Ensuring demand and supply of benzathine penicillin to treat syphilis
Syphilis is an important sexually transmitted infection with long-term complications if left untreated. Benzathine penicillin G (BPG) is WHO’s recommended first-line treatment for syphilis.
Importantly, syphilis in pregnancy may lead to stillbirth, adverse pregnancy outcomes such as low birth weight and pre-term delivery, and babies born with congenital syphilis. WHO estimates that in 2022 there were 8 million new cases of syphilis in adults and 700 000 cases of congenital syphilis leading to 390 000 syphilis related adverse birth outcomes.
Benzathine penicillin G
BPG is a long-acting antibiotic medication that is used for the treatment of several bacterial infections. WHO's clinical guidelines recommend BPG as first-line treatment for syphilis due to its high efficacy. It is also used as the primary treatment for yaws, streptococcal infections, and rheumatic heart disease, among others.
Ensuring countries have access to a secure and affordable quality finished formulation of BPG is an important public health concern to WHO and partners. Quality assured products contribute to building public confidence and facilitate manufacturers’ access to donor-funded markets.
Recommended treatment for syphilis
WHO's recommended treatment for syphilis is either one intramuscular injection for early syphilis, or three injections one week apart for infection of more than two years’ duration or unknown duration. In non-pregnant people if BPG is not available the WHO recommendation is to use doxycycline or ceftriaxone. In pregnant people, treatment options are more limited and the alternative treatment to BPG is daily injections of procaine penicillin for either 10 days (early syphilis) or 20 days (late syphilis or unknown duration of infection).
Treating syphilis with penicillin injection: a solution not used enough
BPG supply issues
Treatment with penicillin has been hampered by periodic shortages and stock-outs at global, national and sub-national levels. Multiple factors are responsible for the unavailability of BPG for syphilis and other conditions which have penicillin as their first line of treatment.
Currently, there are few manufacturers of the active pharmaceutical ingredient (API). The small number of manufacturers reflects a significant investment in production, relatively small demand for BPGs, low price and profit margins, and environmental restrictions in its production that lead to inflexible purchasing cycles. Quality of API is also a concern as there is no BPG API which quality is assured by WHO or by a stringent regulatory authority.
The API is bought by companies (final dose formulators, or FDF) to produce the finished formulation products (FFP). Only one FFP is currently pre-qualified by WHO. These are distributed to global wholesalers or private distributors and purchased directly by donors, government and the private sector. In the case of the BPG market, this landscape is complex and often leads to sole-sourcing by countries. This further complicates access to the medication.
To overcome these obstacles, countries must have an efficient forecasting system that takes into account trends in syphilis prevalence and programmatic efforts to increase testing coverage (as in the case of efforts to eliminate congenital syphilis), adequate procurement infrastructure, and access to funding to purchase buffer stocks when needed. At the country level, regulatory barriers and supply-chain issues have also created stock shortages.
When BPG is in short supply, efforts should be made to reserve sufficient quantities for the treatment of pregnant people. |
BPG demand issues
It is also known that in many countries, health workers’ behaviour can also drive a decrease in demand for BPG. This is led by negative experiences related to low-quality products and misconceptions about better treatment options and the likelihood of serious adverse outcomes. Managing misconception about the use of BPG in pregnancy is particularly critical when no other known drug can cross the placental barrier to treat the fetus.
To increase BPG demand, WHO has developed a training video for health-care providers addressing safety considerations on the use of BPG, including managing reported history of allergy and the risk of reaction, and misconceptions about elevated risk of serious adverse events. The video also provides step-by-step instructions on BPG administration.
WHO's actions to ensure adequate supply of BPG
WHO and partners are working with countries to establish strategies to ensure a secure and affordable supply of quality BPG.
Priority country focused actions:
- strengthen country procurement and demand forecasting for BPG
- strengthen the monitoring of national stock levels.
Priority global and regional actions:
- strengthen mechanisms to expedite shortage notifications
- monitor market dynamics and develop a plan for responding rapidly to shortages when they are identified
- work with BPG manufacturers to help them comply with international quality standards.
Administration of Benzathine benzyl penicillin G (BPG) injection
Training video