Malaria

The disease is caused by several types of unicellular parasites. These are the genera of parasites that cause malaria:

• P. falciparum - endemic in sub-Saharan Africa, Asia, Latin America, and eastern Pacific
• P. vivax - endemic in eastern Africa, Asia, Latin America, and temperate climate zones
• P. ovale - endemic in western Africa
• P. malariae - rarer, endemic in tropical and sub-tropical areas
• P. knowlesi - very rare, endemic in Borneo and Southeast Asia

Of those we have listed, the former is the most common and the main culprit in disease-related deaths. P. vivax, P. ovale and P. malariae typically do not damage vital organs, so death tends to be rarer.

Malaria is transmitted to humans through the bite of an infected female mosquito of the genus Anopheles. Of the 430 subspecies of Anopheles, about 40 are capable of carrying malaria, and they are generally distributed in tropical and subtropical regions. The major transmitters of malaria are the mosquitoes Anopheles funestus and Anopheles gambiae.The mosquito is a heterothermic animal, that is, it can survive only in temperatures above 15-18°C with high humidity. The bite occurs only by the female mosquito and it makes blood meals for the production and maturation of its eggs. Mosquito activity is especially intense during the twilight and night hours but it is possible to be bitten during the daytime as well.

The female mosquito takes up gametocytes of the parasite through a blood meal on an infected person even if that person has no symptoms of malaria. The gametocytes of the plasmodium evolve into sporozoites inside the mosquito; maturation can take place from a few days or weeks as it depends on climate and species. The sporozoites migrate into the salivary glands of the mosquito and will be transmitted to humans through the bite, as the mosquito before sucking the blood material, injects its prey, its saliva which contains an anesthetic and an anticoagulant. In humans, the parasite continues to mature until it localizes in the liver where it invades hepatocytes (liver cells), maturing into schizont, which lyses (dissolution of a cell, caused by the rupture of the cell membrane), releasing the plasmodium into the circulatory stream in the form of a merozoite.P.vivax and P. ovale are the only ones that can develop dormant forms without malaria symptoms, hypnozoites, which can reactivate and cause disease even months after infection. Merozoite invades red blood cells in the blood stream, where it reproduces, developing first into trophozoite, then schizont. The red blood cell ruptures and releases merozoites that will go on to invade other red blood cells, perpetuating the cycle. Some parasites differentiate by developing into gametocytes, male and female, which, if ingested by the mosquito during the bite, will continue the cycle of transmission.

Malaria is mainly prevalent in tropical and sub-tropical areas, in these areas the risk of malaria is very high, because there are several variables such as temperature, humidity and rainfall, which are particularly favorable for mosquitoes to proliferate. Malaria prophylaxis is strongly recommended in these areas. Malaria transmission occurs in areas where the Anopheles mosquito can survive and multiply, and where the parasite is able to complete its growth cycle in the mosquito itself. In many of the malaria endemic countries, the spread does not occur in all areas; in fact, it is not present in some areas that have certain characteristics:

• At very high altitudes;
• During the cold/dry season;
• In the desert (excluding oases)

In general, in regions near the equator the risk of contracting malaria is higher and it is present all year round. In particular, sub-Saharan Africa has the highest rate of infection and death on the entire planet. In Southeast Asia, the Middle East, the Pacific, and Central and South America, malaria is present with varying degrees of endemicity.

Symptoms of severe malaria

Severe malaria is needed when the infection manages to cause severe organ failure or metabolic abnormalities. It is characterized by hyperparasitemia, which is the condition in which more than 5% of red blood cells are infected with parasites. It can manifest as severe anemia, hemoglobinuria, kidney injury, hypoglycemia, metabolic acidosis, blood clotting abnormalities, and respiratory distress syndrome. Severe malaria can also result in cerebral malaria, with seizures, neurological abnormalities, and coma. Complicated malaria is a medical emergency that must be treated promptly.

Symptoms of relapsing malaria

Infections caused by the plasmodia P. vivax and P. ovale, can be relapsing forms of the disease. In fact, the two parasitic forms are able to survive in the host organism due to quiescent forms, called hypnozoites, which months or years later can reawaken regenerating the disease.

Early diagnosis is essential to determine effective treatment and good clinical outcome. Suspicion of malaria may result from clinical examination of the patient, with observation of manifested symptoms, or from medical history (e.g., recent stay in endemic area).

Specific diagnosis by parasite search is based on:

• Microscopic search for parasites in blood, by making the sample on a slide;
• Parasite detection in blood, by rapid immunological tests;
• Parasite nucleic acid detection, by PCR

The choice of elective treatment for malaria is naturally influenced by several factors, such as the determination of the parasite species, the clinical status of the patient, and whether the patient is pregnant or has allergies.

The most frequently used medications include:

• Chloroquine
• Atovaquone-proguanil, trade name: Malarone
• Artemether-lumefantrine, trade name: Coartem
• Mefloquine
• Quinine
• Doxycycline (in conbination with quinine)
• Clindamycin (in conbination with quinine)
• Tetracycline (in conbination with quinine)
• Artesunate

However, the latest World Health Organization (WHO) guidelines on malaria treatment place Artemisinin, in combination with other drugs (ACTs), among the elective drugs.

Behavioral prophylaxis

Prevention for malaria starts with proper behavioral prophylaxis.

• Use an effective mosquito repellent: the Centers for Disease Control and Prevention (CDC) recommends repellents with the following active ingredients: DEET (>25%); Picaridin; IR3535; Eucalyptus Lemon Oil (OLE); Para-menthane-diol; 2- undecanone.
• Cover up: use clothes that cover legs and arms, preferably light colored.
• Check the environment around you: standing water is a perfect habitat for mosquitoes to breed. Make sure there is no stagnant water in: discarded tires or industrial containers, swimming pools, storm drains and saucers. To reduce your risk of transmission, systematic control through pest control campaigns against the Aedes population turns out to be a key intervention.
• Read our in-depth article: Don't get stung!

Antimalarial chemoprophylaxis

Chemo prophylaxis is especially indicated for those heading to malaria-risk endemic areas.

Accurate assessment of one's destination, on the period and duration of stay, the traveler's clinical evaluation, and other factors that can significantly influence the choice of antimalarial prophylaxis is essential for effective choice.

Currently, the most widely used chemo prophylaxis drugs are:

• Atovaquone-Proguanil, trade name: Malarone
• Mefloquine, trade name: Lariam
• Doxycycline, trade name: Bassado, Miraclin

However, it is important to remember that:

• No anti-malarial drug is 100% protective, and it is necessary, as mentioned, to also take personal protective measures (such as: good mosquito repellent, appropriate clothing, and sleeping in a mosquito-free environment as much as possible);
• It is essential to disclose the possible intake of all previously prescribed medications for subsisting conditions to the travel medicine specialist at the pre-trip consultation so that he or she can assess possible drug interactions with the medications that the traveler will have to use for prophylactic or even curative purposes and the likelihood of possible allergy/intolerance.

The choice of the correct pharmacological prophylaxis given the complexity of the subject and the presence of variables of various kinds, clinical, seasonal, geographical, political and climatological, belongs to the competence of the travel medicine specialist, here are some notions regarding the problem of drug resistance.

The development of drug resistance is one of the greatest challenges in the fight against malaria. Resistance to antimalarial drugs has only been confirmed for Plasmodium falciparum and P. vivax. P. falciparum first started to develop resistance to Chloroquine from the 1950s in Southeast Asia and South America. Today, P. falciparum is endemically resistant to the drug in almost all areas where it occurs. P. falciparum has also developed resistance to sulfadoxine/pyrimethamine, mefloquine (Lariam), halofantrine, and quinine. Although resistance to these drugs tends to be much less geographically widespread, in some areas of the world, the impact of multi-drug resistant malaria may be extensive. Resistance to mefloquine is common in parts of Southeast Asia and the Amazon region of South America and sporadically in Africa. Chloroquine-resistant P. vivax malaria has been identified in Southeast Asia, Ethiopia, and Madagascar. Vivax malaria parasites, particularly those from Oceania, show greater resistance to this drug than P. vivax isolates from other regions of the world. (CDC; WHO) For proper prevention to prepare for travel to malaria-prone areas, it is important to be informed. The best way to become informed is through pre-trip counseling done with a Medical Specialist in Travel Medicine. Doctors who are Specialists in Tropical Diseases can inform you about the best measures to take on a case-by-case basis.

No vaccine against malaria is currently available. However, thanks to relentless scientific research efforts, the vaccine RTS,S/AS01, which has shown promising, albeit partial, results, is still being studied.

As of April 2019, WHO is coordinating a pilot vaccination program in Malawi, Ghana, and Kenya, with the goal of vaccinating 360,000 children per year.