Malareich and Pregnancy

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QUESTION

Hi , am 31 weeks pregnant and had to take Malareich as my Anti malaria drug. I did not take the drug until I felt I had malaria, because I had body pains and headaches. Please advise if I will be ok after taking the malareich.

ANSWER

Malareich is a combination drug comprising of sulfadoxine and pyrimethamine, which is one of the medications recommended for treatment of malaria in pregnant women. However it sounds like you took the medication because you thought you had malaria – it is really important to be diagnosed by a doctor. For example, they will be able to ensure that you get the correct type of treatment for the kind of malaria you have. Malareich, for example, is probably not as effective against P. vivax malaria as P. falciparum malaria, but P. vivax is still susceptible to chloroquine, which is another drug that is suitable for the treatment of malaria in pregnant women.

malaria background

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QUESTION

where did malaria come from?

ANSWER

Malaria is a disease caused by a single-celled parasite called Plasmodium. There are many species of Plasmodium, which infect many other animals as well as humans. The types of malaria which infect humans probably evolved from similar Plasmodium species in monkeys and apes; for example, P. vivax is closely related to several species of malaria that infect macaque monkeys in south-east Asia, while P. falciparum, the most severe and deadly kind of malaria, probably evolved from similar infections in chimpanzees and gorillas in central Africa. This transition from other primates to humans occurred many thousands of years ago; further back in time, the types of Plasmodium which infect mammals (rodents can also be infected with Plasmodium) are thought to have jumped over from Plasmodium species which infect birds and reptiles. Even before that, Plasmodium itself seems to have evolved from other types of blood-borne parasites which infect birds and reptiles.

Malaria Symptoms

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QUESTION

What are the symptoms of Malaria?

ANSWER

Symptoms of malaria include fever and flu-like illness, including shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur. Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes) because of the loss of red blood cells. Symptoms usually appear between 10 and 15 days after the mosquito bite. If not treated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs. Infection with one type of malaria, Plasmodium falciparum, if not promptly treated, may cause kidney failure, seizures, mental confusion, coma, and death. In many parts of the world, the parasites have developed resistance to a number of malaria medicines.

For most people, symptoms begin 10 days to 4 weeks after infection, although a person may feel ill as early as 7 days or as late as 1 year later. Two kinds of malaria, P. vivax and P. ovale, can occur again (relapsing malaria). In P. vivax and P. ovale infections, some 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 and begin invading red blood cells (“relapse”), the person will become sick.

Infection with malaria parasites may result in a wide variety of symptoms, ranging from absent or very mild symptoms to severe disease and even death. Malaria disease can be categorized as uncomplicated or severe/complicated. In general, malaria is a curable disease if diagnosed and treated promptly and correctly.

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.

Duration of Malaria Symptoms

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QUESTION

If untreated how long will a person suffer symptoms caused by Malaria?

ANSWER

The answer to that depends a lot on what type of malaria they have as well as their own immune status, and particularly if they have been infected with malaria before. So, for example, P. falciparum is the most severe and deadly kind of malaria, and without treatment, many people who do not have acquired immunity (from previous infections) are likely to die within just a few days. This is the type of malaria that causes the most deaths, and explains why most of the fatalities occur in young children, who have not had the chance to acquire immunity.

In contrast, other kinds of malaria are less severe, and so symptoms can persist before the malaria parasite is naturally cleared by the parasite, usually within 1-2 weeks. In extreme cases, this can last much longer; Plasmodium malariae is the slowest replicating form of malaria, and so frequently causes mild infections which can last weeks, if not months. In some cases, people are infected with low levels of P. malariae for years without even experiencing symptoms, since their own immune system is able to keep levels of the parasite low enough so that they don’t cause noticeable disease.

New Anti-Malarial Drug Target

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An international team of scientists have identified the first reported inhibitors of a key enzyme involved in survival of the parasite responsible for malaria. Their findings, which may provide the basis for anti-malarial drug development, are currently published in the online version of the Journal of Medicinal Chemistry.

Tropical malaria is responsible for more than 1.2 million deaths annually. Severe forms of the disease are mainly caused by the parasite Plasmodium falciparum, transmitted to humans by female Anopheles mosquitoes. Malaria eradication has not been possible due to the lack of vaccines and the parasite’s ability to develop resistance to most drugs.

Led by researchers from the Department of Pediatrics at the University of California, San Diego School of Medicine, the team conducted high-throughput screening of nearly 350,000 compounds in the National Institutes of Health’s Molecular Libraries Small Molecule Repository (MLSMR) to identify compounds that inhibit an enzyme which plays an important role in parasite development: Plasmodium falciparum glucose-6-phosphate dehydrogenase (PfG6PD) is essential for proliferating and propagating P. falciparum.

“The enzyme G6PD catalyzes an initial step in a process that protects the malaria parasite from oxidative stress in red blood cells, creating an environment in which the parasite survives,” said senior author Lars Bode, PhD, assistant professor in the UCSD Department of Pediatrics, Division of Neonatology and the Division of Gastroenterology, Hepatology and Nutrition. People with a natural deficiency in this enzyme are protected from malaria and its deadly symptoms, an observation that triggered the reported research.

The parasitic form of the enzyme (PfG6PD) is what contributes the majority of G6PD activity in infected red blood cells. Because the parasite lives in the blood of a malaria-infected person, the scientists aimed at identifying compounds that inhibit the parasitic form but not the human form of the enzyme. “We didn’t want to interfere with the human form of the enzyme and risk potential side effects,” Bode explained.

Scientific testing had previously been limited by a lack of recombinant PfG6PD. Team members in the lab of Katja Becker, PhD, at the Interdisciplinary Research Center at Justus-Liebig-University in Giessen, Germany produced the first complete and functional recombinant PfG6PD, and researchers led by Anthony Pinkerton, PhD, at Sanford-Burnham Medical Research Institute used it to identify the lead compound resulting from their efforts, ML276.

ML276 represents the first reported selective PfG6PD inhibitor, which stops the growth of malaria parasites in cultured red blood cells – even those parasites that developed resistance to currently available drugs. “ML276 is a very promising basis for future drug design of new anti-malarial therapeutics,” said Bode.

Contributors to the study include Janina Preuss, UC San Diego, Justus-Liebig-University and Sanford-Burnham Medical Research Institute; Esther Jortzik, Stefan Rahlfs and Katja Becker, Justus-Liebig-University; Patrick Maloney, Satyamaheshwar Peddibhotla, Paul Hershberger, Eliot Sugarman, Becky Hood, Eigo Suyama, Kevin Nguyen, Stefan Vasile, Arianna Mangravita-Novo, Michael Vicchiarelli, Danielle McAnally, Layton H. Smith. Gregory P. Roth, Michael P. Hedrick, Palak Gosalia, Monika Milewski, Yujie Linda Li, Eduard Sergienko, Jena Diwan, Thomas D.Y. Chung, and Anthony B. Pinkerton, Sanford-Burnham.

The study was supported by the National Institutes of Health (1R21AI082434), the Deutsche Forschungsgemeinschaft, and an NIH Molecular Libraries grant (U54 HG005033) to the Conrad Prebys Center for Chemical Genomics at Sanford Burnham Medical Research Institute, one of the comprehensive centers of the NIH Molecular Libraries Probe Production Centers Network (MLPCN).

Source: University of California, San Diego Health Sciences

Genetically Engineered Bacteria Prevent Mosquitoes From Transmitting Malaria

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Researchers at the Johns Hopkins Malaria Research Institute have genetically modified a bacterium commonly found in the mosquito’s midgut and found that the parasite that causes malaria in people does not survive in mosquitoes carrying the modified bacterium. The bacterium, Pantoea agglomerans, was modified to secrete proteins toxic to the malaria parasite, but the toxins do not harm the mosquito or humans. According to a study published by PNAS, the modified bacteria were 98 percent effective in reducing the malaria parasite burden in mosquitoes.

“In the past, we worked to genetically modify the mosquito to resist malaria, but genetic modification of bacteria is a simpler approach,” said Marcelo Jacobs-Lorena, PhD, senior author of the study and a professor with Johns Hopkins Bloomberg School of Public Health. “The ultimate goal is to completely prevent the mosquito from spreading the malaria parasite to people.”

With the study, Jacobs-Lorena and his colleagues found that the engineered P. agglomerans strains inhibited development of the deadliest human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98 percent within the mosquito. The proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84 percent.

“We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria,” said Jacobs-Lorena.

Malaria kills more than 800,000 people worldwide each year. Many are children.

The authors of “Fighting malaria with engineered symbiotic bacteria from vector mosquitoes” are Sibao Wang, Anil K. Ghosh, Nicholas Bongio, Kevin A. Stebbings, David J. Lampe and Marcelo Jacobs-Lorena.

The research was supported by National Institute of Allergy and Infectious Diseases, the Bill & Melinda Gates Foundation, the Johns Hopkins Malaria Research Institute and the Bloomberg Family Foundation.

Source: Johns Hopkins Bloomberg School of Public Health

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 Fever and Recovery

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QUESTION

My 21 year old daughter spent 4 months on a study abroad program in Dakar. A week before returning home she started having night fevers and would complain of retrosternal pain and rib and neck and shoulder pain. The next day she would be fine.

The episodes came every other day and eventually it occurred to her that it might be malaria. It was evening so she went to a pharmacy for a rapid diagnostic test which they didn’t have but they felt she had malaria based on her symptoms and gave her a 3 day course of artesunate-mefloquine.

She returned to the United States and a day after taking her last dose, she was seen by a physician and tests were done which showed that she had contracted Plasmodium falciparum malaria. Other than the smears, all her lab tests and CXR were normal and there were no abnormal findings on physical exam, in fact she was the picture of health.

We were told that she was cured and that no follow up was necessary and that she could continue with her planned trip to Thailand the next day. About 6 hours before boarding the plane to Bangkok she developed fever of 100.9 but had absolutely no other symptoms or pain. About an hour later she had a bout of diarrhea. She had one more low grade fever on the flight (99.8). I spoke to another physician who seems more familiar with malaria and was told that she is not actually cured and may continue to have episodic fevers and symptoms for a while or it’s possible she was just suffering from an ordinary garden variety gastrointestinal bug.

I have many questions. I understand that her malaria is the most virulent type. How is it that all her lab work and physical exam is normal 1 day after completing treatment? Can we expect it to remain normal? What causes the episodic fevers if she is supposedly cured? She is on doxycycline again prophylactically (which she was on in Senegal) while in Thailand. Should she be on something else since she did contract malaria on doxycycline? (She took it religiously). Thanks for any advice. She will be seeing a physician in Bangkok ASAP, but since I won’t be there to ask questions, I am hoping you can give me some answers. Your site is the best information I have found on malaria.

ANSWER

Many thanks for the comprehensive information you have provided regarding your daughter’s condition. Even though your daughter did have the most virulent form of malaria, she was very smart to seek treatment relatively promptly, and lucky to receive appropriate medication (artemisinin-based combination therapies, such as artesunate-mefloquine, are recommended by the World Health Organization as first-line treatment against malaria). It is likely due to this prompt and effective action that her lab tests and blood parameters were all normal so soon after treatment; had she waited longer for treatment, the consequences could have been much more severe. No resistance to this medication has been detected in Africa as of yet, so she should be fully cured and thus her health should remain stable; a blood smear, where her blood is examined under a microscope, can determine this; this is a very standard procedure so could easily be carried out in Thailand if she wants.

Fever is a side effect of the body’s immune system responding to a disease threat, so it is not uncommon for some symptoms to carry on after treatment. In addition, mild side effects of anti-malarial medication can often mimic the symptoms of malaria itself, including fever and nausea.

Given also the (entirely reasonable) possibility of an additional, unrelated stomach bug, I suspect that your daughter has successfully beaten off this malaria attack, and while she should remain vigilant if similar symptoms arise again, her health in the future should not be adversely affected at all by this episode.

Also, as mentioned briefly above, medical professionals in Thailand should be well equipped to diagnose and treat malaria if she suspects she has been reinfected. It is worth noting that malaria in south-east Asia has shown signs of resistance to mefloquine (as well as other drugs, such as chloroquine and sulfadoxine-pyrimethamine), so if she does require treatment while there, she should make sure the medication they provide does not contain any of the afore-mentioned compounds.

Regarding doxycycline, it’s great that your daughter took it religiously—that is certainly the first step towards protection. Randomized placebo controlled trials have shown it is between 92-96% effective in preventing P. falciparum malaria, which is very good, but obviously not 100% perfect – even when taken perfectly, some infections do occur. In addition, there is some data which suggests that dairy products, taken together with doxycycline, may limit  the uptake of the drug. This is rarely communicated to patients, who are instead contrarily told sometimes that taking the pills together with dairy products can reduce side effects! As such, please let your daughter know that she should avoid dairy products for 2-3 hours around the time she takes her doxycycline.

Malaria Treatment with Fansidar

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QUESTION

My husband has Malaria following a trip to Kenya and has had a fever for three days. We are in Russia and the only drug available at the pharmacy was Fansidar (we also have some Doxcycyclin). He took three Fansidar tablets last night and feels better but the fever has still not completely gone. What should we do? Take more Fansidar? Thanks for your help.

ANSWER

A single dose of three tablets is the correct amount for an adult over 45kg in weight—do not take any more. Unfortunately, Fansidar is not recommended as the first-line drug against malaria any more since many strains of P. falciparum (the most dangerous type of malaria, and the most common type in Kenya) now have resistance to Fansidar. This could be one reason why the treatment is not fully successful, though it could also be that the treatment has worked, but it will take a day or two more before your husband fully recovers.

Make sure your husband takes in plenty of fluids, and anti-inflammatory drugs such as ibuprofen might help with the fever and any aches he could also be suffering from.

If your husband is still feeling sick after a few days, you should try to have another blood test to see if the malaria parasites are still present in his blood. If you, you should try to find an artemisinin-based combination therapy, such as Coartem, Duo-Cotecxin or Alu. These are the most effective medications against malaria that are currently available, and are recommended as first-line treatment by the World Health Organization (for uncomplicated malaria).