Causes of Malaria

January 2, 2012 by Malaria Q&A

QUESTION

What is malaria usually caused by?

ANSWER

Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites multiply in the liver, and then infect red blood cells. Usually, people get malaria by being bitten by an infective female Anopheles mosquito. Only Anopheles mosquitoes can transmit malaria and they must have been infected through a previous blood meal taken on an infected person. When a mosquito bites an infected person, a small amount of blood is taken in which contains microscopic malaria parasites. About 1 week later, when the mosquito takes its next blood meal, these parasites mix with the mosquito’s saliva and are injected into the person being bitten.

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Mosquito Immune System Can Be Engineered to Block Malaria

December 22, 2011 by Malaria.com

Researchers have demonstrated for the first time that the Anopheles mosquito’s innate immune system could be genetically engineered to block the transmission of the malaria-causing parasite to humans. In addition, they showed that the genetic modification had little impact on the mosquito’s fitness under laboratory conditions.

“The immune system of the Anopheles mosquito is capable of killing a large proportion—but not all—of the disease-causing parasites that are ingested when the mosquito feeds on an infected human,” said George Dimopoulos, PhD, senior author of the study and associate professor in the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. “We’ve genetically engineered this immune system to create mosquitoes that are better at blocking the transmission of the human malaria parasite Plasmodium falciparum. ”

For the study, Dimopoulos and his team genetically engineered Anopheles mosquitoes to produce higher than normal levels of an immune system protein Rel2 when they feed on blood. Rel2 acts against the malaria parasite in the mosquito by launching an immune attack involving a variety of anti-parasitic molecules. Through this approach, instead of introducing a new gene into the mosquito DNA, the researchers used one of the insect’s own genes to strengthen its parasite-fighting capabilities. According to the researchers, this type of genetically modified mosquito could be further developed and used to convert malaria-transmitting to Plasmodium-resistant mosquito populations. One possible obstacle for this approach is the fitness of the genetically modified malaria resistant mosquitoes, since they would have to compete with the natural malaria-transmitting mosquitoes. The researchers showed with their study that the Rel2 genetically modified mosquito strain lived as long, and laid as many eggs, as the non-modified wild type mosquitoes, thereby suggesting that their fitness had not become significantly impaired.

“Malaria is one of world’s most serious public health problems. Mosquitoes and the malaria parasite are becoming more resistant to insecticides and drugs, and new control methods are urgently needed. We’ve taken a giant step towards the development of new mosquito strains that could be released to limit malaria transmission, but further studies are needed to render this approach safe and fail-proof,” said Dimopoulos.
Worldwide, malaria afflicts more than 225 million people. Each year, the disease kills approximately 800,000, many of whom are children living in Africa.

Authors of “Engineered Anopheles immunity to Plasmodium infection” are Yuemei Dong, Suchismita Das, Chris Cirimotich, Jayme A. Souza-Neto, Kyle J. McLean and George Dimopoulos.

The Johns Hopkins Malaria Research Institute is a state-of-the-art research facility at the Johns Hopkins Bloomberg School of Public Health. It focuses on a broad program of basic science research to treat and control malaria, develop a vaccine and find new drug targets to prevent and cure this deadly disease.

The researchers’ findings were published December 22, 2011 in the online journal PLoS Pathogens. Funding was provided by the National Institutes of Health and the Johns Hopkins Malaria Research Institute.

Source: Johns Hopkins Bloomberg School of Public Health

Wolbachia Bacteria Reduce Parasite Levels and Kill the Mosquitos that Spreads Malaria

May 19, 2011 by Malaria.com

Wolbachia are bacteria that infect many insects, including mosquitoes. However, Wolbachia do not naturally infect Anopheles mosquitoes, which are the type that spreads malaria to humans. Researchers at the Johns Hopkins Bloomberg School of Public Health found that artificial infection with different Wolbachia strains can significantly reduce levels of the human malaria parasite, Plasmodium falciparum, in the mosquito, Anopheles gambiae. The investigators also determined that one of the Wolbachia strains rapidly killed the mosquito after it fed on blood. According to the researchers, Wolbachia could potentially be used as part of a strategy to control malaria if stable infections can be established in Anopheles.

“This is the first time anyone has shown that Wolbachia infections can reduce levels of the human malaria parasite (Plasmodium falciparum) in Anopheles mosquitoes,” said Jason Rasgon, PhD, senior author of the study and associate professor with the Johns Hopkins Malaria Research Institute and the Bloomberg School’s W. Harry Feinstone Department of Molecular Microbiology and Immunology.

For the study, Rasgon and his colleagues infected Anopheles gambiae mosquitoes with two different Wolbachia strains (wMelPop and wAlbB). After infection, Wolbachia disseminated widely in the mosquitoes and infected diverse tissues and organs. Wolbachia also seemed to actively manipulate the mosquito’s immune system to facilitate its own replication. Both Wolbachia strains were able to significantly inhibit malaria parasite levels in the mosquito gut. Although not virulent in sugar-fed mosquitoes, the wMelPop strain killed most mosquitoes within a day after the mosquito was blood-fed.

“These experiments show that Wolbachia could be used in multiple ways to control malaria, perhaps by blocking transmission or by killing infected mosquitoes,” said Rasgon.

Worldwide, malaria afflicts more than 225 million people. Each year, the disease kills nearly 800,000, many of whom are children living in Africa.

In addition to Rasgon, the authors of “Wolbachia infections are virulent and inhabit the human malaria parasite Plasmodium falciparum in Anopheles gambiae” include Grant Hughes and Ping Xue of the Johns Hopkins Malaria Research Institute, and Ryuichi Koga and Takema Fukatsu of the National Institute of Advanced Industrial Science and Technology in Tsukuba, Japan.

Funding was provided by the Johns Hopkins Malaria Research Institute and the National Institute of Allergy and Infectious Diseases. The study is published in the May 19, 2011 edition PLoS Pathogens.

Source: Johns Hopkins Bloomberg School of Public Health

Anopheles Mosquitoes

September 13, 2010 by Malaria.com

Anopheles Mosquitoes

Diagram of Adult Female Mosquito

Malaria is transmitted among humans by female mosquitoes of the genus Anopheles. Female mosquitoes take blood meals to carry out egg production, and such blood meals are the link between the human and the mosquito hosts in the parasite life cycle. The successful development of the malaria parasite in the mosquito (from the “gametocyte” stage to the “sporozoite” stage) depends on several factors. The most important is ambient temperature and humidity (higher temperatures accelerate the parasite growth in the mosquito) and whether the Anopheles survives long enough to allow the parasite to complete its cycle in the mosquito host (“sporogonic” or “extrinsic” cycle, duration 10 to 18 days). Differently from the human host, the mosquito host does not suffer noticeably from the presence of the parasites.

Thumbnail of the mosquito distribution map.

Map of the world showing the distribution of predominant malaria vectors

General Information

There are approximately 3,500 species of mosquitoes grouped into 41 genera. Human malaria is transmitted only by females of the genus Anopheles. Of the approximately 430 Anopheles species, only 30-40 transmit malaria (i.e., are “vectors”) in nature.

Geographic Distribution

Anophelines are found worldwide except Antarctica. Malaria is transmitted by different Anopheles species, depending on the region and the environment.

Anophelines that can transmit malaria are found not only in malaria-endemic areas, but also in areas where malaria has been eliminated. The latter areas are thus constantly at risk of re-introduction of the disease.

Anopheles freeborni mosquito pumping blood

Life Stages

Like all mosquitoes, anophelines go through four stages in their life cycle: egg, larva, pupa, and adult. The first three stages are aquatic and last 5-14 days, depending on the species and the ambient temperature. The adult stage is when the female Anopheles mosquito acts as malaria vector. The adult females can live up to a month (or more in captivity) but most probably do not live more than 1-2 weeks in nature.

Eggs

Adult females lay 50-200 eggs per oviposition. Eggs are laid singly directly on water and are unique in having floats on either side. Eggs are not resistant to drying and hatch within 2-3 days, although hatching may take up to 2-3 weeks in colder climates.

Larvae

Mosquito larvae have a well-developed head with mouth brushes used for feeding, a large thorax, and a segmented abdomen. They have no legs. In contrast to other mosquitoes, Anopheles larvae lack a respiratory siphon and for this reason position themselves so that their body is parallel to the surface of the water.

Larvae breathe through spiracles located on the 8th abdominal segment and therefore must come to the surface frequently.

Top: Anopheles Egg; note the lateral floats.
Bottom: Anopheles eggs are laid singly.

Image of a Anopheles larva, floating parallel to water surface

Anopheles Larva. Note the position, parallel to the water surface.

The larvae spend most of their time feeding on algae, bacteria, and other microorganisms in the surface microlayer. They dive below the surface only when disturbed. Larvae swim either by jerky movements of the entire body or through propulsion with the mouth brushes.

Larvae develop through 4 stages, or instars, after which they metamorphose into pupae. At the end of each instar, the larvae molt, shedding their exoskeleton, or skin, to allow for further growth.

Larvae of Anopheles gambiae, the major malaria vector in Africa, can breed in very diverse habitats. Tire tracks habitat.

Larvae of Anopheles gambiae, the major malaria vector in Africa, can breed in very diverse habitats. Rice fields habitat

Larvae of Anopheles gambiae, the major malaria vector in Africa, can breed in very diverse habitats. Irrigation water habitat.

Larvae of Anopheles gambiae, the major malaria vector in Africa, can breed in diverse habitats. Three habitats are shown from left to right: tire tracks, rice fields, and irrigation water.

The larvae occur in a wide range of habitats but most species prefer clean, unpolluted water. Larvae of Anopheles mosquitoes have been found in fresh- or salt-water marshes, mangrove swamps, rice fields, grassy ditches, the edges of streams and rivers, and small, temporary rain pools. Many species prefer habitats with vegetation. Others prefer habitats that have none. Some breed in open, sun-lit pools while others are found only in shaded breeding sites in forests. A few species breed in tree holes or the leaf axils of some plants.

Graph of pupa of Anopheles, illustrating coma shape

Anopheles Pupa

Pupae

The pupa is comma-shaped when viewed from the side. The head and thorax are merged into a cephalothorax with the abdomen curving around underneath. As with the larvae, pupae must come to the surface frequently to breathe, which they do through a pair of respiratory trumpets on the cephalothorax. After a few days as a pupa, the dorsal surface of the cephalothorax splits and the adult mosquito emerges.

The duration from egg to adult varies considerably among species and is strongly influenced by ambient temperature. Mosquitoes can develop from egg to adult in as little as 5 days but usually take 10-14 days in tropical conditions.

Schema of adult Anopheles seen from above, and from the side to show typical resting position)

Anopheles Adults. Note (bottom row) the typical resting position.

Adults

Like all mosquitoes, adult anophelines have slender bodies with 3 sections: head, thorax and abdomen.

The head is specialized for acquiring sensory information and for feeding. The head contains the eyes and a pair of long, many-segmented antennae. The antennae are important for detecting host odors as well as odors of breeding sites where females lay eggs. The head also has an elongate, forward-projecting proboscis used for feeding, and two sensory palps.

The thorax is specialized for locomotion. Three pairs of legs and a pair of wings are attached to the thorax.

The abdomen is specialized for food digestion and egg development. This segmented body part expands considerably when a female takes a blood meal. The blood is digested over time serving as a source of protein for the production of eggs, which gradually fill the abdomen.

Anopheles mosquitoes can be distinguished from other mosquitoes by the palps, which are as long as the proboscis, and by the presence of discrete blocks of black and white scales on the wings. Adult Anopheles can also be identified by their typical resting position: males and females rest with their abdomens sticking up in the air rather than parallel to the surface on which they are resting.

Adult mosquitoes usually mate within a few days after emerging from the pupal stage. In most species, the males form large swarms, usually around dusk, and the females fly into the swarms to mate.

Female Anopheles dirus feeding

Males live for about a week, feeding on nectar and other sources of sugar. Females will also feed on sugar sources for energy but usually require a blood meal for the development of eggs. After obtaining a full blood meal, the female will rest for a few days while the blood is digested and eggs are developed. This process depends on the temperature but usually takes 2-3 days in tropical conditions. Once the eggs are fully developed, the female lays them and resumes host seeking.

The cycle repeats itself until the female dies. Females can survive up to a month (or longer in captivity) but most probably do not live longer than 1-2 weeks in nature. Their chances of survival depend on temperature and humidity, but also their ability to successfully obtain a blood meal while avoiding host defenses.

Factors Involved in Malaria Transmission and Malaria Control

Understanding the biology and behavior of Anopheles mosquitoes can help understand how malaria is transmitted and can aid in designing appropriate control strategies. Factors that affect a mosquito’s ability to transmit malaria include its innate susceptibility to Plasmodium, its host choice, and its longevity. Factors that should be taken into consideration when designing a control program include the susceptibility of malaria vectors to insecticides and the preferred feeding and resting location of adult mosquitoes.

Preferred Sources for Blood Meals

One important behavioral factor is the degree to which an Anopheles species prefers to feed on humans (anthropophily) or animals such as cattle (zoophily). Anthrophilic Anopheles are more likely to transmit the malaria parasites from one person to another. Most Anopheles mosquitoes are not exclusively anthropophilic or zoophilic. However, the primary malaria vectors in Africa, An. gambiae and An. funestus, are strongly anthropophilic and, consequently, are two of the most efficient malaria vectors in the world.

Life Span

Once ingested by a mosquito, malaria parasites must undergo development within the mosquito before they are infectious to humans. The time required for development in the mosquito (the extrinsic incubation period) ranges from 10 to 21 days, depending on the parasite species and the temperature. If a mosquito does not survive longer than the extrinsic incubation period, then she will not be able to transmit any malaria parasites.

It is not possible to measure directly the life span of mosquitoes in nature. But indirect estimates of daily survivorship have been made for several Anopheles species. Estimates of daily survivorship of An. gambiae in Tanzania ranged from 0.77 to 0.84 meaning that at the end of one day between 77% and 84% will have survived. (Charlwood et al., 1997, Survival And Infection Probabilities of Anthropophagic Anophelines From An Area of High Prevalence of Plasmodium falciparum in Humans, Bulletin of Entomological Research, 87, 445-453).

Assuming this is constant through the adult life of a mosquito, less than 10% of female An. gambiae would survive longer than a 14-day extrinsic incubation period. If daily survivorship increased to 0.9, over 20% of mosquitoes would survive longer than a 14-day extrinsic incubation period. Control measures that rely on insecticides (e.g., indoor residual spraying) may actually impact malaria transmission more through their effect on adult longevity than through their effect on the population of adult mosquitoes.

Patterns of Feeding and Resting

Most Anopheles mosquitoes are crepuscular (active at dusk or dawn) or nocturnal (active at night). Some Anopheles mosquitoes feed indoors (endophagic) while others feed outdoors (exophagic). After blood feeding, some Anopheles mosquitoes prefer to rest indoors (endophilic) while others prefer to rest outdoors (exophilic). Biting by nocturnal, endophagic Anopheles mosquitoes can be markedly reduced through the use of insecticide-treated bed nets (ITNs) or through improved housing construction to prevent mosquito entry (e.g., window screens). Endophilic mosquitoes are readily controlled by indoor spraying of residual insecticides. In contrast, exophagic/exophilic vectors are best controlled through source reduction (destruction of the breeding sites).

Insecticide Resistance

Insecticide-based control measures (e.g., indoor spraying with insecticides, ITNs) are the principal way to kill mosquitoes that bite indoors. However, after prolonged exposure to an insecticide over several generations, mosquitoes, like other insects, may develop resistance, a capacity to survive contact with an insecticide. Since mosquitoes can have many generations per year, high levels of resistance can arise very quickly. Resistance of mosquitoes to some insecticides has been documented just within a few years after the insecticides were introduced. There are over 125 mosquito species with documented resistance to one or more insecticides. The development of resistance to insecticides used for indoor residual spraying was a major impediment during the Global Malaria Eradication Campaign. Judicious use of insecticides for mosquito control can limit the development and spread of resistance. However, use of insecticides in agriculture has often been implicated as contributing to resistance in mosquito populations. It is possible to detect developing resistance in mosquitoes and control programs are well advised to conduct surveillance for this potential problem.

Source: CDC