January 2003 Malaria - The Scourge of Humanity Malarial parasites have been with us since the dawn of time. The disease, malaria, is caused by a microscopic protozoan parasite from the genus Plasmodium. These parasites require 2 hosts for the completion of their life cycle, a red blooded vertebrate and a mosquito specie capable of developing and transmitting the parasite. These parasites are quite specific to their hosts (animal and mosquito). There is reptilian malaria, avian (bird) malaria, simian (monkeys and apes) malaria, rodent malaria, and human malaria. Human malaria is caused by 4 species of Plasmodium, Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae, and Plasmodium ovale, all of which, can only be transmitted by Anopheles mosquitoes and only infect humans. Of the 75 or so species of mosquitoes in Florida, 13 are of the Anopheles genus.
Deadly fevers, probably malaria, have been recorded since the beginning of the written word, more than 8,000 years ago. Malaria is worldwide in its distribution, prevalent to a greater or lesser degree on every inhabited continent and on many islands. Of all the diseases of mankind, it is one of the most widespread, best known, and most devastating. Generally associated with tropical or subtropical climates, such is not the case: Sweden, Finland and Northern Russia have, in the past, suffered from severe epidemics. There are no references to malaria in the “medical books” of the ancient Mayan or Aztec civilizations. It is likely that European settlers and slavery brought malaria to the New World within the last 500 years. Malaria was however, recognized as a factor in the colonization of Massachusetts and the Georgia-Carolina coast in the mid-seventeenth century. As recently as the 1930's there were 6 to 7 million cases annually in the continental United States. While nowhere near these levels, malarial transmission still occurs sporadically in this country due to the persistence of the mosquitoes that are capable of transmitting the disease. Each year over a thousand cases of imported malaria are reported in the U.S.
Malaria has undoubtedly played a role in the history of civilization. The ancient Greek civilization’s downfall was partially attributed to the effects of malaria, Alexander the Great’s armies were stopped by malaria, and most recently, the development of many African and Asian countries has been severely affected by this disease. Worldwide, malaria claims 2 to 3 million lives and infects 300 to 500 million people, annually. Ninety per cent of all cases occur in sub-Saharan Africa where it is the main health threat and cause of death to children. Globally, a child dies from malaria every 30 seconds. Needless to say, the economic impact is immense, causing 100's of millions of lost work days annually, lost tourism, and loss of investments.
The malaria parasite inhabits red blood cells, where it multiplies asexually (reproduction without recombination of genes). After 2 to 3 days the red blood cells burst and release large numbers of new parasites, most of which reinfect other red blood cells; thus reinitiating the cycle. Some of the parasites enter liver cells. Before the asexual cycle in red blood cells can be established, the parasite must complete a 5 to 10 day period of multiplication in liver cells. If left untreated, a malaria infection can persist for years, often with an absence of symptoms or a much less severe illness. Such a person is infective to Anopheles mosquitoes that feed on them. Once in the mosquito the parasite undergoes a sexual cycle for 7 to 20 days. Microscopic, spindle shaped forms known as sporozoites are the result of the sexual cycle. This form of the parasite then invades the mosquito salivary glands. The human infection is initiated when sporozoites are injected along with the mosquito’s saliva, when they feed. The sporozoites then enter liver cells where they change form and multiply. After 5 to 10 days this new form exits the liver cells, into the blood, and starts invading the red blood cells. The P. ovale and P. vivax parasites can persist in liver cells for years, giving relapses of the disease years later. Malaria destroys red blood cells in the process of its development but also damages the liver, kidneys, spleen and brain. Chronic infection can cause a level of lifelong disability.
Infection from the 4 different types of Plasmodial parasites creates different symptoms, but generally, overall symptoms may start with a headache, body aches, anorexia and sometimes vomiting...like the flu is coming on. This is followed by chills, teeth chattering and then the sensation of great heat with high fever (up to 106° F), followed by profuse sweating which lasts a few hours as body temperature subsides. The typical malaria symptoms of chills and fever are associated with the rupturing of red blood cells and the release of more parasites. The entire ordeal lasts from 6 to 10 hours and occurs every third day for one to two weeks. Most people survive a bout with malaria. Clinically, the infection varies from a moderately severe to fatal illness, depending upon the species of parasite, the person’s condition, and how soon the patient receives treatment. Mortality from this disease is less than 1%, but the misery and economic loss is immeasurable. Recent data shows that 75% of the annual death caused by malaria is African children. Children under 5 that experience the high fevers and febrile convulsions caused by malaria are also subject to retarded brain development. This result can impair an individual’s higher-order cognitive functions such as planning, decision-making, self-awareness, and social sensitivity. Of all the manifestations of malaria, those affecting cognition and behavior are the subtlest, least defined, and have the most profound implications for children, families, and societies.
Treatment of the malarial disease was started more than 350 years ago, using a toxic plant alkaloid called quinine, which is extracted from the bark of the Cinchona tree in South America. Jesuit missionaries in South America learned of the anti-malarial properties of quinine and introduced it into Europe in the 1630's and into India by 1657. Shortages of quinine sources during World War I led to the search for synthetic anti-malarials. In 1934 a German pharmaceutical company developed chloroquine, a synthetic analogue to quinine. With a synthetic, limitless supply of chloroquine and the new “miracle” pesticide DDT, the World Health Organization (WHO) initiated strategies for the global eradication of malaria in the mid-1950's... then reality struck. The logistics of treating all the infected people was overwhelming. Villages and tribes in remote areas, the lack of a governmental healthcare infrastructure, an inability to educate and a lack of understanding of the problem by the urban populations, were the initial obstacles to be faced. To treat malaria requires prompt and proper administration of the drug, over a period of time, 2 to 8 weeks, depending on the species of malarial parasite being treated. Unfortunately, because of a lack of patient monitoring due to an inadequate medical infrastructure, patients would overdose or stop treatment, because they were feeling better, before the prescribed period of treatment was completed. The result is that the parasite survives, the disease re-occurs, and the malarial parasite becomes resistant to treatment. Resistance also occurred in the mosquito vector populations from the improper, overuse of the insecticide DDT. New anti-malarials and insecticides are being used to combat malaria but drug resistant malaria is occurring in Southeast Asia, South America, Indo-china subcontinent, Indonesia, China and several areas of sub-Saharan Africa. Parasite resistance has gotten so bad, that in parts of Vietnam and Thailand, health authorities have no drugs available that are effective for the treatment of malaria. Malaria, today, is considered a re-emerging mosquito borne disease, on a global scale. Because of drug resistance in the parasite and widespread insecticide resistance in the mosquito vectors, there are fewer options available now than there were 20 years ago. In fact, after spending years bringing the disease under control, more people are dying from malaria now than there were 30 years ago. The disease has spread, because of modern travel, to new areas of the globe. Presently, malaria is endemic in 91 countries, with pockets of transmission occurring in 8 others, making malaria the most prevalent vector (mosquito) borne disease in the world. Given the impact of this parasite, the shortcomings of anti-malarial drugs and vector control, vaccine development is a high priority.
Vaccines are substances that evoke an immune response by the host without causing disease. Immune response is development, by the host, of antibodies to a specific protein antigen. The problem with development of a vaccine for malaria is that there are 4 different species of the human malarial parasite and each specie undergoes many different development stages, in 4 distinct life forms, while completing its life cycle in 2 different hosts, man and mosquito. Despite all the variation in the malarial parasites’ life cycle, the past 20 years of research and the breakdown of the parasites’ genetic code, antigens, in all stages, have been identified that can provide protective immunity. The general consensus of health authorities is that a vaccine is not only needed but is essential to successfully controlling malaria around the world. So, if a vaccine is essential to control and is technologically feasible, why isn’t it being produced? The cost of development will be enormous. It will require the cooperation of governments, academia, and industry. The public sector (governments), will need to contribute financially and ultimately, coordinate the distribution and administration of the vaccine. Unfortunately, the pace of vaccine development is slowing because of just these things, a lack of funding, fragmented governmental efforts, and a limited interest within the vaccine industry because the cost of research and development will far exceed expected returns.
Malaria’s allies are drug resistance in the parasite, pesticide resistance in mosquitoes, breakdown of health-care infrastructure, political and social upheaval, movement of refugees, disruption to the environment that creates breeding ground for the mosquito vectors, malarial programs being cut back or abandoned because of budget restraints, and the incursion of military or tourism into malarious regions and then returning to a non-malarious area. The United States is not immune to the growing threat of malaria. Thousands of U. S. citizens are exposed to resistant forms of malaria every year because of their travels and residing abroad. When they return, over one thousand cases are reported per year. Because of this importation of the disease, a highly susceptible human population, and the presence of Anopheline mosquitoes, serious disease is a real threat. Our health-care infrastructure, established vector control programs and the socio-economic condition we live in, has kept malaria a product of third world countries and an ”event” on the evening news. For about half of the world, malaria is the “event”. The outlook for humanity in the “other” half of the world is grim when it comes to malaria control. The problem is not biological or medical - it is economic and sociologic. Masses of people in tropical and semitropical areas do not have the economic resources with which to combat the mosquito, identify and treat the millions of patients or to institute infrastructure such as water, sewer, garbage, and drainage systems. In many areas, the patients and their families lack social awareness and education needed to identify the problem and thus notify public health authorities. The result is that the disease cycle continues and so does the misery. |