Treatment and Management of Malaria Parasite

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.

Malaria Prevention

QUESTION

What is malaria and the preventive measures?

ANSWER

Malaria is a disease caused by single-celled parasites of the genus Plasmodium. There are currently five species which cause disease in humans, and while each is slightly different, they all act in basically the same way, and cause similar symptoms. Of the five, the most dangerous is Plasmodium falciparum, which can lead to death in a matter of days if not treated promptly.

In terms of prevention, the same basic methods are used to prevent all types of 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.

Malaria Prophylaxis in Ghana, Africa

QUESTION

My husband will be traveling to Ghana soon. We have Mefloquine and Primaquine. Which one do you think is best for prophylaxis in Ghana? He also has Fansidar, but we understand it’s best not to use this for prophylaxis. Thank you for your help!

ANSWER

There are positives and negatives associated with both of these medications. Mefloquine is recommended for travelers in Ghana (whereas the Centers for Disease Control does not explicitly recommend primaquine for this area, since primaquine is particularly effective against Plasmodium vivax malaria, which is almost completely absent from West Africa), and only has to be taken once a week (primaquine must be taken daily).

A disadvantage with mefloquine is that you must start taking it 2 weeks before your trip, whereas primaquine can be started as little as 1-2 days before travel; mefloquine is also not recommended for people with a history of psychiatric or mental problems, as it can cause severe side effects. Even healthy individuals often report disturbing dreams or increased agression/anxiety while taking mefloquine. However, one major disadvantage to primaquine is that you must be tested for G6DP deficiency prior to taking it – your husband may have already done this, prior to being prescribed the drug. People with G6DP deficiency should not take primaquine.

Overall, the decision comes down to personal preference, though from a disease perspective, mefloquine would probably be the better choice for travel to Ghana, given the higher prevalence of P. falciparum malaria in this region, as opposed to P. vivax. Other options to consider would be atovaquone-proguanil (Malarone – expensive, taken daily, but very effective and very well tolerated by most people, with very low side effects) or doxycycline (very cheap, taken daily, is an antibiotic so can prevent some other infections but often results in sun sensitivity, which can be a problem in the tropics). Both of these can be started 1-2 days before arriving in the malarial area.

After you come back, I would be very grateful if you could take our malaria medication side effects survey, as we are very interested in hearing from our readers what their experiences with malaria prophylaxis and treatment have been.

Persistent Antibodies to Malaria?

QUESTION

I had malaria as child, more than 30 years ago. It was successfully treated with no relapse. I have since travelled to malaria- endemic countries, but the last time was over 3 years ago. No symptoms. I recently donated blood and routine screening has detected malaria antibodies. How long do the antibodies persist?

ANSWER

Based on your experience, I would say at least three years! While I doubt your antibodies would persist since your infection as a child, it is more likely that in your more recent trips to malarial areas you have been re-exposed to the parasite, but for whatever reason, the infection didn’t progress into a full-blown episode of malaria. This could well be due to some residual immunity from childhood, or you just received a light enough infection that your general immune system was able to fight off. Either way, this would have produced new antibodies against malaria, which were picked up by the blood screen.

The length of time antibodies persist is important information in the control of malaria, since serological tests (which detect antibodies) can be used for screening of populations in low-transmission environments, but their efficacy is reduced in locations where people have been treated for malaria but their antibodies persist. Also, understanding how antibodies are created and maintained in the body is necessary for gaining an appreciation of how preventive measures, such as bednets, might potentially leave populations more vulnerable to malaria later on, through lack of acquired immunity.

Malaria in the United States, Years Later

QUESTION

For years, I have questioned what sickness I got years ago after a series of bug bites in a bayou in New Orleans. I’ve just read the symptoms described here and they fit everything I was suffering with. I even had problems with my liver, but I was never tested for Malaria because I had immediately left New Orleans for Italy. I never thought of mentioning it. This mysterious illness cropped up in different forms over the years and really I was never the same after it. It has been almost 12 years, and I still suffer from recurring illness which antibiotics help for a while, but it always comes back. Could it be that I have had Malaria in my system all this time?

ANSWER

While malaria was officially eradicated from the US in the 1950s, certainly the swamps and bayous of Louisiana and the rest of the Gulf were a key habitat and a major source of transmission prior to eradication. I just found a news report in the New York Times from October 1883 which reported 16 deaths due to “malarial fever” in the previous week alone!

While these days, virtually all of the 1,500 or so cases of malaria observed in the US every year are attributed to overseas travel, in 2002 a handful of cases of malaria in northern Virginia were believed to be due to local transmission. Prompt treatment, personal protective measures (such as screening houses) and vector control quickly quelled that mini-outbreak.

Given this history along with your symptoms, and particularly your recurrent episodes of fever, I would not rule out malaria, obtained in Louisiana, as a possibility! You should talk to your doctor about the possibility of a serological test for the antibodies against malaria—if positive, you should try to have a blood test done next time you have the recurrence of symptoms. If malaria is confirmed, you should report your case to the Centers for Disease Control (CDC) Domestic Malaria Unit, which monitors all malaria cases in the US.

Malaria Effects on the Body

QUESTION

What are the effects of malaria on the body?

ANSWER

Malaria has a number of effects on the body. The parasite passes from the blood (where it enters via the bite of an infected mosquito) into the liver, where it reproduces and changes form. After a period of 1-4 weeks (usually – it can be longer) in the liver, the malaria parasite re-enters the blood and begins to infect red blood cells, undoing more reproduction inside the cells and then, in synchrony, bursting out once the cycle is complete. This process of reproduction and destroying red blood cells results in a build-up of toxins and debris in the blood; the resultant immune reaction produces side effects which are the common observable symptoms of malaria, such as fever, chills, nausea and aches.

One particular type of malaria, Plasmodium falciparum, is also able to modify the surface of red blood cells it infects. It causes these cells to become “sticky”, so they lodge in the small blood vessels leading up to major organs. This build-up is called sequestration, and results in reduced blood flow and oxygen deprivation in the organs. When sequestration occurs in the blood vessels in the brain, the patient may experience impaired consciousness, psychological disruption, coma and even death – this manifestation is called “cerebral malaria”.

If diagnosed and treated promptly, the malaria parasites in the blood can usually be killed rapidly and the patient will soon enjoy a complete recovery. With two forms of malaria, P. vivax and P. ovale, the parasite can remain dormant in the liver for months or even years, resulting in relapse of disease at a later date. To prevent this from occurring, patients with these types of malaria can sometimes take primaquine, a drug which kills the liver stages of the malaria parasite as well.

Affected by Lariam… How to Help?

QUESTION

Five years ago my husband was working in Africa. To get protection against malaria, he took Lariam. Since then, he became strange, poor sleep, constant depression, insecurity and distrust, inability to concentrate, forgetfulness, anger, strange behavior.

I insisted to see a doctor, but he refuses, saying that this is the problem of diabetes (he has type 2 diabetes) and stress at work.We living 12 years together, I can clearly see it’s more than that.
I tried many different things to prove that he was effected by Lariam to get help. But it did not work. All that I got “I m not crazy.” He’s not but not normal either. it’s ruining our family and lives. We have 2 kids.

Is there any method for establishing the presence of problems (blood test, etc.)?  I was hoping that after he stopped taking Lariam he will feel better. It took 4 years, but no significant changes. How to help him, and is it possible?

ANSWER

Thank you for your question—I am sorry to hear that your husband has been so negatively affected by Lariam. His symptoms are certainly consistent with some of the more unpleasant side-effects of mefloquine (the generic name for Lariam), which have been well reported over the years, and which many sufferers claim have continued long after they have stopped taking the drug.

Lariam was the anti-malarial drug of choice for the US military for many years, and a significant number of servicemen returning from Somalia and Iraq have reported back to the Army’s Surgeon General’s office regarding their on-going psychological symptoms. You can read a report about some of these Lariam cases here.

Roche, the pharmaceutical company that makes Lariam, has recently conceded some of the severe side effects that are associated with the drug, and “Lariam-induced psychosis” is a valid medical diagnosis for people who present with symptoms of paranoia, aggression, anger, hallucinations and other psychological side effects. As such, I think it is important for your husband to realise that you don’t think he is crazy, but that he might be suffering from the late-lasting after effects of a medication, similar effects to that felt by hundreds of US servicemen and other people who have taken Lariam.

Showing him the above document, or many other reports of people will long-lasting Lariam side-effects, might help him realise this is not about being crazy, but about side effects over which he had no control. If he is willing to see a psychiatrist, with the understanding that what he is experiencing is not his fault at all, then you might be able to find some solutions to his behavioural changes.

 

Malaria and Pregnancy

QUESTION

Can your baby become immune if you’re pregnant and you have malaria?

ANSWER

Some of the protective antibodies that the mother produces when she has malaria can pass to her baby via the placenta. There is also evidence for immune system “priming” in foetuses when their mothers have been infected my malaria during pregnancy. However, these potentially protective effects are usually far outweighed by the negative effects of malaria during pregnancy.

Due to changes to the mother’s immune system and also perhaps due to the creation and physiology of the placenta, pregnant women are very vulnerable to malaria. For reasons which are not fully understood, women experiencing their first pregnancy (primagravidae) are most susceptible to malaria and their foetuses are most likely to have severe effects. These effects vary depending on the immune status of the mother and whether she is from an endemic or low transmission malaria environment, but typical results include low birth weight, anaemia and spontaneous abortion—abortion rates due to malaria can vary between 15-70%.

There is also the risk (up to 33% in some studies) that malaria will pass directly from the mother to the baby, either through the placenta or in blood during childbirth—this is called “congenital malaria,” and can manifest as early as 1 day after delivery but a late as months after. The symptoms are similar to that of adult malaria, with fever, anaemia, lethargy, etc.

Given these negative effects, it is very important to protect pregnant women against malaria, and bednet distribution schemes in many places target these women. In high transmission settings, women may also be offered intermittent preventive therapy (IPT) which consists of at least two doses of anti-malarial medication, usually once during the second and once during the third trimester.

Sterilizing Mosquitoes to Fight Malaria

QUESTION

Is it possible to breed mosquitoes in the laboratory and then sterilize them and release them into the environment in order to reduce their rate of reproducing.

ANSWER

That is a very good question, and indeed efforts to genetically modify mosquitoes in order to control the various diseases they transmit are underway in many laboratories across the world.

For almost 15 years, scientists have had the ability to modify mosquitoes so that they are sterile. The aim, as you rightly describe, is then to release these sterile mosquitoes into the wild in order to reduce numbers. If the gene that causes sterility can be passed to future offspring, without any reduction in survival of the insect, then the eventual result will be a total population extinction.

To date, many of the major mosquito disease vector species have been successfully genetically modified, though there are many fewer instances of field testing of these modified insects. For example, in 2000/2001, a World Health Organisation-led project in India created sterile mosquitoes of one species of each of the three main disease vector genera: Culex, Aedes and Anopheles, the latter of which acts as vectors for malaria. However, the project did not, in the end, release any of the modified Anopheles vectors into the wild.

While many scientists applaud the benefits of this approach (such as being very species-specific and being more environmentally friendly than spraying), there are also causes for caution. For example, there are concerns that the loss of mosquitoes in the food chain will have a negative impact on animals that rely on them for food. Similarly, if mosquitoes vanish from an ecosystem, their “niche” may be filled by another organism that is equally or even more dangerous and destructive, such as a crop pest or another disease vector. There is also a worry that changing mosquitoes may have unexpected and dangerous effects on the disease itself, for example forcing it to evolve into a more severe disease or changing its epidemiological patterns in ways we cannot predict in advance.

Finally, not all scientists are convinced that the approach will work in the first place—the sterile mosquitoes will have to survive equally well or better than normal mosquitoes in order to establish in the population, and must be equally or more successful at reproducing. As such, while a lot of money is being poured into GM mosquitoes, it is still the center of vigorous debate.

Perhaps the best indication of this controversy came last year, when Oxitec, a British company, released sterile Aedes aegypti mosquitoes on the Cayman Islands. These mosquitoes are the vectors of dengue fever, and so all eyes are on this study to see whether indeed sterile mosquitoes can survive in a population, and if they do, what other effects they will have longer term on the population size of mosquitoes and the rest of the ecosystem. You can read more information about that here: Oxitec: GM Mosquito Factory.