Congenital Syphilis and Penicillin as Prevention

In this podcast, Melanie Taylor, MD, MPH, discusses her virtual session at CROI 2020, during which she talked about global trends in congenital syphilis, prevention of mother-to-child transmission, and why every pregnant woman with syphilis should receive penicillin.

Additional Resources:

• Taylor M. Syphilis causes stillbirth: penicillin is prevention. Presented at: Conference on Retroviruses and Opportunistic Infections 2020; March 8-11, 2020; virtual. https://www.croiconference.org/sessions/syphilis-causes-stillbirth-penicillin-prevention.
• WHO guidelines on syphilis screening and treatment for pregnant women. Geneva: World Health Organization; 2017. https://www.who.int/medical_devices/diagnostics/selection_in-vitro/selection_in-vitro-meetings/00007_02_WHO_Syphilis_SandT_Pregnant.pdf. 
• World Health Organization. Dual HIV/syphilis rapid diagnostic tests can be used as the first test in antenatal care. Published November 27, 2019. Accessed April 3, 2020. https://www.who.int/publications-detail/dual-hiv-syphilis-rapid-diagnostic-test

Melanie Taylor, MD, MPH, is an infectious diseases physician working at the World Health Organization in Geneva, Switzerland. Specifically, she works on topics related to the vertical transmission of HIV and syphilis. 

TRANSCRIPT:

Amanda Balbi: Hello everyone, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator Amanda Balbi with Consultant360 Specialty Network.

The Conference on Retroviruses and Opportunistic Infections 2020 was a virtual meeting of the minds in infectious disease and public health.

The World Health Organization estimates 660,000 cases of mother-to-child transmission of syphilis occurred in 2016, resulting in 350,000 adverse birth outcomes inclusive of more than 200,000 stillbirths and neonatal deaths. WHO now recommends the use of a rapid dual HIV/syphilis test kit that allows for testing of both infections with a single finger stick. This rapid dual HIV/syphilis test is recommended for the first antenatal care visit for all pregnant women. However, the only medication approved for preventing congenital syphilis is penicillin.

This was the focus of a session at CROI 2020. And today, I’m joined by the speaker—Dr Melanie Taylor, MD, MPH, who is an infectious diseases physician working at the World Health Organization in Geneva, Switzerland. Specifically, she works on topics related to the vertical transmission of HIV and syphilis.

Thank you for joining me today Dr Taylor. Let’s talk more about your session.

To start, what are the global trends in congenital syphilis?

Melanie Taylor: As context for understanding the burden of congenital syphilis, for example, in 2018, UNAIDS estimated that only 160,000 mother-to-child transmissions occurred for the virus HIV. In comparison, during a similar data year—2016—more than 600,000 infants were estimated to have been born with congenital syphilis. Now, what is a bit tragic about that is that these infants … the outcomes of congenital syphilis are easily prevented with a single injection of benzathine penicillin given to the mother.

And what's also notable about that is that benzathine penicillin, in most parts of the world, costs less than US$1, usually around 50 cents, for that single curative injection.  And so we have the opportunity to prevent and eliminate congenital syphilis.

What we've seen regarding trends globally for congenital syphilis is that between the 2 data years of 2012 to 2016, there were some regions that experienced declines, specifically the African region experienced the decline in estimated number of congenital syphilis cases, as did the region of the Western Pacific and also Southeast Asia. There were two regions that experienced increases in estimated number of cases between 2012 and 2016, and these were the Americas region—so, South and North America—as well as the eastern Mediterranean region.

Those areas that experience declines were not due to declines in the burden or the prevalence of maternal syphilis, rather they are due to improvements in the coverage of antenatal care, syphilis screening during pregnancy, and for those women found to be positive, treatment for syphilis with benzathine penicillin.

In these global trends, which we have shown to be … there's a small decline between 2012 and 2016, but the burden is still quite high. So, for example, of those over 600,000 (exactly 661,000 estimated congenital syphilis cases), the burden of that results in more than 350,000 infants that were adverse birth outcomes. Specifically, 200,000 of that 350,000 were stillbirths or neonatal deaths. And the remaining were premature infants, infants with low birth weight, or infants with congenital deformities or clinical signs of congenital syphilis.

So again, the burden of this infection, even though we have a slight global decline in the estimated number of cases, is still very high and results in, as I mentioned, stillbirth and fetal death rates that are higher than the simple mother-to-child transmission rate of HIV, which requires lifelong therapy in the mother, as compared to a single injection of benzathine penicillin at a cost of approximately 50 cents.

We have the opportunity really to address this as a disease that can be eliminated, with improvements in service delivery at the antenatal care stage, which includes syphilis screening for every pregnant woman, and for every pregnant woman found to be positive treatment with benzathine penicillin.

Amanda Balbi: So let’s talk more about your session now. Can you give us a brief overview of what you discussed?

Melanie Taylor: Absolutely. So, the title of the session is quite telling, and what the context of the situation is regarding congenital syphilis is that this preventable condition among infants and newborns is preventable, but it still is responsible for a large burden of adverse birth outcomes, including stillbirths and neonatal deaths globally.

In fact, more than 600,000 infants were estimated to have been born or to have been affected by congenital syphilis in our most recent data reporting year of 2016.

Within the presentation, we present these estimates of the global burden of congenital syphilis. In addition to the prevention, treatment, and the targets for country achievement for validation of elimination of mother-to-child transmission of syphilis.

Amanda Balbi: Absolutely. And should penicillin be given to ALL expecting mothers who have syphilis?

Melanie Taylor: Yes, this is a very good question. Penicillin is currently the only WHO-recommended treatment for pregnant women with syphilis, and thus, as the only recommended treatment, it is true that any woman diagnosed with syphilis during pregnancy should receive benzathine penicillin as treatment [unless they are allergic].

This treatment with benzathine penicillin prevents the occurrence of congenital syphilis by treating the mother who was infected with syphilis, as well as treating an infant that may have been affected by transplacental transfer of the bacteria, Treponema pallidum, that causes congenital syphilis. So indeed, this is a global recommendation for the use of benzathine penicillin among pregnant women who have syphilis.

There are several challenges with giving women this treatment. (1) It's an injection. It is frequently prone to stock out. There were significant stock outs among over 40 countries during the years of 2014 to 2017. And these shortages of benzathine penicillin resulted in women with syphilis that were pregnant going untreated or being treated with alternative, untested antibiotics and infants being born to women that had received no antibiotics or antibiotics that have no evidence for their use in pregnant women.

So, in this regard, it's very important that we embark on looking for an alternative drug for use for treatment of pregnant women with syphilis to prevent vertical transmission. And so, although yes benzathine penicillin is the only recommended drug currently, we are looking and seeking support for identifying alternative treatments in the event that a pregnant woman is, let’s say, allergic to benzathine penicillin, is not tolerant or is unable to accept or tolerate an injection, for places where an injection cannot be given and also in places where, of course, they are experiencing benzathine penicillin shortages. So, in answer to your question, yes, benzathine penicillin should be given to all pregnant women with syphilis [unless they are allergic].

Amanda Balbi: Great. And what would you say are the key take-home messages about congenital syphilis?

Melanie Taylor: The overall key take home messages are that we have seen a small global decline in congenital syphilis, and this decline is related to improvements in the service care delivery of antenatal care, syphilis screening during pregnancy, and treatment of pregnant women with benzathine penicillin.

The challenges related to screening and treatment in pregnant women are that within many countries and at many service care delivery areas, syphilis tests are simply not available. So, for example, a mother may attend several antenatal care visits in good faith that she is receiving quality and comprehensive antenatal care, but that antenatal care may not include a syphilis test, even though over 95% of countries in the world include syphilis screening in their antenatal care guidelines.

Frequently those test kits are not available for women when they are in antenatal care, thus they miss the opportunity to be diagnosed with syphilis during pregnancy and prevent that infection from being transmitted to their unborn infant.

Once a woman is diagnosed with syphilis during pregnancy, another challenge arises in that she needs treatment. And unfortunately benzathine penicillin, although it is very inexpensive, sometimes that treatment is not delivered at the same clinic, and thus the pregnant woman may need to travel to a different clinical site. She may also need to purchase the benzathine penicillin, and in many cases there are stock outs of benzathine penicillin.

So, these issues as take-home points described the challenges that we continue to have with the diagnosis and treatment of syphilis among pregnant women.

Finally, what's important to remember, as has been mentioned before, benzathine penicillin is the only recommended treatment right now recommended by both WHO and US CDC as the treatment for pregnant women with syphilis. When there are shortages or stock outs of this medication, there is no backup. There really is no alternative that has been evaluated in clinical trials to be effective and safe for pregnant women and their unborn infants.

It's important that we embark on clinical trials to identify alternative treatments in order to truly be able to provide treatment in the face of benzathine penicillin shortages, or in the face of situations where a woman cannot receive benzathine penicillin due to allergy or intolerance, etc.

So those are the key take home points. And I think what's important also to remember is that there is the opportunity to eliminate congenital syphilis, because it's simply testing and treatment of pregnant women in antenatal care that can prevent the transmission to the baby.

Amanda Balbi: Absolutely. Thank you again for speaking with me today about your session and research on congenital syphilis.

Melanie Taylor: Thank you. It was a pleasure to talk to you.