Am I more susceptible to malaria?

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QUESTION

I contracted common malaria, vivax?, when i was 20 yrs old from long visit to Papua NewGuinea, 1970. Returned to USA and was treated with chloro, primaquine drugs and really no problems since treatment.

Now going to Thailand for week, Chiang Mai and region. If bitten by local malarial mosq. am i more likely to recur? And should I certainly choose prophylaxis? thnx

ANSWER

If you were treated successfully with chloroquine and primaquine then there is no reason for your malaria to reoccur. Since it has been a long time since you had malaria, you probably also don’t have any antibodies against the parasite in your system anymore; this just means you don’t have any extra immunity against P. vivax (which you might have done if you had returned to a malaria area, and particularly one with the same strain of P. vivax as that which infected you, within a few months or years of being infected the first time), but it doesn’t mean you will be any more susceptible than someone who never had malaria.

In terms of where you are going, the city of Chiang Mai itself is not considered to have malaria transmission, but the areas surrounding it are, particularly as you get closer to the Burmese border. As such, if you will be travelling in rural and/or forested areas, you might want to consider taking prophylactic medication (and other preventative measures, like sleeping under a long-lasting insecticide treated bednet).

Thailand unfortunately has seen the emergence of resistance to a couple widely used prophylactic measures, namely chloroquine and mefloquine (sold as Lariam), so these are not appropriate preventative medicine in this region. Instead, you should consider taking doxycycline or atovaquone-proguanil (sold as Malarone).

Malaria Recurrence

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QUESTION

I had malaria 5 months back it has again reoccurred. this time there has been increase in the size of the spleen. As of now it is being treated but I fear of getting it again. Is it true the malaria which i am down with reoccurs every 6- 8 months ??? Local people call it as registered malaria.. .

ANSWER

There certainly are types of malaria that can reoccur relatively regularly, at various intervals. This malaria is caused by one of two species, either Plasmodium vivax or Plasmodium ovale.

With both, it is important to get it diagnosed via a blood test with a doctor before getting treated again, to make sure it is indeed a relapse of the same malaria, and not a new infection with a different kind, or indeed some other disease (the symptoms of malaria can often be confused with other infections).

There is also medication that can be taken to prevent future relapses and re-occurrences—it is called primaquine, so you should talk to your doctor about the possibility of taking this medication. Please note it is not suitable for people who have G6DP deficiency, so you should be tested for that before taking it.

Long and Short Term Effects of Malaria

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QUESTION

What are the long term and short term effects of malaria in brief please?

ANSWER

The symptoms of malaria as an acute infection vary somewhat depending on the type of malaria, but usual signs include high fever (often in a cyclical pattern, with fever one day, then no fever for one or two days, then a recurrence of fever), chills, body aches and nausea.

For Plasmodium falciparum, the most deadly form of malaria, the infection can progress rapidly if left untreated, with organ failure, impaired consciousness, coma and even death occurring as quickly as a few days after the onset of symptoms.

If the patient is able to survive the infection, or gets treatment in time, there are usually no long term affects of malaria infection. Some people who have suffered severe cerebral malaria (from P. falciparum) may experience some longer term neurological effects. Other types of malaria, such as P. ovale and P. vivax, can form dormant life stages which hide in the liver for weeks, months or even years, leading to relapse at a later date. However, apart from these recurrences, there are also no long term effects of infection with these types of malaria.

Malaria Parasites Classification

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QUESTION

Where are malaria parasites classified?

ANSWER

The parasite that causes malaria comes from the genus Plasmodium, which is part of a Phylum of single-celled protist organisms called Apicomplexa. The Apicomplexans mostly posses an organ called an apicoplast, which is part of an apical structure designed to aid entry into a host cell. The Apicomplexa is split into two Classes, of which Plasmodium belongs to the Aconoidasida (lacking a structure called a conoid, which is like a set of microtubules), and then to the Order Haemosporidia, which contains parasites which invade red blood cells. Within this Order, Plasmodium belongs to the Family Plasmodiidae, which all share numerous characteristics, including asexual reproduction in a vertebrate host and sexual reproduction in a definitive host (a mosquito, in the case of the Plasmodium species that infect all mammals, including humans).

In the case of human malarias, the definitive host is often referred to as the vector. The family contains about twelve genera, of which one is Plasmodium, which itself is now often divided up into numerous sub-genera, and then again into hundreds of different species, of which five infect humans (P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi).

Pathophysiology of Malaria

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QUESTION

What is the pathophysiology of malaria?

ANSWER

Malaria causes disease through a number of pathways, which depend to a certain extent on the species. Malaria is caused by a single-celled parasite of the genus Plasmodium; there are five species which infect humans, beingPlasmodium falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.

All these species are introduced into the human blood stream through the bite of an infected mosquito; the life stage of malaria at this point is called a “sporozoite”, and they pass first to the liver, where they undergo an initial stage of replication (called “exo-erythrocytic replication”), before passing back into the blood and invading red blood cells (called “erythrocytes”, hence this is the “erythrocytic” part of the cycle). The malaria parasites that invade red blood cells are known as merozoites, and within the cell they replicate again, bursting out once they have completed a set number of divisions. It is this periodic rupturing of the red blood cells that causes most of the symptoms associated with malaria, as the host’s immune system responds to the waste products produced by the malaria parasites and the debris from the destroyed red blood cells. Different species of malaria rupture the red blood cells at different intervals, which leads to the diagnostic cycles of fever which characterise malaria; P. vivax, for example, tends to produce cycles of fever every two days, whereas P. malaria produces fever every three.

In addition, Plasmodium falciparum produces unique pathological effects, due to its manipulation of the host’s physiology. When it infects red blood cells, it makes them stick to the walls of tiny blood vessels deep within major organs, such as the kidneys, lungs, heart and brain. This is called “sequestration”, and results in reduced blood flow to these organs, causing the severe clinical symptoms associated with this infection, such as cerebral malaria.

More details on the exact biochemical mechanisms for sequestration and its effect on the pathology of the infection can be found on the Tulane University website.

What Causes Malaria

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QUESTION

What are the causes of malaria?

ANSWER

Malaria is caused  by infection with certain single-celled parasites of the genus Plasmodium. Specifically, there are five species which infect humans: P. falciparum (the most severe and dangerous form of malaria), P. vivax, P. ovale, P. malariae and P. knowlesi.

The symptoms of the disease occur when the parasite enters the blood stream (after a brief 1-3 week period of development in the liver) and begins to enter red blood cells, reproduce inside them, and then burst out, destroying the cell. The debris caused by this bursting, as well as various other aspects of the process, cause the body to mount an intense immune reaction which results in high fever, chills, aches and nausea. For P. falciparum infection, the infection is particularly severe because the parasite causes red blood cells it infects to stick inside the small blood vessels that lead to major organs, reducing blood flow and causing oxygen deprivation. When this occurs in the blood vessels in the brain, the result is impaired consciousness, unconsciousness, coma and even death – hallmarks of what is known as “cerebral malaria,” which is implicated in many of the deaths related to malaria each year.

Repeated Malaria Cases, New Guinea

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QUESTION

Hello, I live in Papua New Guinea. Myself, my wife and my 2 kids (both under 4 years old), get diagnosed with malaria approximately 3-4 times a year, usually vivax or falciparum. Our GP uses a prick of blood and examines under a microscope. Is it that easy/obvious to diagnose under this method and is it common to get this many attacks in a year? I also fear the affects of taking malaria tabs (eg Fansidar, Primaquin, Artemeter, Amodiaquine) this many times, especially for my young kids. Please help!

ANSWER

In high transmission areas, particularly in rural areas in sub-Saharan Africa, it certainly isn’t unusual for children to get as many a 5 or 6 malaria attacks in a year; adults tend to present with fewer clinical episodes, usually because they were heavily exposed as children and thus developed a significant level of immunity against malaria.

If you and your wife didn’t grow up in a malarial area, then you would not have that acquired immunity, and so you would be expected to get sick almost as often as your young children. Papua New Guinea certainly is a high transmission zone, and I think one thing which might help your family is to focus more on malaria prevention. Since malaria is transmitted by mosquitoes, the best way to avoid getting malaria is to avoid getting bitten by mosquitoes. You should all be sleeping under log-lasting insecticide-treated bednets, which kill and/or repel mosquitoes that try to bite you while you sleep (the mosquitoes that transmit malaria, of the genus Anopheles, are most active at dusk, at night, and at dawn—during the heat of the day they usually don’t feed, but may be found in cooler, heavily shaded areas).

You could also try spraying the walls of your house with a long-lasting insecticide like permethrin, which will also kill adult mosquitoes. Making sure your house is well-screened will also prevent mosquitoes from getting in and biting you at night and in the evenings, and if you are going out during these times, you and your family should wear long-sleeved clothing, and exposed skin should be covered with insect repellent. A DEET-based insect repellent is best, but you may not be comfortable using these regularly on young children, since it can have some potentially dangerous long-term effects, particularly on the liver.

In terms of your other questions, looking at your blood under the microscope is the normal way to diagnose malaria in many places, so it sounds like your GP is doing a good job. There is no indication of adverse effects from taking multiple, repeated doses of anti-malarials, but as I mention above, taking additional preventive measures may further help in reducing your family’s malaria incidence.

One thing you might want to talk to your doctor about is the fact that in some cases, Plasmodium vivax can cause relapses of infection weeks or even months after the initial infection. The reason is that P. vivax can form dormant life stages, which can hide out in the liver, and cannot be killed by the normal anti-malarial treatment. However, there is a medication, called primaquine, which can kill these liver forms, and prevent future relapse. People with a deficiency in a particular enzyme, called G6DP, may not be able to take this medication, as it may cause severe anaemia, so prior to taking the drug you might have to be tested for this deficiency. However, it is definitely something you should talk to your GP about.

Please take a moment to complete our Malaria Survey, as it will help us better understand the effects of malaria medications.

Recurrent Malaria

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QUESTION

can malaria represent itself after 50 years?

ANSWER

There are two types of malaria which can lay dormant for long periods of time, though I don’t personally know of more than a handful of cases where the relapse was a matter of decades after the initial infection. These two types are P. vivax and P. ovale, so if you know you were infected with one of these types a number of years ago, it is possible that you could experience a relapse many years later, though as mentioned above, it is rare for the time lapse to be as long as 50 years.

New Partners Join the Asia Pacific Malaria Elimination Network (APMEN)

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The Asia Pacific Malaria Elimination Network (APMEN) has announced two new Partner Institutions have joined the organization: The Mahidol Vivax Research Center and the Malaria Research Centre, Universiti Malaysia Sarawak.

The Mahidol Vivax Research Center (MVRC) established in March 2011 is dedicated to the study of Plasmodium vivax and non falciparum malaria. Its establishment at Mahidol University in Thailand is important to the region, as Mahidol has a long record in the field of tropical disease medicine and research. Mahidol Vivax Research Center was initiated by the Dean of the Faculty of Tropical Medicine, Mahidol University, Associate Professor Pratap Singhasivanon and is directed by Dr. Jetsumon Prachumsri, formerly the leader of malaria research at the Armed Forces Research Institutes of Medical Sciences (AFRIMS) and APMEN Partner Institution representative.

The Malaria Research Centre was established at the Universiti Malaysia Sarawak in 2006 in recognition of the major contribution to malaria research by Professor Balbir Singh, Professor Janet Cox-Singh, and co-researchers at the Malaria Research Laboratory in the Faculty of Medicine and Health Sciences. MRC-UNIMAS is known for its work on Plasmodium knowlesi that was recognised by the World Health Organization (WHO) in 2008 as the fifth species of Plasmodia parasite to infect humans in the wild.

MRC-UNIMAS found that many malaria infections in Sarawak, Malaysia, had been incorrectly diagnosed and a major cause of malaria was Plasmodium knowlesi that is transmitted via the bit of an Anopheline mosquito from long-tail and pig-tail macaques. P knowlesi has also been reported in other parts of Malaysia, Indonesia, and Philippines and may be endemic in more countries in Southeast Asia. The final elimination of malaria in the Asia Pacific region will depend on a greater understanding of P knowlesi and how we can target this zoonosis.

The Malaria Research Centre, Universiti Malaysia Sarawak and the Mahidol Vivax Research Center have already supported APMEN through their active participation at last year’s annual meeting in Kota Kinabalu, Malaysia.

The fourth annual APMEN Annual Meeting will be held in May 2012 in Seoul, Republic of Korea. This year’s meeting will focus on how to sustain the gains made in the elimination of malaria and the importance in the coming years of maintaining successful approaches and their support. The region has many challenges to face in malaria elimination, in particular P. vivax, a type of malaria that is more difficult to diagnose and treat than P falciparum, the type of malaria most often discussed at a global level. APMEN through its information exchange, capacity building, and evidence building and advocacy activities is committed to supporting and maintaining elimination efforts in the Asia Pacific Region.

About the Asia Pacific Malaria Elimination Network
The Asia Pacific Malaria Elimination Network (APMEN) was established in 2009 to bring attention and support to the under-appreciated and little-known work of malaria elimination in Asia Pacific, with a particular focus on Plasmodium vivax.

APMEN is composed of 12 Asia Pacific countries (Bhutan, Cambodia, China, Democratic People’s Republic of Korea, Indonesia, Malaysia, Philippines, Republic of Korea, the Solomon Islands, Sri Lanka, Thailand, and Vanuatu) that are pursuing malaria elimination, as well as leaders and experts from key multilateral and academic agencies. The mission of this diverse but cohesive Network is to collaboratively address the unique challenges of malaria elimination in the region through leadership, advocacy, capacity building, knowledge exchange, and building the evidence base.

Development of the Network took place in 2008 through the leadership of the UCSF Global Health Group (GHG) and the School of Population Health, University of Queensland (SPH/UQ). APMEN collaborates closely with the WHO and is supported by the Australian Government through its international aid agency AusAID with a commitment of nearly $7 million for ongoing support to the Network. This complements Australia’s overall support for malaria control and elimination in the Asia Pacific and globally.

Source: Asia Pacific Malaria Elimination Network (APMEN)

Treatment and Management of Malaria Parasite

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QUESTION

What are the treatments and management of malaria?

ANSWER

Treatment is actually part of the strategy for managing malaria, so I will come back to that later. The other main ways in which malaria is controlled is through prevention, diagnosis (followed by treatment if necessary) and education.

1) Prevention:

There are a number of ways to prevent malaria. These can be placed into two categories: medication and vector protection.

For medication, there are drugs you can take to prevent the malaria parasite from developing after someone is bitten by an infected mosquito. These drugs are known as “chemoprophylaxis.”

There are several different kinds, such as doxycycline, mefloquine (marketed as Lariam), atovaquone-proguanil (marketed as Malarone) and chloroquine—the type you use depends on the type of malaria present in the area. For example, in much of Africa and India, malaria is resistant to chloroquine, so this cannot be used as a prophylactic. In parts of Thailand, resistance to mefloquine has emerged. However, if the appropriate type of prophylaxis is used, it is very effective against malaria.

The problem is that these drugs have not been tested for long-term use, can be expensive and may have side-effects. Therefore they are of limited use for people who live in areas where malaria is endemic, and are more appropriate for travelers who are in malarial areas for short amounts of time. However, anti-malarial medication may be used in a very specific way for people at particularly high-risk for malaria, such as pregnant women and young children. In these cases, the high-risk individuals receive a dose or series of doses of malaria medication in order to prevent malaria. This form of prevention is known as intermittent preventive therapy (IPT).

Vector prevention involves protecting oneself against getting bitten by mosquitoes. This can involve wearing long-sleeved clothing in the evenings and at night, when malaria mosquitoes are most active, or wearing insect repellent on exposed skin. Indoor residual spraying, whereby repellent and insecticides are sprayed inside the house, can also be used to bring down the number of mosquitoes.

Another very effective technique for preventing malaria is to sleep under a long-lasting insecticide-treated bednet. The mesh acts as a barrier against the mosquitoes, and the insecticide impregnated in the mesh further repels the mosquitoes and prevents them from biting through the mesh.

2) Diagnosis

Diagnosis is considered a crucial step in controlling malaria, since it ensures that people are receiving correct medication, whether for malaria or for another condition which is causing their symptoms. Currently, the most commonly observed form of diagnosis is through microscopy of thick and thin blood films, which can be stained if necessary. These should be read by a qualified technician to determine both the species of malaria infection and the intensity of parasitaemia (number of parasites in the blood).

More recently, other methods for diagnosis have emerged. These include the use of rapid diagnostic tests (RDTs) which utilize a drop of blood applied to a reagent strip which very quickly reacts to show whether the patient is infected with malaria. While considered generally more sensitive than blood films, some RDTs don’t test for all types of malaria parasite, and many require that the reagents be kept cold in order for the test to be effective, which can be a problem in some developing countries.

Perhaps the most sensitive test for malaria is through PCR, which can theoretically detect a single malaria parasite in a drop of blood, and also determine the species. However, measures of infection intensity require an alternative form of PCR, called real-time PCR, which can be technologically challenging. All forms of PCR require a lot of expensive equipment and reagents, trained technicians and take several hours to run.

3) Treatment

Malaria treatment can be determined based on the diagnostic results, as well as other factors, such as:

  • The area where the infection was acquired and its drug-resistance status
  • The clinical status of the patient
  • Any accompanying illness or condition
  • Pregnancy
  • Drug allergies, or other medications taken by the patient

Most uncomplicated (i.e. not severe) cases of P. falciparum can be treated with oral medication, such as artemisinin-based combination therapies (ACTs). Artemisinin is given in combination with another anti-malarial drug in order to prevent resistance from developing in the parasite. Patients who have complicated (severe) P. falciparum malaria or who cannot take oral medications should be given the treatment by continuous intravenous infusion, with quinine recommended by WHO as the first-line treatment.

Other drugs, which are used in some settings, are considered second-line or alternative forms of treatment. These include:

  • chloroquine (very rarely used for P. falciparum, due to widespread resistance)
  • atovaquone-proguanil (Malarone®)
  • mefloquine (Lariam®)
  • quinine
  • quinidine
  • doxycycline (used in combination with quinine)
  • clindamycin (used in combination with quinine)

In addition, primaquine is active against the dormant parasite liver forms (hypnozoites) and prevents relapses, for patients with P. vivax or P. ovale malaria. Primaquine should not be taken by pregnant women or by people who are deficient in G6PD (glucose-6-phosphate dehydrogenase). Patients should not take primaquine until a screening test has excluded G6PD deficiency.

4) Education

Through education, people living in at-risk areas for malaria transmission can learn about ways to prevent the disease (see above), as well as what to do if they suspect they are infected (i.e. seek diagnosis). Similarly, education is important for travellers visiting malarial areas, so they know the best ways in which to avoid being infected.