IgG1 and IgG4 Antibody Responses to the Anopheles gambiae Salivary Protein gSG6

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Human antibody response to the Anopheles gambiae salivary protein gSG6 has recently emerged as a potentially useful tool for malaria epidemiological studies and for the evaluation of vector control interventions. However, the current understanding of the host immune response to mosquito salivary proteins and of the possible crosstalk with early response to Plasmodium parasites is still very limited. We report here the analysis of IgG1 and IgG4 subclasses among anti-gSG6 IgG responders belonging to Mossi and Fulani from Burkina Faso, two ethnic groups which are known for their differential humoral response to parasite antigens and for their different susceptibility to malaria. The IgG1 antibody response against the gSG6 protein was comparable in the two groups. On the contrary, IgG4 titers were significantly higher in the Fulani where, in addition, anti-gSG6 IgG4 antibodies appeared in younger children and the ratio IgG4/IgG1 stayed relatively stable throughout adulthood. Both gSG6-specific IgG1 and IgG4 antibodies showed a tendency to decrease with age whereas, as expected, the IgG response to the Plasmodium circumsporozoite protein (CSP) exhibited an opposite trend in the same individuals. These observations are in line with the idea that the An. gambiae gSG6 salivary protein induces immune tolerance, especially after intense and prolonged exposure as is the case for the area under study, suggesting that gSG6 may trigger in exposed individuals a Th2-oriented immune response.

Citation: Rizzo C, Ronca R, Lombardo F, Mangano V, Sirima SB, et al. (2014) IgG1 and IgG4 Antibody Responses to the Anopheles gambiae Salivary Protein gSG6 in the Sympatric Ethnic Groups Mossi and Fulani in a Malaria Hyperhendemic Area of Burkina Faso. PLoS ONE 9(4): e96130. doi:10.1371/journal.pone.0096130

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How Much Time Between Mosquito Bite and Malaria Symptoms?

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QUESTION

If a mosquito carrying malaria is biting you, do you get sick the next day?

ANSWER

No.  There is a delay called the incubation period, which usually is between 7 to 30 days (depending on the malarial parasite the anopheles mosquito is carrying). The shorter periods are observed most frequently  from P. falciparum and the longer ones with P. malariae.

Antimalarial drugs taken for prophylaxis by travelers can delay the appearance of malaria symptoms by weeks or months, long after the traveler has left the malaria-endemic area. (This can happen particularly with P. vivax and P. ovale, both of which can produce dormant liver stage parasites; the liver stages may reactivate and cause disease months after the infective mosquito bite.)

Such long delays between exposure and development of symptoms can result in misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health-care provider. Returned travelers should always remind their health-care providers of any travel in malaria-risk areas during the past 12 months.

Anopheles Mosquitoes and Malaria Transmission

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QUESTION

How are the Anopheles mosquitoes able to transmit human Malaria and others are not? What makes them different from the other genus of mosquito?

ANSWER

This is a great question and in fact scientists are not really sure of the answer. The ability of female Anopheles to transmit malaria is a quirk of evolutionary history. Other species of Plasmodium (the Latin genus name of the group of parasites which cause malaria), for example those that infect birds and lizards, are transmitted by other mosquitoes, such as Culex. When the parasite switched hosts and started infecting mammals, this coincided with the parasite specializing in infecting Anopheles mosquitoes, and this relationship has remained ever since. It is a case of what scientists term “coevolution”, where a parasite and its vector have a tightly coupled and highly specialized relationship.

Bringing Malaria to the United States

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QUESTION

I was recently diagnosed with Malaria still waiting to find out what strand, but either got it in Uganda or Rwanda. I have recently came back to the states and have been bit by mosquito. I have already started to take some medication for it, but I am concerned about spreading the virus to others in the states including my family. Is it possible that if I still have the infection to spread it to others or in the states? If so what should I do.

ANSWER

There actually used to be malaria in the United States, particularly in the southern areas, but concerted mosquito control efforts as well as public health initiatives eradicated it in the 1950s. I don’t think you need to worry too much about transmitting malaria—once you are on treatment, the number of parasites in your blood drops dramatically and it becomes more difficult to transmit the parasite to a mosquito. Also, there are lots of types of mosquitoes in the US, and only those of the genus Anopheles can transmit malaria. As such, if you are concerned about spreading malaria, you should take precautions to protect yourself from mosquitoes especially at night and at dusk and dawn, as this is when Anopheles mosquitoes are most active. The type of mosquitoes which bite during the day usually belong to the genus Aedes, and cannot transmit malaria. During these high risk times of day, you should take care to wear long-sleeved clothing, and also wear insect repellent, preferably containing DEET.

Mosquito Life Cycle

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QUESTION

Please explain the life cycle of a mosquito.

ANSWER

Mosquitoes are insects which go through several life stages, starting out as eggs, then hatching into larvae before developing into adults. Mosquito eggs are laid in slow-moving or stagnant pools of freshwater, to provide suitable habitat for the larvae once they hatch. Different species of mosquito prefer different water conditions; some prefer shaded areas, whereas some prefer more direct sunlight, and some mosquitoes even lay their eggs in very specific habitats, such as brackish water in estuaries. The way the mosquitoes lay their eggs can aid in identifying the genus of mosquito; some genera, such as Culex, lay rafts of many eggs, whereas Anopheles mosquitoes (the ones which transmit malaria to humans) lay their eggs singly. Larvae usually hatch from the eggs after a couple of days. These larvae are predatory, feeding on other aquatic insects and organisms, but themselves can also be eaten by fish, copepods and other creatures. Most larvae lay at an angle to the water surface and breathe through a specialized tube-like organ, known as a siphon, but Anopheles larvae lack the siphon and so much lay parallel to the water’s surface in order to breathe. Each larva must shed its skin (molt) four times, before reaching the stage where it forms a pupa. These four molts take anywhere from 7 to 14 days, depending on the water temperature. The pupa is just like a butterfly pupa – the mosquito does not feed and lays still in a cocoon as it develops into a adult. This process usually takes 2 days, after which the pupa splits and the adult emerges. The length of the full cycle is dependent on whether the conditions were optimal for that species of mosquito, and specifically based on temperature. Male adult mosquitoes usually live for about a week, feeding on nectar – they also possess very bushy antennae for seeking out females to mate with. Female mosquitoes have specialized mouthparts that allow them to feed on blood; they require the extra nutrients that blood provides in order to lay their eggs. The lifespan of a female adult depends on a number of environmental factors, but also her ability to get sufficient blood meals; in nature, they usually live 1-2 weeks.

A schematic of the life cycle is provided below:

Mosquito lifecycle schematic

Schematic of the mosquito lifecycle. Courtesy of Purdue University (Scott Charlesworth): http://extension.entm.purdue.edu/publichealth/insects/mosquito.html

Is Malaria Transmitted by Female Mosquitoes?

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QUESTION

Is malaria caused by only female mosquitoes?

ANSWER

Malaria is only transmitted by female mosquitoes, yes. This is because only female mosquitoes of the genus Anopheles (the genus that transmits malaria in mammals, including humans) feed on blood, and the parasite that causes malaria (called Plasmodium) spends part of its life cycle in the blood. Therefore, when a female mosquito feeds on an infected person, when she sucks up their blood, she also takes up some of the Plasmodium parasites. These parasites mature inside the mosquito, and then, when the mosquito goes to bite another person, she passes some of the mature Plasmodium parasites into that new person’s blood while she feeds. The Plasmodium parasites may then be able to undergo further development in the new host, which may lead to the person experiencing a malaria infection. So, while technically female mosquitoes don’t cause malaria (since the disease is caused by the Plasmodium parasite), female mosquitoes are required to pass it between one person and another.

Malaria in Summer

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QUESTION

Does malaria only occur during summer season?

ANSWER

That depends on where you are. The transmission of malaria depends on the presence of the mosquitoes which are required to transmit the disease (they do this when they bite you).

Many kinds of mosquito transmit malaria, though all are of the genus Anopheles. These different species have different climatic requirements, but all lay their eggs in pools of stagnant water, and the larve likewise live in this stagnant water until they develop into adults. As such, malaria is only transmitted when there are suitable pools of standing, stagnant water available for mosquitoes to breed, and also when the temperature is suitable for mosquito development (optimum temperature for mosquitoes is 25-27 degrees C—the malaria parasite develops most rapidly around this temperature as well, though can survive in temperatures about ten degrees cooler as well).

In some regions of the world, this combination of conditions is only met in the summer time, which means that malaria transmission only occurs during this season. In other parts of the world, such as coastal West Africa, conditions are suitable for mosquito breeding and malaria development all year round, which means that malaria transmission occurs throughout the year.

Do Male Mosquitoes Bite?

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QUESTION

Why do male mosquitoes not bites humans?

ANSWER

Male mosquitoes do not possess the right kind of feeding apparatus to feed on humans—they only feed on nectar. This is because they do not need to produce eggs, which require lots of energy and protein to make, and so the female mosquitoes need a more comprehensive food source than just nectar when they are egg-laying, such as blood. This is why they feed on humans and other animals when egg-laying.

Malaria: Mode of Transmission

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QUESTION

What is the mode of transmission of Malaria?

ANSWER

Malaria is transmitted normally via the bite of an infected mosquito. These mosquitoes, always female and of the genus Anopheles, carry malaria parasites in their salivary glands. The parasites, at this part of their life cycle known as sporozoites, are introduced into the host’s blood when the mosquito takes a blood meal. From there, the sporozoites travel to the liver, reproduce (this process may take several weeks), then finally re-enter the blood stream. At this point, the patient will begin to experience symptoms. Eventually, the malaria parasites change again, into gametocytes, which are picked up by another mosquito, again when it bites the infected person. In this way, the life cycle of the malaria parasite continues.

Because malaria reproduces in the blood and in the liver, in some cases malaria can be transferred via organ transplant or blood transfusion. In addition, malaria parasites can cross the placenta, and so can be transmitted from a mother to her unborn child, either in the womb or during childbirth. This is known as congenital malaria.