Transmission Mode Of Malaria Biology Essay

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Malaria is most frequently transmitted from human to human by the bites of female Anopheles mosquito which is infected with a malaria parasite.

The causative agents in humans are four distinct species of Plasmodium protozoa- P.falciparum, P. vivax, P. ovale, and P. malariae. Of these, P.falciparum accounts for the majority of infections and is the most lethal. The World Health Organization (WHO) estimates that Plasmodium falciparum is responsible for almost one million deaths a year, primarily in young children in sub-Saharan Africa. The total annual infection rate is 350-500 million cases, making malaria one of the most serious public health problems in Africa. There are many vectors of malaria. About 60 species have been identified as vectors for malaria under natural conditions. The parasite's primary hosts and transmission vectors are female Anopheles mosquitoes, while humans and other vertebrates are secondary hosts.

When a mosquito bites an infected individual, it sucks the gametocytes, the sexual forms of the malaria parasite, along with blood. , the parasites reproduce inside the mosquito's body as These gametocytes continue the sexual phase of the cycle and the sporozoites fill the salivary glands of the infected mosquito. about one week later, the mosquito passes the parasite through its saliva to anyone that it bites for its next blood meal, which it needs to nourish its eggs. The mosquito inoculates the sporozoites into human blood stream, thus spreading the infection. Once the parasite enters a human after a mosquito bite, it travels to the liver. In the liver, the malaria parasite rapidly reproduces. Upon maturity, the parasites travel through the bloodstream and infect the red blood cells. The parasites start to multiply withn the red blood cells, until the red blood cells explode, causing the parasites to further spread throughout the human's body and attack more blood cells. Malaria symptoms such as fever and headache develop in seven to 21 days after infection. If left untreated, blood supply is disrupted from flowing to vital organs resulting in coma and death.

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For those who survive, malaria may become chronic, lapsing and remitting over time and requiring intermittent hospitalization and ongoing treatment with anti-malarial drugs like chloroquine, quinine, and amodiaquine. Unfortunately, the dangerous Plasmodium strain is developing treatment resistance to some of these drugs.

At present, there is no vaccine for malaria, although there are several in development. Preventative measures are currently directed at mosquito control.

Other modes of transmission: Rarely malaria can spread by the inoculation of blood from an infected person to a healthy person. In this type of malaria, asexual forms are directly inoculated into the blood and pre-erythrocytic development of the parasite in the liver does not occur. Therefore, this type of malaria has a shorter incubation period and relapses do not occur.

1. Blood transfusion: Because the malaria parasite is found in red blood cells of an infected person, Malaria can be transmitted through a blood transfusion where the recipient receives infected blood. Depending on the type of malaria parasite, a donor can remain contagious from one to 50 years (1-3 years in P. falciparum, 3-4 years in P. vivax, and 15-50 years in P. malariae.)

This is fairly common in endemic areas. Most infections occur in cases of transfusion of blood stored for less than 5 days and it is rare in transfusions of blood stored for more than 2 weeks. Frozen plasma is not known to transmit malaria.

The clinical features of transfusion malaria occur earlier and any patient who has received a transfusion three months prior to the febrile illness should be suspected to have malaria.

A thorough history and screening of blood donors is useful to prevent transmission of malaria through blood transfusions. The time frame of when malaria symptoms appear after infection from a blood transfusion depends on the amount of malaria parasites transmitted through the blood transfusion. Donor blood can be tested with indirect fluorescent antibody test or ELISA, and direct examination of the blood for the parasite may not be helpful.

In endemic areas, it is safe to administer full course of chloroquine to all recipients of blood transfusion.

In transfusion malaria, pre-erythrocytic schizogony does not occur and hence relapses due to dormant hepatic forms also does not occur. Therefore, treatment with primaquine for 5 (or14) days is not indicated.

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Even blood donations from semi-immune persons without clinical symptoms may contain malarial parasites.

Congenital malaria: In congenital malaria, infected mothers transmit malaria parasites to their children before or during birth (Hoffman, 1996). This type of malaria is rare because the placenta often protects the baby from becoming infected with the malaria parasite. In some instances though, the placenta becomes infested with numerous malaria parasites and malaria is passed to the unborn child. Infants who contract malaria in utero are born with malaria symptoms present. Congenital malaria is more common in first pregnancy, among non - immune populations.

Needles

Sharing needles or syringes is one mode of malaria transmission, especially in malaria endemic areas. If a person uses a needle that was previously used on a person infected with the malaria parasite, he/she risks becoming infected. The time frame of when symptoms of malaria appear after infection form a needle depends on the amount of malaria parasites transmitted into the bloodstream through the needle.

Transmission

Malaria transmission rates can differ depending on local factors such as rainfall patterns (mosquitoes breed in wet conditions), the proximity of mosquito breeding sites to people, and types of mosquito species in the area. Some regions have a fairly constant number of cases throughout the year - these countries are termed "malaria endemic". In other areas there are "malaria seasons" usually coinciding with the rainy season.

Large and devastating epidemics can occur when the mosquito-borne parasite is introduced into areas where people have had little prior contact with the infecting parasite and have little or no immunity to malaria, or when people with low immunity move into areas where malaria cases are constant. These epidemics can be triggered by wet weather conditions and further aggravated by floods or mass population movements driven by conflict.

Credit: NIAID 

Life Cycle of Malaria Parasite

The life cycle of malaria provides the basis for understanding malaria vaccines. There are many strategies for developing malaria vaccines, each targeting different stages of the parasite's development. The life cycle of all species of human malaria parasites is essentially the same. It comprises 1) an exogenous sexual phase (sporogony) with multiplication in certain Anopheles mosquitoes and 2) an endogenous asexual phase (schizogony) with parasite multiplication in the gut wall of vertebrate host. The latter phase includes 3)two endogenous asexual phases, the development cycle in the red cells (erythrocytic schizogony) and the phase taking place in the parenchyma cells in the liver (pre-erythrocytic schizogony). Time-frame depends on the malaria parasite species.

(Centers for Disease Control & Prevention., 2007; Garcia et al., 2006).

If A female Anopheles mosquito carrying malaria-causing parasites feeds on a human, it will inject the parasites in the form of elongated sporozoites into the bloodstream of the human. The sporozoites travel to the liver where they enter liver cells ad rapidly divide asexually. This asexual division is known as schizogony.

Over about 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.

The merozoites exit the liver cells and invade other liver cells and re-enter the hosts 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. Once inside the erythrocyte, the merozoite begins to enlarge as a uninucleate cell known as a ring trophozoite. The trphozoite's nucleas then divides asexually to produce a schizont which contains several nuclei. The schizont then divides and produces mononucleated merozoites, the erythrocyte ruptures and releases toxins throughout the body of the host. This asexual 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.

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 gametocytes (cells capapble of producing male and female gametocytes) that circulate in the bloodstream.  Erythrocutes containg gametocytes do not rupture.

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When a mosquito bites an infected human, it ingests the gametocytes. within the gut of the mosquito, 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 within the mosquito's intestinal wall and differentiate into oocysts. 

Within the oocytes, repeated mitotic divisions take place, producing large number of active haploid forms called sporozoites. After about 8-15 days, the oocyst bursts, releasing sporozoites into the body cavity of the mosquito, from which they migrate to and invade the mosquito salivary glands. From there the sporozoites are injected into the bloodstream of a human, thus starting the life cycle of the malaria parasite again.

 The incubation period (time from infection to development of the disease) is usually about 10 to 15 days. This period can be much longer depending on whether any antimalarial medication has been taken.

Pathogenesis

Malaria in humans develops via two phases: an exoerythrocytic and an erythrocytic phase. The exoerythrocytic phase involves infection of the hepatic system, or liver, whereas the erythrocytic phase involves infection of the erythrocytes, or red blood cells.

Some P. vivax and P. ovale sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant in the liver cells for periods ranging from several months (6-12 months is typical) to as long as three years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in these two species of malaria.[32] This is why it's important after these infections to be treated with primaquine to kill the liver stages. (Primaquine cannot be used by people with a condition called G6PD-deficiency.)

The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen.[33] This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria. High endothelial venules (the smallest branches of the circulatory system) can be blocked by the attachment of masses of these infected red blood cells. The blockage of these vessels causes symptoms such as in placental and cerebral malaria. In cerebral malaria the sequestrated red blood cells can breach the blood brain barrier possibly leading to coma.[34]

Although the red blood cell surface adhesive proteins (called PfEMP1, for Plasmodium falciparum erythrocyte membrane protein 1) are exposed to the immune system, they do not serve as good immune targets, because of their extreme diversity; there are at least 60 variations of the protein within a single parasite and effectively limitless versions within parasite populations.[33] The parasite switches between a broad repertoire of PfEMP1 surface proteins, thus staying one step ahead of the pursuing immune system. Thus this increased pathogenecity as compared to other human malaria is related to P. falciparum's:

high reproductive capacity

cytoadherence and sequestration

Pregnant women are especially attractive to the mosquitoes,[35] and malaria in pregnant women is an important cause of stillbirths, infant mortality and low birth weight,[36] particularly in P. falciparum infection, but also in other species infection, such as P. vivax.[37]

Reviews on severe malaria and pathogenesis:

IA Clark, WB Cowden (2003) The pathophysiology of falciparum malaria. Pharmacology & Therapeutics 99, 221-260.

R Idro, NE Jenkins, CRJC Newton (2005) Pathogenesis, clinical features, and neurological outcome of cerebral malaria. The Lancet Neurology 4, 827-840.

CL Mackintosh, JG Beeson, K Marsh (2004) Clinical features and pathogenesis of severe malaria. Trends in Parasitology 20, 597-603.

A Trampuz , M Jereb, I Muzlovic, RM Prabhu (2003) Clinical review: Severe malaria. Critical Care 7, 315-323.

STATISTICS ON MALARIA- prevalence, incidence and death rates

Malaria Worldwide:

Malaria is one of the planet's deadliest diseases and one of the leading causes of sickness and death in the developing world. According to the World Health Organization there are 300 to 500 million clinical cases of malaria each year resulting in 1.5 to 2.7 million deaths worldwide.

Children aged one to four are the most vulnerable to infection and death. Malaria is responsible for as many as half the deaths of African children under the age of five. The disease kills more than one million children - 2,800 per day - each year in Africa alone. In regions of intense transmission, 40% of toddlers may die of acute malaria.

In areas of Africa with high malaria transmission, an estimated 990,000 people died of malaria in 1995 - over 2700 deaths per day, or 2 deaths per minute.

About 40% of the world's population - about two billion people - are at risk in about 90 countries and territories. 80 to 90% of malaria deaths occur in sub-Saharan Africa where 90% of the infected people live. In 2006, malaria was present in 109 countries and territories, 45 of which are in Africa. Approximately 3.3 billion people live in areas where malaria is a constant threat.

Sub-Saharan Africa is the region with the highest malaria infection rate. Here alone, the disease kills at least one million people each year. According to some estimates, 275 million out of a total of 530 million people have malaria parasites in their blood, although they may not develop symptoms.

Of the four human malaria strains, Plasmodium falciparum is responsible for about 95% of malaria deaths worldwide and has a mortality rate of 1-3%.

In the early 1960s, only 10% the world's population was at risk of contracting malaria. This rose to 40% as mosquitoes developed resistance to pesticides and malaria parasites developed resistance to treatment drugs. Malaria is now spreading to areas previously free of the disease.

In 2002, malaria was the fourth cause of death in children in developing countries, after perinatal conditions (conditions occurring around the time of birth), lower respiratory infections (pneumonias), and diarrheal diseases. Malaria caused 10.7% of all children's deaths in developing countries.

In Malawi in 2001, malaria accounted for 22% of all hospital admissions, 26% of all outpatient visits, and 28% of all hospital deaths. Not all people go to hospitals when sick or having a baby, and many die at home. Thus the true numbers of death and disease caused by malaria are likely much higher.

Malaria kills 8,000 Brazilians yearly - more than AIDS and cholera combined.

There were 483 reported cases of malaria in Canada in 1993, according to Health Canada and approximately 431 in 1994. The Centers for Disease Control and Prevention in the United States received reports of 910 cases of malaria in 1992 and seven of those cases were acquired there. In 1970, reported malaria cases in the U.S. were 4,247 with more than 4,000 of the total being U.S. military personnel.

According to material from Third World Network Features, in Africa alone, direct and indirect costs of malaria amounted to US $800 million in 1987 and reached US $1.8 billion annually by 1995.

Malaria costs an estimated $12 billion in lost productivity in Africa.

Travellers from malaria-free areas to disease "hot spots" are especially vulnerable to the disease.

Non-immune pregnant women are at high risk of malaria. The illness can result in high rates of miscarriage and cause over 10% of maternal deaths (soaring to a 50% death rate in cases of severe disease) annually.

Semi-immune pregnant women risk severe anaemia and impaired fetal growth even if they show no signs of acute disease. An estimated 200 000 of their infants die annually as a result of malaria infection during pregnancy.

HIV-infected pregnant women are also at increased risk.

Malaria takes an economic toll - cutting economic growth rates by as much as 1.3% in countries with high disease rates

When insecticide-treated nets are used properly by three-quarters of the people in a community, malaria transmission is cut by 50%, child deaths are cut by 20%, and the mosquito population drops by as much as 90%.

It is estimated that less than 5% of children in sub-Saharan Africa currently sleep under any type of insecticide-treated net.

Sources : The Malaria Control Programme, World Health Organization, Third World Network Features, Health Canada, The Centers for Disease Control and Prevention,

and Desowitz, Robert S. The Malaria Capers (More Tales of Parasites and People, Research and Reality). W.W. Norton & Company, New York, 199

Malaria in the United States

Prevalance of Malaria: In the United States, approximately 1,000 cases are reported annually, which researchers estimate represent only 25 to 50 percent of actual cases. (Source: excerpt from Microbes in Sickness and in Health - Publications, National Institute of Allergy and Infectious Diseases: NIAID)

1,337 cases of malaria, including 8 deaths, were reported for 2002 in the United States, even though malaria has been eradicated in this country since the early 1950's

Of the 1,337 malaria cases reported for 2002 in the United States, all but five were imported, i.e., acquired in malaria-endemic countries.

Between 1957 and 2003, in the United States, 63 outbreaks of locally transmitted mosquito-borne malaria have occurred; in such outbreaks, local mosquitoes become infected by biting persons carrying malaria parasites (acquired in endemic areas) and then transmit malaria to local residents.

Of the ten species of Anopheles mosquitoes found in the United States, the two species that were responsible for malaria transmission prior to eradication (Anopheles quadrimaculatus in the east and An. freeborni in the west) are still widely prevalent; thus there is a constant risk that malaria could be reintroduced in the United States.

During 1963-1999, 93 cases of transfusion-transmitted malaria were reported in the United States; approximately two thirds of these cases could have been prevented if the implicated donors had been deferred according to established guidelines.

Death statistics for Malaria:

The following are statistics from various sources about deaths and Malaria:

Malaria death statistics by worldwide region:

About 1,136,000 deaths from malaria in Africa 2002 (The World Health Report, WHO, 2004)

About 1,000 deaths from malaria in The Americas 2002 (The World Health Report, WHO, 2004)

About 65,000 deaths from malaria in South East Asia 2002 (The World Health Report, WHO, 2004)

About 2,000 deaths from malaria in Europe 2002 (The World Health Report, WHO, 2004)

About 57,000 deaths from malaria in Eastern Mediterranean 2002 (The World Health Report, WHO, 2004)

About 11,000 deaths from malaria in Western Pacific 2002 (The World Health Report, WHO, 2004)

U SHUD LOOK FOR GRAPHS AND TRENDS THAT SHOW INCREASE/ DECREASE IN INCIDENCE N DEATH RATES.