ducks, geese, & sea snakes MOT: fecal-oral LC: Ingestion of cyst »ruptures »vacoular »autoinfection Not conclusively demonstrated 4 Morphological Forms: Vacuolated or central body: 510 um in dm Diagnostic feature Reproductive organelle most predominant forms in fecal specimens Spherical Large central vacuole pushes the cytoplasm & nuclei to the periphery of the cell Amoeba-like forms: Undergoes mitosis Occasionally observed in stool samples Exhibit active extension & retraction of pseudopodia Nuclear chromatin: peripheral clumping Intermediate stage between the vacoular & pre-cystic form Allows the parasite to ingest bacteria to enhance encystment Granular forms: 10-60 um Observed from old cultures Granular contents develop into daughter cells of the amoeba form when the cell ruptures Multiple fission Arise from vacuolated forms Produce many vacuolated forms Cystic form: 3-55 um Prominent & thick osmophilic electron dense wall Demarcated polymorphic, oval or circular Dense body surrounded by a loose outer membranous layer Precyst undergoes schizogony (creation of smaller version of amoeba in the form of a cyst) Thick-walled cyst: responsible for the external transmission Thin-walled cyst: cause of reinfection within a host’s intestinal tract
INTESTINAL PROTOZOANS Signs & Symptoms / Pathology Diagnosis
Often non-specific s/sx May include: diarrhea (sometimes self-limiting), abdominal pain/cramps / discomfort, nausea Profuse, watery diarrhea Fatigue, anorexia, flatulence & other non-specific GIT symptoms Correlates with: enteritis, terminal ileitis, colitis/ulcerative colitis, arthritis Large cases present their stools as asymptomatic Incidental finding/commensal Suggest possibility of asymptomatic carriers Associated with specific forms of B. hominis & the immune status of the patient
Light microscopy (wet mount with or without staining) Vacuolar forms may be destroyed by concentrated techniques or addition of distilled water – only the cyst Immunologic techniques, Invasive techniques (?)
Treatment
Difficult to eradicate because they hide in the intestinal mucus, sticks & holds on to intestinal membranes DOC: Metronidazole / Iodoquinol Asymptomatic: not treatment TMP-SMX TrimethroprimSulfamethoxazole (Cotrimoxazole), Nitazoxamide Diet Mgt: ꜛdiet in fiber, lactose-free
Prevention & Control Safe water Environmental sanitation Handwashing Prevention of food contamination Sterilization (?) Cysts survive up to 19 days in water at normal temperature Resistance to chlorine at the standard concentrations
Epidemiology / Demographics Tropical, subtropical & developing countries Adults > children, immunocompromised patients Incidence in Italy & China 40.7% food handlers in Manila & tertiary hospitals
Causative Agent Naegleria fowleri
Acanthamoeba spp.
Life Cycle / Transmission / Morphology The organism that can exist as an amoeba (trophozoite form) & as a flagellate (swimming form) MOT: swimming/inhaling contaminated water Portal of Entry: olfactory epithelium Habitat: Soil – source of 02, water, temperatures compatible with survival & bacterial food supply Cyst form: Double-thin walled, resistant Flagellate form: Temporary, Trophozoite stage: Infective stage Free-living form Can transform reversibly into a non-reproductive flagellate st age or a resistant cyst Trophozoite stage: Infective / vegetative / active feeding stage Reproduction: binary fission fine, tapering, thorn-like (spiny) locomotion: acanthopodia that arises from the surface of the body moves sluggishly with polydirectional movement uninucleated large with a centrally located dense staining nucleus large endosome, finely granulated cytoplasm, large contractile vacuole host for Legionella spp. Cyst stage: Dormant, resistant PAS: encysts containing cellulose Double walled (ectocyst & endocyst): outer wrinkled wall & inner polygonal-shaped wall Pores or ostioles: seen at the point of contact of the 2 walls *both are diagnostic stages MOT: nasopharyngeal route through breaks in the skin & inhalation Isolated from air, bottled mineral waterm soil, swimming pools, deep well water, contact lens cleaning solutions, etc.
FREE-LIVING PATHOGENIC AMOEBA Signs & Symptoms / Pathology Diagnosis PAM (Primary Amoebic Meningoencephalitis) Rare disease that leads to inflammation of the brain & destruction of brain tissue rapid onset of symptoms (24 hrs to 5-7 days) Early sx: HA, nuchal rigidity, NV, restlessness Late sx: photophobia, lethargy, seizures, confusion, coma, diplopia CSF: ꜛpressure, gray to yellowwhite, with RBCs & WBCs (PMNs) PP: lesions- base orbitofrontal & temporal lobes Brain affected filled with fibrinopurulent exudate Large numbers of amoebic trophozoites (no cysts) seen within edematous & necrotic neural tissue GAE (Granulomatous Amoebic Encephalitis) HA, stiff neck Cerebral hemisphere mostly affected Edematous with extensive hemorrhagic necrosis Cornea (Amoebic Keratitis): trauma to cornea or contact lenses
CSF exam of trophozoites Phase contrast of Giemsa or Wright stain – centrally placed nucleus PCR Assay: identifies N. fowleri DNA on the brain tissue samples ELISA
Treatment Amphotecirin B: IV & intrathecal May be combined with miconazole & rifampicin
Prevention & Control Chlorination of swimming pools
Cranial CT Scan: large lowdensity lesions Cranial MRI: multiple ringenhancing lesions Histology: amoebic trophozoites
5-flurocystosine, ketoconazole, itraconazole, pentaminide, or amphotericin B Keratitis: cotrimoxazole in combnation with pentamidinem, isethionate & Neosporin & avoidance of topical CS
Precaution on use of contact lenses & hot-tub Jacuzzi, etc.
Epidemiology / Demographics 1965, meningoencephalitis Isolated in soil & freshwater, nasal passages & throat of healthy individual Chlorinated swimming pools, freshwater lakes, thermal springs, domestic water supplies, thermally polluted water, sewage, soil, air, humidifier systems, cell cultures Children & young adults 1913 Ubiquitous (everywhere) & worldwide Found in soil, fresh & brackish water
Causative Agent Cryptosporidium hominis C. parvum
Cyclospora cayetanensis
Life Cycle / Transmission / Morphology Exists primarily as oocyst Ingestion of water containing sporulated cyst (infective stage) – “embryonated egg stage-like” Excystation happens in the SI, lungs releasing sporozoites Parasitism: invasion of epithelial cells of SI (habitat) forming trophozoites Reproduction: Asexual – produce schizonts & merozoites (goes out, invade the epithelial cells & undergo another LC) Sexual – microgametes (male) macrogametes (female) Sporulation: produce sporulated oocysts Thin-walled cysts-capable of autoinfection; remains in the body; d/c if goes out (no support) Thick-walled cysts-goes out of the body
Unicellular coccidian Larger than cryptosporidian Exists as oocysts
LC: same ingestion, excystation, reproduction Release: produce unsporulated oocyts which exists the host Sporulation: outside environtment
T: 22-32C No autoinfection
COCCIDIANS (Parasites & the Immunocompromised) Signs & Symptoms / Pathology Diagnosis
Immunocompetent: asymptomatic-diarrhea (1-3 weeks); carrier state Immunocompromised: CD4 count of <200 Diarrhea, fever, NV, signs of dehydration, electrolyte imbalance
Immunocompetent/ Immunocompromised: Severe diarrhea (10-12 weeks) Carrier state (?) controversial Anorexia, wt loss, low grade fever, abdominal pain
Immunoflourence microscopy Usually of stools Visualize oocyts Has higher sensitivity & specificity Can…
Microscopy Usually of stools Visualize oocysts intermittently Techniques used: Wet mount with UV fluorescence of DIC FECT – used to collect minute amount of diarrheic stool Modified Acid Fast / Safranin Test
Treatment
Nitazoxamide: initially used for tapeworms MOA: prevent anaerobic metabolism via inhibition of pyruvate ferredoxin oxidoreductase (PFOR) Paramomycin aminoglycoside
TMP-SMX 2 synergistic drugs Inhibits tetrahydrofolate synthesis (needed for DNA replication & transcription) MOA: PABA analogues
Prevention & Control Immunocompromis ed - handwashing Practice safer sex (cryptosporidium can be transferred thru oro-anal sex, csyt stick on the inner thigh, anus, knees of the patient when touching those parts) Avoid touching farm animals (reservoir host) Avoid touching stools of pets Avoid swallowing water when swimming (chlorine resistance Cryptoporidium) Wash/cook food properly Drink safe water Rolling boil for 1 min Clean ice trays, jars with soap (spores tend to stay there) Water fillers: reverse osmosis, absolute 1 micron, standard 53, cyst reduction removal Handwashing Wash / cook food properly Drink safe water Sanitation Health education
Epidemiology / Demographics Worldwide Associated with AIDS Not uncommon in 1st world countries Outbreak in Milwaukee, 1993 Waterborne diseases Seen in recreational water facilities, contaminated drinking water (ground / bottled water), contaminated undercooked food
Tropical & subtropical All age groups at risk
Cystoisospora belli Other name: Isospora belli
Unicellular coccidian Exists as oocysts Least common among the three Large ellipsoidal oocyst (elongated) “rice grain-, eyes-, cigar-shaped”
Severe diarrhea of weeks Anorexia, wt loss, low-grade fever, malabsorption, crampy abdominal pain & Eosinophilia
LC: same ingestion, excystation, reproduction Release: produce unsporulated oocyts which exists the host Sporulation: outside environtment Oocyst contain sporoblast »mature to oocyst containing sporozoites Less virulent than cyclospora
Toxoplasma gondii
Tachyzoites (trophozoites) Most common form seen on samples Pear-shaped Mobile form, bends/curves sometimes Oocyts: 10-13 um by 9-11 um Round / ovoid, thin wall Definitive host: Cats (Felidae)
Intestinal epithelium: merozoites multiply (schizogony) » differentiation into micro/ macrogametocytes (gametogony) Inside the mature oocyst, 2 sporocyst (each having 4 sphorozoites)
Excretes unsporulated oocyst (no autoinfection) Then eaten up by rats/mice Intermediate host: Rats / mice Tachyzoites: fast-moving trophozoite, able to feed themselves Reside in neural tissues & muscular tissues Then become tissue cysts » bradyzoites (both infective stage) »then ingested by the DH Humans MOT: food/drinks, litter boxes, farm animals, organ transplantation, blood donation, transplacental/*vertical transmission Organs affected: brain, muscles, eyes, heart
Immunocompetent None, self-limiting, mild cases 10-20% develop flu-like illnesses Rarely, may develop chorioretinitis Immunocompromised HA, confusion, seizures (neurologic sxs) HIV pts: Neurologic Toxoplasmosis Most common CNS mass lesion Occurs when CD4 <100 Tumor-like CNS s/sx Death may occur: thru brain herniations Congenital Toxoplasmosis ꜜBW, hepatospleenomegaly, jaundice, MR, hearing loss, chorioretinitis (80%) can be latent CM which you can acquire congenitally
Microscopy Usually of stools Visualize oocysts intermittently Techniques used: Wet mount with UV fluorescence of DIC FECT – used to collect minute amount of diarrheic stool Modified Acid Fast / Safranin Test Duodenal biopsy – isospora tend to invade in the deep epithelial cells of SI causing eosinophilia (other 2 organisms superficial only) String test (Enterotest)
TMP-SMX 2 synergistic drugs Inhibits tetrahydrofolate synthesis (needed for DNA replication & transcription) MOA: PABA analogues
Handwashing Wash / cook food properly Drink safe water Sanitation Health education
Observation of various specimen Blood (routine method for Dx) Bronchioalveolar lavage LN biopsy Other body fluids Amniocentesis
PyrimethamineSulfadiazine (1 line) 2 synergistic drugs Inhibits tetrahydrofolate synthesis (for DNA replication & transcription) MOA: PABA analogues
Other Methods: PCR, ELISA Fundoscopy/Retinal exam – calcifications in the retina MRI – encephalitis UTZ – for pregnant women
Special cases: Ocular toxoplasmosis TMP-SMX (alternative) CS (inflammation of retina) Pregnant women not routinely given because it is highly teratogenic may not be given during organogenesis spiramycin (Macrolide) –prevent protein synthesis
Pregnant women Gloves when handling soil Avoid eating raw meat Wash utensils & food Don’t drink unpasteurized milk Cover children’s sandboxes Avoid cats Cat lovers Keep cats indoors Don’t feed cats with raw meats Don’t adopt stray cats/kittens Clean litter boxes properly Change litter box everyday Clean with scalding water (oocyst resistant to soap) Wear gloves Handwashing after
Tropical & subtropical Risk immunocompromised Common in institutions Affects humans & animals
One of the most common human infections Worldwide prevalence: 2075% (3 out of 4) Philippines: around >25% US: 60M (15% of female in childbearing age) France: eating undercooked meat Central America: stray cats Risks: Can be transmitted from pregnant mother to the unborn child (congenital toxoplasmosis) Immunocompromised pts
Causative Agent Plasmodium spp. P. falcifarum P. vivax P. ovale P. malariae P. knowlesi (DOH, 2009)
Life Cycle / Transmission / Morphology MOT: bite of female anopheles mosquito Blood transfusion Sharing of IV needles Transplacental: transmission upon birth Neonatal malaria Mother seems to be asymptomatic Walking malaria – carriers, asymptomatic Immunity on their RBCs Suppliers of malaria You can find them thru Mass blood smear Mosquito Stage: Sexual stage Sporogony Mosquito infected with gametocytes (micro /macrogametocytes) »female only bites »zygote » ookinete » oocyst containing sporozoites (infective stage) » migrate in the salivary glands » blood meal Asexual Stage: Human Human Liver Stage: Sporozoites » liver (exoerythrocytic schizoint) » schizogony » trophozoite » schizoint (containing merozoites) » liver cell ruptures » end up in RBC P. vivax & P. ovale: stops/sleeps in liver cells called hypnozoites stage Dormant stage Responsible for relapse of malaria Human Blood Stage: Multiplication (doubling/ tripling) Erythrocytic schizony » merozoites » trophozoites » schizont Specialized feature: gametocytes (reproduction) process called gametogony Malaria parasites: P. falcifarum & P. vivax – most infections worldwide dormant liver P. vivax & P. ovale stage (hypnozoites), can reactivate (relapse) & cause malaria for several months to years after the infecting mosquito bite –
PLASMODIUM Spp. Signs & Symptoms / Pathology Diagnosis Pathology: P. falcifarum Adherence to infected RBC to noninfected RBC leading to rosette formation –tissue anoxia Cytoadherance infected RBC become sticky on the surface & walls of t he endothelium diminishing the calibre Process results in: formation of red cell aggregates & intravascular sequestration of RBCs that contain mature forms of the parasite in vital organs (brain & heart) P. vivax, P. malariae, P. ovale No sequestration P. vivax – reticulocytes old RBCs P. malariae –
Classis s/sx of Malaria: Triad: chills » fever » sweating HA, muscle pains Merozoites: hypothalamus » ꜛT causing chills » fever » sweating Can mimic flu Severe Complications: Cerebral malaria – tissue anoxia (causes death), kidney failure Uncomplicated Malaria: Classical malaria- attack last 6-10 hours Tertian: P. falcifarum, P. vivax, P. ovale (every 2nd day) rd Quartan: P. malariae (every 3 day) Severe/Complicated Malaria: Occurs to most persons who have to immunity to malaria Young children & pregnant women P. falcifarum & P. vivax Recrudescence: no clearing Submicroscopic threshold Short term relapse (hours to days to few weeks) P. vivax (parasites cleared) & P. ovale Parasitic relapse
r/o place travelled & blood smears Clinical Diagnosis: Semi-immune: only HA Severe malaria: P. falcifarum Confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties Lab. Finding: because early clinical diagnosis is not typical Microscopy: Thick & thin peripheral blood smears Quality of reagents (early destroyed) Microscopy & experience of microscopist’s experience Standard Exam: st 1 : thick film – 100 microscopic fields, magnification of 600 to 700x Advantages: simple, low cost, quality & quantity diagnosis Sensitivity of peripheral microscopists: 55% Disadvantages: labor intensive Serologic Tests: IFAT RDT (Rapid Diagnostic Test) Lateral flow immunochromatogra phic assay Test strips (dipsticks) Molecular Diagnosis PCR
Treatment P. falcifarum Chloroquine (CQ) & Pyrimethamine Resistant to CQ if given alone Uncomplicated P. falcifarum st line drug 1 combination (Coartem) Artersiminins (Artenether, Artenusate, Dihydrocoteminin) + Lumetantrine P. vivax CQ Severe Malaria IV quinine & quinidine Pregnant: IV then oral Gametocytes & Hypnozoites Primaquine Prophylaxis Doxycycline
Prevention & Control Control & Prevention Chemotherapy: early diagnosis & treatment Long lasting insecticidal nets (LLIN) – even upto 5 years of use Indoor residual spraying (IRS) Vaccines Malaria Control reduce the impact not elimination treat malaria cases properly prevention: vector control Prevent disease: administration of anti-malarial drugs IBT (Intermittent B Treatment) for pregnant & children Activities for Malaria Control Health education (IEC- Information Education Communication) Barriers for Malaria Control: Drug resistant Insecticide resistant
Epidemiology / Demographics Global Burden: 109 endemic countries & territories worldwide 3.3 B at risk Morbidity: approx. 247B annually Mortality: approx. 1M deaths annually 91% Africa 85% children (<5y/o) MDG (Millennium Development Goals #6) Goals for global importance To ꜜM/M Malaria has global importance Top 5 Provinces: Palawan, Isabela, Cagayan, Tawi-Tawi Malaria free 22 provinces: all Visayas except Negros & Antique Catanduanes, Sorgogon, Samar, Leyte, Bohol, Cebu, Masbate, Mariduque, Capiz, Aklan, Benguet
Ensuring Quality: Quality assurance TES (Therapeutic Efficacy Surveillance) Bioassay & susceptibility test monitoring – for effective insecticides for LLIN & IRS
Control phase in the Philippines Malaria not included in 10 leading cause of morbidity Indigenous cases Imported cases
Malariometric Indices: Slide Positivity Ratio:
Annual Parasite Incidence:
P. malaria – long-lasting infections if left untreated can persist asymptomatically in the human host for years & even lifetime; longest IP P. falcifarum severe potentially fatal malaria Estimated 700,000-2,7M deaths annually, most are children dying in Africa Frequent occurrence in the Philippines (60-70%) P. knowlesi monkey-type (primates); thought it is P. malariae –
–
Female Anopheles Mosquito Of 430 known species of anopheles, 30-40 transmit malaria in nature Developmental factors: Ambient T & humidity Higher T accelerate the parasite growth in the mosquito Whether the anopheles survives long enough to allow the parasite to complete its cycle Anthropragic (human) Rain-dependent (beginning & end of the rainy season) Behavior: partially exophilic & exophagic
Breeding Sites: Likes dark clothing Bites at night Slow-flowing, partly shaded stream Shallow collections of fresh water like puddles, ricefields & hoofprints
