Malaria prophylaxis
Encyclopedia
Malaria prophylaxis is a preventative treatment of malaria
.
Most adults from endemic areas have a degree of long-term infection, which tends to recur, and also possess partial immunity
(resistance); the resistance reduces with time, and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. Several malaria vaccine
s are under development.
Recent improvements in malaria prevention strategies have further enhanced its effectiveness in combating areas highly infected with the malaria parasite. Additional bite prevention measures include mosquito and insect repellents that can be directly applied to skin. This form of mosquito repellent is slowly replacing indoor residual spraying, which is shown to have high levels of toxicity by WHO (World Health Organization). Further additions to preventative care are sanctions on blood transfusions. Once the malaria parasite enters the erythorocytic stage, it can adversely affect blood cells, making it possible to contract the parasite through infected blood.
Chloroquine
may be used where the parasite is still sensitive. However due to resistance one of three medications: mefloquine
(Lariam), doxycycline
(available generically), and the combination of atovaquone
and proguanil
hydrochloride (Malarone) is frequently needed. Doxycycline and the atovaquone and proguanil combination are the best tolerated with mefloquine associated with higher rates of neurological and psychiatric symptoms.
, proguanil
, mefloquine
, and doxycycline
are suppressive prophylactics. This means that they are only effective at killing the malaria parasite once it has entered the erythrocytic stage (blood stage) of its life cycle, and therefore have no effect until the liver stage is complete. That is why these prophylactics must continue to be taken for four weeks after leaving the area of risk.
are the only causal prophylactics in current use.
and CDC
for prevention of P. falciparum infection. HPA and WHO advice are broadly in line with each other (although there are some differences). CDC guidance frequently contradicts HPA and WHO guidance.
These regiments include:
In areas where chloroquine remains effective:
What regimen is appropriate depends on the person who is to take the medication as well as the country or region travelled to. This information is available from the UK HPA, WHO or CDC (links are given below). Doses depend also on what is available (e.g., in the US, mefloquine tablets contain 228 mg base, but 250 mg base in the UK). The data is constantly changing and no general advice is possible.
Doses given are appropriate for adults and children aged 12 and over.
Other chemoprophylactic regimens that have been used on occasion:
Prophylaxis against Plasmodium vivax
requires a different approach given the long liver stage of this parasite. This is a highly specialist area.
known as RTS,S
reported that it could protect approximately 50% of inoculated infants and children. The RTS,S vaccine was engineered using genes from the outer protein of Plasmodium falciparum malaria parasite and a portion of a hepatitis B virus and a chemical adjuvant to boost the immune system response. It is being developed by PATH and GlaxoSmithKline
(GSK), which has spent about $300 million on the project, plus about $200 million more from the Bill and Melinda Gates Foundation
, India
and China, illustrating its wide geographical distribution. The first treatment identified is thought to be Quinine
, one of four alkaloid
s from the bark of the Cinchona
tree. Originally it was used by the tribes of Ecuador and Peru for treating fevers. Its role in treating malaria was recognised and recorded first by an Augustine monk from Lima, Peru in 1633. Seven years later the drug had reached Europe and was being used widely with the name ‘the Jesuit's bark’. From this point onwards the use of Quinine and the public interest in malaria increased, although the compound was not isolated and identified as the active ingredient until 1820. By the mid-1880’s the Dutch had grown vast plantations of cinchona trees and monopolised the world market.
Quinine remained the only available treatment for malaria until the early 1920’s. During the First World War German scientists developed the first synthetic antimalarial compound – Atabrin and this was followed by Resochin and Sontochin derived from 4-aminoquinoline
compounds. American troops, on capturing Tunisia during the Second World War, acquired, then altered the drugs to produce Chloroquine
.
The development of new antimalarial drug
s spurred the World Health Organization
in 1955 to attempt a global malaria eradication program. This was successful in much of Brazil, the US and Egypt but ultimately failed elsewhere. Efforts to control malaria are still continuing, with the development of drug-resistant parasites presenting increasingly difficult problems.
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
.
Most adults from endemic areas have a degree of long-term infection, which tends to recur, and also possess partial immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
(resistance); the resistance reduces with time, and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. Several malaria vaccine
Malaria vaccine
Malaria vaccines are an area of intensive research. However, there is no effective vaccine that has been introduced into clinical practice.The global burden of P. falciparum malaria increased through the 1990s due to drug-resistant parasites and insecticide-resistant mosquitoes; this is illustrated...
s are under development.
- Awareness of risk;
- Bite prevention - Travelers to malarious areas are advised to wear long clothes that cover as much of the skin as possible. Exposed parts of the body should be treated with insect repellent. When sleeping, insecticide-impregnated bed nets should be used. See also: Indoor residual sprayingIndoor residual sprayingIndoor residual spraying or IRS is the process of spraying the inside of dwellings with an insecticide to kill mosquitoes that spread malaria. A dilute solution of insecticide is sprayed on the inside walls of certain types of dwellings—those with walls made from porous materials such as mud or...
- Chemoprophylaxis; and
- rapid diagnosis and treatment.
Recent improvements in malaria prevention strategies have further enhanced its effectiveness in combating areas highly infected with the malaria parasite. Additional bite prevention measures include mosquito and insect repellents that can be directly applied to skin. This form of mosquito repellent is slowly replacing indoor residual spraying, which is shown to have high levels of toxicity by WHO (World Health Organization). Further additions to preventative care are sanctions on blood transfusions. Once the malaria parasite enters the erythorocytic stage, it can adversely affect blood cells, making it possible to contract the parasite through infected blood.
Chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
may be used where the parasite is still sensitive. However due to resistance one of three medications: mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
(Lariam), doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
(available generically), and the combination of atovaquone
Atovaquone
Atovaquone is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about US$2.13 per standard 250 mg. tablet...
and proguanil
Proguanil
Proguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
hydrochloride (Malarone) is frequently needed. Doxycycline and the atovaquone and proguanil combination are the best tolerated with mefloquine associated with higher rates of neurological and psychiatric symptoms.
Medications
In choosing the agent, it is important to weigh the risk of infection against the risks and side effects associated with the medications.Suppressive prophylaxis
ChloroquineChloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
, proguanil
Proguanil
Proguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
, mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
, and doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
are suppressive prophylactics. This means that they are only effective at killing the malaria parasite once it has entered the erythrocytic stage (blood stage) of its life cycle, and therefore have no effect until the liver stage is complete. That is why these prophylactics must continue to be taken for four weeks after leaving the area of risk.
Causal prophylaxis
Causal prophylactics target not only the blood stages of malaria, but the initial liver stage as well. This means that the user can stop taking the drug seven days after leaving the area of risk. Malarone and primaquinePrimaquine
Primaquine is a medication used in the treatment of malaria and Pneumocystis pneumonia. It is a member of the 8-aminoquinoline group of drugs that includes tafenoquine and pamaquine.-Radical cure:...
are the only causal prophylactics in current use.
Regimens
Specific regimens are recommended by the WHO, UK HPAHealth Protection Agency
The Health Protection Agency, or, in Welsh, Yr Asiantaeth Diogelu Iechyd is a statutory corporation. It is an independent UK organisation that was set up by the government in 2003 to protect the public from threats to their health from infectious diseases and environmental hazards...
and CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
for prevention of P. falciparum infection. HPA and WHO advice are broadly in line with each other (although there are some differences). CDC guidance frequently contradicts HPA and WHO guidance.
These regiments include:
- doxycyclineDoxycyclineDoxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
100 mg once daily (started one day before travel, and continued for four weeks after returning); - mefloquineMefloquineMefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
228 to 250 mg once weekly (started two-and-a-half weeks before travel, and continued for four weeks after returning); - atovaquoneAtovaquoneAtovaquone is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about US$2.13 per standard 250 mg. tablet...
/proguanilProguanilProguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
(Malarone) 1 tablet daily (started one day before travel, and continued for 1 week after returning).
In areas where chloroquine remains effective:
- chloroquineChloroquineChloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
300 to 310 mg once weekly, and proguanilProguanilProguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
200 mg once daily (started one week before travel, and continued for four weeks after returning);
What regimen is appropriate depends on the person who is to take the medication as well as the country or region travelled to. This information is available from the UK HPA, WHO or CDC (links are given below). Doses depend also on what is available (e.g., in the US, mefloquine tablets contain 228 mg base, but 250 mg base in the UK). The data is constantly changing and no general advice is possible.
Doses given are appropriate for adults and children aged 12 and over.
Other chemoprophylactic regimens that have been used on occasion:
- DapsoneDapsoneDapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...
100 mg and pyrimethaminePyrimethaminePyrimethamine is a medication used for protozoal infections. It is commonly used as an antimalarial drug , and is also used in the treatment of Toxoplasma gondii infections in immunocompromised patients, such as HIV-positive individuals.-Mechanism of action:Pyrimethamine interferes with...
12.5 mg once weekly (available as a combination tablet called Maloprim or Deltaprim): this combination is not routinely recommended because of the risk of agranulocytosisAgranulocytosisGranulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
; - PrimaquinePrimaquinePrimaquine is a medication used in the treatment of malaria and Pneumocystis pneumonia. It is a member of the 8-aminoquinoline group of drugs that includes tafenoquine and pamaquine.-Radical cure:...
30 mg once daily (started the day before travel, and continuing for seven days after returning): this regimen is not routinely recommended because of the need for G-6-PDGlucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...
testing prior to starting primaquine (see the article on primaquinePrimaquinePrimaquine is a medication used in the treatment of malaria and Pneumocystis pneumonia. It is a member of the 8-aminoquinoline group of drugs that includes tafenoquine and pamaquine.-Radical cure:...
for more information). - QuinineQuinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
sulfate 300 to 325 mg once daily: this regimen is effective but not routinely used because of the unpleasant side effects of quinine.
Prophylaxis against Plasmodium vivax
Plasmodium vivax
Plasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring malaria, P. vivax is one of the four species of malarial parasite that commonly infect humans. It is less virulent than Plasmodium falciparum, which is the deadliest of the...
requires a different approach given the long liver stage of this parasite. This is a highly specialist area.
Vaccines
In October 2011, preliminary findings from the Phase III trials of an experimental malaria vaccineMalaria vaccine
Malaria vaccines are an area of intensive research. However, there is no effective vaccine that has been introduced into clinical practice.The global burden of P. falciparum malaria increased through the 1990s due to drug-resistant parasites and insecticide-resistant mosquitoes; this is illustrated...
known as RTS,S
RTS,S
RTS,S or Mosquirix is vaccine for malaria developed by GlaxoSmithKline.In October 2011 it was reported to protect approximately 50% of inoculated infants and children....
reported that it could protect approximately 50% of inoculated infants and children. The RTS,S vaccine was engineered using genes from the outer protein of Plasmodium falciparum malaria parasite and a portion of a hepatitis B virus and a chemical adjuvant to boost the immune system response. It is being developed by PATH and GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
(GSK), which has spent about $300 million on the project, plus about $200 million more from the Bill and Melinda Gates Foundation
History
Malaria is one of the oldest known pathogens, and began having a major impact on human survival about 10,000 years ago with the birth of agriculture. The development of virulence in the parasite has been demonstrated using genomic mapping of samples from this period, confirming the emergence of genes conferring a reduced risk of developing the malaria infection. References to the disease can be found in manuscripts from ancient EgyptAncient Egypt
Ancient Egypt was an ancient civilization of Northeastern Africa, concentrated along the lower reaches of the Nile River in what is now the modern country of Egypt. Egyptian civilization coalesced around 3150 BC with the political unification of Upper and Lower Egypt under the first pharaoh...
, India
History of India
The history of India begins with evidence of human activity of Homo sapiens as long as 75,000 years ago, or with earlier hominids including Homo erectus from about 500,000 years ago. The Indus Valley Civilization, which spread and flourished in the northwestern part of the Indian subcontinent from...
and China, illustrating its wide geographical distribution. The first treatment identified is thought to be Quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
, one of four alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
s from the bark of the Cinchona
Cinchona
Cinchona or Quina is a genus of about 38 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing 5–15 metres in height with evergreen foliage. The leaves are opposite, rounded to lanceolate and 10–40 cm long. The flowers are white, pink...
tree. Originally it was used by the tribes of Ecuador and Peru for treating fevers. Its role in treating malaria was recognised and recorded first by an Augustine monk from Lima, Peru in 1633. Seven years later the drug had reached Europe and was being used widely with the name ‘the Jesuit's bark’. From this point onwards the use of Quinine and the public interest in malaria increased, although the compound was not isolated and identified as the active ingredient until 1820. By the mid-1880’s the Dutch had grown vast plantations of cinchona trees and monopolised the world market.
Quinine remained the only available treatment for malaria until the early 1920’s. During the First World War German scientists developed the first synthetic antimalarial compound – Atabrin and this was followed by Resochin and Sontochin derived from 4-aminoquinoline
4-Aminoquinoline
4-Aminoquinoline is a form of aminoquinoline with the amino group at the 4-position of the quinoline.A variety of derivatives of 4-aminoquinoline are antimalarial agents useful in treating erythrocytic plasmodial infections. Examples include amodiaquine, chloroquine, and hydroxychloroquine....
compounds. American troops, on capturing Tunisia during the Second World War, acquired, then altered the drugs to produce Chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
.
The development of new antimalarial drug
Antimalarial drug
Antimalarial medications, also known as antimalarials, are designed to prevent or cure malaria. Such drugs may be used for some or all of the following:* Treatment of malaria in individuals with suspected or confirmed infection...
s spurred the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
in 1955 to attempt a global malaria eradication program. This was successful in much of Brazil, the US and Egypt but ultimately failed elsewhere. Efforts to control malaria are still continuing, with the development of drug-resistant parasites presenting increasingly difficult problems.