Parasites 1 Flashcards
Antiparasitic MoA Benzimidazoles
Binds to nematode tubulin and prevents microtubule formation, leading to cell death - Albendazole, Mebendazole
Antiparasitic MoA Pyrantel
Nicotinic acetylcholine receptor inhibitors bind to neuromuscular junction receptors causing spastic paralysis of worms
Antiparasitic MoA Ivermectin
Inhibition of glutamate-gated chloride channels - increasing chloride levels causing paralysis of worms
Antiparasitic MoA Praziquantel
Induce an influx of calcium into the worm leading to worm paralysis and worm death
Ascaris lumbricoides Epidemiology
Tropical, poor sanitation and warm weather. 25% of humans infected. Disproportionately affects impoverished children
Ascaris lumbricoides Pathogenesis
Early usually asymptomatic. Eosinophilic pneumonitis Loeffler’s syndrome - dry cough at 1-3 weeks, SOB, asthma-like syndrome associated with allergic response to larvae. Some people may cough up larvae. Intestinal infection commonly causes abdominal discomfort, rarely intestinal obstruction due to a bolus of worms stuck at the ileocaecal valve. Ectopic infection may rarely occur with ‘wandering worms’ - wandering is promoted by fever, anaesthetics, antihelminthic treatment etc
Ascaris lumbricoides Diagnosis
Eggs in stool, occasionally large worm. Adult worms may be detected by colonoscopy, barium meal or ultrasound
Ascaris lumbricoides Treatment
Albendazole, pyrantel
Ascaris lumbricoides Prevention
Improve sanitation, hand hygiene, mass drug administration
Ascaris lumbricoides Summary
Egg: crenelated, adult worm: 20-35cm, large bowel, transmission soil to mouth, Clinical: asymptomatic, Loeffler’s, GI obstruction, cholangitis, peritonitis. Distinct features: lung migration. Eosinophilia only if in lungs. Treatment: Albendazole.
Capillaria philippinensis Epidemiology
Philippines and Thailand, also Taiwan, Japan
Capillaria philippinensis Pathogenesis
Adults in the mucosa and submucosa of upper small intestine -> severe inflammation -> sloughing of mucosa. Worms can multiply within the gut -> internal autoinfection and overwhelming number of worms. Protein-losing enteropathy, malabsorption, watery diarrhoea -> dehydration and wasting (mortality >35% in untreated patients)
Capillaria philippinensis Diagnosis
Symptoms relate to worm burden. Most commonly diarrhoea, abdominal pain, borborygmi, weight loss. Abdominal distension and oedema may develop. Eggs in stool (occasionally larvae in severe cases)
Capillaria philippinensis Treatment
Albendazole, prolonged treatment necessary as larvae buried in mucosa may be insusceptible
Chagas Epidemiology
WHO estimates 5-8mil people worldwide infected. Bolivia is peak, largely central and south America, including Mexico - Bolivia has the highest incidence and prevalence in the Americas, but there are parts of Bolivia where there is no transmission at all – there is no granularity of where the risk areas are – problem for countries, but also for migrant health services – difficult to ascertain lifetime risk and offer testing to everyone (probably the safest)
Chagas Vector
Triatomine bug - painless bite, bigger than mosquitos or midges
Chagas Organism
Trypanosoma cruzi
Chagas Sequelae
2/3 indeterminate - disease free, 1/3 determinate - disease - End organ damage to heart and GI tract (or both
Chagas Transmission
Vector faeces, vertical, transfusion, transplantation, oral ingestion (large dose - fatal)
Chagas Treatment
No evidence clearing the parasite has any impact on sequelae, BUT growing interest to treat women of childbearing age to interrupt vertical transmission
Chagas Atypical presentations
HIV mimic cerebral toxo with SOL/meningoencephalitis, transplant recipients - fever, rash, myocarditis (mimics acute Chagas)
Chagas Exposure
Risk related to duration of exposure to Triatomine, probably need to be living at least 6 months in area, no cases described in traveller
Chagas Life cycle
Bug gets infected from blood meal of infected host, replication occurs in the stomach. Bug bites to take a blood meal, satisfied with blood meal defaecates – causes itch and human scratch inoculates it. Portal of entry mucus membrane of eye – often bite around the eye, defaecates – wipe faeces into eye – Romanya’s sign (infrequent clinical sign) – looks like periorbital cellulitis – manifestation of acute Chagas
Chagas Family
Diagnosis should prompt wider family testing, may have common maternal source
Chagas Natural history
Self-cure does not occur in most infected individuals, paradigm is lifelong infection. Infection does not necessarily lead to disease. Indeterminate ‘have not developed end-organ disease’ – just have a positive antibody test. most determinate disease is isolated cardiac disease, some digestive (megacolon), some unlucky get both
Chagas Cardiac disease
Arrhythmia, Myocardial abnormalities esp DCM -> aneurysms -> thromboembolic events
Chagas GI disease
Megaoesophagus or Megacolon - severe constipation
Chagas Serology
2 tests to confirm, eg RDT screen, ELISA confirm. Titre unhelpful, Ab response to therapy variable
Chagas PCR
Not widely available, only performed if seropositive, helps to guide giving treatment, but killing parasite may not have any impact on whether they develop disease in the future, and the same for those with disease
Chagas Xenodiagnosis
Xenodiagnosis no longer routinely used – put the bug on the patient to bite (painlessly) to take a blood meal – then keep triatomine alive for a few weeks, then examine stomach for whether the parasite present – need to use the right triatomine for the person’s geographical location
Chagas Treatment
Benznidazole or nifurtimox, 60d poorly tolerated 1/3 will not complete - effective for parasite clearance, effect upon clinical endpoints unproven except prevents vertical transmission. BENEFIT trial demonstrated no benefit in reducing progression of cardiac disease
Chagas Treatment who
Indeterminate (pre-disease) seropositive, and immunocompromised with determinate, plus girls and women of child-bearing age, in addition to infants and children - treatment is toxic, lengthy and of variable benefit, but patients often want it as don’t like the idea of parasite
Chagas Treatment future
BENDITA study - shorter courses of benznidazole (2w instead of 60d) + MULTIBENZ study - probably can get away with shorter and lower dose courses
Chagas HTD protocol
Confirm serology, PCR, assess end-organ (cardiac ECG, 5d holter TTE, GI only if sx), explain diagnosis and implications for patient, siblings, children (if female), discuss merits and uncertainties of antiparasitic treatment, treat the underlying end-organ disease, and offer antiparasitic treatment, annual review to follow progression to determinate disease
Chagas Summary
2/3 infections ‘silent’, serodiagnosis then PCR, benznidazole treatment is toxic, therapeutic benefit uncertain - affects parasitological cure but impacts upon future end-organ damage less clear, shorter, better tolerated regimens are shifting balance towards offering treatment to wider range of patients
Chagas Vector control
Spraying campaigns, vector avoidance
Chagas Vertical transmission
Vertical transmission occurs in 5% pregnancies in women with T cruzi infection, without testing the transmission is invisible, antiparasitic treatment of infants is highly effective so early detection and treatment is critical, antiparasitic treatment during pregnancy is contraindicated, but future pregnancies can be protected by treatment, pre-conception antiparasitic treatment prevents almost all vertical transmission
Chagas UK Chagas Hub
Diagnosis gap in London, community engagement to promote diagnosis and engagement in care successful
Chagas Epidemiology
Most important parasitic disease of the Americas, 6-7million infected, 100 million at risk of infection, 25% of Latin America
Chagas Romana’s sign
Parasite enters through eye and looks like periorbital cellulitis
Chagas Pathogenesis
Not well understood, three theories: direct presence of parasite, neuropathy (destruction of ganglionic nerve fibres), autoimmune response - T cruzi Ag elicits a powerful autoimmune response. An efficient immune response can control the infection, leading to an indeterminate form of the disease, while a deficient response can result in chronic complications. Chronic chagas heart disease involves a persistent low-grade immune mediated myocardial injury and parasite-dependent myocardial damage
Chagas Diagnosis acute phase
Blood films/buffy coat/wet prep looking for T cruzi trypomastigotes - parasitaemia may not be detectable -> qPCR
Chagas Diagnosis chronic phase
Serology is gold standard to detect parasite-specific IgG - screen with commercial ELISA confirm positive with in-house IFAT. WHO recommend using 2 different serological assays to confirm T cruzi infection. qPCR to determine if parasitaemia detectable - parasitaemia in pregnant woman increases risk of congenital infection, reactivation in immunosuppressed people, and can be used to monitor response to treatment
Chagas Treatment
Benznidazole or Nifurtimox for 60-90d, treatment women of reproductive age before pregnancy can effectively prevent congenital transmission. Post-partum treatment is also an option
Chagas Control initiatives
Interrupt transfusion transmission through blood donor screening, interrupt vector through residual insecticide spraying - huge endeavour, 100s of 1000s of properties have been upgraded/sprayed - huge infrastructure to do this, cannot ignore zoonosis - it will come back, cannot be eradicated. Limited prospects for vaccine development - intracellular
Cryptosporidium Clinical
Watery diarrhoea, can vary from asymptomatic to life-threatening, 2-4w in immunocompetent, chronic in immunosuppressed, infection does not provide immunity to further infection. Contributes to childhood malnutrition, growth impairment and cognitive deficit
Cryptosporidium Transmission
Faecal oral contaminated foods, aerosolised droplets, note infected children shed oocysts for up to a month after diarrhoea resolved, waterborne outbreaks, chlorine has little effect, water needs to be filtered, small infectious dose (100 oocysts), animal reservoirs
Cryptosporidium Epidemiology
Globally caused 133,000 deaths and loss of 820,000 DALYs
Cryptosporidium Treatment
Mostly self-limited. Paromomycin, nitazoxanide in immunocompetent effective, but not in immunosuppressed - healthy host immune system is essential to effectiveness of nitazoxanide
Cutaneous myiasis Tumbu
C anthropophaga - Botfly D hominis
Cyclospora catetanensis Clinical
Acute self-limiting diarrhoea or asymptomatic, can be more prolonged in immunosuppressed
Cyclospora catetanensis Treatment
SXT
Cystoisospora belli Clinical
Self-limited watery diarrhoea, more prolonged in immunocompromised
Cystoisospora belli Treatment
SXT
Enterobius vermicularis Epidemiology
Cosmopolitan - high and low income countries. Is not soil transmitted (eggs do not need contact with soil to embryonate). Broadest geographic range of any helminth. Commonly found in school-aged children.
Enterobius vermicularis Treatment
Albendazole, Mebendazole, Pyrantel. Repeat treatment after 2-4 weeks is indicated as the eggs survive several weeks in environment and reinfection is frequent. The whole family should be treated, and bed linen/clothes etc should be washed
Enterobius vermicularis Summary
Egg flat on one side. Adult worm 1-2mm in rectum. Transmission faecal-oral. Clinical: asymptomatic, pruritus, vaginal discharge. Distinct feature: family clusters, sellotape test. Eosinophilia unusual. Treatment Albendazole
Free-living amoeba N fowleri reservoir
Warm stagnant water - exists as trophozoite, flagellate, double-walled cyst, including swimming pools
Free-living amoeba Acanthamoeba reservoir
Water salt or fresh, including chlorinated, in addition to soil and air (droplet particles)
Free-living amoeba Balamuthia mandrillaris reservoir
Soil
Free-living amoeba PAM Pathogenesis
N fowleri enter nasal sinuses, migrates along olfactory nerve, incubation 2-5d severe headache, meningism -> coma
Free-living amoeba PAM Diagnosis
Direct exam of CSF (Naegleria, Balamuthia not Acanthamoeba), PCR
Free-living amoeba PAM Treatment
Amphotericin B, Miltefosine, Nitroxoline (none work well, 97% mortality)
Free-living amoeba GAE Pathogenesis
Acanthamoeba more commonly than Balamuthia mandrillaris - intranasal or break in skin followed by spread to CNS over 3-6 months
Free-living amoeba GAE Diagnosis
Amoeba rarely present in CSF, H&E stained specimens cysts and trophozoites are found in tissue (may be mistaken for macrophage)
Free-living amoeba GAE Treatment
Uncertain, Miltefosine, Nitroxoline tried, most patients diagnosed at post mortem
Free-living amoeba Amoebic keratitis
Acanthamoeba infect cornea - trauma then contamination, both trophozoites and cysts can infect, 93% cases occurred in contact lens wearers
Free-living amoeba Amoebic keratitis diagnosis
Corneal scrape, troph and cysts, culture, PCR
Free-living amoeba Amoebic keratitis treatment
PHMB polyhexamethylene biguanide hourly drops, chlorhexidine gluconate, minimum 4-6 weeks
Helminth Disease
Helminth infections are often disablers rather than killers. Most species do not multiply inside the host, so the worm burden depends on level and duration of exposure e- disease is often cumulative, build up of disease over time
Helminth Serology
Cannot distinguish between current and past infections, not useful in endemic areas. None in use for STH except for Strongyloides stercoralis. No antigen tests available. PCR still very expensive to develop and run, not useful in a field situation, not easy on stool (difficult to extract sufficient DNA from stool, in particular from helminth eggs), and so far has not been shown to be more sensitive than stool microscopy
Helminth Mass drug administration
MDA recommended if prevalence >20% - heavy infections are known to inhibit physical and cognitive development in children for Ascaris lumbricoides, Hookworm and Trichuris trichura
Hook worm Epidemiology
Warm moist climates, most important intestinal nematode infection from public health perspective, attach to mucosa in small intestine, blood feeding, infection is through penetration of skin. Infection with Ancylostoma duodenale (2 sets of teeth) or Necator americanus (2 plates)
Hook worm Pathogenesis
Lung migration usually asymptomatic, less commonly eosinophilic pneumonitis Loeffler’s syndrome similar to Ascaris. Adults bite into the mucosa and cause blood loss 50-150ul/worm/day. Worms move frequently leaving persisting haemorrhages due to release of anticoagulant by worms - wound keeps bleeding. Heavy infections may cause 100ml blood loss/day - chronic anaemia may lead to cardiac insufficiency, physical and mental stunting in children, in addition to albumin loss
Hook worm Diagnosis
Stool microscopy for thin walled eggs
Hook worm Treatment
Albendazole, iron therapy for anaemia. Prevention is wearing shoes. Ivermectin may be used, and antihistamines for CLM.
Hook worm Prevention
Break the cycle: improved sanitation, mass drug administration, shoes. Vaccine in development - game changer if effective
Hook worm Cutaneous larva migrans
Intensely pruritic serpiginous rash - creeps along for days, track is inflammatory/allergic response to microscopic larva - IgE mediated release of histamine -> pruritus. Gradually self-resolves as larvae migrate to lungs. A braziliense and A caninum migrate within the superficial layers of the skin but cannot penetrate further. Serpentine erythematous tracts move 2-5cm/day and can last a few weeks. As humans are not the correct host, cannot develop any further, and causes a self-limiting skin reaction, migrating around and will eventually die within the skin and get cleared away
Hook worm Summary
Thin-walled egg, 1cm worm in small bowel, Transmission: skin penetration, Clinical: asymptomatic, cutaneous larva migrans, Loeffler’s, GI upset, anaemia. Distinct feature: lung migration. Eosinophilia can be high. Treatment Albendazole or Ivermectin
Human African Trypanosomiasis Epidemiology
Rural disease, Angola, DRC, South Sudan, mammals are zoonotic reservoir, endemic to rural areas where tsetse reside, epidemics during civil conflict, breakdown of healthcare infrastructure
Human African Trypanosomiasis T brucei gambiense
West African - Chronic 97% of cases. Parasite spreads through lymphatic system to blood stream, symptoms may include malaise, lymphadenopathy, headaches, undulating fever. Late stage invades organs (inc CNS) - headaches, sleep disturbance, personality change, weight loss, coma and death
Human African Trypanosomiasis T brucei rhodesiense
East African - acute 3% of cases, chancre at site of bite in 50%, often leaves altered pigment on healing
Human African Trypanosomiasis Antigenic variation
Variant surface glycoprotein coat is 10um thick, coats entire cell, parasite can switch coat periodically (~weekly) leading to waves of parasitaemia, waves of fever and parasitaemia can be flat as they may overlap
Human African Trypanosomiasis Diagnosis
Blood smear Tbr high level parasitaemia (Tbg not), LP in Tbg parasites often absent but elevated WBC indicative of stage 2 - LP with great caution not to introduce blood (and parasite) into CSF, Card agglutination for Tbg
Human African Trypanosomiasis T bg treatment
Stage 1 Pentamidine, Stage 2 Eflornithine, newer agents Fexinidazole oral and effective both stages, Acoziborole phase 2/3 studies single dose
Human African Trypanosomiasis Tbr treatment
Stage 1 Suramin, Stage 2 Melarsoprol (arsenic)
Leishmania VL symptoms
Fever >2 weeks, splenomegaly or wasting - rule out malaria
Leishmania VL diagnostic algorithm
RDT rK39 serum/plasma if pos =confirmed; neg>DAT if >1:3200 =confirmed, if 1:400-1600 borderline - tissue aspirate/microscopy
Leishmania VL relapse algorithm
Previous VL - tissue aspirate/microscopy essential
Leishmania PKDL features
Papules and nodules with macular hypopigmentation AND lived in or travelled to endemic areas AND/OR PMHx VL treatment
Leishmania PKDL diagnostic algorithm
rK39 (South Asia only) - if positive = probable case, treat
Leishmania VL diagnostics
RDT rK39 - performs well South Asia, reduced sensitivity in East Africa; DAT direct antigen test more sensitive
Strongyloides stercoralis Epidemiology
Worldwide, common in warm and moist climates overlapping with hook worm distribution special feature is autoinfection within life cycle
Strongyloides stercoralis Hyperinfection
RF: Corticosteroids, HTLV-1 (not HIV), malnourished. Leads to faster reproduction cycle, migration to ectopic sites, spread of faecal bacteria to normally sterile sites - can cause recurrent Gram negative bacteraemia, CNS involvement, granulomas and abscesses. Suspect the diagnosis! Eosinophilia rare in hyperinfection - look for larvae in stool and sputum
Strongyloides stercoralis Pathogenesis
Usually asymptomatic, invasion of lungs: Loeffler’s syndrome, Intestine - larvae burrow and damage mucosa. In disseminated disease lung may have respiratory failure +/-pulmonary haemorrhage, Intestine may have submucosal oedema and atrophy, peritonitis due to bowel perforation, secondary bacterial infections of the CNS can cause brain abscess and/or fatal meningitis
Strongyloides stercoralis Diagnosis
Eosinophilia in 80%. Stool microscopy for rhabditiform larvae, rarely adult worm. Stool plate culture or charcoal culture. Serology if immunocompetent (useful in traveller, not those from endemic area)
Strongyloides stercoralis Treatment
Ivermectin, migrating larvae are insusceptible to the drugs, so repeated treatment is necessary. In long-term immunosuppressed patients, regular re-treatments are necessary
Strongyloides stercoralis Prevention
Screen and treat before immunosuppression. Break the transmission cycle: enhanced public health measures, sanitation, mass drug administration, footwear/shoes
Strongyloides stercoralis Cutaneous larva currens
Intensely pruritic - moves linearly for hours (faster moving, short duration than Hook worm) represents IgE mediated response to filariform migration. Resolves quickly when larvae enter circulation
Strongyloides stercoralis Summary
Egg not seen as hatches in intestine. 1mm worm in small bowel. Transmission: skin penetration. Clinical: asymptomatic, larva currens, GI upset, hyperinfection. Distinct feature: autoinfection -> longterm infection. Eosinophilia common (not hyper-infection). Treatment Ivermectin. Ten facts: widespread distribution, walking barefoot on soil contaminated with human faeces, mostly asymptomatic or low grade GI disturbance, autoinfection cycle for decades, serpiginous rash of larva currens. Beware small bowel obstruction (dx on duodenal aspirate). Hyperinfection syndrome, normal/low eosinophils. Cellular immunosuppression including HTLV-1, travellers and migrants are different. Serology, microscopy and charcoal culture are useful.
Toxoplasma gondii Pathogenesis
Toxoplasma is forever - none of the drugs that affect tachyzoites will affect bradyzoites
Toxoplasma gondii Congenital
T1 less likely to infect but more severe, T3 more likely to infect, less severe - cerebral calcification, retinal lesions
Toxoplasma gondii Clinical
Toxo encephalitis - can be reactivation or new acquisition
Toxoplasma gondii Diagnosis
IgG lifelong, rising titre or avidity useful, IgM useful in neonate, PCR on placenta, cord blood, or immunosuppressed patient
Toxoplasma gondii Treatment
Acute not required, Pregnant spiramycin or pyrimethamine/sulfonamide (controversial) - bradyzoites resistant to drug therapy
Toxoplasma gondii Prevention
Avoid undercooked meat and contact with cat faeces (esp kittens <1y) any cause for cat to have diarrhoea can start shedding of oocysts again briefly
Trichinella Epidemiology
Worldwide, parasite of meat eaters. Cases are often clustered, associated with a community feast or a particular butcher’s shop. Domestic pig-rat cycle. Sylvatic cycle in North America associated with bears, and Arctic cycle associated with raw seal and walrus, less commonly Polar bear as bear is cooked
Trichinella Pathogenesis
Acute phase: GI symptoms d2-7, acute inflammatory response d7-21 with fever, myalgia, facial oedema (typically tongue and eyelids), may also have myocarditis due to migrating larvae. Chronic progression to chronic inflammatory cyst stage, with time cysts may start to calcify. They may result in persistent impaired muscle strength, EMG disturbances as well as persistence of inflammatory cells in the muscles
Trichinella Diagnosis
Muscle biopsy
Trichinella Treatment
Albendazole, the earlier the better, as once encapsulated the larvae are very resistant to antihelminthics. Post-exposure prophylaxis with albendazole if given within 6 days of eating raw walrus (kill the adult worms and prevent production of larvae). Chronic stages may be treated with high daily doses of albendazole for extended periods. Corticosteroids may be need for allergic and inflammatory symptoms, often longterm
Trichinella Prevention
Never feed pork to a pig (unless heated to 70oC). Freeze to -15oC for 20 days, or cook >71oC 1min. Current EU legislation all commercially slaughtered pig carcasses are subjected to testing (but this isn’t particularly effective)
Trichomonas Pregnancy
PROM
Trichuris trichura Epidemiology
Primarily in tropical regions. Infection is from ingestion of eggs from the environment. 500 million global infections. Impoverished children are disproportionately affected.
Trichuris trichura Pathogenesis
Worm burrows into intestinal epithelium, feeding on cells and causes small haemorrhages and inflammation (colitis). Moderate to heavy infections can cause oedema and haemorrhagic mucosa with increased risk of bacterial infections. Host immune system may respond - GI lumen but heads buried in mucosa (Th2 response), Ag presentation to GALT, eosinophilia usually mild, immunisation prospects unclear. Immunomodulation possible (Crohn’s) switch from Th1 overstimulation to Th2 by infecting with the worm
Trichuris trichura Diagnosis
Stool microscopy. Direct smear (saline/water), Kato Katz (template 40g sieved faeces with cellophane cover slip, Formol-ether concentration method 2g stool dispersed in 7m 10% formalin in saline or water, sieved, shaken, centrifuged, supernatant poured off, pellet resuspended and examined (this is what is available in LSHTM lab), FLOTAC 1-5g faeces suspended in sodium acetate acetic acid-formalin buffer, centrifuged, pellet resuspended in salt solution and loaded into FLOTAC chamber - examined under microscope
Trichuris trichura Treatment
Albendazole - better to have multiple doses of several days. Benzimidazoles are absorbed in small intestine and therefore do not readily reach the worms in the large intestine
Trichuris trichura Prevention
Break the cycle: better sanitation and hand hygiene
Trichuris trichura Summary
Bulb-ended egg, Adult worm 5cm, large bowel. Transmission soil to mouth. Clinical: asymptomatic, GI upset, stunting, rectal prolapse. Clinical feature: lung migration. Eosinophilia often mild. Treatment Albendazole
Toxocara Epidemiology
Worldwide distribution. Prevalence in dogs ~20% London, 40% Nigeria. Seroprevalence in humans Europe 5%, USA 14%. Peak prevalence of disease in humans is in children
Toxocara Clinical
Visceral larva migrans - wandering larvae in deep organs. Symptoms are caused by inflammatory response to migrating and dying larvae. Covert toxocara in children is a mild subclinical febrile illness, sx can include cough, difficulty sleeping, abdominal pain and headaches. Visceral larva migrans in adults is caused by migration of larvae through internal organs and resulting inflammatory reaction. Death of larvae provoke stronger response, mainly seen in children <5y. Ocular larva migrans is caused by migration of larvae into the posterior segment of the eye, tends to occur in older children (5-10) and young adults. Patients may present with decreased vision. Granuloma formation leading to unilateral visual loss, retinal fibrosis, (may be mistaken for retinoblastoma and enucleation performed!) and retinal detachment.
Toxocara Pathogenesis
Migration of larvae -> eosinophilic tracks and granulomas. Myocardial or CNS involvement can be fatal. Significant association of Toxocara seropositivity and epilepsy. The most common serious pathology is larvae trapped in retina -> granulomatous inflammation
Toxocara Diagnosis
Tissue biopsy, Serology
Toxocara Treatment
Visceral: albendazole +/- corticosteroids. Ophthalmic: as for visceral +/- surgery
Toxocara Prevention
Eggs commonly contaminate parks and children’s play areas (15-25% in UK) so hand washing after play! Eggs may be present on dogs coats (67% of dogs sampled in an Irish dog pound carried embryonated eggs on their coats). In USA infection correlates strongly with dog ownership - infection is from the family pet (?puppy), Control is deworming puppies and preventing them defaecating in children’s play areas. Infection can also occur by ingestion of raw meat containing migrating larvae (eg raw chicken or beef liver, probably a more common route of infection in adults)
Angiostrongylus catonensis Epidemiology
Parasite of rats. Emerging disease with distribution in South Asia, China, Pacific, Australia, Africa and Caribbean (associated with habits of eating raw snails or shrimp)
Angiostrongylus catonensis Clinical
May be benign and self-limiting, however larvae may cause inflammatory granulomatous response with focal necrosis in the brain or anterior chamber of the eye. Eosinophilic meningitis (most common cause worldwide). Symptoms 1+ week after ingestion: often severe headache, neck stiffness, clouded consciousness and visual impairment.
Angiostrongylus catonensis Diagnosis
Eosinophilia, raised cell count on CSF with >25% eosinophils, sometimes larvae. Lesions may be visible on MRI
Angiostrongylus catonensis Treatment
Antihelminthics generally not recommended -> severe inflammation, supportive/symptomatic treatment
Anisakis Epidemiology
Parasite of marine mammals (seals, dolphins) and fish. Distribution worldwide with higher incidence where raw fish is eaten. Delayed gutting allows migration of larvae from viscera to flesh)
Anisakis Pathogenesis
L2 invade gastric or intestinal mucosa -> ulceration, cause tissue necrosis and commonly cause severe epigastric or abdominal pain (often within hours of eating infected fish). Symptoms generally self-limiting. L3 dies after 2-3 weeks and inflammation resolves. However, can cause severe anaphylactic reactions in previously sensitised people (even if fish is cooked). Symptoms may be mistaken for peptic ulcer disease or appendicitis
Anisakis Diagnosis
History of eating fish, eosinophilia
Anisakis Treatment
Albendazole, but unclear
Anisakis Prevention
Larvae killed by freezing fish -20C for >24h or cooking >60C
Gnathostoma spinigerum Epidemiology
SE Asia, more recently Central and South America, China and Africa
Gnathostoma spinigerum Pathogenesis
L3 penetrate gut wall -> epigastric pain. Initial non-specific symptoms include fever, malaise, N&V, diarrhoea and epigastric pain lasting 2-3 weeks, Larvae wander through tissues (>10 years) - symptoms relate to migration. Visceral (eyes, liver, gut, lungs), Cutaneous (most common) painless migrating oedema, CNS (rare) eosinophilic meningitis and myeloencephalitis
Gnathostoma spinigerum Diagnosis
Eosinophilia, history of migrating subcutaneous swellings, history of eating undercooked fish. Serology, Western blot
Gnathostoma spinigerum Treatment
Prolonged albendazole or ivermectin (21d)
Gnathostoma spinigerum Prevention
Cook fish, eels, frogs, birds and reptiles
Echinococcus Epidemiology
Worldwide, RF: dog ownership
Echinococcus Cyst
Germinal membrane -> protoscolices, laminated membrane - carbohydrate rich acellular layer. May contain daughter cysts. Natural evolution is to grow 0-5cm/y
Echinococcus Differential diagnosis
Simple cyst, haematoma, abscess, cystadenoma, cystadenocarcinoma, necrotic liver mets
Echinococcus WHO Classification
CE 1 simple cyst, CE2 cyst with daughter cells, CE3A simple cyst with wall coming away, CE3B CE2 with wall coming away/calcifying. CE4 calcified
Echinococcus Treatment
Viable cyst CE1&2 need treatment, Transitional cyst CE3A/B need treatment, Non-viable CE4&5 don’t need treatment. General principle <5cm = albendazole >5cm without daughter cysts/solid areas = PAIR & albendazole, complex cyst >5cm with daughter cells etc = surgery. Albendazole blocks glucose uptake -> kills cyst. Praziquantel prevents differentiation of protoscolex into cyst (if cyst leaks, prevents dissemination) but does not penetrate into mature cyst - used for perioperative risk of rupture
Echinococcus Diagnosis
Ultrasound is key, Serology (sens/spec ~90%) cannot be used to monitor disease
Echinococcus PAIR
Puncture aspiration injection reaspiration - aim to sterilise cyst content but leave wall in place.
Echinococcus Prevention
Improve facilities at slaughter houses (ban dogs), community education (don’t feed offal to dogs), worm dogs (praziquantel - expensive), stray dog population management, EG95 vaccine for sheep (expensive)
Echinococcus Alveolar
E multilocularis, distribution limited to northern hemisphere invasive parasitic infection primarily of liver, metastasizes to other organs ‘parasitic cancer’ Incubation 5-15y. Diagnosis on imaging (infiltrative growth at margins of lesion, central necrosis, scattered calcification across lesion) Serology, Biopsy if unable to exclude malignancy. Management radical surgery for solitary liver lesions, palliative surgery with lifelong albendazole
Neurocysticercosis Epidemiology
Main cause of acquired epilepsy, important economical losses to pig-raising peasants (affects poorest of the poor), endemic in most non-Muslim developing countries. Caused by Taenia solium
Neurocysticercosis Clinical
May present as diverse neurological symptoms, most frequently seizures (parenchymal), chronic headache and intracranial hypertension (extra-parenchymal)
Neurocysticercosis Diagnosis
The diagnosis of NCC should be based on neuroimaging and supported by specific serological tests. Muscle calcifications on XR, brain imaging MRI better definition, CT better to demonstrate calcification. Serology helps to support the diagnosis made on imaging (Western Blot - Antibody much easier to detect as immune system multiplies it, antigen is very small amount as only produced by the parasite, and more difficult to identify). Parasite DNA can be detected and amplified from serum, CSF, urine - better for extraparenchymal NCC, sensitivity in parenchymal NCC not known.
Neurocysticercosis Treatment
Antiepileptics are extremely important. Challenging as Albendazole may make the condition much worse - need to control inflammation first. Cystic intraparenchymal - albendazole plus steroids if 5-50 cysts. Enhancing intraparenchymal antiinflammatory management. Calcified - no need for antiparasitic treatment. Intraventricular - endoscopic exeresis where available or surgery. Basal - steroids, albendazole, long course, probable VP shunt. Hydrocephalus - VP shunt. The issue is that even at 6 months 40% of cysts still alive after albendazole. Antiparasitic treatment is to prevent future seizures, treatment decisions should be multiD as the treatment is never an emergency
Neurocysticercosis Key concepts
1 NCC is complex 2 No universal Rx 3 Intraparenchymal NCC most Sx can be managed symptomatically, 4 extraparenchymal NCC urgent treatment usually required (surgery or antiparasitic) 5 in expectant (watch/wait) management there is a need for continuous imaging surveillance
Neurocysticercosis Elimination
Attempt in Peru, 7 year project to interrupt transmission through mass treatment of humans and pigs, education, pig culling and replacement - demonstrated that transmission can be interrupted and sustained, however given that a few infective pigs survived it has not yet been possible. Plan for continued targeted and intentional efforts with improved tools (coproantigen stool test, urine ELISA and/or dipstick)
Dracunculus medinensis Clinical
Symptoms: localised itching, swelling, blister, coin shaped wound, white worm emerges. Non fatal, but complications typically occur from secondary infection around emerging worm
Dracunculus medinensis Treatment
No vaccine, drug, surgery or diagnostic test. Worm is extracted by gently soaking the affected area in (contained) water for 20 min and winding the worm around a piece of gauze, can take a few days or weeks to fully remove. If it breaks, is a foreign body with significant risk of infection.
Dracunculus medinensis Prevention
Health education, behavioural change is most effective
Dracunculus medinensis Eradication strategies and obstacles
Break the life cycle, prevent humans drinking contaminated water with copepods, prevent infected humans entering water sources, destroy copepods with ‘Abate’. Obstacles - insecurity, population movement (exacerbated by political insecurity), donor fatigue (filters), community fatigue (loss of engagement in checking filters, esp if low numbers of cases), atypical transmission, pseudo presentation. Newly identified dog infections - animal reservoir undermines likelihood of eradication
Dracunculus medinensis Vector control
1 Filters: Pipe: every person has one. Cloth: every household has one, check for holes, wash out container, fill container, wash cup, wash filter, hang filter to dry. Filter misuse is common. 2 Abate - kills mature copepods, applied in villages that have active cases, every possible water source is mapped and treated, repeated application every 28d until transmission season ends
Dracunculus medinensis Epidemiology
2018: Chad, South Sudan, Angola
