P. knowlesi versus P. falciparum: Treatment and Prevention

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QUESTION

I would like to know about the P. knowlesi – treatment compared to P. falciparum? preventive medicine?

ANSWER

At this point in time, P. knowlesi is completely susceptible to chloroquine, and so can be treated successfully using this drug. P. falciparum, on the other hand, is known to have widespread resistance to chloroquine, and so the World Health Organization recommends that chloroquine should not be used to treat P. falciparum malaria. Instead, for non-complicated malaria, the WHO recommends treatment with artemisinin-based combination therapies (ACTs). These drugs can also be used against other forms of malaria, including P. knowlesi, particularly if the hospital also treats cases of P. falciparum regularly and so has supplies of ACTs on hand. One study even showed that treatment with ACTs (specifically artemether-lumefantrine) was more effective than chloroquine in treating P. knowlesi. Severe cases of either infection should be treated with intravenous artesunate or quinine.

Prevention for both is roughly similar – chemoprophylaxis should be taken by people travelling to an area where transmission of these types of malaria occurs. However, given P. knowlesi‘s susceptibility to chloroquine, this drug is effective as a prophylactic for this malaria species, whereas it is not appropriate for P. falciparum, given high levels of resistance. In terms of prevention of mosquito bites, this differs due to the types of mosquito vectors each of these species of malaria uses. P. knowlesi is only found in south-east Asia, where the mosquitoes that transmit it tend to be forest dwelling. As such, people who spend time in the forest in the evening and at night are most at risk of contracting P. knowlesi. Wearing long-sleeved clothing and insecticide while in the forest may help prevention in this case. P. falciparum is found throughout the world, and uses many different species of mosquito vector. In Africa, the mosquitoes which transmit P. falciparum tend to rest indoors and thus bite people at night while they are sleeping. Therefore, in these settings, it is especially beneficial to sleep under a long-lasting insecticide treated bednet. Indoor residual spraying, which coats the inside walls of a house with insecticide to kill indoor-resting mosquitoes, can also be beneficial.

Antimalarial Drugs During pPregnancy

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QUESTION

What is the safest antimalarial drug to be used by a pregnant woman in her second trimester?

ANSWER

With regards to treating malaria, intravenous artesunate (or quinine, if artesunate is not available) should be used for the treatment of severe/complicated Plasmodium falciparum malaria. Signs of severe and/or complicated malaria include impaired consciousness, organ failure, abnormal bleeding, hypoglycemia, severe anemia and/or inability to ingest medication orally. Treatment for uncomplicated malaria (where the above signs are absent) in pregnant women is usually chloroquine for P. vivax, P. ovale, P. knowlesi and P. malariae, as well as for P. falciparum if there are no reports of this parasite being resistant to chloroquine in the area. In places where P. falciparum is resistant to chloroquine, quinine and clindamycin should be used to treat this parasite in pregnant women.

As for preventative anti-malarials (chemoprophylaxis), if a pregnant woman is travelling to an area where only P. vivax, P. ovale, P. knowlesi, P. malariae or chloroquine-sensitive P. falciparum is transmitted, then she should take chloroquine to prevent malaria. In areas where P. falciparum is resistant to chloroquine, mefloquine is also suitable during pregnancy. Note that in some areas of south-east Asia, there are areas where P. falciparum is resistant to mefloquine, which may prevent its suitability as a prophylactic in this region. Preventing malaria during pregnancy is crucial, since the mother, particularly if it is her first baby, is especially vulnerable to the parasite. Moreover, malaria can have a negative impact on the fetus.

About Malaria Proteins

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QUESTION

Please tell about about malarial causitive proteins.

ANSWER

I’m not sure what your question is, as malaria is not caused by a protein, but rather by a single-celled parasite called Plasmodium, which contains many different types of proteins. Some of these are indeed used for entering host cells and thus causing disease. Many of these proteins, and particularly ones on the surface of the malaria parasite, induce the host’s immune system, and so are called antigens. One of the most well known malaria antigens is called the Duffy antigen, and it is found on two types of malaria (Plasmodium knowlesi and Plasmodium vivax). It is used by the parasite to invade host red blood cells, and it is interesting because many populations of people in Africa have genetic changes in the parts of the red blood cell which the Duffy antigen binds to. This means these people, called Duffy negative, are much less susceptible to these types of malaria than people who are so-called Duffy positive and have normal red blood cells.

Malaria Prophylaxis for Indonesia

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QUESTION

I have been working a 4-week rotation between the USA and East Kalimantan (Borneo) for about 2 years. While on Borneo, I am in the jungle much of the time. I have never contracted malaria. I am embarrassed to say I thought I had been inoculated for malaria when I first started working here. I just spent 10 days in a hospital last month fighting a blood degenerating viral infection not unlike hemophiliac dengue. Is there a preferred Rx I should take for malaria? I have no allergies to medicines that I am aware of. I am 57 year-old male.

ANSWER

Given the amount of time you spend in rural areas of Borneo, you probably should consider anti-malarial medication to prevent infection. There are three types of drug which are recommended against malaria in Indonesia: atovaquone-proguanil (sold as Malarone), mefloquine (sold as Lariam) and doxycycline. Each has pros and cons: Malarone and doxy have to be taken every day, while Lariam is only taken weekly, which might make it more convenient. However, both doxy and Lariam should be taken for a full 4 weeks after leaving the malarial area, while Malarone is only taken for a week after leaving.

In my opinion, Malarone has the fewest and mildest side effects (though some people complain of upset stomachs and disturbed sleep patterns), while doxycycline is sometimes a problem in the tropics since it can cause sun sensitivity. Lariam is not recommended for people with a history of mental illness, and has been reported to have psychiatric side effects, including nightmares, hallucinations and even altered behavior. Of the three, Malarone is the most expensive, and doxycycline usually the cheapest.

In terms of taking them long term, I don’t know of any studies that look at long term usage of Malarone (it is expensive enough that I doubt anyone takes it for very long trips!), while people do safely take doxycycline for periods of several months, and Peace Corps volunteers and American expats routinely take Lariam for periods of several years.

Of course, many people living long term in malarial areas do not find it convenient to take pills to prevent malaria, and focus on other preventative measures, mainly revolving around killing mosquitoes and avoiding being bitten. Sleeping under a long-lasting insecticide treated bednet is one such method, which is cheap, easy and very effective.

Incidentally, the area you are in is interesting from a malaria point of view since it is one of the few places where transmission of Plasmodium knowlesi occurs. This is a type of malaria which was thought to be only present in macaque monkeys, until human cases started becoming more prevalent a few years ago. Now it is considered a “human” type of malaria, and an emerging threat in south-east Asia. It’s important to be aware of it as the mosquitoes which transmit it tend to be forest-dwelling (since that is where the macaques live), and although very easily treated with chloroquine or other anti-malarials, an infection can progress rapidly into quite severe disease.

If you suspect you might have malaria at any point, therefore, it is crucial to get out and get tested at a clinic or hospital, where they can promptly treat you if you test positive. Be aware also that if tested via microscopy, P. knowlesi can often be confused with P. malariae or P. vivax; while the initial treatment is likely to be the same for all three, if you had P. vivax you might be told about taking an additional medication, called primaquine, to prevent future relapses, whereas relapses do not occur with P. knowlesi.

New Malaria Parasites

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QUESTION

I heard researchers have found a new malaria parasite—what is the name?

ANSWER

New malaria parasites are found quite regularly—the parasite that causes malaria, Plasmodium, actually infects birds, reptiles, rodents and non-human primates like monkeys and apes as well as humans. As such, non-human forms of malaria are discovered relatively frequently in other species. For example, a few years ago, some researchers looked at malaria in apes in Central Africa, and found a new species in gorillas, which is so new it has not even been fully described to science yet, and so remains unnamed! It is thought to be very closely related to Plasmodium falciparum, which is the most dangerous type of malaria in humans. Also recently, two new species were observed in chimpanzees, also in Central Africa, and names P. billcollinsi and P. billbrayi.

Even in humans, new infections are sometimes observed. One which has gained a lot of recent attention is not a new species, but what seems to be increasing numbers of cases of a monkey type of malaria (called P. knowlesi) in humans. It is unclear whether this is due to changes within the parasite, or changes to the landscape which might be creating more favorable conditions for the transmission of this malaria to humans. It is even possible that this malaria has always infected humans, and so this is not a new development, but due to diagnostic issues, it was mistaken for other, human malaria species, such as P. vivax and/or P. malariae.

Death from Malaria: Humans and Other Primates

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QUESTION

If not treated in some form, do most who acquire malaria die? What about primates, such as orangutans that live in the wild and would not be treated as such. Do they die or do they become chronically ill within period of remission?

ANSWER

That’s a really good question, and the answer is: it depends! In humans, the most deadly form of malaria is Plasmodium falciparum—when infected for the first time, if not given prompt treatment, many people will die from this infection. However, after repeated infections, people develop acquired immunity to the P. falciparum parasite which means they are increasingly able to survive subsequent infections without treatment. This reason of acquired immunity is why young children, who do not yet have immunity, and visitors to malarial areas tend to have the most severe infections and most require treatment in order to survive.

The other three major forms of human malaria, P. vivax, P. malariae and P. ovale, are generally less deadly, though they can also result in death in some circumstances if the person does not have immunity and is not treated. Although much less common than P. falciparum, P. knowlesi is the fifth type of malaria to infect humans (it is more commonly an infection of macaque monkeys in south-east Asia), and because it replicates in a 24-hour cycle (the other types of human malaria have either a 48 or 72 hour cycle), high parasite loads can establish very quickly, leading to severe disease. As such, P. knowlesi is also quite dangerous and a high proportion of untreated cases result in death.

It is great that you ask about malaria in other primate species—as with humans, some forms of malaria are tolerated reasonably well while others are more deadly. It varies depending on the type of malaria as well as the species of primate. So, for example, P. knowlesi in long-tailed macaques is rarely observed to cause severe disease. In fact, infected macaques sometimes don’t even appear to have any symptoms. In contrast, if rhesus macaques are experimentally infected with P. knowlesi (the transmission range of this type of malaria does not overlap with the natural range of rhesus macaques), almost 100% of them will die without treatment.

You ask specifically about orangutans: one problem is that it is unclear which, and how many, species of malaria infect these apes. Past research has uncovered two species which are thought to be unique to orangutans (namely P. silvaticum and P. pitheci) while molecular studies have also shown non-specific species, namely human P. vivax and macaque P. cynomolgi and P. inui. As such, while originally orangutan malaria was thought to be not very dangerous to these apes, more recently there have been reports of orangutans showing very human-like symptoms suggestive of more advanced disease. However, rarely do studies link symptoms and observations of parasites in the blood, so it is unclear which parasites are causing these symptoms, if indeed it is malaria at all (in some sanctuary/rehabilitation center settings, orangutans exhibiting malaria symptoms have responded positively to treatment with anti-malarials, though this is not definitive evidence that their symptoms were caused by malaria).

So, in short, more research should be done on wild primates, particularly using molecular tools, to ascertain accurately what species of malaria they are infected with, and whether they are associated with symptoms and/or severe disease.

Malaria Parasite

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QUESTION

Which parasite transmits malaria?

ANSWER

Malaria is caused by a parasite called Plasmodium, which is transmitted via the bite of an infected mosquito. The parasite passes into the blood of the human patient when the mosquito bites, via its saliva. There are five species of Plasmodium which normally infect humans: P. falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi. 

Malaria with Liver and Kidney Problems

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QUESTION

Can someone please tell me what kind of malaria this is. What part of the body it attacks, e.g., cerebral? Patient presenting with liver and kidney “problems”. What could these be?

ANSWER

I am not sure I fully understand your question, but the type of malaria which is associated with cerebral malaria, and also tends to have the most adverse effects on other organs (such as the kidneys) is Plasmodium falciparum. However, all species of malaria go through the liver as part of their life cycle, so all may invoke some kidney problems. The four other types of malaria which infect humans are P. vivax, P. ovale, P. malariae and P.knowlesi.

Classification of Malaria

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QUESTION

Classification of malaria

ANSWER

Malaria is caused by a single celled protist of the genus Plasmodium. This genus 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).

What is Malaria?

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QUESTION

what is malaria?

ANSWER

Malaria is a serious and sometimes fatal disease caused by a parasite, of the genus Plasmodium, that infects a certain type of mosquito (of the genus Anopheles) which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. Four kinds of malaria parasites can infect humans: Plasmodium falciparum, P. vivax, P. ovale, P. knowlesi and P. malariae. Infection with P. falciparum, if not promptly treated, may lead to death. Although malaria can be a deadly disease, illness and death from malaria can usually be prevented.