Parasites 2 Flashcards
Baylisascaris procynosis Summary
Zoonotic infection from racoon ascaris. Confirmed in Nth America, Europe and Japan. Human infections are rare and often asymptomatic but can cause 3 major syndromes: VLM (eosinophilia and organ involvement), neural larva migrans (predilection for neural tissue leading to eosinophilic meningitis) and/or ocular larva migrans (DUSN = diffuse unilateral subacute neuroretinits)
Baylisascaris procynosis Life cycle (environment)
Eggs need 2-4 weeks in soil to embryonate and become infective.
Baylisascaris procynosis Life cycle (human)
Humans ingest egg, eggs hatch after ingestion and hatch
Baylisascaris procynosis PPE
Disposable coveralls or old clothes, strong rubber gloves, washable rubber boots, particulate face mask (N95) or better respiratory protection to prevent ingesting any eggs or inhaling faecal bacteria and fungi stirred up in dust
Baylisascaris procynosis Ocular findings
Early: Multifocal grey lesions –> Late: pale optic disc, narrowed retinal vessels, pigmentation alterations -> worm visualisation (occurs in approx 25-40% of cases)
Baylisascaris procynosis DUSN Differential diagnosis
DUSN = Diffuse Unilateral Subacute Neuroretinitis: Toxoplasma, Histo, Syphilis, non-infectious and caused by a worm travelling through the subretinal space: Gnathostoma, Angiostrongylus cantonensis, Baylisascaris procyonsis, Ancylostoma caninum, Toxocara canis
Baylisascaris procynosis Diagnosis
Serology (usually negative as poorly sensitive), if peripheral eosinophilia or concern about VLM
Baylisascaris procynosis Treatment
Neurology: Albendazole and Praziquantel for prolonged duration. Outcomes poor, consider addition of steroids, if high risk exposure can consider preventive therapy with albendazole for 10-20d. Ophthal: preferred therapy is photocoagulation, if not possible can treat with Albendazole +/- scattered photocoagulation. Can also consider adding with heavy exposure load
Baylisascaris procynosis Key points
Baylisascaris is a racoon round worm infection, in which humans can become accidental hosts if ingest old (>2 weeks old) racoon faeces. The eggs are exceptionally resistant to physical and chemical factors. Can be killed with heat. Seen in Nth America, Europe and Japan. Can present with neural, visceral or ocular larva migrans. Nematode causes of DUSN include Baylisascaris spp, Toxocara canis, Ancylostoma caninum, gnathostomiasis, angiostrongyliasis, strongyloidiasis. Treatment is photocoagulation and/or albendazole, and add steroids of neurological disease
Baylisascaris procynosis Retinitis Differential diagnosis
Bacterial (TP, Bartonella, Brucella, Coxiella, Endocarditis, Whipple’s, TB), Viral (CMV, HSV, VZV, HIV SSPE), Fungal (Histo, Blasto, Cocci, Candida, Crypto), Parasitic (Toxocara, Toxoplasma, Baylisascaris procyonis, Gnathostomiasis, Cystercicosis, Onchocerciasis, Loiasis), Non infectious (Sarcoid, connective tissue disorders, vasculitis, lymphoma, leukaemia, drug induced, pregnancy-related etc)
Schistosoma Epidemiology
Fresh water exposure. If no water, no snails, then no disease. Global disease, Sth America Sm, Africa Sm & Sh, SE Asia/China Sj. (now also in Corsica) 300mil+ infected. Tied to aquatic landscape. Only freshwater, not marine.
Schistosoma Pathogenesis
Exposures generally start early in childhood, MDA treatments do not start until 6yo (guidelines about to change), but cumulative exposure already leads to non-specific symptoms of anaemia (iron deficiency and anaemia of inflammation), growth faltering, fatigue, with decreased quality of life, decreased educational performance, decreased cognition, pulmonary hypertension.
Schistosoma Adult worms
Male envelops female to mate, generally in portal vein, and migrate to plexus dependent on species. Worm has double membrane which evades immune system. Worms do not cause damage, but the eggs are toxic and damage tissues
Schistosoma Disease manifestations
Intestinal Sm Sj, Urogenital Sh
Schistosoma Cercariae
Need at least two (male and female) cercariae to penetrate skin, cumulative exposure and
Schistosoma History & Colonialisation
Bilharz doing autopsies in Egypt and noted worms in canal workers. The basic goal of tropical medicine was to render the tropical world fit for white habitation
Schistosoma Life cycle
Eggs hatch releasing miracidia, need to find a snail (that matches their species), mature in the snail to cercariae (fork-tailed) -> can only live 2 days in water, penetrate skin, lose tail, go into venule straight away, circulate for 4-6w then in the portal vein - ventral suckers stick to the portal vein, Sj upper mesenteric plexus, Sm lower mesenteric plexus, Sh vesical plexus, female releases eggs
Schistosoma Cercarial dermatitis
Clinical diagnosis. Occurs a few hours after exposure - self-limiting rash. 1 Cercariae penetrate skin and transform to schistosomula (cercarial dermatitis), schistosomula locate blood capillaries (intravascular migration starts), intravascular migration of schistosomula right heart to lungs to left heart to systemic circulation pneumonitis. Systemic circulation to portal veins.
Schistosoma Katayama fever (acute Schistosomiasis
Serum-sickness type illness - immune complex disease against eggs (fever, urticaria, cough, abdominal pain), usually 4-6w after infection. Usually self-limiting illness in adults with no previous cercarial exposure, often a diagnosis of exclusion, praziquantel treatment may have to be repeated. Sj> Sm>Sh (due to numbers of eggs and their immunogenicity)
Schistosoma Intestinal Schisto
Both Sj and Sm go to portal vein, then Sj migrates to upper mesenteric plexus and Sm to lower mesenteric plexus. Develop pseudopolyps in colon - granulomas develop in wall and can cause obstruction. Screening tests: Faecal occult blood test or faecal calprotectin (nonspecific inflammation) - these tests normalise with treatment.
Schistosoma Urogenital Schisto
Sh migrates to vesical plexus. Early fibrosis, later hydronephrosis. Sh is a carcinogen –> SCC bladder. Genital schistosoma can affect the entire genital tract not just bladder -> damage by eggs causing granulomas that may cause subfertility, also penile lesions etc. Approach to diagnosis using hand-held colposcopes by midwives (decentralising, task-shifting and creating accessible care), symptoms mimic STI symptoms (inflammation in genital tract esp TV) - vaginal discharge, bloody discharge, genital itching, dyspareunia, infertility/subfertiliity, pelvic pain during or after intercourse
Schistosoma Eggs
Spine hooks into tissues - create a lot of blood loss and damage. Eggs trigger strong immune response to cause general/underlying inflammation, usually eosinophilic infiltrate. Multi-organ egg entrapment over years with granuloma, progressive scarring and calcification.
Schistosoma Portal hypertension
Large, congested liver, periportal fibrosis (not classic cirrhosis). The hepatocytes are generally normal, and even though patients have portal hypertension, varices, they have good clotting factors and do not bleed as much as patients with other causes of liver failure
Schistosoma US finding of Sm
Normal -> Starry sky (non-specific) -> Peripheral echogenic ‘pipe stems’ -> central portal wall thickening -> central portal wall thickening with echogenic ‘patches’ protruding into parenchyma -> Echogenic abnormalities reaching from portal hilum to Glisson capsula
Schistosoma FGS and HIV
Women with HIV are 2-4x more likely to develop FGS. Schistosome infections were associated with increased transmission of HIV from both sexes, increased acquisition of HIV in women, and increased progression to death in HIV positive women
Schistosoma Ectopic
Rare, but do occur - mostly with Sh but can occur with Sm. Examples include lung, spinal (presented as transverse myelitis), cerebral - generally treated with steroids and praziquantel
Schistosoma Intestinal diagnosis Sm
Infection: parasitology on stool - egg count (Kato-katz, formol ether), urine antigen (takes 3-4m post infection to go positive), finger prick blood (SEA Ab - soluble egg Ag). Disease: intestinal schistosomiasis (FOB, calprotectin, colonoscopy), Hepatosplenic disease (US), Functional morbidities (Hb anaemia, anthropometrics, fitness tests). If histo available, eggs may be seen in tissue biopsy
Schistosoma Kato-Katz
41.7mg stool x24 = 1g. Eggs per gram Light <100epg, Medium 100-400epg, Heavy >400epg - and think that only half of the eggs actually are released in stool. Only 10% of infected patients will have eggs in stool - the infection rates are probably 6-7 times higher
Schistosoma Coinfection
Can occur, and the worms can mate with each other - ie Sh and Sm coinfection - and can find Sh in stool and Sm in urine when this occurs
Schistosoma Urogenital diagnosis Sh
Infection: parasitology on urine (urine filtration, urine centrifugation), Urine antigen, vaginal/cervical swabs/lavage and semen (Sh PCR or Sh eggs -filtrate not centrifuge), Finger prick (SEA Ab - soluble egg Ag). Disease: Urinary tract pathology (US, cystoscopy, haematuria [dipstick]), FGS (colposcopy, symptomatology similar to STIs), Functional morbidities (Hb, anthropometrics, fitness tests)
Schistosoma Screening & Diagnosis - Returned traveler
- No symptoms: wait 3 months after last freshwater contact, then screen with serology for Schisto Ab. Blood count (eosinophilia), 3x MSU for RBC and ova, 3x stool for ova. 2 Febrile presentation suggesting acute schisto: exclude life-threatening illness (esp malaria). (PZQ not active at this stage, and if given will need repeat PZQ if diagnosis confirmed). 3. Symptoms (haematuria/change in ejaculate) as for 1., and refer to specialty services (urology, gastro, gynae)
Schistosoma Screening & Diagnosis - Patient from endemic country
- No symptoms: screen with Blood count (eosinophilia), 3x MSU for RBCs and ova, 3x stool for ova. Antigen detection CCA - Sm CAA - all types (most sensitive), Serology for Schisto Ab is not that helpful. 2 Symptoms or signs (eg haematuria/splenomegaly): As for 1 and (refer urology, gastro, gynae). NB: antibody titres may remain high for months/years after successful treatment. Ag detection is useful as it does resolve with treatment
Schistosoma Public health measures
Drug treatment: only affects infected people. Engineering (sanitation): affects parasite eggs (but important to consider not just open defecation, open urination also affects transmission). Snail control: molluscicides (restricted use in small scale settings), biological control (unexpected consequences of introducing new species is a major negative, and limits use of biologic control). Engineering (safe water): affects parasite/larvae.
Schistosoma WHO recommendations 2022
Endemic communities with prevalence >10%, recommend annual preventive MDA single dose praziquantel in all age groups (75% of population including adults, children, pregnant women after T1). Health facilities provide access to praziquantel to all infected individuals including children >2 (exclude pregnant T1, children <2y)
Schistosoma Praziquantel
Pro: active against all schistosome species (and also other worms eg cestodes), excellent safety record, generic production. Limitations: Inactive against immature worms and reinfection, cumbersome unpalatable tablets, global shortage of its availability. Side effects: headache, cramps, anaphylaxis (worm load important esp Sm). The decision for 40mg/kg was made by 5 people sitting in a room - it is probably insufficient - need evidence! Always consider giving a higher dose, or repeated doses (especially required because it is not effective against the immature worms). Inequities of treatment: Preschool children, pregnant women, men and women with genital disease
Schistosoma Summary
Water-borne parasitic infection, snail intermediate host. Two clinical syndromes and ectopic presentations (Intestinal Sm Sj, Urogenital Sh, Ectopic). All forms of schistosomiasis cause inflammation before fibrosis. Diagnosis: Endemic (egg detection methods/antigen detection methods), Non-endemic (serology). Control is with praziquantel chemotherapy to school-aged children. No vaccine available. Neglected populations: pre-school aged children, men/women with genital disease, pregnant women
Onchocerca Epidemiology
Onchocerca volvulus, spread by Simulium black fly. “River blindness” Chronic disease causing unremitting misery and nasty clinical and SES consequences. Affects the poorest of the poor, those that live ‘beyond the end of the road’. Population at risk 123 million (96% Africa, 4% Americas, Yemen). Numbers infected 21 million. Blindness 270,000 (most commonly Sub-Saharan savanna). Vision loss 1 million, Skin disease 15 million. Virtually no new blindness.
Onchocerca Prevention
Vector control (larviciding), later MDA (Ivermectin)
Onchocerca Life cycle (human)
Infected fly bites a human, over the course of a year, the larvae injected will mature into adult parasites. Those adult parasites live in subcutaneous nodules and live for 10y or more. During this time, they will release millions of microfilariae (motile and travel about in skin). Microfilariae will live a year or two - most will die in the skin. The dead microfilariae lead to the pathology of the disease. A small proportion will be taken up by a fly when it takes a blood meal.
Onchocerca Life cycle (fly)
Inside the fly within a week the larvae will mature from L1 to L3 and infective on next blood meal
Onchocerca Vector
Simulium (blackfly) only females bite, outdoor, daytime, painful and cannot bite through skin. Breeding site: rapids in rivers ‘white water’ fast-flowing so well-oxygenated, plenty of nutrients for larval requirements
Onchocerca Clinical
Severity depends on length of exposure to bites and density of microfilariae in the skin. Chronic inflammatory response leads to progressive disease. Chronic skin has spotted depigmentation.
Onchocerca Socioeconomic
Stigma with psychological consequences, reduced marriage prospects, personal and family economic impacts. Community desertion of fertile river valley - 15y anthropological study, decimation of family due to complications
Onchocerca Skin
Early reactions to dead microfilariae in upper dermis: Eosinophil due to helminth, Neutrophil attracted by endotoxin-like molecules released from symbiotic rickettsial bacteria Wolbachia released by dead microfilariae. Acute skin lesions are reversible, Chronic (fibrosis and depigmentation, atrophy) are irreversible. Rare hyperreactive form of disease (Sowda) is active killing of microfilariae - high IgE, intensely itchy, inflammatory infiltrate due to altered Th2 response
Onchocerca Complications
1 Epilepsy, usually onset 3-18y, risk increases with microfilarial load, prevalence can be high up to 18%, risk reduced by biannual ivermectin and vector control 2 Dwarfism likely relates to hypopituitarism in oncho-endemic area of Uganda/DRC 3 ‘Nodding disease’ - involuntary nodding movements precipitated by food or cold in children in oncho endemic areas of Uganda/South Sudan/Tanzania, aetiology uncertain, possibly cross-reactivity with developing neurones but not well understood.
Onchocerca Adult worms
Long lived. Present in subcutaneous nodules <2cm diameter, mobile, firm, well-defined, non-tender or painful. Pelvic girdle in Africa, head and shoulders in Guatemala, Mexico and African children. Usually benign cosmetic blemish. Produce millions of larvae
Onchocerca Microfilariae
Found in skin and eyes, not in blood. Taken up by female vector during a blood meal. The majority are not taken up and die within 1-2y. Living microfilariae motile, dead microfilariae provoke immune response. Leads to skin and eye pathology. Some geographical variation in clinical presentation (blindness, itching, skin disease). Not clear why: host, parasite, vector, environment
Onchocerca Wolbachia
Endosymbiotic bacteria in most filarial parasites. Essential for worm development, fertility and reproduction. Survival advantage for parasites. Neutrophil attraction to bacterial Wolbachia prevents eosinophil-=mediated response to nematode worm: immune evasion. Transmitted transovarially from worm to worm (vertical transmission). Chemotherapy of Wolbachia disrupts fertility and can cause worm death. Treatment: Doxycycline 100mg/d depletes Wolbachia from worms - 3 weeks of treatment causes sterility of adult worms for at least 18 months. 4 weeks of treatment kills them. A long multiple-dose treatment regime is a disadvantage for control strategies but because of the logistics of ensuring compliance. but it is not completely unfeasible. There is no donation program. Doxycycline is a viable radical treatment for anyone with an imported infection
Onchocerca Diagnosis
Skin snips from iliac crests: biopsy to saline, leave 30m-24h - wait for microfilariae to emerge, use microscope to count number of emerged microfilariae. Provides evidence of active infection. Serology: ELISA Ov16 POCT, measures IgG - evidence of exposure to infection
Onchocerca Treatment
MoA unclear, probably paralyses parasites including microfilariae, which are then swept into lymphatics and destroyed. Safe for mass distribution, given every 12 months to reduce clinical features (or 3-5m if aiming to reduce transmission). Clinical impact: reverses early changes in eye (esp in cornea) and in skin (inc itching). Also effective for Wuchereria bancrofti, Ascaris, Strongyloides, head lice and scabies.
Onchocerca MDA
Ivermectin, community-directed treatment - stock given to the community elder to control the administration - much more effective than healthcare workers
Onchocerca Who to treat non-endemic areas
Individual clinical care, light infections, usually short mild exposure in travellers, patients not exposed to further infection. Doxycycline 100mg/d for 4w for radical cure. Or treat with ivermectin 6 monthly depending on reappearance of microfilariae or recurrence of symptoms. 2/3 expected to relapse within 6 months of each dose
Onchocerca Who to treat - endemic areas
Public health programmes: priority for control is communities with high endemicity (eg prevalence >60% in adults) but need to treat all affected communities for elimination (transmission). Morbidity: High prevalence -> high parasite density -> more pathology. MDA (treat everyone in community regardless of infection or disease status every 12 months for control, every 3 or 6 months for elimination, community directed treatment is highly successful. Adult worms are long-lived, programme must last 10 years at least (ivermectin kills mf but not adult worms) Evidence of elimination after 15-17 years of ivermectin in Mali and Senegal. Transmission also halted in foci in Uganda, Sudan, Ethiopia, Nigeria and Niger.
Onchocerca Elimination
WHO 2030 roadmap to eliminate onchocerciasis in 12 countries. Treatment programme no longer needed for 30 million people.
Onchocerca Co-infection with Loa loa
DEC toxic in oncho (it makes vision worse), ivermectin can be fatal in loiasis. Infections coexist in West-Central Africa (Nigeria to Angola). Can screen communities for high loa Ab levels, and in those with high prevalence, use LoaScope - POCT to determine microfilarial load in individual - identifies the people with high levels of loa loa who may be at high risk of severe adverse response to ivermectin - treat everyone else with ivermectin. Consider treating those excluded with doxycycline
Onchocerca Future planning
Ivermectin-tolerance (less effective than it used to be, not yet a major problem, but means new onchocerciasis treatments, especially those that will kill adult worm [macrofilariae]). Promising new drug - Moxidectin (supercharged ivermectin) is a long-lasting microfilaricide
Onchocerca Summary
Onchocerciasis is a chronic disease causing unremitting misery and nasty clinical and socioeconomic consequences. It is caused by infection with the filarial parasite Onchocerca volvulus, spread by the blackfly vector. 99% of cases occur in Africa. This disease causes eye disease, including blindness, skin disease, including unremitting itching. It also causes epilepsy. This is a disease for which we do have effective tools for disease control and elimination (Vector control based on regular larviciding, mass drug treatment with ivermectin). New drugs, especially a safe microfilaricide and short course treatment for Wolbachia would reduce over reliance on ivermectin and would speed elimination.
Onchocerca Nodules
Do not cause significant issues - most are found on bony prominences, mostly asymptomatic. Nodules in the upper body probably have no effect on the development of eye disease. It is the dying microfilariae that cause eye disease.
Onchocerca Skin disease - acute
Massive skin infestation by microfilaria, live mf cause minor symptoms, dying mf create inflammatory reactions which provoke the reactions seen in the skin. Acute phase: severe itching, secondary skin infections due to scratching, disturbed sleep, poor performance. NB - these stages are reversed with ivermectin treatment.
Onchocerca Skin disease - chronic
Irreversible, will still have ongoing itch so still benefit from treatment. Thickening of the skin (Lizard skin), atrophy (the skin looks old even in young adults). Hanging groin (rare caused by inguinal LN dragging the atrophied skin downwards creating a large skin fold). Leopard skin dermatitis (the most common chronic disease). All these conditions are associated with itching which will still be relieved with ivermectin but skin changes are irreversible.
Onchocerca Neurological effects
Children: Growth restriction (Nakalanga syndrome), Nodding syndrome (bizarre disease), Increased mortality. Adults: onchocerciasis-associated epilepsy
Onchocerca Eye
Microfilariae can be found at any component of the eye. Conjunctiva (pruritus and pigmentation), Punctate keratitis (white linear opacity -> inflammatory response -> opacities - these are dying microfilariae stuck in the cornea, repeated heavy infections create irreversible changes, however if it is treated in the first instance, it can be reversible). Sclerosing keratitis (develop at 9 o’clock and 3 o’clock - the space between is affected, sometimes called ‘semilunar keratitis - gradually the rest of the cornea becomes opaque. As the visual axis [pupil] is covered the vision is progressively impaired)
Onchocerca Anterior chamber between cornea and iris
Space full of liquid - aqueous humour - microfilariae love it, sometimes stick on inside of cornea and cause inflammation, sometimes into the iris -> iritis/anterior uveitis -> cause further issues due to inflammation. Pupil begins to stick down and creates further issues with vision
Onchocerca Posterior segment
Chorioretinitis (inflammatory process provokes increasingly destructive chorioretinitis with loss of vision, most often beginning at the periphery). Optic atrophy (inflammatory changes lead to optic atrophy. The retina showing typical effects including clumping of pigment and atrophy of the optic nerve)
Onchocerca Major causes of blindness
Sclerosing keratitis, anterior uveitis (often associated with glaucoma and secondary cataract), progressive chorioretinitis, optic atrophy. NB if there is severe sclerosing keratitis it is impossible to see pathology in the rest of the eye
Onchocerca Community impact
Amadi village South Sudan, 800 of 5000 inhabitants severely visually impaired - significant impact on productivity of community and flow on effects for healthcare and access
Onchocerca Loa encephalopathy
The microfilariae of loa loa are in the blood. Ivermectin causes microemboli of microfilariae (they all stick together). As opposed to Oncho where the microfilariae are in the tissue. LoaScope is a significant advance (only issue is there are not enough and they are too expensive). Subconjunctival haemorrhages appear around the time of neurological issues, and therefore are not a useful predictor. Most patients can be supported through the loa encephalopathy, but depends on the resources available
Onchocerca Vector
Simulium damnosum 95% of transmission in Africa. Eggs 3d in water, several larval instars for 7-12d, then pupae for 3-5d, hatch to adult into terrestrial environment. Mate soon after emerging, female stores sperm, and fertilise the egg as it is being laid. S naevi group (larvae sit on crabs) as opposed to S damnosum which sit on aquatic vegetation
Onchocerca Blood meal
Bites are red and inflamed, with a central area of blood - do not have hypodermic mouth parts like mosquitoes) - similar to horse flies and midges - they cut their way in using lacinial teeth, mandible, then pool feeding and suck the blood
Onchocerca Vector control
1 Larvicides: concentrated at identifiable points (breeding sites in white water rapids) 2 Aim for low toxicity to non-target organisms, use an emulsion or as particles which the larvae will filter and eat (Temephos = Abate emulsion forms bubbles in river, the blackflies filter it out and ingest it, and Bacillus thuringiensis are especially suitable) 3. apply to rivers above breeding sites - insecticide will wash down to blackfly larvae (apply for minimum 10min to ensure lethal dose) 4 repeat the dose one a week to kill every generation 5 measure river discharge before every treatment to make sure that the dilution of the insecticide is correct 6 success of vector control is measured by the reduction of biting rates
Onchocerca Planning to review elimination strategies
Planning: choose sentinel sites for epidemiological and entomological evaluation (check the oncho is disappearing from people and flies). Phase1 Stop MDA, vector control or elimination in support, Phase2 think eliminated transmission, need a survey to confirm this is the case. Phase3 occasional surveys to confirm that there has been no recrudescence or reinvasion
Onchocerca Enacting the review of elimination
Choosing sentinel sites: first line villages - these are villages along the river near productive breeding sites, they would be the most difficult to treat to check the process is effective. Sentinel sites need to be ~40km apart (flies can fly ~20km). Vector surveys: sit and roll trousers up, wait for fly to come to you - catch before they bite you. Preserve fly in 95% ethanol, send to laboratory, there they will be analysed in batches by PCR to determine if they are carrying infective (L3) Onchocerca volvulus larvae - do this with the vector heads - the infective stage is in the head of the black fly
Onchocerca Control mechanisms
Vector control - stop the vector being infected or stop the vector from transmitting, Kill the adult filariae in nodules, kill the microfilariae in skin
Onchocerca Paradigm shift from Control to Elimination
Elimination: not ‘business as usual’, the disease must be fully mapped to identify where transmission is ongoing, treatment strategies will need to be analysed to interrupt transmission as soon as possible. Control is elimination as a public health problem. reduction of blindness and skin problems to insignificant levels, largely achieved except in conflict countries, however there is a constant risk of recrudescence, some treatment and surveillance will be needed for decades.
Onchocerca Post-elimination
Post-elimination surveillance is essential for timely detection of a possible reintroduction of infection. Remember vector control does not do anything for those who are already infected. It may stop other people suffering in future, but does not help those that are already infected. WHO guidelines for stopping MDA and verifying elimination of human onchocerciasis - it tells you the end point, but is not completely clear about how to reach that end point. ATP = annual transmission potential. Seroprevalence in <10yo means they haven’t been infected in over 10y (the average adult worm survives 10y).
Onchocerca Elimination strategy
Interventions in a defined geographical area have reduced O volvulus infection and transmission to a point where the parasite population is believed to be irreversibly moving to its demise/extinction (below breakpoint). Interventions at that point can be stopped. Post intervention surveillance for an appropriate period has demonstrated no recrudescence of transmission to a level suggesting recovery of the O volvulus population. Additional surveillance (post-elimination surveillance) is necessary, for timely detection of infection reintroduced from other areas by population movements or vector invasion. Elimination mapping required to ‘prove zero’ - identification of all areas where transmission is ongoing, coordination with LF treatment, including stopping treatment.
Onchocerca Ivermectin
Ivermectin approved for two diseases but countries must have capacity to distribute. Ivermectin is produced based on a fermentation process therefore demand needs to be calculated well in advance. Currently production is geared mostly for 1x/yr treatment - increasing demands for lymphatic filariasis
Onchocerca Twice yearly treatments
Advantages: reduces transmission particularly in early rounds (skin microfilaria kept at zero), may speed up the achievement of a ‘closed system’, has more effect on adult worms, may increase overall ‘annual’ coverage. Reduces treatment time to 6-7 years, therefore easier to proclaim an endpoint and proclaim success in elimination. Disadvantages: change in CDTI philosophy (distribution times more controlled from central level, more control from central level, no reduction in transmission after several years of treatment). Extra costs involved (retraining, logistics in country). More Ivermectin needed
Onchocerca Alternative treatments
More frequent use of ivermectin used with success in Central America. Other strategies include macrofilaricide which would shorten the treatment period considerably. A macrofilaricide with (microfilaricidal action) would be ideal BUT treatment in Loa loa coendemic areas need a macrofilaricide with no microfilaricidal effects. Doxycycline kills Wolbachia in Onchocerciasis and LF but there is no Wolbachia in Loa loa. It has an impact on parasite reproduction and a delayed microfilaricide effect
Onchocerca Challenges: Capacity building
Public health capacity (epidemiology, modelling, geostatistical evaluation, integration into primary healthcare for sustainability, social sciences). Laboratory capacity (national laboratories, suitable equipment, entomologists - especially important in the elimination and post-elimination phase)
Onchocerca Challenges: Sustainability
The length of treatment to finish the task: when the programme began it was forecast that treatment would be necessary for 10-15y. Computer modelling now suggests 16-25y if once per year therapeutic coverage >65% and geographical coverage is 100%, depending on initial prevalence. Low coverage may need 35+ years. Post surveillance - difficult to find funding, when no treatment. Effects of missed treatment rounds (post COVID, post conflict and post Ebola)
Onchocerca Challenges: Conflict
Working in conflict and post-conflict areas: apart from a few foci in Ethiopia the remaining foci to treat are in DRC, Sudan, Angola, CAR and Yemen. Infrastructure in these countries is mostly badly maintained or destroyed by war, human resources are limited and health services are inadequate. These programmes are therefore more costly to run and a flexible approach is required. Funding needs to be maintained but these countries are often ‘orphan countries’
Onchocerca Challenges: Loiasis
For control strategies it was considered ethical to treat with ivermectin but not in hypo-endemic countries (MEC/TCC guidelines). For elimination all communities must be treated including hypoendemic (where many do not have onchocerciasis). Need to identify patients at risk <30,000 mf/ml Loa loa - treat all those not at risk of SAEs with ivermectin. Test and treat using Smart Phone technology has proved successful and it will become a new strategy - can only use LoaScope between 10am and 3pm which limits its use. Around 2% people excluded from ivermectin Rx in hypoendemic areas. Modelling underway to see if this is significant for transmission
Onchocerca Challenges: New Drugs
Research for macrofilaricide. Emodepside a veterinary product, Tripe drug therapy (Ivermectin, DEC, Albendazole) have shown macrofilaricidal. Repeated doses of Moxidectin. For Loa loa (macrofilaricide without microfilaricidal activity - will avoid severe adverse event as microfilaria will die of their own accord) New anti-Wolbachia medication under investigation
Onchocerca Challenges: data and specificity
Remarkable results for coverage but strategies need adapting to specificities of elimination
Onchocerca Challenges: Country Ownership
OCP and APOC were Regional Programmes with central funding. Ministries gave important political support including for cross border activities but had no real ownership, countries made little financial contribution. Now ESPEN is facilitating national ownership - insufficient domestic funding in many countries, lack of technical capacity. National committees are often underfunded, and rely on very limited ESPEN staff for advice leading to long delays
Onchocerca Challenges: The need for advocacy
No quick fix, many people have forgotten the disease. Not high on the health agenda for many countries, but risk of recurrence if not eliminated
Onchocerca Transmission zone
An area where a local cycle of Onchocerca volvulus transmission is maintained, giving rise to local infections. Foci come in different shapes and sizes based on existing river systems. These foci can cross national and international borders - effective collaboration across administrative borders is very important. Simulium are very mobile and with the winds can travel 400km, so there is always a risk of reinvasion. Transmission can occur when treatment is not carried out ‘across the border’ (national or provincial) with local vectors
Onchocerca Force of infection
Force of infection is the rate at which a predisposed person acquires an infection. In the transmission zone, the force of infection varies depending on the location of the breeding sites and their varying ecosystems, and the baseline prevalence rate. In onchocerciasis endemic countries where the intervention is only an annual dose of ivermectin distributed, transmission interruption may never be attained.
Onchocerca Kinship
Kinship enhanced CDTI was better than the classical CDTI system - CDTI = Community directed treatment with ivermectin. Essentially if there is kinship and community members involved, rather than healthcare workers - there is improved uptake. When just using community leader/elder, sometimes this makes it less desirable than general community members. Additionally, the performance of a community health worker (CHW) is reduced with increasing number of individuals he or she serves (this usually relates to being involved outside kinship group, and therefore not only increases distance travelled, but reduces efficiency)
Onchocerca Slash and clear strategy
A method of physical vegetation removal to deny Simulium damnosum breeding habitat and delay repopulation of the vector. Challenge: it is effective if done within a radius of 2km from the community. Community members have machetes and thrashers - do not buy them equipment, it will be more sustainable if the locals use their own equipment, giving equipment will disempower. This is particularly effective in smaller streams
Onchocerca Monthly Simulium fly population surveillance
Entomologists provide data to the community. They discuss their experience concerning the data presented. Slash and clear and their responsibilities are discussed and agreed upon. The S&C activities should be done within 2km radius from the community. The role of entomologists in monitoring impact is agreed upon. Usually, entomological surveillance is done over a period of 12 months to determine 1. High biting seasons 2 when community self help S&C should be done and 3 the months for follow-up S&C exercise
Onchocerca Challenges: Serology
Serology implies exposure, does not give knowledge of infection, and will remain positive for many years even when transmission no longer exists. This results in delayed decisions for the commencement of the Post Treatment Surveillance (PTS) period and elimination of onchocerciasis. In some areas, the current serological tools experience cross-reaction with other filarial worms such as mansonella species (M persistans, M ozzardi, M streptocerca) resulting in elevated seropositivity
Onchocerca Challenges: Entomology
Lack of well-trained and experienced Simulium vector entomologists. Need to be able to determine there is a prevalence of flies carrying infective larvae (L3) in the head of less than 0.1% of flies
Microfilaria Filarial nematodes
Live as adults in tissues (males and females), indirect life cycles: spread via biting insect. Adult females produce live L1 larvae (microfiliariae). Mf circulate in blood or tissues, gets picked up by biting insect. The Mf then develops inside the insect from L1 to L2 to L3. L3 is the infective stage, transmitted to the next host when insect bites again. Long pre-patent periods (3-9 months, depending on species), long-lived as adults (6-20 years, depending on species)
Microfilaria Treatment
All available drugs are primarily microfilaricidal (acts on larvae but not adult worms), although some evidence of macrofilaricidal (adult) effects after multiple treatment rounds
Microfilaria Ivermectin
Oncho, not Loa loa. Binds with high affinity to glutamate-gated chloride channels, causing increase in chloride ions resulting in paralysis of worms. Also works against Ascaris, Strongyloides, scabies and head lice
Microfilaria Diethylcarbamazine (DEC)
LF and Loa loa, not Oncho. MoA unclear, appears to involve immune system components and paralysis of worms.
Microfilaria Albendazole
Used in combination with Ivermectin or DEC in MDAs
Microfilaria Sheath
Flexible, bag-like structure covering outside of the Mf. Consists mainly of carbohydrate remnants from the egg stage. Provides extra protection for the Mf. Useful for diagnostic purposes
Mansonella Vector
Culicoides midges and Simulium blackflies
Mansonella Epidemiology
M perstans (sub-Saharan Africa, Central and Sth America, Caribbean), M streptocerca (W Africa), M ozzardi (Central and South America and Caribbean).
Mansonella Clinical
Generally mild, viewed as non-pathogenic. Can be associated with angioedema, pruritis, fever, headaches, arthralgias, and neurologic manifestations. (Mansonella streptocerca may cause skin manifestations including pruritus, papular eruptions and pigmentation changes, similar to that of Onchocerciasis).
Mansonella Locations of adults and mf
M. perstans adults in body cavities (pleural, peritoneal). Mf in blood. Mo adults in subcut tissue or body cavities. Mf in skin or blood. Ms adults in dermis, Mf in skin or blood. Mf of all three are unsheathed. Diagnostic: Mf in blood film/skin snip (need to distinguish from other filarial Mf, look for size, sheath and nuclei at tail). Antifilarial drugs generally not effective, some effect of DEC plus Mebendazole for Mp and Ivermectin for Mo.
Lymphatic filariasis Epidemiology
W bancrofti (~107 mil cases worldwide), B malayi (~13mil cases in Asia), B timori (~0.8mil cases on Timor and Flores Islands only). Currently in 72 countries. 36 million disfigured or incapacitated. >900mil people at risk, >25mil men with genital disease >15mil people with lymphoedema of leg. LF requires prolonged exposure, relatively inefficient transmission. Global distribution through sub-Saharan Africa, South and SE Asia. Sth America
Lymphatic filariasis Periodicity
Nocturnal: Wb, Bm. (Diurnally subperiodic Wb in blood at all times but increased in daytime) (Nocturnally subperiodic Bm zoonotic strains in Malaysia, Phillippines, Indonesia)
Lymphatic filariasis Symptoms
Often asymptomatic for years but Mf in blood. Early: episodic attacks of fever associated with inflammation of LN (often groin), lymphoedema, hydrocele in men. Chronic obstructive stage: Repeated episodes of inflammation and lymphoedema leads to lymphatic damage, fibrosis, chronic swelling and ultimately elephantiasis of the legs, arms, scrotum, vulva and breasts. Chyluria (lymph fluid in urine). Skin changes including depigmentation and warts, recurrent bacterial cellulitis (often streptococcal). Most people develop these symptoms years after first being infected
Lymphatic filariasis Pathogenesis
Adult male and female live in lymphatic vessels -> inflammation, fibrosis and blockage.
Lymphatic filariasis Tropical pulmonary eosinophilia
<1% of filarial cases. More common in South and SE Asia, more common in younger men (15-40). Potentially serious lung disease with dry nocturnal cough, wheezing and fever, extremely high peripheral eosinophilia and extremely high serum IgE. Generally Mf negative. Resulting from immune hyperresponsiveness to Mf in the pulmonary capillaries. Responds rapidly to antifilarial treatment (DEC), if untreated may lead to development of chronic interstitial lung disease
Lymphatic filariasis Diagnosis
Mf in blood (thick) film is gold standard. Sample at night 10pm-2am and microscopic examination. Pros: inexpensive and low tech. Cons: impractical. Sensitivity can be improved by membrane filtration (1-3ml blood through filter, examine filter under microscope). RDTs exist, Wuchereria circulating filariasis Ag sens >90% - sample can be collected at any time of day, Brugia Ab detection, Alere Filariasis test strip - fingerprick, now replacing Ag for Wb mapping, monitoring and transmission assessment surveys (but issues with crossreactivity with Loa loa). ELISA also available but problems with cross-reactivity with other filarial species and Strongyloides.. US - filarial dance sign - characteristic movement of adults in lymphatics
Lymphatic filariasis Treatment
DEC kills circulating Mf and prolonged treatment eventually kills adult worms. DEC has dangerous side effects in presence of onchocerciasis - Mazzotti reaction - life threatening (depending on level of Ov infection) characterised by fever, urticaria, swollen lymph nodes, hypotension, oedema, and abdominal pain within 7d of treatment, so Ivermectin is used instead. Ivermectin only kills Mf, Albendazole reduces Mf. Note: many patients with LF are no longer infected with living parasites and do not benefit from antifilarial drug treatment. Lymphoedema and hydrocele - keep clean, elevate affected areas, emollient creams, improve circulation with massage and exercise, compression bandages, treat skin infections with antibiotics
Lymphatic filariasis Control
1997 WHO “eliminate LF as a public health problem’ - MDA for at least 5 years with >65% coverage of total at-risk population. MDA with DEC and Albendazole, or IVM & Albendazole (in areas endemic for Oncho) or Albendazole twice per year (in areas endemic for Loa loa). China achieved elimination by 1 large scale repeated blood surveys to target drug treatment to infected individuals 2 MDA (DEC) for everyone in hyperendemic areas 3 Introduction of DEC-fortified salt (in some regions DEC-Soy) for 3-6 months with several repeats. 2006 declared eliminated from China
Onchocerca Epidemiology
19 million infected (99% Africa) 1% in Northeast of Sth America, 240 million at risk. Blindness 1.15 million (most commonly Sub-Saharan Savanna), Skin disease 14.6 million
Onchocerca Pathogenesis
Pathology is associated with Mf in Eye -> blindness, and Skin -> severe dermatitis. Adult worms form subcutaneous nodules, not directly harmful to the patient. Most Mf die as larvae in host (naturally). Inflammatory reaction to dead and dying Mf is responsible for the disease manifestations
Onchocerca Adult worms
Long lived 10-15y. Worms mature in 7-15m in subcutaneous tissue -> adult male and female in subcut nodules. Adults become encased in fibrous subcutaneous nodules: 1-5cm diameter, mobile, firm, well defined, non tender or painful. 2-50 adult worms per nodule. Most commonly pelvic girdle or head and shoulders. Female worm produces ~200 mf each day that migrate through the skin, eyes and other tissues.
Onchocerca Diagnosis
Mf in skin, organs and eyes (not blood) - normally appear 7-15m after infection. Motile and will continue to travel around the body, If not ingested by Simulium will die after 1-2 years. Dying and dead Mf provoke strong immune response = skin and eye pathology
Onchocerca Onchodermatitis
Pruritis, loss of elasticity, atrophy, pigment changes (leopard skin, crocodile skin, elephant ‘atrophy’ skin, hanging groin (lymphadenitis))
Onchocerca Eye lesions
Death of Mf and inflammation -> fibrosis and scarring - lesions in both anterior and posterior chamber of the eye -> blindness
Onchocerca Diagnosis
Skin snips incubated in saline 1-4h for motile Mf. Giemsa staining: no sheath, tail free of nuclei, (Mansonella spp smaller with nuclei to tip of tail). RDT Biplex for Oncho and LF Ab - monitoring post-control areas and detecting cases in low-prevalence areas
Onchocerca Treatment
Nodulectomy. Ivermectin kills microfilariae but not adult worms. If very high levels of Mf may give reactions so may need steroids together. Do not give Ivermectin when Loa loa present (risk of meningoencephalitis). Do not use DEC (Mazzotti reaction). Doxycycline kills Wolbachia in Onchocerciasis and LF but there is no Wolbachia in Loa loa. It has an impact on parasite reproduction and a delayed microfilaricide effect
Onchocerca Control
Community directed treatment with Ivermectin (except Loa loa endemic regions). Annual treatment for 12-15y at 80% coverage required to break transmission. Larviciding
Loa loa Epidemiology
Obstacle to Onchocerciasis and LF control. Up to 13m infected in West and Central Africa (30 million at risk).
Loa loa Clinical
Most obvious when adult worm crosses the eye = painful. Hypersensitivity to parasite Ag secreted by migrating adults can cause CALABAR swellings (episodic angioedema), most common on extremities, duration 1-4d
Loa loa Diagnosis
Mf in blood (thick) film. Sample at day 10am-2pm. Sheath, stains with haematoxylin but not Giemsa (‘ghost’ on Giemsa). Flattened nuclei go to tip of tail, other: eosinophilia, serology)
Loa loa Treatment
Dangerous in heavy infections (esp. Ivermectin) can lead to meningoencephalitis due to blockage of cerebral capillaries by dead Mf. Dependent on Mf load (if high >1000/ml) need to reduce Mf load before treating with DEC/Ivermectin - start with low dose albendazole plus steroids until reduced Mf, then give DEC or Ivermectin
Microfilaria Wolbachia
A ‘parasite’ within a parasite - obligate endosymbiotic alpha-proteobacteria, infecting may insects (inc Mosquitoes) and some filarial nematodes (Brugia, Wb, Mo, Mp, Oncho - NOT Loa). In filarial nematodes it infects the female reproductive organs, including the eggs (vertical transmission) and is needed for fertility. Appears to be essential for adult worm fertility/viability/survival. Cannot be cultured outside filarial host. Sensitive to tetracyclines (inc doxycycline) and rifampicin but not penicillin or gentamicin. Killing Wolbachia (using doxycycline) sterilises the female worm and over an extended period of time weakens the adults.
Loa loa Doxycycline
Does not kill Mf directly, but as it sterilises adult female worm it reduces Mf levels over time. Rx 4 weeks for LF, 6 weeks for Oncho. Loa loa does not have Wolbachia so is of no use. Problematic to use in MDAs - length of treatment, compliance, pregnancy and children
Lymphatic filariasis Summary
Adults in lymphatics, Mf in blood, Disease caused by adults. Treat DEC
Onchocerca Summary
Adults in subcut nodules, Mf in skin (and eyes). Disease caused by Mf. Treat with Ivermectin
Loa loa Summary
Adults in subcut (causing Calabar swellings) and subconjunctival tissues. Mf in blood. Disease caused by adults. Treat by reducing burden with Albendazole, followed by DEC/Ivermectin once safe
Cestodes General
Platyhelminths - ribbon-like flatworms. No such thing as free-living. Adult worms lives in small intestine of vertebrate animals (definitive host). Larval stages live in tissues of vertebrates and invertebrates (intermediate host). Adults have flat segmented bodies, with a head (scolex, used for attachment to intestinal wall), a neck region (germinal region) and a body (strobila) consisting of a series of segments (proglottids). Hermaphrodites (no separate sexes). No mouth, no intestine, no anus (all nutrients are absorbed through the surface tegument)
Cestodes Definitions
Scolex= head segment. Rostellum= protrusion at the end of the scolex. Strobila= body of tapeworm. Proglottids= individual segments in the strobila. Operculum=“lid” (on the eggs of some species). Metacestode= larval stage found in an intermediate host. Protoscolex=young larval stage of Echinococcus/Taenia. Cysticercoid= small cyst containing a single evaginated scolex, often in intermediate insect host (e.g Hymenolepsis). Cysticercus= fluid filled cyst containing an invaginated scolex in tissues of intermediate host (e.g Taenia). Hydatid cyst= fluid filled cyst containing many protoscoleces of Echinococcus. Hexacanth embryo= six hooked larvae inside the egg. Oncosphere= larval stage once its been ingested by an intermediate host. Coracidia, procercoid, plerocercoid= different larval stages of pseudophyllid cestodes.
Cestodes Anatomical regions
1 Scolex (suckers, grooves and/or hooks for attachment to intestinal wall). 2 Neck (germinal portion). 3 Strobila (body, consists of a series of segments, called proglottids [immature->mature->gravid). Hermaphroditic - male and female reproductive system is present and complete in each segment. No body cavity, no intestinal canal, soft sponge-like tegument, absorbing nutrients. Excretory, muscle and nervous systems are present
Cestodes Cyclophyllids
Taenia, Hymenolepsis, Echinococcus - scolex has suckers and/or hooks, branching uterus, proglottids containing eggs are released from adult worms. Both eggs and proglottids in stool if definitive host (not for intermediate host of T solium or Eg). Eggs are not operculated
Cestodes Pseudophyllids
Diphyllobothrium, Spirometra - scolex has slit-like grooves (bothria), uterus not branching, eggs released from proglottids (proglottids generally remain attached to adult worm). Eggs in stool (Definitive host - D, not for intermediate host S). Eggs operculated, gives rise to ciliated larvae
Cestodes Treatment
Praziquantel - MoA calcium influx into the whole parasite, muscle contraction and surface modifications resulting in paralysis and death of worm
Cestodes Hexacanth embryo
Hexacanth = hooklets that the larvae will use as it exits the egg and uses it to penetrate the intestinal wall
Diphyllobothrium Epidemiology
Fish tape worm, ~20 million infected worldwide. D latum (Freshwater fish Europe, Nth America), D pacificum (Marine fish Sth America Sth Asia), D nihonkaiense (Pacific Salmon Japan and US Pacific coast). Definitive host: human, dog, cat, fox, bear (fish-eating mammals, zoonotic). 1st intermediate host: copepods, 2nd intermediate host fresh water fish (or marine fish). Route of infection: ingestion of raw or undercooked fish containing plerocercoid larvae
Diphyllobothrium Clinical
GI disturbance, anaemia (Vit B12 deficiency in ~40%)
Diphyllobothrium Diagnosis
Eggs in stool
Diphyllobothrium Treatment
Praziquantel (and vit B12)
Diphyllobothrium Control
Cook fish (63oC), Freezing fish (-20oC 24h to a week depending on size of fish). Current EU food hygiene legislation requires all fish sold for raw consumption to be frozen first
Spirometra Epidemiology
Sparganosis - Spirometra mansoni, S mansonoides, etc Definitive hosts: Canids and Felines (domestic or wild). 1st intermediate copepod, 2nd intermediate fish, amphibians, reptiles. Mainly found in East Asia, including China (80% of reported cases), Korea, Taiwan
Spirometra Pathogenesis
Depends on site and activity of larvae: larvae can move around body vigorously (‘creeping tumour’) (most common form). Ocular infection: oedema and pain around and in eye, may cause blindness if untreated. S proliferum can be lethal to humans - the larva proliferates by breaking itself down into segments, each segment then developing into a new plerocercoid larvae within the human host (multiplying)
Spirometra Treatment
Surgical removal of larvae (anti-helminthic drugs generally not useful)
Spirometra Control
Clean water, cooking fish/amphibian/reptile meat, avoid contact with raw amphibian flesh
Hymenolepsis nana Epidemiology
Definitive host: humans, rodents. Intermediate host arthropods (eg flea, flour, beetles, dung beetles). Cosmopolitan, common in temperate zones, more common in children. Human infection is by infection of 1 embryonated eggs (from human or rodent faeces) or 2 cysticercoid-containing arthropod. The intermediate host is optional. Human can harbour both the adult and larval stages of the parasite. Autoinfection can occur when eggs hatch inside intestine. 2-3 weeks to develop into adult worm in small intestine.
Hymenolepsis nana Clinical
Light infections often asymptomatic, Heavy infections non-specific, may give abdominal pain, diarrhoea, anorexia. Children with heavy infection may suffer more severe symptoms than adults
Hymenolepsis nana Diagnosis
Eggs in stool
Hymenolepsis nana Treatment
Praziquantel is effective against both adults and larvae
Hymenolepsis nana Control
Hygiene, sanitation, rodent control, insect control
Taenia saginata Epidemiology
Beef tapeworm, worldwide distribution [anywhere cattle is raised and beef consumed]. Definitive host = humans, Intermediate host = cattle, buffalo (wild ruminants also eg llamas). Human infection by ingestion of under-cooked or raw muscle meat infected with the larvae (cysticercus). 2-3 months to develop into adult in small intestine.
Taenia saginata Clinical
Nausea and mild abdominal pain, anal pruritis due to active exit of gravid proglottids
Taenia saginata Diagnosis
Eggs and/or proglottids in stool
Taenia saginata Treatment
Praziquantel (or niclosamide)
Taenia saginata Control
Meat inspection of bovine muscle at abattoirs. Cooking meat to 56oC. Hygiene and sanitation: environmental decontamination very difficult, eggs are very resistant to most environmental conditions and can survive for several years on pastures. Eggs are disseminated widely in the environment by water, sewage effluents, wind, flies and birds
T solium Epidemiology
Humans can act as definitive or intermediate host. Two types of disease - 1 intestinal infection with adult worm (infection by ingestion of uncooked pig meat infected with larval form). 2 tissue infection with larval form (cysticercosis) - infection by ingestion of eggs from environment (human faeces).
T solium Clinical
Often asymptomatic or mild
T solium Diagnosis
Eggs or proglottids in stool. Proglottids <15 main branches
T solium Treatment
Praziquantel (or niclosamide) BUT possibility of larval disease (cysticercosis)
T solium Control
Meat inspection of pork meat, cooking meat, hygiene and sanitation, antihelminthic treatment of pigs (oxfendazole), Pig vaccine (TSOL18, Cystvax)
T solium cysticercosis Cysticercosis
Ingestion of T solium eggs (not meat): larval establishment in tissues (humans become accidental intermediate hosts). Faecal-oral route: human to human transmission (hygiene, and may affect people who do not eat pork), or sometimes autoinfection (self-to-self). Any tissue may be affected.
T solium cysticercosis Cysticercus
Invaginated protoscolex (“outside-in”) - invaginated in intermediate host, evaginated in definitive host (proglottids will grow from neck region). Die off eventually and become calcified
T solium cysticercosis Histology
Protoscolex with hooks in cyst
T solium cysticercosis Radiology
Calcified lesions - can be anywhere in body
T solium cysticercosis Neurocysticercosis
Estimated 50 million people infected with neurocysticercosis across the world, with approximately 50,000 deaths each year. Neurocysticercosis is the most frequent preventable cause of epilepsy in LMIC
T solium cysticercosis Clinical
Silent/symptomatic depending on site/numbers. Muscle - expands so no or little disease symptoms. Brain - no ability to expand = disease. Eye - problem usually when treated due to the inflammation
T solium cysticercosis Diagnosis
Imaging, serology. Neurocysticercosis (CNS lesions, focal lesions, convulsions, intracranial hypertension). Stage of cyst: live, dying, strong inflammatory reaction, calcified
T solium cysticercosis Treatment
Depends on site, number and symptoms. Albendazole and/or praziquantel plus steroids (surgery, antiepileptics, analgesics)
T solium cysticercosis Control
Humans are the only source of eggs = good sanitation, hygiene
Echinococcus granulosis Epidemiology
Cystic echinococcus, hydatid disease, dog tapeworm. Definitive host is dogs. Intermediate host ruminants (sheep). Humans are accidental intermediate host. Sheep farming - most of the world. Wild cycle: ruminant and canid (wallaby and dingo in Australia). Adult <1cm, scolex with 4 suckers and 2 rows of hooks. Typical transmission: dogs ingest offal (livestock). Human accidental ingestion of faeces (from dog) containing egg. Risk often associated with sheep farming/sheepdogs, and in communities living close to their dogs/domestic animals (also sylvatic cycle involving some wild animals). Eggs may be dispersed by wind, rain, herbivores and insects. Reported to remain infective for several years, can survive freezing conditions.
Echinococcus granulosis Pathogenesis
Larvae - found within the hydatid cyst developing inside the intermediate host, proliferation of new larval stages (protoscolices) from germinal cells inside cyst). Cyst grows slowly but steadily (~1-5cm per year). Brood capsules develop inside the cyst and may contain thousands of scolices ‘hydatid sand’. Host-derived collagen capsule, inside is a germinal layer (parasite derived), from that germinal layer -> proliferation of new larval stages within cyst. Within cyst there are protoscolices, development of daughter cysts within the main cyst. Fluid (hydatid sand) - fluid will contain protoscolices, will see invaginated and evaginated protoscolices containing crown of hooks, suckers, and neck region from which the proglottids will grow. Granular material are called calcareous corpuscles (calcium bodies, common in all cestodes). Symptoms are caused by developing larval cyst. Symptoms vary depending on the organ involved. Most common site is liver (~75% of cases), but can occur anywhere in the body. Abdominal pain, hepatic mass, bile duct obstruction (liver). Chest pain, cough, shortness of beath (lungs), may be asymptomatic for years. Rupture of cyst (trauma, surgery) may cause severe anaphylaxis
Echinococcus granulosis Diagnosis
Imaging, serology
Echinococcus granulosis Treatment
Depends on site, size, stage. Medical: Benzimidazole +/- praziquantel. Surgical: cyst removal, PAIR (puncture, aspiration, injection of scolicide, respiration) - need to remove germinal layer otherwise it will regrow)
Echinococcus granulosis Control
Carcass removal to prevent dogs scavenging, cooking dog food, deworm dogs, controlling stray dog populations
Echinococcus multilocularis Epidemiology
Alveolar echinococcosis (Alveolar hydatid disease). Fox tape worm. Humans accidental intermediate hosts. Definitive host: fox, coyote, dog, cat. Intermediate host: rodents, human. Proliferative -> one of the world’s most dangerous zoonoses. Hunting and berry picking, exposure to foxes - Northern hemisphere. Most cases in Tibetan plateau, spread through central Europe, spreading to Scandinavia - spreading is a problem. Adult <0.5cm, scolex with 4 suckers and 2 rows of hooks.
Echinococcus multilocularis Pathogenesis
Similar to E granulosis but cysts very slow growing, often asymptomatic for 5-15y. Do not have defined collagen capsule around them -> tumour like growth. Cysts mainly in liver, symptoms include weight loss, abdominal pain, general malaise, hepatic symptoms (jaundice etc). Larval metastases may spread to other organs (lungs, brain, spleen) to form new cysts. Untreated is progressive and fatal.
Echinococcus multilocularis Treatment
At early stage if cyst is confined: radical surgery, followed by longterm benzimidazole. Later stages very difficult.
Echinococcus multilocularis Control
More difficult than E granulosis as life cycle involves wild animals. Hygiene: washing of wild berries and mushrooms. Deworming of domestic dogs and cats may help.
Cestodes Pathogenesis
Adult cestodes (when human acts as definitive host) usually cause minor intestinal disease only, but D latum competes for host vitamin B12. Larval cestodes (when human acts as intermediate host) can cause severe disease - T solium - cysticercosis, Echinococcus - hydatid disease
Cestodes Stages in humans
Adult: T saginata, T solium, Diphyllobothrium, Hymenolepsis. Larvae: T solium, Echinococcus, Spirometra - remember the ones that have the more severe outcomes are generally the intermediate hosts
Cestodes Diagnosis
Adult cestodes - identification of eggs/proglottids in stool. Larval cestodes - imaging techniques and/or serology for cysticercosis and hydatid disease
Cestodes Treatment
Adult cestodes: praziquantel (or niclosamide). Larval cestodes: praziquantel or albendazole or surgery for cysticercosis. Albendazole or mebendazole or surgery for hydatid disease
Cestodes Control
Hymenolepsis (hygiene and sanitation, vermin control - rodent & insect). Taenia (meat inspections to prevent infected meat reaching the food chain, proper cooking of meat, improved hygiene and sanitation). Diphyllobothrium (proper cooking/freezing of fish). Echinococcus (regular deworming of dogs and elimination of strays, improved slaughterhouse procedures, washing wild berries/mushrooms)
Leishmaniasis Broad classifications
Visceral: ‘Kala-azar’, and skin complication PKDL ‘post-kala-azar leishmaniasis’. Cutaneous: localised, mucocutaneous, mucosal. Americas (‘New world’), and non-Americas (‘Old world’)
Visceral leishmania Epidemiology
Africa, ME, South Asia, Central and South America. Decreasing trend in South Asia, tends to have epidemic wave pattern every 6-10 years. African numbers stable. Population displacement affects in conflict areas - this plus climate change is changing the location of the sandflies, and making predictions increasingly difficult. General trend across Americas is going down (Brazil carries the largest numbers in Sth America, and is decreasing). Overall, likely underreported. Reported 374 deaths in 2023
Visceral leishmania Cause
Africa, South Asia: L donovani. Middle East, Central Asia, Americas L infantum
Visceral leishmania Vector
Phlebotomine (Old World), Lutzomyia (New World): 1.3-3.5mm length, weak flyers, only female take blood, bite hurts, peridomestic (around house, esp cracked mud walls), zoophilic, indoor biting (respond to IRS), feeds at night, rest during the day in dark, humid, sheltered sites.
Visceral leishmania Risk factors
Transmission: sandfly density, human parasite reservoir, proximity to dogs (reservoirs), sandfly infection rate, human-sandfly interactions. Risk of VL disease: proximity to previous VL cases, poor health/immune status (malnutrition, HIV, TB and other immune-suppressive conditions. There have been clusters associated with IVDU.
Visceral leishmania Natural history of infection and VL disease
Depends on immune response. There are likely 2-30% who are asymptomatic, but who are at risk of transmission. If looking at elimination/eradication - do we treat asymptomatics and how? Versus vaccination. Elimination - <1 case per 10,000 at the district level in country - if that is maintained for 3y, then the disease has been eliminated in the area. Bangladesh has reached it, India is close. Nepal is still a way off.
Visceral leishmania Control
Parasite (strain, drug resistance), Reservoir (Anthroponotic, zoonotic, VL cases, PKDL, asymptomatic), Treatment vector control (current strategies, access, resistances, compliance, side effects, cost), Host (Demographic [age gender\, socioeconomic [poverty, cast, cattle], genetics, immunity/coinfections [HIV, TB, malaria], nutritional status), Environmental (seasonality, cycling)
Visceral leishmania Diagnosis
Clinical suspicion: fever >=2w and splenomegaly -> rK39 RDT if positive, treat with VL drugs, if negative refer to clinical guidelines. If past history of VL, need to refer for parasitological diagnosis as rK39 will not distinguish previous from current. Gold standard is visualisation of LD bodies in Giemsa stained smears (spleen 93-99% sens, BM 53-86%, LN 54-65%), Requires high operator skill level - ID and quantification of LD bodies. Spleen 0.1% life threatening haemorrhage. Culturing increases sensitivity, but difficult. In areas/populations with high HIV prevalence, all VL cases should be tested for HIV - all HIV cases in endemic areas should be clinically screened for VL. Where to puncture? spleen more sensitive, but risk of bleed. Bone marrow is standard, though less sensitive, has no absolute contraindications
Visceral leishmania PCR
PCR is very sensitive, will detect asymptomatics, may lead to over treatment, limited feasibility outside referral/research centre, qPCR may help but need to be standardised and evaluated. Likely to be more useful in PKDL. Useful for diagnosis at species level (L infantum vs L donovani) - but many regions only have one cause so epidemiology remains key. Clinical and epidemiological relevance in areas where both species coexist (ie China)
Visceral leishmania Serology
Monoclonal spot test, can differentiate asymptomatic from symptomatic. Expensive and not feasible in the field
Visceral leishmania rK39
Easy to use, cheap, heat stable, commercial. Should be available at local CDCs. 97-100% sensitive in Asia, not so high in Africa. Critical to be used with clinical definition (will identify some asymptomatic infections, stays positive for months-years post treatment, may lead to over-diagnosis and mis-diagnosis). Other ICTs available with lower sensitivities (not all rks are equal, rk16 = 92% sens, Rk28 may be more useful in African setting. Quality control and assurance are critical. Unknown sensitivity in HIV-VL coinfected patients). Advantages: simple to perform with minimal training, does not require laboratory, finger prick whole blood, serum or plasma. Kits can be transported and stored at ambient temperature (up to 30oC), results available in 10-20min. Disadvantages: cannot distinguish between active cases and relapse in previously treated cases. In patients with advanced HIV infection a negative result cannot rule out the diagnosis of VL
Visceral leishmania Importance of accurate diagnosis
Early and accurate laboratory diagnosis is essential before initiating treatment for several reasons: 1 Clinical features of VL resemble those of several other diseases. 2 Effective drugs are available but they need to be administered for long periods and are potentially toxic and expensive. 3 VL is usually fatal if not treated in a timely manner. 4. Untreated cases are reservoirs of infection and therefore put the community at risk of ongoing transmission.
Visceral leishmania Case definition
Fever >38oC for 2 weeks (bacterial infection excluded) + splenomegaly + serological and/or parasitological confirmation ( eg rK39 positive)
Visceral leishmania Clinical manifestation
Variable incubation 30-100+ weeks, low grade fever 99%, hepatosplenomegaly/lymphadenopathy 98%, bone marrow hyperplasia, anaemia 96%, leucopaenia, thrombocytopaenia, hypergammaglobulinaemia, epistaxis 10%, proteinuria, haematuria. Mortality: haemorrhages 10%, suprainfections. Other sx may include reduced appetite 30% and loss of weight 87%, cough 50%, diarrhoea 50%
Visceral leishmania L donovani
Eastern Africa, Indian Subcontinent: fever, hepatosplenomegaly, pancytopaenia, malnutrition. Consider HIV co-infection in those with relapse. Both regions tend to have older children, adolescents and adults
Visceral leishmania L infantum
South America: typically <5yo with fever, hepatosplenomegaly anaemia, failure to thrive, severe malnutrition. Consider HIV coinfection in any adult patient. Southern Europe/Middle East: typically immunocompromised, post-transplant, HIV-coinfected. IVDU in Southern Europe
Visceral leishmania Differential diagnosis
Chronic malaria (usually longstanding disease), Schistosomiasis (chronic course, signs of portal hypertension, epidemiology of the disease/exposure history and no fever), typhoid fever (acute/subacute), tuberculosis (usually significant respiratory symptoms and signs, splenomegaly is rare unless miliary form), haematological malignancies (possible but are rare), any cause of fever and splenomegaly
Visceral leishmania The aim of drug treatment
1 Reduce parasite burden (without killing the patient) and 2 Improve complications from immunosuppression, anaemia, malnutrition, so that 3 Cell mediated immunity can return (which makes the patient permanently immune to Leishmania)
Visceral leishmania Treatment L donovani - Indian subcontinent
1 LAmB 3-5d or 2 LAmB stat + Miltefosine 7d or 3 LAmB stat + paromomycin 10d or 4 Miltefosine + paromomycin 10d, or 5 AmB 15-20 doses, or 6 Miltefosine 28d.
Visceral leishmania Amphotericin
LAmB needs a test dose (<1/1000 anaphylactoid reaction), common side effects: shivering, fever, chills, lower back pain, mild to moderate hypokalaemia, resolves with slowed infusion. Can be implemented in rural areas if reliable cold-chain <25oC. Evidence based on AmBisome, very few bioequivalence studies for LAmB, but LAmB is much better tolerated. Infusion takes 2h (lengthy)
Visceral leishmania Miltefosine
Miltefosine the only oral drug reasonably well tolerated, but teratogenic (28d needs 5m contraception, 10d need 3m contraception). Alkyl phospholipid originally anti-cancer drug. Previously recommended as monotherapy for 28d, now only in combination. Some GI intolerance (anorexia, vomiting 38%, diarrhoea 20%). Recent evidence of reduced drug susceptibility in India and Nepal (host and parasite-related), Probable ocular toxicity
Visceral leishmania Paromomycin
Aminoglycoside antibiotic, IM used only in combination with another drug. Minimum 10d treatment. Common side effects: fever and pain at site of infection, transient elevation of transaminases. Uncommon: vomiting and diarrhoea, ALP/Bili elevation, injection-related abscess, hearing damage (transient and not clinically detectable at this dose), fall in Hb (haemolysis), kidney damage (rare at this dose)
Visceral leishmania Treatment L donovani East Africa
1 Pentavalent antimonials IM/IV + paromomycin for 17d or 2 pentavalent antimonials IM/IV 30d or 3 LAmB 6-10d
Visceral leishmania Pentavalent antimonials
Cardiac/hepatotoxicity
Visceral leishmania Treatment L infantum - all regions
1 LAmB 3-6d or 2 Pentavalent antimonials IM/IV for 28d, or 3 LAmB high dose 2d, or 4 AmB 20-30 doses
Visceral leishmania Vaccination
No vaccine for general use in humans, (Brazil has vaccine for dogs). First generation vaccine candidates: whole killed parasites or extracts, efficacy inconclusive or negative. Second generation vaccines: recombinant proteins and genetic vaccines, still in pre-clinical development phase. Unlikely that a prophylactic vaccine will be available within the next 5-10y for any form of leishmaniasis
Visceral leishmania Post Kala azar dermal leishmaniasis (PKDL)
Is a complication of visceral leishmaniasis. Common in areas endemic for VL caused by L donovani. Characterised by rash after episode of VL. In contrast to VL (patients are typically not ill, PKDL is not fatal, main issue is that of aesthetics). However, it is a public health problem (based on existing evidence PKDL is a major reservoir of L donovani, In South Asia, PKDL typically does not self heal, needs to be treated if transmission of disease is to be limited, estimated 5-10% of VL cases go on to develop PKDL, incidence 4.8/1000 in India, interval 0-3y post initial VL infection). A neglected disease within a neglected disease - very poor evidence base and understanding of PKDL as a disease process, limited evidence on pathogenesis or risk factors, confirmatory diagnosis is difficult, needs experienced and skilled HR, Serological diagnosis difficult to interpret, very little evidence on management (no evidence on skin penetration of existing drugs, no evidence of ‘end point’ of treatment, very limited evidence on treatments)
Visceral leishmania PKDL Diagnosis
Assess clinical signs and symptoms (think of differential diagnosis - leprosy, fungal infection), VL endemic area? History of VL? (10% have no history of VL), rK39 (a positive test does not confirm diagnosis of PKDL), Slit skin smear examination under the microscope (Gold standard but sensitivity only 40-60% in nodular lesions, in macular lesions even lower). Algorithm: typical appearance and distribution of papules and nodules and/or macular hypopigmentation AND lived in or travelled to VL endemic areas AND/OR past history of VL treatment (if not - consider DDx), rK39 positive (only in Asia) -> probable PKDL -> Treat: Africa (only grade 2 and 3), Asia (ideally treat all - in elimination context). If no response refer for further testing at tertiary care - if positive - retreatment, if negative - expert clinical opinion/consensus for DDx
Visceral leishmania PKDL Treatment
Limited evidence - one RCT in India, WHO guidelines created from 15 cases. Current recommendation East Africa: Combination pentavalent antimonials IM/IV plus paromomycin for 17d, OR pentavalent antimonial for 30-60d, or LAmB 20d, or Miltefosine 28d. Current recommendation in South Asia (Bangladesh, India, Nepal): Miltefosine 12w or AmB 60-80 doses over 4 months, or LAmB 3w. Evidence of declining efficacy, 15% relapse at 18m, in vitro susceptibility towards miltefosine of parasites isolated after relapse was significantly lower (>2 fold) in comparison with the pre-treatment isolates. Similar patterns observed in VL patients relapsing to MF monotherapy. Use of a failing monotherapy to treat a major reservoir of disease is not a good idea…
Visceral leishmania PKDL Complications
Irreversible keratitis secondary to Miltefosine - the new recommendations are going to suggest NOT to give 12w Miltefosine for patients with PKDL (even though the treatment has a public health benefit)
Visceral leishmania PKDL Challenges
Do we even need to treat all the patients from a public health perspective? (Do all of these patients transmit disease?), How to accurately diagnose these patients? (urgent need for validation of qPCR and field operative RDTs or LAMP, validation of diagnostic clinical algorithm, need for end-points to be established). Need for standardisation of methods to monitor clinical improvement (for field practitioners - simple and feasible, crucially also to standardise clinical trial endpoints)
Visceral leishmania HIV/VL coinfection
Major clinical, diagnostic and epidemiological implications. The two diseases are mutually reinforcing (HIV infected people are particularly vulnerable to VL, while VL accelerates HIV replication and progression to AIDS). Poor treatment outcomes and higher mortality in coinfection regardless of the drug used, coinfected patients frequently relapse and may act as a reservoir for drug resistant parasites . Coinfected patients are thought to be more infective (‘super spreaders’) -> poses difficult challenges to sustained elimination efforts. May attend with strange presentations (pulmonary, intestinal, ocular, consider atypical disseminated disease). Immunosuppression means atypical inflammatory responses (no fever at initial diagnosis, exaggerated inflammatory reaction once treated IRIS-like). Likely to have a higher probability of being infected, limited evidence from Southern Spain in SOT shows 35x higher probability of asymptomatic serological conversion. VL-HIV can be considered lie TB-HIV - a lifelong relapsing disease when immunity fails. Multiple relapses, limited use for rK39 diagnostics - probably need to continue doing bone marrow aspirates
Visceral leishmania HIV/VL treatment
LAmB and Miltefosine (East Africa 28d, South Asia 14d)
Visceral leishmania HIV/VL/TB confection
20% of VL-HIV patients are coinfected with TB. New clinical entity, very high mortality. Xpert testing in all VL-HIV critical. Low MDR TB prevalence. High incidence of fatal IRIS, poor response to monotherapy, delay ART>3w, need 6w admission. Treatment cascade: VL Rx d0 - TB Rx d7 - ART d29
Visceral leishmania Summary
A growing problem in Asia and Southern Europe; all adults presenting with VL should be offered screening for HIV. HIV patients living in very endemic areas should be clinically screened for VL regularly. Role and mechanism in surveillance needs to be established, particularly in the elimination. Consider other causes of poor immunity - solid organ transplants, diabetes etc. Still major knowledge gaps - primary/secondary prophylaxis. HIV-VL-TB ‘tri-infection’ is a serious clinical management challenge
Cutaneous leishmaniasis Epidemiology
Neglected tropical diseases but important to remember not confined to the tropics. Variable clinical pattern dependent on species. 21 different species - geographically confines, and can cause different syndromes depending on the host response. Est 1.5 million cases per year. Reduced health-related QoL, scarring, anatomical damage, stigma. North Africa and Southern Europe (Mediterranean) are important regions for CL. IDSA have guidelines for treatment - the map demonstrates the overlap of different species. Epidemiology in UK: significant cause of dermatological disease in travellers. HTD 223 cases 60% ‘New World’, 8% of these had mucosal involvement. The commonest region of acquisition for non-American is the Mediterranean
Cutaneous leishmaniasis Different disease
Localised cutaneous, mucocutaneous, and some rarely have mucosal-only disease - classically NON painful
Cutaneous leishmaniasis Vector
New world Lutzomyia, Old world Phlebotomine. Being infected doesn’t feel good for the vectors, so they may take multiple blood meals in close proximity on the same person
Cutaneous leishmaniasis Typical features
Up to 12 weeks after a sandfly bite. Enlarging or non-healing skin lesion ulcer, nodule, keratotic plaque), exposed sites, lack of response to antibacterial treatments, recent travel. For DTM&H only need to think about localised (LCL), mucocutaneous (MCL). Diffuse CL is interesting as it relates to immune system.
Cutaneous leishmaniasis Clinical presentations
Different presentations for different species. Not always well circumscribed - some self-healing can occur with central scarring, and circular. Can get lymphangitic spread.
Cutaneous leishmaniasis Investigation
Microscopy of biopsy or slit skin smear (Giemsa) - impression slide, Histology (granulomatous inflammation), Culture (Novy-Nicolle-McNeil), Leishmania DNA (better on fresh) - useful to determine species to guide with treatment. No role for serology in cutaneous disease (often negative, if it is positive it doesn’t mean it is the cause of the lesion, nor does it suggest visceralisation - highly variable)
Cutaneous leishmaniasis Treatment
Lots of treatments, none work particularly well. Heat/surgery/destructive measures are not particularly effective. Challenge to determine which treatment to advise
Cutaneous leishmaniasis Treatment considerations
Which species (Mucosal potential - some have predilection for spreading to mucosal surface in nose, mouth or throat - want to prevent that happening - classically L brazilienses (subgroup of Viania) found in Americas), location of lesion (and the patient), size of lesion, number of lesions, age of the patient, comorbidities, recurrent lesion, adverse effects. Guidance exists, but is not justified by strong data - agree that L viani is the risk, and about 8% of those with CL will develop mucosal lesion. Depends on how to approach risk IDSA suggests systemic treatment for CL that has risk of ML (USA are very medicolegally driven), cultural position is, PAHO recommends intralesional treatment in localised L braziliensis and L amazonensis - tablets in children - this relates to public health response
Cutaneous leishmaniasis What species are at risk of ML
L viania braziliensis mainly, but also Lv guyanensis and Lv panamensis. High risk south of the Amazon basin in parts of Bolivia, Peru and Brazil. Moderate risk areas are south of Nicaragua to the Amazon basin. Low risk areas for ML are in Viannia-endemic regions north of Costa Rica - but until someone does significant genomic and epidemiological work, this will not be well understood
Cutaneous leishmaniasis Treatment complications
Pentavalent antimonial drugs sodium stibogluconate and meglumine antimoniate (parenteral including intralesional, malaise, QT prolongation). Miltefosine (oral, 28d for CL, teratogenic, N&V, ocular inflammation) LAmB. The skin is less inclined to allow drugs into it (what enters the reticuloendothelial system doesn’t enter the skin well)
Cutaneous leishmaniasis Treatment for non-American CL
Conservative, Intralesional pentavalent antimonial, Miltefosine, IV or IM pentavalent antimonial, IV LAmB, IV or IM pentamidine, imidazole antifungals, surgery. Cryotherapy, thermotherapy >50oC, tropical paromomycin, photodynamic therapy, allopurinol
Cutaneous leishmaniasis Treatment for American CL
IV or IM antimonial, IV LAmB, Miltefosine 28d, IV/IM pentamidine - want to treat any of the organism that may transmit to the nose or other mucosal surfaces
Cutaneous leishmaniasis Immunosuppression
1 Organ transplantation 2 Methotrexate 3 Biologics TNFa inhibitors, 4 HIV - however Prednisolone is probably more likely contributing worldwide (in LMIC pred treats a lot of conditions, and for prolonged periods, people can buy without prescription, plus there are limited options for steroid-sparing)
Cutaneous leishmaniasis Prevention
Avoid sandfly bites, insect repellent, long sleeves, insecticide treated bed nets (the net needs to be smaller than mosquito), sleeping undercover, vector control programmes
Cutaneous leishmaniasis Summary
Vector-borne NTD, large burden of disease, different presentations. American or non-American leishmaniasis (need to consider risk for mucosal disease, Vianna subgenus species or other), then the number and lesion of lesions, local or systemic treatment, immunosuppressed
Entamoeba histolytica/dispar Amoebic dysentery
Most people infected with true E histolytica will remain asymptomatic and ultimately clear the infection. A small proportion develop invasive intestinal amoebiasis, characterised by abdominal pain and bloody diarrhoea. Can become fulminant, with very high mortality. Can be chronic with intermittent but long-lasting symptoms
Entamoeba histolytica/dispar Amoebic liver abscess
Male:female 7:1 (no gender bias with amoebic dysentery). Gut invasion must have preceded spread to the liver, but many ALA patients do not report a prior attack of bloody diarrhoea. Absence of faecal cysts does not exclude a diagnosis of ALA
Entamoeba histolytica/dispar Diagnosis
Wet-film microscopy on faecal samples (concentrated, fixed and stained), Serology (cheap, usually strongly positive in ALA), Ag detection not very reliable, NAAT available
Entamoeba histolytica/dispar Treatment
Invasive amoebiasis is almost exclusively treated with metronidazole or other 5-nitroimidazole drugs (equally but no more effective). Should be followed by a luminal amoebicide - choice depends on what is licensed locally. Paromomycin is most effective for luminal E histolytica
Giardia intestinalis Life cycle (human)
Human ingests infective cyst through contamination of water, food or hands/fomites. Excyst into trophozoites. Both trophozoites and cysts are excreted in stool, trophozoites do not survive, but cysts go on to propagate infection
Giardia intestinalis Clinical
Often non-specific. Diarrhoea, malaise, flatulence, foul-smelling faeces, weight loss. Extraintestinal symptoms involving eyes, skin, joints and urinary tract in a third of patients.
Giardia intestinalis Pathogenesis
Malabsorption of glucose, water and sodium. Diffuse microvillus shortening. Loss of epithelial barrier function - increased intestinal permeability. Apoptosis of enterocytes.. Giardiasis is a significant cause of malnutrition, growth impairment and cognitive deficit in children. Infection with G intestinalis in young children both affects and is affected by the microbiome.
Giardia intestinalis Diagnosis
Wet film microscopy on faecal samples - cysts are easy to recognise, direct fluorescence antibody staining of cysts. Ag detection (less sens than DFA), PCR
Giardia intestinalis Epidemiology
Endemic in many LMICs. Primarily in young children, who shed large numbers of cysts. Adults shed few cysts, even though exposed, suggests development of a degree of immunity. Mainly person-to-person transmission. Epidemics occur all over the world (noted difference from E histolytica/dispar), all ages affected (mainly symptomatic adults as well as children). Transmission by food, water, person-to-person. G intestinalis is easily acquired because infectious dose is very small (~10 cysts), cysts are resistant to chlorine and other disinfectants, efficacy of the conventional wastewater treatment processes at removing cysts is limited. Cysts remain viable for weeks in cold water. There are animal reservoirs for some genotypes
Giardia intestinalis Treatment
Metronidazole is still widely used and is normally effective. Tinidazole seems to be slightly better. Nitazoxanide is also licensed for the treatment of giardiasis. Paromomycin appears to be effective and is regarded as safe in pregnancy. Treatment failures with nitroimidazoles are not uncommon. Drug resistance is a growing problem.
Trichomonas vaginalis Clinical
Almost exclusively sexually transmitted. Most common signs and symptoms in women (purulent vaginal discharge, vaginal and vulvar erythema, urethra commonly infected causing dysuria) and men (urethral discharge and/or dysuria, spontaneous loss of infection seems to be frequent), the overwhelming majority of infections are asymptomatic (men 98.5% women 73%). Trichomoniasis has been convincingly linked to adverse birth outcomes (significant associations found with low birthweight) and increased risk of both acquiring and transmitting HIV (general consensus)
Trichomonas vaginalis Diagnosis
Wet film microscopy, Culture will detect 10-30% more but takes longer. Rapid antigen detection kits provide the speed of wet film and better sensitivity than culture. PCR and other NAATs probably the most sensitive.
Trichomonas vaginalis Treatment
Metronidazole 2g stat, but tinidazole is significantly more effective (10x more expensive). Metronidazole resistance is a rare but real problem
Dientamoeba fragilis Summary
Amoeboid appearance but is related to trichomonads. Pathogenicity is controversial and variable. Reported symptoms are non-specific (diarrhoea, abdominal pain). The trophozoite will not be found by light microscopy unless specimens are rapidly fixed and stained. if using PCR, the infection rate is high in the general population. Treatment: Metronidazole - not particularly effective. Clioquinol - more effective in relieving symptoms. Tetracycline - also used. Secnidazole - may be the best. But is treatment justified?
Balantioides coli Summary
The only ciliate normally to infect humans. Both cyst and trophozoite are much larger (>50um) than other gut protozoa. Very common in pigs, but rare in humans. A large bowel parasite. Frequently asymptomatic but can occasionally invade like E histolytica and cause colitis, dysentery and death. Metronidazole seems to be effective but few recent reports available.
Blastocystis sp Summary
Very common, probably part of the normal healthy gut flora. Pathogenicity controversial - may actually be a marker of a healthy gut. Genetically very diverse. Peripheral mitochondria and nuclei, cysts are difficult to identify - look like an empty or granular ring
