Leya Ahmed
Mr. March
Science
28 November 2018
Malaria
Introduction
Malaria is a fatal infection spread by any female anopheles mosquito infected with a malaria causing single-celled plasmodium parasite. The plasmodium parasite travels through the body, directly killing the liver and red blood cells in the process. There is a region below the equator called the malaria belt. The malaria belt consists of parts of Latin America, Sub Saharan Africa, South Asia, and Southeast Asia. Malaria most commonly affects:
Persons under the age of five
Persons with other pre-existing conditions
Pregnant women
Travelers without past exposure to malaria
In 2016, 216 million cases of malaria were diagnosed worldwide. Of those cases, 445,000 (~21%) people passed away due to the infection, directly. 1,700 cases were in the US, mostly being from people who had traveled to areas close to or in the malaria belt (who returned) and immigrants from similar areas. Malaria is an expensive infection for countries to control or eradicate. Rural and poverty stricken countries along the malaria belt spend money on free health care clinics for citizens and some free treatments, but most staff are volunteers, not well trained professionals, and drugs are getting stolen to be resold for a profit. Some countries have programs that show potential, but only a handful of them have successfully eliminated malaria and kept that status. The majority (91%) of deaths related to malaria occur in Africa, most of those being children’s. Some medications sold and bought abroad could be banned for not working, counterfeit or tainted. The safest place to buy malaria treatments are in the US, when prescribed by a doctor. There are no malaria vaccines in use yet, but scientists are currently working on developing one. After returning from a country on or along the malaria belt, travelers are not allowed to donate blood within a year of traveling to reduce the chances of malaria infected blood. In the US, there were 97 verified cases of malaria between 1963 and 2012, an average of 1.97959183673469 cases each year. ~50% of the world's population is at risk of contracting malaria. Over 100 countries and territories have had cases of malaria. Some warm climates have successfully eradicated malaria, and other never had it to begin with. The fast growing population of the anopheles gambiae in Africa is very efficient at spreading malaria and gaining new resistances to drugs and treatments. An eradication campaign during the 1950’s failed due to mosquitoes developing resistances to the insecticides intended to eliminate them. Although Africa is the country with the most cases of malaria, this campaign never reached Africa. Malaria can also be spread through airports and airplanes. The CDC is working with the U.S. Agency for International Development (USAID) doing research on the best prevention treatments, worth $3,000,000,000, and it is also collaborating with UNICEF and The World Bank on malaria control programs. Certain temperatures during seasons, and sometimes year round, are not suitable for some plasmodium species. One species is not able to complete its cycle in temperatures under 20°C (68°F), so malaria cannot be spread by that plasmodium species. Transmission also cannot take place in
High altitudes
Colder seasons (fall – winter)
Deserts (not including the oases)
Areas with successful control/elimination programs
Regarding warmer regions, transmission of malaria can happen during all seasons and is more intense. The highest regions of malaria transmission are Sub Saharan Africa and Oceania (Papua New Guinea). Cooler regions transmission is less intense and seasonal. A certain plasmodium is more common in cool regions due to its high tolerance of the cold. Some consequences of malaria can affect the brain, resulting in palsies, ataxia, difficulties regarding speech, deafness and blindness. Malarial infections during pregnancy can cause a low birth weight, the greatest risk of death in newborn babies during their first few months of life. Malaria control programs have saved 3,300,000 lives and cut the mortality rate of malaria down by almost half (45%). The average cost of treatment, prevention and death every year is over USD$12,000,000,000. Malaria was a public health problem in the US during the 1940’s. Using insecticide-treated nets (ITN’s) has reduced the deaths in children by about 20%. The number of people sleeping under ITN’s has increased in recent years. After using ITN’s, from 2005 to 2007, the amount of children with cases of malaria in Zanzibar under the age of two reduced drastically from 22% to less than 1%. Every minute, two children will die of malaria, 3,000 will die every day. Malaria is the largest killer of children in the world. Because of the cost of malaria control, it drains economies in Africa, making the economic growth 1.3% each year. 70% of cases in Africa are resistant to common treatments, including Chloroquine and Sulfadoxine-Pyrimethamine. Less than 5% of children in Africa sleep underneath an ITN that can reduce malaria infections up to 50% in most high transmission areas. Mosquitoes are not found in Iceland, but they are found in neighboring countries. In Greenland, there are two species of mosquitoes, in Norway and Britain there are 28, and in some east of Iceland, there are as many as 41 different species. Mosquito larvae grow and live in shallow pools of water, like river beds and tide pools. In recent studies, scientists have proven that malaria can be transmitted from monkeys to humans.
Cycle
There are hundreds of plasmodium species, but only five can cause malaria in
humans. Those are plasmodium falciparum, plasmodium knowlesi, plasmodium ovale, plasmodium vivax and plasmodium malariae. Mosquitoes are attracted to the carbon dioxide (CO2) that we exhale and bodily odors, like sweat. When a mosquito is infected with malaria, it has tiny sporozoites waiting in its salivary glands. Once it bites a human, the sporozoites exit the salivary glands of the mosquito and travel into the bloodstream. Now in the bloodstream, the sporozoites travel to the liver where they will begin asexual reproduction, where a single organism produces offspring by themselves. Depending on the species, the plasmodium could stay in the liver for a few weeks or multiple months to years. Plasmodium knowlesi, plasmodium falciparum and plasmodium malariae stay in the liver for seven to 14 days, where they enter schizogony, maturing from sporozoites into merozoites. Regarding the other two plasmodium, plasmodium ovale and plasmodium vivax, they stay in the liver for a while, maturing into hypnozoites from sporozoites, then into merozoites. This causes a long delay between initial infection and when symptoms start to show. Everything that has just taken place is classified as the exoerythrocytic phase, which means that it occurred outside of a red blood cell. The exoerythrocytic phase usually does not have symptoms. The merozoites exit the liver and enter the bloodstream. When the plasmodium species invade red blood cells, they each have a preference. Plasmodium ovale and plasmodium falciparum tend to invade red blood cells of all ages, plasmodium vivax invades younger and not mature red blood cells, and plasmodium malariae and plasmodium knowlesi most commonly invade older, mature red blood cells. Plasmodium vivax invades red blood cells using a surface receptor called the Duffy Antigen. Regarding persons with sickle cell anemia and other diseases, their blood cells do not have this receptor, therefore giving those with some disease a sort of protection against a certain plasmodium species. The following occurs in the red blood cell, so it is called the erythrocytic phase. This phase lasts two to three days, and the merozoites transform multiple times in the red blood cell.
1st transformation: The merozoites becomes an early trophozoite, and looks like a tiny wedding ring in the red blood cell.
2nd transformation: The early trophozoite becomes a late trophozoite, growing larger.
3rd transformation: The late trophozoite further matures into a schizont. The schizont digests hemoglobin and leaves behind hemozoin, that looks like a brown smudge under a microscope. The schizont enters a replicative phase, where it becomes multiple merozoites.
The red blood cell pops, releasing merozoites into the bloodstream. Left with a choice, the merozoites can either repeat the erythrocytic phase, thus producing more merozoites, or they can enter gametogony. Some redo the erythrocytic phase and others enter gametogony. In Gametogony, merozoites divide to become gametocytes. The gametocytes say in red blood cells, waiting to be picked back up again by another female anopheles mosquito. Once in the gut of a mosquito, the gametocytes mature then fuse into zygotes during sporogony (sexual reproduction). The zygote then becomes an ookinete, then an oocyst. The oocyst is filled with sporozoites. When the oocyst ruptures, similarly to the red blood cells in the erythrocytic phase because of the presence of TNFα (Tumor Necrosis Factor alpha) and other inflammatory cytokines, sporozoites travel back up to the salivary glands to repeats the cycle of malaria! When TNFα and similar interferences are released, small fevers occur that can induce fevers, that can also aid in the rupture of red blood cells. The time between fevers depends on the plasmodium species.
Plasmodium species
Time between fevers
Name of fevers
Plasmodium malariae
72 hours
Quartan
Plasmodium ovale
48 hours
Tertian
Plasmodium vivax
48 hours
Tertian
Plasmodium knowlesi
24 hours
N/A
Plasmodium falciparum
Varies (24 hours – 48 hours)
Malignant tertian
There are four common symptoms of Hemolytic Anemia (when red blood cells rupture) which are extreme fatigue, jaundice, headaches and splenomegaly. Most cases of malaria are classified as uncomplicated malaria, due to the symptoms be mild. Plasmodium falciparum causes the most infections. Most infected red blood cells are identified by the spleen and killed. Plasmodium falciparum, however, creates a sticky protein that coats the outside of the red blood cell with little bumps. This causes other red blood cells to stick to it, creating a blockage in blood vessels. Blood vessels are how red blood vessels move, so with a blockage, infected red blood cells cannot reach the spleen. This also causes restricted blood flow to vital organs. Without blood, organ failure can quickly establish itself in the body. Symptoms of organ failure in cerebral malaria, which affects the brain, are comas, seizures and a different mental state. In the liver, bilious malaria, symptoms include diarrhea, vomiting, jaundice and liver failure. The spleen, lungs and kidneys are also affected. These scenarios are complicated malaria. Enlargement of the spleen and liver, hyperreactive malarial splenomegaly, is a symptom of complicated malaria. Repeated infections of plasmodium malariae can cause Nephrotic syndrome (a disease in the kidneys).
Diagnosis
A thick blood smear can show merozoites, early and late trophozoite and schizonts in red blood cells. A thin blood smear can identify what type of plasmodium is infecting the patient. Having more than 5% of red blood cells infected makes treatment harder and worse outcomes are common. Urine the color of tea is also a symptom of malaria.
Treatment
Depending on the stage of infection, medication needs can vary. Medications heavily depend on the severity of the infection, the age and weight of the patient, the geography of the site of initial infection and plasmodium species. Suppressive treatment is prescribed to travelers before they head to a country on or around the malaria belt. It kills sporozoites in the bloodstream before they enter the liver. Therapeutic treatment is given during a current malaria infection, eliminating merozoites in the erythrocytic phase. Gametocidal treatment kills gametocytes to prevent the spread of malaria and to lower the chance of future resistances against future infections. Radical treatment kills hypnozoites in the liver during their dormant phase (plasmodium vivax and plasmodium ovale). Most cases of of uncomplicated malaria get cured with treatment, but after recovery, some patients can still experience symptoms. Recrudescence is when an ineffective treatment did not kill all of the malaria infection. This is a common problem in areas with a high malarial resistance. Relapse is when merozoites were eliminated in the blood, but hypnozoites still remain in the liver. Reinfection is when the treatment worked, but the patient was reinfected with a different series of malaria. This is a common problem in endemic areas. A past infection may produce a tolerance of malaria, but never immunity. Treatments are normally given either a day before departure or four to six weeks before departure.
Prevention
Malaria is most commonly spread by mosquitoes. Anything that can prevent mosquito bites (ITN’s, mosquito repellent creams and sprays, full body clothing, etc.) prevents malaria. Malaria can also be spread by organ donations, blood transfusions, dirty needles, other contaminated surgical tools and in some rare cases, monkeys.
Works Cited
https://www.unicef.org/health/files/health_africamalaria.pdf
https://www.cdc.gov/parasites/malaria/index.html
https://www.medicinenet.com/is_malaria_contagious article.htm#how_does_malaria_spread
https://www.why.is/svar.php?id=5488