1. www.FrancheskaCamilo.com
Malaria
Prepared by: Francheska Camilo González
Research Paper Project - MICR 4505 - 8072
Prof. Eva Rodríguez
UIPR – Recinto Metro
February11, 2014
English version: February 27, 2014
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Malaria by Francheska Camilo González
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2. This article is dedicated to my dog: Sassy Camilo González (January 5, 2007 - February 20,
2014), which received Doxycycline as part of treatment during their stay in a Veterinary
Hospital. We love you and we will always remember you like Sassy La Campeona "Sassy the
Champion".
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3. INTRODUCTION
Malaria is a parasitic disease transmitted to humans by bites of mosquitoes of the genus
Anopheles [1]. Malaria is the most common systemic disease in the world, being reported 200 to
500 million cases and 1 million deaths from this parasitic disease
[1]
. In countries with a climate
temperate, the mosquitoes can carry malaria, but in the winter season, the parasite tends to
disappear [3].
ALTERNATE NAMES [3, 18]

Quartan malaria

Biduoterian fever

Falciparum malaria

Blackwater fever

Plasmodium

Tertian malaria
CAUSES
Malaria is caused by a parasite that is transmitted from one human to another by bites of
infected Anopheles mosquitoes
[3, 18]
. Now once is the host infected (human), the parasites
migrate through the bloodstream to the liver, where they have several cycles of asexual
multiplication, and then enter to the bloodstream to infect red blood cells
[3, 4, 18]
. Most symptoms
are caused by the release of merozoites (shape acquired by the maturation stage of the
parasite or sporozoite after migrate through the bloodstream until to the liver) in the blood, is
produced anemia due to destruction of red blood cells, and large amounts of hemoglobin
released into circulation by the breakdown of red blood cells [3, 18].
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4. Figure 1: Malaria Transmission Cycle
Source: EuroClinix.net.
<http://www.euroclinix.net/malaria-transmission.html>
Available: January 16, 2014.
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5. SYMPTOMS
The Malaria symptoms usually appear in 7-15 days after the bite of an infected mosquito
[2]
.
Early symptoms are often difficult to recognize, as these commonly include fever, headache,
chills and vomiting
[2]
. In endemic areas, the children with severe disease often report severe
anemia or cerebral malaria
[2]
. In such areas, individuals can gain some partial immunity to the
disease, facilitating the occurrence of asymptomatic infections [2].
Figure 2: Symptoms of Malaria
Source: Young Doctors’ Research Forum
< http://www.medilinks.blogspot.com/2010/11/malaria-malaria-is-caused-by-parasite.html>
Available: February 15, 2014.
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6. PREVENTION, DIAGNOSIS AND TREATMENT
The travelers going to countries such as Afghanistan, Angola, Argentina, Azerbaijan, and other
areas of risk by the presence of malaria should call to the Center for Disease Control and
Prevention (CDC) of the United States, for information about the types of malaria, preventive
drugs, and times of the year that should not travel to these areas
[3, 5, 18]
. In areas with a higher
incidence of Plasmodium falciparum, are recommended antimalarial treatments such as
atovaquone / proguanil (Malarone), doxycycline and mefloquine, and repellents with DEET
concentrations of about 35% as prevention methods
[1, 3, 18]
. The World Health Organization
(WHO) recommends confirming the diagnosis with parasitological methods, prior to
administering any treatment for malaria
[2]
. For those infected with Plasmodium falciparum
individuals, there is a treatment know as Artemisinin-based Combination Therapy [2].
Table 1: Effects and complications of malaria [3, 18]
Complication
Effect of the disease, condition or complication
Hemolytic anemia [3, 18]
The body's immune system to attack mistakenly the individual's
own red blood cells, causing that to disintegrate, and hemolysis
occurs [8].
Kidney failure [3, 18]
The kidneys losing their ability to remove waste and
concentrate urine without losing electrolytes [9].
Hepatic Impairment [3,18]
The liver lose their ability to carry out its synthetic and
metabolic function, causing complications such as excessive
bleeding, infection and kidney failure, and increased brain
pressure [10 , 11].
Encephalitis
[3, 18]
Meningitis [3, 18]
Pulmonary edema [3, 18]
Ruptured spleen [3, 18]
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Inflammation in the brain and spinal cord because of a viral
infection [12].
Inflammation of the thin tissue that originates around the brain
and spinal cord [13].
Abnormal accumulation of fluid in the lungs, especially in the
area between the capillaries and alveoli, which can cause
swelling [14].
Massive internal bleeding (hemorrhage) [3, 18].
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7. Figure 3: Malaria parasites destroying red blood cells
Photograph by Albert Bonniers Forlag
Source: National Geographic
<http://science.nationalgeographic.com/science/photos/malaria/#/malariaparasites_1059_600x450.jpg>
Available: February 13, 2014.
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8. PROBLEM
Resistance to antimalarial drugs is the main problem of malaria
[2]
. It has been detected in four
countries of the Greater Mekong Subregion (Cambodia, Myanmar, Thailand and Vietnam), that
the parasite has shown artemisinin resistance
[2]
. In these areas, it is assumed that the
resistance pattern is because the patients are abandoning their treatment when the symptoms
subside, and are treated with an oral artemisinin monotherapy (partial treatment in which there
is not a second drug), which allows the existence of parasites that are resistant in the blood, and
transmission to other mosquitoes, and from these to other individuals
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Malaria by Francheska Camilo González
[2]
.
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9. WHAT IS THE BIOTECHNOLOGY AND HOW COULD HELP TO FIGHT MALARIA?
WHAT IS THE BIOTECHNOLOGY?
Biotechnology is technology application that uses systems based in biology to create or modify
products or processes having a specific use, such as the development of treatments for
diseases, among other technological applications [6].
RESEARCH TO SEARCH A TREATMENT FOR MALARIA
Researchers at the National Center of Biotechnology of CSIC and the U.S., led by Dr. Mariano
Esteban, with the use of biotechnology applications, developed a new combined immunization
protocol for vector to remove an infection caused by the parasite Plasmodium (the causative
agent of malaria) in a murine model
[7]
. In a phase III clinical trial with 15,450 children, they
showed that the vaccine (RTS, S/AS01), for a period of one year, produced a 50% reduction
against malaria in children 5 to 17 months of age
[7]
. Also with the use of technological
applications, in the published studies by the group of Esteban (Journal of Immunology:
"Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case Study with Malaria Vaccine Based
on the Circumsporozoite Protein", published in May 21, 2012
[15]
), it was demonstrated that with
vaccination in two phases, in where the first phase is administrated a chimeric protein (CS 14K), and after two weeks is administrated an attenuated virus (MVA-CS) produced by the CS
protein, is obtained the complete protection in mice with the parasite Plasmodium yoelii [7].
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10. Increased incidences Malaria and the need for identification of new drugs and treatments
require a search for alternatives to inhibit infection of different stages of the life cycle of the
malaria parasite in the vertebrate host
[20]
. Dr. Photini Sinnis and his research group composed
of Dr. David Mirelman, Dr. Melissa Cabinian and Dr. Alida Coppi, conducted two experimental
trials in which were used allicin to determine efficacy against erythrocytic stages in vivo and the
sporozoite infectivity in vivo
[20]
. In the experimental testing to determine the effectiveness
against the erythrocytic stages in vivo , they proceeded to inject mice females "Swiss Webster",
with 2 x 105 parasites "GFP- expressing P. berghei", and subsequently proceeded to inject 8
mg/kg of allicin (in DMEM without Cys/Met)
[20]
. In the assay for determining the sporozoite
infectivity in vivo, they proceeded to inject female mice "Swiss Webster" with 5-8 mg/kg of allicin
(in DMEM without Cys/ Met). Subsequently, they proceeded to inject 104 P. yoelii sporozoites,
and after 40 hours, they isolated the total RNA, to quantify the malaria infection by reverse
transcription using real time PCR
[20]
. The experimental tests showed that allicin, a cysteine
protease inhibitor present in teeth of garlic freshly crushed, was effective in both assays and
could be used as a useful drug for the prophylaxis and malaria
[20]
. In the scientific article
"Allylation of Intraerythrocytic Hemoglobin by Raw Garlic Extracts", indicated that the
phenomenon of induced vasodilation by the garlic could lead to new research on the changes
that natural products exert on the proteome
[21]
. This is important, because the progress in the
genomic and proteomic studies, could facilitate the identification of new Plasmodium
antigens[19].
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11. DETECTION OF MALARIA
Detection of antigens, antibodies and genetic material are part of the basic principle of
molecular diagnostic tests
[16]
. Advances in molecular biology, the development of robotic
technology, the proteomic and genomic sequencing are significant contributors to the
development of more specific tests that help identify biomarkers , and with the use of the
methodology of biotechnology can produce high purity reagents and identify the genes that
encoding specific antigens, production of monoclonal antibodies, and others
[16]
. In a study to
detect cases of malaria in the Vall d' Hebron Hospital - Barcelona, were carried out various
diagnostic tests to a group of 26 patients in which were suspected had contracted malaria while
traveling to their country of origin
[17]
. To determine the presence of the parasite in the blood of
these patients were carried out laboratory tests like the Thin Extension of Blood, Drop Thick,
and the Rapid test for antigen detection of Plasmodium [17]. The Rapid Test to Antigen Detection
of Plasmodium is a laboratory test used in biotechnology to diagnose infection with the malaria
parasite (Plasmodium spp.)
[16, 17]
. This test is based on the identification of biomarkers such as
protein-rich in histidine 2 (PRH2), and Dehydrogenase enzyme of lactate (pLDH)
[16, 17]
. These
serve to establish a differential diagnosis or by mixed infection, because the diagnostic strips
have monoclonal antibodies at its distal end, which allows recognize pLDH, which containing
the specific antibodies against the Plasmodium falciparum [16].
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12. CONCLUSION
Malaria is a major public health problem
[7]
. From these infections caused by this parasitic
disease, there is an infection rate of about 225 million people, and about 1 million deaths
annually
[7]
. These numbers are increasing, because in some regions of the world, mosquitoes
that carry malaria have developed resistance to insecticides and antibiotics, allowing the spread
of the disease and makes difficult to control the rate of disease
[3]
. The Malaria is dangerous
parasitic disease, because is potentially mortal and transmitted to humans by the bites from
mosquitoes that are infected with parasites of the genus Plasmodium, and as a conclusion, that
if the disease is not controlled by suitable preventive methods, will survive those parasites that
are resistant, allowing the transmission of this to other mosquitoes, and from these to other
individuals.
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13. REFERENCES
1. Pontificia Universidad Católica de Chile, Facultad de Medicina, Centro de
Investigaciones Médicas. Malaria. Available: December 17, 2013
http://www.virus.med.puc.cl/viajero/malaria.html
2. Organización Mundial de la Salud. Paludismo. Available: December 17, 2013
http://www.who.int/mediacentre/factsheets/fs094/es/
3. MedlinePlus. Malaria. Available: December 17, 2013
http://www.nlm.nih.gov/medlineplus/spanish/ency/article/000621.htm
4. ANLIS. Malaria o Paludismo. Available: December 17, 2013
http://www.anlis.gov.ar/inst/consulta/infecciosas/malaria/malaria.htm#es%20trasmitida
5. CDC. Malaria Information and Prophylaxis, by Country [A] Available: February 11, 2013
http://www.cdc.gov/malaria/travelers/country_table/a.html
6. Grupo Biotecnología. ¿Qué es la Biotecnología?. Available: December 17, 2013
http://www.grupobiotecnologia.com.ar/ver-que-es-la-biotecnologia-52
7. Real Academia Nacional de Farmacia. Vacuna frente a malaria. Available: December
17, 2013
http://www.ranf.com/enfermedades-olvidadas/noticias-enfermedades/1562-vacunafrente-a-malaria.html
8. NYU Langone Medical Center. Anemia Hemolítica Autoinmune.
Available: January 16, 2014
http://www.med.nyu.edu/content?ChunkIID=121184
9. Salud Médica. Insuficiencia Renal Aguda. Available: January 16, 2014
http://www.saludmedica.com/tema/insuficiencia-renal-aguda
10. EcuRed. Insuficiencia Hepática. Available: January 16, 2014
http://www.ecured.cu/index.php/Insuficiencia_hep%C3%A1tica
11. Cirrosis.net. Insuficiencia Hepática. Available: January 16, 2014
http://cirrosis.net/insuficiencia-hepatica/
12. EIS IFAS University of Florida. ¿Qué es la Encefalitis?. Available: January 16, 2014
http://eis.ifas.ufl.edu/spwhat.htm
13. MedlinePlus. Meningitis. Available: January 16, 2014
http://www.nlm.nih.gov/medlineplus/spanish/meningitis.html
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14. 14. Salud180. Edema pulmonar. Available: January 16, 2014
http://www.salud180.com/salud-z/edema-pulmonar
15. Vijayan, A., Gomez, C., Espinoza, D., Goodman, A., Sanchez-Sampedro, L., Sorzano,
C., Zavala, F., Esteban, M. Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case
Study with Malaria Vaccine Based on the Circumsporozoite Protein.
Available: January 16, 2014
http://www.jimmunol.org/content/early/2012/05/21/jimmunol.1102492
16. Hernández - Hernández, F., Rodríguez, M. Avances biotecnológicos en el diagnostico
de enfermedades infecciosas. Available: January 16, 2014
http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0036-36342009000900008
17. De la Vega, F., López, I., Saura, J., Gabaldón, F. Malaria. Una vieja enfermedad en un
nuevo siglo. Available: January 16, 2014
http://www.enferaclinic.org/premios/PrTERUMO/XI/Malaria.pdf
18. MedlinePlus. Malaria. Available: February 15, 2014
http://www.nlm.nih.gov/medlineplus/ency/article/000621.htm
19. Valencia, S. La Malaria: Estrategias actuales para el desarrollo de una vacuna efectiva.
Available: February 11, 2014
http://www.accefyn.org.co/revista/Vol_29/113/113_535_546.pdf
20. Coppi, A., Cabinian, M., Mirelman, D., Sinnis, P. Antimalarial Activity of Allicin, a
Biologically Active Compound from Garlic Cloves. Available: February 11, 2014
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472199/?report=classic
21. Bonaventura, J., Rodríguez, E., Beyley, V., Vega, I. Allylation of Intraerythrocytic
Hemoglobin by Raw Garlic Extracts. Available: February 11, 2014
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132946/?report=classic
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