Background information
Malaria, a mosquito borne transmissible disease of both human beings and some animals is a pertinent disease in the 21st century which accounts for more than 650, 000 deaths annually (WHO, 1147). The prevalence of malaria is highest in the tropical and subtropical regions. Adverse effects of the disease is an equally major public health issue that affects maternal and child health. In the developing countries, malaria is a leading cause of maternal and child health. Consequentially, it is a pertinent public health disease. This manuscript offers a succinct analysis of the disease while appraising its causative agents, life cycle, pathophysiology, diagnosis, prevention, treatment, epidemiology and management. Finally, the manuscript offers my personal experiences with the disease. The overriding thesis statement in the manuscript is that malaria is a pertinent disease that is of major public health concern and as such, proper management is needed.
Disease overview
Malaria is mainly transmitted by mosquitoes of the Anopheles spp through a blood meal. Through the mosquito bite, parasites are introduced into the blood of humans where they move to the liver from where they reproduce and grow. Mosquito anopheles females of the species ovale, falciparum, malariae and vivax are primarily responsible for the transmission (Network, Malaria Genomic Epidemiology, 1197-1204). Various methods of diagnosing the disease are in existence including molecular techniques albeit microscopic observation and biochemical tests for the presence of parasites are the most commonly used diagnostic techniques due to their cost effectiveness. Malaria is mostly prevalent in developing nations of the tropical and subtropical regions where its prevalent is highest. These regions include Sub Saharan Africa, Asia, and Latin America. Other than the case fatalities, economic losses that come with the disease have been documented with values placed at USD 12 billion annual losses due to the disease.
Epidemiology and disease burden
According to WHO estimates, malaria is responsible for 650,000 deaths annually. In 2012 alone, 1.3 million deaths were reported up from 1 million deaths in 2009 (World Health Organization 1147-1152). More than 60% of the reported cases are mainly for children aged 15 years and younger. Additionally, more than 126 million pregnant women are at risk of malaria infections annually according to WHO estimates. In sub-Sahara Africa, malaria accounts for more than 300,000 infant mortality according to 2013 statistics by the WHO. In Europe on the other hand, malaria affects a documented 10,000 persons while the United States accounts for 1400-1500 cases annually. Between 1993 and 2003, a total of 900 people dies with malaria in Europe alone. However the high incidence of malaria in endemic regions has been reduced by up to 60 % according to the WHO statistics mainly due to effected intervention strategies. The use of insecticides for instance, accounted for a 62% drop in the number of reported cases in 2004 as Seder, (1359-1365) documents. In Africa however, despite wide spread malaria eradication strategies at the turn of the millennium, the disease has only been reduced by a paltry 40% hitherto.
Presently, malaria is endemic in the areas around the equator with Africa accounting for the most endemic regions.
Occurrence of Malaria
Causes
The occurrence of malaria is a complex interplay between factors that come together to proliferate the disease. From vector based conditions to human related factors, the interplay serves exacerbate the disease burden. This segment appraises the interplay of these factors.
Malaria is caused by the malaria parasites of the plasmodium genus. The plasmodium species ovale, falciparum, knowlesi, malariae and vivax are documented as causative agents. However, the species falciparum accounts for the highest percentage of the most infective malarial species at 75% while P. vivax accounts for 21%. P. falciparum also accounts for majority of malaria related mortality whereas P, vivax causes majority of the life threatening forms of malaria.
Malarial Life cycle
The malarial cycle presents insights into the adverse events and episodes of the disease. The life cycle involves the transmission of the infective form called the sporozoite during a blood meal. A female anopheles mosquito serves as a vector for transmitting malaria and they serve the role of a definitive host by transmitting the sporozoite into the secondary host- the humans. The infective sporozoite then travels into the infected persons’ liver cells (hepatocytes) via the blood stream where asexual reproduction takes place resulting in numerous merozoites (Prapansilp 190-197). The asexually produced merozoites then move into the red bold cells of the human host where asexual reproduction takes place resulting in the production of new infective forms of the merozoites. Consequentially, these cells bursts bringing forth the infective cycle. Remaining merozoites subsequently develop into gametocytes which later on form the female and male gametes. A blood meal from a female anopheles mosquito results in the taking up of the gametocytes which later on mature in the gut of the mosquito. The fusion of the female and male gametes results in the formation of the ookinete which develop into sporozoites, the infective motile forms of malaria which move to the vectors salivary glands and are transmitted during a blood meal. Documented evidence shows that malaria can also be transmitted during blood transfusions albeit a very rare occurrence (Prapansilp 190-202).
Adverse events- Recurrent malaria
Malarial symptoms may resurface after an asymptomatic phase as Murray (413-431) documents. Depending on the recurrence of malaria, it can be classified as either a reinfection, a relapse or a recrudescence whereby symptoms resurface after a non-symptomatic phase for the later. Recurrent malaria occurs when inadequate treatment of malaria is done or when the malarial parasite stay longer in the host’s blood stream as Ashley (411-423) opines. These parasites survive in the host as dormant hypnozoites in the hosts liver cells and they re-emerge after 8 to 24 weeks in what is termed as a relapse. Relapse of malaria is typical with the malarial species P. vivax and P. ovale.
Pathophysiology
The development of malaria takes place in two stages as Prapansilp (220)documents. One phase takes place in the liver of the host (the exoerythrocytic phase) while the second phase occurs in the erythrocytes (erythrocytic phase). Upon taking a blood meal, sporozoites from the saliva of the infected anopheles migrate via the blood stream into the host’s hepatocyte where asexual and asymptomatic division takes place between eight to thirty days.
The asymptomatic phase is followed by the division of the sporozoites in the host’s cells producing countless merozoites which move into the host’s erythrocytes and commence the erythrocytic phase of the life cycle. Multiplication in the hosts RBC takes place asexually over time while new RBC are invaded. These invasion of the host’s RBC accounts for the episodes of fever which occur due to the countless merozoites that escape the RC.
Additionally, some sporozoites especially of the Plasmodium vivax do not enter the exoerythrocytic phase of the cycle but release hypnozoites which remain inactive for periods between seven to ten months or several years according to some findings as Prapansilp (190-202) documents. This latency period may come to an end resulting in the reactivation of the merozoites. According to Prapansilp (213)hypnozoites cause the long incubation times and are equally responsible for the documented relapses like the one observed in P. vivax.
The inability of the host defense systems to detect the long latency period of the merozoites within its cells lies in the fact that the infective forms hide in the host’s liver and RBC making them invisible to the host’s immune system. However, infected erythrocytes which circulate the human system are destroyed in the spleen. However, Ashley (423) documents the unique evasive strategy employed by the parasite in evading this destruction. The P. falciparum contains adhesive proteins on the infected RBC’s cells which result in the sticking of blood cells to the small blood vessel’ wall. The parasite is then sequestered from passing through spleen’s circulation. Blocking the microvasculature results in cases such as placental malaria as Prapansilp (200-202) documents. Furthermore, sequestered erythrocytes can equally break the blood brain barrier causing adverse effects such as celebral malaria Ashley 433).
Genetics, resistance and adverse malaria episodes
The plasmodium species, especially the P. falciparum, has placed discriminatory pressure on the human DNA as Ashley (423) opines. Such selective pressure has led to the witnessed high levels of malaria related deaths and morbidity more so in the falciparum sp. consequentially, this has led to intensified research work on the same in a bid to identify the genetic components which confer resistance to the plasmodium species. Several genetic markers have been documented hitherto in this regard including glucose-6-phosphate dehydrogenase deficiency, thalassaemia traits, sickle cell trait, and the lack of Duffy antigens as responsible for the observed resistance.
Adverse effects of malaria have equally been documented including malarial hepatitis other than the documented cerebral malaria. However, liver dysfunctions due to malaria are not common and only results when one has an underlying liver condition like chronic liver disease. Although malarial hepatitis and other related adverse effects are rare occurrences, there has been a considerable rise in documented cases especially in the Southern parts of Asia and in India. Additionally, persons with liver complications have an augmented risk of adverse malarial events and a higher risk of death.
Human efforts
The persistence of malaria is largely attributable to many reasons among which is the ineffectual implementation of preventable techniques. Various techniques of eradicating malaria have been devised among which are the elimination of mosquitoes, the production of efficacious drugs and the development of vaccines. Malarial presence in a place needs the presence of a high populace, a rich breeding site for female anopheles mosquitoes and a high transmission rate between vector and the human host. According to the World Health Organisation (1056) the lowering of either of the listed parameters can effectively eradicate malarial incidences as was the case in Europe, the Middle East and the U.S. However, the failure to eradicate the parasite globally can result in the reintroduction of the same in the areas where it has been expunged, if conditions revert to favor breeding.
Additionally, preventive techniques can often times prove more cost effective than treatment efforts. However, these preventive methods are out of rich to many people in malaria endemic areas where poverty is prevalent. Consequentially, malaria continues to thrive in such places. The costs of controlling the disease versus the elimination programs put in place for the same is different in countries. Herein, wide discrepancies can also be seen in different economies. In china for instance, the government announced a strategy to eliminate malaria in 2010 and the budget estimates for the same was insignificant compared to the total health budgetary allocation. In Tanzania on the other hand, where the disease is wider spread, an equal amount represents the entire budgetary allocation for health services. These discrepancies serve to show the inequalities and challenges that come with eliminating the disease.
Control measures and persistence of the disease
Various control measures are in place for combating malaria. Vector control measures is one such measure whereby malaria transmission is reduced by targeting the vectors. In this regard, various measures have been adopted including the use of effectual insect repellants, sleeping inside insecticide treated nets (ITNs), using ACTs (artemisinin based combination therapies) and indoor residual spraying in managing the mosquitoes.
Mosquito nets serve to keep mosquitos from people thereby reducing infection rates. Nets are however not effectual on their own and have to be treated with effectual insecticides which can repel mosquitoes. Treated nets offer more than 70% protection from malaria likened to not using a net at all and it offers more than 40% protection compared to using an untreated net. According to the World Health Organization (1156) using treated nets averted the potential loss of life for nearly 250,000 infants in Africa between 2000 and 2008. Pyrethroids are the effective insecticide in treating nets due to its low toxicity.
Treatment and resistance leading to proliferation
The first line treatment of malaria are antimalarial medications and they are used based on the severity of the disease. Oral medication is commonly used to treat uncomplicated and simple forms of the condition. Antimalarial such as lemefantrine, sulfadoxine and amodiaquine are commonly used in this regard. P. falciparum on the other hand is managaed by artemisinin which may be used alongside other antimalarials. ACT (Artemisin Combination Therapy) is equally effectual in reducing the drug resistance of single dose drugs by the parasite. According to the WHO (1130), ACTs are effectual by 90%in treating non complicated malaria.
Additionally, P. falciparum causes the most severe form of malaria. This form possess a medical emergency since it has the highest mortality rate at more than 50%. A classic example of this form of malaria is cerebral malaria which is neurological. Once diagnosed, IV antimalarial drugs are used in mitigating the condition.
The problem of drug resistance is a present day reality that affects most diseases and also malarial treatment efforts. Drug resistance by malarial parasites has been documented in all major drugs with the exception of artmenisisns, whose use in enedice regions remains a challenge due to cost constraints. Additionally, the use of pyrethrins has equally recorded resistance in species especially in Africa (World Health Organisation 1013).
Human activity and malaria
The activity by man bears a double edged property in the elimination and proliferation of the disease. For instance, human efforts in eliminating the disease has led to the production of numerous drugs and insecticides. However, the production of substandard products, ineffectual use of drugs among a host of reasons has proliferated the complexity of the disease further.
Construction of dams especially in developing countries as catchment areas for water has equally exacerbated the condition further by creating the perfect breeding sites for mosquitoes. Additionally, the release of sterile mosquitoes into the wild to curb mosquito numbers has proved ineffective hitherto in addressing the disease burden.
Research critique (The RTS, S Clinical Trials Partnership (2014)
The disease burden of the disease especially in Asia, South America and in developing countries has led to efforts being put in finding a possible malaria vaccine. In as much as research work in this regard still remain in infancy stages progress has been made by a number of researchers. This segment critiques a noteworthy research in this regard.
The RTS, S Clinical Trials Partnership (2014) presents the first clinically tried vaccine, the most advanced and the most promising vaccine trial that holds promise in checking the disease burden of malaria. The RTS, S/AS01 has undergone a level 3 evaluation in developing countries especially in Africa where it has been tried. The mechanism of the vaccine targets the erythrocytic phase of the plasmodium falciparum and causes cellular and humoral immune responses against the proteins of the sporozoites in the RBC and in the liver schizonts. RTS,S/AS01 has been ear marked for upgrade due to the witnessed positive results among study participants after its implantation.
The methodology of the study involved the random selection of 6, 537 infants and children between ages 5 and 17 who were given the RTS,S/AS01 Vaccine. Clinical malaria was then observed 18 months post baseline and after administration of 3 doses of the RTS,S/AS01 vaccine. Results indicated that the vaccine efficacy was 46% for the children and 34% for all the severe cases. Among the infants, the vaccine efficacy was 27% in preventing malaria.
Personal application
Personally, I have not contracted the disease due to its low to zero incidence in my area. However, the effectual prevention strategies that led to its eradication can be borrowed in endemic areas in order to reduce the disease burden.
Conclusion
Concussively, malaria presents a modern day public concern area especially in developing countries where the disease is endemic. Albeit numerous interventions are in place and have been successfully implemented, more still needs to be done especially in the area of vaccine development. The RTS, S Clinical Trials Partnership offer a positive step in this direction.
Works cited
Ashley, Elizabeth A., et al. "Spread of artemisinin resistance in Plasmodium falciparum malaria." New England Journal of Medicine 371.5 (2014): 411-423.
Murray, Christopher JL, et al. "Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013." The Lancet 384.9947 (2014): 1005-1070.
Network, Malaria Genomic Epidemiology. "Reappraisal of known malaria resistance loci in a large multicenter study." Nature genetics 46.11 (2014): 1197-1204.
Prapansilp, Panote, and Gareth DH Turner. "MicroRNA in Malaria." MicroRNAs in Medicine (2013): 183-197.
Rts, S. C. T. P. "Efficacy and safety of the RTS, S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites." PLoS medicine 11 (2014).
Seder, Robert A., et al. "Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine." Science 341.6152 (2013): 1359-1365.
World Health Organisation. "WHO estimates of the causes of death in children." The Lancet 365.9465 (2005): 1147-1152.
