A pathogen’s reproductive success depends crucially on: It’s ability to find a suitable host In order for a species of pathogen to survive every sick host needs to infect 1 new host on average. 1 new infection/host -> pathogen level in host population does not change < 1 new infection/host -> pathogen goes extinct >>1 new infection/host -> e.g. epidemic, or highly endemic disease area Reproductive succes = transmission success 1Vector borne transmission Two hosts: vertebrate and vector How to maximize transmission? High virulence in mosquito? High virulence in human? The importance of the mode of transmission No! Yes, can be advantageous 2Pathogen density inside host Virulence Correlation between virulence in human host and transmission Generalized relationship between virulence and number of pathogens inside host Pathogen density inside host Porb. Infedtion Vector High virulence increase probability of vector being infected with pathogen 3Plenty of other highly virulent Infectious diseases that are not transmitted by vectors Other modes of transmission select for high virulence as well For example: !• !Water-borne transmission • Sit-and-wait transmission Vector borne diseases tend to be more highly virulent 4Summary so far, Infectious diseases “aim” to maximize their transmission rate The correlation between reproductive success and virulence depends on transmission mode Vector-borne transmission tends to result in high virulence in vertebrate hosts The virulence of pathogens can adapt swiftly to a new transmission mode, or to a shift in transmission intensity Either by evolutionary changes in the organism, or by the replacement of one species by closely related, less virulent one 5The Dynamics of Vector-Borne disease (1) Vector competence: the ability of a vector to transmit a pathogen Two important definitions: (2) Vectorial capacity: rate at which future inoculations arise from a currently infective case For example, Can the pathogen grow inside the vector? Can the vector be transmitted by the vector? 6Vectorial capacity = C m = number of vectors per human a = number of human blood meals per mosquito per day V = vector competence P = daily survival rate n = incubation period in vector (extrinsic incubation period) The average number of new infections arising daily from a single infection 7What are the most “sensitive” components of vectorial capacity? Number of human blood meals per mosquito per day Daily survival rate 8For example, 1) If we reduce (m) mosquito abundance by 10% -> C reduces by 10% 2) If we reduce (a) human biting rate from 90% to 81% (=10% reduction) -> a2 reduces from 0.81 to 0.65 (= 20% reduction) 3) If we reduce mosquito daily mosquito survival from 90% to 81% -> Pn from 0.28 to 0.08 (assuming n = 12 days) -> -loge P increases from 0.105 to 0.210 7-fold reduction of C 9For a species of pathogen to survive, each infected host needs to infect at least one other host (on average). One more parameter that is relevant: r = rate at which people recover from infection (= 1/number of recovery days) Number of days people remain infective. ma2VPn R= -r ln P R= Basic Reproduction Number 10- Vectorial capacity is very difficult to measure -> many parameters that are difficult to estimate: m = number of vectors per human -> mark-release-recapture studies 1] capture a lot of mosquitoes (> thousands) 2] mark them with fluorescent powder 3] release 4] recapture them and determine proportion Example: - 5,000 mosquitoes are marked and released - 15,000 are recaptured of which 1,500 were marked -> 10% -> If the marked mosquitoes represent 10% of recaptured mosquitoes, they also represent 10% of total population => 5,000x10= 50,000 Measuring Vectorial Capacity 11Estimating m = number of vectors per human Indirect or genetic methods: - estimate the effective (=genetic) size of mosquito populations using genetic tools How does the genetic size correlate to absolute numbers? - depends on how many females and males contribute to the next generation - some estimates suggest actual size (census size) = 5x effective size - takes about a year of work for one population Measuring Vectorial Capacity 12a = number of human blood meals per vector per day -> blood meal analyses of blood fed mosquitoes provides a proportion of human host preference X number of total blood meals taken every day. e.g. if we assume that vector blood feeds every 5 days if human host preference = 10% a= 1/5 x 0.1= 0.02 (a2 = 0.0004) if human host preference = 90% a= 1/5 x 0.9 =0.18 (a2 = 0.0324) V = vector competence -> infect mosquitoes in the lab and examine how many can transmit after a certain time e.g if 100 mosquitoes are fed on infectious blood meal, and 50 of those are capable of infecting a new host after the incubation period, vector competence = 50/100 = 0.5 (or 50%) Measuring Vectorial Capacity 13P = daily survival rate 1] In case of mosquitoes: examine the structure of the ovary -> this can tell you how many times a mosquito has laid eggs -> from this you can get a very rough idea of age based on how often mosquitoes can lay eggs (appr. every 3-5 days) 2] Mark-Release-Recapture -> based on the reduction of recaptured mosquitoes over time. This has a very large uncertainty associated with it, unless recapture rates are high n = incubation period in vector (extrinsic incubation period) Lab based experiment can tell you how long it takes for an infected vector to become infectious (=capable of transmission to new host). -> This period often lasts 8-14 days for many vector borne pathogens -> But: The extrinsic incubation period is very dependent on temperature: high temp = shorter incubation period = higher VC Measuring Vectorial Capacity 14Measuring Basic Reproductive Number r= recovery rate This is the number of days that hosts remain infective -> determine how long pathogens are present in the blood (or skin (in case of riverblindness)) So, it is very difficult to determine Vectorial Capacity and Basic Reproduction Number! 15Another more practical estimate of the force of transmission Entomological Inoculation rate (EIR) The number of times