Introduction
The reemergence of brucellosis in Central Asia and the Middle East (Godfroid, et al., 2005; Seleem, Boyle, & Sriranganathan, 2009; Pappas, Papadimitriou, Akritidis, Christou & Tsianos, 2013) is a large part because of its changing epidemiology (Dahouk et al., 2007); the role of animal husbandry tradition; and a culture of raw milk consumption. These factors are also major reasons for the continued persistence in many countries around the world (Zhong et al., 2013; Wallach, 1997).
One health implication of human brucellosis (Brucella melitensis ; the most common and virulent species of human brucellosis), one of the most widespread zoonotic diseases in the world, is the potential role in of the bacteria in inducing fetal loss. The etiology of abortions and stillbirths are complex and can be attributed to either non-infectious causes (e.g., congenital anomalies, placental insufficiency, placental abruption and asphyxia), or to infectious agents (Goldenberg & Thompson, 2003). Approximately 9 to 15 percent of stillbirths are caused by infectious diseases and in particular, infections during early in pregnancy (Gibbs, 2002). Economic factors can influence the role of infectious diseases and stillbirths. In middle- and low-income countries 50 percent or more of stillbirths can be attributed to infections, whereas, in high income countries, only 10 to 25 percent of maternal or fetal infections can account for stillbirths (Goldenberg & Thompson, 2003; Goldenberg, McClure, Saleem & Reddy, 2010). Specific infectious agents linked to stillbirths include syphilis, malaria, toxoplasmosis, parvovirus B-19, chorioamnionitis, and Listeria monocytogenes . Less definitive links to stillbirths include the genital mycoplasmas, Chlamydia trachomatis , HIV, and group B streptococci. and others (Gibbs, 2002; Goldenberg & Thompson, 2003).
It has been well documented that animal strains of brucellosis cause abortions of fetuses and ‘reproductive failure,’ in cows, dogs, goats, horses, pigs, sheep and even camels. (Lopes, Nicolino, & Haddad, 2010; Ocholi, Kwaga, Ajogi & Bale, 2005; Samartino, & Enright, 1993)B. Melitensis can be transmitted to humans only from goats or sheep, through consumption of unpasteurized milk and cheese; through close contact with animals (i.e. hunting, milking, or caring for sick [veterinarians]); through meat processing and meat consumption; or through inhalation or airborne of the pathogen. Rarely, the bacteria can be transmitted from person-to-person either via sexual contact or airborne transmission.
The study of the link between human B. melitensis and the termination of births in humans is a topic that has received a dearth of attention. Few studies have examined relationship of human stillbirths and B. melitensis , especially at the cohort or population level (for exceptions see: Gulsun, Aslan, Satici, & Gul, 2011, and Rujeni, & Mbanzamihigo, 2014). Others are case reports of stillbirth and abortions that are limited in scope and sample size (Karcaaltincaba, Sencan, Kandemir, Guvendag‐Guven, & Yalvac, 2010; Goldenberg et al., 2010; Mosayebi, Movahedian, Ghayomi, & Kazemi, 2005). These studies, however, point to the strong possibility that brucellosis is a risk for adverse health outcome to the human fetus.
In this paper we explore the relationship between human B. melitensis and stillbirths specifically in the civil population of Malta during the period 1919 to 1954. The Maltese islands present a rare opportunity for a population-based inquiry into the potential adverse effects of brucellosis on fertility through fetal loss. The advantages of the study site include the following population-based attributes: First, brucellosis (a.k.a. Malta or Mediterranean Fever) was a notifiable disease since the early 20th century and it remained endemic throughout the study period. Second, monthly statistics of births and stillbirths by sex were published since 1900. Third, pregnant women were at continuous and at high exposure to brucellosis because of high fertility rates owing to their adherence to strict Catholic precepts (Tripp & Sawchuk, 2015; 2017). Finally, throughout the study period, the health care infra-structure was rudimentary along with little available pre-natal care for expectant mothers putting the vast majority of women at risk for fetal loss (Savona Ventura & Grech, 1985; Seers, 1957; Tripp & Sawchuk, 2015).