Slowing global antimicrobial resistance to syphilis and other STIs

Antimicrobial resistance (AMR) is a global public health threat. Every year, a growing number of bacteria, viruses, fungi, and parasites become resistant to existing medications, making common infections harder to treat and increasing the risk of disease transmission, severe illness, and death.

Antimicrobials are critical tools for fighting disease and include antibiotics, antivirals, and anti-fungal medicines. But AMR is on the rise, due to drug overuse and misuse as well as poor access to water, sanitation, and hygiene.

AMR is a challenge that affects many diseases, including HIV, TB, malaria, pneumonia, and sepsis. CHAI is helping to slow the spread of antimicrobial resistance by ensuring that patients have access to appropriate treatment and adhere to correct medicine regimens. Our approach is informed by insights learned from our work around AMR among pregnant women infected with syphilis and the antibiotic used to treat that infection: benzathine benzylpenicillin.

Benzathine benzylpenicillin as a case study

Benzathine benzylpenicillin is the only proven and WHO recommended medicine to prevent the transmission of syphilis from a pregnant woman to the fetus. Annually, about one million pregnant women get a syphilis infection, many of whom do not get tested or treated. Consequently, they are at risk for an adverse birth outcome, with about two-thirds resulting in stillbirths or neonatal death.

It is estimated that in sub-Saharan Africa, 11 percent of all stillbirths each year are due to syphilis, and nearly all of them could be prevented through benzathine benzylpenicillin treatment. The drug is extremely affordable costing as little as 20 cents per dose. But access has been an issue, leading to the use of sub-optimal alternatives that encourage antimicrobial resistance.

From 2014 to 2016, global shortages of benzathine benzylpenicillin drastically impacted public health interventions around the world. With almost one in two countries reporting national stockouts, health providers were forced to resort to alternative treatments (Figure 1). This not only led to poorer health outcomes for mother-to-child transmission of syphilis, but also increased risks for resistance.

Figure 1. Countries with reported shortages of benzathine benzylpenicillin during 2014–2016.

To address supply shortages of benzathine benzylpenicillin, CHAI partnered with the Bill & Melinda Gates Foundation and the World Health Organization (WHO) in 2016. CHAI conducted a market assessment that revealed the marketplace is highly fragmented with many small buyers. These buyers source from over 30 suppliers of the antibiotic. High fragmentation and low market prices make producing benzathine penicillin commercially unattractive relative to other penicillin products. When the production of active pharmaceutical ingredient (API), the biologically active component of the drug, was interrupted in 2014 to 2015 due to external factors, a lack of information and understanding caused severe disruptions along the supply chain.

In response, CHAI worked with each level of the supply chain to increase transparency in the market. As a result, suppliers accelerated API production in new facilities, distributors with additional inventory on hand were activated, and governments were able to identify and register new suppliers.

Although not all underlying risks have been resolved, the market conditions have improved significantly. The number of surveyed countries that reported shortages has dropped to six in 2019, down from 39 in 2016 (Taylor, unpublished). The actions that led to more reliable supplies of benzathine benzylpenicillin in the market are reducing the use of alternative products and associated risks for antimicrobial resistance.

Replicating the success in new health areas

CHAI is now partnering with the Ethiopian, Indian, Kenyan, Nigerian, South African, and Ugandan governments to test and treat more pregnant women for syphilis and supporting governments to build an approach towards addressing other sexually transmitted infections (STIs). By leveraging the lessons learned from benzathine benzylpenicillin, we can also help governments improve treatment supply chains and reduce AMR for other STIs, notably gonorrhea, which is a key global health priority, to prevent antimicrobial resistance.

These lessons also have much broader implications. The issue of AMR affects the fight against many diseases. Consequently, CHAI is developing an approach towards AMR that cuts across all aspects of our work and that of the governments we support. This approach builds on CHAI’s core areas of expertise, featuring increased vaccination drives, community health worker training, and improved lab systems across entire health systems to address multiple diseases.

By taking a holistic approach that combines large scale community testing and treatment with targeted and specialized management of severe and/or resistant cases, CHAI hopes to reduce antimicrobial resistance across different disease areas. And by leveraging lessons from benzathine benzylpenicillin, we hope to fast track progress, leading to better patient outcomes and reduced disease burden on already strained public health systems.

To learn more, watch, Treating Syphilis with Penicillin injection: a solution not used enough produced by the World Health Organization (WHO).