The World Health Organization (WHO) launched a campaign for the elimination of mother-to-child transmission (EMTCT) of syphilis in 2007 (1). EMTCT of syphilis has been defined as an incidence of <50 per 100,000 cases of congenital syphilis (CS). Although gains have been made over the last decade, the estimated global prevalence of maternal syphilis in 2016 was 0.69% (95% confidence interval [CI]: 0.51–0.87) leading to a global CS rate of 473 (385–561) per 100,000 live births and an estimated 661,000 (538,000-784,000) infants born with congenital syphilis per year, including 355,000 (290,000-419,000) adverse birth outcomes and a further 306,000 (249,000-363,000) asymptomatic infants at risk of neurodevelopmental and physical sequelae (2). These global estimates are almost double in the WHO AFRO region, where the maternal syphilis prevalence is estimated as 1.62% and CS rates at 1,119 per 100,000 live births (2).

In recent years, there has been a marked increase in notifications of early infectious maternal syphilis in high-income countries (3–5). High maternal syphilis prevalence is no longer limited to low-income countries. Congenital syphilis is also a re-emerging infection of global importance (6, 7). For example, countries, such as Japan, Australia, and New Zealand, have reported congenital syphilis outbreaks in recent years (8). In the USA, there has been a rise in congenital syphilis in both prevalence and geographical spread (6, 9).

Congenital syphilis is a devastating but entirely preventable disease. The risk of vertical transmission is significantly high in early infectious syphilis in the mother but can occur in secondary and latent syphilis. Untreated gestational syphilis will result in an adverse birth outcome in approximately 80% of cases (10). To achieve WHO accreditation for EMTCT of syphilis, a country must attain rates of 95% for each of (i) antenatal attendance, (ii) antenatal syphilis testing, and (iii) adequate treatment of pregnant women with benzathine penicillin >28 days pre-delivery (11). WHO guidelines for the prevention of mother-to-child transmission (PMTCT) of syphilis also include re-testing pregnant women in the third trimester, partner notification, and surveillance of congenital syphilis rates (12). A secondary analysis of Demographic and Health Survey (DHS) and Service Provision Assessment Survey (SPA) data recently indicated that only 23.8% of Malawian women were likely to access services in line with this recommendation (13). While major gains have been made in terms of the coverage of antenatal testing through the use of rapid point of care tests, there remain health systems and socio-cultural barriers to women accessing appropriate and timely treatment.

The WHO strategy for EMTCT of syphilis acknowledges that, in high prevalence settings, the elimination target of <50 per 100,000 cases of congenital syphilis/live births will be unattainable even with 95% coverage of testing and treatment (14). Treatment failure due to HIV co-infection, re-infection in late pregnancy, and treatment administered late in pregnancy will contribute to persistent congenital infection. The estimated antenatal prevalence of syphilis in Malawi is approximately 2% but has been reported as high as 8% in specific populations (15). Ultimately, combined approaches to interrupt community transmission of the disease alongside efforts to improve the management of infection in pregnancy will be required. Sub-national identification of areas of high prevalence of gestational syphilis may help to target resources aimed at the reduction of sexually transmitted infections in the community as well as areas of need for more intensive strategies for PMTCT.

Established risk factors for gestational syphilis infection in Africa include co-infection with HIV, living in urban centers, maternal education, maternal age, and key populations, including sex workers and lower socio-economic profile (16–18). In this analysis, we modeled the geographical variation in the risk of gestational syphilis over time. The aim was to identify sub-national areas of high syphilis risk and the relative contribution of currently measured and potentially modifiable risk factors.

Figure 1 shows the time series distribution of monthly maternal syphilis prevalence throughout the study period. Nationally, there has been an increase in prevalence among women tested from 0.23% (116 of 50,544) in January 2014 to 2.5% (1,220 of 48,795) in February 2021. From 2019, there have been episodes of marked alternating increase and decrease in prevalence.

The changes in the spatial distribution of prevalence over time are shown in Figure 2. In general, prevalence has mainly increased mostly in the southern region. In 2014, there was a small number of districts with elevated prevalence, mostly in the southern region. By 2021/2022, most districts in southern Malawi had a prevalence ranging between 2% and 4%.

Over time, the risk of syphilis, as estimated by the SIR, increased (Figure 3). The highest risk was generally found in several districts in the southern region. However, by 2022, there was a decrease in maternal syphilis prevalence in the southern region.

To the best of our knowledge, this is the first report of the geospatial distribution of maternal syphilis in an African country using routinely collected health system data. This method has been extensively used to map the evolving problem of syphilis in pregnant women and their infants in both the United States (24, 25) and Brazil (26–33). Leveraging routinely collected data in this way provides a return for investment on district-level data collection. It further supports the development of “precision” public health, which seeks to harness epidemiological data for optimal allocation of available resources.

High-quality district-level data is required to support the development of a national strategy with the aim of attaining international health policy targets. In Brazil, regional-level data identified regions with high migration and high tourist levels as “hotspots” for congenital syphilis (34). In China and Brazil, geospatial methods identified divergence in the development of syphilis and HIV epidemics (35, 36), while in South Africa, a cross-sectional spatial analysis of HIV and syphilis hotspots also showed that they did not overlap (37). In China, syphilis prevalence was associated with areas of rapid economic development (38). In our analysis, we identified a trend of increasing syphilis prevalence over time, which was concentrated in the southern region of Malawi and along the lake shore. It is possible that this is due to the higher levels of urbanization, the presence of major trade routes, and increased migration for work and trade in these areas, but additional targeted surveillance would be required to further explore these possibilities.

By utilizing available district-level demographic data, it is possible to explore risk factors within a population that may contribute to a relatively higher risk of maternal syphilis in that region. In Malawi, regions with a higher HIV prevalence among women of childbearing age also exhibited a higher risk of maternal syphilis. This is in keeping with a 2010 geospatial analysis of HIV prevalence in Malawi, which showed a similar increased risk of HIV in the southern region (39). Based on these observations, the proposed integration of EMTCT programs for HIV and syphilis should be effective in Malawi (40). Our data also support the notion that fewer years of maternal education was associated with an increased risk of maternal syphilis in Malawi. Similar associations have been noted with epidemiological analyses from Brazil (31, 41, 42). Economic and cultural factors that contribute to vulnerability with respect to the sexual health of young women may be different in Malawi and visualizing this by region can support the need for targeted interventions in certain regions.

The observed plateau and decrease in syphilis risk between 2020 and 2022 could have been partly due to the COVID-19 pandemic, which caused some disruptions to the health service, leading to a decrease in syphilis notifications across the country. Decreases in syphilis notifications attributable to the pandemic have been observed in some settings (43, 44). However, more research works are needed to ascertain the true cause of the decrease in the risk in Malawi.

The major strength of this study is the wide geographical distribution of health facilities from which data is drawn, which provides confidence in the representativeness of our results. A further strength is the modeling approach used, which takes into consideration the spatial and temporal structure of the data so that the estimates are more likely to capture underlying heterogeneities between regions. The major limitation of this study relates to the quality of the data used. Since routine HMIS data are dependent on health facilities reporting their data into the central system, missing data are not uncommon and mostly affect small rural health facilities that may not have adequate infrastructure and personnel. We have mitigated this problem as much as possible by doing a district-level analysis using a Bayesian analytical approach, but the results of the study need to be interpreted in light of this limitation. Another limitation is the use of DHS estimates, which assumed that covariate values were constant over the study period. A further limitation of the HMIS data is the inability to capture certain syphilis-related outcomes. For example, gestational syphilis case data may not be representative as pregnant women not presenting at the facility for ANC visits are not included in our estimates. An important limitation of this data is that current standard antenatal testing for syphilis in Malawi is a Treponemal-only rapid Point-of-Care Testing (POCT), but we cannot rule out VDRL or RPR use in some centers in earlier years. We do not have clinical information to confirm the stage or acuity of infection. In addition, there is no existing surveillance for congenital syphilis at the time of delivery in the current dataset analyzing this outcome of EMTCT impossible.

The results of this study highlight the importance of high-quality district-level data to support precision public health that can be improved by employing low-cost regular and consistent auditing of the routine data as a way of improving the quality and investing in electronic data capture at the point of care to minimize data entry errors. Presently, data entry at source is still paper based. This approach may be particularly valuable in low- and middle-income countries where resources are scarce, and interventions need to be targeted for maximum effect. The results of this study need to be interpreted considering the limitations discussed and should be used to support the design of definitive epidemiological studies. Based on our results, future areas of study should target vulnerable young women, be integrated with HIV services, and be focused on regions of rapid development and high migration in Malawi. Modification to the HMIS dataset to enable surveillance of congenital syphilis that links STI and antenatal clinic data is urgently required, as is an investment into data quality and completeness at the district level.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

BF conceived the study. JC and PM also helped in conceiving the study. JC collated the data, analyzed the results, and fitted the models. VG and PM provided advice on statistical modeling and critically reviewed the methods. AM, SY, WO, CMc, CMo, and EC provided insight into maternal syphilis in Malawi. SY authorized the use of DHIS data and clarified data collection systems. All authors contributed to the article and approved the submitted version.