Predicted Impact of Mass Drug Administration on the Development of Protective Immunity against Schistosoma haematobium

Abstract

Previous studies suggest that protective immunity against Schistosoma haematobium is primarily stimulated by antigens from dying worms. Praziquantel treatment kills adult worms, boosting antigen exposure and protective antibody levels. Current schistosomiasis control efforts use repeated mass drug administration (MDA) of praziquantel to reduce morbidity, and may also reduce transmission. The long-term impact of MDA upon protective immunity, and subsequent effects on infection dynamics, are not known. A stochastic individual-based model describing levels of S. haematobium worm burden, egg output and protective parasite-specific antibody, which has previously been fitted to cross-sectional and short-term post-treatment egg count and antibody patterns, was used to predict dynamics of measured egg output and antibody during and after a 5-year MDA campaign. Different treatment schedules based on current World Health Organisation recommendations as well as different assumptions about reductions in transmission were investigated. We found that antibody levels were initially boosted by MDA, but declined below pre-intervention levels during or after MDA if protective immunity was short-lived. Following cessation of MDA, our models predicted that measured egg counts could sometimes overshoot pre-intervention levels, even if MDA had had no effect on transmission. With no reduction in transmission, this overshoot occurred if protective immunity was short-lived. This implies that disease burden may temporarily increase following discontinuation of treatment, even in the absence of any reduction in the overall transmission rate. If MDA was additionally assumed to reduce transmission, a larger overshoot was seen across a wide range of parameter combinations, including those with longer-lived protective immunity. MDA may reduce population levels of immunity to urogenital schistosomiasis in the long-term (3–10 years), particularly if transmission is reduced. If MDA is stopped while S. haematobium is still being transmitted, large rebounds (up to a doubling) in egg counts could occur.

Possible changes in the transmissibility of trachoma following MDA and transmission reduction: implications for the GET2020 goals

“…However, if immunity was longer-lived and MDA was assumed to reduce transmission, a large over-shoot in measured egg count was observed. This modelling work was supported by antibody data suggesting MDA and transmission reduction may disrupt the development of protective immunity or alter existing population immunity [ 5 ].…”

“…While our results in this study are theoretical, the rationale behind them has a sound biological basis. Recent work by Mitchell et al [ 5 ] found that if protective immunity to schistosomiasis was short-lived, antibody levels declined to pre-intervention levels during or after MDA. However, if immunity was longer-lived and MDA was assumed to reduce transmission, a large over-shoot in measured egg count was observed.…”

“…The role of mass drug administration (MDA) and the implementation of transmission reduction measures are essential to successfully control and eliminate a wide range of infectious diseases, such as: malaria [ 3 ], trachoma [ 4 ], schistosomiasis [ 5 – 7 ], onchocerciasis [ 8 ], and lymphatic filariasis [ 9 ]. However, for diseases in which immunity to infection is acquired through repeated infections, it has been suggested that dramatically lowering transmission in a short time period may lead to unintended outcomes on the prevalence of infection and disease [ 3 , 10 – 13 ]; if transmission is reduced, individuals who have not recently experienced an infection may have less immune protection than before transmission was reduced [ 6 , 7 , 12 ].…”

A new global strategy for the elimination of schistosomiasis

“…8,9 It has been stated that MDA may reduce population immunity in the long term and if stopped can lead to large rebounds in egg counts. 10,11 Moreover, multiple rounds of MDA among school children have resulted in a reduced efficacy of PZQ which poses a threat to global MDA programs. 12 Parasitological cure depends on the treatment dose.…”

The temporal patterns of disease severity and prevalence in schistosomiasis

“…Mathematical modeling of disease dynamics has proved to be a useful tool in many human infections, in particular, to understand the transmission characteristics of parasitic diseases in order to develop and evaluate the effects of control programs, [7][8][9] and to make predictions on the effects of different intervention options, [10][11][12] also exploring control strategies targeted at high-risk behavioral groups. 13,14 Transmission models of schistosomiasis have been in existence since the 1960s.…”