Is Doxycycline along with Quinine Bisulphate cure for Plasmodium falciparum malaria?

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Is Doxycycline along with Quinine Bisulphate cure for Plasmodium falciparum malaria?

The issue: Malaria Malaria is an infectious disease that causes high chills and fever, due to parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. According to the CDC, ‘Malaria is a complex and deadly disease that puts approximately 3.3 billion people at risk in 109 countries and appears to the world.’ (1) Most deaths occur among children living in Africa, where a child dies every minute from malaria. There are five species of Plasmodium, which infect to human. Among then P. falciparum is the most predominant human-infective species in the tropics, which result in a severe form of malaria. (2)

Explanation of Malaria

As can be seen in figure 1, there are sequences of four phases: ‘one sexual without multiplication and three asexual with multiplication.’ (4) The genus Anopheles is the only insect capable of harbouring the human malaria parasite. Therefore, the sexual and first asexual phases occur in Anopheles mosquitos. (5) The second asexual phase is in the liver or other tissues, and the third in the blood, which may be repeated many times and each asexual phase begins with feeding and growth. Every phase ends when new invasive parasites appear, and some parasites become sex-cells, called gametocytes, which start a new cycle if taken into an Anopheles.

malaria struggle and convulse and finally fall into a coma. (4) d

The sexual phase (fertilisation) A female Anopheles sucks a blood from an infected person. Gametocytes escape from red blood cells to become free gametes (male and female). The male gamete produces up to 8 flagella and these tears themselves free and each with a male nucleus is attached. If a female gamete is found, then ‘fertilisation produces a zygote and develops into the invasive ookinete, which bores into the stomach wall and becomes an oocyst’ (6) (fugure2).

The first asexual phase (Sporogony) The oocyst grows, then divides to produce thousands of invasive sporozoites. The mature cyst bursts and the free sporozoites migrate through the body of the mosquito and invade her salivary glands (figure 3).

The second asexual phase (Hepatic Schizogony) Sporozoites are injected into the blood, when the mosquito feeds again. They invade liver cells and ‘become hepatic trophozoites’. (4) These grow, and then divide to produce thousands of invasive merozoites into the blood.

The third asexual phase (Erythrocytic Schizogony) Merozoites invade red blood cells and become erythrocytic trophozoites (figure 4). These grow and then become schizonts, which divide internally into ‘8 to 16 new merozoites.’ (4) Merozoites are released and the cycle starts again when mature the red blood cell bursts.

Proposed treatment: Doxycycline with Quinine Bisulphate (used since 2007)

Doxycycline can be used in combination with Quinine bisulphate to kill the malarial parasites. (9)

Doxycycline is used to cure a wide variety of bacterial infections, including those that cause acne. This treatment is known as a tetracycline antibiotic which is used to prevent malaria. This antibiotic treats only bacterial infections and it works by stopping the growth of bacteria. Doxycycline will not work for viral infections such as common cold and flu. However, it is also a relatively ‘efficacious causal prophylactic drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria.’ (10)

Quinine is a cinchona alkaloid that consists of the aryl amino alcohol group of drugs (figure 5). It is a basic compound and always presented as a salt. Quinine is effective at killing Plasmodium and they work against those forms of Plasmodium that has developed resistance to other drugs. (11) In the red blood cell, the merozoites digest the haemoglobin, using the amino acids for its own growth. The residual haemoglobin is potentially toxic, but Plasmodium neutralises it by converting it into an insoluble precipitate called haemozoin. Quinine appears to interfere with production haemozoin and the free haemoglobin accumulates, which interrupt the growth of merozoites. (6)

Lab Method

“A quinine doxycycline-experimental study was carried out at the Department of Medicine, Combined Military Hospital Malir Cantonment Karachi Pakistan, from January 2003 to December 2004.” (12) This study selected 100 adult males who were infected by Plasmodium Falciparum (exclude complicated malaria patients). The patients started with Quinine Bisulphate 10mg/body weight in kg 8 hourly until the clearance of malarial parasites for duration of 3 to 7 days. At the same time, Doxycycline (100mg) was taken 12 hourly for 7 days. The patients’ vital signs were recorded for 4 hours and they were tested twice a day for any side effects of the drugs or for any development of disease. Malarial parasite index was counted by taking a blood sample of the patient and calculated as WBC count/microliter x parasite count/microliter/100. The patients stayed in the hospital for 28 days for late treatment failure.

Analysis of Researchers Results

Table 1 shows, the patients who entered this study and the all patients were recovered from malaria infection. The patients were between 16 to 49 years old, mean age of 31. Fever lasted for 3 days in maximum number of patients and for 6 days in only 5 patients.

Mean duration of Doxycycline with quinine bisulphate treatment till the clearance of malarial parasites was 4.63 ± 1.38 days (range 1 to 7 days). Duration of treatment was 5 days in maximum number of patients while only 6 patients had to take quinine for 7 days. In this study, they also recorded the side effects, but early or late failures had not been reported from the patients. Table 2 shows the malaria parasites are increasingly decreasing from day 1 to 7. During the 28 days observation period there was no recurrence and all patients were discharged from the hospital in good health.

Validity and Reliability of the Results

This study produced valid data, since the controlling variables determine that the variables measured relevant to the issue and were also measured in an appropriate way to create accurate results. First of all, doxycycline with quinine used in this experiment was controlled by one hundred adult male patients who were infected by Plasmodium Falciparum (uncomplicated malaria patients). This would guarantee that the progress of this study was not determined by these factors and so would ensure that the results were valid in this respect. Moreover, the same amount of doxycycline (100mg was taken 12 hourly for 7 days) with quinine (10mg/body weight in kg 8 hourly for 3-7 days) was provided to the patients, meaning that the results are substantiated in their validity, as the patients were cured through the use of the same method and so correct controlling variables. Additionally, the relevant dependent variables were measured to ensure that the experiment is valid in helping to provide evidence as to whether this method could be used to help solve the issue. The variables looked at whether the malaria parasite index was cleared appropriately, which would determine the duration of quinine bisulphate treatment, as well as the development of any complications of the disease. This measurement was carried out with the use of the blood samples which were taken for counting malarial parasite index (was calculated as WBC count/microlitre x parasite count/microlitre /100), which was a valid way to take measurements, since it allowed for precise observation of malaria parasites. In this study, the results produced were reliable, since they do clearly demonstrate repeatability by using a large sample group. This ensures that in each individual repetition of the experiment results were very similar. Therefore, this will reinforce the findings and shows that this study is repeatable. On the other hand, it has not been performed by any other researchers, thus there is no evidence of reproducibility of this study. On that account, we cannot know that if the experiment were carried out elsewhere, whether it would maintain the same results. Thus, this reduces the overall reliability of the study.

Validity of Tables

Table 1 shows the patients’ profile, in which considered as a valid source of information as it shows the control group (100 males aged 16-49 infected with Plasmodium Falciparum malaria) and the range of fever and parasites clearance time in a day and duration of the treatment which determines success in cure Plasmodium Falciparum malaria. This result shows no drop outs or late of early failures among the patients, which mean the process of this result is clear and appropriate. In addition, the data presented is relevant to the investigation. For example, table 2 presents the mean value of the primary end points which allow the reader to understand clearly how malaria parasites were decreasing day by day. Moreover, the table shows the data with various factors such as minimum, maximum and mean values of malarial parasites as it presents practical and reasonable manner. The manner in which the data is processed is clear and appropriate as 6 scientists have researched. Thus, it ensures that the data was appropriately analysed and explained.

Implication of this Treatment

Table 3 shows how malaria affects the economics of Africa. Since malaria appears in many developing countries, the costs of the drugs are one of the important factors to treat the patients, because malaria is truly a disease of poverty. People who tend to live in malaria-prone rural areas in poorly-constructed houses have higher chances to get infected by malaria, but they are awfully poor. Thus, one of the economic implications of this combination of drug (doxycycline along with Quinine bisulphate) is that it is relatively cheaper than other drugs, which means the poor can afford the cost of this treatment. Furthermore, this could reduce the incidences of malaria as the poor would purchase this treatment and thus, overall malaria which could be achieved by this treatment and so this research could have positive economic implications. Additionally, this treatment can be applied to all society. Most deaths occur among in Africa and as a result, adults lose workdays and children spend days away from school. On the other hand, malaria mortality rates among children in Africa can be reduced by using doxycycline along with quinine, as this treatment is very effective (all the patients were recovered from malaria infection in this study). Therefore, this will improve the living conditions of populations in endemic area, individually and as communities. However, some patients may have adverse effects using this treatment, such as ‘sensitivity to the sun, stomach upset if taken on without food and vaginal yeast infection in women.’ (9) The consequence of this is that, if patients who live in doctorless village and have this treatment without knowing the side effects, it will cause another disease. Overall, this research could reduce the number of patients, if the patients use the combination of doxycycline and quinine appropriately and so have positive and negative social implications. Thus, Africa will reduce perpetuating the vicious cycle of poverty and succeed in achieving rapid economic development at the same time, as quinine doxycycline combination is inexpensive and effective.

Benefits and Risks of Scientists’ Method

One of the major benefits of this treatment is that it is very effective and tolerable in curing Plasmodium Falciparum malaria. According to this original article, this study has shown a mean parasite clearance time of 3 days using doxycycline along with quinine bisulphate which is consistent with other studies from around the world. Additionally, the cost of treatment is an important factor in determining the best possible antimalarial therapy in a developing country. Artemisinin is a current drug against Plasmodium Falciparum malaria. However, even though artemisinin-based combination therapy has been elaborated to replace Plasmodium Falciparum malaria treatment in many parts of the world, but the cost is about 10 times more than quinine-based combination therapy. Thus, doxycycline along with quinine bisulphate is the first-line therapy for falciparum malaria and other treatments are reserved for selected cases.

On the other hand, the negative aspect of this treatment is that quinine doxycycline combination only can treat Plasmodium Falciparum, so this study excluded complicated malaria patients who are infected with Plasmodium Vivax, Plasmodium Malaria and Plasmodium Ovale. Moreover, since they also excluded the patients who are younger than 15, women and pregnant women, doctors cannot be sure of how this combination of the drugs effect to these groups.

Alternative Method One: Clindamycin

Clindamycin is an antibiotic medication, which blocks the ribosomes of microorganisms. It is generally used to treat infections with anaerobic bacteria. (14) One the other hand, it can also be used to cure protozoal diseases, such as malaria. Clindamycin is effective against P. falciparum, but it is a slow-acting drug with a mean parasite clearance time of four to six days and a mean fever clearance time of three to five days. However, as quinine doxycycline combination is inapplicable to treat malaria during pregnancy, the ASM recommends using clindamycin along with quinine.

Alternative Method Two: Precautions with tools

Today, a combination of available tools is present to prevent, diagnose and treat malaria. The long-lasting insecticidal nets (LLINs), indoor residual spraying (in which insecticides are sprayed on the walls of homes) and intermittent preventive treatment for pregnant women (IPTp) are the primary tools used to prevent malaria infection in high transmission settings (15). Mosquitos can be killed in these ways, but the most effective is to spray the interior walls and ceilings of houses with a persistent insecticide. This method is most likely to kill female Anophelines since they rest after blood meals.

Conclusion

The quinine doxycycline combination appears to be effective in curing Plasmodium Falciparum malaria. It also gives hopes some other combinations of drugs will give good results to malaria patients. However, we need to investigate the applications of this combination of the drugs to other patient groups (complicated malaria, young, and women patients).

Bibliography:

  1. "Impact of Malaria." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 26 Mar. 2014. Web. 10 Jan. 2015. <http://www.cdc.gov/malaria/malaria_worldwide/impact.html>.
  2. Carrington, Mark. "Malaria." Biological Sciences Reviews Sept. 2010: 22-25. Web. 2 Jan. 2015.
  3. "Malaria Biology." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 9 Nov. 2012. Web. 07 Jan. 2015. <http://www.cdc.gov/malaria/about/biology/>.
  4. Knell, A. J. Malaria: A Publication of the Tropical Programme of the Wellcome Trust. Oxford: Oxford UP, 1991. Print.
  5. Finkel, Micheal. "Malaria: Stopping A Global Killer." - National Geographic Magazine. N.p., July 2007. Web. 10 Jan. 2015. <http://ngm.nationalgeographic.com/2007/07/malaria/finkel-text/1>.
  6. Finkel, Elizabeth. "Scientists Find a New Way to Exploit and Attack Malaria." Smithsonian. N.p., Sept. 2012. Web. 10 Jan. 2015. <http://www.smithsonianmag.com/science-nature/scientists-find-a-new-way-to-exploit-and-attack-malaria-17404786/?no-ist>.
  7. Shear, Margaret. "Table of Contents: June 2005." PLOS Biology : Publishing Science, Accelerating Research. N.p., June 2005. Web. 22 Feb. 2015. <http://www.plosbiology.org/article/browseIssue.action?issue=info:doi/10.1371/issue.pbio.v03.i06>.
  8. Krishan, Maggon. "Malaria Review: Info & Updates." Clinical Sciences. N.p., 05 Apr. 2012. Web. 23 Feb. 2015. <https://clinicalsciences.wordpress.com/article/malaria-review-info-updates-3fy5eowy8suq3-68/>.
  9. "Doxylar (doxycycline)."Netdoctor. N.p., 28 June 2011. Web. 10 Jan. 2015. <http://www.netdoctor.co.uk/infections/medicines/doxylar.html>.
  10. "Doxycycline Hyclate (Doxycycline 50mg Capsules)." Doxycycline Hyclate. N.p., n.d. Web. 10 Jan. 2015. <http://www.nhs.uk/medicine-guides/pages/MedicineOverview.aspx?condition=Bacterial+infections&medicine=doxycycline+hyclate&preparationDoxycycline+50mg+capsules>.
  11. "Quinine: MedlinePlus Drug Information." U.S National Library of Medicine. U.S. National Library of Medicine, 2 Jan. 2011. Web. 10 Jan. 2015. <http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682322.html>.
  12. Ejaz, Amer, Khurram Haqnaqwaz, Zakir Hussain, Rafi Butt, and Hussain Bux. "Treatment of Uncomplicated Plasmodium Falciparum Malaria with Quinine-doxycycline Combination Therapy." Journal of Pakistan Medical Association (2007): 502-04. Web. 12 Nov. 2014. <http://jpma.org.pk/full_article_text.php?article_id=1225>.
  13. "Global Strategy on Malaria." Global Malaria Action Plan: Executive Summary. N.p., n.d. Web. 17 Jan. 2015. <http://www.rollbackmalaria.org/gmap/0-5.html>.
  14. Lell, Bertrand, and Peter G. Kremsner. "Clindamycin as an Antimalarial Drug." Clindamycin as an Antimalarial Drug: Review of Clinical Trials. N.p., Aug. 2012. Web. 18 Jan. 2015. <http://aac.asm.org/content/46/8/2315.full>.
  15. Spilsbury, Richard. "Fighting Malaria: Global Problem." Pharmaceutical Industry. New York, NY: Rosen Central, 2011. 32-35. Print.

Review of Sources:

For my research, I used a book from the National Geographic Magazine in order to gather the information about malaria. I constituted the source reliable, because it has some of the world's top scientists, researchers, and photographers worked to make this article as there is clear indication as who wrote this article so that this article contains a great amount of depths. For example, it is clearly well structured and explained how malaria develops which would contain reliable data with scientific reasoning. Furthermore, it is peer-viewed by other scientist, which is important as having experts read the paper and review, since review ensures that this article is credible. Additionally, this source is valid as it links to the subject of malaria and their symptoms and treatments. As assessing the possibilities of an available treatment for the same issue, this is relevant since it is important to know about these. Secondly, I used the paper of ‘J Pak Med Assoc 2007’ by 6 scientists, which was reliable source in providing me with various data and scientific method and the results. It was written by six scientists and this individual is a recognised expert with appropriate qualifications, so the source can be seen as reliable to a great extent. Furthermore, this article contains citation that link to articles or proof of almost every statement made and the fact that it is not a private company eliminates the possibility that the information is written from a scope which aims to sell treatments, it can be considered a very reliable resource. Moreover, this source is valid since the researchers’ intention was to cure malaria using quinine doxycycline and as the data in the paper prove that this source is valid. Furthermore, this paper can give an accurate representation of treatment for malaria as it contains data from 2007.

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