PREVENTION AND CONTROL OF MALARIA IN AFRICA



 The prevention of malaria disease in endemic areas can be achieved through the use of prophylactic drugs, eradication of mosquitoes and the prevention of mosquito bites. The continued existence of malaria in any area requires a combination of high human population density, high mosquito population density and high rates of transmission from humans to mosquitoes and vice-versa. If any of these is significantly reduced, the incidence of malaria will gradually fade from that area. Many researchers are of the opinion that prevention of malaria may be more cost-effective than treatment of the disease in the long run. Unfortunately the capital costs required are beyond the reach of many
poor countries. It has been argued that in order to meet the Millennium Development Goals, money should be redirected from HIV/AIDS treatment to malaria prevention, which for the same amount of money would provide greater benefit to African economies (Hull, Kelvin, 2006).

Prevention and control of malaria disease can be achieved through vector control, the use of prophylactic drugs, vaccination and education.

Vector control    
Before the introduction of insecticides malaria was successfully eradicated or controlled by removing or poisoning the aquatic habitats of the larva stages. The poisoning was achieved by applying oil to places with standing water. These methods have seen little application in Africa for more than half a century (Killeen et al., 2002).
Efforts to eradicate malaria by eliminating mosquitoes have been successful in some areas. Malaria was once common in the United States and Southern Europe, but the draining of Wetland breeding grounds and better sanitation, in conjunction with the monitoring and treatment of infected humans eliminated it from affluent regions. Malaria was eliminated from the Northern parts of the USA in the early twentieth century, and the use of DDT eliminated it from the South by 1951. In the 1950s and 1960s, there was a major public health effort to eradicate malaria worldwide by selectively targeting mosquitoes in areas where malaria was rampant (Gladwell, 2001). However, these efforts have failed to eradicate malaria in many parts of the developing world including Africa.


Another effort which was targeted against mosquitoes was indoor residual spraying (IRS). This is a practice of spraying insecticides on the interior walls of homes in malaria affected areas. The principle is based on the fact that mosquitoes rest on a nearby surface after feeding to digest the blood meal. Thus, if the walls of dwellings have been coated with insecticides, the resting mosquitoes will be killed before they can bite another victim.

Historically, the first and most popular insecticide used for IRS is DDT. Initially, this agent was exclusively used to combat malaria and the outcome was successful. However, with time, its use spread to agriculture. This led to the evolution of resistant mosquito strains in many regions. Thus the use of DDT as a pest control rather than disease control agent and it’s over spraying on crops, rendered it ineffective and contributed to its failure. During the 1960s, awareness of the negative consequences of the indiscriminate use of DDT increased and ultimately led to the ban on its agricultural applications in many countries in the 1970s.

Although DDT has never been banned for use in malaria control, there are other insecticides suitable for IRS. Some advocates have claimed that bans are responsible for tens of millions of deaths in tropical countries where DDT had once been effective in controlling malaria. Furthermore, most of the problems associated with DDT use stem specifically from its industrial-scale application in agriculture rather than its use in public health (Tia et al., 2006).

The World Health Organization (WHO) currently advises the use of 12 different insecticides in IRS operations. These include DDT and a series of alternative insecticides (such as pyrethroids, permethrin and deltamethrin) to both combat malaria in areas where mosquitoes are DDT-resistant, and to slow the evolution of resistance. One problem with all forms of indoor residual spraying (IRS) is insecticide resistance via evolution of mosquitoes. According to a study published on mosquito behaviour and vector control, mosquito breeds that are affected by IRS are endophillic species (mosquitoes that tend to rest and live indoors). However, due to the irritation caused by spraying, their evolutionary descendants are tending towards becoming exophillic (mosquitoes that tend to rest and live outdoors). This behaviour renders the use of IRS impotent in controlling mosquitoes (Pates and Cutis, 2005).
Vector control can also be achieved through the use of mosquito nets and bed-clothes.  Mosquito nets help to keep mosquitoes away from people, and thus, greatly reduce the infection and transmission of malaria.  The nets are not a perfect barrier, so they are often treated with an insecticide designed to kill the mosquito before it has time to search for a way past the net.  Insecticide treated nets (ITN) are estimated to be twice as effective as untreated ones, (Hull, Kelvin, 2006) and offer 70% protection compared to no net at all (Bachou et al, 2006).  Although, ITN are proven to be very effective, less than 2% of children in urban areas in sub-Saharan Africa are protected by it.  Since the Anopheles mosquitoes feed at night, the preferred method is to hang a large “bed net” above the centre of a bed such that it drapes down and covers the bed completely.

The distribution of mosquito nets impregnated with insecticide (often permethrin or deltamethrin) has been shown to be extremely effective method of malaria prevention, and it is also one of the most cost-effective methods of prevention.  It can be obtained from the United Nations (UN) or World Health Organization (WHO) at subsidized costs.  For maximum effectiveness, the nets should be retreated with insecticides every six months.  This process poses a significant logistical problem in rural areas.  To overcome this, new technologies like Olyset or Dawa-plus allow for production of long-lasting insecticidal mosquito nets which can last for approximately five years (Matuschewski, 2006).  This technology protects people sleeping under the net and simultaneously kills mosquitoes that come in contact with them.

Unfortunately, the cost of treating malaria is high relative to income, and the illness results in lost wages.  Consequently, the financial burden means that the cost of a mosquito net is often unaffordable to people in developing countries, especially for those most at risk.  Only one out of twenty people in Africa own a bed net (Hull, Kelvin 2006).  Although mosquito nets are shipped into Africa from Europe mainly as free development help, the nets quickly become expensive trade goods.  They are mainly used for fishing, and by combining hundreds of donated nets, Whole River sections can be completely shut off, catching even the smallest fish.  This abuse of donated mosquito net is quite frustrating and may discourage the donor agencies.
Recently, sterile insect technique has emerged as a potential mosquito control method.  The technique involves the use of genetically modified mosquitoes (which could be made to be malaria-resistant) to replace the existent parasite population.  Researchers at imperial college London created the world’s first transgenic malaria mosquito with the first plasmodium-resistant species announced by a team at case Western Reserve University in Ohio in 2002.  Successful replacement of existent populations with genetically modified ones relies upon a drive mechanism, such as transposable elements to allow for non-mendelian inheritance of the gene of interest.  However, this approach contain many difficulties and 34% of the malaria research and control community say that such an approach is at least 5-10 years away from introduction (Ito et al., 2002).

Vaccines for malaria are under development with no completely effective vaccine yet available.  The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunizing mice with live, radiation attenuated sporozoites, providing protection to about 60% of the mice upon subsequent injection with normal viable sporozoites (Nussenzweig et al., 1967).  Since the 1970s, there has been a considerable effort to develop similar vaccination strategies within humans.  It was determined that an individual can be protected from P. falciparum infection if they receive over 1000 bites from infected irradiated mosquitoes (Hoffman et al., 2002).

It has been generally accepted that it is impractical to provide at-risk individuals with this vaccination strategy, but that has been recently challenged with work being done by Dr. Stephen Hoffman of Sanara who is one of the key researchers that originally sequenced the genome of P. falciparum.  His work most recently has revolved around solving the logistical problem of isolating and preparing the parasites equivalent to 1000 irradiated mosquitoes for mass storage and inoculation of human beings.  The company has recently   received several multi-million dollar grants from the Bill and Melinda Gates foundation and the US government to begin early clinical studies in 2007 and 2008.

Also, much work has been performed to try and understand the immunological process that provides protection after immunization with irradiated sporozoites.  After the mouse vaccination study in 1967, it was hypothesized that the injected sporozoites themselves were being recognized by the immune system, which was in turn creating antibodies against the parasite.  It was determined that the immune system was creating antibodies against the circum-sporozoite protein (CSP) which coated the sporozoite (Zavala et al., 1983).
Presently, there is a huge variety of vaccine candidates on the table.  Pre-erthrocytic vaccines (vaccines that target the parasite before it riches the blood), in particular vaccines based on CSP, make up the largest group of research for the malaria vaccine.  Other vaccine candidates include: those that seek to induce immunity to the blood stages of the infection; those that seek to avoid more severe pathologies of malaria by preventing adherence of the parasite to blood venules and placenta; and transmission-blocking vaccines that would stop the development of the parasite in the mosquito right after it has taken a blood meal from an infected person (Maltuschewski, K. 2006).

The first vaccine developed that has undergone field trials, is the SPf66, developed by Manuel Elkin Patarroyo in 1987.  It presents a combination of antigens from the sporozoite (Using CS repeats) and merozoite parasites.  During phase I trials 75% efficacy rate was demonstrated and the vaccine appeared to be well tolerated by subjects and immunogenic.  The phase II and III trials were less promising, with the efficacy falling to between 38.8 and 60.2%.  A trial was carried out in Tanzania in 1993 demonstrating the efficacy to be 31% after a year’s follow up, however the most recent (though controversial) study in the Gambia did not show any effect. Despite the relatively long trials periods and the number of studies carried out, it is still not known how SPf66 vaccine confers immunity; it therefore remains an unlikely solution to malaria.

The RTS, S/ASOZA vaccine is the candidate furtherest along in vaccine trials.  It is being developed by a partnership between the PATH malaria vaccine initiative (a grantee of the Gates foundation), the pharmaceutical company Glaxosmithkline, and the Walter      Reed Army institute of Research (Heppner et al., 2005).  In the vaccine a portion of CSP has been fused to the immunogenic “S antigen” of the hepatitis B virus; this recombinant protein is injected alongside the potent ASO2A adjuvant (Matuschewki, 2006).  In October 2004, the RTS, S/ASO2A researchers announced result of a phase IIb trial, indicating the vaccine reduced infection risk by approximately 30% and severity of infection by over 50%.  The study looked at over 2,000 Mozambican Children (Alonso et al., 2004).  More recent testing of the RTS, S/ASO2A vaccine has focused on the safety and efficacy of administering it earlier in infancy.

Other methods of preventing malaria such as educating those in developing countries on how to recognize early symptoms of malaria has reduced the number of cases by as much as 20%. Education can also inform people to cover areas of stagnant, still water e.g. water tanks which are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people.  This is most put in practice in urban areas where there are large centres of population in a confined space and transmission would be most likely in these areas.
The malaria control project is currently using down time computing power donated by individual volunteers around the world to simulate models of the health effects and transmission dynamics in order to find the best method or combination of methods for malaria control.  This modeling is extremely computer sensitive due to the simulations large human population with a vast range of parameters related to biological and social factors that influence the spread of the disease.  It is expected to take a few months using volunteered computing power compared to the 40 years it would have taken with the current resources available to the scientist who developed the program.  An example of the importance of computer modeling in planning malaria eradication program is shown in the paper by Aguas and others.  They showed that eradication of malaria is crucially dependant on finding and treating the large number of people in endemic areas with asymptomatic malaria, who act as a reservoir for infection (Aguas et al., 2008).
In conclusion, education plays a major role in the control and prevention of malaria people need to know about the simple things to do to prevent malaria.  Things like clearing the bushes around living areas, draining or application of oil on the surfaces of stagnant waters, sleeping under mosquito nets and the use of antimalarial prophylaxis.  Also early identification and treatment of patients with malaria has been found to be helpful in preventing complications of malaria.  

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