Malaria; Management, Chemoprophylaxis, Prevention and Global Impact Flashcards
How prolific is malaria? Where is it often found? 02:40
- Found in more than 100 countries, affecting 3 billion people
- Mainly in tropical regions of the world, including:
• large areas of Africa/Asia
• Central and South America
• Haiti and the Dominican Republic
• Parts of the Middle East
• Some Pacific Islands - Anopheles mosquito not native to the UK; but about 1,400 travellers diagnosed w/malaria from above areas in 2012, with 2 dying (most P. falciparum, with P. vivax next most common)
- Other strains not as common
How deadly is malaria?
- WHO reports states that 207 million cases of malaria worldwide in 2012
- 627,000 deaths
»> Accounts for 10% deaths in Sub-Saharan Africa
How does risk of contracting malaria increase?
• Proportional to number of times bitten by Anopheles spp.
- Asia/South-Central America inhabitants; on average bitten once or twice a year by infective mosquito
- Sub-Saharan Africa inhabitants; on average bitten 1,000 times a year by P. falciparum infected Anopheles.
What factors affect travellers’ exposure to malaria?
- Optimum conditions for malaria transmission are high humidity and ambient temp. of 20 - 30ºC
- Doesn’t normally occur in regions with temperature below the 16ºC isotherm (line like equator)
- Parasite maturation in Anopheles mosquito does not take place > 2000m
- Seasonal rainfall increases mosquito breeding; malaria is highly seasonal (humidity presence encourages breeding)
- More common in rural areas (8x higher transmission in a village than a town in Sub-Saharan Africa)
- Backpackers staying in cheap accommodation have a higher risk of being bitten compared to air-conditioned hotels; holes in malaria nets, windows not sealed etc.
- Outdoors between dusk and dawn = Anopheles spp. fave time to bite
What is the ABCD approach to malaria prophylaxis?
- Awareness of risk; find out whether you’re at risk of getting malaria before travelling
- Bite prevention; avoid bites by using insect repellent (DEET), covering arms and legs w/insecticide-treated mosquito net
- Check whether you need to take malaria prevention tablets; if you do, make sure you take the right antimalarial tablets at right dose, and finish course
- Diagnosis; seek immediate medical advice if you develop symptoms, including up to a year after returning from travelling
Why is there no malaria vaccine?
- Much more complicated than virus etc.
- Complexity of life cycle
- Lots of mutations
What advice is there availible to patients for bite prevention?
- Staying somewhere w/A/C and screening on doors and windows, make sure they’re closed during sleep, sleep under intact mosquito net treated w/insecticide
- Use insect repellent on skin and in sleep environments, re-apply frequently (most effective contain DEET; diethyltoluamide)
- DEET not recommended for babies < 2 months old
- Wear loose-fitting trousers instead of shorts, shirts with long sleeves; particularly important during early evening and night, when mosquitoes prefer to feed (DO NOT EXPOSE SKIN)
»> No evidence that homeopathic remedies, electronic buzzers, vitamins B1 or B12, garlic, yeast extract spread (Marmite), tea tree oils or bath oils offer any protection
What is the choice of malaria chemoprophylaxis based upon?
- Destination (prophylaxis against which strain?)
- Medical history, allergies
- Current medication
- Previous history w/antimalarials
- Age
- Pregnancy
Why take malaria chemoprophylaxis?
Can reduce risk of malaria by 90%
What is causal prophylaxis?
- Targets liver (exo-erythrocytic stage) stage
- Takes 7 days to develop
- Continue for 7 days after leaving malarious zone
What is suppressive prophylaxis?
- Erythrocytic stage
- Continue for 4 weeks after leaving malarious zone; need to wait for exo-erythrocytic stages to ‘play their course’ as these drugs are ‘suppressive’; only target RBC stage
Are there any chemoprophylactic options against hypnozoites?
- No prophylactic drugs against these stages (P. vivax, P. ovale)
- BUT, can be treated
What is the relevant distribution of drug resistant malaria and its different strains?
- Chloroquine-resistant falciparum malaria universal; DO NOT give CQ if suspected P. falciparum
»> Check ACMP (Advisory Committee on Malaria Prevention for UK Travellers) for up to date information on P. falciparum - No recorded resistance to P. ovale
- 1 resistance to P. malariae
- CQ-resistant P. vivax about
- P. vivax w/reduced susceptibility to primaquine (which targets hypnozoite stage)
- Some P. falciparum resistant to artemisinin
Which phase of malaria infection is Malarone (atovaquone + proguanil) effective against? How is it taken? Efficacy against?
- Prevents development of liver schizonts; causal prophylactic
- Take for 1-2days before entering & 7 days after leaving endemic area
- Works on erythrocytic stages too (for treatment as well as prophylaxis)
- 90% efficacy against P. falciparum, w/efficacy against P. vivax too
What are the S/Es associated w/Malarone (atovaquone + proguanil)? CIs?
S/Es:
- Headache
- GI upset
- Skin rash
- Mouth ulcers
CI:
- Pregnant/breastfeeding
- Or in people with renal problems (can accumulate)
How is the quinine analogue Mefloquine (Lariam) taken? Why is is taken this way?
• Suppressive prophylactic
- Take for 21 days before entering, and 28 days after leaving endemic area
- 21 days prior; associated w/psychotropic S/Es; drug is racemic mix, + enantiomer is antimalarial, - enantiomer is psychotropic
- 28 days after; no activity in liver stages (only erythrocytic; ‘wait it out’)
When is malaria chemoprophylaxis w/Mefloquine (Lariam) not recommended? What S/Es may present otherwise?
Not recommended in:
- Epilepsy
- Seizures
- Depression, or other MH problems, or if familial history of these problems, severe heart or liver problems.
S/Es:
- Dizziness
- Headache
- Sleep disturbances (insomnia, vivid dreams)
- Psychiatric reactions (anxiety, depression, panic attack, hallucinations) - more common in young men
»> Hence 21 day pre-period to observe for S/Es
How is Doxycycline given for malaria chemoprophylaxis? How does it work?
- Prevents development of erythrocytic stages; suppressive prophylactic
- Taken for 1-2days before entering, 28 days after leaving
Who is Doxycycline CI in, and what are its common S/Es?
CI:
- Pregnant/breast-feeding
- Children U12 (tetracycline; risk of permanent tooth discolouration)
- Liver problems
S/Es: - Sunburn due to photosensitivity - Stomach upset - Heartburn - Thrush - Taken w/food >>> Doesn't reduce effectiveness of contraceptive pill
When is chloroquine and proguanil taken together for malaria chemoprophylaxis?
- Rarely recommended due to high P. falciparum resistance
- But, occasionally recommended for certain destinations where P. falciparum is less common than other types e.g. India, Sri Lanka
What bad press surrounded Mefloquine (Lariam), and why is this peak?
- Potential psychotropic effects very widely reported
- Could affect adherence; but then result in actual malaria infection.
What does ayurvedic medicine say WRT malaria prophylaxis?
- “Stepping out of the home w/an empty stomach is the first thing people should avoid”
> Not malnourished so not too dumb
Which areas result in the greatest no. of malaria deaths from UK travellers?
- P. falciparum
- Usually where CQ-resistant P. falciparum is endemic
»> 78% reported cases had not taken any chemoprophylaxis, or the wrong ones (e.g. for wrong strain)
What factors affect malaria chemoprophylaxis adherence?
- Effectiveness
- S/Es
- Previous experience of antimalarials (everyone blames them for unrelated tings)
- Dosing convenience
- Practitioner’s recommendation was important for 63% of travellers
- Travellers stopping antimalarials early after returning from holiday = big cause
What is the clinical presentation of malaria?
- Diagnosed and treat PROMPTLY; full recovery can be expected
- Incubation period for P. falciparum/vivax/ovale; 8-12 days, with P. malariae having 18 days - 8 weeks (Cheryl Cole was back for a year before showing symptoms… hypnozoites; can be delayed for several months)
- Pro-dromal symptoms (non-specific):
• Headache
• Muscular aches and pains
• Malaise
• N&V second week after exposure. - Paroxysmal episode of chills and fever (classic fever)
- Thrombocytopenia; low platelets (haemorrage risk)
- Jaundice; yellowing, bilirubin in liver
What are the three stages of malarial febrile paroxysms (sudden fever)?
Cold stage:
- Marked vasoconstriction, lasts for 30-60 mins
- Patient feels cold and uncomfortable
- Marked shivering
- Temp. rises rapidly, often to as high as 41ºC
Hot stage:
- Abruptly follows, lasts 2-6 hours
- Patient intensely hot and uncomfortable
- Delirium (singing etc.)
Sweating stage:
- Bedclothes drenched
- Fatigued and exhausted but otherwise well; often sleeps - exhausting for body
What causes malarial febrile paroxysms?
- Schizonts burst out of erythrocytes
- Lots of endotoxins; massive inflammatory response
How pathogenic are the different strains of malaria to RBCs etc?
- P. vivax and P. ovale; only young RBCs
- P. falciparum; attacks all RBCs (much bigger infection of RBCs; release stage much more dramatic, 40,000 - 50,000 merozoites from a cell)
How is P. falciparum more peak?
- Much more likely to lead to anaemia (40,000-50,000 merozoites release from one RBC)
- RBCs are more highly infected; develop knobs and stick to endothelium, causes severe organ damage to kidneys, liver, brain GIT
»> SERIOUS
What occurs when > 2% RBCs are infected?
- P. falciparum normally
- Cerebral malaria & blackwater fever (urine turns black because of blood in urine)
What is cerebral malaria?
- Consistent release of pathogen leads to marked rise in temperature
- Patient experiences rapid deterioration in consciousness (clogging in microvasculature), convulsions, coma, death.
What is blackwater fever?
- Dark brown urine from intravascular haemolysis in blood stream, kidneys start to pass metabolites
- Leads to acute renal failure
»> ONLY P. falciparum
Why can splenic rupture occur from malaria? What can this lead to?
- Spleen enlarged from severe anaemia
- Jaundice
- Diarrhoea
What metabolic disturbances may arise from malaria complications?
- Acidosis
- Hypoglycaemia
- Pulmonary oedema
»> Ventilator (50% chance mortality)
What occurs to children that survive malaria?
Permanent effects of malaria:
- Cerebral palsy
- Blindness
- Deafness
- Cognition & learning
- 10% have persistent language deficit w/defects
- Decreased life expectancy
- Increased epilepsy incidence
What is tropical splenomegaly syndrome?
Malaria is hyperendemic; response to antimalarial therapy
What is the link of malaria to HIV?
- Transmission linked
- HIV prevalent in P. falciparum endemic areas
What is the prognosis for pregnant women who are infected w/malaria?
- High maternal mortality
- Risk of LBW and infant mortality too
How is severe malaria (usually P. falciparum) treated?
- Quinine dihydrochloride infusion or IM TDS
• Haemodialysis
• Respiratory support
• Glucose
• Blood transfusions
• BZDs in children (prevent fitting)
»> Quinine works on RBC stage only; suppressive, takes a while but reliable
What are the S/Es associated w/quinine?
Cinchonism (OD of quinine):
- Tinnitus
- Vertigo
If a patient is infected w/P. vivax/ovale, what are the treated with?
14 days of primaquine (PQ) to clear hypnozoites (not in G6PD deficiency)
What does emergency standby treatment of malaria entail?
- Speedy treatment of malaria essential
- Travellers advised to carry a course of emergency treatment if travelling to areas remote from medical attention
- “If you’ve got the drugs and maybe the symptoms, just take the drugs”
Various emergency treatments:
• Malarone (atovaquone + proguanil)
• Riamet (artemether + lumefantrine)
• Quinine + doxycycline
> > > Patient then needs to seek medical advice ASAP to ensure treatment has been adequate and that no other illness is involved.
