Parasite Predicament

Explore the basics of human malaria—where does malaria occur, how is the parasite transmitted, and how does it cause illness and learn about one genetic mutation that provides some degree of protection from malaria.

MALARIAL TRANSMISSION

Malaria is a disease caused by parasites in the genus Plasmodium. Four species (P. falciparum, P. vivax, P. malariae, and P. ovale) cause malaria in humans and each is transmitted by the bite of an infected female mosquito (Anopheles sp.), which passes the parasite from the mosquito’s saliva into a person’s bloodstream, where the parasite then travels to the liver. Malaria is currently the largest cause of child mortality in sub-Saharan Africa, but is spreading because of environmental degradation and climate change.

Transmission differs in intensity depending on factors such as local rainfall patterns, location of mosquito breeding sites, presence of various mosquito species and Plasmodium species. Some areas are malaria zones throughout the year, while others have malaria “seasons” that usually coincide with the local rainy season. Over 40 percent of the world’s population live in the regions where malaria is most prevalent, around the equatorial zone, although climate change may be promoting the spread of malaria to adjacent regions.

Symptoms

Infected people start showing symptoms between day eight to day twenty-five. Symptoms are often flu-like and include headache, fever, shivering, joint pain, hemoglobin in urine and convulsions. Patients often display a cyclical symptom called paroxysm, where there is a feeling of coldness, then shivering, fever and sweating, repeating every two or three days. Further complications can occur including trouble breathing, kidney failure and death.

Environment

Currently, malaria is common in tropical and subtropical regions around the world, due to suitable mosquito habitat in these equatorial regions. However, as climates continue to change and global temperatures rise, that suitable habitat for malaria carrying mosquitos will expand. Both natural factors (such as climate change leading to more mosquito breeding sites, temperature changes that accommodate vector reproduction), and manmade factors (such as conflict, war, agricultural projects, damn, mining, and logging) lead to the malaria epidemic. As your patient was recently traveling, it is important to know the affect of global warming on the distribution of malaria. The movement of populations, both temporarily and permanently affect the spread of malaria. The largest and most devastating malarial epidemics occur in regions that have had little contact with the malaria parasite, and have little to no immunity to the parasite.

CONNECTION BETWEEN SICKLE CELL AND MALARIA

Sickle Cell Disease

Sickle cell disease is a genetic disease that affects the hemoglobin molecule in red blood cells. Normal red blood cells are round like doughnuts, and they move through small blood vessels in the body to deliver oxygen. Diseased red blood cells become hard, sticky and shaped like sickles used to cut wheat. When these hard and pointed cells go through the small blood vessels, they clog the blood flow and break apart. This can cause pain, organ damage and a low red blood cell count or anemia.

Hemoglobin

Each person has two copies of the gene for hemoglobin. Normal hemoglobin is referred to as Hemoglobin A. The letters AA are used to indicate that both hemoglobin genes are normal. The gene that causes sickle cell anemia is referred to as Hemoglobin S. There are three possible combinations of the genes for hemoglobin:

AA  Individual is homozygous for the hemoglobin A gene. So both copies of the gene code for normal hemoglobin and the person does not have the disease.

AS  Individual is heterozygous. One copy of gene codes for normal hemoglobin and other copy of the gene codes for sickled hemoglobin. This person does not have the disease and will not develop it later in life. This person is considered a carrier of the gene.

SS  Individual is homozygous for the sickled hemoglobin S gene; both copies of the gene code for diseased hemoglobin. This person suffers from sickle cell anemia.

Sickle cell anemia serves as a protective mechanism against malaria. Malaria is a deadly disease found in countries along the equator. People with sickle cell anemia are protected from malaria while those with normal hemoglobin are susceptible to it. Over the years, people with sickle trait migrated to other continents. Sickle cell disease is seen predominantly in the African descendant populations but is also seen in people of other ethnic groups, including individuals from parts of the Middle East, Central India, and countries bordering the Mediterranean sea, particularly Italy and Greece.

A 36-year old woman has been rushed to the hospital. Her symptoms are similar to those of the flu, but she has not responded to antiviral influenza medicine. The patient’s family history is recorded, as well as a recent travel record. The travel record from the last two years includes a camping trip in the southwestern United States, a layover in Turkey on the way to a weeklong safari in Mauritania and a 3-day cruise around the Caribbean.

Pre-Lab Questions:

• Why would travel history be important for physicians to note?
• Why would family history be important for physicians to note?
• Make a hypothesis: Do you think the patient has malaria? Why?

A 36 year old woman has been rushed to the hospital. Her symptoms are similar to those of the flu, but she has not responded to antiviral influenza medicine. The patient’s family history is recorded, as well as a recent travel record. The travel record from the last two years includes a camping trip in the northwestern United States, and a cruise around the Mediterranean.

The patient’s family history reveals that the patient’s maternal aunt and paternal grandfather had Sickle Cell Disease, a heritable disease. The patient is being tested for Sickle Cell Disease, but these results have not been received yet. Sickle Cell trait (the state of being a carrier for sickle disease) may reduce the severity of malaria because it changes the shape of the red blood cell where the malaria parasite lives.  The malaria parasite does not fit into a sickle shaped red blood cell.

Since the patient does not know if she is a carrier for Sickle Cell trait, and based on the patient’s recent travel, the patient will be tested for malaria. Malaria is a parasite-borne infectious disease. The mosquito’s bite introduces the parasite from the mosquito’s saliva into the person’s blood. The parasite then travels to the liver where it matures and reproduces. The parasite ruptures from the liver and infects red blood cells and multiplies further. This cycle causes fevers, headache, shivering, joint pain, vomiting, yellowing of the skin (jaundice), retinal damage and convulsions. A hallmark of malaria is the cyclical occurrence of sudden coldness followed by shivering, fever and sweating every 36-48 hours.

To test your patient for malaria, you will use an enzyme-linked immunosorbent assay (ELISA), which will demonstrate the presence of malarial antibodies with color change. An ELISA tests for the presence of a specific antigen for a particular antibody. Antigens serve as the target for the receptors of an immune response. Antibodies are large Y-shaped proteins that identify and neutralize pathogens.

Malarial transmission is influenced by several mitigating factors. Students are encouraged to explore these factors in a post-laboratory extension.

Explore malaria with the Malaria Atlas Project

Malaria, the disease caused by parasites of the genus Plasmodium, is a global health concern. Half of the human population is at risk of contracting malaria, yet the parasite is confined to a narrow climatic range. Temperatures must be high enough and rainfall must be frequent enough for the parasite’s vector to maintain activity, feed and reproduce. The Malaria Atlas Project provides access to maps, data and literature, which can be used to explore the geographic distribution of Plasmodium and its arthropod vectors, the prevalence of malarial infection globally and regionally, and the occurrence of blood disorders related to malaria. Information available through the Malaria Atlas Project can be implemented in a variety of classroom exercises including the exploration of climate and the implications for climate change in the context of malaria and human health.

This post-laboratory extension is intended to provide an open, flexible framework that is not necessarily a continuation of our Parasite Predicament activity but can be tailored to introduce biological concepts illustrate the connection between disciplines.

Blood disorders and malaria

A number of blood disorders are known to affect the malaria parasite (Plasmodium sp.) at its human-blood-borne life stage, resulting in decreased fitness of the parasite and thereby reducing its effect on its human host. Sickle cell anemia, which provides carriers a high tolerance to malaria infection, is the best documented of these disorders and brings a plethora literature and multimedia material suitable for introducing new concepts to students. For example, students could explore the mechanisms by which evolution works—occurrence of the sickle cell allele is closely tied to the presence of malaria in the environment. Moreover, sickle cell is not a perfect solution to malaria and has resulted in evolutionary tradeoffs, which manifest in a suite of health concerns unrelated to malaria and reduce the fitness of sickle cell carriers outside of malaria habitat. This video discusses the research that led to the discovery of the link between sickle cell and malaria. The Malaria Atlas Project offers access to datasets that can be used to explore the connection between malaria and sickle cell in a statistical framework. Classroom exercises can be tailored to be as simple as graphing malaria vs. sickle cell occurrence in a set of countries or as complicated as calculating significance (T or p values) to look at the relationship between blood disorders and malaria.

This option provides a natural transition from our Parasite Predicament activity to our Mystery of the Crooked Cell activity, introduces students to the interconnected nature of malaria and sickle cell, and provides a connection between biology, data management and mathematics.

Malaria prevention and public health

Malaria has been and continues to be among humanity’s most pressing health concerns; it sickens hundreds of millions and kills hundreds of thousands of people each year. Developing countries, which lack regular access to quality healthcare, are hit hardest by malaria. Using malaria as a case study in public health offers students an opportunity to study the Plasmodiumlifecycle (how it infects humans and how it causes illness), historical and contemporary preventative measures (e.g., mosquito nets, anti malarial meds…), efforts to develop new methods of prevention, detection and treatment, and to explore the ways in which societies in developing and developed countries deal with a persistent public health concern. Here, UNICEF’s introduction to malaria can act as a guide. Teachers may elect to have students create a media campaign (poster, website, video…) to build awareness of malaria and its impact. Alternatively, maps and/or data available on the Malaria Atlas website can be used to examine the global prevalence of malaria in a socioeconomic context (i.e., developed vs. developing countries).

This option provides the opportunity to expand on the laboratory-based concepts of malaria/antigen detection introduced in the Parasite Predicament activity and considers broader human-health implications.

Global climate change and the link to malaria

• Global temperatures are expected to rise.
• If global temperatures rise and if accompanied by adequate rainfall, then the risk of malaria may increase.
• Warmer temperatures reduces the time to maturity in the parasites life cycle, increasing the likelihood that a mosquito will transmit a mature malarial parasite before the mosquito dies.
• Climatic conditions are expected to become more conducive to malarial transmission in east Africa, central Asia, China, Europe and the Eastern US.
• There are varying opinions on the severity of the spread-The fringes of malaria-affected areas are likely to see in an increase in malaria, but overall since 1900, cases of malaria have decreased due to public health efforts (economic development, medication, insecticides, mosquito nets, etc).

The effects of global climate change are apparent today; one of the potential effects may be the spread of malaria due to warming global temperatures. Malaria is a disease caused by a protozoan parasite (Plasmodium falciparum) that is transmitted by the bite of a female mosquito (Anopheles sp.) passing the parasite from the mosquitos’ saliva into a persons’ bloodstream and then travels to the liver. Infected people start showing symptoms between eight to twenty five day. Symptoms are often flu-like and can include headache, fever, shivering, joint pain, hemoglobin in urine and convulsions. Patients often display a cyclical symptom called paroxysm, where there is a feeling of coldness, then shivering, fever and sweating, repeating every two or three days. Further complications can occur including trouble breathing, kidney failure and death.

Currently, malaria is common in tropical and subtropical regions around the world, due to suitable mosquito habitat in these equatorial regions. It is suggested that as climates continue to change and global temperatures rise, that suitable habitat for malaria carrying mosquitos will expand. Optimal temperatures for Anopheles mosquitos ranges between 20–30°C, with sufficient rainfall and humidity. Climate change may alter the behavior and geographic range of the mosquitos, as well as the life cycle of the parasite. Warmer temperatures can equate to a more rapidly digested blood meal, more frequent blood meals and accelerated development of the parasite. Mosquitos are most likely to spread to the outward fringes of their range and to higher elevations as temperatures become more hospitable. It has been suggested there will be an increase of malaria outbreaks in the East African highlands, when comparing climate data from 1950-2002 concurrent with an increase in the frequency of malaria cases. This study also postulated that a half degree centigrade increase in average global temperature trend will result in a 30–100% increase in mosquito abundance.

Climate change will not equate to unbounded expansion of mosquitos into new habitats, localized weather patterns will result in wetter and drier regions. Mosqutios require sufficient rainfall and standing water for the aquatic stage of the life cycle. With average global temperatures expected to increase from 1.4-5.8°C by the end of the 21st century, broad scale impacts of climate change will have devastating effects on the planet and the human race. The current exponential growth of the human population along with poor access to healthcare in malaria stricken regions when accompanied by land use changes (i.e., deforestation) are likely only to favor mosquito breeding and increase the spread of malaria to a larger human population. The spread of malaria due to global warming is arguably one of the most pressing climate change related health issues facing the world in the very near future.

References 

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Hay, S.I., D.J. Rogers, S.E. Randolf, D.I. Stern, J. Cox, G.D. Shanks, and R.W. Snow. 2002. Hot topic or hot air? Climate change and malaria resurgence in East African highlands. Trends in Parasitology. 18:530-534.

Hay, S.I., J. Cox, D.J. Rogers, S.E. Randolf, D.I. Stern, G.D. Shanks, M.F. Myers, and R. W. Snow. 2002. Climate change and the resurgence of malaria in East African Highlands. Letters to Nature. 415:905-909.

Marten, W.J.M., T.H. Jetten, J. Rotmans, and L.W. Niessen. 1995. Climate change and vector-borne diseases. Global Environmental Change. 5:195-209.

Martens, W.J.M., L.W. Niessen, J. Rotmans, T.H. Jetten, and A.J. McMichael. 1995. Potential impact of global climate change on malaria risk. Environmental Health Perspectives. 103:458-464.

Pascual, M. J.A. Ahumada, L.F. Chaves, X. Rodó, and M. Bouma. 2006. Malaria resurgence in the East African Highlands: Temperature trends revisited. PNAS. 103:5829-5834.

Patz, J.A. and S.H. Olson. 2006. Malaria risk and temperature: Influences from global climate change and local land use practices. PNAS. 103:5635-5636.

Patz, J.A., D. Campbell-Lendrum, T. Holloway, and J.A. Foley. 2005. Impact of regional climate change on human health. Nature. 438:310-317.

Tanser, F.C., B. Sharp, and D. le Sueur. 2003. Potential effects of climate change on malaria transmission in Africa. The Lancet. 362:1792-1798.

van Lieshout, M., R.S. Kovats, M.T.J. Livermore, and P. Martens. 2004. Climate change and malaria: analysis of the SRES climate and socio-economic scenarios. Global Environmental Change. 14:87-99.