* An essay prepared for my Infection & Immunity exam. The headings are partly there to help me structure the essay when writing it, and partly to help me memorise it and would not be left in for a hand in essay *
Q – Malaria will always be with us; discuss this assertion
INTRODUCTION – effect of malaria globally, outline of essay. WHO numbers.
Malaria is a vector borne parasitic disease which infects the red blood cells of humans. The parasite itself belongs to the genus plasmodium, and has several species which infect humans. P falciparum is frequently fatal, whereas P ovale, P vivax and P malariae are not typically fatal; however P vivax causes the greatest number of malaria infections.
Female Anopheles mosquitoes are the vector and primary (definitive) host for malaria; infective sporozoites present in the saliva enter humans (secondary hosts) when the mosquito takes a blood meal.
As malaria is transmitted by the Anopheles mosquito, the question of its presence in the future is tied to the prevalence of this particular arthropod. Natural interventions such as a change in behaviour, prevalence or fecundity of the Anopheles mosquito are unlikely, as such; we must look towards human intervention as the cause of any change in the state of malaria in coming years.
VACCINE – types, when,
The most obvious route to eradicating a given disease is to develop a vaccine to improve or attain immunity in the host. As multiple diseases such as poliomyelitis, smallpox and measles have been either eradicated or diminished into relative obscurity by effective vaccines, a malaria vaccine may appear to be the most likely factor in diminishing malaria in the future.
Even 20 years ago the biological research community was optimistic about the idea of a malaria vaccine; however this dream has not come to fruition. This is due to the fact that identifying the parasite molecules important in induction of immunity was more difficult than expected.
Progress has been made, safe yet ineffective vaccines were tested in the 90’s while the RTS,S vaccine could reduce the effects of severe malaria while having no impact on mortality.
There are three main groups of malaria vaccine being developed (of which there are subtypes), each of which targets a different stage of the malaria lifecycle.
The pre-erythrocytic stage vaccines induce an immune response which destroy sporozoites before they can invade a hepatocyte. Sporozoites spend a brief period in the circulation (minutes, giving the body a small window to act) and any schizont which gets to the liver stage can potentially release over 10,000 merozoites, requiring a high efficacy from the vaccine to stop this.
Blood stage vaccines attempt to destroy merozoites. This is difficult to achieve because of strain variability. While a blood stage vaccine may not be able to prevent multiplication, it would likely be able to mitigate it and thus prevent severe malarial anaemia, one of the major factors in fatal malaria. Thus, this type of vaccine shows promise in reducing mortality of malaria but not incidence.
Transmission blocking vaccines promote an immune response which target gametocytes, intercede with fertilisation or otherwise stop development of malaria while it is still in the mosquito. This vaccine differs from the aforementioned examples as it infers no immunogenic protection for the individual, instead providing protection communally when a group are all vaccinated.
The development of a malaria vaccine is to some extent an inevitability (the WHO aim for an effective, safe vaccine by 2025). This hopefully means that in a matter of decades there will be a vaccine which severely diminishes the impact of malaria worldwide. We are left with a more pertinent question: what of the near future?
PREVENTION – nets, attack the vector,
Without a cure, prevention is preferable to treatment as treatment options are more expensive and less available in malaria endemic areas (typically poor third world).
Mosquito netting is currently the most important factor in reducing the burden of malaria. The weave of these nets is fine enough to prevent mosquitos from passing through, and they are draped over windows or sleeping areas to prevent mosquito bites during the night. The application of insecticide to these nets – insecticide treated nets (ITN’s) – provides greater protection than untreated nets with the drawback being that insecticide must be reapplied periodically.
This reapplication can be problematic in rural areas, although long lasting ILN’s are available which last up to 5 years at little extra cost. These nets use a synthetic pyrethoid insecticide; however overreliance on one class of these insecticides seems to be bringing about resistance in the vector population. There is another negative externality in that people using nets are protected from bites while mosquitos are deflected towards those without nets.
There has been increasing finance for malaria control (over the period of 04-09) however the WHO is still approximately 4 billion $ short of achieving targets for 2010. Smaller investments are made to countries with a greater malaria burden and this may be the reason they are less successful in reducing this burden.
Another method of prevention is to target the vector. One example is the sterile insect technique (SIT), wherein male insects are bred in the lab, made sterile via irradiation and released into the wild. The intention is that female eggs are not fertilised leading to a population crash. SIT has been successful in several cases (the tsetse fly in Zanzibar, the screw-worm fly in North America) but it’s use in malaria is yet to be seen.
One novel preventative measure takes the idea of targeting the vector literally, by using a laser system to kill mosquitos. A prototype developed by intellectual ventures purported to detect female mosquitoes by unique wing beat patterns and fires a blue laser, killing the mosquito. This project is unlikely to be effective, having been criticised for being overly complex and unsuited to third world use (where electricity will most likely be unavailable).
A more promising yet still novel approach is to help the mosquito vector resist infection. Experiments using the bacteria Wolbachia pipientis to induce immune response and reduce transmission of plasmodium in infected Anopheles gambiae mosquitoes appear effective. As well as the inhibited development of plasmodium, Wolbachia also has a lifespan shortening effect. Plasmodium requires around 9 days in the primary host to mature ergo fewer old mosquitos in the population reduces the infection chance. Both of these effects act individually to reduce the vectoral capacity of mosquitos but have an even more profound effect in unison.
As alluded to earlier, prevention is limited by finance. The countries bearing the greatest malarial burden are poor third world nations (such as sub Saharan Africa), where optimal ITN coverage is not fully achieved. Western largess aids these areas enormously, but at the current rate prevention goals will never be entirely met.
Other methods of prevention are in an early, nascent state. Many show promise but few if any can be put into real world practice soon. The overall burden of malaria is being gradually reduced year upon year (the WHO world malaria report 2010 found that both the incidence of malaria and the deaths caused by malaria have steadily decreased over the last decade), yet continues to kill approximately 1 million people annually.
Vaccines which significantly marginalise malaria’s impact on global health will appear over the next several decades. Prior to this however, without a significant increase in funding or economic upliftment in Africa, prevention of malaria will never be fully realised where it matters the most.
Thus malaria will not always be with us, but will be a serious yet diminishing concern for the next several decades.
- Hoffman et al – ‘Malaria Vaccine Development’ (96)
- Pampana – ‘Textbook of Malaria Eradication’ (69)
- WHO world malaria report (2010)
- Kambris et al – ‘Wolbachia stimulates immune gene expression and inhibits plasmodium development in plasmodium gambiae’ PLoS (2010)