Parasites 2 Flashcards

Question

Schistosoma FGS and HIV

Answer 1

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

Answer 2

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

Answer 3

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

Answer 4

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

Answer 5

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

Answer 6

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)

Answer 7

1. 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)

Answer 8

1. 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

Answer 9

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.

Answer 10

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)

Answer 11

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

Answer 12

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

Answer 13

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.

Answer 14

Vector control (larviciding), later MDA (Ivermectin)

Answer 15

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.

Answer 16

Inside the fly within a week the larvae will mature from L1 to L3 and infective on next blood meal

Answer 17

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

Answer 18

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.

Answer 19

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

Answer 20

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

Answer 21

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.

Answer 22

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

Answer 23

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

Answer 24

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

Answer 25

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

Answer 26

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.

Answer 27

Ivermectin, community-directed treatment - stock given to the community elder to control the administration - much more effective than healthcare workers

Answer 28

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

Answer 29

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.

Answer 30

WHO 2030 roadmap to eliminate onchocerciasis in 12 countries. Treatment programme no longer needed for 30 million people.

Answer 31

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

Answer 32

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

Answer 33

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.

Answer 34

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.

Answer 35

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.

Answer 36

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.

Answer 37

Children: Growth restriction (Nakalanga syndrome), Nodding syndrome (bizarre disease), Increased mortality. Adults: onchocerciasis-associated epilepsy

Answer 38

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)

Answer 39

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

Answer 40

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)

Answer 41

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

Answer 42

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

Answer 43

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

Answer 44

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

Answer 45

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

Answer 46

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

Answer 47

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

Answer 48

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

Answer 49

Vector control - stop the vector being infected or stop the vector from transmitting, Kill the adult filariae in nodules, kill the microfilariae in skin

Answer 50

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.

Answer 51

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).

Answer 52

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.

Answer 53

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

Answer 54

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

Answer 55

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

Answer 56

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)

Answer 57

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)

Answer 58

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'

Answer 59

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

Answer 60

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

Answer 61

Remarkable results for coverage but strategies need adapting to specificities of elimination

Answer 62

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

Answer 63

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

Answer 64

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

Answer 65

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.

Answer 66

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)

Answer 67

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

Answer 68

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

Answer 69

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

Answer 70

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

Answer 71

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)

Answer 72

All available drugs are primarily microfilaricidal (acts on larvae but not adult worms), although some evidence of macrofilaricidal (adult) effects after multiple treatment rounds

Answer 73

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

Answer 74

LF and Loa loa, not Oncho. MoA unclear, appears to involve immune system components and paralysis of worms.

Answer 75

Used in combination with Ivermectin or DEC in MDAs

Answer 76

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

Answer 77

Culicoides midges and Simulium blackflies

Answer 78

M perstans (sub-Saharan Africa, Central and Sth America, Caribbean), M streptocerca (W Africa), M ozzardi (Central and South America and Caribbean).

Answer 79

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).

Answer 80

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.

Answer 81

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

Answer 82

Nocturnal: Wb, Bm. (Diurnally subperiodic Wb in blood at all times but increased in daytime) (Nocturnally subperiodic Bm zoonotic strains in Malaysia, Phillippines, Indonesia)

Answer 83

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

Answer 84

Adult male and female live in lymphatic vessels -> inflammation, fibrosis and blockage.

Answer 85

<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

Answer 86

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

Answer 87

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

Answer 88

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

Answer 89

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

Answer 90

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

Answer 91

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.

Answer 92

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

Answer 93

Pruritis, loss of elasticity, atrophy, pigment changes (leopard skin, crocodile skin, elephant 'atrophy' skin, hanging groin (lymphadenitis))

Answer 94

Death of Mf and inflammation -> fibrosis and scarring - lesions in both anterior and posterior chamber of the eye -> blindness

Answer 95

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

Answer 96

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

Answer 97

Community directed treatment with Ivermectin (except Loa loa endemic regions). Annual treatment for 12-15y at 80% coverage required to break transmission. Larviciding

Answer 98

Obstacle to Onchocerciasis and LF control. Up to 13m infected in West and Central Africa (30 million at risk).

Answer 99

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

Answer 100

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)

Answer 101

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

Answer 102

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.

Answer 103

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

Answer 104

Adults in lymphatics, Mf in blood, Disease caused by adults. Treat DEC

Answer 105

Adults in subcut nodules, Mf in skin (and eyes). Disease caused by Mf. Treat with Ivermectin

Answer 106

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

Answer 107

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)

Answer 108

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.

Answer 109

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

Answer 110

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

Answer 111

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

Answer 112

Praziquantel - MoA calcium influx into the whole parasite, muscle contraction and surface modifications resulting in paralysis and death of worm

Answer 113

Hexacanth = hooklets that the larvae will use as it exits the egg and uses it to penetrate the intestinal wall

Answer 114

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

Answer 115

GI disturbance, anaemia (Vit B12 deficiency in ~40%)

Answer 116

Eggs in stool

Answer 117

Praziquantel (and vit B12)

Answer 118

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

Answer 119

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

Answer 120

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)

Answer 121

Surgical removal of larvae (anti-helminthic drugs generally not useful)

Answer 122

Clean water, cooking fish/amphibian/reptile meat, avoid contact with raw amphibian flesh

Answer 123

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.

Answer 124

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

Answer 125

Eggs in stool

Answer 126

Praziquantel is effective against both adults and larvae

Answer 127

Hygiene, sanitation, rodent control, insect control

Answer 128

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.

Answer 129

Nausea and mild abdominal pain, anal pruritis due to active exit of gravid proglottids

Answer 130

Eggs and/or proglottids in stool

Answer 131

Praziquantel (or niclosamide)

Answer 132

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

Answer 133

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).

Answer 134

Often asymptomatic or mild

Answer 135

Eggs or proglottids in stool. Proglottids <15 main branches

Answer 136

Praziquantel (or niclosamide) BUT possibility of larval disease (cysticercosis)

Answer 137

Meat inspection of pork meat, cooking meat, hygiene and sanitation, antihelminthic treatment of pigs (oxfendazole), Pig vaccine (TSOL18, Cystvax)

Answer 138

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.

Answer 139

Invaginated protoscolex ("outside-in") - invaginated in intermediate host, evaginated in definitive host (proglottids will grow from neck region). Die off eventually and become calcified

Answer 140

Protoscolex with hooks in cyst

Answer 141

Calcified lesions - can be anywhere in body

Answer 142

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

Answer 143

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

Answer 144

Imaging, serology. Neurocysticercosis (CNS lesions, focal lesions, convulsions, intracranial hypertension). Stage of cyst: live, dying, strong inflammatory reaction, calcified

Answer 145

Depends on site, number and symptoms. Albendazole and/or praziquantel plus steroids (surgery, antiepileptics, analgesics)

Answer 146

Humans are the only source of eggs = good sanitation, hygiene

Answer 147

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.

Answer 148

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

Answer 149

Imaging, serology

Answer 150

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)

Answer 151

Carcass removal to prevent dogs scavenging, cooking dog food, deworm dogs, controlling stray dog populations

Answer 152

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.

Answer 153

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.

Answer 154

At early stage if cyst is confined: radical surgery, followed by longterm benzimidazole. Later stages very difficult.

Answer 155

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.

Answer 156

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

Answer 157

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

Answer 158

Adult cestodes - identification of eggs/proglottids in stool. Larval cestodes - imaging techniques and/or serology for cysticercosis and hydatid disease

Answer 159

Adult cestodes: praziquantel (or niclosamide). Larval cestodes: praziquantel or albendazole or surgery for cysticercosis. Albendazole or mebendazole or surgery for hydatid disease

Answer 160

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)

Answer 161

Visceral: 'Kala-azar', and skin complication PKDL 'post-kala-azar leishmaniasis'. Cutaneous: localised, mucocutaneous, mucosal. Americas ('New world'), and non-Americas ('Old world')

Answer 162

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

Answer 163

Africa, South Asia: L donovani. Middle East, Central Asia, Americas L infantum

Answer 164

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.

Answer 165

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.

Answer 166

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.

Answer 167

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)

Answer 168

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

Answer 169

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)

Answer 170

Monoclonal spot test, can differentiate asymptomatic from symptomatic. Expensive and not feasible in the field

Answer 171

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

Answer 172

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.

Answer 173

Fever >38oC for 2 weeks (bacterial infection excluded) + splenomegaly + serological and/or parasitological confirmation ( eg rK39 positive)

Answer 174

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%

Answer 175

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

Answer 176

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

Answer 177

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

Answer 178

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)

Answer 179

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.

Answer 180

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)

Answer 181

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

Answer 182

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)

Answer 183

1 Pentavalent antimonials IM/IV + paromomycin for 17d or 2 pentavalent antimonials IM/IV 30d or 3 LAmB 6-10d

Answer 184

Cardiac/hepatotoxicity

Answer 185

1 LAmB 3-6d or 2 Pentavalent antimonials IM/IV for 28d, or 3 LAmB high dose 2d, or 4 AmB 20-30 doses

Answer 186

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

Answer 187

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)

Answer 188

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

Answer 189

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...

Answer 190

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)

Answer 191

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)

Answer 192

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

Answer 193

LAmB and Miltefosine (East Africa 28d, South Asia 14d)

Answer 194

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

Answer 195

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

Answer 196

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

Answer 197

Localised cutaneous, mucocutaneous, and some rarely have mucosal-only disease - classically NON painful

Answer 198

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

Answer 199

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.

Answer 200

Different presentations for different species. Not always well circumscribed - some self-healing can occur with central scarring, and circular. Can get lymphangitic spread.

Answer 201

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)

Answer 202

Lots of treatments, none work particularly well. Heat/surgery/destructive measures are not particularly effective. Challenge to determine which treatment to advise

Answer 203

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

Answer 204

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

Answer 205

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)

Answer 206

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

Answer 207

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

Answer 208

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)

Answer 209

Avoid sandfly bites, insect repellent, long sleeves, insecticide treated bed nets (the net needs to be smaller than mosquito), sleeping undercover, vector control programmes

Answer 210

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

Answer 211

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

Answer 212

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

Answer 213

Wet-film microscopy on faecal samples (concentrated, fixed and stained), Serology (cheap, usually strongly positive in ALA), Ag detection not very reliable, NAAT available

Answer 214

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

Answer 215

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

Answer 216

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.

Answer 217

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.

Answer 218

Wet film microscopy on faecal samples - cysts are easy to recognise, direct fluorescence antibody staining of cysts. Ag detection (less sens than DFA), PCR

Answer 219

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

Answer 220

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.

Answer 221

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)

Answer 222

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.

Answer 223

Metronidazole 2g stat, but tinidazole is significantly more effective (10x more expensive). Metronidazole resistance is a rare but real problem

Answer 224

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?

Answer 225

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.

Answer 226

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

Parasites 2 Flashcards

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