Malaria may weaken the skeleton

Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by parasitic protozoans (a group of single-celled microorganisms) belonging to the Plasmodium type. Malaria causes symptoms that typically include fever, feeling tired, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.
3.2 millions

people in risk
214 millions

cases in 2015

Of all malaria deaths occur in sub-Saharan Africa
The history
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Although the parasite responsible for P. falciparum malaria has been in existence for 50,000–100,000 years, the population size of the parasite did not increase until about 10,000 years ago, concurrently with advances in agriculture and the development of human settlements. Close relatives of the human malaria parasites remain common in chimpanzees. Some evidence suggests that the P. falciparum malaria may have originated in gorillas.
References to the unique periodic fevers of malaria are found throughout recorded history. Hippocrates described periodic fevers, labelling them tertian, quartan, subtertian and quotidian. The Roman Columella associated the disease with insects from swamps.Malaria may have contributed to the decline of the Roman Empire, and was so pervasive in Rome that it was known as the "Roman fever". Several regions in ancient Rome were considered at-risk for the disease because of the favourable conditions present for malaria vectors. This included areas such as southern Italy, the island of Sardinia, the Pontine Marshes, the lower regions of coastal Etruria and the city of Rome along the Tiber River. The presence of stagnant water in these places was preferred by mosquitoes for breeding grounds. Irrigated gardens, swamp-like grounds, runoff from agriculture, and drainage problems from road construction led to the increase of standing water.
The term malaria originates from Medieval Italian: mala aria—"bad air"; the disease was formerly called ague or marsh fever due to its association with swamps and marshland. The term first appeared in the English literature about 1829.Malaria was once common in most of Europe and North America, where it is no longer endemic, though imported cases do occur.
Scientific studies on malaria made their first significant advance in 1880, when Charles Louis Alphonse Laveran—a French army doctor working in the military hospital of Constantine in Algeria—observed parasites inside the red blood cells of infected people for the first time. He, therefore, proposed that malaria is caused by this organism, the first time a protist was identified as causing disease. For this and later discoveries, he was awarded the 1907 Nobel Prize for Physiology or Medicine. A year later, Carlos Finlay, a Cuban doctor treating people with yellow fever in Havana, provided strong evidence that mosquitoes were transmitting disease to and from humans. This work followed earlier suggestions by Josiah C. Nott, and work by Sir Patrick Manson, the "father of tropical medicine", on the transmission of filariasis.

Chinese traditional Chinese medicine researcher Tu Youyou received the Nobel Prize for Physiology or Medicine in 2015 for her work on antimalarial drug artemisin.

In April 1894, a Scottish physician Sir Ronald Ross visited Sir Patrick Manson at his house on Queen Anne Street, London. This visit was the start of four years of collaboration and fervent research that culminated in 1898 when Ross, who was working in the Presidency General Hospital in Calcutta, proved the complete life-cycle of the malaria parasite in mosquitoes. He thus proved that the mosquito was the vector for malaria in humans by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. For this work, Ross received the 1902 Nobel Prize in Medicine. After resigning from the Indian Medical Service, Ross worked at the newly established Liverpool School of Tropical Medicine and directed malaria-control efforts in Egypt, Panama, Greece and Mauritius.The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed in 1900. Its recommendations were implemented by William C. Gorgas in the health measures undertaken during construction of the Panama Canal. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against the disease.

Joseph Smith
British doctor Ronald Ross received the Nobel Prize for Physiology or Medicine in 1902 for his work on malaria

The medicinal value of Artemisia annua has been used by Chinese herbalists in traditional Chinese medicines for 2,000 years. In 1596, Li Shizhen recommended tea made from qinghao specifically to treat malaria symptoms in his "Compendium of Materia Medica". Artemisinins, discovered by Chinese scientist Tu Youyou and colleagues in the 1970s from the plant Artemisia annua, became the recommended treatment for P. falciparum malaria, administered in combination with other antimalarials as well as in severe disease. Tu says she was influenced by a traditional Chinese herbal medicine source, The Handbook of Prescriptions for Emergency Treatments, written in 340 by Ge Hong. For her work on malaria, Tu Youyou received the 2015 Nobel Prize in Physiology or Medicine.
Life cycle
In the life cycle of Plasmodium, a female Anopheles mosquito (the definitive host) transmits a motile infective form (called the sporozoite) to a vertebrate host such as a human (the secondary host), thus acting as a transmission vector. A sporozoite travels through the blood vessels to liver cells (hepatocytes), where it reproduces asexually (tissue schizogony), producing thousands of merozoites. These infect new red blood cells and initiate a series of asexual multiplication cycles (blood schizogony) that produce 8 to 24 new infective merozoites, at which point the cells burst and the infective cycle begins anew.
Other merozoites develop into immature gametocytes, which are the precursors of male and female gametes. When a fertilized mosquito bites an infected person, gametocytes are taken up with the blood and mature in the mosquito gut. The male and female gametocytes fuse and form an ookinete—a fertilized, motile zygote. Ookinetes develop into new sporozoites that migrate to the insect's salivary glands, ready to infect a new vertebrate host. The sporozoites are injected into the skin, in the saliva, when the mosquito takes a subsequent blood meal.
Only female mosquitoes feed on blood; male mosquitoes feed on plant nectar and do not transmit the disease. The females of the Anopheles genus of mosquito prefer to feed at night. They usually start searching for a meal at dusk and will continue throughout the night until taking a meal. Malaria parasites can also be transmitted by blood transfusions, although this is rare.

Owing to the non-specific nature of the presentation of symptoms, diagnosis of malaria in non-endemic areas requires a high degree of suspicion, which might be elicited by any of the following: recent travel history, enlarged spleen, fever, low number of platelets in the blood, and higher-than-normal levels of bilirubin in the blood combined with a normal level of white blood cells.
Malaria is usually confirmed by the microscopic examination of blood films or by antigen-based rapid diagnostic tests (RDT). In some areas, RDTs need to be able to distinguish whether the malaria symptoms are caused by Plasmodium falciparum or by other species of parasites since treatment strategies could differ for non-P. falciparum infections. Microscopy is the most commonly used method to detect the malarial parasite—about 165 million blood films were examined for malaria in 2010. Despite its widespread usage, diagnosis by microscopy suffers from two main drawbacks: many settings (especially rural) are not equipped to perform the test, and the accuracy of the results depends on both the skill of the person examining the blood film and the levels of the parasite in the blood. The sensitivity of blood films ranges from 75–90% in optimum conditions, to as low as 50%. Commercially available RDTs are often more accurate than blood films at predicting the presence of malaria parasites, but they are widely variable in diagnostic sensitivity and specificity depending on manufacturer, and are unable to tell how many parasites are present.
In regions where laboratory tests are readily available, malaria should be suspected, and tested for, in any unwell person who has been in an area where malaria is endemic. In areas that cannot afford laboratory diagnostic tests, it has become common to use only a history of fever as the indication to treat for malaria—thus the common teaching "fever equals malaria unless proven otherwise". A drawback of this practice is overdiagnosis of malaria and mismanagement of non-malarial fever, which wastes limited resources, erodes confidence in the health care system, and contributes to drug resistance. Although polymerase chain reaction-based tests have been developed, they are not widely used in areas where malaria is common as of 2012, due to their complexity.
Methods used to prevent malaria include medications, mosquito elimination and the prevention of bites. There is no vaccine for malaria. The presence of malaria in an area requires a combination of high human population density, high anopheles mosquito population density and high rates of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these is lowered sufficiently, the parasite will eventually disappear from that area, as happened in North America, Europe and parts of the Middle East. However, unless the parasite is eliminated from the whole world, it could become re-established if conditions revert to a combination that favors the parasite's reproduction. Furthermore, the cost per person of eliminating anopheles mosquitoes rises with decreasing population density, making it economically unfeasible in some areas.

Prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the initial costs required are out of reach of many of the world's poorest people. There is a wide difference in the costs of control (i.e. maintenance of low endemicity) and elimination programs between countries. For example, in China—whose government in 2010 announced a strategy to pursue malaria elimination in the Chinese provinces—the required investment is a small proportion of public expenditure on health. In contrast, a similar program in Tanzania would cost an estimated one-fifth of the public health budget.
In areas where malaria is common, children under five years old often have anemia which is sometimes due to malaria. Giving children with anemia in these areas preventive antimalarial medication improves red blood cell levels slightly but did not affect the risk of death or need for hospitalization.
An advertisement for quinine as a malaria treatment from 1927
Malaria is treated with antimalarial medications; the ones used depends on the type and severity of the disease. While medications against fever are commonly used, their effects on outcomes are not clear.
Simple or uncomplicated malaria may be treated with oral medications. The most effective treatment for P. falciparum infection is the use of artemisinins in combination with other antimalarials (known as artemisinin-combination therapy, or ACT), which decreases resistance to any single drug component. These additional antimalarials include: amodiaquine, lumefantrine, mefloquine or sulfadoxine/pyrimethamine. Another recommended combination is dihydroartemisinin and piperaquine. ACT is about 90% effective when used to treat uncomplicated malaria. To treat malaria during pregnancy, the WHO recommends the use of quinine plus clindamycin early in the pregnancy (1st trimester), and ACT in later stages (2nd and 3rd trimesters). In the 2000s (decade), malaria with partial resistance to artemisins emerged in Southeast Asia. Infection with P. vivax, P. ovale or P. malariae usually do not require hospitalization. Treatment of P. vivax requires both treatment of blood stages (with chloroquine or ACT) and clearance of liver forms with primaquine. Treatment with tafenoquine prevents relapses after confirmed P. vivax malaria.
Severe and complicated malaria are almost always caused by infection with P. falciparum. The other species usually cause only febrile disease. Severe and complicated malaria are medical emergencies since mortality rates are high (10% to 50%). Cerebral malaria is the form of severe and complicated malaria with the worst neurological symptoms. Recommended treatment for severe malaria is the intravenous use of antimalarial drugs. For severe malaria, parenteral artesunate was superior to quinine in both children and adults. In another systematic review, artemisinin derivatives (artemether and arteether) were as efficacious as quinine in the treatment of cerebral malaria in children. Treatment of severe malaria involves supportive measures that are best done in a critical care unit. This includes the management of high fevers and the seizures that may result from it. It also includes monitoring for poor breathing effort, low blood sugar, and low blood potassium.
And now
If they do the same in people, they could stunt the growth of children infected with the disease.
Malaria parasites leave a trail of destruction in an infected person's body. The microscopic invaders massacre red blood cells, produce harmful chemicals, and sometimes damage the brain. A new mouse study suggests that the parasites can also weaken bones. If they do the same in people, they could stunt the growth of children infected with the disease. But the study also provides some good news, identifying a potential way to prevent the skeletal decline with a compound similar to vitamin D.
Regina Joice Cordy
"It's important work," says parasitologist Regina Joice Cordy of Emory University in Atlanta, who wasn't connected to the study. "It's taken us a step further," she adds, in understanding the long-term effects of malaria infections.
alaria parasites, which are transmitted through the bite of an infected mosquito, cause the most destruction during the part of their life cycle when they dwell in red blood cells circulating through the body. There, they reproduce and feast on oxygen-carrying hemoglobin proteins, releasing noxious byproducts. The parasites eventually explode from the blood cells, killing them in droves. Although researchers have also detected the parasites in bone marrow, where blood-forming stem cells reside, no one has known until now whether they damage the skeleton.

To find out, a team led by graduate student Michelle Lee and immunologist Cevayir Coban of Osaka University in Japan infected mice with either of two species of malaria parasites. The rodents' immune systems fought off the parasites, but the animals' skeletons showed the effects of the infection. "We found bone loss for both types of infections," Coban says. In adult mice, the spongy material inside the bones began to break down. It contained more gaps, and support structures were thinner and less numerous. Similar changes occur in the bones of people with osteoporosis, Coban says.

In young mice, the bones also grew slower than normal. As a result, the animals' thigh bones were about 10% shorter than those of their uninfected counterparts, the researchers report online today in Science Immunology.
The parasites might trigger these problems, the scientists hypothesized, by upsetting the normal balance between cells known as osteoclasts, which dissolve bone, and cells called osteoblasts, which build it back up. The researchers discovered that both types of cells shut down when the mice were infected with malaria. Once the animals had eliminated the parasites, both cell types started working again. But bone breakdown outpaced bone restoration, suggesting that osteoclasts were working harder.

Why do the mice's bones deteriorate even after their immune system ousted the parasites? Lee, Coban, and colleagues suspected that the culprit was chemical waste released by the parasites, including the residue of digested hemoglobin, a molecule called hemozoin. In malaria-infected mice, the researchers found, hemozoin seeped into the bones, turning them black. It was still there 2 months after the parasites had been eliminated. To gauge the impact of hemozoin and other parasite wastes, the team cultured bone marrow cells in a cocktail of these substances. The mixture spurred the cells to release inflammation-promoting molecules known to spur osteoclast production.
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That mechanism suggested a way to block the parasite's bone-destroying effects. Coban and colleagues gave infected mice alfacalcidol, a derivative of vitamin D that treats osteoporosis by suppressing osteoclasts and stimulating osteoblasts. The drug prevented bone loss in the mice.

Cordy says the proposed bone-destroying mechanism is plausible. The key question, she says, is whether it occurs in humans. So far, Coban says, the researchers don't have direct evidence that malaria triggers bone loss in people. Children in malaria-prone areas often grow abnormally slowly, but researchers aren't sure whether malaria or other diseases that are prevalent in these areas are to blame. If further studies confirm the new findings, treating kids with alfacalcidol or related molecules, along with antimalarials, might lead to a growth spurt.

Alexandra Bubenets
Assistant in a big medical organisation
The Malaria Eradication Research Agenda (malERA) initiative was a consultative process to identify which areas of research and development (R&D) needed to be addressed for the worldwide eradication of malaria.
A vaccine against malaria called RTS,S, was approved by European regulators in 2015. It is undergoing pilot trials in select countries in 2016.
Immunity (or, more accurately, tolerance) to P. falciparum malaria does occur naturally, but only in response to years of repeated infection. An individual can be protected from a P. falciparum infection if they receive about a thousand bites from mosquitoes that carry a version of the parasite rendered non-infective by a dose of X-ray irradiation. The highly polymorphic nature of many P. falciparum proteins results in significant challenges to vaccine design. Vaccine candidates that target antigens on gametes, zygotes, or ookinetes in the mosquito midgut aim to block the transmission of malaria. These transmission-blocking vaccines induce antibodies in the human blood; when a mosquito takes a blood meal from a protected individual, these antibodies prevent the parasite from completing its development in the mosquito.Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have been inadequate on their own. For example, SPf66 was tested extensively in areas where the disease is common in the 1990s, but trials showed it to be insufficiently effective.

I think if we unite and work harder and more effectively, malaria will cease to be such a formidable disease. It is necessary to develop the fight against insect vectors, to conduct more clinical studies, to take preventive measures and everything will be fine.
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