One of the oldest diseases in the world, syphilis is making an alarming comeback, with leading scientists describing it as a public health crisis and failure, given that the STI, which can have dire and fatal consequences especially for newborn babies, is curable with early treatment.
The return of the disease was recently under discussion at the international Conference on Retroviruses and Opportunistic Infections (CROI), where scientists, clinicians and public health advocates gathered in Denver in March, writes Biénne Huisman in Spotlight.
Professor Khalil Ghanem of Johns Hopkins University School of Medicine told delegates that there was a paucity of data – “while syphilis continues to increase, with clinicians caring for patients with complex clinical presentations”.
He said there was little systematic information on how to manage cases of advanced syphilis, like neurosyphilis (syphilis in the central nervous system) and ocular syphilis (syphilis in the eyes).
The disease is often referred to as “the great imitator”, due to its variable clinical manifestations that can mimic other diseases. In its severe forms, it can cause chronic multiple organ damage in adults.
The infection can also be passed on from mother to baby during pregnancy, resulting in congenital syphilis, causing premature birth, miscarriage, stillbirth and birth defects. In most cases, however, the bacterial infection is transmitted sexually.
Latest available figures from the World Health Organisation for congenital syphilis – dated 2016 – show that globally, there were an estimated 661 000 cases that year; including 143 000 stillbirths, 61 000 neonatal deaths, and 109 000 surviving infants with a clinical diagnosis.
South Africa has more recently reported a rise in STIs in Gauteng, and in 2021 the National Institute of Communicable Disease published a report on congenital syphilis in the country.
‘A failure of the healthcare system’
Epidemiologist Alex de Voux, from the University of Cape Town, moderated a session on syphilis at CROI. Speaking to Spotlight between sessions, she said the return of syphilis was “a failure of healthcare systems (in South Africa and abroad) – because we have the tools, we know how to test for it, and we know how to treat it”.
“The most extreme outcomes of congenital syphilis are stillbirths and neonatal deaths. We don’t even really understand the extent of longer term outcomes: neurological complications, skeletal deformations, impaired mental health development… And all of these significant complications arise from an easily preventable infection. Remember, we use penicillin, which has been around for ages. The treatment hasn’t changed in all this time.”
Figures presented at CROI from the US Centres for Disease Control and Prevention (CDC) reported a 76% increase in cases between 2013 and 2017. The WHO estimates that 7.1m people between 15 and 49 were infected with syphilis in 2020.
In 2018, at least 33 927 cases of syphilis were reported in 29 European Union member states, as recorded by the European Surveillance System (TESSy), at a rate of seven cases per 100 000 population.
The reported syphilis rates were nine times higher in men than in women, showing a peak onset age of 25 to 45 years, in men.
Syphilis and HIV
One study presented at the conference surveyed 20 000 MSM (men who have sex with men) across 10 cities in India, noting dramatic increases in syphilis in every city. It found syphilis was most prevalent in older MSM, pointing to a need for STI control efforts in this population.
“Among people with HIV, syphilis infection was associated with elevated (HIV) viral loads, raising concerns for transmission of HIV,” the study authors wrote.
Another study in Cologne, Germany, investigated 60 patients co-infected with syphilis and acute HIV. The study cites “rising co-infection rates and the unique interaction between these two sexually transmitted infections”.
“Syphilis enhances HIV transmission and acquisition, while HIV accelerates the progression of syphilis…”
An ancient condition, the oldest artistic representation of syphilis is considered to be on a Peruvian jug dating back to the 16th century, depicting a mother suffering from syphilis holding a child. But infections dropped sharply with the availability of penicillin in the 1940s.
However, over the past two decades, scientists have reported an alarming spike in cases. This has been attributed by some to a drop in condom use. The reasons for a decrease in condom use is not clearly understood – one possible factor is a false sense of security, given lower HIV transmission rates, effective HIV treatment, and the availability of HIV transmission prevention in the form of pre-exposure prophylaxis (PrEP).
PrEP contains a combination of two antiretroviral medicines which are highly effective at preventing HIV infection when taken as prescribed by people without HIV, while not offering protection against other STIs like syphilis. Access to condoms may also be a factor.
In South Africa, the number of condoms distributed by the government has decreased dramatically over the past five years.
Sex partners
Risk factors associated with acquired syphilis are sexual behaviour, serosorting (a strategy that involves selecting sexual partners of the same HIV status) among people with HIV, multiple sexual partners, the use of PrEP to compensate for HIV risk behaviour, and dating apps.
Dr Angélica Espinosa Miranda, STI unit co-ordinator at the Brazilian Ministry of Health, told CROI delegates that under-diagnosis of syphilis in pregnancy, especially in regions with limited healthcare access, was a huge factor.
This resonates with De Voux’s research in South Africa, which found congenital syphilis cases to be gravely under-reported.
Congenital syphilis is a notifiable condition in this country: if a doctor delivers a baby believed to be infected, by law, this must be reported to the NICD.
De Voux’s study found that the number of reported congenital syphilis cases in the healthcare system between January 2020 and June 2022 – 36 cases for every 100 000 live births – was at least half the figure estimated by WHO scientists, bolstering the hypothesis of a high number of undiagnosed syphilis cases here.
The 2021 NICD report found that from 1 July 2017 to 31 December 2020, there were 794 clinical notifications of congenital syphilis and 11 170 RPR positive results from infants/ children < 2 years (RPR, or rapid plasma reagin, is the blood test used to screen for syphilis).
“Over this period there was a steady increase in both the number of clinical notifications and the number of RPR positive results from infants/ children,” it read.
The increase was despite the National Strategic Plan for HIV, TB and STIs (2017-2022) setting out to “virtually eliminate congenital syphilis by reducing incidence to 50 or fewer cases per 100 000 live births”.
Shortly after the report’s release, speaking at a webinar on Prevention of Mother-to-Child Transmission of Communicable Infections hosted by the National Department of Health, Dr Neil Moran said rates of syphilis had spiralled over the years and had adverse outcomes on the foetus and on the baby.
“We have a syphilis epidemic,” he said. Moran is head of clinical obstetrics and gynaecology in the KwaZulu-Natal Department of Health.
More recently, in the SA Journal of Child Health, paediatric experts P Appalsamy and N Naidoo, from the University of KwaZulu-Natal, wrote that congenital syphilis should be a medical rarity by now, but the recent global resurgence, despite preventive measures and effective treatment, has had significant impact on health systems, with existing data on the burden of congenital syphilis and preventable factors coming mainly from developed countries.
In a retrospective chart review of 46 mothers and their 47 newborns admitted to the nursery at Prince Mshiyeni Memorial Hospital, Durban, between January 2018 and March 2021 with symptomatic congenital syphilis, they found that 12 (26%) of the infants died – 50% of them within 24 hours of birth.
Factors associated with death were hydrops fetalis, seizures, low Apgar scores and the need for resuscitation at birth, they wrote, and the average length of stay was 19.7 days. Nineteen neonates required admission to ICU for invasive ventilation, 13 required non-invasive ventilation, and 14 required inotropic support.
They wrote that most mothers accessed antenatal care (83%), with 71% testing negative for syphilis at booking. Inadequate treatment of the partner, untreated and inadequately treated maternal syphilis, lack of follow-up testing plans with absent repeat testing at 32-34 weeks’ gestation were the main modifiable factors.
The authors said their study highlighted the burden of disease in the neonatal population as reflected by the need for intensive care, a prolonged hospital stay and predictors of mortality.
Health system failures are related to maternal testing, treatment and tracing, they added, and strengthening of existing programmes and measures like extended re-testing protocols and mass treatment of sexually active adults needed to be explored to curb the rise of congenital syphilis.
Penicillin treatment
Miranda said ensuring infected pregnant women receive timely and appropriate penicillin treatment is critical to preventing congenital syphilis. “It’s the only effective treatment during pregnancy. But challenges remain, like limited healthcare access and penicillin shortages in some countries.”
When penicillin cannot be used (due to unavailability or allergy in a patient) the WHO’s STI guidelines suggest using doxycycline 100 mg twice daily orally for 30 days.
Worldwide penicillin shortages are also affecting South Africa. De Voux said clinics and hospitals try to make sure stocks prioritise pregnant women.
“But that means that sometimes other infected people are treated with something much more burdensome. Instead of penicillin injections, they get tablets – doxycycline – which has gastrointestinal side effects, so ….an upset stomach. You have to try to minimise the side effects with food.”
The experts stressed the need to invest in developing new strategies – antibiotics apart from penicillin – to treat syphilis, saying a vaccine is crucial but agreeing that this scientific solution remains elusive.
Congenital-Syphilis-Quarterly-Surveillance-Report
Spotlight article – Syphilis rates are spiking around the world (Creative Commons Licence)
Spotlight article – In-depth: The state of congenital syphilis in SA (Creative Commons Licence)
See more from MedicalBrief archives:
Gauteng Health flags rise in STI infections
Alarm at spiralling number of US babies born with syphilis
Meta-analysis of STI prevalence in sub-Saharan Africa
New STI guidelines emphasise screening