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PA514: Parasitic Disease ASHLEY RAMOS, PA-C Instructional Objectives 27. Differentiate parasitic diseases by epidemiology, etiologies, risk factors, genetic influences, pathophysiology, signs/symptoms, physical examination. (CO1, CO2) 28. Distinguish parasitic diseases as acute, chronic, urgent, o...

PA514: Parasitic Disease ASHLEY RAMOS, PA-C Instructional Objectives 27. Differentiate parasitic diseases by epidemiology, etiologies, risk factors, genetic influences, pathophysiology, signs/symptoms, physical examination. (CO1, CO2) 28. Distinguish parasitic diseases as acute, chronic, urgent, or emergent. (CO3, CO4) 29. Select the most appropriate clinical diagnostic tests available to classify the type of parasitic diseases. (CO3) 30. Interpret the results of diagnostic tests to establish the diagnosis of parasitic diseases. (CO3) 31. Apply the current and emerging pharmacologic and other nonpharmacologic evidencebased practices used in the treatment of parasitic diseases. (CO4) 32. Formulate an age appropriate, comprehensive treatment plan for individual patient with parasitic diseases. (CO4) 33. Identify the age-appropriate health screening and health promotion/disease prevention strategies for patients with parasitic diseases. (CO5) Parasitic Infections Extraintestinal Protozoa ◦ Malaria Intestinal protozoa ◦ Entamoeba histolytica (Amebiasis ) ◦ Giardia lamblia Helminth infestations ◦ Enterobius vermicularis (Pinworm) ◦ Ascaris lumbricoides (Roundworm) ◦ Ancylostoma duodenale (Hookworm) ◦ Trematode Fluke infections ◦ Cestodes (Tapeworms) Sexually Transmitted Parasites o Trichomoniasis 3 Parasitic Infections Definition A parasite is: 1. An organism that grows, feeds, and is sheltered on or in a different organism while contributing nothing to the survival of its host. 2. a. One who habitually takes advantage of the generosity of others without making any useful return. 4 Malaria Malaria •Protozoan disease transmitted by the bite of an infected female Anopheles mosquitoes •Blood parasites of the genus Plasmodium •Approximately 156 named species of Plasmodium which infect various species of vertebrates. •Four are known to infect humans: • • • • P. falciparum P. vivax P. ovale P. malariae 6 MalariaEpidemiology • Endemic in most of the tropics • High burden in Sub-Saharan Africa • In 2021/2022, malaria caused an estimated 247 million clinical episodes and 619,000 deaths. • ~2,000 cases diagnosed in United States each year – most of which are travelers and immigrants traveling from countries where transmission occurs. Statistics from World Health Organization, 2022 World malaria report 7 The Life Cycle of Malaria (Plasmodium) Stages: Sporozoite Hypnozoite Merozoite/Trophozoite Schizont Gametocyte 8 Malaria: Clinical Presentation Incubation time 8-60 days Flu-like illness Beginning of disease may only include headache, malaise, fatigue, nausea, muscular pains, slight diarrhea and slight increase of body temperature Followed by bouts of fever accompanied by other symptoms and alternating with periods of freedom from any feeling of illness. 10 Malaria: Clinical Presentation ◦ Malaise ◦ Abrupt chills ◦ Fever rising to 39 to 41 C (102 to 106 F) ◦ Body aches ◦ Fatigue ◦ Abdominal discomfort ◦ Rigors occurring at regular intervals ◦ Tachycardia, thready pulse ◦ Headache ◦ Nausea/vomiting ◦ Diaphoresis ◦ Hepato/splenomegaly (> 4 days of symptoms) 12 Uncomplicated Malaria Can be broken up into 3 different stages: The cold stage (shaking/chills) The hot stage (fever, HA, vomiting) The sweating stage (diaphoresis, return to normal temp, fatigue) Uncomplicated Malaria: Physical Exam Fever Diaphoresis Weakness Splenomegaly Jaundice ◦ Sclera icterus Hepatomegaly Tachypnea Tachycardia Severe/Complicated Malaria Generally caused by infections with P. falciparum that result in: •Organ failure •Cerebral malaria • impaired consciousness • generalized seizures • coma • Other neurological abnormalities •Severe anemia •Hemoglobinuria •Disseminated intravascular coagulation (DIC) •Acute Respiratory Distress Syndrome •Hypotension •AKI 15 Malaria Complications Cerebral Malaria Mechanisms unknown Theory that adherence of parasitized erythrocytes to the cerebral vasculature leads to obstruction of the microcirculation, anoxia or metabolic disturbances affecting brain function, resulting in coma. 16 Manifestations of Severe Falciparum Malaria •Unarousable coma/cerebral malaria : Failure to localize or respond appropriately to noxious stimuli; coma persisting for >30 min after generalized convulsion •Acidemia/acidosis: Arterial pH of <7.25, base deficit >8 meq/L, or plasma bicarbonate level of <15 mmol/L; venous lactate level of >5 mmol/L; manifests as labored deep breathing, often termed “respiratory distress” •Severe normochromic, normocytic anemia: Hematocrit of <15% or hemoglobin level of <50 g/L (<5 g/dL) with parasitemia level of >10,000/μL •Renal failure: Serum or plasma creatinine level of >265 μmol/L (>3 mg/dL); urine output (24 h) of <400 mL for adults or <12 mL/kg for children; no improvement with rehydration •Pulmonary edema/adult respiratory distress syndrome: Noncardiogenic pulmonary edema, often aggravated by overhydration •Hypoglycemia: Plasma glucose level of <2.2 mmol/L (<40 mg/dL) •Hypotension/shock: Systolic blood pressure of <50 mmHg in children 1–5 years or <80 mmHg in adults; core/skin temperature difference of >10°C; capillary refill >2 s •Bleeding/disseminated intravascular coagulation: Significant bleeding and hemorrhage from the gums, nose, and gastrointestinal tract and/or evidence of disseminated intravascular coagulation •Convulsions: More than two generalized seizures in 24 h; signs of continued seizure activity, sometimes subtle (e.g., tonic-clonic eye movements without limb or face movement) Malaria: Diagnosis • Thin and thick peripheral blood smears • Examined at 8-hr intervals x 3 days • Confirm presence of parasite within RBCs (trophozoites and schizonts) • CBC, CMP • Leukocytosis • Leukopenia • Anemia • Thrombocytopenia Malaria 19 Malaria 20 Malaria- Treatment • If in United States needs to be reported to local health department •Treatment is dependent on • Clinical status • Species • Area of infection (possible resistance to drug) • Pregnancy status • https://www.cdc.gov/malaria/resources/pdf/Malaria_Managment_Algorithm_202208. pdf • https://www.cdc.gov/malaria/resources/pdf/Malaria_Treatment_Table_202208.pdf Malaria: Treatment •Main drugs: Chloroquine, Mefloquine (in areas of chloroquine resistance) •Alternative drugs: • Atovaquone/proguanil (Malarone) • Primaquine 22 Quinoline Derivatives Drugs included: chloroquine, amodiaquine, quinine, quinidine, mefloquine, primaquine, lumefantrine, and halofantrine In general have activity against the erythrocytic stage of infection *Primaquine also has activity against intrahepatic form and gametocytes MOA: concentrates within parasite acid vesicles and raises internal pH resulting in inhibition of parasite growth Chloroquine •Synthetic 4-aminoquinoline •Use is now limited due to P. falciparum resistance •Also used in prophylaxis •Dosages: 250mg, 500mg tablets; •Dosing: • 500mg/wk x1-2 weeks before exposure • 500mg q 6 hr x 2 doses then 500mg/wk if given after exposure • 1000mg x1, then 500mg x1 at 6, 24, 48h (uncomplicated, tx) •ADRs: GI upset, pruritus, HA, blurred vision Common ADRs of Chloroquine Malaria: Prevention ◦Prophylaxis against mosquitoes ◦mosquito netting around beds, mosquito repellents such as N,N-diethylmetatoluamide (deet), and wearing protective clothing, especially between dusk and dawn. ◦Chemoprophylaxis ◦Chloroquine, Mefloquine, Malarone ◦Should begin 1 to 2 wk before traveling to, and continue for 4 wk after returning from, an endemic area. 28 Malaria Informatio n and Phrophylax is by Country Malaria prophylaxis against malaria in adults Malaria prophylaxis against malaria in adults Amebiasis GI protozoan infection caused by Entamoeba histolytica ◦ Ingestion of viable cysts from fecally contaminated water, food, or hands ◦ Food-borne exposure most common form of transmission ◦ Passed by the fecal-oral route. Infections increased in developing countries with inadequate sanitation 33 Amebiasis-Epidemiology •Underdeveloped tropical regions with poor sanitation systems and hygiene (children 5 and younger) • Mexico, India, Africa and parts of Central and South America are common places •Developed countries • Travelers to tropical places that have poor sanitary conditions • Immigrants from those areas • People who live in institutions with poor sanitary conditions • MSM •Worldwide is the 2nd most common cause of death due to parasitic infection (1st is Malaria) Amebiasis- Risk factors •immunosuppression •cancer •alcoholism •malnutrition •recent travel to endemic region •steroid use •pregnancy Amebiasis E. histolytica exists in two forms: the trophozoite and the cyst. Cysts are found predominately in formed stool and once ingested are resistant to gastric acid 36 Amebiasis Once in the gut cysts differentiate into the trophozoite form. Trophozoites colonize the lumen and the mucosa of the large intestine ◦Invasion of tissues via portal circulation to the liver (metastatic abscess) Trophozoites predominate in liquid stools (no matter what causes the diarrhea) but rapidly die outside the body. 37 Life Cycle of E. Histolytica 38 Amebiasis – Clinical Presentation •Most infected persons are asymptomatic but chronically pass cysts in stools. •If symptomatic, symptoms are gradual with an onset of days or weeks after infection •Cramps •Bloody/watery diarrhea •Wt loss •Fatigue •Increased flatulence 39 Amebiasis – Clinical Presentation •Amebic dysentery is characterized by episodes of: • Frequent (semi)liquid stools (10-12 stools/day)that often contain blood, mucus, and live trophozoites Lower abdominal pain • Malaise • Wt loss 40 Amebiasis – Physical Exam • Abdominal distention •Generalized abdominal tenderness •Hyperperistalsis •RUQ tenderness (liver abscess) •Fever (severe disease) Amebiasis – Extraintestinal infections Clinical Presentation • Can spread to other organs, but most commonly if there is an extraintestinal infection it will be of the liver •Symptoms/physical exam • Fever • RUQ pain • Hepatomegaly • Wt loss • NO DIARRHEA 42 Amebiasis – Diagnosis Stool test ◦Shows cysts and/or trophozoites Serological/antigen tests ◦Can detect antibodies up to 10 years after infection ◦Not as reliable as stool tests LFTs o increased ALP Amebiasis – Diagnosis Liver imaging (US, CT, MRI, radioisotope) ◦Can show location and size of hepatic abscesses ◦US --> cystic intrahepatic cavity with round, well-defined hypoechoic mass ◦CT --> low density mass with peripheral enhancing rim Sigmoidoscopy, colonoscopy, rectal biopsy ◦Shows ulcers Amebiasis - Treatment If patient is asymptomatic: Luminal amebicide (iodoquinol or paromomycin) x7-10 days Acute symptoms: Metronidazole or tinidazole PLUS luminal amebicide x 7-10 days Alternative: tetracyline + luminal amebicide --> chloroquine Liver abscess or any other extraintestinal amebiasis: If > 5cm --> drain and then treat with medication Metronidazole or tinidazole PLUS luminal amebicide followed by chloroquine 45 Amebiasis – Treatment/follow-up Severe infection IVF Electrolyte replacement Opioids Follow-up 2-4 weeks post treatment 3 stool samples at 2-3 day intervals Colonoscopy 46 PO Metronidazole (Flagyl) Class: Antiprotozoal, Antibacterial, Nitroimidazole Dosages: 250mg or 500mg MOA: inhibits nucleic acid synthesis by disrupting the DNA and resulting in inhibition of protein synthesis and cell death in susceptible organisms Absorption: 80% from GI tract Metabolism: liver Elimination: 8 hr half life in adults; excreted primarily in urine ADRs: GI upset, HA, metallic taste, bacterial infection CIs: pregnancy in first trimester, EtOH use Pt ed: take with food, no EtOH used while taking or 3 days after completion ADRs of metronidaz ole Luminal Amebicide Include drugs: iodoquinol, paromomycin, diiodohydroxyquinoline, diloxanide furoate Work in the intestinal lumen and are only active against the intestinal forms of amebiasis Used for asymptomatic and mild-moderate disease Paromomycin (Humatin)- PO Class: intestinal amebicide Dosages: 250mg capsule; dosing = 25-35mg/kg/day divided TID MOA: Acts directly on ameba; has antibacterial activity against normal and pathogenic organisms in the GI tract; interferes with bacterial protein synthesis by binding to 30S ribosomal subunits Absorption: poor oral absorption Elimination: 100% in feces ADRs: GI upset, heartburn, nausea, vomiting CIs: intestinal obstruction Giardiasis – “backpacker’s diarrhea” Giardia lamblia Pear shaped, flagellated protozoan Second most common parasitic infection in the U.S. after pinworm Transmission via fecal-oral route Commonly water-borne because Giardia is resistant to chlorine levels in normal tap water and survives well in cold mountain streams 52 Giardiasis – Epidemiology Widespread throughout the world More common in area with poor sanitary condition and limited watertreatment facilities Risk Factors: ◦ Child ◦ Working with children ◦ Lack of access to safe drinking water ◦ Unprotected anal sex ◦ Living in endemic areas ◦ Being a traveler ◦ Immunocompromised Giardiasis – Life Cycle Humans acquire giardiasis by ingesting the cyst form of the parasite After contact with the gastric contents, the parasite excysts and transforms to two trophozoites (binary fission) Trophozoites cause disease by attaching to the epithelium of the small intestine via a ventral sucking disk Trophozoites that do no attach then revert back to the infectious cyst in the large intestine and passed in the stool 54 Giardiasis Giardia lamblia 55 Giardiasis – Clinical Presentation ◦ Diarrhea usually has mucus, foul smelling, “floats” (steatorrhea) ◦ Nausea ◦ Vomiting ◦ Malaise ◦ Flatulence ◦ Cramping, ◦ Weight loss ◦ Dehydration ◦ Asymptomatic (50%) 56 Giardiasis: Diagnosis ◦ Stool antigen detection assays ◦ Sensitivity of examination of a single stool is only 50-70% ◦ This increases to 85-95% with three serial specimens ◦ Stool PCR assays ◦ Stool microscopy ◦ Cysts have 4 nuclei ◦ Trophozites have 2 nuclei, 4 pairs of flagella, and adhesive disc 57 Giardiasis: Treatment Hydration Metronidazole 250mg TID x 5 days Alternatives Tinidazole 2g once Nitazoxanide 500mg BID x3 58 Giardiasis: Complications Dehydration Persistent or recurrent symptoms Failure to thrive in children Rare complications: ◦ Reactive arthritis ◦ IBS ◦ Lactose intolerance Helminth infestations Helminth infestations • Macroscopic parasitic worms • 3 groups • Cestodes (tapeworms) • Trematodes (flukes) • Nematodes (roundworms) • Enterobius vermicularis (pinworm) • Ascaris lumbricoides (giant roundworm) • Ancylostoma duodenale (hookworm) • Onchocerca volvus (River blindness) Life cycle includes: egg --> larvae --> adult Pinworm Enterobius vermicularis 62 Pinworm An intestinal infestation (cecum) by Enterobius vermicularis characterized by perianal itching. Infestation usually results from finger transfer of ova from the perianal area to fomites (clothing, bedding, furniture, rugs, toys), from which the ova are picked up by the new host, transmitted to the mouth, and swallowed. The female worm migrates to the perianal region (usually at night) to deposit ova within the skinfolds 63 Pinworm- Epidemiology One of the most common nematode infections worldwide ◦ #1 helminthic infection in the US Occurs in both temperate and tropical climates Humans only natural host Children 5-10 years old Pinworm Enterobius vermicular is 65 Pinworm- Clinical Presentation • Perianal pruritus (crawling sensation that is worse at night) •Insomnia •Wt loss •Enuresis •Irritability •Secondary skin infections •Asymptomatic Pinworm-Diagnosis Visual inspection of anal verge and undergarments Scotch tape/Paddle test: ◦Ova obtained in early morning by patting child around perianal skinfolds and put sticky side down on glass slide and view under microscope ◦This procedure should be repeated on 3-5 successive mornings/nights if necessary to rule out pinworm infestation. 67 Pinworm: Treatment ◦Albendazole, mebendazole or pyrantel ◦All are given in a single dose and then repeated 2-4 weeks later ◦All clothing, bedding must be washed ◦HANDWASHING! ◦Showers preferred to decrease bath water contamination 68 Pinworm: Treatment ◦Mebendazole 100 mg po (regardless of age) ◦Albendazole 400mg on an empty stomach ◦Pyrantel pamoate 11 mg/kg (maximum 1 g) po ◦Available OTC in the US ◦Favored for pregnant women ◦Topical malathion or ivermectin around perineum Mebendazole (Emverm) Class: anthelmintic Dosages: 100mg chewable tablet MOA: Inhibits the formation of helminth microtubules; selectively and irreversibly blocks glucose uptake and other nutrients in susceptible adult intestine-dwelling helminths Absorption: poor oral absorption Elimination: 100% in feces ADRs: abdominal pain, diarrhea, flatulence, n/v, hepatitis, seizures (rare), SJS or TEN when administered with metronidazole CIs: pregnancy, concurrent use of metronidazole Giant Roundworm Ascaris lumbricoides 71 Roundworm Ascaris lumbricoides - Epidemiology Ascariasis is the most common roundworm infection worldwide ◦Most common in Asia ◦Children age 2-10 y/o Favored in tropical climates, but also in dry areas during the rainy season Transmission: contaminated water or food The infection is most common in areas with poor sanitation practices asocial with fecal contamination of soil, water, and food. 72 the migration of larvae through the lungs as a necessary part of their lifecycle Taken from OSU College of Biological Sciences 74 Roundworm: Clinical Presentation ◦Asymptomatic ◦Early phase (pulm manifestations) ◦ Fever, coughing, and wheezing ◦Late phase (intestinal manifestations) ◦ Nausea/vomiting ◦ abdominal cramps, colonic obstruction, biliary obstruction, intestinal perforation 75 Roundworm Ascaris lumbricoides o Stool microscopy o Eggs o Adult worms oEndoscopy oERCP (biliary obstruction) Roundworm: Treatment ◦Mebendazole 100 mg BID x 3 days or 500mg x1(regardless of age) ◦Albendazole 400mg on an empty stomach ◦Pyrantel pamoate 11 mg/kg (maximum 1 g) po ◦Available OTC in the US ◦Favored for pregnant women Adequate sanitation and avoiding uncooked foods. 77 Roundworm: Treatment NGT IVF Surgical removal Endoscopy 78 Hookworm Ancylosto ma duodenale 79 Hookworm Ancylostoma duodenale 80 Hookworm Ancylostoma duodenale •A. duodenale is widely distributed in the Mediterranean basin, India, China, Japan, and the Pacific coastal areas of South America but is rare in the USA and equatorial Africa •Transmission: penetration of the skin by the larvae • Need 1. fecal contamination of soil, 2. favorable soil conditions, 3. contact of human skin with contaminated soil •Other species: Ancylostoma ceylanicum, and Necator americanus 81 Hookworm Lifecycle 82 Hookworm: Clinical Presentation Reflect the 4 phases of hookworm infection: ◦Dermal penetration by infecting larvae ◦ Focal pruritic maculopapular rash at site of penetration “ground itch” ◦Transpulmonary passage ◦ Mild cough, pharyngeal irritation, blood-tinged sputum, low-grade fever ◦Acute GI symptoms ◦ Nausea, diarrhea, vomiting, mid-epigastric pain, increased flatulence, wt loss ◦Chronic nutritional impairment ◦ Blood loss during attachment to the intestinal mucosa ◦ iron-deficiency anemia and hypoproteinemia, causing pallor, dyspnea, weakness, tachycardia, impotence, and edema. Hookworm Disease develops from a combination of factors: ◦Heavy worm burden ◦Prolonged duration of infection ◦Inadequate iron intake Hookworm: Diagnosis and Treatment Diagnosis: Treatment: Stool sample with oval hookworm eggs General support and correction of anemia may be needed first if the infection is heavy and the anemia is severe PCR for species-specific diagnosis Hypochromic microcytic anemia Eosinophilia Mebendazole is the drug of choice (BID x 3 days) Oral iron Nutritional support 85 Sexually Transmitted Parasites Trichomoniasis GU infection caused by Trichomonas vaginalis Transmission: sexual intercourse; vertical transmission (mother-baby) Most common nonviral STI worldwide Humans only natural host Trichomoniasis – Clinical Presentation • Purulent malodorous thin discharge • Burning with urination •Genital itching •Urinary frequency/urgency • Dyspareunia Trichomoniasis – Physical Exam Findings • Green-yellow, frothy malodorous discharge • Erythema of genitalia • Punctate hemorrhages (vaginal mucosa/cervix) Trichomoniasis – Complications • Urethritis • Cystitis • PID • Prostatitis • Epididymitis • Infertility • Increased risk of HIV and other STIs • Preterm delivery • Low birth weights Trichomoniasis – Diagnostic testing • + nucleic acid amplification test (NAAT) • Wet mount • + culture • + rapid antigen • + nucleic acid probe Trichomoniasis – Treatment/Follow-up Nitroimidazole class ◦Metronidazole (pregnancy safe) ◦ 2g once or 500mg BID x 7 days PO ◦Tinidazole ◦ 2g once or 500mg BID x 5 days PO ◦Secnidazole ◦ 2g once (granule packets) ◦Treat ALL sexual partners Repeat testing in all patients with a vagina ◦ NAAT or previous modality Sources Strayer, D.S. & Saffitz, J.E. (2020). Rubin’s pathology mechanisms of human disease (4th ed.). Wolters Kluwer. Whalen, K. (2023). Lippincott illustrated reviews pharmacology (8th ed.). Wolters Kluwer. Cornelissen, C. N. & Metzgar, M. (2020). Lippincott illustrated reviews microbiology (4th ed.). Wolters Kluwer. Centers for Disease Control and Prevention. (2019, September 17). DPDx- Laboratory identification of parasites of public health concern hookworm (intestinal). https://www.cdc.gov/dpdx/hookworm/ Weller, P. & Leder, K. (2023 Aug 31). Hookworm Infection. Uptodate. https://www.uptodate.com/contents/hookworm-infection?search=hookworm&source=search_result &selectedTitle=1~56&usage_type=default&display_rank=1#H2 Weller, P. & Leder, K. (2022 Oct 19). Ascariasis. Uptodate. https://www.uptodate.com/contents/ascariasis?search=ascaris%20lumbricoides&source=search_res ult&selectedTitle=1~44&usage_type=default&display_rank=1#H2442323937 Weller, P. & Leder, K. (2023 Nov 06). Enterobiasis. Uptodate. https://www.uptodate.com/contents/enterobiasis-pinworm-and-trichuriasis-whipworm? source=history_widget

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