Is eradication of congenital syphilis feasible?
05/03/2012 Comments Off on Is eradication of congenital syphilis feasible?
On 1 March, the Global Congenital Syphilis Partnership held a press conference to announce the launch of a global campaign to eradicate congenital syphilis, motivated by evidence from a seven-country pilot study that used a rapid blood test for screening. The aim of the studies was to test pregnant women for syphilis, treat any who were positive early in their pregnancies to avoid transmission of syphilis to their babies during pregnancy, and where possible also test and treat their husbands/partners.
If pregnant women are screened and treated as required in an antenatal visit early in pregnancy, congenital syphilis will be treated in the woman and prevented in the infant, but this is only as long as the woman is not re-infected during the rest of her pregnancy. To avoid that, her partner needs to be tested with her and both need to have an injection of penicillin if positive for syphilis. If the woman has more than one partner, then contact tracing and screening will also be needed.
Screening of pregnant women for syphilis is a long-time public health measure, and has been recommended as a routine antenatal test by WHO and other national, regional and global public health bodies for many decades now. However, periodic studies in the latter half of the 20th century showed that many women are not screened during antenatal care, others have not returned for their results, and still others are not screened because they have not attended for antenatal care at all, or only very late. Hence, efforts to eliminate congenital syphilis have failed. Although in most countries the rates appear to have been falling over the years, the burden of disease remains heavy.
Untreated syphilis in pregnancy leads to adverse pregnancy outcomes in more than half the women with active disease, including early fetal loss, stillbirth, prematurity, low birthweight, neonatal and infant death and congenital disease among newborn babies. Similarly to HIV, syphilis in pregnancy is both sexually transmitted and transmitted through blood in shared needles by injecting drug users. Testing for both syphilis and HIV at the same time makes good sense in antenatal care settings, since the blood taken to screen for syphilis can also be tested for HIV, though treatment modalities are of course quite different.
In 2008, the latest year for which global data are available, approximately 1.9 million pregnant women were infected with active syphilis resulting in approximately 300,000 stillbirth sor early fetal losses, 140,000 neonatal deaths, and 380,000 infants that were preterm, of low birthweight, or had congenital disease associated with syphilis.
Several new factors mean that it is becoming more feasible to lower these rates. First, the development of a rapid blood test for syphilis means health workers can get a result in only a few minutes without the need for laboratory facilities, as the kit includes a built-in testing mechanism. If the test is positive for syphilis, an injection of penicillin can be given immediately. This is sufficient as treatment, and as long as there is adequate availability of penicillin, and unless re-infection is a risk, does not require follow-up.
The other important facilitating factor is that more and more women in the developing world are attending for antenatal care, and more often making more than one visit. Ensuring that all of them are tested is a major task, however. According to a 2011 WHO report:
“In 2010, 63 low- and middle-income countries reported on the proportion of women attending antenatal care tested for syphilis at the first visit. In this subgroup, 17 low- and middle-income countries reported having achieved the global target of testing at least 90% of women attending antenatal care at the first visit for syphilis (Belize, Chile, Cuba, Fiji, Gabon, Grenada, Guyana, Kiribati, Malaysia, Mauritius, Namibia, Oman, Samoa, Seychelles, Sri Lanka, Uruguay and Venezuela (Bolivarian Republic of)). Overall global median testing coverage did not improve from 2008 to 2010 (Table 7.2). Nevertheless, median testing coverage improved in Latin America and the Caribbean (from 73% in 2008 to 80% in 2010) and in East, South and South-East Asia (from 52% to 78%). In 27 reporting countries from sub-Saharan Africa, a median of only 59% of pregnant women were tested for syphilis. Eight low- and middle-income countries reported not offering routine syphilis screening in antenatal care in 2010.”
Hence, there are big “ifs”. Shortages of essential medicines are well known. And re-infection is often a risk because husbands and other sex partners historically were often not tested and treated at the same time as the woman, or at all. To get most partners into antenatal clinics for testing will be one of the more difficult challenges for antenatal programmes, and may not be seen as a priority, given all the other demands on antenatal care these days which are not being met, such as the need for more trained midwives. Other cadres of health workers can be trained to do the test and give injections, but this too would take resources and people and time.
I am concerned that the new Global Congenital Syphilis Partnership is about congenital syphilis and therefore neonates only, and that the UNAIDS-led Global Plan toward the Elimination of New Infections among Children by 2015 and Keeping Their Mothers Alive, launched last year, which includes a global initiative to eliminate congenital syphilis, is about women and children only. But shouldn’t women and men be the focus of treatment in order to prevent syphilis in neonates? Luckily, unlike with PMTCT, efforts to reduce congenital syphilis must treat the pregnant woman to protect the fetus but will programmes also bring in the men?
My other concern is the use of the words “eradicate” and “eliminate” in the descriptions of the goals of this and other initiatives, such as the prevention of mother-to-child transmission of HIV, also in the UNAIDS Global Plan, and the so-called “Golden Moment” in relation to unmet need for family planning. The Americas and the Asia-Pacific region and several countries have developed integrated initiatives to eliminate mother-to-child transmission of both HIV and syphilis, given their common target groups and service delivery platforms.1
Can these new global health initiatives make such massive advances in reducing major disease burdens in a few short years that they will be able to eradicate or eliminate them? Do they think such claims are necessary to gain credibility? Smallpox is the only disease that has ever been eradicated to date. Should we not continue to occupy the more cautious terrain of public health agencies and experts in terms of expectations? Perhaps this is an old-fashioned view.
The figures for declines in neonatal deaths are encouraging, even if they are happening less quickly than other infant and child mortality declines. In 2009, an estimated 3.3 million babies globally died in the first month of life, compared with 4.6 million in 1990. This is in spite of world population growth. More than half of all neonatal deaths occurred in five countries of the world (which also account for 44% of global live births): India 27.8% (19.6% of global live births), Nigeria 7.2% (4.5%), Pakistan 6.9% (4.0%), China 6.4% (13.4%), and Democratic Republic of the Congo 4.6% (2.1%). Between 1990 and 2009, the global neonatal mortality rate declined by 28% from 33.2 deaths per 1,000 live births to 23.9. The proportion of child deaths that are in the neonatal period increased in all regions of the world, and globally is now 41%. Thus, neonatal mortality rates were halved in some regions of the world, though Africa’s rate only dropped 17.6% (43.6 to 35.9). These reductions are impressive and give much hope of future successes.
At the press conference, Peter Piot, formerly head of UNAIDS and now head of the London School of Hygiene & Tropical Medicine (LSTHM), in his introduction, described treatment of congenital syphilis as a low-hanging fruit, and Joe Cerrell, representative of the Bill & Melinda Gates Foundation for Europe, said, referring to the new test kits: “We have a simple solution to save a million children’s lives each year.”
Rosanna Peeling from LSHTM handed out a Rapid Syphilis Toolkit produced by the School and reported that 30 countries have already started scaling up rapid antenatal syphilis/HIV tests. She talked about wanting to avoid “more vertical programming” with this new programme. However, her definition of an “integrated programme” in this instance was the two-for-one combination of syphilis and HIV testing of pregnant women at one go. Given the limitations of antenatal care and the real meaning of integration, this is hardly it. The seven country studies have not yet been published, however, and details of what this does mean in practice were not provided.
In the pilot programme in Brazil, presented by Adele Benzaken, in the Amazon region they have shown that it is possible to do these tests in a very rural, hard-to-reach region. Yet they will have to test and treat two million pregnant women and their partners each year. Brazil has got a Brazilian pharmaceutical company to produce the test kits, thus controlling cost, and are funding 95% of the programme themselves (Simone Diniz, personal communication). Given their success with HIV, again optimism is warranted.
In China, the head of the National STD Control Programme said that it was precisely in the rural areas of the country that they have a major outreach problem that must be solved. China thought they had eradicated syphilis, but it returned in the 1980s. With the mass internal migration that has taken place in China in recent decades, eradication may be more difficult, especially since migrant women do not have access to health insurance and get far poorer maternity care.
“Eradication” or “elimination” of congenital syphilis, rather than “control” has a very different meaning and implications. To achieve eradication of syphilis in women and children, according a paper by specialists from the Centers for Disease Control and Prevention (USA), published in RHM in 1995, you need:
- a control measure that is completely effective in breaking up transmission
- effective case detection and surveillance
- recognition of the disease as of socioeconomic importance in the countries concerned
- reasons to attempt eradication as opposed to control
- adequate financial, administrative, person power and health service resources, and
- the necessary socio-ecological conditions.
Most low-resource countries couldn’t possibly meet these conditions. Still, syphilis in pregnant women could be reduced far more if antenatal care programmes were doing what all the guidelines and protocols have been telling them for years that they’re supposed to be doing – a range of antenatal screening tests that include not only syphilis and HIV, but also screening and treatment for anaemia, malaria and TB, and all the other checks that contribute to healthy pregnancies and babies.
What was not raised at all in the press conference were other STIs, in addition to syphilis and HIV. More than 448 million new cases of four bacterial STIs – gonorrhoea, chlamydia, and trichomoniasis as well as syphilis – are estimated to have occurred in 2005 alone. These also contribute to major morbidity and even mortality. The point was made in this press conference that when HIV testing was made the screening priority in pregnancy by the global AIDS community, a lot of routine syphilis testing stopped. We should take good note, since this is a prime example of why so many of us working in health believe that vertical programming is a big mistake.
 The test used in the pilot studies, carried out by the London School of Hygiene & Tropical Medicine, cost US $1 per kit. However, in Brazil, where one of the studies took place, a national pharmaceutical company is producing their own test kits for use in scaling up the programme, whose price is likely to be far lower (Simone Diniz, personal communication 24 February 2012).
 Oestergaard MZ, Inoue M, Yoshida S, et al. Neonatal Mortality Levels for 193 Countries in 2009 with Trends since 1990: A Systematic Analysis of Progress, Projections, and Priorities. PLoS Medicine 2011. http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001080.Mikkel Oestergaard and colleagues develop annual estimates for neonatal mortality rates and neonatal deaths for 193 countries for 1990 to 2009, and forecasts into the future.
 For a discussion of this sort of assessment of complex health issues in: Richard F, Hercot D, Ouédraogo C, et al. Sub-Saharan Africa and the health MDGs: the need to move beyond the “quick impact” model. Reproductive Health Matters 2011;19(38):42–55.
 RHM has a paper in press for May 2012 that illustrates this in relation to declines in maternal mortality in Shanghai.
 Kennedy MG, Spink Neumann M, Fichtner RR, et al. Can we eradicate syphilis in pregnant women and newborns? Should we try? Reproductive Health Matters 1995;3(6):94–103.
 World Health Organization.Prevalence and incidence of selected sexually transmitted infections: Chlamydia, Neisseria gonorrhoeae, syphilis and Trichomonas vaginalis. Geneva: WHO, 2011.