To the best of our knowledge, this is the first comparative study aimed at describing the epidemiological pattern of Treponemal infection within a regional context taking into consideration the four HIV/STI sentinel sites (Ho, Hohoe, Tongu and Krachi-West) in the Volta Region. The cumulative rate of Treponemal infection over the five-year review period (2013-2017) was 0.38% among the 7,805 pregnant women in the Sentinel Survey and 2.38% in the population-based survey among the 17,744 apparently healthy adult population. The five-year cumulative rate observed among the 16,858 asymptomatic adult population who fell below 50 years of age was 2.31% (Table 1). The infection rates recorded in this study are lower compared to the 5.1% reported in Southern Ethiopia , 3.7% in Gondar, Ethiopia , 5.1% in Uganda , 3.0% in Madagascar  and 7.2% in Tanzania . However, similar reports have been observed in other jurisdictions including 1.1% in Ethiopia , 0.5% in South Africa , 1.1 % in Nigeria  and 2.9% in Hungary . Although we recorded a relatively low infection rate in this study in comparison to other settings, our findings suggest that Treponemal infection is persistent in the population and this constitutes an important public health issue in the current study jurisdiction. The phenomenon poses a challenge to WHO’s efforts in achieving total elimination of congenital transmission of Treponemal infection by 2015 .
In general, the cumulative and yearly prevalence of Treponemal infection were significantly higher in the population-based group as compared to that recorded in the Sentinel Survey (p< 0.05), except for year 2017 where the difference was comparable between the two groups (p=0.1416) (Table 1). Thus, our earlier finding of a difference in the rate of Treponemal infections between the two sample groups was not limited to the Ho sentinel site , but represents a regional picture. Earlier reports in other African countries also corroborated the results of this study. Studies in Tanzania [31-33], Uganda  and Zambia  reported that sexually transmitted pathogens were 10-30% lower in pregnant women in the Sentinel Survey compared to individuals in the general population. The finding of a lower rate of Treponemal infection in the Sentinel Survey compared to the population based group  raises important questions about the representativeness of the use of pregnant women for population estimates in the study jurisdiction. According to Boisson, et al.  and Zaba and Gregson , biases exist for using pregnant women as proxy for estimating the prevalence of sexually transmitted pathogens. In the opinion of Gregson, et al. , not all pregnant women would attend antenatal clinic, and attendance may also differ by socio-economic status, age, locality, educational status, parity, ethnic group and religion. Moreover, the use of pregnant women for population estimates may not account for the burden in non-pregnant women of similar reproductive age bracket as well as men in the general population . The reason for the significant reduction in the proportion of Treponemal infection (3.08%) in 2016 to 0.85% 2017 in the donor population within a year is unclear from this study. However, this may be due to the selection criteria or testing effect.
In the present study, there was generally an increasing rate of Treponemal infection with increasing age in both the sentinel survey and population based group (Table 3). The findings are in concordance with those reported by Endris, et al.  in Ethiopia, Pham, et al.  in Zimbabwe, Yang, et al.  in China and Noyola, et al.  in Mexico. The possible explanation to the high prevalence of Treponemal infection among the older population in this study could be due to the less common use of condom and keeping multiple sexual partners which could predispose them to a higher risk of infection. This view was also corroborated by Endris, et al. . In this study, we recorded Treponemal infection rates of 0.31% and 2.22% among the younger group in the sentinel survey and the general population respectively. Though the rate is lower compared to the older population, it suggests that Treponemal infection also exists among the younger generation in the study region. Hence, this calls for the up-scaling of activities aimed at reducing the infection rate among the younger population through early identification and treatment to break the spread from affected persons, and discouraging the youth from engaging in unprotected sexual intercourse with multiple partners and education among others.
In the multisite analysis, we found the cumulative Treponemal infection rate to be highest in Hohoe (4.6%), followed by Ho (2.02%), Krachi-West (1.34%) and Tongu (1.18%) during the five-year period under review (Table 4). The cumulative prevalence of Treponemal infection was significantly higher in the population-based sample compared to the Sentinel Survey in all the sentinel sites except Krachi-West, whiles the yearly infection pattern in both populations at all the sentinel sites presented with a characteristic undulating trend (Figures 1A, 1B, 1C, and 1D). Hohoe and Ho sentinel sites are located within urban Ghana whiles Krachi-West and Tongu sites are of rural origin . There is a strong and consistent link between conditions prevalent in urban areas and the spread of sexually transmitted infections. Factors including urban poverty, resulting from inequalities in socio-economic status among dwellers could lead to the dependence of girls and women on men who are gainfully employed for economic survival resulting in high rates of unintended pregnancies and sexually transmitted infections .
In the present study, we observed a significant gender disparity of Treponemal infection for the five year under review. The male subpopulation recorded higher Treponemal infection (2.4%) compared to their female counterparts (1.5%) (p=0.0433) (Figure 2A). Though not statistically significant, the infection rate among the younger male subpopulation was higher than their female peers (Figure 2B). In our previous study, we have observed male preponderance to Treponemal infection , and also in the works of Anwar, et al. . On the contrary, Coffin, et al.  and Gao, et al. , opined that females were more susceptible to Treponemal infection than their male counterparts. The higher infection rate observed among the male subpopulation could possibly be due in part to the disproportionate gender distribution of the donor participants which was skewed towards the male population.
The present study suffers from some limitations worth mentioning, as treponematoses endemicity of study area, choice of testing method and difference in STI risk exposures (pregnant women are an HIV/STI risk population due to exposure to unprotected sex, while the STI risk of donor population is unknown) are crucial for results interpretation. This study employed retrospective data on treponemal test results from donor population and published data of HSS results of syphilis surveillance among pregnant women. Treponema antibodies may persist for life whether an infection is treated or not, whereas RPR decreases in titre and could vanish when successful treatment is given . Since RPR testing was not performed for the donor population and Sentinel Survey until 2015, as well as, given the fact that the study jurisdiction is known to be yaws endemic , it is possible that the results from this study could be overestimated. This is because immunochromatographic based testing method is unable to differentiate between the causative organism for yaws (Treponema pertenue) and Treponema pallidium. A previous study undertaken by Dassah, et al.  which involved retesting of archived 2007 HSS samples of Ghanaians found that over 50% of samples considered to have “active infection” using the HSS strategy were classified as past or treated infections based on the WHO recommended algorithm.