INTRODUCTION

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed livestock, including cattle, sheep, goats, and pigs [1]. It is caused by FMD virus (FMDV), a member of the genus Aphthovirus within the family Picornaviridae [2]. FMD adversely affects the productivity and profitability of livestock production systems by reducing animal performance and causing substantial economic losses. In dairy cattle, FMD has been associated with impaired reproductive performance through multiple physiological mechanisms. Affected animals frequently experience reduced feed intake because of painful oral lesions, resulting in negative energy balance and disruption of reproductive endocrine function [3, 4]. Infection occurring during the breeding period may impair fertilization and early embryonic development up to the morula stage [5]. Furthermore, FMD has been associated with increased age at first calving [6], higher embryonic mortality [7], an increased incidence of reproductive disorders [8], elevated services per conception (S/C), prolonged days open, and extended calving intervals [9, 10]. These adverse reproductive consequences may prevent heifers from achieving the fertility performance commonly reported for Holstein–Friesian cattle under tropical production systems, including first-service conception rate (FSCR) of approximately 24%–47.3% [11, 12], pregnancy rate (PR) of 57.77%–65% [13, 14], and S/C ranging from 1.98 to 2.53 [14, 15]. In addition, FMD infection may increase the risk of culling among surviving dairy cattle because of subsequent infertility and reduced reproductive efficiency [16].

After more than three decades of disease-free status, FMD re-emerged in Indonesia in May 2022, with confirmed cases rapidly spreading across several regions, including Malang Regency, East Java [17]. Molecular characterization demonstrated that the causative FMDV belonged to the O/ME-SA/Ind-2001e lineage [18], which was first detected in Myanmar in 2017 before subsequently spread to Thailand, Vietnam, Malaysia, and, subsequently, Indonesia [19]. The 2022 outbreak caused severe economic losses in the Indonesian dairy sector. Smallholder dairy farmers experienced substantial reductions in milk production, increased calf mortality, and considerable financial losses, estimated at approximately US$2,500 per farmer in herds averaging 6.8 lactating cows [20]. Milk production in Holstein–Friesian (HF) cows reportedly declined by up to 48% following FMD infection [21], while calf mortality reached 17.8% [20]. Despite these documented production losses, information regarding the reproductive consequences of FMD in Indonesian dairy cattle remains limited.

Vaccination remains one of the principal strategies for controlling FMD, alongside strict biosecurity measures and the continuous development of effective multivalent vaccines [22–24]. Nevertheless, concerns have been raised regarding the potential reproductive effects of FMD vaccination in dairy cattle. Previous studies have reported transient adverse effects following vaccination, including reduced feed intake and increased body temperature [25–27]. Such temporary physiological disturbances may compromise oocyte quality, alter progesterone secretion, and increase the risk of early embryonic loss [28, 29]. During the nationwide vaccination campaign following the 2022 outbreak, anecdotal observations from Indonesian dairy farmers and veterinarians suggested increased culling and reduced reproductive performance after vaccination. However, robust scientific evidence distinguishing the reproductive effects of vaccination from those of natural FMD infection under field conditions remains scarce.

Previous investigations evaluating the reproductive consequences of FMD infection or vaccination have largely relied on comparisons between independent groups of animals. Although informative, such study designs are susceptible to between-animal variability arising from genetic background, management practices, nutritional status, environmental conditions, and individual reproductive potential. Consequently, the independent effects of natural FMD infection and vaccination on fertility remain difficult to distinguish. To date, no published study has used a within-animal before-and-after design to evaluate reproductive performance in HF heifers maintained under tropical smallholder dairy production systems before-and-after FMD infection or vaccination. Such a design allows each animal to serve as its own control, thereby minimizing individual-level confounding and improving the precision of treatment-effect estimation [30]. Moreover, no field study has directly quantified and compared the magnitude of reproductive changes associated with natural clinical FMD infection and vaccination within the same study population during the Indonesian FMD outbreak [31]. Addressing these knowledge gaps is essential for developing evidence-based reproductive management strategies and optimizing vaccination programs in FMD-endemic developing countries.

Therefore, this study aimed to evaluate within-animal changes in reproductive performance before-and-after three different exposure conditions: (i) clinical FMD during the outbreak, (ii) clinical FMD following vaccination, and (iii) vaccination without subsequent clinical FMD. The study further aimed to compare the magnitude of reproductive effects associated with natural FMD infection and vaccination using paired reproductive records from the same animals. We hypothesized that natural clinical FMD infection would result in greater impairment of reproductive performance than vaccination and that any reproductive effects associated with vaccination would be comparatively smaller and transient. The findings are expected to provide robust field-based evidence to support reproductive management strategies, optimize vaccination scheduling, and guide FMD control policies in dairy production systems within FMD-endemic developing countries.