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The potential contribution of mass treatment to the control of Plasmodium falciparum malaria.

Okell LC, Griffin JT, Kleinschmidt I, Hollingsworth TD, Churcher TS, White MJ, Bousema T, Drakeley CJ, Ghani AC - PLoS ONE (2011)

Bottom Line: We also estimate the effects of using gametocytocidal treatments such as primaquine and of restricting treatment to parasite-positive individuals.In conclusion, mass treatment needs to be repeated or combined with other interventions for long-term impact in many endemic settings.The benefits of mass treatment need to be carefully weighed against the risks of increasing drug selection pressure.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modeling, Imperial College London, London, United Kingdom. l.okell@imperial.ac.uk

ABSTRACT
Mass treatment as a means to reducing P. falciparum malaria transmission was used during the first global malaria eradication campaign and is increasingly being considered for current control programmes. We used a previously developed mathematical transmission model to explore both the short and long-term impact of possible mass treatment strategies in different scenarios of endemic transmission. Mass treatment is predicted to provide a longer-term benefit in areas with lower malaria transmission, with reduced transmission levels for at least 2 years after mass treatment is ended in a scenario where the baseline slide-prevalence is 5%, compared to less than one year in a scenario with baseline slide-prevalence at 50%. However, repeated annual mass treatment at 80% coverage could achieve around 25% reduction in infectious bites in moderate-to-high transmission settings if sustained. Using vector control could reduce transmission to levels at which mass treatment has a longer-term impact. In a limited number of settings (which have isolated transmission in small populations of 1000-10,000 with low-to-medium levels of baseline transmission) we find that five closely spaced rounds of mass treatment combined with vector control could make at least temporary elimination a feasible goal. We also estimate the effects of using gametocytocidal treatments such as primaquine and of restricting treatment to parasite-positive individuals. In conclusion, mass treatment needs to be repeated or combined with other interventions for long-term impact in many endemic settings. The benefits of mass treatment need to be carefully weighed against the risks of increasing drug selection pressure.

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Potential for elimination by mass treatment.(A) Example simulation of a mass treatment programme in a non-seasonal scenario where multiple rounds of MDA are carried out, and the interval in between treatment rounds is less (every 4 months) or more (every 6 weeks) than the critical interval required to achieve <0.1% slide prevalence. (B) Model-estimated minimum frequency of mass treatment required in a large population to bring slide-prevalence to 0.1% or less for at least 50 consecutive days in non-seasonal settings: MDA versus MSAT with PCR as a screening tool. (C) Model-estimated annual mean slide-prevalence after 10 years of MDA repeated every year or every 6 months, according to baseline slide-prevalence prior to intervention. Moderate seasonality is assumed (see Figure 2A). D) example stochastic simulations of transmission over time assuming a small human population (n = 1000) with 1 round of MDA before the peak transmission season in year 1. A single simulation in which MDA succeeds in eliminating infection locally is shown in black. E) and F) Model-estimated probability of local elimination at different transmission intensities in a population of (E) 1000 or (F) 10,000, following MDA of different intensities. Results are based on 500 stochastic realizations per plotted point. Moderate seasonality is assumed (see Figure 2A). All simulations in this figure assume a low level of vector control at baseline which is maintained over time (the baseline slide-prevalence shown is in the presence of vector control).
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pone-0020179-g003: Potential for elimination by mass treatment.(A) Example simulation of a mass treatment programme in a non-seasonal scenario where multiple rounds of MDA are carried out, and the interval in between treatment rounds is less (every 4 months) or more (every 6 weeks) than the critical interval required to achieve <0.1% slide prevalence. (B) Model-estimated minimum frequency of mass treatment required in a large population to bring slide-prevalence to 0.1% or less for at least 50 consecutive days in non-seasonal settings: MDA versus MSAT with PCR as a screening tool. (C) Model-estimated annual mean slide-prevalence after 10 years of MDA repeated every year or every 6 months, according to baseline slide-prevalence prior to intervention. Moderate seasonality is assumed (see Figure 2A). D) example stochastic simulations of transmission over time assuming a small human population (n = 1000) with 1 round of MDA before the peak transmission season in year 1. A single simulation in which MDA succeeds in eliminating infection locally is shown in black. E) and F) Model-estimated probability of local elimination at different transmission intensities in a population of (E) 1000 or (F) 10,000, following MDA of different intensities. Results are based on 500 stochastic realizations per plotted point. Moderate seasonality is assumed (see Figure 2A). All simulations in this figure assume a low level of vector control at baseline which is maintained over time (the baseline slide-prevalence shown is in the presence of vector control).

Mentions: We investigated what intensity of mass treatment programme would be required for elimination of infection in the simulated population. For all results presented in this section we assumed a low level of existing vector control prior to mass treatment that had reduced slide-prevalence of infection by 20–30% from its initial level (see Text S1). We then assume that this level of vector control is either maintained or scaled up. The relationship between the frequency at which mass treatment is repeated and the potential for control and elimination of infection in large populations has been previously characterized in relation to trachoma control [14]. If MDA rounds are repeated indefinitely, and each successive round of MDA can be carried out before the prevalence of infection has recovered following the previous MDA round, the parasite could theoretically be eliminated (Figure 3A). The maximum time interval between successive rounds of treatment so that slide-prevalence on average reaches a pre-elimination threshold of 0.1% is called the critical interval. The critical interval depends on speed of resurgence in transmission and therefore the initial transmission intensity (Figure 3B). Where slide-prevalence of infection is low (<5%), six-monthly rounds of MDA or MSAT using PCR screening are predicted to be sufficient to bring prevalence to the pre-elimination threshold (Figure 3B). In medium-to-high transmission settings, treatment would need to be highly frequent to achieve this target with either strategy. These results in medium-to-high transmission settings are also sensitive to the assumed level of repeated non-participation: if a sufficiently large proportion of the population never participated in mass treatment then however frequently mass treatment was carried out it would not be sufficient to reduce prevalence to zero. In medium-to-high transmission settings, less frequent rounds of mass treatment could sustain an appreciable impact on transmission if they were ongoing (Figure 3C). For example, annual MDA is estimated to lower mean EIR by 20% where baseline slide-prevalence is 40%, while six-monthly treatment rounds could achieve a 30% reduction in the same scenario.


The potential contribution of mass treatment to the control of Plasmodium falciparum malaria.

Okell LC, Griffin JT, Kleinschmidt I, Hollingsworth TD, Churcher TS, White MJ, Bousema T, Drakeley CJ, Ghani AC - PLoS ONE (2011)

Potential for elimination by mass treatment.(A) Example simulation of a mass treatment programme in a non-seasonal scenario where multiple rounds of MDA are carried out, and the interval in between treatment rounds is less (every 4 months) or more (every 6 weeks) than the critical interval required to achieve <0.1% slide prevalence. (B) Model-estimated minimum frequency of mass treatment required in a large population to bring slide-prevalence to 0.1% or less for at least 50 consecutive days in non-seasonal settings: MDA versus MSAT with PCR as a screening tool. (C) Model-estimated annual mean slide-prevalence after 10 years of MDA repeated every year or every 6 months, according to baseline slide-prevalence prior to intervention. Moderate seasonality is assumed (see Figure 2A). D) example stochastic simulations of transmission over time assuming a small human population (n = 1000) with 1 round of MDA before the peak transmission season in year 1. A single simulation in which MDA succeeds in eliminating infection locally is shown in black. E) and F) Model-estimated probability of local elimination at different transmission intensities in a population of (E) 1000 or (F) 10,000, following MDA of different intensities. Results are based on 500 stochastic realizations per plotted point. Moderate seasonality is assumed (see Figure 2A). All simulations in this figure assume a low level of vector control at baseline which is maintained over time (the baseline slide-prevalence shown is in the presence of vector control).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3101232&req=5

pone-0020179-g003: Potential for elimination by mass treatment.(A) Example simulation of a mass treatment programme in a non-seasonal scenario where multiple rounds of MDA are carried out, and the interval in between treatment rounds is less (every 4 months) or more (every 6 weeks) than the critical interval required to achieve <0.1% slide prevalence. (B) Model-estimated minimum frequency of mass treatment required in a large population to bring slide-prevalence to 0.1% or less for at least 50 consecutive days in non-seasonal settings: MDA versus MSAT with PCR as a screening tool. (C) Model-estimated annual mean slide-prevalence after 10 years of MDA repeated every year or every 6 months, according to baseline slide-prevalence prior to intervention. Moderate seasonality is assumed (see Figure 2A). D) example stochastic simulations of transmission over time assuming a small human population (n = 1000) with 1 round of MDA before the peak transmission season in year 1. A single simulation in which MDA succeeds in eliminating infection locally is shown in black. E) and F) Model-estimated probability of local elimination at different transmission intensities in a population of (E) 1000 or (F) 10,000, following MDA of different intensities. Results are based on 500 stochastic realizations per plotted point. Moderate seasonality is assumed (see Figure 2A). All simulations in this figure assume a low level of vector control at baseline which is maintained over time (the baseline slide-prevalence shown is in the presence of vector control).
Mentions: We investigated what intensity of mass treatment programme would be required for elimination of infection in the simulated population. For all results presented in this section we assumed a low level of existing vector control prior to mass treatment that had reduced slide-prevalence of infection by 20–30% from its initial level (see Text S1). We then assume that this level of vector control is either maintained or scaled up. The relationship between the frequency at which mass treatment is repeated and the potential for control and elimination of infection in large populations has been previously characterized in relation to trachoma control [14]. If MDA rounds are repeated indefinitely, and each successive round of MDA can be carried out before the prevalence of infection has recovered following the previous MDA round, the parasite could theoretically be eliminated (Figure 3A). The maximum time interval between successive rounds of treatment so that slide-prevalence on average reaches a pre-elimination threshold of 0.1% is called the critical interval. The critical interval depends on speed of resurgence in transmission and therefore the initial transmission intensity (Figure 3B). Where slide-prevalence of infection is low (<5%), six-monthly rounds of MDA or MSAT using PCR screening are predicted to be sufficient to bring prevalence to the pre-elimination threshold (Figure 3B). In medium-to-high transmission settings, treatment would need to be highly frequent to achieve this target with either strategy. These results in medium-to-high transmission settings are also sensitive to the assumed level of repeated non-participation: if a sufficiently large proportion of the population never participated in mass treatment then however frequently mass treatment was carried out it would not be sufficient to reduce prevalence to zero. In medium-to-high transmission settings, less frequent rounds of mass treatment could sustain an appreciable impact on transmission if they were ongoing (Figure 3C). For example, annual MDA is estimated to lower mean EIR by 20% where baseline slide-prevalence is 40%, while six-monthly treatment rounds could achieve a 30% reduction in the same scenario.

Bottom Line: We also estimate the effects of using gametocytocidal treatments such as primaquine and of restricting treatment to parasite-positive individuals.In conclusion, mass treatment needs to be repeated or combined with other interventions for long-term impact in many endemic settings.The benefits of mass treatment need to be carefully weighed against the risks of increasing drug selection pressure.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modeling, Imperial College London, London, United Kingdom. l.okell@imperial.ac.uk

ABSTRACT
Mass treatment as a means to reducing P. falciparum malaria transmission was used during the first global malaria eradication campaign and is increasingly being considered for current control programmes. We used a previously developed mathematical transmission model to explore both the short and long-term impact of possible mass treatment strategies in different scenarios of endemic transmission. Mass treatment is predicted to provide a longer-term benefit in areas with lower malaria transmission, with reduced transmission levels for at least 2 years after mass treatment is ended in a scenario where the baseline slide-prevalence is 5%, compared to less than one year in a scenario with baseline slide-prevalence at 50%. However, repeated annual mass treatment at 80% coverage could achieve around 25% reduction in infectious bites in moderate-to-high transmission settings if sustained. Using vector control could reduce transmission to levels at which mass treatment has a longer-term impact. In a limited number of settings (which have isolated transmission in small populations of 1000-10,000 with low-to-medium levels of baseline transmission) we find that five closely spaced rounds of mass treatment combined with vector control could make at least temporary elimination a feasible goal. We also estimate the effects of using gametocytocidal treatments such as primaquine and of restricting treatment to parasite-positive individuals. In conclusion, mass treatment needs to be repeated or combined with other interventions for long-term impact in many endemic settings. The benefits of mass treatment need to be carefully weighed against the risks of increasing drug selection pressure.

Show MeSH
Related in: MedlinePlus