Drugs to Treat Pregnant Woman with Malaria

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QUESTION:

What are the drugs for a pregnant woman who has malaria for the first to third trimester?

ANSWER:

The treatment of malaria in pregnant women has become more challenging in recent years, as many types of malaria are developing resistance to the standard arsenal of drugs. In locations where the dominant form of malaria is still chloroquine-sensitive, chloroquine can be used safely throughout pregnancy.

However, given the high levels of chloroquine-resistance, other drug regimens may be required. Currently, first-line treatment options for uncomplicated malaria caused by Plasmodium falciparum (many strains of which are resistant to chloroquine), is quinine plus clindamycin (doxycycline is contraindicated in pregnant women). In the second and third trimesters, artesunate plus clindamycin can be administered, or the artemisinin-based combination therapy (ACT) commonly used in that region, although some of these combinations, particularly those containing artemether, have limited safety testing in pregnant women. In general, the paucity of controlled, randomized trials has posed a problem to creating safe and effective recommendations for the treatment of malaria in pregnant women.

Diagnosis of malaria or another condition?

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QUESTION:

Patient is responding to malaria intravenous medicines but the blood test are not showing any strains of malaria parasites.
Is it possible it is malaria or some other disease?

ANSWER:

I’m afraid it is hard to answer this without more information regarding what steps have been taken to diagnose infection, what medication is being given, and what other clinical information is available. Intravenous medication for malaria is usually quinine or artesunate, and it is unlikely that any medical institution or practitioner would give these unless they had seen malaria on testing, as these agents are generally reserved for severe disease. Another thought is that they are using doxycycline, which is an antibiotice with a broader spectrum of use, and the patient’s improvement is due to the drug taking care of something else other than malaria (Babesia, Bartonella, Borrelia).

Causes of malaria, treatment with drugs and emerging resistance

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QUESTION:

What is malaria and what causes it besides bacteria? What is the name of the causal agent for malaria, which drug is used to cure it and how do the pathogens become resistant to the drugs?

ANSWER:

There are many questions in there! Malaria is actually caused by a single-celled animal, called a protozoan; it’s not a bacterial disease. There are different species of these protozoans, which form a genus called Plasmodium; the different species cause different types of malaria, for example Plasmodium falciparum, the most deadly and severe form, and Plasmodium vivax, which is widespread throughout the world but is a less acute infection. These different forms of malaria are each treated with different medications, depending on what is most effective and available; P. vivax, for example, can be treated with chloroquine, whereas in many places, P. falciparum has become resistant to this drug. In areas where resistance to chloroquine has emerged, other drugs are used; in Africa, artemisinin-based combination therapies (ACTs) are commonly used against chloroquine-resistant P. falciparum. Other drugs used to treat malaria include quinine compounds such as quinine sulphate, mefloquine, sulfadoxine-pyrimethamine and medications combining proguanil with atovaquone (marketed as Malarone).

The emergence of resistance to these drugs is a worrying phenomenon with respect to malaria; it is such a widespread and deadly disease, that the consequences of failed treatment are very high. Resistance can be caused by many factors, at the level of the drug, the human host, the mosquito host and also the malaria parasite itself. For example, poor drug compliance during treatment can lead to a failure to clear an infection completely, allowing the remaining parasites, which were less susceptible to the drug, to survive and reproduce. With successive generations, natural selection will lead to the evolution of strains of malaria parasites which are firmly resistant to that drug. The same process occurs when mass drug administration programmes, for example in areas of high malaria endemicity, give people sub-therapeutic doses of medication (in other words, doses of the drug that are too low to kill the parasite). Another problem is when people are not checked for their infection status after having been treated for malaria; if treatment fails for some reason, they will still have parasites in their blood, and should be treated again to ensure that all the malaria has been killed. If this doesn’t happen, the parasites can carry on reproducing, as in the processes described above. For these reasons, it is crucially important for people to be given accurate doses of medication, to ensure that they complete the full course of treatment, and that once treatment has been completed, they are accurately tested as negative for the malaria parasite. Finally, there are factors related to the affinity of the malaria parasite to its vector mosquito hosts which can lead to the emergence of drug resistant strains. For example, it has been shown that strains of malaria which are resistant to chloroquine are better able to survive and reproduce inside their mosquito hosts, leading to a greater population size of resistant parasites compared to drug-susceptible ones. It is for these reasons that malaria treatment and control programmes are now being very careful with the ways in which they administer drugs and monitor infections, in order to limit any further reisstance developing; similarly, pharmaceutical and biochemical researchers are constantly on the look-out for new compounds or methods of killing malaria parasites, which can be developed into new forms of treatment.

In which country did malaria start?

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QUESTION:

In which country did malaria start?

ANSWER:

That’s an interesting question! In terms of the evolution of the disease, the different types of malaria probably evolved in different places; it is hypothesised for example, that P. falciparum evolved from a related strain of malaria that is found in gorillas in central Africa, so the human form also probably originates from that area. Although an exact date for the origin of P. falciparum is still under debate, it was probably sometime around 10,000 years ago,  long before modern countries existed in the region!

As for when malaria was first recorded in human populations, it was known in ancient China, as long ago as 2700 BCE, when the ancient Chinese medical text, Nei Ching, was written. Two and a half thousand years later, in around 200 BCE, there are descriptions of the use of Artemisia annua for the treatment of malarial-type fevers; extracts from this plant, known as artemisinins, are still used for the treatment of malaria today.

Malaria was also known from Europe by the 4th century BCE when it was described by ancient Greek writers. The Romans too were aware of malaria and the risks it posed; they even associated the disease with stagnant water (required by mosquitoes to breed, though it is unclear whether they actively understood the association between mosquito bites and the fevers), which led to extensive public drainage works in order to eliminate bodies of standing water.

Given the lack of written histories, it is more difficult to determine the earliest understanding of malaria in the Americas. However, when the Spanish arrived in the 15th century, they learned of local remedies that the indigenous populations had for various fevers; one of these natural medicines was the bark of a tree of the genus Chichona. More commonly called quinine, this compound is still used as an anti-malarial in modern times.

Nowadays, vector control measures, efficient health monitoring systems and treatment availability has much reduced and in some cases even eradicated the transmission of malaria from most of the United States, Europe and even large parts of China. The greatest burden of the disease continues to be in the tropical regions of the world, and in particular, in sub-Saharan Africa.

Does malaria spread from a person to another?

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QUESTION:

Can malaria spread from one person to another?

ANSWER:

Usually, no. In most cases, the malaria parasite has to first pass from a human host into a mosquito as the mosquito takes a blood meal, and then from the mosquito into another human via the mosquito’s saliva. This severely limits the amount of person-to-person transmission that exists. In fact, the only mechanisms for direct transmission between humans are when malaria parasites are passed between a mother and her unborn child via the placenta (congenital transmission) and through unscreened blood transfusions.

Congenital malaria is the more common type of human-to-human transmission; across various surveys of newborns in West Africa, between 8-24% were found to be infected with malaria parasites.

All four main species of human malaria (P. falciparum, P. vivax, P. ovale and P. malariae) have been implicated in congenital transmission. Infection with malaria during pregnancy not only puts the mother at greater risk of severe disease episodes (probably through reduced immunocompetence during pregnancy) but may also negatively impact the baby; although in endemic areas it is rare for babies to be symptomatic for malaria when acquired congenitally, even if they have parasitaemia, they have been shown to have a higher mortality rate than non-infected newborns. In non-endemic areas, babies with congenital malaria often display symptoms, which usually manifest themselves between 2 and 8 weeks after birth. Both quinine and artemisinin-based therapies have been successfully used to treat congenital malaria.

Malaria infection as a result of blood transfusion was first identified in 1911 and is one of the most common illness transmitted via transfusion, although the risk of being infected, particularly in non-endemic countries, is very low.

As it is difficult to screen blood directly for malaria infection, a number of standards have been put in place by blood-collection services to reduce the risk of obtaining blood containing malaria parasites. For example, in many places, you will not be allowed to donate whole blood if you have visited an endemic malarial region in the last three months, nor should you donate if you have previously had malaria unless you have been symptom-free for at least three years.

Due to the longevity of Plasmodium malariae in the blood, you are unlikely to be able to donate blood if you have ever been confirmed as positive for P. malariae. Serological screening of blood for malaria antibodies has recently been shown to be a sensitive method for testing for malaria in blood, although it is expensive and therefore not cost-effective for screening every sample, especially in non-endemic countries. However, it can be effective and efficient to avoid wastage when employed together with a travel-based questionnaire to ascertain donors who are high-risk for malaria.

It is worth mentioning that transmission of malaria via plasma only is very uncommon, and so frequent travellers or residents in malarial areas, who may be denied the right to donate whole blood, should ask about the possibility of donating plasma instead.

Médecins Sans Frontières Calls for Switch from Quinine to Artesunate

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After the revision of World Health Organization (WHO) guidelines yesterday,  international medical humanitarian organization Médecins Sans Frontières (Doctors Without Borders) calls for a drug proven to reduce deaths in children suffering from severe malaria to be immediately rolled out in African countries.

In its new report, entitled “Making the Switch,” Médecins Sans Frontières (MSF) calls on African governments to follow new World Health Organization (WHO) guidelines, and switch from the far less effective quinine to artesunate, which could avert nearly 200,000 deaths each year. MSF also calls on WHO and donors to support governments so this urgent treatment change can happen quickly.

“When children arrive at the clinic with severe malaria, they often are having convulsions, vomiting or at risk of going into shock, and you just want to be able to give them effective treatment quickly,” said Veronique De Clerck, Medical Coordinator for MSF in Uganda. “For decades, quinine has been used in severe malaria, but it can be both difficult to use and dangerous, so it’s time to bid it farewell.  With artesunate, we now have a drug that saves more lives from severe malaria, and is safer, easier and more effective than quinine.”

Quinine has to be given three times a day in a slow intravenous drip that takes four hours, a treatment that is burdensome for both patients and health staff. Artesunate, in contrast, can be given in just four minutes, by giving a patient an intravenous or intramuscular injection.

A landmark clinical trial in late 2010 concluded that the use of artesunate to treat children with severe malaria reduces the risk of death by nearly a quarter.  The study, carried out in nine African countries, found that for every 41 children given artesunate over quinine, one extra life was saved.  Because of the complexities of administering quinine, children in the trial who were assigned to receive quinine were almost four times more likely to die before even receiving treatment.

MSF participated in the trial through its research affiliate Epicentre, with a research site in Uganda. MSF has since changed its own treatment protocols and now plans to work with national health authorities to roll out artesunate in its projects over the coming months.

The evidence is overwhelming, but MSF’s report stresses that change will not happen on its own. While WHO has now issued new guidelines recommending artesunate for treating severe malaria in children in Africa, it needs to also develop a plan to help countries make this switch.  African governments must urgently change their treatment protocols and donors must send a clear signal to countries that they will support the additional cost where needed.  Artesunate is three times more expensive, but the difference in cost of US$31 million each year for a global switch is very little for the nearly 200,000 lives that researchers say could be saved.

“We’ve been here before—when WHO changed its treatment recommendations for simple malaria in 2001 it took years for countries to actually make the switch, and shockingly, in some countries the far inferior drugs are still being used ten years on,” said Dr. Martin De Smet, who coordinates MSF’s malaria work.  “With severe malaria, WHO needs to make sure that the change is much less sluggish, so lives can be saved immediately.  There’s simply no excuse not to make the switch now.”

MSF provided malaria treatment to around one million people in 2010.  Severe malaria kills over 600,000 African children under the age of five annually.  Each year, around eight million simple malaria cases progress to severe malaria, where patients show clinical signs of organ damage, which may involve the brain, lungs, kidneys or blood vessels.

More information: Full MSF Report (PDF)

Source: MSF

Malaria Prevention

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Photo by Matthew Naythons, MD

Malaria prevention consists of a combination of mosquito avoidance measures and chemoprophylaxis. Although very efficacious, none of the recommended interventions are 100% effective.

Mosquito Avoidance Measures

  • Because of the nocturnal feeding habits of Anopheles mosquitoes, malaria transmission occurs primarily between dusk and dawn.
  • Contact with mosquitoes can be reduced by remaining in well-screened areas, using mosquito bed nets (preferably insecticide-treated nets), using a pyrethroid-containing flying-insect spray in living and sleeping areas during evening and nighttime hours, and wearing clothes that cover most of the body.
  • All travelers should use an effective mosquito repellent. [Read more…]

Malaria Treatment

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Malaria can be a severe, potentially fatal disease (especially when caused by Plasmodium falciparum) and treatment should be initiated as soon as possible.

Patients who have severe P. falciparum malaria or who cannot take oral medications should be given the treatment by continuous intravenous infusion.

Most drugs used in treatment are active against the parasite forms in the blood (the form that causes disease) and include:

  • chloroquine
  • atovaquone-proguanil (Malarone®)
  • artemether-lumefantrine (Coartem®)
  • mefloquine (Lariam®)
  • quinine
  • quinidine
  • doxycycline (used in combination with quinine)
  • clindamycin (used in combination with quinine)
  • artesunate (not licensed for use in the United States, but available through the CDC malaria hotline)

In addition, primaquine is active against the dormant parasite liver forms (hypnozoites) and prevents relapses. 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.

How to treat a patient with malaria depends on:

  • The type (species) of the infecting parasite
  • 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

If you have or suspect you have malaria, you should contact your doctor immediately.

Source: Centers for Disease Control (CDC)