malaria by francheska camilo

02/11/2014 Malaria by Francheska Camilo González

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


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".


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].


Figure 1: Malaria Transmission Cycle

Source: EuroClinix.net.

<http://www.euroclinix.net/malaria-transmission.html>

Available: January 16, 2014.

http://www.euroclinix.net/malaria-transmission.html


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.

http://www.medilinks.blogspot.com/2010/11/malaria-malaria-is-caused-by-parasite.html


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]

Inflammation in the brain and spinal cord because of a viral infection [12].

Meningitis [3, 18]

Inflammation of the thin tissue that originates around the brain and spinal cord [13].

Pulmonary edema [3, 18]

Abnormal accumulation of fluid in the lungs, especially in the area between the capillaries and alveoli, which can cause swelling [14].

Ruptured spleen [3, 18] Massive internal bleeding (hemorrhage) [3, 18].


Figure 3: Malaria parasites destroying red blood cells

Photograph by Albert Bonniers Forlag

Source: National Geographic

<http://science.nationalgeographic.com/science/photos/malaria/#/malaria-

parasites_1059_600x450.jpg>

Available: February 13, 2014.


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 [2].


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].


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].


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].


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.


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-vacuna-

frente-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

http://www.virus.med.puc.cl/viajero/malaria.html

http://www.who.int/mediacentre/factsheets/fs094/es/

http://www.nlm.nih.gov/medlineplus/spanish/ency/article/000621.htm

http://www.anlis.gov.ar/inst/consulta/infecciosas/malaria/malaria.htm#es%20trasmitida

http://www.cdc.gov/malaria/travelers/country_table/a.html

http://www.grupobiotecnologia.com.ar/ver-que-es-la-biotecnologia-52

http://www.ranf.com/enfermedades-olvidadas/noticias-enfermedades/1562-vacuna-frente-a-malaria.html

http://www.ranf.com/enfermedades-olvidadas/noticias-enfermedades/1562-vacuna-frente-a-malaria.html

http://www.med.nyu.edu/content?ChunkIID=121184

http://www.saludmedica.com/tema/insuficiencia-renal-aguda

http://www.ecured.cu/index.php/Insuficiencia_hep%C3%A1tica

http://cirrosis.net/insuficiencia-hepatica/

http://eis.ifas.ufl.edu/spwhat.htm

http://www.nlm.nih.gov/medlineplus/spanish/meningitis.html


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.salud180.com/salud-z/edema-pulmonar

http://www.jimmunol.org/content/early/2012/05/21/jimmunol.1102492

http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0036-36342009000900008

http://www.enferaclinic.org/premios/PrTERUMO/XI/Malaria.pdf

http://www.nlm.nih.gov/medlineplus/ency/article/000621.htm

http://www.accefyn.org.co/revista/Vol_29/113/113_535_546.pdf



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