Antiprotozoan agents

Descrição

From the 12-03-14 Drugs and Disease lecture.
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Resumo de Recurso

Questão Responda
How does malaria present? As paroxysms of fever, chills, and sweats, which result in anaemia and the deaths of millions of people each year.
Where do chemoprophylactic drugs block the malarial growth and replication cycle? What do they not do? Chemoprophylactic drugs block the link between the exoerythrocytic and the erythrocytic stages of Plasmodium spp. infection, but do not kill the sporozoites on entry into the human host.
How does proguanil prevent malarial disease? It is a dihydrofolate reductase inhibitor, which inhibits folate synthesis and thus DNA synthesis in the invading Plasmodium species.
How does chloroquine prevent malarial disease? It prevents the polymerisation of haem, thus maintaining an environment toxic to the parasite, and which can also be used to treat acute attacks.
How quickly did resistance to proguanil develop? Within a year (first introduced in 1948, resistance first noticed in 1949).
How quickly did resistance to chloroquine emerge? In 12 years - chloroquine was introduced in 1945 and resistance emerged in 1957.
Other than resistance of Plasmodium species, what other problems are there with chemoprophylactic drugs which mean that they are unlikely to eradicate malaria? They must be taken strictly in inconvenient regimens at different times, and they have unpleasant side effects such as nausea and vomiting, so it is unlikely that continuous prophylaxis would be maintained in the population at risk.
Why is the population at risk of Plasmodium spp. infection/malarial disease changing? Because the geographical habitat of the malarial vector, the female Anopheles mosquito, is changing as a result of climate change.
What gene therapies are being explored to eliminate malaria? Genetically modified mosquitoes that are resistant to Plasmodium species are being produced in the hope that this resistance will spread and replace the pathogenic Anopheles mosquitoes.
What problems exist with gene therapies being developed to eliminate malaria? Not enough is known about the coevolutionary processes underlying Plasmodium/mosquito interactions, and it is not known if simply introducing a resistance allele will be enough, or if environmental factors with affect refractoriness, and, finally, it is not known what the evolutionary effects in terms of the virulence of the parasite will be (Boete, 2013). Successfully spreading a resistance gene throughout all malarial mosquitoes is a gargantuan task, which seems impossible to achieve.
What is the simplest non-pharmaceutical preventive technique to avoid malaria? The use of mosquito nets - as mosquitoes are most active and more likely to bite at dust and dawn when most people are sleeping - and wearing clothing that leaves little skin exposed.
What chemical preventive techniques may be applied to mosquito nets or skin to avoid malaria? Insecticide may be applied to mosquito nets to make them more effective and insect-repellant may be applied to the skin to avoid infection by deterring mosquitoes.
What benefits are there to preventive methods such as mosquito nets/fully covering clothing/insect-repellants? They are simple, cheap, and effective.
What is true of the socioeconomic status of the areas that malaria is prevalent in? Malaria is found in areas of economic deprivation/poverty.
Is there a vaccine available to protect against malaria? An effective protein subunit vaccine has been developed by GlaxoSmithKline but it is only effective in 1/3 of children it is administered to, and social deprivation in malarial countries means that a population-wide vaccination strategy is highly unlikely to be possible/successful.
How long does natural immunity to malaria last if an individual is absent from a malarial area? Natural immunity does not always prevail when an individual is absent from a malarial area for more than 6 months, so it is not clear whether or not regular anti-malarial booster vaccinations would be necessary, or how feasible this would be to implement.

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