Microbio - Niche Infections and the Globo Ones Flashcards
Rapid neurological degeneration with normal Ix think
Prion disease
Type of encephalopathy in prion disease
Spongifom
Prion protein - normal and changes in disease
Prion protein gene on chromosome 20 - mainly expressed in CNS
When it is in a-helical structure it is protease sensitive, however when it is in the b-pleated sheet configuration it is not.
Prion disease promotes irreversible conversion from a-helical to B-pleated sheet.
Trigger remains unclear in sporadic cases.
Prion Disease Classification
Sporadic:
Creutzfeldt-Jakob Disease (80%)
Acquired (<5%):
- Kuru
- variant CJD
- iatrogenic CJD: GH, Blood, Surgery
Genetic (15%):
PRNP mutations
eg. Gerstmann-Straussler-Sheinker syndrome, Familial Fatal Insomnia
Sporadic CJD - presentation, epi, causes
Rapid dementia with: myoclonus, cortical blindness, akinetic mutism, LMN signs
Mean age onset 65 yrs (range 45-75 yrs)
Incidence 1/million/year
Death within 6/12
Cause uncertain
- ? somatic PRNP mutation
- ? spontaneous conversion of PrPc to PrPsc
- ?? Environmental exposure to prions
Sporadic CJD - Diagnosis
- EEG - periodic, triphasic complexes (non-specific), 2/3 abnormal
- MRI- basal ganglia – increased signal
cortical/striatal signal change on diffusion weighted imaging MRI - CSF increased 14-3-3 protein, S100 (markers of neuronal damage)
- Neurogenetics to r/o genetic cause
- Tonsillar biopsy NOT useful
- Brain biopsy
- Autopsy – by experienced pathologist - spongiform vacuolation and PrP amyloid plaques
Sporadic CJD - Differentials
Alzheimer’s disease Vascular dementia Mixed dementia (AD + vascular) CNS neoplasm eg. glioma, metastases Cerebral vasculitis Paraneoplastic syndrome Familial CJD vCJD
Variant CJD - Background
- Atypical CJD in teenagers and young people
- First reported in 1990s in 1990s
- Thought to link to mad cow disease (BSE)
- Younger age of onset (median age 26 yrs)
- Median survival time 14 months
- Psychiatric onset: dysphoria, anxiety, paranoia, hallucinations
- Then neurological: peripheral sensory symptoms, ataxia, myoclonus, chorea, dementia
vCJD- Diagnosis
- MRI brain - positive pulvinar sign (bilateral FLAIR hyperintensities involving the pulvinar thalamic nuclei)
- EEG – non-specific slow waves
- CSF – 14.3.3, S100 not useful
- Neurogenetics (almost 100% are MM at codon 129 so far)
- Tonsil biopsy 100% sensitive and specific –> eliminates need for further investigation to exclude other treatable causes, important for therapeutic trials and early treatment. May be positive in incubation period prior to clinical onset. See FLORID PLAQUES.
- (Brain biopsy)
- Autopsy
- PrPSc type 4t detectable in CNS + most lympo-reticular tissues
Iatrogenic CJD - Causes
Human cadaveric growth hormone
Corneal transplants
Neurosurgical procedures eg. dural grafts, pre-1991
Blood transfusions, other blood products
Other surgical procedures? - appendicectomy and tonsillectomy in vCJD
Iatrogenic CJD - Clinical Features
Progressive ataxia initially
Dementia and myoclonus later stages
Speed of progression depends on route of inoculation (CNS inoculation fastest)
Prion Genetics
3 Aspects:
Codon 129 polymorphism
- Methionine – Methionine (MM) - found in nearly 100% of vCJD
- Methionine – Valine (MV)
- Valine – Valine (VV)
Specific PRNP mutations (~30 so far, all AD)
Consider other neuro-genetic conditions eg. Huntington’s, spinocerebellar ataxia
Familial Prion Disease - GSS, FFI, CJD
Fix is crucial: dementian, “MS”, ataxia, psych
- EEG - non-specific
- MRI - basal ganglia: sometimes high signal
- Neurogenetics crucial
- If -ve: SCA, Huntington’s
- Autopsy
Familial Prion Disease - GSS(Gerstmann-Straussler-Scheinker syndrome)
Slowly progressive ataxia
Diminished reflexes
Dementia
Onset age 30-70 years
Survival 2-10 years
PRNP P102L, but several other mutations
Familial Prion Disease - Familial Fatal Insomnia (FFI)
Untreatable insomnia --> psych issues Dysautonomia Ataxia (thalamic degeneration) PRNP D178N +/ pyramidal/extrapyramidal signs, late cognitive decline
Kuru
Longest incubation - up to 45 years
From endocannabolism
Progressive cerebellar syndrome –> death within 2 years
Dementia late or absent
CJD Treatment
Symptomatic: clonazepam – mycolonus (can also give valproate, levetiracetam, piracetam)
Delaying prion conversion:
- quinacrine
- pentosan (intra-ventricular administration)
- tetracycline
Anti-prion antibody (prevents peripheral prion replication and blocks progression to disease in infected mice but does not get into CNS)
Depletion of neuronal cellular prion protein (prevents onset of disease in mice and blocks neuronal cell loss + reverses early spongiosis)
Fungi - Types of Yeast
Candida
Cryptococcus
Histoplasma (Dimorphic)
Fungi - Types of Moulds
Aspergillus
Dermatophytes
Agents of mucormycosis
Candida - Gram Stain
+ve budding yeast
Candidiasis
Primary or secondary mycotic infection caused by members of the genus Candida.
Clinical manifestations:
- Acute, subacute or chronic, episodic.
- Involvement may be localized to the mouth, throat, skin, scalp, vagina, fingers, nails, bronchi, lungs, or the gastrointestinal tract, or become systemic as in septicaemia, endocarditis and meningitis.
Distribution: World-wide.
Aetiological Agents: Candida albicans, C. glabrata, C. tropicalis, C. krusei. C. parapsilosis, C. guilliermondii and C. pseudotropicalis.
All are ubiquitous and occur naturally on humans.
Screening test for C. albicans - characteristic germ tubes on fluorescence?
Candida Endophtalmitis
- Often associated with candidemia, indwelling catheters or drug abuse, however it is rare in patients with severe neutropenia.
- Lesions are often localized near the macula and patients complain of cloudy vision.
- Exogenous Candida endophthalmitis is rare, but cases have been reported following ocular trauma or surgery.
- Similarly, conjunctival and corneal infections have also been recorded following trauma.
Chronic oral candidiasis
- Tongue and mouth corners (angular cheilitis)
- Suggests underlying immune deficiency.
- Characteristic white pseudomembrane composed of cells and pseudohyphae of C. albicans.
Stain for invasive candidiasis postmortem
Periodic Acid-Schiff (PAS) stained section.
Blastoconidia and branched pseudohyphae.
Candidiasis - Diagnosis
- Blood cultures for candidaemia, other samples for short term fungal culture.
- B D Glucan assay (serology)
- Imaging e.g. for hepatosplenic candidaisis
Candidiasis - Rx
- At least 2 weeks of antifungals from first negative blood cultures.
- ECHO and fundoscopy
- Echinicandin empirically and for non-albicans Candida
- Fluconazole for Candida albicans
- Ambisome (e.g. CNS), Fluconazole (e.g. urine) or Voriconazole (e.g. CNS) for organ-based disease.
Cryptococcosis
- Chronic, subacute to acute pulmonary, systemic or meningitic disease
- Initiated by the inhalation of the fungus.
- Primary pulmonary infections have no diagnostic symptoms and are usually subclinical.
- On dissemination, the fungus usually shows a predilection for the central nervous system, however skin, bones and other visceral organs may also become involved.
Distribution: World-wide.
Aetiological Agent: Cryptococcus neoformans.
Susceptibility greatly increased in pts with impaired T-cell immunity e.g. AIDS (2nd most common cause of death in AIDS)
Life cycle: eucalyptus tree –> bird excreta –> spores –> inhaled –> alveoli –> CNS
Crytococcus neoformans var. gattii
Causes a meningitis in apparently immunocompetent individuals in tropical latitudes, esp. SE Asia and Australia
High incidence of space-occupying lesions in brain and lung
Increased resistance to amphotericin B clinically
Cryptococcal Meningitis CSF stain
India ink - budding yeast cell surrounded by characteristic wide gelatinous capsule.
Cryptococcomas on MRI appear as
discrete white masses
Cryptococcus gattii on agar
typical brown colour effect due to phenol oxidase activity.
Cryptococcosis - Diagnosis
Diagnosis almost entirely around detection of Cryptococcal antigen in blood or CSF
Typical clinical features
Immunosuppressed host
Often culturable from blood, body fluids
Cryptococcosis - Management
3/52 Amphotericin B +/- flucytosine
Repeat LP for pressure management
Secondary suppression with fluconazole
Some evidence that high dose fluconazole effective
Aspergillosis - Genera
- Spectrum of diseases of humans and animals caused by members of the genus Aspergillus including:
(1) mycotoxicosis due to ingestion of contaminated foods
(2) allergy and sequelae to the presence of conidia or transient growth of the organism in body orifices
(3) colonization without extension in preformed cavities and debilitated tissues
(4) invasive, inflammatory, granulomatous, necrotizing disease of lungs, and other organs
(5) systemic and fatal disseminated disease (rare). - The type of disease and severity depends upon the physiologic state of the host and the species of Aspergillus involved.
Distribution: World-wide.
Aetiological Agents: Aspergillus fumigatus, A. flavus, A. niger, A. nidulans and A. terreus.
Aspergillus stain
Methenamine silver (GMS) –> fungal hyphae - balls or dichotomously branched
Aspergillosis - Management
- Voriconazole
- Ambisome
- Caspofungin/Itraconazole less good
- At least 6 weeks of therapy
- Duration based on host/radiological/mycological factors
Dermatophyte Infection
Tinea
Onchomycosis
Tinea pedis - organisms
Trichophyton rubrum or T. interdigitale, less commonly by Epidermophyton floccosum
Tinea cruris - organisms
Groin
T. rubrum and E. floccosum
Tinea capitis - organisms
T. rubrum and T. tonsurans
Onchomycosis - organisms
Trichophyton spp, Epidermophyton spp, Microsporum spp.
Pityriasis Versicolor - Organisms
MALASSEZIA FURFUR
M. sympodialis, M. globosa, M. restricta, M. obtusa, and M. slooffiae
Mucormycosis
Immunocompromised patients, poorly controlled Diabetes mellitus
Cellulitis of the orbit and face progress with discharge of black pus from the palate and nose.
Retro-orbital extension produces proptosis, chemosis, ophthalmoplegias and blindness.
As the brain is involved, there are decreasing levels of consciousness.
Rhizopus spp, Rhizomucor spp, Mucor spp
Mucormycosis - Rx
Surgical debridement very important, antifungal: Amphotericin, posaconazole
Targets of Antifungal Therapy
Cell membrane - Fungi use principally ergosterol instead of cholesterol
DNA Synthesis- Some compounds may be selectively activated by fungi, arresting DNA synthesis.
Cell Wall - Unlike mammalian cells, fungi have a cell wall
Antifungals Targeting Cell Wall
Polyene antibiotics:
- Amphotericin B, lipid formulations
- Nystatin (topical)
Azole antifungals (far less toxic than amphotericin):
- Ketoconazole
- Itraconazole
- Fluconazole
- Voriconazole
- Miconazole, clotrimazole (and other topicals)
Antifungals Targeting DNA/RNA Synthesis
Pyrimidine analogues e.g. Flucytosine
Flucytosine is an anti-metabolite type of antifungal drug. It is a synthetic fluorinated pyrimidine (FC –> FU, humans lack the enzyme that converts this) which is available for intravenous infusion or oral administration.
It is marketed as Ancotil.
Restricted spectrum of activity:
Acquired Resistance- result of mono therapy, rapid onset
Due to:
1) Decreased uptake (permease activity)
2) Altered 5-FC metabolism (cytosine deaminase or UMP pyrophosphorylase activity)
Uses:
- Monotherapy now limited
- In combination with amphotericin B or fluconazole for candidiasis, crypto coccus and ?aspergillosis
SEs:
- Infrequent – include D&V, alterations in liver function tests and blood disorders.
- Blood concs need monitoring when used in conjunction with Amphotericin B.
Antifungals Targeting Cell Wall
Echinocandins e.g. Caspofungin acetate (Cancidas)
Azoles - MOA
In fungi, the cytochrome P450-enzyme lanosterol 14-a demethylase is responsible for the conversion of lanosterol to ergosterol
Azoles bind to lanosterol 14a-demethylase inhibiting the production of ergosterol
Some cross-reactivity is seen with mammalian cytochrome p450 enzymes
- Drug Interactions
- Impairment of steroidneogenesis (ketoconazole, itraconazole)
Water-Soluble Triazoles
Voriconazole - similar structure to fluconazole but WATER SOLUBLE. limited spectrum of activity against fungi but also good oral bioavailablity and tissue penetration.
Structural similarity between azaleas and triazoles predicts that cross-resistance between these drugs is likely to occur.
Lipophilic Triazoles
- Posaconazole and itraconazole
- Not generally detected in CSF - debate re CNS penetration
- These azoles have extended spectrums of acivity when compared to fluconazole or voriconazole, but their lipophilic nature impairs gastrointestinal absorption
- Long side chain may help binding of drug to erg11
Echinocandin Antifungals
- Target fungal cell wall
- Caspofungin, micafungin, anidulafungin
- All have low oral bioavailablility so must be given IV due to large molecular weight
- All drugs have very similar spectrum of action. Primarily active against candida and aspergillus species.
- Degraded in the liver and excreted in the bile.
- Important to note that urine and csf concentrations are negligible.
Echinocandins - Pharmacology/MOA
Cyclic lipopeptide antibiotics that interfere with fungal cell wall synthesis by inhibition of ß-(1,3) D-glucan synthase.
Loss of cell wall glucan results in osmotic fragility
Spectrum:
- Candida species including non-albicans isolates resistant to fluconazole
- Aspergillus spp. but not activity against other moulds (Fusarium, Zygomycosis)
- No coverage of Cryptococcus neoformans
Polyene Antifungals
- Amphotericin B
- Therapy for systemic fungal infection
- Binds sterols in fungal cell membrane
- Creates transmembrane channel and electrolyte leakage –> loss of transmembrane potential –> impaired cellular function
- Active against most fungi except Aspergillus terreus, Scedosporium spp.
- Very little resistance despite long use
- Tendency to form miolecular aggregates which cause red cell lysis and lodge in the renal tubules causing drug reactions and renal impairment (liposomal amphotericin B prevents this by holding the drug in a phospholipid bilyaer - can also get ampB colloidal dispersion and ampB lipid complex)
Amphotericin B - Nephrotoxicity
Most significant delayed toxicity
Renovascular and tubular mechanisms
- Vascular-decrease in renal blood flow leading to drop in GFR, azotemia
- Tubular-distal tubular ischemia, wasting of potassium, sodium, and magnesium
Enhanced in patients who are volume depleted or who are on concomitant nephrotoxic agents
Zoonoses - Transmission
Every day contact with animals- Scratches or bites
By-products (feces/urine)- Contaminated soil, Litter
Foodstuffs- Carcass processing, Milk and milking, Raw/undercooked meats
Cambylobacter
Reservoir: Poultry (80% UK cases), Cattle
Transmission: Contaminated food
Clinical presentation: Diarrhoea, Bloating, Cramps
Investigations: Stool culture
Management: Supportive
Salmonella
Reservoir: Poultry, Reptiles/amphibians
Transmission: Contaminated food, Poor hand hygiene
Clinical presentation: Diarrhoea, Vomiting, Fever
Investigations: Stool culture
Management: Supportive, Ciprofloxacin, Azithromycin
Bartonella henselae
Reservoir: Kittens > cats
Transmission: Scratches, Bites, Licks of open wounds, Fleas
Causes two diseases:
- Cat Scratch Disease
- Bacillary angiomatosis
Bartonella is a slightly curved Gram negative rod. Kittens are more likely to infect people because they scratch more often and have a higher prevalence of Bartonella. Prevalence in cats of all ages can be 30 to 50%.
Bartonella henselae - Cat Scratch Disease - Presentation, Ix, Rx
Clinical presentation
- Macule at site of innoculation
- Becomes pustular
- Regional adenopathy
- Systemic symptoms
- 14% of cases can progress to more severe symptoms which can include eye problems, encephalopathy, arthritis, osteolysis, vascular system lesions, hepatitis, or pneumonia.
Investigations: Serology
Management: Erythromycin, Doxycycline
Bartonella henselae - Bacillary angiomatosis - Presentation, Ix, Rx
Clinical Presentation
- Occurs in immunocompromised
- Skin papules
- Disseminated multi-organ and vasculature involvement
Investigations: Histopathology, Serology
Management: Erythromycin, Doxycycline, PLUS rifampicin
Mostly in HIV - infected and other immuno-suppressed individuals. Much more severe disease than is CSD.
Vascular lesions may involve many organs, with skin being the most common.
Prevention: Wash hands after handling cats, Use flea control, Do not let cats lick areas of abraded skin or open wounds.
Toxoplasmosis
Reservoir: Cats, Sheep
Transmission: Infected meat, Faecal contamination
Clinical Presentation
- Fever
- Adenopathy
- Still-birth
- Progressive visual, hearing, motor, & cognitive issues
- Seizures
- Neuropathies
Investigations- Serology
Management- Spiramycin, Pyrimethamine plus sulfadiazine
Brucellosis
Reservoir: Cattle, Goats
Transmission: Unpasteurised milk, Undercooked meat, Mucosal splash, Aerosolisation/inhalation
Clinical Presentation
- Fever
- Back pain
- Orchitis
- Focal abscesses (Psoas, liver etc)
Investigations: Blood/pus culture, Serology
Management: Doxycycline PLUS Gentamicin OR Rifampicin
Incubation period- usually 30 days but can be up to 5 months
Symptoms - non-specific. Fever, chills, headache, myalgia, arthralgia, anorexia, fatigue, lymphadenopathy and splenomagaly.
The ratio to subclinical to clinical cases is 1:1 to 12:1.
Coxiella burnetii - Q fever
Reservoir: Goats, Sheep, Cattle
Transmission:
- Aerosolisation/inhalation of secretions, waste, or milk of infected animals
- Unpasteurised milk
Clinical Presentation
- Fever
- ‘Flu-like illness
- Pneumonia
- Hepatitis
- Endocarditis
- Focal abscesses (Para-vertebral/discitis etc)
Investigations: Serology
Management: Doxycycline
(hydroxychloroquine)
Rabies (Lyssa virus)
Reservoir: Dogs, Cats, Bats
Transmission: Bites, Scratches, Contact with infected fluid
Clinical Presentation
- Seizures
- Excessive salivation
- Agitation
- Confusion
- Fever
- Headache
Investigations: Serology, Brain biopsy, (USA saliva PCR)
Management: Immunoglobulin, Vaccine
Rate Bite Fever
Reservoir: Rats
Transmission: Bites, Contact with infected urine or droppings
Responsible agents either: Streptobacillus moniliformis or Spirillum minus. Very common carriage.
Clinical presentation
- Fevers
- Polyarthralgia
- Maculopapular progressing to purpuric rash
- Can progress to endocarditis
Investigations: Joint fluid microscopy & culture, Blood culture
Management: Penicillins
Hantavirus Pulmonary Syndrome
Reservoir:
- Deer mouse; Sin Nombre virus
- White footed mouse; Sin Nombre virus
- Cotton rat; Black canal virus
- Rice rat; Bayou virus
Transmission:
- Contact with infected urine or droppings
- Aerosolisation
Clinical presentation:
- Fever
- Myalgia
- ‘Flulike illness
- Respiratory failure
- May progress to bleeding, renal failure
Investigations: Serology, PCR
Management: Supportive
Western & southern USA and most of central & South America
HPS has also been linked with hypertensive renal disease in the inner city
Viral Haemorrhagic Fever
Reservoir:
- Ebola - ? Bats
- Marburg - ? Bats
- Lassa – Rats
- CCHF - ticks
Caused by a number of viruses – Lassa, Marburg, Ebola, and Congo-Crimean Hemorrhagic Fever
Transmission: Contact with fluids of infected
Clinical presentation
- Fever
- Myalgia
- ‘Flulike illness
- Bleeding
Investigations: Serology, PCR
Management: Supportive
Rickettesia
Transmitted via ticks on small rodents. “Spotted rocky mountain fever” Symptoms include: fever, constitutionals and vasculitis. Dx = Serology Tx = Doxycycline.
Plague
Organism: Yersinia Pestis Found on rats, transmitted by fleas Bubonic – Swollen LNs + Dry gangrene. Pneumonic – resp issues and bloody sputum. Dx = PCR
Treatment = “plague Causes Dry Gangrene Slowly” C = Chloramphenicol D = Doxycline G = Gentamicin S = streptomycin
Anthrax
Organism: Bacillus Anthracis
Cutaneous = painless round black lesion
Pulmonary = mediastinal haemorrhage, pleural effusion, lymphadenopathy
Tx = Doxycycline.
Leptospirosis
Organism: L. Interrogans (Gm –ve motile spirochaete)
Transmitted from farm animals (urine) or contaminated water (urine).
Symptoms: Constitutionals
Complications: Jaundice, renal issues, myocarditis, uveitis.
Treatment: Doxycyline.
Lyme Disease
Organism: Borrelia Burgoferia
Transferred via Ixodes tick (lives on deers) therefore associated with hiking.
Symptoms:
PHASE 1 – Erythema chronicum migrans aka Bulls eye rash, and flu like symptoms
PHASE 2 – Malaise, Carditis, Meningitis
PHASE 3 – Neurological signs, and arthriti.
Tx = Doxycycline.
Leishmania
- Organism: Unicellular protozoa
- Spread by sandflies (common in south America, north Africa and the middle east)
- Dx = Can be cultured on NMN medium (novy-macneal-nicolle) medium.
Signs and symptoms:
- Visceral aka Kala Azar – Caused by L. Donovani. Can be fatal: Constitutional, Hepatosplenomegaly, BM invasion, Post Kala-azar dermal leishmaniasis (PKDL)
- Cutaneous (commonest) – caused by L. Major and L Tropica, Scaly ulceration
- Mucocutaneous – caused by L Braziliensis: Mucous membrane destruction via ulceration, Deforming facial lesions
PKDL= macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well.
Trypansoma
Organism: Flagellate, unicellular protozoa.
Spread by the Tse-Tse fly.
Aka. Sleeping sickness
Signs and symptoms:
- Constitutionals
- Sleep Disturbance
- Neuro issues
- Lethargy
- Lymphadenopathy
T. Brucei Gambiense - Gradual infection. Commonest subtype.
T Brucei. Rhodeisiense- Rapid infection
T. Cruzii aka Chagas Disease
T. Cruzii aka Chagas Disease
Found in Brazil, transmitted by the Reduviid bug.
Acute = “purple eyelids” + constitutionals.
Chronic = Affects the oesophagus, heart and GI tract.
Helminths
WORMS
Helminths have parasitised humans for millennia
A parasite does not “want” to kill its host
Most worms cause little (if any) damage
When damage occurs, it may be:
oSlow: the worm, or its progeny, attempts to escape
oRapid: tissue damage as humans are not the natural host
Many worms have very complex lifecycles and cannot complete the lifecycle in one host
Types of Helminths
Cestodes (tape worms)
- Hydatid
- Pork / Beef / Fish tape worm
Trematodes (Flukes)
- Lung, liver, intestinal
- Blood (Schistosoma)
Nematodes (Roundworms)
- Hookworms
- Ascarids
- Strongyloides
Cestodes (tapeworms)
- Beef and pork tape worms are worms of human beings
- Echinococcus (Hydatid) is a dog tape worm
- These things cause trouble when humans become an accidental intermediate host
- Cyst formation in tissues causes mass effect
- Diagnosis with serology and imaging
- Treatment is difficult (but not always required)
Treatment and Prevention of Cestodes
Of worms: easy
- Praziquantel for human tape worms
- Praziquantel for dogs (Echinococcus)
Of cysts: difficult
- Hydatid: drugs don’t penetrate –> PAIR, Surgery, long term albendazole, praziquantel
- Cysticercosis: dying worms cause trouble –> Albendazole, praziquantel and STEROIDS.
Prevention:
- Hygiene, de-worm dogs, cull foxes.
Schistosomiasis
Probably the most common imported non-GI helminth
4 species, found in Africa, SE Asia and South / Central America
Lifecycle:
- Cercariae invade human skin when in contact with contaminated water.
- Worms develop in venous plexus
- Eggs excreted in faeces or urine
- Hatch into miracidia, which parasitise snails
- Snails release cercariae
Adult schistosomes lay eggs:
- Migration of eggs through bladder or bowel causes damage
- Retrograde passage of eggs into the liver causes “cirrhosis”
Diagnosis Microscopy: - Urine: S. haematobium - Stool: S. mansoni, S. japonicum Serology Biopsy
Treatment:
Easy - praziquantel
Prevention: Hard - Kill snails - Destroy snail habitat - Mass treatment - Interrupt transmission: no swimming, no washing etc.
Soil Transmitted Helminths
Very well adapted to humans and cause little pathology
3 main pathogens are:
- Ascaris lumbricoides – ingested with food
- Trichuris trichiura – ingested with food
- Hookworm – transdermal infection
- Plus (special case): Strongyloides stercoralis – transdermal infection
Cause disease through:
- Migration (ascaris, hookworm and strongyloides)
- Intestinal obstruction (ascaris)
- Malabsorption and blood loss (all of them)
- Psychological distress
Strongyloides
The only helminth capable of autoinfection
Therefore worm burden not related to infectious dose
Lifecycle:
- Larvae invade skin
- Mature into adult pinworms in the small bowel
- Eggs produced, hatch into rhabtidiform larvae
- These mature into filariform larvae (infectious)
- These can autoinfect via perianal skin
Damage:
- Hyperinfection
- Larva currens
- Malabsorption etc
- Generally asymptomatic
Treatment: ivermectin
Prevention: hygiene
Filariasis
A variety of nematode infections spread by blackflies and mosquitoes
Divided according to where the adult worm lives
- Lymphatic filariasis (Wuchereria, Brugia)
- Subcutaneous filariasis (Onchocerciasis, Mansonella, Loa loa)
- Serous cavity filariasis (Mansonella, Dirofilaria)
Adult worms release larvae (microfilariae) taken up by vector
Damage to tissues results either from:
- Adult worms: lymphatic filariasis (elephantiasis, scrotal swelling), also oncho (nodules)
- Microfilariae: Onchocerciasis (depigmentation, river blindness)
Diagnosis:
- Find microfilariae (blood film examination, skin snips)
- Find antibodies (ELISA, IFAT)
- Find adults (US – “dance sign”, Loa Loa migration)
Myiasis
- Parasitisation of human flesh by fly larvae
- Very common in some areas
- Occasionally imported
- Mainly: Bot (S. america) and Tumbu (Africa)
- Local damage as the maggot eats necrotic flesh
- Treatment: removal of larva by asphyxiation or surgery
MDRTB
Resistance to rifampicin and isoniazid
Which 3 countries account for most of the world/s TB
India
China
Russia
Risk factors for MDR TB in Europe
- Pooled risk for MDRTB 10.2 in previous treated vs never treated
- 6 national studies in: MDRTB more likely to be foreign born, younger than 65, male and HIV positive
- Prior TB therapy (OR-7.4)
- Presence of cavities (OR-2.6)
- History of imprisonment (OR-2.1) (between 1 and 23 treatment cycles)
- Recreational drug use (OR-3.0)
- HIV not associated with resistance (OR-0.3)
XDRTB
Resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).
