The outbreaks of malaria are not uncommon and it is fatal disease if left untreated. Malaria is actually a infectious disease transmitted by mosquito and is caused by a protozoan of the genus Plasmodium. It has a very common occurrence in the tropical and the subtropical countries including America, Africa and Asia. Malaria affects 350-500 million people all over the world every year and about 1-3 million people lose their lives because of this fatal disease. 90% of the deaths due to malaria occur in the sub-Saharan Africa. Malaria is a major hindrance in the economic development of any nation as it is associated with the poverty. Basically five species of Plasmodium are known to infect humans with malaria but the species Plasmodium falciparum is known to be the most fatal one. Another species Plasmodium knowlesi generally causes heavy mortality in the population of macaques but can also affect the human population.
Anopheles mosquito is the vector of Plasmodium. When the mosquito bites an infected person along with the blood meal the malarial parasites enter into the body of the mosquito where they develop further. After one week of development the parasites are again transferred into the blood of a human being through the saliva of the mosquito. The parasites then migrate to their favourite site of development which is the liver. Between the period of two weeks and several months the parasites start multiplying and invade the red blood cells and start causing fever and headache. The conditions when worsen may result in coma and even death of the individual. Presently a number of drugs are available for the treatment of malaria but in the last five years the use of artemisinin derivative has increased while preparing the anti-malarial drugs. Severe malaria is treated intravenously or intramuscularly. Resistance has been developed against a well known drug chloroquine. The spread of malaria can be prevented by minimizing the mosquito bites by using mosquito nets, mosquito repellents and use of insecticides. The mosquito population can be prevented from spreading by draining the stagnant water which may encompass the eggs and the larval stages of the mosquitoes.
Indications of malaria
The major symptoms of malaria are fever, shivering, joint pain, anemia, vomiting, hemoglobinuria, retinal damage and convulsions. The preliminary symptom of malaria is cyclical occurrence of coldness which is followed by rigor and then fever which is followed by sweating which lasts for 36-48 hours in case of P. falciparum infection. The fever is alone capable of causing brain damage. Malaria may also cause cognitive impairment in the children. Cerebral malaria is very common among children where whitening of the retina is present and later on brain damage may occur. Malaria especially when P.falciparum is involved develops after 6-14 days after infection. The side effects of malaria include coma and death if left untreated. Young children and pregnant women are at greater risk of getting infected. The other symptoms of malaria include enlarged spleen or splenomegaly, severe headache, cerebral ischemia, hepatomegaly or enlarged liver, hypoglycemia, hemoglobinuria and renal failure. The failure of kidneys result in the occurrence of blackwater fever where red blood cells burst and the hemoglobin is leaked into the urine. Malaria if left untreated may cause death within few hours or days. The fatality of malaria can increase up to 20% in extreme cases. Developmental impairments have been observed in the children who have suffered from malaria at the early stage of their lives. Chronic malaria has not been found associated with P. falciparum but is associated with P. vivax and P. ovale. In chronic malaria the parasite may remain inactive for many years and may not be noticed in the blood stream. The largest incubation period has been observed in case of P. vivax of 30 years.
Causes
Parasites
Malaria parasites belong to genus Plasmodium and in humans the species which are responsible for causing malaria are P. falciparum, P. malariae, P. vivax, P. ovale and P. knowlesi. The major malarial infections about 80% are generally caused by P. falciparum and it is responsible for about 90% deaths of people all over the globe. Parasitic species of Plasmodium also infect birds, reptiles, chimpanzees, monkeys.
Life cycle of malaria parasite and the vector Anopheles mosquito
The definitive host and the vector of the malaria parasite are the female mosquitoes of the genus Anopheles and humans and other vertebrates are the secondary hosts. The life cycle of the parasite begins after the ingestion of the sporozoites of the parasite from the bloodstream of an infected human or any other vertebrate. The sporozoites are taken in the salivary glands by the female mosquito. The sporozoites then convert into gametocytes and enter the gut of the mosquito and differentiate into male and female gametocytes and fuse together. They produce an ookinete which enters the gut lining and later on produces an oocyst in the gut wall. When the oocyst ruptures it produces sporozoites which enter the salivary glands of the mosquito and are ready to infect the human host through the mosquito bite. This type of transfer is generally called ass the anterior station transfer. The sporozoites are transferred through the saliva of the mosquito in the human blood stream.
The male mosquitoes feed on nectar and plant juices so are not responsible for acting as vectors. Only female mosquitoes feed on blood and act as vectors. The females basically prefer to feed at night. Malaria parasites may also get transferred through blood transfusion but this method is very rare.
Pathogenesis
After the transfer of the sporozoites into the blood stream of the humans by the mosquito the sporozoites reach the liver and start infecting the liver cells or hepatocytes. In the liver cells the sprozoites get transformed into merozoites which rupture the liver cells and escape in the blood stream again. After reaching the bloodstream the merozoites start infecting the red blood cells and get converted into ringed forms called trophozoites which are the feeding stage of the parasite. The trophozoites then convert into schizonts which are the reproducing stage and again get converted into merozoites. Sexual forms called the gametocytes are taken by the mosquito in the salivary glands and the cycle repeats again.
Malaria in humans develops in two phases. The first one is the exoerythroctic phase and the second one is the erythrocytic phase. As the name suggests exoerythrocytic phase involves the infection of the liver and the erythrocytic phase involves the infection of the red blood cells. When a infected mosquito bites a human in order to get a blood meal the sporozoites enter the blood stream and enter the liver and within 30 minutes of their arrival in the liver cells they start destroying them. They remain the liver cells for about a period of 6-15 days and develop into merozoites and are released into the blood stream after rupturing the liver cells. Now begins the erythrocytic cycle when the merozoites enter the red blood cells. The parasite remains undetected in the liver cells by covering itself by the cell membrane of the ruptured liver cell.
Within the red blood cells the merozoites divide again and again asexually increasing in numbers and every time they invade fresh red blood cells thus, infecting the cells and destroying them. The destruction of the red blood cells by the merozoites results in the appearance of the waves of fever. The parasite remains protected from the immune system of the host as it spends most of its time in the liver cells and the red blood cells. The circulating infected blood cells are destroyed in the spleen. To avoid this parasite P. falciparum displays adhesive proteins on the walls of the infected red blood cells so that they may get attached to the walls of the small blood vessels and pass easily through the circulation of the spleen. High endothelial venules get blocked by attachment of masses of infected red blood cells. Due to this symptoms of coma may occur.
Diagnosis
The malaria parasite was first observed in the blood by Charles Laveran in 1880. Urine and saliva can also be used for the diagnosis of the parasite. The best identification of the malaria parasite can be done by microscopic examination of the blood film as all the four species of the malaria parasites have distinguishing features. Both thick and thin blood films are used for this purpose. Thin blood films are like the ordinary blood films and are generally used for the identification of the parasite and also support best medium for the preservation of the parasite. Thick films require larger volume of blood and are not supportive for identification of the parasites. P.malariae and P.knowlesi resemble very much in their characteristics so can be easily distinguished by PCR and monoclonal antibody panels. Areas where microscopy is not available the parasite can be identified by commercial antigen tests.
Prevention
Malaria can be prevented by controlling the spread of the vector. This practice has been found to be successful in some countries. Use of the pesticide DDT has been proved successful in some parts of Africa for control of the vector but it has caused the mosquitoes to become resistant to it so can’t be used in future. Sterile insect technique is under progress. The development of the transgenic insects can be beneficial as the population of the wild mosquitoes can be made malaria resistant. Researchers at Imperial College London created the first transgenic malaria mosquito in 2002 and it was designated as the first Plasmodium resistant species. Use of laser in killing of mosquitoes is also under practice.
For the treatment of malaria several drugs are available but they should be handled with care. Drugs are taken either daily or weekly depending upon the condition of the victim. Use of the prophylactic drugs for curing malaria is risky as it can cause side effects. Quinine was used to treat malaria in the early 17th century but with research and development of technology many new alternatives of quinine made their existence. The alternatives include chloroquine, quinacrine and primaquine basically used during the 20th century. At present quinine is still in use and is used against the chloroquine resistant malaria parasite P.falciparum. Modern drugs include mefloquine, doxycycline and a combination of atovaquone and proguanil hydrochloride. The use of prophylactic drugs imparts only partial immunity. Vaccines for curing malaria are under development and no vaccine is presently totally effective in controlling the spread of malaria.
Truly speaking malaria is a curse on the progress of any nation. We must try to take preventive measures in order to remain free from this disease.
