Malaria
What is Malaria?
Malaria is a potentially fatal mosquito-borne blood disease caused by a Plasmodium parasite which is transmitted to humans via the bite of the Anopheles mosquito. The mosquitoe must have been infected through a bite taken from an infected person before it can transmit to the next person it bites. 1 week after, the parasites mix with the mosquito’s saliva and are injected into the next person being bitten.After a bite, the parasites enters the human being's bloodstream and multiply in the liver before destroying the red blood cells.
There are 4 kinds out of over 100 malaria parasites that infect humans and they are Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. P. knowlesi, is a type of malaria that naturally infects macaques in Southeast Asia which also infects humans resulting in malaria that is transmitted from animal to human (“zoonotic” malaria). P. falciparum is the type of malaria that can result in severe infections and if not promptly treated, may lead to death.
Malaria is typically found in tropical and subtropical climates where the parasites can live. P.Falciparum parasite is very common in many countries in Africa south of the Sahara desert and people who are heavily exposed to the bites of mosquitoes infected with P. falciparum are most at risk of dying from malaria. People who have low immunity such as young children, pregnant women, immune-suppressed patients or travelers coming from areas with no malaria and people with no medical access are more likely to become very sick and die. As a result of all the above factors, an estimated of 90% deaths from malaria occur in Africa south of the Sahara especially in children under 5 years of age.
Malaria is a potentially fatal mosquito-borne blood disease caused by a Plasmodium parasite which is transmitted to humans via the bite of the Anopheles mosquito. The mosquitoe must have been infected through a bite taken from an infected person before it can transmit to the next person it bites. 1 week after, the parasites mix with the mosquito’s saliva and are injected into the next person being bitten.After a bite, the parasites enters the human being's bloodstream and multiply in the liver before destroying the red blood cells.
There are 4 kinds out of over 100 malaria parasites that infect humans and they are Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. P. knowlesi, is a type of malaria that naturally infects macaques in Southeast Asia which also infects humans resulting in malaria that is transmitted from animal to human (“zoonotic” malaria). P. falciparum is the type of malaria that can result in severe infections and if not promptly treated, may lead to death.
Malaria is typically found in tropical and subtropical climates where the parasites can live. P.Falciparum parasite is very common in many countries in Africa south of the Sahara desert and people who are heavily exposed to the bites of mosquitoes infected with P. falciparum are most at risk of dying from malaria. People who have low immunity such as young children, pregnant women, immune-suppressed patients or travelers coming from areas with no malaria and people with no medical access are more likely to become very sick and die. As a result of all the above factors, an estimated of 90% deaths from malaria occur in Africa south of the Sahara especially in children under 5 years of age.
Transmission of Malaria
Besides contracting malaria from the bite of an infected Anopheles Mosquito, the parasites lies in the red blood cells of the person bitten hence it can also be transmitted to others via :
- Organ transplant
- Blood transfusion
- sharing of needles/syringes with contaminated blood
- From a mother to her unborn infant before or during delivery (aka “congenital” malaria)
Malaria is not a contagious disease, it does not spread through respiratory droplets, sharing of food, sex or casual contact like sitting next to an infected person.
Besides contracting malaria from the bite of an infected Anopheles Mosquito, the parasites lies in the red blood cells of the person bitten hence it can also be transmitted to others via :
- Organ transplant
- Blood transfusion
- sharing of needles/syringes with contaminated blood
- From a mother to her unborn infant before or during delivery (aka “congenital” malaria)
Malaria is not a contagious disease, it does not spread through respiratory droplets, sharing of food, sex or casual contact like sitting next to an infected person.
Symptoms of Malaria
For most people, symptoms begin 10 days to a month after infection. Although some people may feel symptomatic as early as 7 days or as late as 1 year later. P. vivax and P. ovale, these two kinds of malaria can recur aka relapsing malaria as these parasites can remain dormant in the liver for several months up to about 4 years after a person is bitten by an infected mosquito. When these parasites come out of hibernation, they begin to invade and destroy red blood cells resulting in a relapse of the disease.
when the patient feels ill they will experience the following symptoms:
- Flu-like symptoms: Fever, chills, headache, tiredness and muscle aches
- Gastrointestinal symptoms: Abdomen pain, nausea, vomiting and diarrhoea
- Destruction of red blood cells result in Anemia and Jaundice
- Renal (Kidney) in severe cases : Kidney failure
- Neurological symptoms in severe cases : Seizures, mental confusion, coma
Severe Malaria can cause death hence early diagnosis plus treatment is critical for a patient's recovery.
For most people, symptoms begin 10 days to a month after infection. Although some people may feel symptomatic as early as 7 days or as late as 1 year later. P. vivax and P. ovale, these two kinds of malaria can recur aka relapsing malaria as these parasites can remain dormant in the liver for several months up to about 4 years after a person is bitten by an infected mosquito. When these parasites come out of hibernation, they begin to invade and destroy red blood cells resulting in a relapse of the disease.
when the patient feels ill they will experience the following symptoms:
- Flu-like symptoms: Fever, chills, headache, tiredness and muscle aches
- Gastrointestinal symptoms: Abdomen pain, nausea, vomiting and diarrhoea
- Destruction of red blood cells result in Anemia and Jaundice
- Renal (Kidney) in severe cases : Kidney failure
- Neurological symptoms in severe cases : Seizures, mental confusion, coma
Severe Malaria can cause death hence early diagnosis plus treatment is critical for a patient's recovery.
Diagnosis of Malaria
1. Travel history to Malaria prone areas raise a suspicion of Malaria when fever manifests
2. Physical examination may show fever, enlarged spleen and liver
3. Diagnostic tests: Blood test to examine for presence of malaria parasites in blood. Malaria can very rapidly become a severe and life-threatening disease hence early diagnosis and treatment is critical. Several antigen detection tests like rapid diagnostic tests (RDTs) using a "dipstick" is available however they cannot confirm the species or the parasitemia. Parasite nucleic acid detection using polymerase chain reaction (PCR) is more sensitive and specific than microscopy but can be performed only specific laboratories. PCR is a very useful tool for confirmation of species and detecting of drug resistance mutations.
1. Travel history to Malaria prone areas raise a suspicion of Malaria when fever manifests
2. Physical examination may show fever, enlarged spleen and liver
3. Diagnostic tests: Blood test to examine for presence of malaria parasites in blood. Malaria can very rapidly become a severe and life-threatening disease hence early diagnosis and treatment is critical. Several antigen detection tests like rapid diagnostic tests (RDTs) using a "dipstick" is available however they cannot confirm the species or the parasitemia. Parasite nucleic acid detection using polymerase chain reaction (PCR) is more sensitive and specific than microscopy but can be performed only specific laboratories. PCR is a very useful tool for confirmation of species and detecting of drug resistance mutations.
Treatment of Malaria
The disease should be treated as early as possible before it becomes serious and life-threatening. Malaria can be cured with anti-malaria drugs. The type of drugs and length of treatment depend on the type of malaria parasites, where the person was infected (which country as some places have parasites resistant to multiple drugs), their age, whether they are pregnant, and how sick they are at the start of treatment.
For uncomplicated Malaria
1. P. falciparum malaria parasites or Species Not Identified which is acquired in areas Without Chloroquine Resistance
- oral chloroquine of 600 mg should be given initially, followed by 300 mg base at 6, 24, and 48 hours after the initial dose for a total chloroquine dose of 1,500 mg base
- Alternatively, hydroxychloroquine may be used at a dose of 800 mg given initially, followed by 400 mg at 6, 24, and 48 hours after the initial dose for a total hydroxychloroquine dose of 1,550 mg base
2. P. falciparum malaria parasites or Species Not Identified which is acquired in areas With Chloroquine Resistance
- atovaquone-proguanil (Malarone) or artemether-lumefantrine (Coartem) are fixed dose combination medicines that can be used for non-pregnant adults and pediatric patients.
- Quinine sulfate plus doxycycline, tetracycline, or clindamycin is the next treatment option. Quinine treatment should continue for 7 days for infections acquired in Southeast Asia and for 3 days for infections acquired in Africa or South America.
Take note that treatment with mefloquine is associated with rare but potentially severe neuro-psychiatric reactions when used at treatment doses hence this is always the last option if other medicines cannot be used.
3. P. malariae and P. knowlesi: As there's noevidence of chloroquine resistance in P. malariae and P. knowlesi species hence chloroquine or hydroxychloroquine may be used for treatment of these infections. Quinine sulfate plus doxycycline, tetracycline, or clindamycin can also be used as treatment options.
4. P. vivax and P. ovale :
- Chloroquine (or hydroxychloroquine) remains an effective choice for all P. vivax and P. ovale infections except for P. vivaxinfections acquired in Papua New Guinea or Indonesia.
- For people who acquired malaria from Papua New Guinea or Indonesia, they should initially be treated with a regimen recommended for chloroquine-resistant P. vivax infections. The three treatment regimens are quinine sulfate plus doxycycline or tetracycline, or atovaquone-proguanil or mefloquine.
- Infections with P. vivax and P. ovale can relapse due to parasites that remain dormant in the liver. To eradicate them, patients should be treated with a 14-day course of primaquine phosphate 30 mg. As primaquine can cause hemolytic anemia in persons with glucose-6-phosphate-dehydrogenase (G6PD) deficiency, they must be screened for G6PD deficiency prior to starting primaquine. For those with borderline G6PD deficiency, primaquine may be given at the dose of 45 mg orally one time per week for 8 weeks. Primaquine must not be used during pregnancy. For those with true G6PD, cnsult an infectious disease specialist on alternative treatment.
Treatment of Malaria in Pregnant Woman
Malaria infection in pregnant women is associated with high risks of both maternal and perinatal morbidity and mortality as the parasites replicate in the placenta. Malaria infection during pregnancy can lead to miscarriages, low birth weight, perinatal death, premature deliveryand congenital infection.
1. For pregnant women diagnosed with uncomplicated malaria caused by P. malariae, P. vivax, P. ovale, or chloroquine-sensitive P. falciparum infection, prompt treatment with chloroquine is recommended (dose as per non-pregnant adult). Alternatively, hydroxychloroquine may be given.
2. For pregnant woman diagnosed with uncomplicated malaria caused by chloroquine-resistant P. falciparum infection, prompt treatment with either mefloquine or a combination of quinine sulfate and clindamycin is recommended.
3. For pregnant women diagnosed with uncomplicated malaria caused by chloroquine-resistant P. vivax infection, prompt treatment with mefloquine.
4. For P. vivax or P. ovale infections, primaquine phosphate which is used for radical treatment of hypnozoites should not be given during pregnancy. Pregnant patients should be maintained on chloroquine prophylaxis for the duration of their pregnancy which is is 300mg orally once per week. After delivery, pregnant patients who do not have G6PD deficiency should be treated with primaquine. Pregnant women diagnosed with severe malaria should be treated aggressively with parenteral antimalarial therapy.
Doxycycline and tetracycline are generally not indicated for use in pregnant women unless benefits outweigh benefits. Atovaquone/proguanil and artemether-lumefantrine are classified as pregnancy category C medications and are generally not indicated for use in pregnant women. However if other treatment options are not available and if the potential benefit is judged to outweigh the potential risks, then it can be considered as a treatment option.
Treatment of severe Malaria
Severe malaria disease with complications should be treated aggressively with infusion form of antimalarial therapy (quinidine gluconate) regardless of the species of malaria seen on the blood smear. Oral antimalarial drugs are not recommended. No renal adjustment for the dosing for initial therapy but if renal failure persists or the patient does not improve clinically, the maintenance dosage should be reduced by one third to one half on the third treatment day. As quinidine gluconate is harmful to the heart (ventricular arrhythmia, hypotension, hypoglycemia, and prolongation of the QTc interval) and so a baseline ECG should be done before initiating therapy and patients should be on cardiac monitoring and glucose monitoring once qunidine treatment commences. Intravenous artesunate is available as an investigational new drug if quinidine is not suitable but may not be available at certain medical institutions.
As with treatment of uncomplicated P. falciparum, quinidine/quinine therapy should be combined with doxycycline, tetracycline, or clindamycin. If the patient is unable to tolerate oral medication, intravenous doxycycline 100mg every 12 hours or clindamycin 5 mg base/kg every 8 hours may be given until the patient can be switched to oral therapy. Rapid intravenous administration of doxycycline or clindamycin should be avoided. Oral dosing of medications are: doxycycline 100 mg every 12 hours, tetracycline 250mg every 6 hours or clindamycin 20 mg base/kg/day divided three times per day for 7 days.
In randomized controlled trial, exchange transfusion has not been proven beneficial although it had been an option in the treatment of severe malaria since 1974. Exchange transfusion works by removing infected red cells, improving the rheological properties of blood, and reducing toxic factors such as parasite-derived toxins, harmful metabolites, and cytokines. The risks and side effects of exchange transfusion include fluid overload, febrile and allergic reactions, metabolic disturbances, red blood cell allo-antibody sensitization, transmissible infection, and line sepsis. So always weigh benefits against risks.
The disease should be treated as early as possible before it becomes serious and life-threatening. Malaria can be cured with anti-malaria drugs. The type of drugs and length of treatment depend on the type of malaria parasites, where the person was infected (which country as some places have parasites resistant to multiple drugs), their age, whether they are pregnant, and how sick they are at the start of treatment.
For uncomplicated Malaria
1. P. falciparum malaria parasites or Species Not Identified which is acquired in areas Without Chloroquine Resistance
- oral chloroquine of 600 mg should be given initially, followed by 300 mg base at 6, 24, and 48 hours after the initial dose for a total chloroquine dose of 1,500 mg base
- Alternatively, hydroxychloroquine may be used at a dose of 800 mg given initially, followed by 400 mg at 6, 24, and 48 hours after the initial dose for a total hydroxychloroquine dose of 1,550 mg base
2. P. falciparum malaria parasites or Species Not Identified which is acquired in areas With Chloroquine Resistance
- atovaquone-proguanil (Malarone) or artemether-lumefantrine (Coartem) are fixed dose combination medicines that can be used for non-pregnant adults and pediatric patients.
- Quinine sulfate plus doxycycline, tetracycline, or clindamycin is the next treatment option. Quinine treatment should continue for 7 days for infections acquired in Southeast Asia and for 3 days for infections acquired in Africa or South America.
Take note that treatment with mefloquine is associated with rare but potentially severe neuro-psychiatric reactions when used at treatment doses hence this is always the last option if other medicines cannot be used.
3. P. malariae and P. knowlesi: As there's noevidence of chloroquine resistance in P. malariae and P. knowlesi species hence chloroquine or hydroxychloroquine may be used for treatment of these infections. Quinine sulfate plus doxycycline, tetracycline, or clindamycin can also be used as treatment options.
4. P. vivax and P. ovale :
- Chloroquine (or hydroxychloroquine) remains an effective choice for all P. vivax and P. ovale infections except for P. vivaxinfections acquired in Papua New Guinea or Indonesia.
- For people who acquired malaria from Papua New Guinea or Indonesia, they should initially be treated with a regimen recommended for chloroquine-resistant P. vivax infections. The three treatment regimens are quinine sulfate plus doxycycline or tetracycline, or atovaquone-proguanil or mefloquine.
- Infections with P. vivax and P. ovale can relapse due to parasites that remain dormant in the liver. To eradicate them, patients should be treated with a 14-day course of primaquine phosphate 30 mg. As primaquine can cause hemolytic anemia in persons with glucose-6-phosphate-dehydrogenase (G6PD) deficiency, they must be screened for G6PD deficiency prior to starting primaquine. For those with borderline G6PD deficiency, primaquine may be given at the dose of 45 mg orally one time per week for 8 weeks. Primaquine must not be used during pregnancy. For those with true G6PD, cnsult an infectious disease specialist on alternative treatment.
Treatment of Malaria in Pregnant Woman
Malaria infection in pregnant women is associated with high risks of both maternal and perinatal morbidity and mortality as the parasites replicate in the placenta. Malaria infection during pregnancy can lead to miscarriages, low birth weight, perinatal death, premature deliveryand congenital infection.
1. For pregnant women diagnosed with uncomplicated malaria caused by P. malariae, P. vivax, P. ovale, or chloroquine-sensitive P. falciparum infection, prompt treatment with chloroquine is recommended (dose as per non-pregnant adult). Alternatively, hydroxychloroquine may be given.
2. For pregnant woman diagnosed with uncomplicated malaria caused by chloroquine-resistant P. falciparum infection, prompt treatment with either mefloquine or a combination of quinine sulfate and clindamycin is recommended.
3. For pregnant women diagnosed with uncomplicated malaria caused by chloroquine-resistant P. vivax infection, prompt treatment with mefloquine.
4. For P. vivax or P. ovale infections, primaquine phosphate which is used for radical treatment of hypnozoites should not be given during pregnancy. Pregnant patients should be maintained on chloroquine prophylaxis for the duration of their pregnancy which is is 300mg orally once per week. After delivery, pregnant patients who do not have G6PD deficiency should be treated with primaquine. Pregnant women diagnosed with severe malaria should be treated aggressively with parenteral antimalarial therapy.
Doxycycline and tetracycline are generally not indicated for use in pregnant women unless benefits outweigh benefits. Atovaquone/proguanil and artemether-lumefantrine are classified as pregnancy category C medications and are generally not indicated for use in pregnant women. However if other treatment options are not available and if the potential benefit is judged to outweigh the potential risks, then it can be considered as a treatment option.
Treatment of severe Malaria
Severe malaria disease with complications should be treated aggressively with infusion form of antimalarial therapy (quinidine gluconate) regardless of the species of malaria seen on the blood smear. Oral antimalarial drugs are not recommended. No renal adjustment for the dosing for initial therapy but if renal failure persists or the patient does not improve clinically, the maintenance dosage should be reduced by one third to one half on the third treatment day. As quinidine gluconate is harmful to the heart (ventricular arrhythmia, hypotension, hypoglycemia, and prolongation of the QTc interval) and so a baseline ECG should be done before initiating therapy and patients should be on cardiac monitoring and glucose monitoring once qunidine treatment commences. Intravenous artesunate is available as an investigational new drug if quinidine is not suitable but may not be available at certain medical institutions.
As with treatment of uncomplicated P. falciparum, quinidine/quinine therapy should be combined with doxycycline, tetracycline, or clindamycin. If the patient is unable to tolerate oral medication, intravenous doxycycline 100mg every 12 hours or clindamycin 5 mg base/kg every 8 hours may be given until the patient can be switched to oral therapy. Rapid intravenous administration of doxycycline or clindamycin should be avoided. Oral dosing of medications are: doxycycline 100 mg every 12 hours, tetracycline 250mg every 6 hours or clindamycin 20 mg base/kg/day divided three times per day for 7 days.
In randomized controlled trial, exchange transfusion has not been proven beneficial although it had been an option in the treatment of severe malaria since 1974. Exchange transfusion works by removing infected red cells, improving the rheological properties of blood, and reducing toxic factors such as parasite-derived toxins, harmful metabolites, and cytokines. The risks and side effects of exchange transfusion include fluid overload, febrile and allergic reactions, metabolic disturbances, red blood cell allo-antibody sensitization, transmissible infection, and line sepsis. So always weigh benefits against risks.
Prevention of Malaria
1. Always check the country you are travelling to, is it listed as a Malaria prone area, if so consult a doctor at least 4-6 weeks before travelling for evaluation on which anti-malaria drugs you should take as prophylaxis.
2. Many research has been ongoing to invent a malaria vaccine however due to the complexity of the parasites, scientists are still doing more trials to produce an effective vaccine.
3. Prevention from mosquito bites include: sleeping under a mosquito net, spraying insect repellents and covering your skin to minimize exposure.
4. Malaria prophylaxis drugs : There are country specific anti-malaria drugs due to the presence of resistance. Also drugs are not 100% protective hence personal protection equipment to prevent bites are also important. Different drugs have different duaration, side effects and drug-drug interactions.
Atovaquone/Proguanil (Malarone) : 50 mg atovaquone and 100 mg proguanil 1 tab. daily
Chloroquine: 300 mg base once weekly
Doxycycline: 100mg once daily
Mefloquine (Lariam) : 250 mg base once weekly
Primaquine
1. Always check the country you are travelling to, is it listed as a Malaria prone area, if so consult a doctor at least 4-6 weeks before travelling for evaluation on which anti-malaria drugs you should take as prophylaxis.
2. Many research has been ongoing to invent a malaria vaccine however due to the complexity of the parasites, scientists are still doing more trials to produce an effective vaccine.
3. Prevention from mosquito bites include: sleeping under a mosquito net, spraying insect repellents and covering your skin to minimize exposure.
4. Malaria prophylaxis drugs : There are country specific anti-malaria drugs due to the presence of resistance. Also drugs are not 100% protective hence personal protection equipment to prevent bites are also important. Different drugs have different duaration, side effects and drug-drug interactions.
Atovaquone/Proguanil (Malarone) : 50 mg atovaquone and 100 mg proguanil 1 tab. daily
- Advantages :
- Can be started 1-2 days before traveling which is good for last minute travelers.
- Daily dose
- Convenient for those on short trips as you only need to take the medicine for 7 days after traveling rather than 4 weeks for some medications.
- Well tolerated with minimal side effects
- Available in Pediatric tablets
- Disadvantages
- Contraindicated in women who are pregnant or breastfeeding a child < 5 kg
- Contraindicated in those with renal disease
- More expensive
- Need to take daily medicine
- Side effects : Abdominal pain, nausea, vomiting, elevated liver enzymes levels
Chloroquine: 300 mg base once weekly
- Advantages:
- Once a week dose of medication
- Ideal for long trips since its weekly medication
- For those already taking long term hydroxychloroquine for rheumatologic conditions, they may not have to take an additional medicine
- Safe for all trimesters of pregnancy
- Disavantages
- Cannot be used in areas with chloroquine or mefloquine resistance
- May exacerbate psoriasis
- For short trips, some people would rather not take medication for 4 weeks after travel
- Medication need to be started 1-2 weeks prior travel hence it is not a good choice for last-minute travelers
- Side effects: Blurry vision, tinnitus, hearing loss
Doxycycline: 100mg once daily
- Advantages :
- Some prefer to take daily medicine
- Good for last-minute travelers because the drug is started 1-2 days before traveling
- Least expensive medicine
- Some people who are already taking doxycycline for prevention of acne do not have to take an additional medicine
- It can also prevent some additional infections (e.g., Rickettsiae and leptospirosis) and so it may be suitable by people who do lots of hiking, camping, wading and swimming in fresh water
- Disadvantages :
- Contraindicated in pregnant women and children <8 years old
- Some people prefer not take a medicine every day
- Hassle to take medication continuously for 4 weeks after travel
- Women prone to get vaginal yeast infections after taking antibiotics
- Increased risk of sun sensitivity
- Gastrointestinal side effects of doxycyline
- Side effects: Photosensitivity, vaginal candidiasis, abdominal pain, diarrhea
Mefloquine (Lariam) : 250 mg base once weekly
- Advanatages :
- Some people prefer to take weekly medicine
- Good choice for long trips because it is taken only weekly
- Can be used during pregnancy
- Disadvantages:
- Cannot be used in areas with mefloquine resistance
- Contraindicated in patients with certain psychiatric conditions
- Contraindicated in patients with a seizure disorder
- Not recommended for persons with cardiac conduction abnormalities
- Need to start medications 2 weeks before travel hence it is not a good choice for last-minute travelers
- Some people prefer not take a weekly medication
- For trips of short duration, some people prefer not take medication for 4 weeks after travel
- Side effects: Insomnia, paranoia, hallucinations, seizures
Primaquine
- Advantages :
- Most effective medicine for preventing P. vivax
- Good choice for shorter trips because you only have to take the medicine for 7 days after traveling rather than 4 weeks
- Good for last-minute travelers because the drug is started 1-2 days before traveling to an area where malaria transmission occurs
- Some people prefer to take a daily medicine
- Disadvantages:
- Contraindicated in G6PD patients
- There are costs and delays associated with getting a G6PD test done; however, it only has to be done once. Once a normal G6PD level is verified and documented, the test does not have to be repeated the next time primaquine is considered
- Contraindicated pregnant women
- Contraindicated in lactating women unless the infant has also been tested for G6PD deficiency
- Some people prefer not to take daily medicine
- Gastrointestinal side effects
- Side effects: Abdominal pain, nausea, vomiting, acute hemolysis in patients with G6PD deficiency