Design and analysis of small-scale transmission experiments with animals

Abstract

Interactions between pathogens and hosts at the population level should be considered when studying the effectiveness of control measures for infectious diseases. The advantage of doing transmission experiments compared to field studies is that they offer a controlled environment in which the effect of a single factor can be investigated, while variation due to other factors is minimized. This paper gives an overview of the biological and mathematical aspects, bottlenecks and solutions of developing and executing transmission experiments with animals. Different methods of analysis and different experimental designs are discussed. Final size methods are often used for analysing transmission data, but have never been published in a refereed journal; therefore, they will be described in detail in this paper. We hope that this information is helpful for scientists who are considering performing transmission experiments.

Estimation of Transmission Parameters of H5N1 Avian Influenza Virus in Chickens

“…For the high-dose experiment the estimates of the reproduction number are 1.7 (95%CI: 0.40–6.6) in case of an exponentially distributed infectious period and 1.2 (95%CI: 0.37–2.9) in case of a fixed infectious period. Although the difference between the two experiments is not statistically significant (p = 0.23) [23] , it does hint at the possibility of a role of the inoculation dose in impacting on the transmission dynamics. If all experiments with unvaccinated birds are combined the outcome is that 14 out of 22 initially susceptible contact birds are infected.…”

Estimation of Transmission Parameters of H5N1 Avian Influenza Virus in Chickens

“…For the high-dose experiment the estimates of the reproduction number are 1.7 (95%CI: 0.40–6.6) in case of an exponentially distributed infectious period and 1.2 (95%CI: 0.37–2.9) in case of a fixed infectious period. Although the difference between the two experiments is not statistically significant (p = 0.23) [23] , it does hint at the possibility of a role of the inoculation dose in impacting on the transmission dynamics. If all experiments with unvaccinated birds are combined the outcome is that 14 out of 22 initially susceptible contact birds are infected.…”

Sample Size Considerations for One-to-One Animal Transmission Studies of the Influenza A Viruses

“…Note that the analytical solution of q for small N is q  =  R 0 /( R 0 + N −1) which is different from what has been previously discussed [22]. Since the one-to-one transmission experiment handles the binary outcome (i.e.…”

Colonization and Transmission of Methicillin-Resistant Staphylococcus aureus ST398 in Nursery Piglets

“…An important issue to consider is the dose required for successful transmission of MRSA ST398 to susceptible animals. In this study, the dose used to inoculate the seeders was relatively high (ϳ9 ϫ 10 8 CFU), which possibly resulted in a higher level of "infectiousness" of the seeders, i.e., a higher number of bacteria transmitted than the number of bacteria transmitted under field conditions (23). Still, preliminary data showed that such a high dose was necessary to achieve colonization (unpublished data).…”

Estimation of Transmission Parameters of H5N1 Avian Influenza Virus in Chickens

“…For the high-dose experiment the estimates of the reproduction number are 1.7 (95%CI: 0.40–6.6) in case of an exponentially distributed infectious period and 1.2 (95%CI: 0.37–2.9) in case of a fixed infectious period. Although the difference between the two experiments is not statistically significant (p = 0.23) [23] , it does hint at the possibility of a role of the inoculation dose in impacting on the transmission dynamics. If all experiments with unvaccinated birds are combined the outcome is that 14 out of 22 initially susceptible contact birds are infected.…”

Sample Size Considerations for One-to-One Animal Transmission Studies of the Influenza A Viruses

“…Note that the analytical solution of q for small N is q  =  R 0 /( R 0 + N −1) which is different from what has been previously discussed [22]. Since the one-to-one transmission experiment handles the binary outcome (i.e.…”

Colonization and Transmission of Methicillin-Resistant Staphylococcus aureus ST398 in Nursery Piglets

“…An important issue to consider is the dose required for successful transmission of MRSA ST398 to susceptible animals. In this study, the dose used to inoculate the seeders was relatively high (ϳ9 ϫ 10 8 CFU), which possibly resulted in a higher level of "infectiousness" of the seeders, i.e., a higher number of bacteria transmitted than the number of bacteria transmitted under field conditions (23). Still, preliminary data showed that such a high dose was necessary to achieve colonization (unpublished data).…”

Estimation of Transmission Parameters of H5N1 Avian Influenza Virus in Chickens

“…For the high-dose experiment the estimates of the reproduction number are 1.7 (95%CI: 0.40–6.6) in case of an exponentially distributed infectious period and 1.2 (95%CI: 0.37–2.9) in case of a fixed infectious period. Although the difference between the two experiments is not statistically significant (p = 0.23) [23] , it does hint at the possibility of a role of the inoculation dose in impacting on the transmission dynamics. If all experiments with unvaccinated birds are combined the outcome is that 14 out of 22 initially susceptible contact birds are infected.…”

Sample Size Considerations for One-to-One Animal Transmission Studies of the Influenza A Viruses

“…Note that the analytical solution of q for small N is q  =  R 0 /( R 0 + N −1) which is different from what has been previously discussed [22]. Since the one-to-one transmission experiment handles the binary outcome (i.e.…”

Colonization and Transmission of Methicillin-Resistant Staphylococcus aureus ST398 in Nursery Piglets

“…An important issue to consider is the dose required for successful transmission of MRSA ST398 to susceptible animals. In this study, the dose used to inoculate the seeders was relatively high (ϳ9 ϫ 10 8 CFU), which possibly resulted in a higher level of "infectiousness" of the seeders, i.e., a higher number of bacteria transmitted than the number of bacteria transmitted under field conditions (23). Still, preliminary data showed that such a high dose was necessary to achieve colonization (unpublished data).…”