Malarial Prophylaxis

Every year more than 125 million people visit over 100 countries endemic for Malaria. Each year up to 30,000 travelers are estimated to contract Malaria and late or wrong Malaria diagnosis in their home country may make things worse for them. Fever occurring in a traveler within three months of leaving a Malaria-endemic area is considered a medical emergency and should be investigated urgently. Malaria is contracted by the bite of a female anopheles mosquito. It is not contagious, and cannot be transmitted from person to person.

Malaria prophylaxis is the prevention of Malaria. Malaria is thought to be one of the oldest infectious diseases, evolving around 10,000 years ago. The development of new antimalarial drugs spurred the World Health Organization in 1955 to attempt a global Malaria eradication program. This was successful in much of Brazil, the US and Egypt but ultimately failed elsewhere. Efforts to control Malaria are still continuing. 

As there is no vaccine available for protection against Malaria despite decades of research, there is a need for an alternative method that offers a fairly reliable protection against Malaria. And as Malaria can be severe in the non-immune, all visitors from non-malarious area to a malarious area should be protected. Antimalarial drugs offer protection against clinical attacks of Malaria.

The risk of contracting Malaria depends on the region visited, the length of stay, time of visit, type of activity, protection against mosquito bites, compliance with chemoprophylaxis etc. 

Risk for Travelers

Risk can differ substantially even for persons who travel or reside temporarily in the same general areas within a country. For example, travelers staying in air-conditioned hotels may be at lower risk than backpackers or adventure travelers.

Basic Prevention

The ABCD of Malaria prevention are:

A. Awareness of risk;
B. Bite prevention – Travelers to Malarious areas are advised to wear long clothes that cover as much of the skin as possible. Exposed parts of the body should be treated with insect repellent. When sleeping, insecticide-impregnated bed nets should be used. 
C. Chemoprophylaxis
D. Rapid Diagnosis and Treatment

Suppressive Prophylaxis

Chloroquine, Proguanil, Mefloquine and Doxycycline are suppressive prophylactics. This means that they are only effective at killing the Malaria parasite once it has entered the erythrocytic stage (blood stage) of its life cycle, and therefore have no effect until the liver stage is complete. That is why these prophylactics must be continued to be taken for four weeks after leaving the area of risk. 

Causal Prophylaxis

Causal prophylactics target not only the blood stages of Malaria, but the initial liver stage as well. This means that the user can stop taking the drug seven days after leaving the area of risk. Malarone and Primaquine are the only causal prophylactics in current use.

Chemoprophylaxis

Chemoprophylaxis is the strategy that uses medications before, during, and after the exposure period to prevent the disease caused by Malaria parasites. The aims of Malaria treatment in broad terms are to alleviate symptoms, to prevent relapses and to prevent further transmission of the parasite. There are approximately 14 antimalarials that are advised for use in the prevention and treatment of uncomplicated Malaria.

Drug Regimens

The following regimens are recommended by the WHO, UK HPA and CDC:

1. Chloroquine 300 to 310 mg once weekly, and Proguanil 200 mg once daily (started one week before travel, and continued for four weeks after returning);
2. Doxycycline 100 mg once daily (started on day before travel, and continued for four weeks after returning);
3. Mefloquine 228 to 250 mg once a week (started two-and-a-half weeks before travel, and continued for four weeks after returning);
4. Malarone (Atavaquone + Proguanil) 1 tablet daily (started one day before travel, and continued for one week after returning).

Doses depend on what is available (eg in the US, Mefloquine tablets contain 228 mg base, but in the UK they contain 250 mg base). The data is constantly changing and no general advice is possible. Doses given above are appropriate for adults and children over 12 years of age. 

Chloroquine, Mefloquine are safe in pregnancy, Doxycycline is not. 

While chemoprophylaxis in pregnancy appears efficacious, a major question remains – which agents are safest for both the woman and the fetus? Some drugs routinely used in non-pregnant individuals should not be offered to pregnant women because of known direct effects on the fetus. Doxycycline is teratogenic, and Primaquine poses a significant of fatal intravascular hemolysis in G6PD deficient fetuses. Other drugs, such as Atovaquone / Proguanil and Artesunate, are not well studied in pregnancy, and therefore are not recommended for use unless other options are not available. 

Given these reaction profiles, Chloroquine or Mefloquine are usually the best choice with their superior safety and efficacy.

*Chloroquine is widely used because it is inexpensive and well tolerated, with only pruritus, mouth ulcers and gastrointestinal upset as the most common adverse effects. Persons who experience uncomfortable side effects after taking Chloroquine may tolerate the drug better by taking it with meals.

*Mefloquine is usually well tolerated, but can cause dose-related neuropsychiatric effects; it is contraindicate in those with a history of epilepsy or psychiatric disease.

The World Health Organization (WHO) recommends Chloroquine as first-line prophylaxis in pregnancy (plus Proguanil if the region exhibits emerging Chloroquine resistance). In areas with proven Chloroquine resistance, Mefloquine is the drug of choice. 

The Centers for Disease Control and Prevention (CDC) also advises use of Chloroquine (or Mefloquine in regions with Chloroquine resistance). The CDC discourages the use of Atovaquone/Proguanil, Doxycycline, and Primaquine, due to known adverse fetal effects or inadequate experience in pregnancy. 

Chemoprophylaxis Regimen:
 Malaria chemoprophylaxis with Mefloquine or Chloroquine should begin 1-2 weeks before travel to malarious areas. Beginning the drug before travel allows the antimalarial agent to be in the blood before the traveler is exposed to malaria parasites. In addition to assuring adequate blood levels of the drug, this regimen allows for evaluation of any potential side effects. Chemoprophylaxis should continue during the stay in Malarious area and for 1-4 weeks after departure from the area. Chemoprophylaxis can be started earlier if there are particular concerns about tolerating one of the medications. Starting the medication 3-4 weeks in advance allows potential adverse events to occur before travel. If unacceptable side effects develop, there would be time to change the medication before the traveler’s departure.

Antimalarials and Pregnancy: CDC Recommendations
Travel during Pregnancy to Areas without Chloroquine-Resistant P falciparum: Pregnant women traveling to areas where chloroquine-resistant P falciparum has not been reported may take chloroquine prophylaxis. Chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for Malaria prophylaxis; therefore, pregnancy is not a contraindication for Malaria prophylaxis with chloroquine phosphate or hydroxychloroquine sulfate.
Travel during Pregnancy to Areas with Chloroquine-Resistant P falciparum: Mefloquine is currently the only medication recommended for malaria chemoprophylaxis during pregnancy. A review of Mefloquine use in pregnancy from clinical trials and reports of inadvertent use of Mefloquine during pregnancy suggest that its use at prophylactic doses during the second and third trimesters of pregnancy is not associated with adverse fetal or pregnancy outcomes. More limited data suggest it is also safe to use during the first trimester.

Because of insufficient data regarding the use during pregnancy, atovaquone/proguanil is not currently recommended for the prevention of Malaria in pregnant women. Doxycycline is contraindicated for Malaria prophylaxis during pregnancy because of the risk of adverse effects of tetracycline, a related drug, on the fetus, which include discoloration and dysplasia of the teeth and inhibition of bone growth. Primaquine should not be used during pregnancy because the drug may be passed transplacentally to a glucose-6-phosphate dehydrogenase (G6PD)-deficient fetus and cause hemolytic anemia in utero. 
How to protect yourself

Know the Facts
Persons who are traveling to malaria risk areas can almost always prevent this potentially deadly disease if they correctly take an effective antimalarial drug and follow measures to prevent mosquito bites.

Know the Symptoms
Despite these protective measures, travelers may become infected with malaria. Malaria symptoms can include:
• fever
• chills
• headache
• flu-like symptoms
• muscle aches 
• fatigue
• low blood cell counts (anemia) 
• yellowing of the skin and whites of the eye (jaundice)

When Symptoms Appear, Seek Immediate Medical Attention
Malaria is always a serious disease and may be a deadly illness. Travelers who become ill with a fever or flu-like illness either while traveling in a malaria-risk area or after returning home (for up to 1 year) should seek immediate medical attention and should tell the physician their travel history.

Personal Protection Measures
It must be remembered that no chemoprophylaxis regime provides 100% protection. Therefore it is essential to prevent mosquito bites as well as to comply with chemoprophylaxis. Anopheles mosquitoes bite at nights, with peak biting between 10pm and 4am and Malaria transmission occurs at these hours. Travelers must take personal protective measures against mosquito bites at nights. 

• Remaining in well-screened areas after dusk, using mosquito nets, and wearing clothes that cover most of the body are some simple but effective measures. 
• In addition, mosquito repellents like N,N diethylmetatoluamide (DEET) can be used. It is better to have a pyrethrum-containing space spray to use in living and sleeping areas during evening and night hours. Travelers should take a flying insect spray on their trip to help clear rooms of mosquitoes. In the United States, permethrin (Permanone) is available as a liquid or spray. Overseas, either permethrin or another insecticide, deltamethrin, is available and may be sprayed on bed nets and clothing for additional protection against mosquitoes. 
• Protect infants (especially infants under 2 months of age not wearing insect repellent) by using a carrier draped with mosquito netting with an elastic edge for a tight fit. 
• Clothing, shoes, and camping gear, can also be treated with permethrin. Treated clothing can be repeatedly washed and still repel insects. Some commercial products (clothing) are now available in the United States that have been pretreated with permethrin. 
• It is advisable to quickly report any febrile illness and disclose your travel histories to your healthcare providers.
Know the Signs and Symptoms of Malaria

You can still get malaria despite taking an antimalarial drug and using protection against mosquito bites. Taking an antimalarial drug greatly reduces your chances of getting malaria. Symptoms are very flu-like and can include fever, shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur.

Malaria symptoms will occur at least six to nine days after being bitten by an infected mosquito. Therefore, fever in the first week of travel in a malaria-risk area is unlikely to be malaria; however, ill travelers should still seek immediate medical care and any fever should be promptly evaluated.

Recommendations for travelers to malaria endemic areas
All travelers to malaria-endemic areas are at risk of contracting Malaria and being non-immune, P falciparum infection in these individuals can become severe. Therefore, all travelers to Malaria endemic areas are advised to use an appropriate chemoprophylaxis and personal protection measures to prevent Malaria. However, it should be remembered that, regardless of methods employed, Malaria can still be contracted. Symptoms can develop as early as 8 days after initial exposure in a Malarious area and as late as several months after departure from a Malarious area. Malaria is easily treatable early in the course of the disease but delay in treatment can lead to serious or even fatal consequences. Therefore, individuals who develop symptoms of malaria should seek prompt medical help, including blood smear (or QBC test) for malaria.

Dr Sulbha Arora MD DNB
Scientific Director
Deccan Fertility Clinic and Keyhole Surgery Center

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