U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH NIH News

 

National Institute of Allergy and Infectious Diseases (NIAID)

 

For Immediate Release: Thursday, April 21, 2011

 

Life Cycle of Malaria Parasites in the Human Body: A mosquito infects a person by taking a blood meal. First, sporozoites enter the bloodstream, and migrate to the liver. They infect liver cells (hepatocytes), where they multiply into merozoites, rupture the liver cells, and escape back into the bloodstream. Then, the merozoites infect red blood cells, where they develop into ring forms, trophozoites and schizonts which in turn produce further merozoites. Sexual forms (gametocytes) are also produced, which, if taken up by a mosquito, will infect the insect and continue the life cycle.

 

 

 

 

NIH STATEMENT ON WORLD MALARIA DAY

APRIL 25, 2011

Statement of B.F. (Lee) Hall, M.D., Ph.D., and Anthony S. Fauci, M.D., National Institute of Allergy and Infectious Diseases, National Institutes of Health

 

 

In commemorating World Malaria Day and reflecting on this year’s theme, “Achieving Progress and Impact,” we celebrate the important strides made in many regions of the world to control malaria, while acknowledging the enormous challenges that remain.

 

In 2000, an estimated 350 million to 500 million clinical cases of malaria occurred worldwide and more than 1 million people died from the disease, according to the World Health Organization (WHO). By 2009, there were about 225 million cases of clinical malaria and 781,000 deaths.

 

Decreases in cases of malaria occurred in all affected regions, with the greatest decline in the number of malaria deaths occurring in Africa. Furthermore, in 2010, WHO certified that two countries, Morocco and Turkmenistan, had eliminated malaria-that is, reduced the incidence of infections in their countries to zero. Although these numbers reflect significant improvements, the global burden of malaria remains far too high and will require sustained and coordinated efforts from the international community to reduce it further.

 

Today we enter the third year of the Global Malaria Action Plan (GMAP), developed by the Roll Back Malaria (RBM) Partnership,  The GMAP, an international framework for coordinated action against malaria, sets ambitious goals to control, eliminate and eradicate malaria.

 

The National Institutes of Health is committed to supporting the GMAP. To make continued progress and achieve long-term GMAP goals, we must build a sustainable pipeline of new products, novel interventions and innovative strategies to diagnose, treat and prevent malaria as well as interrupt its transmission. Below we describe examples of significant advances made in these areas during the past year.

 

The emergence and spread of parasites resistant to conventional anti-malarial drugs threatens treatment efforts.

 

Recently, NIH grantees identified a novel compound that rids mice of malaria-causing parasites with a single oral dose. This compound acts on a novel target in the parasite that may allow it to kill parasites that have developed resistance to other antimalarial drugs. Further studies will determine whether this compound can become a new therapy. Similarly, insecticide resistance can undercut mosquito-control strategies for containing malaria. Although research on insecticides with novel mechanisms of action continues, such compounds, like current insecticides, run the risk of selecting for the emergence and spread of mosquitoes resistant to the new insecticide. Therefore, novel approaches must be pursued.

 

NIH-funded researchers recently identified a genetically modified fungus that blocks development of malaria parasites in the mosquito and thereby interrupts malaria transmission. Because the fungi do not kill the mosquitoes, they would be unlikely to develop resistance. Such fungi could become an important malaria intervention if future studies demonstrate that they are safe and effective.

 

Within the next few months, we expect to learn the results of a large-scale clinical trial in Africa of a candidate malaria vaccine known as RTS,S. We all hope that an effective vaccine that confers protection against the most deadly type of disease, Plasmodium falciparum malaria, soon will be available. Meanwhile, efforts to develop new and improved malaria vaccines continue globally, with 16 candidates currently in preclinical development and another 23 in clinical trials.

 

Early this year, we joined with others in announcing a renewed interest in the possible eradication of malaria, as described in the Malaria Eradication Research Agenda (MalERA), the result of a global consultation effort among multiple stakeholders and disciplines. A key message of MalERA is that the tools to eradicate malaria do not exist and must be developed. A major challenge will be to continually assess the changing epidemiology of malaria as control and elimination efforts prove successful to ensure that appropriate tools and interventions are developed and effectively deployed.

 

To bridge clinical and field research with new laboratory-based methods in immunology, molecular biology and genomics, we at the NIH National Institute of Allergy and Infectious Diseases recently launched a network of International Centers of Excellence for Malaria Research.  This network, which supports teams of scientists conducting research in more than 20 malaria-endemic countries, will provide new insights from research conducted in the context of rapidly changing malaria epidemiology.

 

A strong foundation of scientific insight, technological innovation and effective implementation has enabled us to achieve progress and advance several fronts in the fight against malaria. We must sustain this critical foundation as we continue to work together toward our shared goals of global malaria control, elimination and eradication.

 

For more information on malaria, visit NIAID’s Malaria Web portal <http://www.niaid.nih.gov/topics/Malaria/Pages/default.aspx>.

 

Lee Hall, M.D., Ph.D., is Chief of the Parasitology and International Programs Branch in the NIAID Division of Microbiology and Infectious Diseases. Anthony S. Fauci, M.D., is Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland

 

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at <http://www.niaid.nih.gov>.

 

About the National Institutes of Health (NIH):

 

NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <www.nih.gov>.

 

 

 

‘Malaria

 

 

Credit: NIAID

Glossary

Diploid: Cells containing a full set of chromosomes.
Gametes: Reproductive elements, male and female.
Gametocytes: Precursors of the sexual forms of the malaria parasite, which release either male or female gametes within the stomach of the mosquito.
Haploid: Cells containing a half set of chromosomes.
Merozoite: The form of the malaria parasite that invades red blood cells.
Oocyst: A stage of the malaria parasite within the mosquito which is produced when male and female gametes combine.
Ookinete: The actively moving zygote of the malarial organism that penetrates the mosquito stomach to form an oocyst under the outer gut lining.
Sporozoite: The infectious form of the malaria parasite, which is injected into people by mosquitoes.
Zygote: The diploid cell resulting from union of a male and a female gamete.

Life Cycle of the Malaria Parasite

  1. A female Anopheles mosquito carrying malaria-causing parasites feeds on a human and injects the parasites in the form of sporozoites into the bloodstream. The sporozoites travel to the liver and invade liver cells.
  2. Over 5-16 days*, the sporozoites grow, divide, and produce tens of thousands of haploid forms, called merozoites, per liver cell. Some malaria parasite species remain dormant for extended periods in the liver, causing relapses weeks or months later.
  3. The merozoites exit the liver cells and re-enter the bloodstream, beginning a cycle of invasion of red blood cells, asexual replication, and release of newly formed merozoites from the red blood cells repeatedly over 1-3 days*. This multiplication can result in thousands of parasite-infected cells in the host bloodstream, leading to illness and complications of malaria that can last for months if not treated.
  4. Some of the merozoite-infected blood cells leave the cycle of asexual multiplication. Instead of replicating, the merozoites in these cells develop into sexual forms of the parasite, called male and female gametocytes, that circulate in the bloodstream.
  5. When a mosquito bites an infected human, it ingests the gametocytes. In the mosquito gut, the infected human blood cells burst, releasing the gametocytes, which develop further into mature sex cells called gametes. Male and female gametes fuse to form diploid zygotes, which develop into actively moving ookinetes that burrow into the mosquito midgut wall and form oocysts.
  6. Growth and division of each oocyst produces thousands of active haploid forms called sporozoites. After 8-15 days*, the oocyst bursts, releasing sporozoites into the body cavity of the mosquito, from which they travel to and invade the mosquito salivary glands. The cycle of human infection re-starts when the mosquito takes a blood meal, injecting the sporozoites from its salivary glands into the human bloodstream .

* Time-frame depends on the malaria parasite species.

 

 

 

 

NIH-sponsored Research Yields Promising Malaria Drug Candidate

In Mice, Compound Cleared Malaria parasites Quickly

 

A chemical that rid mice of malaria-causing parasites after a single oral dose may eventually become a new malaria drug if further tests in animals and people uphold the promise of early findings. The compound, NITD609, was developed by an international team of researchers including Elizabeth A. Winzeler, Ph.D., a grantee of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

“Although significant progress has been made in controlling malaria, the disease still kills nearly 1 million people every year, mostly infants and young children,” says NIAID Director Anthony S. Fauci, M.D. “It has been more than a decade since the last new class of antimalarials—artemisinins—began to be widely used throughout the world. The rise of drug-resistant malaria parasites further underscores the need for novel malaria therapies.”

Dr. Fauci adds, “The compound developed and tested by Dr. Winzeler and her colleagues appears to target a parasite protein not attacked by any existing malaria drug, and has several other desirable features. This research is also a notable example of successful collaboration between government-supported scientists and private sector researchers.”

The study, in the Sept. 3 issue of Science, was led by Thierry T. Diagana, Ph.D., of the Novartis Institute for Tropical Diseases (NITD), and Dr. Winzeler. Dr. Winzeler is affiliated with The Scripps Research Institute and the Genomic Institute of the Novartis Research Foundation, La Jolla, Calif.

Work on what eventually became NITD609 began in Dr. Winzeler’s lab in 2007. Scientists screened 12,000 chemicals using an ultra-high throughput robotic screening technique customized to detect compounds active against Plasmodium falciparum, the most deadly malaria parasite. The screen identified a chemical with good parasite-killing abilities and the potential to be modified into a drug. Medicinal chemists at the NITD then synthesized and evaluated about 200 versions of the original compound to arrive at NITD609, which could be formulated as a tablet and manufactured in large quantities. NITD609 is one of a new class of chemicals, the spiroindolones, which have been described in recently published research by Dr. Winzeler and colleagues as having potent effects against two kinds of malaria parasites.

“From the beginning, NITD609 stood out because it looked different, in terms of its structure and chemistry, from all other currently used antimalarials,” says Dr. Winzeler. “The ideal new malaria drug would not just be a modification of existing drugs, but would have entirely novel features and mechanism of action. NITD609 does.”

In the current study, the scientists detail attributes of NITD609 that suggest it could be a good malaria drug. For example

  • In test-tube experiments, NITD609 killed two species of parasites in their blood-stage form and also was effective against drug-resistant strains. In humans, malaria parasites spend part of their life cycle in the blood and part in the liver.
  • The compound worked faster than some older malaria drugs, although not as quickly as the best current malaria drug, artemisinin.
  • Other laboratory tests showed that NITD609 is not toxic to a variety of human cells.

When given orally to rodents, the compound stayed in circulation long enough to reach levels predicted to be effective against malaria parasites. According to Dr. Winzeler, if NITD609 behaves similarly in people, it might be possible to develop the compound into a drug that could be taken just once. Such a dosage regimen, she says, would be substantially better than the current standard treatment in much of the world in which uncomplicated malaria infections are treated for three to seven days with drugs that are taken between one and four times daily.

“We were excited by the potential NITD609 showed in the first series of test-tube experiments,” says Dr. Winzeler. “We became even more enthusiastic when our co-investigators at the Swiss Tropical Institute in Basel tested NITD609 in a mouse model of malaria.”

Typically, she says, rodents infected with the mouse malaria parasite, Plasmodium berghei, die within a week. But a single large dose of NITD609 cured all five infected mice that received it, while half of six mice receiving a single smaller dose were cured of infection. Three doses of the smaller amount of NITD609 upped the cure rate to 90 percent.

The researchers also compared NITD609 with other malaria drugs in P. berghei-infected mice. “No other currently used malaria drug was as potent,” says Dr. Winzeler. NITD609’s effectiveness in relatively few doses is a key point in its favor, she adds. A novel malaria drug that works in as few doses as possible leaves less opportunity for parasites to develop drug resistance.

Additional tests in animals are under way and NITD609 could enter early-stage safety testing in humans later this year, says Dr. Winzeler. But, she adds, many drug candidates fail in clinical trials and thus it will be important for the community to continue to work on developing other potential antimalarial compounds.

To learn how parasites might develop resistance to this potential drug, the researchers also exposed parasites to sublethal levels of NITD609 continuously for several months until drug-resistant strains emerged. Then they analyzed those strains and determined that resistance results from a single change in one of the parasite’s genes. The gene contains the code to make a protein called PfATP4, which allows substances to cross cell membranes. No other anti-malaria drugs act on the PfATP4 protein, notes Dr. Winzeler. Having information in hand about the genetic basis for NITD609 resistance at this early stage of the compound’s development is advantageous, she adds, because it will allow scientists to rapidly detect drug-resistant strains in clinical settings if the compound is eventually approved as a drug for human use.

More information about malaria and NIAID’s research programs on the disease is available on the NIAID malaria Web portal.

###

References:

M Rottmann et al. Spiroindolones, a new and potent chemotype for the treatment of malaria. Science DOI: 10.1126/science.1193225 (2010).

BKS Yeung et al. Spirotetrahydro β-carbolines (Spiroindolones): A new class of potent and orally efficacious compounds for the treatment of malaria. J. of Medicinal Chemistry DOI: 10.1021/jm100410f (2010).

NIAID Malaria Research Program

Nearly one million people die of malaria every year, mostly infants, young children, and pregnant women, and most of them in Africa. Finding effective ways to control and eventually eradicate the disease is a high priority of NIAID.

Malaria Basic Biology

NIAID plays a unique role in the global effort against malaria in that it funds the majority of basic malaria research. The NIAID Malaria Research Program encompasses a broad range of topics, covering the full cycle of malarial disease–from parasite to mosquito to human host. Increased knowledge of these three elements and the multifaceted interactions among them is critical in developing effective tools to prevent and control malaria.

Parasite Biology

Malaria can be caused by several species of Plasmodium parasites, each of which has a complex life cycle (see illustration). Research in recent decades has shed light on many aspects of Plasmodium biology, broadening understanding of how parasites interact with the human immune system, cause human disease, and are transmitted by mosquitoes. Still, in these fundamental areas and others, important questions remain unanswered and new questions have arisen. NIAID supports basic research on parasite biology to unravel the complexities of such crucial processes and increase knowledge of disease transmission, parasite immune evasion, and the emergence of drug resistance.

Vector Biology

 

 

Anopheles albimanus mosquito feeding on a human arm. This mosquito is a vector of malaria and mosquito control is a very effective way of reducing the incidence of malaria.

Malaria parasites are transmitted to human hosts by mosquitoes of the genus Anopheles. A diverse group of Anopheles (between 30 to 40 species) serves as vectors of human disease. Several physiological, behavioral, and ecological characteristics determine how effective various Anopheles species are as vectors of malaria. NIAID supports research on such characteristics to better understand the parasite-vector relationship and determine why some mosquito species transmit malaria parasites while others do not.

Disease Pathogenesis

Malaria pathogenesis is the process by which malaria parasites cause illness, abnormal function, or damage in their human hosts. “Uncomplicated” malaria entails a series of recurring episodes of chills, intense fever, and sweating and sometimes includes other symptoms such as headache, malaise, fatigues, body aches, nausea, and vomiting.

In some cases, and especially in groups such as children and pregnant women, the disease can progress to “severe malaria,” including complications such as cerebral malaria/coma, seizures, severe anemia, respiratory distress, kidney and liver failure, cardiovascular collapse, and shock. Long-term impacts include death, disability, and significant socioeconomic burden on societies where the disease is prevalent. A better understanding of the biological processes underlying the progression of infection to disease is urgently needed to reduce the morbidity and mortality of malaria.

Genomics

Within the last 5 years, the completion of several genome projects related to malaria has marked the beginning of a new era of malaria research. NIAID-supported researchers have sequenced the genomes of the Anopheles gambiae mosquito, a major malaria vector, and of Plasmodium falciparum, the deadliest malaria parasite. These accomplishments, in conjunction with National Institutes of Health-funded sequencing of the human genome, have provided scientists with unprecedented information on complete sets of human, parasite, and mosquito genes. Through such advances, as well as ongoing and planned genomics projects on additional parasites and vectors, NIAID hopes to supply scientists with the tools needed to identify targets for effective disease interventions.

Immunology

The interaction between the Plasmodium parasite and host immune system during infection strikes a tenuous balance. The relationship can elicit protective immunity or trigger harmful immune responses. The complex nature of both the malaria parasite and the human immune response has made it difficult to unravel the mechanisms of protection or pathology in humans. An improved understanding of the immunology of malaria is likely to provide key insights into ways to enhance human immunity while reducing disease pathogenesis.

Epidemiology

Epidemiological data is critical to both developing novel vaccines and drugs and implementing effective control and prevention programs. Understanding malaria on a population level and determining the biological, behavioral, and environmental factors that influence malaria epidemiology and transmission are especially important as the global community strengthens antimalaria efforts.

Medications

Several drugs, most of which are also used for treatment of malaria, can be taken preventively. Modern drugs used include mefloquine (Lariam), doxycycline (available generically), and the combination of atovaquone and proguanil hydrochloride (Malarone). Doxycycline and the atovaquone and proguanil combination are the best tolerated with mefloquine associated with higher rates of neurological and psychiatric symptoms.  The choice of which drug to use depends on which drugs the parasites in the area are resistant to, as well as side-effects and other considerations. The prophylactic effect does not begin immediately upon starting taking the drugs, so people temporarily visiting malaria-endemic areas usually begin taking the drugs one to two weeks before arriving and must continue taking them for 4 weeks after leaving (with the exception of atovaquone proguanil that only needs be started 2 days prior and continued for 7 days afterwards). Generally, these drugs are taken daily or weekly, at a lower dose than would be used for treatment of a person who had actually contracted the disease. Use of prophylactic drugs is seldom practical for full-time residents of malaria-endemic areas, and their use is usually restricted to short-term visitors and travelers to malarial regions. This is due to the cost of purchasing the drugs, negative side effects from long-term use, and because some effective anti-malarial drugs are difficult to obtain outside of wealthy nations.

Quinine was used historically, however the development of more effective alternatives such as quinacrine, chloroquine, and primaquine in the 20th century reduced its use. Today, quinine is not generally used for prophylaxis. The use of prophylactic drugs where malaria-bearing mosquitoes are present may encourage the development of partial immunity.

Vector control

Efforts to eradicate malaria by eliminating mosquitoes have been successful in some areas. Malaria was once common in the United States and southern Europe, but vector control programs, in conjunction with the monitoring and treatment of infected humans, eliminated it from those regions. In some areas, the draining of wetland breeding grounds and better sanitation were adequate. Malaria was eliminated from most parts of the USA in the early 20th century by such methods, and the use of the pesticide DDT and other means eliminated it from the remaining pockets in the South by 1951.  In 2002, there were 1,059 cases of malaria reported in the US, including eight deaths, but in only five of those cases was the disease contracted in the United States.

 

Before DDT, malaria was successfully eradicated or controlled also in several tropical areas by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larva stages, for example by filling or applying oil to places with standing water. These methods have seen little application in Africa for more than half a century.

Sterile insect technique is emerging as a potential mosquito control method. Progress towards transgenic, or genetically modified, insects suggest that wild mosquito populations could be made malaria-resistant. Researchers at Imperial College London created the world’s first transgenic malaria mosquito, with the first plasmodium-resistant species announced by a team at Case Western Reserve University in Ohio in 2002. Successful replacement of current populations with a new genetically modified population, relies upon a drive mechanism, such as transposable elements to allow for non-Mendelian inheritance of the gene of interest. However, this approach contains many difficulties and success is a distant prospect. An even more futuristic method of vector control is the idea that lasers could be used to kill flying mosquitoes.

Indoor residual spraying

Indoor residual spraying (IRS) is the practice of spraying insecticides on the interior walls of homes in malaria affected areas. After feeding, many mosquito species rest on a nearby surface while digesting the bloodmeal, so if the walls of dwellings have been coated with insecticides, the resting mosquitos will be killed before they can bite another victim, transferring the malaria parasite.

The first pesticide used for IRS was DDT. Although it was initially used exclusively to combat malaria, its use quickly spread to agriculture. In time, pest-control, rather than disease-control, came to dominate DDT use, and this large-scale agricultural use led to the evolution of resistant mosquitoes in many regions. The DDT resistance shown by Anopheles mosquitoes can be compared to antibiotic resistance shown by bacteria. The overuse of anti-bacterial soaps and antibiotics led to antibiotic resistance in bacteria, similar to how overspraying of DDT on crops led to DDT resistance in Anopheles mosquitoes. During the 1960s, awareness of the negative consequences of its indiscriminate use increased, ultimately leading to bans on agricultural applications of DDT in many countries in the 1970s. Since the use of DDT has been limited or banned for agricultural use for some time, DDT may now be more effective as a method of disease-control.

Although DDT has never been banned for use in malaria control and there are several other insecticides suitable for IRS, some advocates have claimed that bans are responsible for tens of millions of deaths in tropical countries where DDT had once been effective in controlling malaria. Furthermore, most of the problems associated with DDT use stem specifically from its industrial-scale application in agriculture, rather than its use in public health.

The World Health Organization (WHO) currently advises the use of 12 different insecticides in IRS operations, including DDT as well as alternative insecticides (such as the pyrethroids permethrin and deltamethrin). This public health use of small amounts of DDT is permitted under the Stockholm Convention on Persistent Organic Pollutants (POPs), which prohibits the agricultural use of DDT. However, because of its legacy, many developed countries previously discouraged DDT use even in small quantities.

One problem with all forms of Indoor Residual Spraying is insecticide resistance via evolution of mosquitos. According to a study published on Mosquito Behavior and Vector Control, mosquito species that are affected by IRS are endophilic species (species that tend to rest and live indoors), and due to the irritation caused by spraying, their evolutionary descendants are trending towards becoming exophilic (species that tend to rest and live out of doors), meaning that they are not as affected—if affected at all—by the IRS, rendering it somewhat useless as a defense mechanism.

Mosquito nets and bedclothes

Mosquito nets help keep mosquitoes away from people and greatly reduce the infection and transmission of malaria. The nets are not a perfect barrier and they are often treated with an insecticide designed to kill the mosquito before it has time to search for a way past the net. Insecticide-treated nets (ITNs) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net. Although ITNs are proven to be very effective against malaria, less than 2% of children in urban areas in Sub-Saharan Africa are protected by ITNs. Since the Anopheles mosquitoes feed at night, the preferred method is to hang a large “bed net” above the center of a bed such that it drapes down and covers the bed completely.

Vaccination

Immunity (or, more accurately, tolerance) does occur naturally, but only in response to repeated infection with multiple strains of malaria. Vaccines for malaria are under development, with no completely effective vaccine yet available. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunizing mice with live, radiation-attenuated sporozoites, providing protection to about 60% of the mice upon subsequent injection with normal, viable sporozoites. Since the 1970s, there has been a considerable effort to develop similar vaccination strategies within humans. It was determined that an individual can be protected from a P. falciparum infection if they receive over 1,000 bites from infected yet irradiated mosquitoes.

Other methods

Education in recognizing the symptoms of malaria has reduced the number of cases in some areas of the developing world by as much as 20%. Recognizing the disease in the early stages can also stop the disease from becoming a killer. Education can also inform people to cover over areas of stagnant, still water e.g. Water Tanks which are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people. This is most put in practice in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas.

The Malaria Control Project is currently using downtime computing power donated by individual volunteers around the world (see Volunteer computing and BOINC) to simulate models of the health effects and transmission dynamics in order to find the best method or combination of methods for malaria control. This modeling is extremely computer intensive due to the simulations of large human populations with a vast range of parameters related to biological and social factors that influence the spread of the disease. It is expected to take a few months using volunteered computing power compared to the 40 years it would have taken with the current resources available to the scientists who developed the program.

An example of the importance of computer modeling in planning malaria eradication programs is shown in the paper by Águas and others. They showed that eradication of malaria is crucially dependent on finding and treating the large number of people in endemic areas with asymptomatic malaria, who act as a reservoir for infection. The malaria parasites do not affect animal species and therefore eradication of the disease from the human population would be expected to be effective.

Other interventions for the control of malaria include mass drug administrations and intermittent preventive therapy.

Furthering attempts to reduce transmission rates, a proposed alternative to mosquito nets is the mosquito laser, or photonic fence, which identifies female mosquitoes and shoots them using a medium-powered laser. The device is currently undergoing commercial development, although instructions for a DIY version of the photonic fence have also been published.

Another way of reducing the malaria transmitted to humans from mosquitoes has been developed by the University of Arizona. They have engineered a mosquito to become resistant to malaria. This was reported on the 16 July 2010 in the journal PLoS Pathogens. With the ultimate end being that the release of this GM mosquito into the environment, Gareth Lycett, a malaria researcher from Liverpool School of Tropical Medicine told the BBC that “It is another step on the journey towards potentially assisting malaria control through GM mosquito release.”

Treatment

When properly treated, a patient with malaria can expect a complete recovery.[ The treatment of malaria depends on the severity of the disease; whether patients who can take oral drugs have to be admitted depends on the assessment and the experience of the clinician. Uncomplicated malaria is treated with oral drugs. The most effective strategy for P. falciparum infection recommended by WHO is the use of artemisinins in combination with other antimalarials artemisinin-combination therapy, ACT, in order to avoid the development of drug resistance against artemisinin-based therapies.

Severe malaria requires the parenteral administration of antimalarial drugs. Until recently the most used treatment for severe malaria was quinine but artesunate has been shown to be superior to quinine in both children and adults. Treatment of severe malaria also involves supportive measures.

Infection with P. vivax, P. ovale or P. malariae is usually treated on an outpatient basis. Treatment of P. vivax requires both treatment of blood stages (with chloroquine or ACT) as well as clearance of liver forms with primaquine.

Epidemiology

 

 

Countries which have regions where malaria is endemic as of 2003 (colored yellow). Countries in green are free of indigenous cases of malaria in all areas.

 

 

Disability-adjusted life year for malaria per 100,000 inhabitants in 2002.

 

It is estimated that malaria causes 250 million cases of fever and approximately one million deaths annually. The vast majority of cases occur in children under 5 years old; pregnant women are also especially vulnerable. Despite efforts to reduce transmission and increase treatment, there has been little change in which areas are at risk of this disease since 1992. Indeed, if the prevalence of malaria stays on its present upwards course, the death rate could double in the next twenty years. Precise statistics are unknown because many cases occur in rural areas where people do not have access to hospitals or the means to afford health care. As a consequence, the majority of cases are undocumented.

Although co-infection with HIV and malaria does cause increased mortality, this is less of a problem than with HIV/tuberculosis co-infection, due to the two diseases usually attacking different age-ranges, with malaria being most common in the young and active tuberculosis most common in the old. Although HIV/malaria co-infection produces less severe symptoms than the interaction between HIV and TB, HIV and malaria do contribute to each other’s spread. This effect comes from malaria increasing viral load and HIV infection increasing a person’s susceptibility to malaria infection.

Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; however, it is in sub-Saharan Africa where 85– 90% of malaria fatalities occur. The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other.  In drier areas, outbreaks of malaria can be predicted with reasonable accuracy by mapping rainfall. Malaria is more common in rural areas than in cities; this is in contrast to dengue fever where urban areas present the greater risk. For example, several cities in Vietnam, Laos and Cambodia are essentially malaria-free, but the disease is present in many rural regions. By contrast, in Africa malaria is present in both rural and urban areas, though the risk is lower in the larger cities. The global endemic levels of malaria have not been mapped since the 1960s. However, the Wellcome Trust, UK, has funded the Malaria Atlas Project to rectify this, providing a more contemporary and robust means with which to assess current and future malaria disease burden.