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
