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Age-shifting in malaria incidence as a result of induced immunological deficit: a simulation study.

Pemberton-Ross P, Smith TA, Hodel EM, Kay K, Penny MA - Malar. J. (2015)

Bottom Line: While both PEV and SMC programmes are predicted to have overall strongly positive health effects, a shift of morbidity into older children is predicted to be induced by either programme if transmission levels remain static and not reduced by other interventions.Conversely, short-lived transient changes in incidence measured soon after introduction of a new intervention may give over-positive views of future impacts.Complementary intervention strategies could be designed to specifically protect those age-groups at risk from burden shift.

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical and Public Health Institute, 4002, Basel, Switzerland. peter.pemberton-ross@unibas.ch.

ABSTRACT
Effective population-level interventions against Plasmodium falciparum malaria lead to age-shifts, delayed morbidity or rebounds in morbidity and mortality whenever they are deployed in ways that do not permanently interrupt transmission. When long-term intervention programmes target specific age-groups of human hosts, the age-specific morbidity rates ultimately adjust to new steady-states, but it is very difficult to study these rates and the temporal dynamics leading up to them empirically because the changes occur over very long time periods. This study investigates the age and magnitude of age- and time- shifting of incidence induced by either pre-erythrocytic vaccination (PEV) programmes or seasonal malaria chemo-prevention (SMC), using an ensemble of individual-based stochastic simulation models of P. falciparum dynamics. The models made various assumptions about immunity decay, transmission heterogeneity and were parameterized with data on both age-specific infection and disease incidence at different levels of exposure, on the durations of different stages of the parasite life-cycle and on human demography. Effects of transmission intensity, and of levels of access to malaria treatment were considered. While both PEV and SMC programmes are predicted to have overall strongly positive health effects, a shift of morbidity into older children is predicted to be induced by either programme if transmission levels remain static and not reduced by other interventions. Predicted shifting of burden continue into the second decade of the programme. Even if long-term surveillance is maintained it will be difficult to avoid mis-attribution of such long-term changes in age-specific morbidity patterns to other factors. Conversely, short-lived transient changes in incidence measured soon after introduction of a new intervention may give over-positive views of future impacts. Complementary intervention strategies could be designed to specifically protect those age-groups at risk from burden shift.

No MeSH data available.


Related in: MedlinePlus

Averted episodes of uncomplicated malaria in each age group per person-year, in each year of the 20 year course of the SMC programme.
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Fig4: Averted episodes of uncomplicated malaria in each age group per person-year, in each year of the 20 year course of the SMC programme.

Mentions: The simulated SMC programme assumes frequent treatment, resulting in predictions of much larger numbers of episodes averted than the PEV programme Figure 2, but with both programmes, over the whole of the 20 year follow-up period, the average predicted number of malaria episodes show an excess in certain age groups compared to the control untreated cohort. In the PEV simulation, episodes of averted uncomplicated disease are predicted in the five youngest age groups (0–1, 1–2, 2–3, 3–4 and 4–5 year olds) in all years of the programme (Figure 3), but this is accompanied by an excess of episodes predicted in all age groups between 5 and 20 years of age. No effect in the age groups older than 20 years old is observed in the predictions due to the 20 year time span of the simulation follow-up, and the lack of appreciable predicted population effect on transmission of simulated PEV introduced via EPI [5]. The first observed onset of excess episodes for the 5–6 year old age group occurs as early as 4–5 years after the start of vaccination, the earliest time point a vaccinated child would reach this age. A similar temporal pattern to the onset of excess uncomplicated cases is predicted for the SMC programme (Figure 4) although this intervention affects older age groups than the PEV programme and is thus accompanied by a relatively quicker onset and greater number of averted cases in the treated age groups, particularly in the 4–5 year old age group. The age and time pattern of clinical cases averted, and subsequent excess of cases in the intervened individuals, is also predicted for the averted DALYs distribution over time, Figures 5 and 6. After the initial year of the PEV programme, Figure 5, DALYs are averted constantly in the 0–1 and 1–2 year old age groups. However, as the study progresses excess DALYs are seen in an increasing number of age groups, as more age cohorts comprise previously vaccinated individuals with reduced natural immunity compared to same age control cohorts. The peak of the distribution of excess DALYs remains constant around the 4–5 and 5–6 year old age groups. A similar pattern of excess cases and DALYs are seen in the SMC programme, Figure 6, affecting older age groups than the PEV due to the older ages of intervention coverage. Averted DALYs in the youngest age groups are predicted in the first year of the SMC programme, much sooner than in the PEV programme.Figure 2


Age-shifting in malaria incidence as a result of induced immunological deficit: a simulation study.

Pemberton-Ross P, Smith TA, Hodel EM, Kay K, Penny MA - Malar. J. (2015)

Averted episodes of uncomplicated malaria in each age group per person-year, in each year of the 20 year course of the SMC programme.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4513612&req=5

Fig4: Averted episodes of uncomplicated malaria in each age group per person-year, in each year of the 20 year course of the SMC programme.
Mentions: The simulated SMC programme assumes frequent treatment, resulting in predictions of much larger numbers of episodes averted than the PEV programme Figure 2, but with both programmes, over the whole of the 20 year follow-up period, the average predicted number of malaria episodes show an excess in certain age groups compared to the control untreated cohort. In the PEV simulation, episodes of averted uncomplicated disease are predicted in the five youngest age groups (0–1, 1–2, 2–3, 3–4 and 4–5 year olds) in all years of the programme (Figure 3), but this is accompanied by an excess of episodes predicted in all age groups between 5 and 20 years of age. No effect in the age groups older than 20 years old is observed in the predictions due to the 20 year time span of the simulation follow-up, and the lack of appreciable predicted population effect on transmission of simulated PEV introduced via EPI [5]. The first observed onset of excess episodes for the 5–6 year old age group occurs as early as 4–5 years after the start of vaccination, the earliest time point a vaccinated child would reach this age. A similar temporal pattern to the onset of excess uncomplicated cases is predicted for the SMC programme (Figure 4) although this intervention affects older age groups than the PEV programme and is thus accompanied by a relatively quicker onset and greater number of averted cases in the treated age groups, particularly in the 4–5 year old age group. The age and time pattern of clinical cases averted, and subsequent excess of cases in the intervened individuals, is also predicted for the averted DALYs distribution over time, Figures 5 and 6. After the initial year of the PEV programme, Figure 5, DALYs are averted constantly in the 0–1 and 1–2 year old age groups. However, as the study progresses excess DALYs are seen in an increasing number of age groups, as more age cohorts comprise previously vaccinated individuals with reduced natural immunity compared to same age control cohorts. The peak of the distribution of excess DALYs remains constant around the 4–5 and 5–6 year old age groups. A similar pattern of excess cases and DALYs are seen in the SMC programme, Figure 6, affecting older age groups than the PEV due to the older ages of intervention coverage. Averted DALYs in the youngest age groups are predicted in the first year of the SMC programme, much sooner than in the PEV programme.Figure 2

Bottom Line: While both PEV and SMC programmes are predicted to have overall strongly positive health effects, a shift of morbidity into older children is predicted to be induced by either programme if transmission levels remain static and not reduced by other interventions.Conversely, short-lived transient changes in incidence measured soon after introduction of a new intervention may give over-positive views of future impacts.Complementary intervention strategies could be designed to specifically protect those age-groups at risk from burden shift.

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical and Public Health Institute, 4002, Basel, Switzerland. peter.pemberton-ross@unibas.ch.

ABSTRACT
Effective population-level interventions against Plasmodium falciparum malaria lead to age-shifts, delayed morbidity or rebounds in morbidity and mortality whenever they are deployed in ways that do not permanently interrupt transmission. When long-term intervention programmes target specific age-groups of human hosts, the age-specific morbidity rates ultimately adjust to new steady-states, but it is very difficult to study these rates and the temporal dynamics leading up to them empirically because the changes occur over very long time periods. This study investigates the age and magnitude of age- and time- shifting of incidence induced by either pre-erythrocytic vaccination (PEV) programmes or seasonal malaria chemo-prevention (SMC), using an ensemble of individual-based stochastic simulation models of P. falciparum dynamics. The models made various assumptions about immunity decay, transmission heterogeneity and were parameterized with data on both age-specific infection and disease incidence at different levels of exposure, on the durations of different stages of the parasite life-cycle and on human demography. Effects of transmission intensity, and of levels of access to malaria treatment were considered. While both PEV and SMC programmes are predicted to have overall strongly positive health effects, a shift of morbidity into older children is predicted to be induced by either programme if transmission levels remain static and not reduced by other interventions. Predicted shifting of burden continue into the second decade of the programme. Even if long-term surveillance is maintained it will be difficult to avoid mis-attribution of such long-term changes in age-specific morbidity patterns to other factors. Conversely, short-lived transient changes in incidence measured soon after introduction of a new intervention may give over-positive views of future impacts. Complementary intervention strategies could be designed to specifically protect those age-groups at risk from burden shift.

No MeSH data available.


Related in: MedlinePlus