Traditional approaches to malaria control Vector control Surveillance indoor pesticide treatments spray walls elimination of breeding sites Treatment of active cases e g chloroquine 4 More surveillance Entomological problems Surveillance systems have degenerated Vector control infrastructure has degenerated Insecticide resistance expensive chemicals Common problem in public health Almost all older insecticides are now of little effect forcing the use of much more As control strategies are successful in reducing a disease and concern about the disease wanes it becomes harder to justify the expense of maintaining the program Scarce dollars are shifted to other pressing problems But eventually the disease returns sometimes now with resistance to the original insecticides and drugs Chloroquine based on chemical structure of quinine Initially remarkably inexpensive 4 cents dose and effective Resistance appeared first in 1957 in an area on the Thailand Cambodia border Mining attracted many non immune workers to the area and also created lots of ditches ponds etc that bred lots of Anopheles mosquitoes leading to frequent malaria epidemics To combat this public health officials started a program where chloroquine was added to table salt attempt to treat people with a prophylactic dose Resistance based on an ability to rapidly excrete the drug via an ABC transporter 40X faster than wild type parasites appeared then spread throughout SE Asia then into Africa now everywhere Consequence of failure to consider what would happen when parasites are exposed to a drug for a long time i e failure to account for evolution New drugs Little interest from the big pharmaceutical companies orphan diseases most who require the drugs are too poor to pay much so little economic incentive to invest in R D common problem in many tropical diseases Most effort now funded by WHO Gates Foundation similar NGOs Some newer drugs available eg atovaquone proguanil Malarone sulfadoxine pyrimethamine Fansidar doxycycline All are many times more expensive than chloroquine Some new drugs based on traditional cures eg Artimisin from Chinese Artemesia plants Artemisin combination therapy ACT now the standard but resistance has already appeared especially in Thailand Myanmar border area New developments Entomological Perspective Residual indoor spraying of insecticides is still used but much less frequently due to insecticide resistance Nets are treated with permethrin or other fast acting contact insecticide Odor of sleeping people draws in mosquitoes that contact the net and are killed Practical considerations cost of nets ease cost of replenishing insecticide treatment of nets Our best current tool insecticide treated bednets Insecticide treated bednets reduce the number of infectious bites open bars bites prevented filled bars bites received Note that night time peak at 3 am is when the threat is the greatest Vaccine development Anti sporozoite Anti gametocyte Anti merozoite Multi functional vaccine contains peptides from several different stages of the parasite Very dificult problem with no real success until very recently Why Parasites mostly cryptic inside host cells Tremendous amount of genetic diversity very hard to find universal antigens Parasites selected for ability to evade host immunity Field trials of candidate vaccines ongoing Results In the 14 months after the first dose of vaccine the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0 32 episodes per person year in the RTS S AS01 group and 0 55 episodes per person year in the control group for an efficacy of 50 4 95 confidence interval CI 45 8 to 54 6 in the intention to treat population and 55 8 97 5 CI 50 6 to 60 4 in the per protocol population Vaccine efficacy against severe malaria was 45 1 95 CI 23 8 to 60 5 in the intention to treat population and 47 3 95 CI 22 4 to 64 2 in the per protocol population Vaccine efficacy against severe malaria in the combined age categories was 34 8 95 CI 16 2 to 49 2 in the per protocol population during an average follow up of 11 months Serious adverse events occurred with a similar frequency in the two study groups Among children in the older age category the rate of generalized convulsive seizures after RTS S AS01 vaccination was 1 04 per 1000 doses 95 CI 0 62 to 1 64 1st malaria vaccine to show efficacy in field trials Update After four doses protection reduction in cases over 4 years was Clinical malaria 39 Severe malaria 29 Malaria hospitalization 37 Immunity fades over time but natural immunity due to malaria exposure builds up WHO the Vaccine Alliance sponsoring a widespread vaccination campaign across the most endemic areas of sub Saharan Africa between 2022 and 2025 1st vaccine to be deployed in the field Update 2 BioNTech is leading an effort to develop a mRNA vaccine for malaria in 2022 BioNTech with Pfizer previously developed a highly effective mRNA vaccine for Covid 19 Possible complication mRNA vaccines require a cold chain with storage on dry ice hard to accomplish in rural sub Saharan Africa Lymphatic Filariasis Lymphatic filariasis Also called elephantiasis 1 2 billion people at risk About 120 million infected in 72 countries Over 40 million disabled Note Filariasis is a general term for infection with nematode parasites River blindness is another example Nematode Parasites Wuchereria bancrofti most common worldwide Brugia malayi southeast Asia Brugia timori southeast Asia Reservoirs Only humans are known as reservoirs anthroponosis So very few animal models are available to study disease