Malaria

Agent Epidemiology History Symptoms Vector Distribution

Reservoirs Transmission Life Cycle Morphology

Sickle Cell Anemia Diagnosis Terms Other Sources

Name: Gk. Mal-aria= Bad Air

Synonym: Jungle Fever

Parasite: Plasmodium

Agent:

-Subkingdom: Protozoa, Phylum: Apicomplexa, Genus: Plasmodium

-four types Plasmodium infect humans:

P. vivax: name comes from very active ameboid motility, the parasite takes strange forms during the growth period, vivax in Latin means vigorous

P. ovale: known only since 1922, name comes from ovoid shape of infected distinction between P. vivax made by size and color of nucleus

P. malariae: asexual cycle occupies 72 hrs (other forms 48 hrs)

P. falciparum: gametocyte elongated (in contrast to others ovoid) and develop late, infect at all stages of red blood cells and thus large % of cells parastized, cytoadherance

Source: Markell, Edward, John David, Krotoski, Wojiech. Medical Parasitology. Eighth Edition. (Philadelphia, Saunders, 1999). p. 95-98

Epidemiology:

-Over 2 billion (41% world population) lives in malaria-risk area

-Infects 300-500 million people per year, 90% of whom are in sub-Saharan Africa

-Kills over 1 million people each year and some estimate as many as 2.5 million

-Leading Infectious killer of children. World wide a child dies of malaria every 30 seconds

-Disease Burden increasing due to: weakening public health, agricultural practices, global warming, lack of vaccine, drug resistance in parasite and vector, population growth in endemic areas, increased travel

http://www.niaid.nih.gov/newsroom/focuson/bugborne01/malaria.htm

History of Disease:

-6000-5500 B.C. : Deadly fevers, probably malaria, recorded since the beginning of written work

-2700 BC: Chinese “Ne Ching” describes as recurrent fevers and splenomegaly

-1600 B.C.: References in Vedic scripture

-500 B.C.: Hippocrates: association between swampy waters and air with fever

-Referred to in terms of febrile cycle: quotidian (24 hr), tertian (48 hr) and quartan (72 hr cycles)

-Believed to have started in Southeast Asia and spread first to Africa and then Europe. Americas no earlier that 16th century

- 1600s: Jesuit missionaries in South America learned about the antimalarial properties of the bark of Cinchona and brought to Europe and to India by the mid-1650s

-1775: One of first U.S. military expenditures was for quinine for the troops

-1861-5: During American Civil War 50% of white soldiers and 80% of black soldiers of the Union Army got malaria annually

-1880: Charles Laveran detects malaria in blood

-1897: Ronald Ross demonstrates vector as female mosquito

-1898: Developmental cycle in the mosquito was shown and the transmission to man upon taking a blood meal

-1927: J. Wagner von Juaregg was awarded the Nobel Prize in medicine for treating Syphilis with malaria. Inoculation with malaria produced fevers to burn syphilis bacteria. And then given quinine for malaria. Used until mid-1950s

-mid-1950s: WHO initiated global strategies for global eradication

-2002: Complete genetic code known

http://www.idrc.ca/books/reports/1996/01-05e.html

Symptoms:

-high fever, headache, photophobia, muscle ache and pain, anorexia, vomiting, possible splenamegaly (may not present these symptoms with P. vivax and mild strains of ovale)

Malarial Paroxysm:

Cold stage: typically starts with shaking chill that lasts 10 to 15 min or longer. patient may complain of extreme cold but the temperature is high. And the skin may be pale and cyanotic.

Hot stage: next follows and extreme hot phase where the patient becomes flushed and may seem agitated, restless, disoriented or even delirious. This may last 2-6 hrs for P. vivax and ovale, about 6 hrs in P. malariae, and longer in P. falciparum (between 10 and 36 hrs)

Sweat stage: sweat profusely for several hours and feel much better. Patient weak and exhausted tends to fall asleep

Depending on species: Cycle repeats every 36-72 hrs and initial attacks last 2-24 weeks

P. vivax––incubation 8-13 days primary attacks may last 3 weeks to 2 months. relapses occur in half the cases.

P. ovale––Incubation 8-17 days. early symptom recovery common (may be after 6-10 paroxysm)

P. malariae––Incubation 2 to 4 weeks. attacks last 3 to 24 weeks in Caucasians, shorter in blacks

P. falciparum––Incubation 5-12 days. attacks rarely exceed 2-3 weeks but complications and death may result

Complications: Due to P. ovale: Anemia

Due to P. vivax: Anemia, rupture spleen

Due to P. malariae: long standing infection can cause kidney failure

Due to P. falciparum: may lead to further complications than relatively benign species vivax, ovale, and malariae

-Capillary obstruction, decreased blood flow, tissue hypoxia, infarcation and death

-Cerebral malaria: most serious complication and can result in death. Severe headache may be presenting symptom which is followed by drowsiness, confusion and coma

-Anemia: due to the heavy parasite load

-Renal disease (esp. in kids)

-Blackwater fever: results from massive intravescular hemolysis and hemoglobinuria

-Dysenteric malaria: characterized by abdominal pain, nausea, vomiting, and upper GI bleeding. Liver may be enlarged and tender, skin icteric and urine contain bile

-Algid malaria: characterized by rapid development of hypotension and impairment of vascular perfusion

-Pulmonary Edema

-Tropical Splenomegaly syndrome (TSS): spleen becomes enormous in size

-Hypoglycemia

Source: Markell, Edward, John David, Krotoski, Wojiech. Medical Parasitology. Eighth Edition. (Philadelphia, Saunders, 1999). p. 95-98

Vector:

Female Anopheline Mosquito

1. 2.

1. http://www.malariajournal.com/

2. http://www.niaid.nih.gov/newsroom/focuson/bugborne01/malaria.htm

- in 60 of 200 Anopheles. various species of malaria have different temperature requirements for development in the mosquito host

-Common Vectors: Africa- A. gambiae s.s. , A. arabiensis, A. funestus

Asia- A. dirus, A. maculatus

South America- A. darlingi, A. albimanus

A female mosquito takes her blood mead from a human hand

Photo by Dept. of Bio., U. of Alberta, (c) BIODIDAC.

-Some disease-carrying Mosquitoes breed in tires and other artificial containers

Distribution:

http://www.who.int/ith/chapter05_m08_malaria.html

P. vivax:

80% of cases (most morbidity)

-only species that range extends to temperate regions

-most common in India and central and South America

P. Ovale:

-distribution mainly in tropical Africa and supplants P. vivax on West African coast

occasionally reports in South America and Asia

P. malariae:

-world-wide where other species of malaria are found, but less common

P. falciparum:

15% of cases (most mortality)

-tropics and subtropics

Source: Markell, Edward, John David, Krotoski, Wojiech. Medical Parasitology. Eighth Edition. (Philadelphia, Saunders, 1999). p. 95-98

Reservoirs:

-Human, especially those from immune carriers who move to non-endemic area

Transmission:

-Through infected Anopheles mosquito bite

-transmission by transfusion and shared syringes very rare but known

-congenital transmission rare

-Immunity: relative and generally strain specific

Life Cycle:

http://www.vnh.org/Malaria/ch1.html

Shobhona Sharma, The Institute for Fundamental Research, Bombay, India

http://www.malaria.org./

IN OTHER WORDS:

In mosquito: (sexual reproduction)

1. When a female Anopheline mosquito bites infected host (human), she draws blood containing female and male gametocytes into her stomach.

2. As the blood temperature falls, the male or microgametocyte undergoes a process of maturation that results in the production of gametes, the extrusion of these spindle shaped gametes is known as exflagellation

3. Female or macrogametocyte matures simultaneously and may be fertilized by the microgametocyte to form a zygote

4. Zygote becomes elongated and active and is known as an Ookinete

5. Ookinete penetrates cells of the stomach wall and rounds just under the outer covering of the stomach to become an oocyst

6. Growth of the oocyst allows the production of many slender, thread-like haploids called sporozoites. Sporozoites break out and wander throughout the body and enter salivary glands of mosquito.

7. Those sporozoites that enter the salivary glands of the mosquito may be inoculated into the next person bitten

In human: (asexual reproduction=schizogony)

8. Sporozoites that are injected into the blood stream leave the blood vascular system within 40 min and invade the parenchymal cells of the liver

9. Asexual reproduction takes place in the liver. P. vivax and P. ovale enter a resting stage where the parasite is known as hypnozoite. Hypnozoites reactivation is the source of the relapse characteristics in these species.

10. Asexual reproduction known as schizogony produces thousands of tiny merozoites in each schizont

11. Rupture of the infected hepatic cells releases merozoites into the circulation (erthrocytic schizogony. At the end of the schizogonic cycle, the infected blood cells rupture, freeing merozoites which go on to infect other red blood cells. It is believed that if a lot burst at the same time, there volume of toxic material in the blood stream may be sufficient to bring about malarial paroxysm. Theorized fever peaks may have regulatory effect on the developmental cycle

12. Usually after the patient has become clinically ill, gametocytes appear in the bed blood cells. These forms continue the asexual cycle grow but do not divide and finally form the male and female gametocyte.

13. If ingested by an Anopheles mosquito undergo the same cycle of sexual fusion and development to sporogony

Source: Markell, Edward, John David, Krotoski, Wojiech. Medical Parasitology. Eighth Edition. (Philadelphia, Saunders, 1999). p. 95-98

Phillips, 2001 Clin Microbiol Rev

Morphology:

1. 2.

3. 4.

5. 6.

1. Sporozoites of Plasmodium; approximate length of each = 10 µm. This life cycle stage is produced by the oocyst (see below), migrates to the mosquito's salivary glands, and is injected when the mosquito feeds.

2. Gametocytes of Plasmodium falciparum in a blood smear. Note the characteristic shape.

3. Ring stages of Plasmodium falciparum. Note the multiple infections of some cells

4. Trophozoites (late ring stages) of Plasmodium falciparum.

5. Oocysts of Plasmodium on the surface of a mosquito gut. The dark material is partially digested blood inside of the mosquito gut.

6.Hemozoin (digested hemoglobin) deposited in the cells of the spleen in a human infected with malaria. (Original image from "Parasites in Human Tissues," Department of Parasitology, Kyungpook National University School of Medicine, Korea.)

http://www.biosci.ohio-state.edu/~parasite/plasmodium.html

Sickle Cell Anemia:

Sickle cell trait is the genetic condition selected for in regions of endemic malaria People with normal hemoglobin (2 normal genes, HbA and HbA) are susceptible to Plasmodium and thus can be infected with malaria and die. People with sickle cell disease (2 sickle genes HbS and HbS) are susceptible to death from sickle cell disease. People with one sickle cell trait and one normal trait (HbA and HbS), have a much greater chance of surviving malaria and are not effected by the adverse effects of sickle cell disease

1. 2.

1. http://www.fda.gov/fdac/features/496_sick.html

2. http://sickle.bwh.harvard.edu/malaria_sickle.html

For more information: http://sickle.bwh.harvard.edu/malaria_sickle.html

http://www.SCInfo.org/

Diagnosis:

-Microscopy: Physician performs blood tests to determine presence and type

-Fluorescent staining with quantitative buffy coat method

-Immunological Capture: ParaSite F. and Malaquick test

-Antibody based detection

Source: Markell, Edward, John David, Krotoski, Wojiech. Medical Parasitology. Eighth Edition. (Philadelphia, Saunders, 1999). p. 95-98

Terms:

Antigenic Polymorphism: specific to P. falciparum, large family of genes which encode surface proteins. Capable of shifting antigenic type during a single infection, immunity to Type A does not mean immunity to next antigenic type. This makes P. falciparum particularly hard to prevent and treat

Cytoadherence: Specific to P. falciparum, results from expression of parastized red blood cell and stage-specific parasite derived ligands which caused blood cells to adhere together and small vessels may plug with these parastized cells

Gametocyte: A cell derived from a merozoite, that can undergo development into a gamete

Merozoite: a product of schizogony which can infect new host cells and undergo another round of schizogony or become a gametocyte

Schizogony: The process of asexual reproduction in the human liver by which the nucleus undergoes several divisions prior to cell division. Sometimes referred to as the ring cycle

Trophozoite: the feeding stage of a protozoan parasite (intracellular)

Source: Markell, Edward, John David, Krotoski, Wojiech. Medical Parasitology. Eighth Edition. (Philadelphia, Saunders, 1999). p. 95-98

For more information contact sshamos@stanford.edu

Other sources:

Global Fund to fight AIDS, Tuberculosis, and Malaria:

http://www.globalfundatm.org/

Easy to read WHO publication on what is malaria:

http://www.who.int/inf-fs/en/InformationSheet01.pdf

Technical malaria database by WHO/TDR:

http://www.wehi.edu.au/MalDB-www/who.html

Maps of malaria distribution within Africa with relation to weather, populations and species:

http://www.mara.org.za/mapsinfo.htm

Lots of information and links:

http://www.malaria.org./

Navy Health Center on Disease, Life Cycle, Distribution:

http://www.vnh.org/Malaria/ch1.html