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Neglected diseases Flashcards

1
Q

What is a communicable disease?

A

Infectious disease

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2
Q

Where are communicable diseases common?

A

Populations living in poverty without adequate sanitation and in contact with infectious vectors, domestic animals and livestock

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3
Q

What is a neglected disease?

A

Diverse group of communicable diseases in tropical and subtropical conditions

Often overlooked by industry and those instrumental in drug access (Government, media)

Some are even found in the US where there are high levels of poverty (these diseases are spreading)

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4
Q

What 3 conditions used to be neglected diseases?

A

HIV/AIDs

Malaria

TB

There are now medicines for these

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5
Q

Why are neglected diseases overlooked by drug developers?

A
  • Cannot recover the cost for developing and producing treatments for these diseases
  • In underdeveloped nations- industries mainly focus on these diseases affected by the western world where they can get their money e.g. cancer, cardiovascular disease
  • Generally do not cause dramatic outbreaks worldwide that would kill large numbers of people
  • Limited funding for basic research
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6
Q

What 3 main regions of the world do these neglected diseases come from and what is the problem?

A

India, South America and Africa

They all have large populations but the government is investing very little money into the healthcare system

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7
Q

How are parasites transmitted?

A

Vectors

Contaminated water and soil

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8
Q

Why do we need to treat neglected diseases?

A
  • Drug resistant organisms
  • Few newly approved therapies and only a handful of novel drugs
  • International travel and immigration means that these diseases are no longer geographically restricted
  • Diseases e.g. Ebola spread around the world very quickly
  • Significant mortality- social and economic consequences
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9
Q

What are the disadvantages of current treatments?

A
  • Decades old
  • Resistance
  • Serious side effects
  • Poor patient compliance
  • Limited efficacy
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10
Q

What is malaria caused by?

A

Protozoan parasite genus Plasmodium (eukaryote)

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11
Q

Malaria is caused by Plasmodium, a eukaryote. What are its features and makes it characteristic?

A
  • Has two hosts in its life cycle. Insect host (sexual) and vertebrate host
  • 14 chromosomes in the nucleus
  • Genetic material in the mitochondria
  • Genetic material in the apicoplast, a double-membrane organelle making it very characteristic
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12
Q

How is malaria transmitted?

A

Infected female Anopheles mosquito

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13
Q

What can an initial infection of malaria lead to?

A

Anaemia, cerebral malaria and eath

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14
Q

Why is it not possible to spread malaria in the northern hemisphere?

A

Mosquitoes do not exist here

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15
Q

Malaria can be transmitted through a blood contaminated needle. True or false?

A

True

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16
Q

What are the 4 species of malaria that affect humans and which one is the most fatal one?

A
  1. Plasmodium falciparum (malignant, most dangerous, tertian)
  2. Plasmodium vivax (benign, tertian)
  3. Plasmodium malariae (quartan)
  4. Plasmodium ovale (tertian)
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17
Q

What does tertian and quartan mean?

A

Tertian- fever occurs every 48 hours

Quartan - fever occurs every 2 hours

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18
Q

What is the life cycle of malaria?

A
  1. Infected female Anopheles mosquito parasite and injects sporozoite
  2. Sporozoites travel to liver and take up residence in hepatocytes
  3. Sporozoites multiply asexually and become merozoites. Liver cells then burst releasing it into the blood (7-10 days)
  4. In the blood, merozoites invade erythrocytes and multiply until the cell bursts
  5. The cycle then repeats itself. Merozoites invade RBCs, multiplies and bursts. Each time, it causes fever and chilld
  6. After several asexual cycles, the merezoites can invade RBCs and instead of replicating, developing into sexual gametocytes
  7. Mosquitoes bite infected humans. It digests gametocytes which allow development into mature sex cells (gametes)
  8. Gamete - zygote - oocyte.
  9. When oocyte ruptures, it releases sporozoites which move to salivary glands of mosquito
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19
Q

What drug is effective against the exoerythrocytic and gametocytic form in malaria?

A

Primaquine

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20
Q

What drugs are effective against the erythrocytic form in malaria?

A
  • Artemisinin
  • Chloroquine
  • Quinine
  • Mefloquine
  • Pyrimethamine
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21
Q

Quinine:
What groups are fundamental for action?

What type of malaria is it particularly good for?

What is the relevance of its stereochemistry?

A
  • Benzene ring and tertiary amine fundamental for action
  • From bark of cinchona tree
  • Good for chloroquine-resistant strains of Plasmodium falciparum

Both diastereomers are active against malaria:

i) Quinine - must abundant
3R:4S:8S:9R

ii) Quinidine
3R:4S:8R:9S

Its epimers are inactive

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22
Q

All quinoline- based antimalarials have which 2 funtional groups?

A

Tertiary amine

Benzene ring

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23
Q

Quininacrine is good for what conditions?

A

Malaria and tapeworm infections

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24
Q

Chloroquine:

What is its structure?

What are its side effects

A
  • Chiral centre and used as a racemic mixture
  • Chlorine in the compound increases activity
  • Most effective and safe medicine to treat malaria
  • Limited side effects- muscle problems, appetite loss, diarrhoea
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25
Q

What 5 drugs are under the class quinoline-based compounds?

A
  1. Quinine
  2. Quinacrine
  3. Chloroquine
  4. Mefloquine
  5. Pamaquine
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26
Q

What is mefloquine used for and how is it taken?

What is the problem with mefloquine?

What is the structure?

A

Treatment for mild to moderate malaria- once a week dosing

Prophylaxis- once a week 1 or 2 weeks before potential exposure and continue for 4 weeks after

Sold as a racemate

Problems:

  • Resistance common in Asia
  • Side effects are more serious - depression, hallucinations, anxiety, seizures and ringing in the ears
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27
Q

What is amodiaquine used for?

Does it have a long half-life?

What is it usually given with and why?

What are the side effects associated with it?

A
  • Uncomplicated Plasmodium falciparum (works against chloroquine-resistant PF)
  • It has a long half-life
  • Given with artesunate in ACT to reduce risk of resistance

Rare but serious side effetcs- liver problems or low blood cell levels

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28
Q

What is the MOA of chloroquine and other quinolone-based compounds?

A
  • Haemaglobin is transported into the food vacuoles of the plasmodium where digestion of the haemaglobin supplies the organism with a source of amino acids
  • Free heme is not metabolised as it is toxic to Plasmodium cells and instead, Plasmodium polymerises free heme to form hemozoin (non-toxic)
  • Quinolines bind hemes together via a pi-pi interaction preventing polymerisation into hemozoin
  • This allows poisoning of plasmodium

Works at erythrocyte stage

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29
Q

What is ACT and why is it used?

A

Artemisinin- based combination therapies to prevent resistance in malaria treatment

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30
Q

Name a drug under the artemisinin class?

A

Artesunate

From sweetworm wood (Chinese herbal medicine)

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31
Q

What is the MOA of artemisinins?

A
  • Works at erythrocyte stage
  • Contains Oxygen-oxygen peroxide bond which is very reactive and allows the compound to have anti-malarial activity - free radical production
  • Iron 2 reacts with peroxide - oxidation into iron 3
  • The compound then either breaks down into:

i) Non toxic metabolite + toxic iron radical
or
ii) Alkylating radical which covalently binds to the heme (Heme-artemisinin adduct) stopping polymerisation into the non-toxic form hemozoin

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32
Q

What are the two ACT combinations?

A
  1. Artesunate and amodiaquine

Acute uncomplicated Plasmodium falciparum
Side effects- nausea, loss of appetite, abdo pain

  1. Artesunate and mefloquine

1st line treatment in Thailans
Uncomplicated falciparum
Side effects of mefloquine (depression, hallucinations, seizures) seem to be reduced when in this combination

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33
Q

What is the MOA of proguanil in malaria?

A
  • Dihydrofolate reductase inhibitor (DHFR)
  • Prodrug that metabolises into cycloguanil
  • Stops production of tetrahydrofolate, which is a cofactor in synthesis of amino and nucleic acids
  • Therefore stops cycle of malaria

Although humans have DHFR, it is selective to malaria

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34
Q

What are the 3 conditions under kinetoplastid disease?

A
  1. Leishmania
  2. Sleeping sickness
  3. Chaga’s disease
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35
Q

What are kinetoplastids? What is a distinguishing feature of them?

A
  • Protozoa
  • Eukaryotic and possess normal eukaryotic organelles
  • Kinetoplasts - organelle with a large massed DNA
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36
Q

What vector causes Leishmania?

A
  • Female sandfly of the genus Phlebotomus
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37
Q

Who does Leishmania effect?

A

Humans, dogs, foxes

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38
Q

What are the 2 types of Leishmaniasis?

A
  1. Cutaneous
    - Self-healing or chronic lesions on the skin or mucous membranes
    - Skin sores usually start at site of the bite
    - Not life-threatening
    - Not usually treated with drugs unless re-occurring
  2. Visceral
    - 2-8 months after initial bite
    - Parasite damages immune system
    - Fatal without treatment
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39
Q

What is the life cycle of Leishmaniasis?

A
  1. Infected sandfly bites and injects promastigotes into skin of host
  2. Macrophages phagocyte promastigotes that differentiate into amastigotes and multiply in cells of various tissues
  3. Macrophages burst releasing more amastigotes that are re-phagocytosed
  4. Uninfected sandfly bites and ingests amastigotes
  5. Amastigotes differentiate into promastigote stage and divides in the midgut of the fly
  6. Promastigotes migrate to proboscis (sucking mouthpart) and are now able to transmit the disease
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40
Q

What are the 3 drugs used to treat visceral leishmaniasis and which one can also treat cutaneous?

A
  1. Sodium stibogluconate antimonium (Sb) complex
  2. Amphotericin B
  3. Pentamidine works against both
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41
Q

What is sodium stibugluconate antimonium (Sb) complex used for?

How does it work?

What are some side effects?

A
  • Visceral leishmaniasis
  • Inhibition of DNA replication via inhibiting topoisomerase enzymes and cell signalling via inhibiting tyrosine photsphatases
  • Nausea, loss of appetite, muscle pain
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42
Q

What is amphotericin B used for?

How does it work?

A
  • Visceral leishmaniasis if nothing else wors

- Forms pores in cell membrane that cause rapid leakage of potassium, sodium, chloride and hydrogen ions - cell death

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43
Q

What is Pentamidine used for in leishmaniasis?

How is it given and why?

What are some side effects?

What is its MOA?

What is its pharmacophore?

A

Visceral and cutaneous leishmaniasis

Via IV, IM or inhalation. It has a lack of oral bioavailability and poor BBB penetration

Side effects - low blood sugar, nausea, low BP

Hydrogen bonds to DNA of parasite at N3 of adenosine via amidine moiety
This stops DNA replication and causes death of parasite

Pharmcophore- dibasic

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44
Q

How have they tried to make a new drug from pentamidine and why?

A

Dibasic pharmacophore with a different linker to try and improve oral bioavailability and enhance cell permeability

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45
Q

What causes Human African trypanosomiasis?

A

Trypanosoma brucei

Sleeping sickness

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46
Q

What is the vector for sleeping sickness?

A

Tstetse fly

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47
Q

What are the two forms of sleeping sickness?

A
  1. TBG - 95% cases
    West and central Africa
    Chronic infection
    Latent and symptomless for months and years. Symptoms may only emerge in advanced disease states where CNS is affected
2. TBR 
Eastern and Southern Africa
Acute infection
Symptoms weeks-months after infection
Develops rapidly and invades CNS
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48
Q

What are the 2 stages of symptoms for sleeping sickness and what are the treatment options?

A
  1. Haemolymphatic
    - Parasites multiply in subcutaneous tissues, blood and lymph
    - Boughts of fever, headaches, joint pains and itching
    - Treatment options- pentamidine, suramin
  2. Neurological
    - Parasite crosses BBB and infects the CNS
    - Behaviour change, confusion, sensory disturbances
    - Lethal without treatment
    - Melarsoprol, eflornithine
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49
Q

Why can you not use pentamidine in the neurological stage of sleeping sickness?

A

Cannot cross BBB

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50
Q

What is the lifecycle for sleeping sickness?

A
  1. Tstetse fly bites human and injects metacyclic trypomastigotes
  2. Metacyclic trypomastigotes transform into bloodstream tyrpomastigotes which are carried to other sites
  3. Trypomastigotes multiply by binary fission in various body fluids (blood, lymph, spine)
  4. Trypomastigotes in blood
  5. Tstetse fly bites human and bloodstream trypomastigotes are ingested
  6. Bloodstream trypomastigotes transform into procyclic trypomastigotes in midgut of fly. Then these divide by binary fission
  7. Procyclic trypomastigotes leave the midgut and transform into epimastigotes
  8. Epimastigotes multiply in salivary glands and transform into metacyclic trypomastigote
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51
Q

What is the diagnostic stage for sleeping sickness?

A

Trypomastigotes in blood

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52
Q

How does eflornithine work in Neurological stage of sleeping sickness?

A
  • Originally developed as an anti-cancer drug
  • Inhibitor of ODC (ornithine decarboxylase)
  • ODC catalyses decarboxylation of L-ornithine into putrescine, a step in polyamine synthesis
  • Mimics L-ornithine which is commonly used in many living organisms and prevents decarboxylase via covalently bonding to ODC
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53
Q

What causes Chagas disease?

A

Trypanosomiasis Cruzi

Kissing disease

54
Q

What is the vector in Chagas disease?

A

Triatomine bugs

Large blood sucking insects

55
Q

What are the symptoms of Chagas disease?

A

Acute stage

  • Fever, malaise, facial oedema (especially on the eye)
  • Often resolves spontaneously in 4-6 weeks

Chronic stage has 2 phases:
i) Chronic asymptomatic. Patients can transmit the parasite to others whilst showing no signs on the disease, and can last 10 years-life)

ii) Chronic symptomatic
- Involves the GI tract
- Leading cause of infectious cardiomyopathy worldwide

56
Q

What is the cycle of Chagas disease?

A
  1. Triatomine bug bites skin, and metacyclic trypomastogotes enter wound via mucosal membrane e.g. conjuctiva
  2. Metacyclic trypomastigotes transform into amastigotes
  3. Amastigotes multiply by binary fission in cells of infected tissues
  4. Intracellular amastigotes transform into trypomastigotes, burst the cell and enter bloodstream. (These can infect other cells to produce more intracellular amastigotes resulting in disease manifestation)
  5. Triatomine bug bites and ingests tyrpomastigotes
  6. Converted to epimastigotes in mid gut and multiplied
  7. Converted to metacyclic trypomastigotes in hindgut
57
Q

How do you treat Chaga’s disease?

How does it work?

A

Nitroaryl compounds e.g. benznidazole (imidazole ring, nitro group)

  • Effective in early disease

Converts into nitroso imidazole. This inhibits trypanothione by breaking a sulphur-sulphur bond

Trypanothione function = defence against oxidative stress and essential for the disease to survive

58
Q

What patient groups are nitroaryl compunds e.g. benznidazole contraindicated in?

A

Severe liver and renal impairment

Pregnancy- crosses placenta and causes teratogenicity

59
Q

What are helminth infections and how are they transmitted?

A

Worms that are parasitic in humans

  • Increased travel and immigration
  • Transmitted via meat
  • Transmitted by eggs present in human faeces which contaminates soil where sanitation is poor
60
Q

Why is there limited investment in helminth infection treatments?

A

Lack of acute lethality

61
Q

Where do worms reside in the body and what are the symptoms?

A

Most localise in intestinal tract but some can pass to other organs e.g. heart, liver and lungs making them hard to remove

Can be asymptomatic however have the potential to cause anaemia as well as liver, eye and blood vessel damage

62
Q

What are the natural remedies for worm infections?

A

Black walnut and male fern

Tansy tea is highly toxic to intenal parasites

63
Q

What are the two categories of helminths?

A
  1. Platyhelminths (flatworms) e.g. cestode

2. Nematodes (roundworms)

64
Q

What is the helminth infection cycle?

A
  1. Eggs/worms in faeces passed into environment
  2. Cattle and pigs become infected by ingesting contaminated vegetation
  3. Oncospheres hatch, penetrate intestinal wall and circulate to muscles
  4. Oncospheres develop into cysterici in muscle (infective stage)
  5. Humans eat raw/infected meal
  6. Scolex (end of worm that has suckers and hooks) attaches to small intestine
65
Q

What 3 drugs can be used to treat helminth infections?

A
  1. Diethylcarbamazine
  2. Benzimidazoles
  3. Ivermectin
66
Q

What is the MOA of diethylcarbamazine in treating worm infections?

A

Still unclear but thought to inhibit microtubule polymerisation which is vital for cell division

67
Q

What is the MOA of benzimidazoles in treating worm infections?

Give an example of a drug in this class

A

Mebendazole

Prevents microtubule polymerisation which is vital for cell division

68
Q

How was ivermectin developed?

A

From avermectin, a strain of Streptomyces bacteria

Greater potency and lower toxicity

69
Q

What is the MOA of ivermectin in treating worm infections?

A

Binds GABA gated chloride channels of parasites

This causes chloride ion influx and hyperpolarisation - Paralysis of the worm

70
Q

What is leprosy caused by?

How is it spread?

A

Mycobacterium leprae and Mycobacterium lepromatosis

Spread by sneezing, air droplets and close contact

71
Q

What is a Mycobacteria and what main property does it have?

What kind of drug would you therefore want in treating Mycobacteria?

A

Acid-fast bacilli

Not readily stained by the gram method because if the high surface lipid content (mycolic acids) so is neither gram positive or negative

Cell envelope = mainly responsible for the pathogenicity

You want a lipophilic drug however if it is too lipophilic, bioavailability will be quite poor- need to have a good balance

72
Q

What are the symptoms of leprosy and what can it lead to?

A

Inflammatory disease of Peripheral nerves and mucosa of upper respiratory tract

Primary external sign - skin lesions (light or dark patches)

Can cause permanent eye, nerve, limb and skin damage

Can lose limbs

73
Q

How can you diagnose leprosy?

A

Diagnosis is based on skin lesions consistent with leprosy and definite sensory loss, and positive skin smears

74
Q

How do you treat leprosy and what is the MOA and side effects?

A

Treatment with dapsone :

Used in combination with rifampicin and clofazimine for leprosy treatment.

Side effects- nausea, loss of appetite

Severe side effects- decrease in blood cells and RBC breakdown

MOA - antibiotic
Antimetabolite- inhibits bacterial synthesis of dihydrofolic acid via competition with para-aminobenzoate for the active site of dihydropteroate synthase

75
Q

What is a virus?

What are its features?

A

Virus – non-cellular infectious agent which take over a host cell to survive and multiply. They are not living.

It consists of an envelope protein, envelope, viral genome and capsid (protein shell of virus). Membrane envelope develops from previous host cell that has been infected by virus

Can be single or double stranded RNA or DNA

76
Q

How are viruses transmitted?

A
  • Air/physical contact/mosquitoes e.g. Zika virus
77
Q

Give 3 examples of past widespread viruses?

A
  1. Smallpox
  2. Influenza pandemic e.g. Spanish flu
  3. Ebola
78
Q

What does a virus do?

A

Infects cells and forces them to work. It exploits proteins in cells to produce new viral proteins, which are then replicated and assembled into a new virus which can then go on to infect another cell

79
Q

What is the general process for a virus invading a cell?

A
  1. receptor binding on host cell
  2. Fusion with membrane to release subvirion
  3. Release viral genome
  4. Translation for vital proteins
  5. Genome multiplication
  6. Assembly, packaging and release to form a progeny virus
80
Q

What is a vaccine?

A

Biological preparation that improves immunity to a particular disease

Typically contains an agent that resembles a disease-causing microorganism and is often made from weakened/killed forms of the microbe, its toxins or one of its surface proteins.

81
Q

How do vaccines work?

A

The agent stimulates the body’s immune system to recognise it as foreign, destroy it and remember it for future encounters (memory B lymphocytes -plasma cells that secrete antibodies which in future would bind to virus and present the antigens, making it easy to be found by the immune cells)

82
Q

What are the limitations of vaccines?

A

Rapid gene mutations

Constant changes to the amino acid composition of glycoproteins present on the viral surface

Some can only be effective for a short period due to mutated forms of the virus that cannot be recognised by these B lymphocytes so need further vaccines with different strains e.g. flu

83
Q

What are some disadvantages of antiviral drugs??

A

Way to slow down reproduction and not a total cure

Because viruses use the host cells to replicate, it is difficult to design safe and effective drugs and difficult to find targets that don’t harm the host cells

Viral variation

However- are effective in viral outbreaks and immunocompromised patients

84
Q

What are the DNA viruses?

A

Hepes simplex 1 and 2
Varicella zoster
Cytomegalovirus

85
Q

What are the RNA viruses?

A

Infleunza
HIV
Heptatitis C

86
Q

What is the process of DNA virus replication?

A
  1. Host cell membrane fuses with viral envelope and nucleocapsid enters cytoplasm
  2. Viral capsid is uncoated and viral DNA enters host cell’s nucleus
  3. Viral DNA replication in nucleus
  4. Transcription to produce mRNA and translation via ribosomes into capsid and spike proteins
  5. New nucleocapsid is formed
  6. Virus buds through nuclear membrane, and acquires spikes and final envelope via Golgi
  7. Exocytosis to release new virion
87
Q

What is antigenic shift?

A

Birds to humans

88
Q

What is antigenic drift?

A

Humans-pigs-humans

89
Q

What does the neuraminidase antigen do?

A

Catalyse the hydrolysis of terminal sialic acid residues from newly formed virions and from the host cell receptors. So it promotes the release of pyogeny viruses from its host cell to infect other cells

90
Q

How does amantadine and rimantadine work?

A

M2 ion channel disrupters

Inhibits penetration and uncoating of the virus

The M2 channel functions in transporting protons with the gradient from the vacuolar space into the interior of the virion- acidification results in disassociation of ribonucleoproteins and initiation of viral replication

91
Q

How does zanamivir work? What is the problem with this?

What patient group is it contraindicated in?

A

Binds to neuraminidase protein

Treatment of A and B

However, benefit in healthy patients is small so the risk of virus strain resistance, side effects and financial cost outweighs benefits for prophylaxis and treatment

Side effects- asthma, COPD so contraindicated in this patient group

92
Q

How does oseltamivir work?

PHE recommends the use of this for what patient groups?

What is a problem with this drug?

A

Neuraminidase competitive inhibitor

Prevention and treatment of A and B

PHE recommends use for people who have complications/high risk e.g. hospitalised, pregnancy, >65

Side effects – nausea, vomiting, liver inflammation

Resistance is starting to happen, with a higher associated risk with pneumonia

93
Q

What is AIDs?

A

AIDs- acquired immune deficiency syndrome (disease spectrum of HIV)

94
Q

What cells do HIV infect?

A

Primarily infects CD4+ cells, T cells, macrophages and dendritic cells

95
Q

Outline HIV progression

A

Initial infection- brief period of influenza-like illness

Prolonged period without symptoms

As infection progresses, interferes more and more with the immune system making person more susceptible to TB and other opportunistic infections

AIDs. CD4 < 200

Often complicated by infection of the lung known as pneumocystis pneumonia, severe weight loss. Karposi’s sarcoma- common cancer in AIDs

96
Q

What are the two variants of HIV?

A

HIV 1

HIV 2

97
Q

What is the process of HIV infecting cells?

A

Retrovirus

  1. Fusion of HIV to the host cell surface (gp120 on virus connecting to CCR5 and CXCR4 receptor on host cell and CD4 receptor on host cell)
  2. Contents of virus enters the host cell
  3. Viral DNA is formed by reverse transcription
  4. Viral DNA is transported across the nucleus and integrates into host DNA via integrase
  5. New viral RNA is used as genomic RNA and used to make viral proteins
  6. New viral RNA and proteins move to cell surface and new immature HIV forms
  7. Virus matures via protease releasing individual HIV proteins
98
Q

Why are reverse transcriptase inhibitors good?

A

Unique to HIV so ideal target

99
Q

What are the 2 types of reverse transcriptase inhibitors and give MOA and examples?

A
  1. Nucleoside-like compounds, binds at polymerase site of action

Abacavir, Lamivudine and Zidovudine (AZT)

  1. Non-nucleoside reverse transcriptase inhibitors- hydrophobic molecules binding to hydrophobic allosteric binding site of RT causing enzyme to change shape

Nevirapine

100
Q

What are the side effects of nucleoside like RT inhibitors?

A

Nausea, vomiting, acid reflux

Long therapy - anaemia, neutropenia, liver heart and muscle disease

101
Q

What are the side effects of non-nucleoside RT inhibitors?

A

Severe liver toxicity usually in first 6 weeks of treatment

102
Q

What is the MOA of saquinavir?

What is used alongside it as a booster?

A

Protease inhibitors

HIV protease cleaves newly synthesised piolyproteins at appropriate places to create mature HIV

Side effects - mild GI symptoms e.g. nausea

Ritonavir increases its effect

103
Q

What is the MOA of maraviroc?

What are the side effects?

A

Negative allosteric modulator of CCR5 receptor

Binds to CCR5 blocking HIV gp120 from associating with the receptor

Side effects – liver problems, skin and allergic reactions

104
Q

What type of RNA does HIV contain?

A

Two identical (+) single stranded RNA

105
Q

What type of RNA does hep C contain?

A

+ strand RNA

106
Q

What type of proteins does the Hep C virus have in their lipid envelope?

A

E1 and E2 glycoproteins

It is a small virus

107
Q

What are the symptoms of Hep C?

A

Often asymptomatic, but chronic infection - scarring of liver and cirrhosis - liver failure and cancer

Fatigue, jaundice, abdominal pain

108
Q

What are the causes of transmission for hep C?

A

Mother -child in pregnancy

Blood transfusion

Sex

Piercing/tattooing with contaminated instruments

Unsafe injection

Contaminated blood products

109
Q

What is the life cycle of HCV?

A
  1. Same as other viruses (binding and internalisation, cytoplasmic release and uncoating, translation)
  2. Once in the hepatocyte, the virus takes over portions of the intracellular machinery to replicate.
  3. The virus genome is translated to produce a single protein (3011 amino acids)
  4. Polyprotein is processed by proteases to produce 3 virion associated structures and 7 non-structural proteins
  5. RNA replication
  6. Packaging and assembly
  7. Virion maturation and release
110
Q

Is there a vaccine for hep C?

A

No

111
Q

What is HCV therapy and what is a side effect of them?

A

HCV therapy usually pegylated IFN-alpha administered once a week plus daily oral ribavirin for 24-48 weeks

Ribavirin:

  • Used with other drugs
  • Side effects so needs to be avoiding by male and female during and after pregnancy
  • Guanosine (ribonucleic) analogue used to stop viral RNA synthesis and viral mRNA capping
  • Prodrug- phosphorylated into a nucleotide analogue

Interferons:

  • Small natural proteins which are produced by host cells as response to foreign invaders
  • Most used is IFN-alpha
112
Q

What are novel therapies for HCV?

A

Protease inhibitors: Simeprevir

  • Indicated as part of triple therapy (decreases resistance) with PEG IFN-alpha and ribavirin
  • Good for genotype 1
  • Not good as a single therapy
  • Side effects= itching, sensitivity to sunlight, rash, nausea

Polymerase inhibitors: Sofosbuvir

  • Nucleotide blocking CNS5B RNA polymerase
  • Expensive
  • Can be used alone and in combination and there are few cases of resistance
  • Side effects- headache, nausea, rash
  • Only administered orally
113
Q

What is an arbovirus?

A

Any group of virus which are transmitted via mosquitoes, ticks or other arthropods

114
Q

West Nile, dengue, Zika, Yellow fever are all under what type of virus?

A

Flavivirus

115
Q

What is the only 2 Flavivirus’ where a vaccine exists?

A

Yellow Fever (10 year protection) and Japanese encephalitis

Partially effective Dengue vaccine does exist but WHO only recommends to use in areas where disease is common

116
Q

What are the symptoms of Dengue fever?

A

Symptoms- high fever, headache, characteristic skin rash

Rarer- Life-threatening dengue haemorrhagic fever (bleeding, low levels of platelets and blood plasma leakage) - dengue shock syndrome with dangerously low BP

117
Q

How is dengue fever transmitted?

A

Transmitted via Aedes Aegypti mosquito, that usually bite in the early morning and evening

118
Q

What is the treatment for the febrile phase of dengue fever?

A

Bed rest

Max dose paracetamol

Avoid aspirin, ibuprofen, ABX

Oral rehydration therapy due to vomiting and high temp

There have been drugs (ribavirin and celgosivir) but have shown limited efficacy

119
Q

What is the treatment for haemorrhagic fever and shock syndrome?

A

Fluids

Blood transfusions

Oxygen therapy

Dopamine, adrenaline

120
Q

How is the zika virus spread?

A

Female Aedes aegypti mosquito

Sexual transmission or during pregnancy and delivery

121
Q

What are the symptoms of zika virus?

A

Causes no or mild symptoms

However, if spread to baby - microcephaly (small head associated with incomplete brain development), severe brain malformations and other birth defects

In adults, may cause Guillain-Barre syndrome – rapid onset muscle weakness caused by the immune system damaging peripheral nervous system

122
Q

What is the treatment for Zika virus?

A

Paracetamol and rest

123
Q

How is West nile spread?

A

Culex mosquitos and ticks

Primary hosts are birds, so the virus remains within a bird-mosquito-bird cycle however there have been infections in humans

124
Q

What are the symptoms of West Nile?

A

Asymptomatic in 80% of cases

Symptoms- fever, headache, tiredness, rash on trunk of body

Can be severe disease (neuroinvasive) – coma, disorientation, convulsions, paralysis

125
Q

How do you treat West Nile?

A

Hospitalisation, IV fluids, respiratory support

126
Q

How is Chikungunya spread?

A

From Aedes aegypti and albopictus mosquitos

127
Q

What are the symptoms of Chikungunya?

Who are the high risk patients?

A

Symptoms similar to dengue and Zika

Does not often result in death but the symptoms can be severe and disabling e.g. joint pain may persist for months

At risk = newborns, >65 years, and those with comorbidities such as high BP and diabetes

Can cause encephalitis, infectious arthritis

128
Q

How do you treat Chikungunya?

What classes of medicines do you want to avoid and why?

A

Therapy

No specific antiviral treatment

Relieving symptoms and management of electrolyte and haemodynamic balance

No commercial vaccine

Ribavirin has been used to treat chikungunya induced arthritis and was shown to be beneficial to reduce joint and tissue swelling

Using corticosteroids, NSAIDs and ABXs could result in thrombocytopenia, GI bleeding and renal failure

129
Q

How do you prevent flaviviruses?

A
  • Insect repellent and nets
  • Avoid contaminated needles etc
  • Protected sex
  • Do not store water in open containers otherwise they could become a breeding site for mosquitoes
130
Q

How is Ebola transmitted?

A

Transmitted from fruit bats to animals to humans via eating

Through broken skin/membranes/body fluids, or from infected people

Sex

Contaminated blood/equipment

131
Q

What are the symptoms of Ebola?

A

Symptoms-fever, muscle ache, nausea, rash, diarrhoea

Body’s immune response and damage to vascular system causes blood to leak from veins

Multi-organ failure around 8 days after onset of symptoms

High mortality

132
Q

What is Ebola survival dependent on?

A

Early, strong immune response with improvement after first week

However, long term health problems

ETMM (5 decks)

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