CS3 - NTD Schistosomiasis 1 Flashcards
What is haematuria? What are the two types?
Haematuria is the presence of blood in the urine. There are two types:
Gross haematuria: Blood is clearly visible in the urine.
Microscopic haematuria: Blood is only visible under a microscope and is the most common type.
What type of antibiotic is trimethoprim and is it bactericidal?
Trimethoprim is an antibiotic that is bacteriostatic, not bactericidal. It inhibits bacterial dihydrofolate reductase, which is involved in folic acid synthesis, preventing the bacteria from replicating.
How does dihydrofolate reductase (DHFR) activity differ between bacteria and humans, and how is it relevant to trimethoprim’s action?
Dihydrofolate reductase (DHFR) is more active in bacterial cells (60 times more than in humans). Trimethoprim targets and inhibits bacterial DHFR, preventing folic acid synthesis necessary for DNA replication in bacteria, while having a minimal effect on human DHFR. This selective inhibition contributes to trimethoprim’s antibacterial action.
What are the common and more serious causes of haematuria?
Common causes:
Bacterial or viral infections (e.g., Streptococcus)
Infection/inflammation of the urinary tract or prostate
Trauma
Urinary tract stones
Enlarged prostate (benign prostatic hyperplasia)
Vigorous exercise (e.g., long-distance running)
Sexual activity
Endometriosis
More serious causes:
Cancer of the bladder, kidney, or prostate
Blood-clotting disorders (e.g., hemophilia)
Sickle cell disease
Glomerulonephritis
What to check when diagnosing
History Taking
Presenting Complaint
History of Presenting Complaint
Past Medical History
Drug History
Allergies
Family History
Social History Travel History
Systems Review
Social History
What is the difference between morbidity and mortality?
Morbidity refers to the condition of being diseased or the rate of disease in a population. It indicates the prevalence or incidence of diseases or medical conditions within a specific group or community, including the severity and impact on daily life.
Example: The number of people affected by diabetes in a population.
Mortality refers to the incidence of death within a population. It measures the number of deaths due to specific diseases, conditions, or causes, often expressed as a death rate or mortality rate.
Example: The number of deaths due to heart disease in a given year.
What are the common urology tests used for diagnosing urinary conditions?
A:
Urine Tests:
Urine Dipstick: Used to detect the presence of blood, infection, protein, glucose, or other substances in the urine.
Urine Culture: To identify bacterial infection and determine the appropriate antibiotic treatment.
Blood Tests:
Kidney, Liver, or Bone Function Tests: These assess the function of organs and systems involved in waste filtration and metabolism.
Full Blood Count (FBC): Provides information on overall health and can detect a variety of disorders, including anemia and infection.
Imaging Tests:
CT Scan: Offers detailed cross-sectional images of the urinary tract and other organs, useful in detecting stones, tumors, or abnormalities.
X-rays: Provide detailed images to identify issues with the urinary tract, such as stones or structural problems.
Computer Reconstruction: Helps in creating detailed 3D models of the urinary system for in-depth analysis.
Flexible Cystoscopy:
A procedure where a cystoscope (a small telescopic camera) is inserted into the bladder to visually inspect the bladder for abnormalities such as tumors, stones, or infections.
Transurethral Resection (TUR) and Biopsy:
TUR: A procedure used to remove tissue from the bladder or prostate for treatment or diagnosis.
Cystoscope Biopsy: Involves taking a tissue sample from the bladder through the cystoscope for histopathological examination to diagnose conditions like cancer.
These tests are used to diagnose, monitor, and manage various urological conditions.
What are common test results found in urinalysis and their potential meanings?
Haematuria:
Meaning: Presence of blood in the urine.
Possible Causes:
Infection (e.g., UTI)
Kidney stones
Bladder or kidney tumors
Trauma to the urinary tract
Glomerulonephritis
Proteinuria:
Meaning: Presence of excess protein in the urine.
Possible Causes:
Kidney disease (e.g., glomerulonephritis, nephrotic syndrome)
Hypertension
Diabetes
Urinary tract infection
Pyuria:
Meaning: Presence of pus or white blood cells in the urine, indicating infection or inflammation.
Possible Causes:
Urinary tract infections (UTIs)
Inflammatory conditions (e.g., interstitial cystitis, prostatitis)
Kidney infection (pyelonephritis)
Positive Nitrite:
Meaning: The presence of nitrites in the urine, suggesting bacterial infection, specifically by gram-negative bacteria like Escherichia coli.
Possible Causes:
Urinary tract infection (UTI), typically caused by nitrate-reducing bacteria
What is eosinophilia, and what does it indicate in a blood test?
Eosinophilia:
Definition: An elevated number of eosinophils in the blood, typically greater than 0.5x10^9/L.
Normal Range: 0.02–0.5x10^9/L
Eosinophil Characteristics:
Diameter: ~8μm
Bi-lobed nucleus
Cytoplasmic granules
Pink staining with eosin in blood smears
Causes of Eosinophilia:
Parasite Infections: Eosinophils play a major role in defending against parasitic infections, such as helminthic (worm) infestations.
Allergic Reactions: Elevated eosinophil levels can occur due to conditions like allergic asthma, allergic rhinitis, or eczema.
Inflammation: Eosinophils are involved in the inflammatory response, particularly in conditions like eosinophilic granulomatosis with polyangiitis.
Drug Reactions: Some medications can induce eosinophilia as an adverse effect.
Autoimmune Diseases: Eosinophils can be elevated in diseases like rheumatoid arthritis or systemic lupus erythematosus (SLE).
Without Anaemia: The absence of anaemia in the presence of eosinophilia may indicate an immune-mediated or allergic response, rather than a blood loss or hematologic disorder.
Elevated eosinophil counts indicate that the immune system is reacting, often in response to infection or inflammation, and additional investigations may be needed to determine the underlying cause.
What does asymmetrically diffuse mucosal wall thickening and calcification at the urinary bladder indicate on a CT scan?
Asymmetrical Diffuse Mucosal Wall Thickening:
Potential Causes:
Bladder Inflammation: Conditions like cystitis (bladder infection) or interstitial cystitis can cause mucosal thickening.
Bladder Cancer: Tumors may cause irregular, asymmetrical thickening of the bladder wall.
Bladder Stones: Chronic irritation from stones can cause mucosal changes.
Chronic Infection: Chronic bacterial or viral infections can lead to persistent bladder wall thickening.
Calcification in the Urinary Bladder:
Potential Causes:
Bladder Stones: The presence of calcification is common in bladder stones, which can form from minerals in the urine.
Previous Infection: Past infections, particularly with organisms that can calcify the bladder wall (e.g., schistosomiasis), may lead to calcification.
Malignancy: Certain types of bladder cancer (like squamous cell carcinoma) can cause calcification within the bladder wall.
Calcified Tumors: Benign or malignant tumors may calcify, appearing on imaging.
Conclusion:
Asymmetrical mucosal thickening and calcification in the bladder on a CT scan suggest potential bladder pathology, such as infection, stones, or malignancy. Further diagnostic tests, such as cystoscopy or biopsy, may be needed to confirm the diagnosis.
What do multiple erythematous nodular lesions and hemorrhage in the bladder mucosa suggest on cystoscopy?
Erythematous Nodular Lesions:
Potential Causes:
Interstitial Cystitis (IC): Chronic bladder inflammation often presents with erythematous (red) nodular lesions on cystoscopy. IC is associated with pain and urgency.
Bladder Cancer: Tumors may cause irregular, red, and nodular lesions on the bladder mucosa.
Chronic Infection: Recurrent bladder infections may cause the formation of erythematous nodules in the bladder lining.
Schistosomiasis: This parasitic infection can cause nodular, inflamed, and hemorrhagic lesions in the bladder mucosa, leading to changes observed during cystoscopy.
Hemorrhage (Blood in Mucosa):
Potential Causes:
Bladder Tumors: Hemorrhage in the bladder mucosa is often seen in malignancies, especially invasive cancers such as transitional cell carcinoma or squamous cell carcinoma.
Bladder Infection: Severe infections, particularly those caused by bacterial pathogens, can lead to hemorrhagic cystitis, where blood is seen in the bladder mucosa.
Trauma or Injury: Injury to the bladder from instrumentation or other mechanical trauma can cause localized bleeding and erythema.
Radiation Cystitis: Prior radiation therapy to the pelvic area can lead to radiation-induced cystitis, presenting as hemorrhage and erythematous changes in the mucosa.
What is schistosomiasis?
Schistosomiasis is a parasitic infection caused by trematode worms (schistosomes), typically acquired through contact with contaminated water.
What are the main species of Schistosoma responsible for schistosomiasis?
The main species are Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum.
How is schistosomiasis transmitted?
It is transmitted through skin contact with freshwater that contains cercariae, the larval form of the schistosome.
What is the lifecycle of the Schistosoma parasite?
The lifecycle includes eggs released into water, hatching into miracidia, which infect snails; cercariae are released from snails, which penetrate human skin and develop into adult worms in the bloodstream.
What are the common symptoms of schistosomiasis?
Symptoms include fever, chills, abdominal pain, diarrhea, blood in urine, and hepatosplenomegaly, which may appear weeks to months after infection.
What complications can arise from untreated schistosomiasis?
Chronic infections can lead to liver fibrosis, portal hypertension, bladder cancer, and neurological damage.
How is schistosomiasis diagnosed?
Diagnosis is typically made through stool or urine microscopy to detect eggs, or serological tests for antibodies or antigens.
What is the treatment for schistosomiasis?
The primary treatment is praziquantel, which causes paralysis and disintegration of the parasite.
What are the mechanisms of action of praziquantel in treating schistosomiasis?
Praziquantel increases the permeability of the schistosome’s cell membrane to calcium ions, causing muscle paralysis and disintegration of the parasite.
What are the key preventive measures for schistosomiasis
Preventive measures include avoiding contact with contaminated water, improving sanitation, and mass drug administration in endemic areas.
Where do the adult stages of Schistosoma mansoni, Schistosoma japonicum, Schistosoma mekongi, and Schistosoma intercalatum reside in infected hosts?
They reside in the mesenteric venous plexus, and their eggs are shed in faeces.
Where do the adult worms of Schistosoma haematobium reside in infected hosts?
The adult worms of S. haematobium are found in the venous plexus of the lower urinary tract.
How are the eggs of Schistosoma haematobium shed?
he eggs of S. haematobium are shed in urine.
What is the path of the Schistosoma cercaria after it penetrates the skin?
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.
What does “A” represent in the parasite’s journey?
“A” refers to parasites entering the gastroduodenal, hepatic, or splenic arteries to reach the liver.
What does “B” represent in the parasite’s journey?
B” refers to parasites entering the mesenteric arteries and moving through the hepatic portal vessels to the liver.
What does “C” represent in the parasite’s journey?
C” refers to parasites entering vessels leading to the bladder, from where they could also reach the liver.
Why is the journey of the Schistosoma cercaria challenging for the parasite?
The parasite must evade numerous host immune responses to reach its preferred site.
What is the origin of schistosomiasis, and how does it relate to animals and humans?
Schistosomiasis may have originally been a disease of animals that evolved into a zoonosis. Its life cycle includes both animals and humans as reservoirs.
What is the lifespan of an adult schistosome in the definitive host?
The lifespan of an adult schistosome is about 3–5 years, but they can live up to 40 years in the definitive hosts (humans).
When is serologic testing used for schistosomiasis, and what does it detect?
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.
Why may serologic testing not be suitable for determining active infection in patients with a history of repeated infections and treatments?
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.
What are the common symptoms of schistosomiasis?
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.
What are the effects of repeated schistosomiasis infections in children?
Children with repeated infections may develop anaemia, malnutrition, and learning disabilities.
What is Katayama fever, and what are its features?
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.
What is the acute clinical manifestation of schistosomiasis in the skin?
An immediate, pruritic, maculopapular eruption at the site of cercarial skin penetration within 1 day following exposure.
What are the systemic symptoms of acute schistosomiasis?
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.
What are the chronic clinical manifestations of schistosomiasis?
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.
What causes intestinal schistosomiasis, and which species are involved?
Schistosoma mansoni and Schistosoma japonicum adult worms live in the mesenteric veins, causing intestinal schistosomiasis.
What symptoms are associated with intestinal schistosomiasis?
Symptoms are caused by parasite eggs passing through or becoming trapped in intestinal tissues, leading to mucosal granulomatous inflammation, microulcerations, and superficial bleeding.
What causes hepato-splenic schistosomiasis, and which species are involved?
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.
What are the consequences of hepato-splenic schistosomiasis, especially in childhood?
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.
Where do adult Schistosoma haematobium worms live, and how are their eggs excreted?
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.
How many eggs do female S. haematobium release per day, and what happens to the eggs?
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.
What are the symptoms and pathological changes associated with urogenital schistosomiasis (UGS)?
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.
What increased health risk is associated with urogenital schistosomiasis (UGS)?
Urogenital schistosomiasis increases the risk of HIV transmission.
What happens when granulomas form around schistosomal eggs?
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.
What are the effects of clusters of living eggs in urogenital schistosomiasis (UGS)?
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.
What cancer risk is associated with urogenital schistosomiasis (UGS)?
Urogenital schistosomiasis is associated with squamous cell carcinoma of the urinary bladder. Schistosoma haematobium is classified as a carcinogen.
Where are schistosomal eggs deposited during established active urogenital schistosomiasis infection?
During active infection, eggs are frequently deposited in genital organs such as the cervix, seminal vesicles, and prostate.
hat cognitive and social impacts are associated with schistosomiasis?
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.
What is the current state of research on the neurological impairments caused by schistosomiasis?
Studies on the mechanisms involved in the neurological impairment caused by schistosomiasis are scarce.
What is chemoprophylaxis in the context of schistosomiasis?
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.
What can happen when mass drug administration (MDA) is disrupted in regions with high schistosomiasis transmission?
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.
What is the effect of praziquantel in treating schistosomiasis?
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.
What is the primary purpose of a Phase 1b clinical trial?
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.
What is the underlying pathogenesis of the symptoms presented in Katayama fever and chronic schistosomiasis?
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.
What are the complexities around vaccine development for schistosomiasis and why is a standard vaccine for travellers not available?
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.
What are the mechanisms of action of praziquantel in the treatment of schistosomiasis, and what are its adverse drug reactions (ADRs) and cautions/contraindications?
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.
What are the pros and cons of Mass Drug Administration (MDA) in the control of schistosomiasis infection?
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
What are the mechanisms of action of oxamniquine and metrifonate in the treatment of schistosomiasis, and what are their adverse drug reactions (ADRs) and cautions/contraindications?
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.
What is the rationale behind new drug discovery in the treatment of schistosomiasis, and what are the mechanisms of action of candidate molecules?
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.
