Malaria Effects on the Body

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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.

Reoccurring Malaria

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QUESTION

Can malaria reoccur year after year from a single infection? I have been told that it comes back every year by many people. I have had malaria once and it never came back after successful treatment. My thinking is that once the parasite has been eliminated from the system it is gone unless you get bitten again.

ANSWER

There are several different types of malaria that infect humans, and two of these species (Plasmodium ovale and Plasmodium vivax) can recur from year to year after a single infection.

The way it happens is that these types of malaria are able to form dormant life stages which hide in the liver. Most malaria medication only targets the blood stage form of malaria, and so these liver stages escape being killed by the medication, and can survive for long periods of time without the patient knowing about them. Then, at some point later (no one knows exactly what triggers the relapse—there is evidence that infection with other forms of malaria can instigate relapse, or being bitten by mosquitoes, or even just the climate), the liver stages activate again and re-enter the blood stream, which causes a renewal of symptoms.

It is possible to prevent these relapses—there is one type of medication, called primaquine, which is able to kill the dormant liver stages and thus completely clear the patient of malaria. However, it is important to talk to your doctor before taking primaquine, as it is not suitable for some people (especially those with G6DP deficiency).

Apart from these two types of malaria, the other three forms that infect people (P. falciparum, P. malariae and P. knowlesi) cannot reoccur in the same way as described above – if you have been infected with one of these, and then been successfully treated, you cannot get the disease again unless you are bitten by another infected mosquito.

Malaria Prevention

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QUESTION

What are the ways in which you can prevent yourself from being infected with malaria?

ANSWER

Malaria prevention consists of a combination of mosquito avoidance measures (since malaria is transmitted by infected mosquitoes) and chemoprophylaxis (medication to prevent the establishment of malaria in your body, if you do get bitten). 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.
  • The most effective repellent against a wide range of vectors is DEET (N,N-diethylmetatoluamide), an ingredient in many commercially available insect repellents. The actual concentration of DEET varies widely among repellents. DEET formulations as high as 50% are recommended for both adults and children older than 2 months of age (see the Protection Against Mosquitoes, Ticks, and Other Insects and Arthropods section later in this chapter). DEET should be applied to the exposed parts of the skin when mosquitoes are likely to be present.
  • In addition to using a topical insect repellent, a permethrin-containing product may be applied to bed nets and clothing for additional protection against mosquitoes.

Chemoprophylaxis

      • All currently recommended primary chemoprophylaxis regimens involve taking a medicine before travel, during travel, and for a period of time after leaving the malaria endemic area. Beginning the drug before travel allows the antimalarial agent to be in the blood before the traveler is exposed to malaria parasites.
      • Presumptive antirelapse therapy (also known as terminal prophylaxis) uses a medication towards the end of the exposure period (or immediately thereafter) to prevent relapses or delayed-onset clinical presentations of malaria caused by hypnozoites (dormant liver stages) of P. vivax or P. ovale. Because most malarious areas of the world (except the Caribbean) have at least one species of relapsing malaria, travelers to these areas have some risk for acquiring either P. vivax or P. ovale, although the actual risk for an individual traveler is difficult to define. Presumptive anti-relapse therapy is generally indicated only for persons who have had prolonged exposure in malaria-endemic areas (e.g., missionaries, volunteers).
      • In choosing an appropriate chemoprophylactic regimen before travel, the traveler and the health-care provider should consider several factors. The travel itinerary should be reviewed in detail and compared with the information on where malaria transmission occurs within a given country to determine whether the traveler will actually be traveling in a part of the country where malaria occurs and if significant antimalarial drug resistance has been reported in that location.
      • The resistance of P. falciparum to chloroquine has been confirmed in all areas with P. falciparum malaria except the Caribbean, Central America west of the Panama Canal, and some countries in the Middle East. In addition, resistance to sulfadoxine–pyrimethamine (e.g., Fansidar) is widespread in the Amazon River Basin area of South America, much of Southeast Asia, other parts of Asia, and in large parts of Africa. Resistance to mefloquine has been confirmed on the borders of Thailand with Burma (Myanmar) and Cambodia, in the western provinces of Cambodia, in the eastern states of Burma (Myanmar), on the border between Burma and China, along the borders of Laos and Burma, and the adjacent parts of the Thailand–Cambodia border, as well as in southern Vietnam.
      • Additional factors to consider are the patient’s other medical conditions, medications being taken (to assess potential drug–drug interactions), the cost of the medicines, and the potential side effects.

The medications recommended for chemoprophylaxis of malaria may also be available at overseas destinations. However, combinations of these medications and additional drugs that are not recommended may be commonly prescribed and used in other countries. Travelers should be strongly discouraged from obtaining chemoprophylactic medications while abroad. The quality of these products is not known, and they may not be protective and may be dangerous. These medications may have been produced by substandard manufacturing practices, may be counterfeit, or may contain contaminants. Additional information on this topic can be found in an FDA document

Purchasing Medications Outside the United States.

Herbal Treatment for Malaria

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QUESTION

Can any form of malaria be treated by herbs or plants, and how long does it take to recover from malaria?

ANSWER

Actually, two of the most important kinds of anti-malarial medication are derived by substances found naturally in plants, though they need to be processed in certain ways before the full pharmaceutical effect is felt.

Quinine, administered intravenously, is currently the first-line treatment for complicated malaria (i.e. when the patient has a history of high fever, plus additional severe symptoms such as impaired consciousness). It is derived from the bark of trees of the genus Cinchona, which are native to the tropical rainforests of western South America. Long known to native populations for its medicinal properties, it became known to Europeans in the early 17th century when the Countess of Chinchón, the wife of the viceroy of Peru at the time, was cured by it, having been suffering from what was likely malaria.

Similarly, artemisinin, currently used in combination with other anti-malarial compounds as the first-line treatment against non-complicated malaria (these combinations are known as artemisinin-based combination therapies, or ACTs), is derived from wormwood, a shrub native to Asia but now found throughout the world. As with the Cinchona trees, traditional healers in China had used wormwood to treat fever for thousands of years, but its use had been forgotten in modern times, until its rediscovery in the 1970s. Nowadays, artemisinin is not recommended for treatment alone, as it is feared this will lead to resistance developing, and so it is only used in the combination therapies described above.

If treated promptly, and with the correct form of medication, recovery from malaria can take only a few days. If not, recovery can take much longer (even up to weeks), and in the case of P. falciparum malaria, the most deadly kind, the infection can become life threatening in only a day or two. P. knowlesi (found in parts of south-east Asia), though less fatal than P. falciparum, can also become severe rapidly, and so prompt treatment is especially necessary for these two kinds of malaria.

Symtoms of Malaria

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QUESTION

Please tell me the symptoms of malaria.

ANSWER

Symptoms of malaria include fever and flu-like illness, including shaking chills, headache, muscle aches, and tiredness. Due to the way in which the malaria parasite reproduces in the human body, fevers occurring in a cyclical fashion (i.e. high fever one day, no fever the next day, then recurrence of fever on the third or fourth day, depending on the type of malaria) are a characteristic symptom of malaria, but may not be present in all cases. 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. When blood supply to the brain is disrupted during malarial infection, the resulting condition, characterised by seizures, mental confusion, coma, and death, is known as “cerebral malaria”, and is associated with Plasmodium falciparum, the most deadly form of malaria.

Please check your article: Symptoms and Causes of Malaria

Prevention of Malaria

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QUESTION

What is the prevention of malaria?

ANSWER

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.
  • The most effective repellent against a wide range of vectors is DEET (N,N-diethylmetatoluamide), an ingredient in many commercially available insect repellents. The actual concentration of DEET varies widely among repellents. DEET formulations as high as 50% are recommended for both adults and children older than 2 months of age (see the Protection Against Mosquitoes, Ticks, and Other Insects and Arthropods section later in this chapter). DEET should be applied to the exposed parts of the skin when mosquitoes are likely to be present.
  • In addition to using a topical insect repellent, a permethrin-containing product may be applied to bed nets and clothing for additional protection against mosquitoes.

Read the full article about Malaria Prevention.

Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. Vivax

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Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv).

Methods and Findings

In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10–43, p≤0.001) in children receiving SP-AQ and 12% (95% CI, −11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9–54, p = 0.012) and Pv incidence was 23% (95% CI, 0–41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4–51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, −24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%–2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention.

Conclusions

IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.

Trial registration

ClinicalTrials.gov NCT00285662

Please see later full article for the Editors’ Summary (link below).

Citation: Senn N, Rarau P, Stanisic DI, Robinson L, Barnadas C, et al. (2012) Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial. PLoS Med 9(3): e1001195. doi:10.1371/journal.pmed.1001195

Academic Editor: Sanjeev Krishna, St George’s Hospital Medical School, United Kingdom

Received: July 5, 2011; Accepted: February 9, 2012; Published: March 27, 2012

Funding: This work was supported by a grant to the PNG Institute of Medical Research from the Bill & Melinda Gates Foundation’s Global Health Program (Grand ID# 34678). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.

Competing interests: SJR is a member of the PLoS Medicine Editorial Board. The authors have declared that no competing interests exist.

Abbreviations: AE, adverse event; AQ, amodiaquine; AS, artesunate; ATP, according to protocol; EPI, Expanded Programme on Immunization; Hb, hemoglobin; IPT, intermittent preventive treatment; IPTi, intermittent preventive treatment in infants; IRR, incidence rate ratio; LDR-FMA, ligase detection reaction/fluorescent microsphere assay; mITT, modified intention to treat; PE, protective efficacy; Pf, Plasmodium falciparum ; PNG, Papua New Guinea; Pv, Plasmodium vivax ; PYAR, person-year at risk; SAE, serious adverse event; SP, sulfadoxine-pyrimethamine

Authors: Nicolas Senn1,2,3,4#, Patricia Rarau1#, Danielle I. Stanisic1,5, Leanne Robinson1,5, Céline Barnadas1,5, Doris Manong1, Mary Salib1, Jonah Iga1, Nandao Tarongka1, Serej Ley1, Anna Rosanas-Urgell1, John J. Aponte6, Peter A. Zimmerman7, James G. Beeson5,8, Louis Schofield5, Peter Siba1, Stephen J. Rogerson2, John C. Reeder8, Ivo Mueller1,5,6*

1 Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea, 2 Department of Medicine, University of Melbourne, Melbourne Australia, 3 Swiss Tropical and Public Health Institute, Basel, Switzerland, 4 University of Basel, Basel, Switzerland, 5 Infection and Immunity Division, Walter and Eliza Hall Institute, Melbourne, Australia, 6 Barcelona Centre for International Health Research (CRESIB), Barcelona, Spain, 7 Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, United States of America, 8 Burnet Institute, Melbourne, Australia

Full Article:Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial (PDF)

Source: PLOS Medicine

Copyright: © 2012 Senn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Malaria Symptoms

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QUESTION

How does the virus cause the symptoms?

ANSWER

Malaria is actually not caused by a virus—it is caused by a microscopic single-celled parasite called Plasmodium. Several different species cause malaria in humans, the most common of which are P. vivax and P. falciparum.

To describe the process in a very oversimplified way, the malaria parasites cause disease by infecting red blood cells, multiplying inside them, then simultaneously bursting out again, destroying then red blood cell in the process. The sudden destruction of lots of red blood cells, plus the debris and waste products left behind by the malaria parasites, stimulate a rapid immune reaction, which itself causes the rapid spike of fever. The characteristic cycles of fever sometimes seen with malaria sufferers occurs because the malaria parasites synchronise their emergence from the red blood cells. The destruction of red blood cells, together with concurrent physiological changes associated with immune response and inflammation, can also lead to decreased haemoglobin levels and anaemia.

More severe clinical symptoms are often seen with P. falciparum malaria infection, particularly if not promptly diagnosed and treated. This is because the P. falciparum parasite infects a red blood cell, it changes the surface of the cell and makes it “sticky”; when the red blood cell then tries to pass through the small blood vessels that lead into the body’s organs, it becomes stuck. This process is known as “sequestration”. If enough red blood cells become sequestered in the organs, it can reduce blood flow to the organ, resulting in oxygen deprivation. When this happens in the blood vessels in the brain, the patient may experience impaired consciousness, confusion and even coma and death—this manifestation is known as “cerebral malaria.”

Malaria Testing

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QUESTION

My daughter is in Kigoma, Tanzania and has the symptoms of Malaria. She was given Duo Cotecxin and it seems to have started making her feel better. But after reading up on all the different types of Malaria parasites I am wondering if a blood test reading at a clinic would be recommended or is it too late for an accurate reading now that she is on meds?

ANSWER

I am always very nervous about people given malaria medication without a proper blood test-based diagnosis. The symptoms of malaria can sometimes be very general, and I have recently seen some data from elsewhere in Tanzania whereby clinics are giving virtually everyone who comes in with a fever malaria medication, even if the blood tests are negative! This is a sure way to develop resistance to malaria drugs, plus exposes people to the potential side effects of medication that they may not need, while also failing to diagnose or treat them for whatever other condition they may also have.

In your daughter’s case, since she is feeling better, it may be that she did indeed have malaria. Regardless, now that she is taking the treatment, she should make sure to finish the full dose of pills. It still could also be worth going in for a blood test. In any case it will put your mind at rest, and if there are still traces of the parasite in her blood, then you will know for sure that she had malaria. Moreover, it might tell you which type of malaria she had. While P. falciparum is the most common form of malaria in sub-Saharan Africa, cases of other types, such as P. vivax and P. ovale, are being reported more and more frequently.

These two types can form liver stages (called hypnozoites) which can stay dormant for weeks, months or even years after the initial infection. During this period, the patient will experience no symptoms; then, when the hypnozoites activate and re-enter the blood again, the patient will get a “relapse” of the malaria symptoms. The only drug available to kill these liver stages is primaquine; as such, if your daughter is positively diagnosed with P. vivax or P. ovale malaria, she should be aware of the possibility of a relapse, and perhaps discuss with a doctor the possibility of taking primaquine.

I hope she recovers fully and enjoys her stay in Kigoma—I spent almost a month out there last year!

Duo-Cotecxin and Fansidar as Treatment

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QUESTION

My husband weighs and has malaria. He was told by the pharmacist to take 2 tablets stat, then 1 daily for five days followed by 3 Fansidar tablets. We live in Papua New Guinea. I see on the Duo-Cotecxin web site the dose is three tabs daily. Which is correct?

ANSWER

Fansidar is a very different drug to Duo-Cotecxin—it is made of a combination of sulfadoxine and pyrimethamine, whereas Duo-Cotecxin is an artemisisin-based combination therapy (ACT), consisting of dihydroartemisinin together with piperaquine. As such, the dosages and time courses of therapy are likely to be different. However, Fansidar is not usually recommended as treatment anymore—it appears to have low efficacy against Plasmodium vivax and in the 1980s and 1990s, the World Health Organisation and Center for Disease Control (CDC in the US) only recommended it for use against chloroquine-resistant P. falciparum.

However, nowadays, both organisations recommend ACTs (like Duo-Cotexcin) to treat all uncomplicated P. falciparum infection as well. Therefore, unless your husband has been diagnosed with P. ovale or P. malariae malaria (both of which are sometimes found in PNG), Fansidar probably should not have been the first-line treatment given to him. Keep a close watch over his recovery, and if there is any sign of reccurrence of the symptoms, go back to the doctor for another malaria test.