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Flashcards in Malaria E-book Deck (24)
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1
Q

Malaria occurs through

A

the transmission of plasmodium parasite, through the bite of a female Anopheles mosquito.

2
Q

Types of malaria

A

Plasmodium falciparum is the most common type of malaria parasite, prominently in Africa, and is the main reason for malaria deaths worldwide. Plasmodium vivax mainly found in America and Asia. The P. vivax parasite has milder symptoms than P. falciparum, but may cause relapses as it can stay in the liver for up to 3 years. Plasmodium ovale is found in western Africa and is
very uncommon. Plasmodium malariae and Plasmodium knowlesi are very rare However, P. knowlesi may be transmitted to humans from monkeys through bites from mosquitoes known as Anopheles balabacensis.
After an individual has been bitten, the infection develops in the liver and then travels into the bloodstream where the red blood cells become infected. This leads to the parasite to grow and multiply in the red blood cells, causing red blood cells to burst at regular intervals (infected blood cells burst every 48-72 hours), releasing more parasites in the blood. Every time the blood cells burst the symptoms of fever, chills and sweats are amplified

3
Q

There are 5 species of plasmodium can infect humans and cause illness:

A
● Plasmodium falciparum ( P. falciparum)
● Plasmodium malariae (P. malariae)
● Plasmodium vivax (P. vivax)
● Plasmodium ovale (P. ovale)
● Plasmodium knowlesi (P. knowlesi)
4
Q

The most common form of malaria is caused by

A

● Plasmodium falciparum ( P. falciparum)

5
Q

Which infections can cause rapidly progressive severe illness or death

A

P. falciparum and P. knowlesi

6
Q

less likely to cause severe manifestations.

A

P. vivax, P. ovale, or P. malariae

7
Q

Shorter incubation periods are observed most frequently

with

A

P. falciparum

8
Q

Longer incubation periods are observed most frequently

with

A

P. malariae

9
Q

General symptoms include

A
  • Fever (often 39oC or higher), sweats and/or chills — (absence of fever should not remove the suspicion of malaria).
  • Headache.
  • General malaise, lethargy and fatigue
    — drowsiness is more common in children than adults.
  • Anorexia, gastrointestinal disturbance (such as nausea, abdominal pain, vomiting, diarrhoea) and jaundice.
  • Poor feeding in children.
  • Myalgia and arthralgia.
  • Sore throat, cough, lower respiratory tract symptoms and respiratory distress.
  • Confusion
10
Q

Plasmodium vivax and Plasmodium ovale

A

In P. vivax and P. ovale infections they are rarely complicated, however there is evidence on the risk of serious and fatal complications due to P. vivax infections. Both P. vivax and P. ovale infection produce hypnotize forms that are dormant in the liver

11
Q

The classical malaria paroxysm presents in three stages;

A

a cold stage, followed by a hot stage, with a terminal sweating stage.

  1. Individuals may shiver and their teeth may chatter, in cases of intense peripheral vasoconstriction – their skin may be cold, cyanosed and goose-pimpled. This initial
    stage can usually last 10-30 minutes, occasionally up to 90 minutes.
  2. Once the hot stage starts, shivering will cease and the skin will then become hot and dry with symptoms of face flushing. Vomiting is also common in this phase and
    sometimes diarrhoea, severe retro-orbital headache, extreme thirst and altered consciousness may occur – convulsions may occur in young children.
  3. Within 2-6 hours, an individual will enter third stage, which is known as the sweating stage; this entails sudden profuse sweating, starting at the temples and then becoming generalised. Temperature will then fall rapidly and the individual will start to feel ‘well’, however they will also experience extreme tiredness and may fall asleep. The sweating stage can last 2-3 hours, with the entire process lasting around 6-10 hours.
12
Q

Plasmodium falciparum

A

In P. falciparum malaria, an onset of fever occurs after a few days of prodromal symptoms started during the last days of the incubation period (usually 9-14 days). Initially, the fever is irregular but usually occurs daily.
This fever may intermittent or continuous and will show no signs of periodicity until the illness has continued for a week or more. Anorexia, dyspepsia, epigastric discomfort, nausea and vomiting and watery diarrhoea are also frequent and may be misdiagnosed as a GI infection.
Herpes labialis, a dry cough and an increase in respiratory rate may also be observed.
On non-specific physical examination, a tender spleen, orthostatic hypotension and jaundice may be observed. Moreover, the pulse may be rapid (100-120 bpm) and blood pressure may be low (90-100 mmHg, systolic).

13
Q

Plasmodium malariae

A

P. malaria causes the mildest and most persistent form of malaria infection. After the incubation period, prodromal symptoms which resemble those of vivax malaria can occur after the onset of fever. The onset is usually gradual but are typically separated by intervals of 72h.

14
Q

Plasmodium knowlesi

A

P. knowlesi is a species of plasmodium which has been most recently been identified as an agent of human malaria. On the basis of clinical features, it is not possible distinguish knowlesi malaria from vivax or falciparum malaria. However hyperparasitemia and other complications are fairly common

15
Q

Drugs for chemoprophylaxis of Malaria

A

Drugs for chemoprophylaxis of Malaria
● Chloroquine
It may lower blood glucose and increase muscle weakness.
Handle with care in elderly and in patients with neurological disorders, avoiding in
epilepsy.
Avoid in severe gastrointestinal disorders, renal impairment and moderate to severe
hepatic impairment.
Side effects at malaria prophylactic doses are usually not serious.
It can be used by pregnant or breastfeeding women since the benefit is higher than the risk.
● Doxycycline
Muscle weakness may be increased.
Use with caution in renal impairment and use with caution or avoid in hepatic impairment.
Avoiding sunlight or if not possible use high protection.
Common side effects include dyspnoea; hypotension; peripheral oedema; tachycardia, angioedema; diarrhoea; headache; hypersensitivity; nausea; pericarditis; photosensitivity reaction; skin reactions; vomiting.
When traveling to malarious areas is unavoidable during pregnancy, doxycycline can be used for malaria prophylaxis if other regimens are unsuitable, and if the entire course of doxycycline can be completed before 15 weeks’ gestation. This is because doxycycline affects skeletal development.
Not for use when breastfeeding.
● Proguanil Hydrochloride
Use with care in renally impaired patients; adjust doses if necessary.
Benefit of prophylaxis outweighs risk in pregnancy, adequate folate supplements should be given to mother.
Not known to be harmful during breastfeeding.
● Mefloquine
Avoid if history of psychiatric disorders or convulsions.
Cautions include cardiac conduction disorders; epilepsy; infants under 3 months (5 kg);
traumatic brain injury, cautioned in renal impairment, avoid in severe hepatic impairment.
Side effects may include anxiety; depression; diarrhoea; dizziness; gastrointestinal discomfort; headache; nausea; skin reactions; sleep disorders; vision disorder and
vomiting.
Manufacturer advises contraception during prophylaxis and for 3 months after stopping.
Avoid in pregnancy (particularly in the first trimester).
Minimal risk in breastfeeding.
● Atovaquone with Proguanil Hydrochloride
Diarrhoea or vomiting reduces the absorption of atovaquone. If occurs, speak to your doctor.
Avoid if eGFR<30.
Side effects include: abdominal pain; appetite decreased; cough; depression; diarrhoea; dizziness; fever; headache; nausea; skin reactions; sleep disorders and vomiting.
Avoid in pregnancy and breastfeeding unless it is essential

16
Q

Chemoprophylaxis should be started

A

Chemoprophylaxis should be started one week before travel. This increases to 2-3 weeks for mefloquine and reduces to 1-2 days before travel for atovaquone/proguanil hydrochloride and doxycycline.
Travellers also taking warfarin should begin chemoprophylaxis 2–3 weeks before departure,
and their INR should be stable before departure. INR should be measured before starting chemoprophylaxis, 7 days after starting, and after completing the course. For prolonged stays, the INR should be checked at regular intervals.

17
Q

For long-term prophylaxis

A

chloroquine and proguanil may be used. Mefloquine is licensed for up to 1 year (although, if tolerated short term, there is no evidence of harm when used for up to 3 years). Doxycycline can be used for up to 2 years, and atovaquone/proguanil hydrochloride can be used for up to 1 year.

18
Q

Prophylaxis should be continued for

A

Prophylaxis should be continued for 4 weeks after return to the UK, except for atovaquone/proguanil which should be stopped 1 week after return. However, if atovaquone/proguanil is discontinued fewer than 7 days after return, or if suppressive prophylaxis (chloroquine, doxycycline, proguanil, mefloquine) is discontinued fewer than four weeks after return, no additional antimalarials are required.
If patients feel unwell in the first year of return to the UK, an urgent blood test for malaria is essential; the highest risk is in the first three months.

19
Q

Pharmacotherapy of Malaria

A
  1. Artemisinin Combination Therapy (ACT)
  2. Atovaquone-proguanil
  3. Artesunate
  4. Quinine
  5. Quinine plus doxycycline
  6. Chloroquine
  7. Primaquine
20
Q

Malaria caused by unknown species or mixed infection

A

If the infective species is unknown or the infection is mixed (i.e. more than one plasmodium parasite), then the initial treatment should be with:
Quinine by intravenous infusion if patient is unable to take oral therapy,
● Adult: 10mg/kg every 8 hours (max. per dose 700mg), infused over 4 hours. Change to oral chloroquine as soon as the patient’s condition permits, reduce dose to 5-7mg/kg if parenteral treatment is required for more than 48 hours.
OR
Malarone® (atovaquone-proguanil 250/100mg tablets),
● Adult: 4 tablets once daily for three days
OR
Riamet® (artemether with lumefantrine 20/120mg tablets),
● Adult (body weight 35kg and above): Initially 4 tablets, followed by 4 tablets for 5 doses each given at 8, 24, 36, 48 and 60 hours (total = 24 tablets over 60 hours).
Falciparum malaria can progress quickly in unprotected individuals so antimalarial treatment should be considered in those with features of severe malaria and possible exposure, even if the initial blood tests are negative.

21
Q

Malaria caused by Plasmodium Falciparum

A

By Mouth: Quinine, Malarone® (atovaquone-proguanil) or Riamet® (artemether with lumefantrine) is given for falciparum malaria orally, if the patient is able to swallow and there are no serious manifestations.
Doses for Malarone® and Riamet® are the same as for Malaria caused by unknown species or mixed infection.
For Quinine (by mouth):
● Child: 10mg/kg every 8 hours (max. per dose 600mg) for 7 days, to be given together with or followed by either doxycycline (in children over 12), or clindamycin.
● Adult: 600mg every 8 hours for 5-7 days, to be given together with or followed by either doxycycline or clindamycin.
Quinine Sulphate (by IV infusion), for patients who are seriously ill and/or are unable to swallow:
● Adult: Loading dose 20mg/kg (max. per dose 1.4g), infused over 4 hours.
LOADING DOSE SHOULD NOT BE GIVEN IF PATIENT HAS RECEIVED QUININE OR MEFLOQUINE DURING THE PREVIOUS 12 HOURS. Maintenance dose 10mg/kg
every 8 hours (max. per dose 700mg) until patient can swallow tablets to complete 7 day course, maintenance dose to be given 8 hours after the start of the loading dose and infused over 4 hours. To be given together with or followed by doxycycline or clindamycin, reduce maintenance dose to 5-7mg/kg if parenteral treatment is required for more than 48 hours.
Oral quinine is given for five to seven days, together or followed by either doxycycline or clindamycin for seven days (unlicensed use).
Doxycycline (by mouth),
● Child (12-17 years): 200mg daily for 7 days
● Adult: 200mg daily for 7 days
Clindamycin (by mouth),
● Child: 7-13mg/kg every 8 hours (max. per dose 450mg) for 7 days
● Adult: 450mg every 8 hours for 7 days
Alternatively, pyrimethamine with sulfadoxine may be given as a single dose (unlicensed use)
with or after a course of quinine, instead of doxycycline or clindamycin, if the parasite is likely to be sensitive.
Malarone® or Riamet® may be given instead of quinine; it is not necessary to give doxycycline, clindamycin or pyrimethamine with sulfadoxine with or following treatment with Malarone® or Riamet®.
In pregnancy, falciparum malaria is particularly dangerous, especially during the last trimester.
Quinine given by mouth or intravenously are both safe for use in pregnant women.
Clindamycin should be given after quinine (unlicensed use). Doxycycline should be avoided in pregnancy due to known abnormal teeth and skeletal development in the foetus.
Pyrimethamine with sulfadoxine, Malarone® and Riamet® should also be avoided in pregnancy due to lack of information.
In Breastfeeding women,
● Quinine is present in milk but not known to be harmful
● Malarone® used only if no suitable alternative; breastfeeding to be avoided during and for at least 1 week after taking Riamet®.
● Doxycycline and pyrimethamine with sulfadoxine to be avoided
● Only a small amount of Clindamycin present in milk, potentially too little to be harmful

In difficult cases of plasmodium falciparum induced malaria, including in pregnancy, specialist advice should be sought as intravenous Artesunate may be available for ‘named patient’ use.
Mefloquine is rarely used for treatment of falciparum malaria due to resistance concerns and Chloroquine is now ineffective against plasmodium falciparum in most parts of the world

22
Q

Non-falciparum Malaria caused by Plasmodium vivax and less commonly, plasmodium ovale and P.malariae. P.knowlesi

A

By Mouth: Chloroquine is the given treatment for non-falciparum malaria. In children, the dose is initially 10mg/kg (max per dose 620mg), then 5mg/kg after 6-8 hours (max per dose 310mg) then 5mg/kg daily (max per dose 310mg) for 2 days. In adults, the dose is initially 620mg, then 310mg after 6-8 hours, then 310g daily for 2 days, approximate total cumulative dose of 25mg/kg of base.
Chloroquine is adequate as a single treatment for P.malariae and P.knowlesi infections but an additional radical cure to destroy parasites in the liver (to prevent relapse) is required for P.vivax and P.ovale infections. Primaquine (unlicensed) is given for a radical cure after
chloroquine; the dose is usually given for 14 days but is dependent on the infecting parasite.
For chloroquine-resistant non-falciparum malaria, treatment with Malarone® (unlicensed indication), quinine or Riamet® (unlicensed indication) can be used. Primaquine should still be given for radical cure.
By Intravenous Infusion: Quinine (unlicensed use) can be given IV for patients who are unable to take oral therapy. As soon as the patient is able to take oral therapy, treatment should be switched to oral Chloroquine as outlined above.
In pregnancy, the adult treatment doses for non-falciparum malaria of Chloroquine can be given. The radical cure given if the infection is caused by P. vivax or P. ovale should be postponed until after the pregnancy. Chloroquine should be given weekly during the pregnancy and switched to primaquine radical cure after the pregnancy

23
Q

Treatment regimens for uncomplicated malaria in adults

A
  • Oral quinine sulphate 600 mg/8 h for 5e7 days plus
    doxycycline 200 mg daily (or clindamycin 450 mg/8 h for pregnant women) for 7 days
  • Atovaquoneeproguanil (Malarone): 4 ‘standard’
    tablets daily for 3 days or
  • Co-artem (Riamet): if weight > 35 kg, 4 tablets then 4 tablets at 8, 24, 36, 48 and 60 h
24
Q

Drug treatment of severe or complicated malaria

A
  • Quinine: loading dose of 20 mg/kg quinine dihydrochloride in 5% dextrose or dextrose saline over 4h. Followed by 10 mg/kg every 8 h for first 48 h (or until patient can swallow). Frequency of dosing should be reduced to 12 hourly if intravenous quinine continues for more than 48 h.
  • Alternative rapid quinine loading regimen (adults only) 7 mg/kg quinine dihydrochloride over 30 min using an infusion pump followed by 10 mg/kg over 4 h.
  • Parenteral quinine therapy should be continued until the patient can take oral therapy when quinine sulphate 600 mg should be given 3 times a day to complete 5-7 days of quinine in total.
  • Quinine treatment should always be accompanied by a second drug: doxycycline 200 mg (or clindamycin 450 mg 3 times a day for pregnant women, 7-13 mg/kg 3 times a day for children), given orally for total of 7 days from when the patient can swallow.
  • Artesunate regimen: appropriate for adults only on expert advice. 2.4 mg/kg given as an intravenous injection at 0, 12 and 24 h then daily thereafter. A 7-day course of doxycycline should also be given.