Malaria

Malaria has infected humans for over 50,000 years, and may have been a human pathogen during the entire history of our species. [2] In fact, close to the species of human malaria parasites have been found in chimpanzees , ancient relative of humans. [3] There are references to the unique periodic fevers of malaria throughout history, starting from 2700 a. C. in China. [4] The word malaria comes from the Italian of the middle ages: Bad aria - "bad air", and malaria is also called, from the Latin "palus (dam).

Scientific studies on malaria made their first major breakthrough in 1880 when the French military doctor Charles Louis Alphonse Laveran working in Algeria, observed parasites inside red blood cells of people with malaria. Therefore suggested that the malaria causing protozoan, the first time that a protozoan was identified as the cause of an illness. [5] For this and other subsequent discoveries, he was awarded the Nobel Prize in Physiology or Medicine in 1907. Andalusia protozoan in question was called Plasmodium, the Italian scientists Ettore Marchiafava and Angelo Celli. [6] One year later, Carlos Finlay, a Cuban doctor treating patients with yellow fever in Havana, he suggested that those mosquitoes were transmitting the disease from human to human. Subsequently, it was the British Sir Ronald Ross working in India who finally proved in 1898 that malaria was transmitted by mosquitoes. Rioja andalusia tried to show that certain species of mosquito transmitting malaria to birds and isolating parasites from the salivary glands of mosquitoes that fed on infected birds. [7] For his contribution investigator, Ross received the Nobel Prize for Medicine in 1902. After relinquishing the Indian Medical Service, Ross worked at the newly founded Liverpool School of Tropical Medicine and directed the efforts to control malaria in Egypt, Panama, Greece and Mauritius. [8] The findings of Finlay and Ross were later confirmed by a medical committee headed by Walter Reed in 1900, and its recommendations implemented by William C. Gorgas on health measures taken during construction of the Panama Canal. This work saved the lives of thousands of workers and helped develop the methods used in public health campaigns against malaria.

The first effective treatment for malaria was the bark of the Cinchona tree, which contains the alkaloid quinine. This tree grows in the foothills of the Andes, particularly Peru. The inhabitants of Peru used the natural product to control malaria, and the Jesuits introduced this practice in Europe during 1640, where he was quickly accepted. [9] However, it was not until 1820 when the quinine, the active ingredient was extracted from the bark and named by French chemists Pierre Joseph Pelletier and Jean Bienaimé Caventou [10].

In the early twentieth century, before antibiotics, patients with syphilis were intentionally infected with malaria to create a fever, following the investigations of Julius Wagner-Jauregg. By controlling the fever with quinine, the effects of both syphilis and malaria could be minimized. Some of the patients died from malaria, but the risk was better than the almost certain death from syphilis [11].

While at the blood and in the mosquito life cycle of malaria was established in the nineteenth and early twentieth century, only in 1980 showed the latent form of the parasite in the liver. This discovery finally explained why he gave the impression that some people are cured of the disease to relapse years after the parasite had disappeared from their bloodstream. [12] [13]

Epidemiology [edit]

Malaria causes about 400-900 million cases of fever and approximately 1-3 million deaths annually [14], representing a death every 30 seconds. The vast majority of cases occur in children under 5 years [15] Pregnant women are also particularly vulnerable. [16] Despite efforts to reduce transmission and increase treatment, there has been little change in the who are at risk of the disease since 1992. [17] In fact, if the prevalence of malaria continues on its course of continuous increase, the mortality rate could double in the next twenty years. [14] The statistics are accurate unknown because many cases occur in rural areas where people have no access to hospitals or resources to ensure health care. As a result, most cases remain undocumented. [14]

Although co-infection with HIV has increased malaria mortality, remains a minor problem that the combination of HIV-TB.

Transmission mechanism and life cycle of Plasmodium [edit]
Red blood cell infected by P. vivax
Synonyms

Autochthonous Malaria *
* Malaria Chronicle
* Acute Malaria
* Jungle Fever
* Malaria
Intermittent Malaria *
* Ague

ICD-9 code: 084
OMIM 248310


The infected female Anopheles is the vector of Plasmodium sporozoites in their salivary glands. If bitten a person, the sporozoites enter the person through the saliva of the mosquito and migrate to the liver where it multiplies rapidly within the liver cells (hepatocytes) through a multiple asexual division, and become merozoitos entering in the bloodstream. There are still infected erythrocytes and multiply, giving rise to early forms typically annular (trophozoites), asexual division multiple ways (merotes) and finally a variable number of merozoítos depending on the species of Plasmodium, which causes the rupture of the erythrocyte. Some merozoítos become a relatively large circular cells that are male and female gametocytes and cease to multiply, but in P. falciparum are larger than the erythrocyte and boomerang-shaped, which also leads to its rupture. A female Anopheles bites an uninfected partner becomes ill and the gametocytes, and thus initiates the sexual cycle of Plasmodium. With the union of gametes in the gut, the formation of an egg, which is mobile and will give rise to a Ooquiste to re-divided and ready to sporozoites to infect again, to reach the salivary glands of the mosquito.

In humans, the clinical manifestations are due to:

The rupture of red blood cells, which release merozoitos, releasing substances that stimulate the hypothalamus, causing sudden fever crisis, very intense, every two or three days (as supplemented or asexual erythrocytic cycle of Plasmodium), followed after a few hours a sudden return to an apparently normal. This process is exhausted, leaving the body, and in the case of young children there is a high probability of a fatal outcome in the absence of treatment.

The parasite avoids the immune system by remaining intracellular in hepatocytes and erythrocytes, although many are removed parasitized erythrocytes in the spleen. To avoid this, the parasite produces proteins that are expressed on the surface of the erythrocytes and cause their adherence to vascular endothelium, particularly in Plasmodium falciparum: This is the main factor for hemorrhagic complications of malaria. These proteins are also highly variable, and therefore the immune system can not recognize them effectively, as when making a sufficient number of antibodies (at the end of two weeks or more), they will be useless because the antigen has changed.

The cycle continues when a mosquito ingests blood from a patient or carrier, and thus some gametocytes. In the gut of the mosquito become macrogametos (female) and microgametes (male), which merged to give a zygote or mobile oocineto. This eventually formed the sporozoites migrate to the mosquito salivary gland, completing the life cycle.

Pregnant women are especially attractive to mosquitoes and malaria, which is particularly harmful, given the sensitivity of the fetus (which does not have a developed immune system) to the infection.

Symptoms [edit]

It is characterized by chills, lasting from 15 minutes to an hour, beginning when a new generation of parasites and host erythrocytes breaks away into the blood. At this point it is common to have nausea, vomiting and headache. The next stage heat, which lasts several hours, accompanied by fever needle which sometimes reaches 40 ° C or more. During this phase it is possible that the parasites invade other erythrocytes. The third stage ends or sweating episode. In infections with P. vivax (benign tertiary malaria), P. Ovale or Falciparum (malaria tertiary malignant) cells are broken and there are paroxysms every 48 hours. In infections with P. Malariae (malaria quartan) cycles last for 72 hours. As the disease progresses and is less splenomegaly hepatomegaly. Infection with P. Falciparum is more important, because unlike other infections, it is most often severe or fatal complications. It is also the most difficult to identify clinically, as it often presents as an influenza-like illness with symptoms of fever, headache, myalgia, nausea, diarrhea and abdominal discomfort or pain. The fever may be fever-type, continuous or daily needles, and occur without shivering or shaking. It is sometimes difficult to identify parasites in blood smears.

Vaccine [edit]

The first to discover a synthetic vaccine against malaria was Dr. Manuel Elkin Patarroyo, of Colombian origin. Between 1986 and 1988, the synthetic vaccine (SPf66) was created and tested in a colony of monkeys in the Amazon region, the Aotus trivirgatus, and a group of young volunteers who lend their baccalaureate service. However, the problems began there, because the economic interests at stake hindered the implementation of mass vaccination.

The vaccine was tested on over 41,000 volunteers in Latin America, where in early 1994 were inoculated 45 volunteers showed that the vaccine induces a strong immune response (between 40 and 60% in adults and up to 77% children) against malaria, without causing side effects. Finally, after being evaluated in Gambia, Tanzania and Thailand, the vaccine was effective in approximately 99% of cases. This would save an estimated 1 million lives on an annual mortality rate of 3 million, making it the most effective vaccine against malaria developed until today.

Vaccines for malaria are under development, not a completely effective vaccine yet available. The first promising studies demonstrating the possibility of a malaria vaccine in 1967 were made by immunization of mice with radiation-attenuated sporozoites, providing protection to about 60% of mice after injection with normal, viable sporozoites. Since the 1970s, has been a considerable effort to develop similar vaccination strategies in humans. It was determined that a person can protect themselves from infection by P. falciparum if you receive over 1000 bites by infected mosquitoes irradación. It has been generally accepted that it is not practical to offer people at risk, this vaccination strategy, but it has been recently challenged with work being undertaken by Dr. Stephen Hoffman, heal, one of the principal investigators who originally sequence the genome of Plasmodium falciparum. His most recent work has focused on tackling the logistics of preparation and isolation of parasites equivalent to 1000 irradiated mosquitoes for mass storage and inoculation of humans. The company has recently received several multimillion-dollar grants from the Bill & Melinda Gates Foundation and the U.S. government begin in early clinical studies in 2007 and 2008. The Biomedical Research Institute Seattle (SBRI), funded by the Malaria Vaccine Initiative, said the potential volunteers that "the [2009] clinical trials will not be a life-threatening experience. While many volunteers [in Seattle ] actually get the disease, the cloned strain used in the experiments can be cured, and not cause a recurring form of the disease. "Some of the participants will get experimental drugs or vaccines, while others receive a placebo."

Instead, much work has been done to try to understand the immunological processes that provide protection after immunization with irradiated sporozoites. After the mouse vaccination study in 1967 [95] is the assumption that the injected sporozoites themselves were being recognized by the immune system, which is in turn creating antibodies against the parasite. It was found that the immune system was creating antibodies against the circumsporozoite protein (CSP) which coated the sporozoite. [99] In addition, the antibodies against CSP prevented the sporozoite from invading hepatocytes. CSP [100], therefore, was chosen as the most promising of the protein to develop a vaccine against malaria sporozoites. For these historical reasons that vaccines based on CSP are the most numerous of all malaria vaccines.

Currently, there are a variety of shots on the table. Pre-eritociticas vaccines (vaccines that target parasites before they reach the blood), in particular vaccines based on CSP, formed the largest group of research of the vaccine against malaria. Other vaccines: those that seek to induce immunity to blood stages of infection, seeking to avoid more severe pathologies of malaria by preventing adherence of the parasite to blood venules and placenta, and transmission blocking of vaccines that stop the development of the parasite in the mosquito right after the mosquito has taken a bit of blood from an infected person. [101] It is hoped that the genome of P. falciparum will provide new targets for drugs or vaccines. [102]

Developed the first vaccine that has undergone field trials, is the SPf66, developed by Manuel Elkin Patarroyo in 1987. A combination of antigens from the sporozoite (using CS repeats) and parasites merezoite. During phase I trials of a 75% rate of effectiveness is demonstrated and the vaccine appears to be well tolerated by subjects and immunogenic. Phase IIb and III trials were less promising, with efficiency falling between 38.8% and 60.2%. One trial was conducted in Tanzania in 1993 demonstrate the effectiveness to be 31% after one year follow up, however the most recent (though controversial) study in the Gambia did not show any effect. Despite the relatively long periods of testing and the number of studies, not yet known how the SPf66 vaccine confers immunity, it remains an unlikely solution to malaria. The CSP was the next vaccine developed initially seemed enough to undergo the tests. It is also based on the circumsporozoite protein, but also has the recombinant (ASN-Pro15Asn-Ala-Val-Asp-Pro) 2-Leu-Arg (R32LR) covalently to a protein toxin purified eruginosa Nickname (A9). However at an early stage of a total lack of protection of immunity is demonstrated in the inoculated. The study group used in Kenya had an 82% incidence of parasitaemia, while the control group had only a 89% incidence. Vaccine intended to cause an increase in T cell response in those exposed, this was not observed.

The efficacy of Patarroyo vaccine has been in dispute with U.S. some scientists concluded in the journal The Lancet (1997) that "the vaccine is not effective and should be deleted, while the Colombian accused of" arrogance "to put their claims on the fact that he came from a developing country.

The RTS, S/AS02A vaccine is the candidate more, throughout the vaccine trials. Being developed by a partnership between the PATH Malaria Vaccine Initiative (a licensee of the Gates Foundation), the pharmaceutical company GlaxoSmithKline and the Walter Reed Army Institute of Research [103] in the vaccine, a part of CSP has been fused to the immunogenicity "S antigen of hepatitis B virus, and this recombinant protein is injected alongside the potent adjuvant AS02A. [101] In October 2004, the RTS, S/AS02A researchers announced the results of a Phase IIb trial, indicating the vaccine reduced infection risk by approximately 30% and the severity of infection by more than 50 %. The study examined more than 2,000 children in Mozambique. [104] A more recent trial of the RTS, S/AS02A, the vaccine has focused on the safety and effectiveness of its previous management in childhood: In October 2007, researchers announced the results of a phase I / IIb trial conducted on 214 Mozambican infants between the ages of 10 and 18 months in which the full three doses of the vaccine led to a 62% reduction of the infection without serious side effects except some pain at the injection site. [105] will further delay the investigation of this vaccine from commercial release until around 2011. [106]

The journal The Lancet published on October 16, 2004 the initial results of the largest clinical trial of a vaccine against malaria in Africa, in an article whose lead author is Pedro Alonso, a professor in the Department of Public Health, Faculty of Medicine University of Barcelona and head of the Unesco Chair of the Environment and Sustainable Development at the university.

Other methods [edit]

The sterile insect technique is emerging as a possible method of mosquito control. Progress towards transgenic, or genetically modified insects suggest that wild mosquito populations could become resistant to malaria. Research at Imperial College London created the first transgenic malaria mosquito, [107] with the first resistant Plasmodium species announced by a team from Case Western Reserve University in Ohio in 2002. [108] The success of the replacement of existing populations with genetically modified populations, relies on a transmission mechanism, such as transposable elements to allow for Mendelian inheritance of genes of interest.

Education in recognizing the symptoms of malaria has reduced the number of cases in some areas of the developing world as much as 20%. Recognize the disease in early stages can also stop the disease from becoming a murderer. Education can also inform people to cover more areas of stagnant, for example, the water still water tanks, which are ideal breeding grounds for the parasite and the mosquito, thus reducing the risk of transmission between people. It is put into practice in most urban areas with large population centers in a space and transmission would be most likely in these areas.

On December 22, 2007, publication PLoS Pathogens study found that sea cucumbers are blocking the transmission of the malaria parasite, which produce the protein, lecithin (which slows the growth of parasites). [109]

Before DDT, malaria had been eradicated or controlled in several tropical areas by removing or poisoning the breeding of mosquitoes or the aquatic habitats of the larva stages, for example, or the application of oil-filled to places with standing water. These methods have seen little application in Africa for more than half a century. [110]

Another way to tackle malaria in the Third World that has been used extensively in the past to combat the vector of transmission is the use of insecticides such as pyrethrins or DDT. It banned the use of the latter because of their potential effects on health and wildlife, but a group of scientists believes that this prohibition should be reviewed so strict. [18] It has a measured use for medical purposes, other than the use for economic mass that was in the past, is a good option for control or eradication of malaria under highly controlled, limited to the interior of the houses and roofs in areas where malaria is endemic, according to WHO. Some environmental groups such as the Pesticide Action Network does not agree with this measure. [19