C18 Summary

MedEd

zoonosis

disease transmitted from a vertebrae animal to human

e.g. ebola, salmonellosis, rabies

arbovirus

distinct group of unrelated viruses that infect arthropod vectors

e.g. mosquitoes, ticks

causative agents of malaria

Plasmodium falciparum = most common, malignant tertiary fever (36-48hr)

Plasmodium ovale
Plasmodium vivax
= tertian fever (48hr)

Plasmodium malariae
Plasmodium knowlesi
= quotidian fever (72hr)

replication + transmission of malaria

via female Anopheles spp. mosquito

sporozoites in to human when infected mosquito bites

gametocytes out of human (pass on to mosquito when taking blood meal)

in human, exo-erythrocytic cycle in liver makes a schizont which ruptures -> blood

in blood, erythrocytic cycle makes mature trophozoite -> schizont which ruptures and gametocytes

in mosquito, microgamete enters macrogamete and ookinete -> oocyst forms, which ruptures to release sporozoites

can also be transmitted via transfusion, congenital and needle stick injury

clinical features malaria

general = headaches, lethargy, ischaemia, N+V, diarrhoea, anaemia

cyclical paroxysms = chills -> fevers -> sweats

complicated malaria:

P. falciparum (36-48hr fever) = coma, pulmonary oedema, renal failure, shock, lactic acidosis, splenomegaly, death

P. vivax/ovale (48hr fever) = splenic rupture

P. malariae (72hr fever) = glomerulonephritis and immune complexes

malaria treatment

ACT = artemisinin combination therapy
e.g. artemisinin + chloroquine

falciparum malaria:
- IV ACT (artesunate) until oral can be tolerated
- artemether with lumefantrine
- quinine

- WHO says no monotherapy to prevent resistance

malaria prevention

Mosquirix vaccination prevent liver infection, but poor efficacy and wanes after 4yrs

insecticide impregnated mosquito nets
removal of standing water
release of sterile male mosquitoes

prophylaxis in endemic areas
for adults in areas of chloroquine-resistant P falciparum: mefloquine, doxycycline etc. used
for children chloroquine, proguanil, mefloquine used

malaria diagnosis

gold standard = blood smear

thick smear for detection of parasitaemia (% of infected RBCs)

thin smear for identification of species

artemisinin MOA

catalyses heme-iron which releases radicals which kills parasite

artesunate MOA

binds multiple target but MOA not understood

chloroquine MOA

interferes with parasite's ability to used Hb as nutrient

causes build up of toxic by product -> kills parasite

resistance common

quinine

used in areas of chloroquine resistance

MOA not fully understood

primaquine

used for treatment of dormant P. vivax/ovale

thought to inhibit respiratory chain

african trypanosomiasis causative agents

african trypanosomiasis = sleeping sickness

spread by Tsetse fly (Glossina spp.)

Trypanosoma brucei rhodesiense = 10%, very quick + acute onset, "East African", wild animals/livestock thought to be primary reservoir

Trypanosoma brucei gambiense = 90%, slow + insidious, "West African", humans thought to be primary reservoir

sleeping sickness stage I

haemolymphatic phase

trypanosomes multiply in skin + lymph nodes

fever
headaches
lymphadenopathy (Winterbottom's sign)
itchy skin

sleeping sickness stage II

neurological phase

trypanosomes cross the BBB into the CNS

confusion
change in personality
sleep disturbance
coma
death

african trypanosomiasis transmission + lifecycle

extracellular

infected Tsetes fly (genus Glossina) injects metacyclic trypomastigotes into skin tissue

parasites enter lymphatic system -> bloodstream

in host they become trypomastigotes and carried around body

tsetes fly takes blood meal and ingests trypomastigotes, cycle in fly takes around 3 weeks

rarely gambiense can be acquired congenitally

sleeping sickness diagnosis + treatment

needs definitive diagnosis by microscopy + stage of infection

complex dosing regimens if CNS involvement

drugs have adverse side effects

stage I = fexinidazole (first line) pentamidine, suramin

stage II = melarsoprol, eflornithine, fexinidazole (non-severe first line)

chaga's disease causative agent

trypanosoma cruzi
spread by triatomine "kissing" bugs - defecate into bite wounds

can also be via transplant, oral and congenital

predominantly found in S America, but hotspots in regions of migration

phases of chaga's

acute phase = Romana sign - unilateral, painless periorbital swelling

indeterminate phase = asymptomatic

chronic (20-30%) =
cardiac form - pseudocysts cause massive infiltration + cardiomegaly
GI form - infiltrates megaoesophagus + megacolon

triatomine bug lifecycle

blood meal, faeces containing trypomastigotes enter bite wound

at wound site, become amastigotes

amastigotes multiply by binary fission in cells, transform into trypomastigotes then burst out of cell into bloodstream

triatomic bug takes blood meal, multiply in midgut back into trypomastigotes

chaga's treatment

NECT = nifurtimox-elfornithine combination therapy

benznidazole

leishmaniasis causative agent

Leishmania spp.
vector = phlebotomine sandflies
only infects phagocytic cells

avoids immune surveillance, inhibits innate immune response

primary replication in neutrophils, "hides" in macrophages, releases LCF to attract more neutrophils

distribution in Americas, N Africa, Middle East

leishmaniasis cutaneous form

most common, sub clinical

non-ulcerating lesions -> ulcerating lesions + scarring

caused by L. tropica, L. aethiopica and L. mexicana

most common is Oriental sore

diffuse cutaneous = anergic, widespread non-ulcerating nodules

leishmaniasis muco-cutaenous

S America

reaction at bite, metastasises to mucous membranes

chronic non-healing ulcers that destroy tissues + cartilage

pathogen = L. braziliensis

visceral leishmaniasis

a.k.a Kala-azar

pathogens = L. donovani, L. infantum, L. chagasi

fatal untreated

incubation of 1-2months -> 10 yrs

low grade fever, progressive hepatosplenomegaly, anaemia, wasting

PKDL = post kala-azar dermal leishmaniasis (pigmentation changes and extensive facial lesions)

leishmaniasis lifecycle

sandfly takes blood meal, injects promastigotes

promastigotes phagocytosed, become amastigotes

amastigotes multiply in cells and infect other cells

sandfly ingests infected macrophages from human

transform from amastigotes back into promastigotes

leishmaniasis treatment

mainly for visceral, useful to know species + type of infection

visceral = liposomal amphotericin B

all forms = miltefosine

dengue cause

dsRNA flavivirus
vector = Aedes spp. mosquito

4 serotypes

adapted to urban areas, prevention measures such as larvicide, no standing water, fogging and nets useful

dengue clinical features

25% get sick

mild dengue = fever, N+V, rash, peri-orbital pain, aches

warning signs = severe abdominal pain, persistent vomiting, rapid breathing, fatigue, hepatomegaly, blood in vomit/stool, bleeding gums or nose

severe dengue = 3-7 days after onset
severe plasma leakage (shock + resp. distress)
severe bleeding/haemorrhage
severe organ involvement (liver, CNS, heart)

dengue diagnosis

less than 5 days post fever = viral RNA

5+ days post fever = IgM (recent) or IgG (lifetime)

dengue treatment + prevention

supportive care only

severe = emergency, fluid replacement needed

infection provides immunity for specific serotype, but re-infection can increase risk of severe + further increased if different serotype

prevention = avoiding bites, larval source management

vaccine available, but only after infection (antibody-dependent enhancement)

yellow fever cause

acute viral haemorrhagic disease

primary reservoir thought to be monkeys

human-human transmission via Aedes aegyptii mosquito

periodic outbreaks when infection introduced to urban area with little immunity and high mosquito density

seen in Africa and C + S America (tropical)

yellow fever clinical features

incubation = 3-6 days

mild = fever, muscle pain, headache, N+V
will resolve 3-4 days later

15% progress to severe 24hrs after initial resolution

severe = high fever, jaundice, renal failure, bleeding from mouth, nose, eyes, GI tract

yellow fever diagnosis + treatment

early diagnosis = RT-PCR blood/urine test
can also look for virus-specific IgM ELISA

differentials = malaria, viral hepatitis (fulminant), dengue etc.

supportive management
vaccine = life attenuated, effective, recommended in endemic areas

and prevention of vector

JEV cause + epidemiology

culex spp. mosquito

main cause of encephalitis in Asia, 1 in 250 progress into severe disease

differentials = meningitis, encephalitis

JEV clinical features

incubation = 5-15 days (very few get ill)

mild = fever, headache, vomiting

severe = neurological Sx, high fever, stiff neck, seizures, coma, 30% death, 30-50% permanent neurological/psych issues

JEV diagnosis + management

CSF for virus-specific IgM antibodies

supportive treatment only

vaccine available, over 90% effective, good for 3yrs

zika cause

vector = Aedes agyptii

two lineages: African + Asian

zika clinical features

incubation = 3-10 days

mostly asymptomatic, may have: fever, rash, malaise, joint pain, headache

complications = Guillan-Barre syndrome (acute inflammatory demyelinating polyneuropathy), myelitis
presenting with paraesthesia, muscle weakness, pain

in pregnancy can lead to microencephaly, congenital zika syndrome (malformations) or miscarriage/preterm

zika treatment

supportive management

no vaccine

vector control, barrier contraception if at risk (avoid congenital)

helminths

broad term for parasitic worms which invade body

series of eukaryotic multi-cellular macro-parasites, many of which reside in GI tract or invade blood/ lymph vessels

3 groupings:
nematodes (roundworms)
trematodes (flukes)
cestodes (tapeworms

ascariasis cause + epidemiology

nematode - creamy white round worm
13-35cm long

Ascaris lumbricoides

effects up to 1 billion people a year

ascariasis migratory phase

eosinophilia (high level)

pneumonitis

Loffler's syndrome (rare, self-limiting, benign pulmonary oedema)

ascariasis intestinal phase

can be asymptomatic

obstruction

perforation

anaemia

failure to thrive

ascariasis hepatobiliary/pancreatic phase

due to migration into biliary tree

ascariasis lifecycle + transmission

faecal-oral route

ingestion of embryonated eggs, resistant to stomach acid

eggs hatch in gut lumen, larvae penetrate into circulatory system

migrate to lungs, further development, coughed up and re-enter GI tract

further mature to adult form in gut, produce eggs which are passed in faeces

unfertilised = not infective

fertilised eggs develop to infectivity after 18 days depending on conditions

ascariasis treatment

hookworm cause + epidemiology

nematode

Necator americanus = affects 80% of the world

Ancylostoma duodenale = "old world"

Ancylostoma carinum = infects dogs, not adapted to humans but can cause skin manifestations

hookworm presentation

ground itch or cutaneous larva migrans = blister-like eruption + itch at site of entry

often asymptomatic but can attach to gut causing blood, protein + fluid loss:

failure to thrive/malnutrition
anaemia
hypoproteinaemia
enteritis
eosinophilia

can cause cardiac, resp + GI complications

hookworm lifecycle

infected individual defecates eggs which hatch in soil

motile filariform larvae after 5-10 days = infective, are chemoattracted to host

infect by burrowing through skin into circulatory system

migrate to lungs + develop, ascend to pharynx and are swallowed

mature in jejunum, release eggs into faeces

hookworm treatment

schistosomiasis cause + epidemiology

trematode/fluke

genera Schistosome

most prevalent in Africa

S. haematobium = urogenital

S. mansoni + S. japonicum = intestinal + hepatic

schistosomiasis presentation

"Swimmer's itch" = inflammation, itching at source

acute = Katayama syndrome (nocturnal fever, cough, myalgia, headache + abdo tenderness)

chronic = hepatosplenomegaly, fibrosis, haematuria, haemospermia, miscarriage, infertility, cancer, portal hypertension, ascites

dependent on organism

rarely migrate to CNS causing seizures/paralysis/inflammation

schistosomiasis lifecycle

infected human sheds eggs into environment (water)

eggs hatch + parasites infect freshwater snail (intermediate hosts)

parasite matures into sporocysts within snail + released into water again

free-swimming cericariae penetrate host skin into circulation (as schistosomulae)

migrate to liver where they develop + mature

in S. haematobium migrate to venous plexus of bladder, secrete eggs -> released in urine

in S. mansoni + S. japonicum migrate to mesenteric veins of intestine + secrete eggs into GI tract -> faeces

schistosomiasis diagnosis + treatment

hydatid disease cause

cestode
human echinococcosis

causative agents = Echinococcus granulises + multiocularis

dog/fox are definitive hosts, humans are intermediates

cystic + alveolar forms

hydatid presentation

5-15yrs incubation

commonly affects lungs (chronic cough, chest pain, SOB) + liver (abdo pain, N+V)

alveolar is more fatal, signs include weight loss, hepatic failure, abdo pain as usually liver lesion
larvae may spread to lymph + blood

diagnosis usually incidental

hydatid lifecyle

ingested eggs, oncospheres released in gut

spreads via circulation, cysts in organs

humans = dead end host

hydatid treatment

taeniasis forms + causes

human tapeworm, cestode

taenia saginata = beef, ingestion of contaminated + undercooked meat

taenia solium = pork, ingestion of contaminated + undercooked meats + eggs

taenia asiatica

humans definitive host

taeniasis presentation

intestinal: fullness, anaemia, weight loss, B12 deficiency, nausea, abdominal pain

cysticercosis (PORK) = cysts cause inflammation, scarring etc., can die + calcify, can also infect CNS

neurocysticercosis = headaches, seizures, muscle weakness, confusion, blindness, meningitis

taeniasis lifecycle

eggs in faeces ingested by cattle or pigs

in animal intestine oncospheres hatch, invade wall, migrate to muscle where they become cysticerci

humans ingest infected meat

in intestine cysticercus develops over 2 months into adult, reside in small intestine

produce proglottids which mature, detach and are passed in faeces

helminths diagnosis

microscopy of urine/faeces for most + serological testing

schistosomiasis = kato katz stool microscopy, urine, ELISA, PCR

hydatid = scans + surgical exploration

niclosamide

first line for tapeworms/taeniasis

MOA = blocks glucose uptake, oxidative phosphorylation + anaerobic metabolism in tapeworm

may cause mild GI Sx

mebendazole

for ascariasis and hookworm

also for pinworms, whipworms, cutaneous larva migrans

MOA = selectively inhibits synthesis of microtubules - blocks polymerisation of tubulin

contraindicated in pregnancy

SE include dizziness, neutropenia, alopecia, skin reactions

also need to treat any underlying anaemia etc.

albendazole

similar to mebendazole so used in ascariasis, hookworm, hydatid, taeniasis

prevents glucose uptake like mebendazole

praziquantel

first line for schistosomiasis

also used for taeniasis

single dose, 40mg/kg

MOA = paralysis of larvae + adult worms

SE include nausea, dizziness, drowsiness, headache

levisamole

used for ascariasis and hookworms

MOA = nicotinic ACh receptor agonist, paralyses helminth

hydatid treatment

surgical removal of cysts

albendazole as cover
or mebendazole/praziquantel

elephantiasis

also known as lymphatic filariasis, nematodes

obstruction of lymphatic system

diethylcarbamazine treatment

onchocerciasis

river blindness

filarial worm Onchocerca volvulus - but transmitted by black flies

treatment = ivermectin

helminths summary flashcard

see image :)

amoebiasis

amoebic dysentry
caused by ingestion of mature cysts, cysts + trophozoites passed in faeces

Entamoeba histolytica

presents as diarrhoea (+/- blood and mucus), abdominal pain
amoebic liver abscess (ALA) = URQ pain, clay colour stool, dark urine, fever, chills, night sweats

symptomatic treatment = metronidazole, tinidazole, omidazole

asymptomatic treatment. = diloxanide furoate

giardiasis

caused by Giardia duodenal

asymptomatic, or acute presentation of gassy diarrhoea, greasy floating stool, stomach cramps, N+V

treated with metronidazole, tinidazole or nitazoxanide

metronidazole

treatment for amoebic dysentry + giardiasis

nitazoxanide

used if needed in cryptosporidiosis and for giardiasis

MOA = disrupts metabolism + induces lesions in cell membranes

cryptosporidiosis

caused by Cryptosporidium hominis + parvum

presents as asymptomatic in immunocompetent

immunosuppressed = diarrhoea, vomiting, stomach cramps

treatment = rehydration, Nitazoxanide if needed

prevention + control of vector borne diseases

insecticide impregnated nets

indoor residual spraying, outdoor fogging

larvicide

tsetse fly traps

mass drug administration

water treatment

ADR definition

NICE: response to medicinal product which is noxious + unintended

relationship between medicinal product + adverse event is either known or strongly suspected

pharmacodynamic ADR

= what drug does to body

drug effect scaled up or down

e.g propanolol reducing effects of salbutamol

pharmacokinetic ADR

= ADME, what body does to drug

changes in ADME alter effect of drug

e.g. NSAIDs reduce antihypertensive action of diuretics by reducing renal blood flow

adherence

extent to which patient's actions match agreed recommendations (shared plan)

e.g. doctor prescribes, instructs only to take when in pain, so patient does this

enhancing adherence = key to patient safety

5 dimensions: socioeconomic, therapy related factors, patient related factors, condition related factors, health system factors

adherence = (no. of doses taken/no. of prescribed doses) x 100

compliance

act of following a medical regime or schedule correctly and consistently

"do as I say"

e.g. doctor prescribes, patient takes even if not sure why

concordance

joint agreement about medication plan

"do you agree to do as I say?"

e.g. patient needs meds, doesn't want tablets, injections done instead

ABCDEF classification of ADRs

Augmented = dose related, common, exaggeration of normal action, toxic + side effects
e.g. bleeding due to warfarin

Bizarre = non-dose related, unexpected, immunological/hypersensitivity/idiosyncratic
e.g. anaphylaxis to penicillin

Chronic = dose (cumulative) + time related, uncommon, persists
e.g. HPT suppression by corticosteroids

Delayed = time-related, take time to become apparent, uncommon
e.g. tardive dyskinesia, leucopenia

End of Use = withdrawal, uncommon
e.g. insomnia + anxiety after bento withdrawal

Failure = drug not working, dose-related, often due to DDIs

DoTS classification of ADRs

Do = Dose
supra-therapeutic dose (toxic effects)
standard therapeutic dose (collateral effects)
sub-therapeutic dose (hypersensitivity in susceptible patients)

T = Timing
will be time independent or time dependent

S = Susceptibility
age, gender, disease states, pregnancy, ethnicity, poly pharmacy

explain how all drugs have both beneficial and adverse effects

no drug is 100% specific for 1 receptor subtype, will always be a knock-on effect
also, not all tissue perfect

TD50 = dose of drug causing toxicity in 50% of population

ED50 = dose of drug effective in 50% of population

therapeutic index = TD50/ED50
larger TI = safer