CS3 - NTD Schistosomiasis 1 Flashcards

Question

What is the path of the Schistosoma cercaria after it penetrates the skin?

Answer 1

The cercaria penetrates the skin of the lower body, invades the vasculature, and travels through veins to the heart, lung, back to the heart, and then the abdominal aorta.

Answer 2

"A" refers to parasites entering the gastroduodenal, hepatic, or splenic arteries to reach the liver.

Answer 3

B" refers to parasites entering the mesenteric arteries and moving through the hepatic portal vessels to the liver.

Answer 4

C" refers to parasites entering vessels leading to the bladder, from where they could also reach the liver.

Answer 5

The parasite must evade numerous host immune responses to reach its preferred site.

Answer 6

Schistosomiasis may have originally been a disease of animals that evolved into a zoonosis. Its life cycle includes both animals and humans as reservoirs.

Answer 7

The lifespan of an adult schistosome is about 3–5 years, but they can live up to 40 years in the definitive hosts (humans).

Answer 8

Serologic testing detects antibodies to the adult worm. It should be performed at least 6 to 8 weeks after a likely infection to allow for full development of the parasite and antibody production.

Answer 9

In patients who have been repeatedly infected and treated, specific antibodies may persist even after cure, so serologic testing cannot distinguish between resolved and active infection.

Answer 10

Symptoms include frequent, painful, or bloody urine, abdominal pain, bloody diarrhoea, anaemia, fever, chills, muscle aches, bladder inflammation and scarring, lymph node enlargement, secondary blood disorders (due to colon damage), and potentially bladder cancer.

Answer 11

Children with repeated infections may develop anaemia, malnutrition, and learning disabilities.

Answer 12

Katayama fever is an acute manifestation of schistosomiasis. Its typical features include fever, an urticarial rash (swimmer’s itch), enlarged liver and spleen, and bronchospasm.

Answer 13

An immediate, pruritic, maculopapular eruption at the site of cercarial skin penetration within 1 day following exposure.

Answer 14

Systemic symptoms include fever, fatigue, myalgia, malaise, non-productive cough, eosinophilia, patchy infiltrates, weight loss, dyspnoea, diarrhoea, diffuse abdominal pain, toxaemia, hepatosplenomegaly, and widespread rash.

Answer 15

Chronic symptoms affect the gastrointestinal and urogenital tracts, leading to hepatosplenic and pelvic organ diseases, portal and pulmonary hypertension, abdominal ascites, upper gastrointestinal varices and haemorrhage, female genital schistosomiasis, infertility, increased risk of HIV-1 transmission, and squamous cell carcinoma of the bladder.

Answer 16

Schistosoma mansoni and Schistosoma japonicum adult worms live in the mesenteric veins, causing intestinal schistosomiasis.

Answer 17

Symptoms are caused by parasite eggs passing through or becoming trapped in intestinal tissues, leading to mucosal granulomatous inflammation, microulcerations, and superficial bleeding.

Answer 18

Schistosoma japonicum and Schistosoma mansoni eggs can be swept into the small portal branches of the liver by blood flow, where granulomas form around the trapped eggs in periportal tissues, causing hepato-splenomegaly.

Answer 19

High-intensity childhood infections often lead to hepato-splenomegaly (enlarged liver and spleen). In some individuals, egg-induced granulomatous responses cause severe periportal fibrosis and extensive, often irreversible, liver and spleen pathology.

Answer 20

Adult S. haematobium worms live in the pelvic venous plexus. The eggs can traverse the blood vessel wall and the wall of the bladder to enter the lumen of the bladder, where they exit the body with urine.

Answer 21

Female S. haematobium release up to 3000 eggs per day. Half of these eggs are excreted in the urine, while the remaining eggs become entrapped in the capillary beds of pelvic end organs, particularly in the bladder, ureters, and genital tract.

Answer 22

Symptoms and pathological changes are associated with the deposition of eggs in bladder tissue, leading to chronic immune-mediated disease, erythematous nodular lesions, and haemorrhage in the bladder mucosa.

Answer 23

Urogenital schistosomiasis increases the risk of HIV transmission.

Answer 24

Granulomas form around the eggs as part of the immune response, leading to tissue inflammation and damage. This process is responsible for the pathological changes in affected organs, such as the bladder, liver, or intestines, depending on the species.

Answer 25

Clusters of living eggs cause intense inflammatory reactions, tissue eosinophilia, ulceration, and bleeding. This inflammation can lead to bladder wall thickening, development of masses, and pseudopolyps.

Answer 26

Urogenital schistosomiasis is associated with squamous cell carcinoma of the urinary bladder. Schistosoma haematobium is classified as a carcinogen.

Answer 27

During active infection, eggs are frequently deposited in genital organs such as the cervix, seminal vesicles, and prostate.

Answer 28

Schistosomiasis is associated with learning and memory deficits in children, and reduced attention levels, impaired work capacity, and cognitive deficits in adults. The disease is strongly correlated with poverty, lack of basic sanitary conditions, and contributes to the inhibition of social development and a low quality of life in affected areas.

Answer 29

Studies on the mechanisms involved in the neurological impairment caused by schistosomiasis are scarce.

Answer 30

Chemoprophylaxis refers to the use of medications to prevent infection, particularly in areas where schistosomiasis is endemic. Commonly used drugs for prevention include praziquantel, which is effective in treating the infection and can also be used in mass drug administration campaigns to reduce transmission.

Answer 31

Disruptions in mass drug administration (MDA) can lead to severe rebound disease, particularly in areas with high transmission rates, as the interruption allows for the resurgence of the infection.

Answer 32

Praziquantel kills established adult schistosomes (more effective against males than females), reducing morbidity in treated patients. However, it is ineffective against juvenile worms and does not prevent reinfection. Its overall effect on disease transmission is transient, as prevalence quickly returns to baseline levels after treatment.

Answer 33

The primary purpose of a Phase 1b clinical trial is to provide the first introduction of a pharmaceutical product into patients with the disease of interest. It focuses on determining the safety, metabolism, pharmacokinetic properties, and clinical pharmacology of the product.

Answer 34

Katayama fever: This acute manifestation of schistosomiasis is primarily due to the immune response to migrating schistosomula and egg deposition. The fever, rash, and bronchospasm are a result of the host’s hypersensitivity reaction to the presence of the parasite, leading to inflammation, eosinophilia, and immune-mediated tissue damage. Chronic schistosomiasis: The pathogenesis is mainly driven by the host’s immune response to trapped eggs in tissues. Granulomas form around the eggs, leading to chronic inflammation and fibrosis. In urogenital schistosomiasis, this results in bladder wall thickening, ulceration, and the development of pseudopolyps. In hepatosplenic schistosomiasis, it leads to portal hypertension, hepatosplenomegaly, and fibrosis. Over time, the chronic inflammation and fibrosis can cause significant tissue damage and dysfunction, potentially resulting in squamous cell carcinoma in the bladder or liver.

Answer 35

Complexities in vaccine development: Schistosomiasis has a complex lifecycle involving multiple stages in different hosts, including snails and humans. Each stage of the parasite’s lifecycle presents different challenges for immune targeting. The adult worm, eggs, and larvae exhibit immune evasion strategies, including antigenic variation and the ability to suppress the host’s immune response, making it difficult to develop a vaccine that offers long-term protection. Challenges for travellers: Developing a vaccine for travellers is particularly difficult because of the variability in schistosomiasis strains across regions, differences in host immune responses, and the need for a vaccine that works in diverse populations. Additionally, schistosomiasis can be contracted through exposure to contaminated water, and immunity to the parasite typically requires repeated exposure, making it challenging to induce sufficient immunity in travellers who may only experience short-term exposure.

Answer 36

Mechanism of action: Praziquantel works by binding to the schistosome's cell surface and causing an increase in calcium ion influx, leading to muscle contraction, paralysis, and detachment of the parasite from the host tissue. It also disrupts the integrity of the parasite's tegument, making it vulnerable to immune attack and ultimately leading to parasite death. Adverse drug reactions (ADRs): Common ADRs include headache, dizziness, abdominal pain, nausea, vomiting, and diarrhea. In some cases, more severe reactions such as fever, rash, and allergic reactions may occur due to the immune response against dying parasites (a phenomenon known as the Jarisch-Herxheimer reaction). Cautions/contraindications: Cautions: Praziquantel should be used cautiously in patients with hepatic dysfunction, as it is metabolized by the liver. It should also be used carefully in pregnant women (especially in the first trimester) and breastfeeding mothers. Contraindications: Praziquantel is contraindicated in patients with known hypersensitivity to the drug and in cases of ocular cysticercosis, as it may cause inflammation in the eye.

Answer 37

Pros: Rapid reduction in prevalence: MDA can effectively reduce the prevalence of schistosomiasis in endemic regions by treating large populations, including asymptomatic individuals who may be unknowingly infected. Cost-effective: When implemented in high-risk areas, MDA programs can be a cost-effective way to reduce morbidity and control transmission. Reduced transmission: Mass treatment lowers the number of infected individuals, leading to a decrease in the number of parasite eggs shed into the environment, which reduces transmission cycles. Cons: Rebound disease: If MDA is disrupted, there can be a rapid rebound of disease transmission, particularly in areas of high transmission, leading to the resurgence of infection. Ineffectiveness against juvenile worms: MDA with praziquantel does not target juvenile schistosomes, meaning reinfection can still occur after treatment. Limited impact on long-term transmission: The overall impact on long-term transmission can be transient, as the parasite population may quickly return to baseline levels without sustained control measures, such as improving sanitation or access to clean water. Drug resistance concerns: Although resistance to praziquantel has not been a major issue so far, there are concerns that overuse could lead to resistance over time

Answer 38

Oxamniquine: Mechanism of action: Oxamniquine selectively targets S. mansoni by causing paralysis and tegumental damage, which leads to the death of the parasite. It is believed to inhibit the parasite’s metabolism by interfering with DNA synthesis. ADRs: Common ADRs include dizziness, headache, nausea, abdominal pain, and skin rashes. Less frequently, more serious reactions like fever or allergic reactions may occur. Cautions/contraindications: Caution is needed in patients with hepatic dysfunction as oxamniquine is metabolized in the liver. It should be avoided in pregnant women, particularly during the first trimester, due to lack of safety data. Metrifonate: Mechanism of action: Metrifonate acts by inhibiting the enzyme acetylcholinesterase in schistosomes, leading to paralysis and death of the parasite. It primarily targets S. haematobium and S. intercalatum. ADRs: Common ADRs include gastrointestinal symptoms like nausea, vomiting, diarrhea, as well as dizziness and headache. It may also cause muscle weakness or an allergic reaction in some individuals. Cautions/contraindications: Metrifonate should be used with caution in patients with a history of asthma or other respiratory conditions, as it can cause bronchospasm. It is contraindicated in patients with known hypersensitivity to the drug and should be avoided in pregnant women, especially in the first trimester.

Answer 39

Rationale for new drug discovery: Resistance to existing drugs: Although praziquantel is the mainstay of treatment, there are concerns about the development of drug resistance, particularly with long-term use. New drugs are needed to overcome this potential issue. Ineffectiveness against certain stages: Praziquantel is ineffective against juvenile schistosomes, so there is a need for drugs that can target different stages of the parasite's lifecycle. Better safety profile: Current treatments may have limitations, including adverse drug reactions and contraindications, so safer alternatives are needed. Improved control of transmission: New drugs with better pharmacokinetics and modes of action could lead to more effective mass drug administration programs, preventing reinfection. Mechanisms of action of candidate molecules: Fasciolosis and schistosomiasis drug candidates (e.g., Oxfendazole): Mechanism: Inhibits tubulin polymerization, disrupting the parasite's cytoskeletal structure, leading to paralysis and death of the schistosome. Nitazoxanide: Mechanism: Interferes with the energy metabolism of the parasite by inhibiting pyruvate-ferredoxin oxidoreductase (PFOR), which disrupts the parasite's anaerobic metabolism. Benzimidazoles (e.g., Albendazole): Mechanism: Inhibits tubulin polymerization, leading to damage to the parasite’s microtubules and interfering with its ability to absorb glucose, ultimately causing its death. Oxaboroles (e.g., SCYX-7158): Mechanism: Targets the parasite’s 20S proteasome, a crucial enzyme involved in protein degradation, disrupting the parasite’s ability to regulate cellular processes and leading to its death. Thiol-based compounds: Mechanism: These compounds inhibit the enzyme thioredoxin reductase, which is involved in the parasite's defense against oxidative stress. The inhibition leads to parasite damage and death due to oxidative damage.

CS3 - NTD Schistosomiasis 1 Flashcards

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