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A Social Issue Neglected Tropical Diseases and Three Major Infectious Diseases

Malaria

Anopheline mosquitoes are disease vectors (carriers) that, when infected with Plasmodium parasites, spread malaria to people by piercing the skin. Malaria has been known to human for over 4,000 years and is said to have derived its contemporary name from mal’aria, which means “bad air” in Italian.
According to the report from the World Health Organization (WHO) published in 2014, about 3.3 billion people worldwide are at risk of contracting this disease. The range of symptoms for patients with this disease varies widely, from no fever or any other symptoms at all, to severe disease progression and even death. The mortality rate of patients with complications associated with falciparum malaria is particularly high and calls for immediate treatment.

Causes of Infection

Disease Agent

Plasmodium parasites

<Microscopic view of Plasmodium falciparum in red blood cells> CDC

Vector

Anopheline mosquitoes

Anopheles mosquito> James Gathany
CDC

Malaria is caused by Plasmodium parasites that are spread to humans through the bite of infected Anopheline mosquitoes. There are four species of parasites that cause this disease: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale. Two of these - P. falciparum and P. vivax - are the most common. A fifth form of malaria caused by P. knowlesi, a species that usually causes malaria among monkeys in forested areas in Southeast Asia, has recently been reported.
When an Anopheline mosquito takes a blood meal from a human, the sporozoites that are injected with the saliva of the mosquito grow in the person’s liver cells before then migrating to the blood and growing in the red blood cells resulting in merozoite production. These merozoites cause the red blood cells to rupture and will continue to invade red blood cell after another in what is a continual cycle.
It is when these red blood cells rupture that malarial symptoms or attacks occur. Usually, malarial attacks will happen every other day with “tertian parasites” (P. vivax) and every third day with “quartan parasites” (P. malariae). Attacks by falciparum malaria are often irregular.

Route of Infection

Reference:U.S. Centers for Disease Control and Prevention,"Malaria" Accessed March 19, 2014,
http://www.cdc.gov/dpdx/malaria/

Symptoms

Blood-stage parasites (merozoites) are the cause of all clinical symptoms associated with malaria. When the parasite develops in an erythrocyte, many known and unknown toxic substances collect in that cell. These substances are then dumped into the bloodstream once the infected cell ruptures.
A period of time (incubation period) lasting for seven to thirty days will usually pass before the first symptoms appear. The infection may result in a wide variety of symptoms ranging from very mild or no symptoms at all to severe disease and even death, depending on the type of malaria parasite and whether or not complications exist. With P. vivax and P. ovale infections, patients who have experienced an initial episode with this disease can relapse months or years later without any symptoms present. Malarial relapses are triggered by a different mechanism from the re-manifestations of symptoms due to falciparum malaria that requires particular medical attention.

Symptoms by Plasmodium parasites

Falciparum malaria

This malaria causes a daily fever (in some cases, several times a day). Since these fevers occur irregularly, however, they are not an effective diagnostic criterion. Falciparum malaria is characterized by accompanying complications collectively called “severe and complicated malaria”. This refers to cerebral malaria with abnormal behavior, impaired consciousness, seizures, coma and/or other neurologic abnormalities, severe anemia due to hemolysis (destruction of red blood cells), acute respiratory distress syndrome (ARDS), abnormal blood coagulation, and low blood pressure caused by cardiovascular collapse, etc. Some of these symptoms can occur together, making the most serious cause of death from falciparum malaria.

Vivax malaria

Attacks occur every 48 hours with symptoms that include fever, chills, sweating, headaches, nausea and vomiting, as well as body aches and general malaise.

Ovale malaria

Attacks occur every 48 to 50 hours, sharing common symptoms with tertian malaria.

Quartan malaria

Attacks occur every third day.

 

Diagnosis and Treatment

In general, when diagnosed and treated quickly and correctly, malaria is curable.

Diagnosis

Diagnosis requires finding parasites in a Giemsa-stained, thin blood film, usually with a microscope. The so-called “dipstick test” is used for more detailed diagnoses. Further, firm diagnosis requires the confirmation of compatible symptoms such as mild anemia, a slight decrease in blood platelets (thrombocytopenia), and elevated bilirubin and aminotransferases.

 
Treatment

The severity of malaria depends on the type of malaria parasites. Symptoms caused by tertian malaria, ovale malaria and quartan malaria are relatively mild, while falciparum malaria causes more serious symptoms, is accompanied by complications, and can be fatal.
Drugs such as chloroquine are administered for vivax malaria, ovale malaria, and quartan malaria. The treatment for falciparum malaria largely depends on the presence or absence of complications.

Uncomplicated falciparum malaria

Artemisinin-based combination therapy (ACT) is the most recommended treatment for falciparum malaria.

Severe and complicated falciparum malaria

Since the mortality rate is high when left untreated, immediate medical attention is essential. The most important objective is to promptly increase concentrations of the therapeutic drugs in the blood and this may require combination treatments based on the artemisinin derivatives, adjunct treatment, and later supportive treatments that include fluid administration.

 

Prevention

Eradicating malarial vectors using insecticide-treated mosquito nets and by spraying indoors with residual insecticides are the most recommended preventive techniques. DEET, an insect repellent, is also effective. The Olyset® Net, developed by Sumitomo Chemical, Co. Ltd., is recommended as an insecticidal mosquito net because it is safe and has long-lasting insecticidal efficacy.
Anti-malarial drugs also have some preventive effects. WHO (World Health Organization) recommends sulfadoxine/pyrimethamine for pregnant women beyond early pregnancy as well as three-time administration in children in regions at high risk of infection.

Regions at High Risk of Infection

Malaria is often found in areas with high humidity, high temperatures, and high precipitation. The regions with the highest infection risks are sub-Saharan Africa and Papua New Guinea, followed by some parts of Asia, Latin America, and Europe. Ninety seven(97)countries and territories have had continuing malaria transmission as of 2013. Advanced non-endemic countries sometimes encounter the so-called “imported malaria”.

Infected Area Map

Infected Area Map

Estimated Number of Infected People

It is estimated that there were about 214 million cases of malarial infection in 2015.

Estimated Number of Deaths

Malaria caused about 438,000 deaths in 2015, with more than 90% of those deaths in Africa.

Initiatives by Pharmaceutical Companies and NGO

Many organizations are working to control malaria. Among these are the President’s Malaria Initiative (PMI), WHO, the Medicine for Malaria Venture (MMV), and the Japan Pharmaceutical Manufacturers Association Antimalarial Drug Development Project (JPMW).

The President’s Malaria Initiative (PMI)

The President’s Malaria Initiative (PMI) is a U.S. government program designed to reduce malaria deaths by half in target countries in sub-Saharan Africa where infection rates are particularly high. It was announced on June 30, 2005 by U.S. President George W. Bush, who pledged, in cooperation with U.S. private companies, to increase U.S. funding for malaria in sub-Saharan Africa by more than U.S.$1.2 billion over five years (fiscal 2006 to fiscal 2010).
In partnership with African governments, PMI has developed a number of plans to control malaria to date. PMI has been driven by the U.S. Agency for International Development (USAID) with participation from CDC. Many NGOs and other organizations are also taking part or lending support: WHO, the World Bank, Roll Back Malaria (RBM), UNICEF, the International Red Cross Society, and the Global Fund to Fight AIDS, TB (tuberculosis), and Malaria. PMI currently has the following four programs targeting people at high risk of infection (pregnant women and children under five) in 19 countries and territories in sub-Saharan Africa and the Greater Mekong Subregion:

  • long-lasting insecticide-treated nets
  • artemisinin-based combination therapies (ACTs)
  • preventive treatment for pregnant women
  • indoor residual spraying with approved insecticides

WHO

WHO launched the Global Malaria Programme (GMP) to control malaria. GMP is staffed by people who help to prevent, control, and study malaria as well as set evidence-based policies and guidelines for monitoring malaria in cooperation with experts. GMP has, on its own initiative, collected data on malaria control from all over the world.
Major GMP partners include the African Leaders Malaria Alliance, the Global Fund to Fight AIDS, TB and Malaria, the Foundation for Innovative New Diagnostics, Imperial College London and numerous other public organizations, universities and similar groups. GMP also receives support from the Bill & Melinda Gates Foundation, the Canadian International Development Agency, the governments of Australia, Norway, Japan, the Russian Federation and the United Kingdom, and the U.S. Agency for International Development.
WHO adopted a new strategy in May 2015, "The WHO Global Technical Strategy for Malaria 2016-2030",

to achieve the following:

  • reducing malaria case incidence by at least 90% by 2030
  • reducing malaria mortality rates by at least 90% by 2030
  • eliminating malaria in at least 35 countries by 2030
  • preventing a resurgence of malaria in all countries that are malaria-free

MMV

The Medicine for Malaria Venture (MMV) is an NPO founded in 1999 in Switzerland through a government–private partnership. MMV contributes to the control of malaria through the development and distribution of effective and accessible antimalarial drugs.

Eisai

Eisai, in cooperation with multiple research institutes, researches and develops drugs and vaccines for combating malaria and other NTDs.

References
WHO- Malaria, accessed February 16, 2017
http://www.who.int/topics/malaria/en/
CDC- Malaria, accessed February 16, 2017
http://www.cdc.gov/malaria/