Strategies and missed opportunities in achieving triple elimination of mother-to-child transmission (EMTCT) of HIV, syphilis, and hepatitis B virus: a scoping review

Strategies and missed opportunities in achieving triple elimination of mother-to-child transmission (EMTCT) of HIV, syphilis, and hepatitis B virus: a scoping review | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Strategies and missed opportunities in achieving triple elimination of mother-to-child transmission (EMTCT) of HIV, syphilis, and hepatitis B virus: a scoping review Fikir Kibret , Morkor Newman Owiredu , Caitlin Quinn , Magdalena Barr-DiChiara , Olufunmilayo Lesi , Niklas Luhmann , Chelsea Morroni , Agnes Chetty , Akudo Ikpeazu , Casimir Manzengo Mingiedi , Deyer Gopinath , Cheryl C. Johnson , Aliza Monroe-Wise , View ORCID Profile Alison L. Drake doi: https://doi.org/10.1101/2025.06.26.25330370 Fikir Kibret 1 Department of Global Health, University of Washington , Seattle, WA, United States Find this author on Google Scholar Find this author on PubMed Search for this author on this site Morkor Newman Owiredu 2 Department of Global HIV , Hepatitis and Sexually Transmitted Infections Programme, World Health Organization, Geneva, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Caitlin Quinn 2 Department of Global HIV , Hepatitis and Sexually Transmitted Infections Programme, World Health Organization, Geneva, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Magdalena Barr-DiChiara 2 Department of Global HIV , Hepatitis and Sexually Transmitted Infections Programme, World Health Organization, Geneva, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Olufunmilayo Lesi 2 Department of Global HIV , Hepatitis and Sexually Transmitted Infections Programme, World Health Organization, Geneva, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Niklas Luhmann 2 Department of Global HIV , Hepatitis and Sexually Transmitted Infections Programme, World Health Organization, Geneva, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Chelsea Morroni 3 Centre for Reproductive Health, University of Edinburgh 4 Botswana Harvard Health Partnership Find this author on Google Scholar Find this author on PubMed Search for this author on this site Agnes Chetty 5 HIV, Tuberculosis and Hepatitis Programme, World Health Organization , Africa Regional Office Find this author on Google Scholar Find this author on PubMed Search for this author on this site Akudo Ikpeazu 5 HIV, Tuberculosis and Hepatitis Programme, World Health Organization , Africa Regional Office Find this author on Google Scholar Find this author on PubMed Search for this author on this site Casimir Manzengo Mingiedi 6 Department of Global HIV , Hepatitis and Sexually Transmitted Infections Programme, World Health Organization, Afro Regional Office Find this author on Google Scholar Find this author on PubMed Search for this author on this site Deyer Gopinath 5 HIV, Tuberculosis and Hepatitis Programme, World Health Organization , Africa Regional Office Find this author on Google Scholar Find this author on PubMed Search for this author on this site Cheryl C. Johnson 2 Department of Global HIV , Hepatitis and Sexually Transmitted Infections Programme, World Health Organization, Geneva, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Aliza Monroe-Wise 2 Department of Global HIV , Hepatitis and Sexually Transmitted Infections Programme, World Health Organization, Geneva, Switzerland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alison L. Drake 1 Department of Global Health, University of Washington , Seattle, WA, United States Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alison L. Drake For correspondence: adrake2{at}uw.edu Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF ABSTRACT Eliminating mother-to-child transmission (EMTCT) of HIV, syphilis, and hepatitis B virus (HBV) is a global public health priority. Despite progress towards reducing rates of mother-to-child transmission (MTCT) of HIV, global progress toward EMTCT of syphilis and HBV remains suboptimal. We systematically searched records in PubMed capturing the synergistic challenges and potential strategies in achieving triple EMTCT between January 1, 2013, and April 27, 2023. After screening 547 records, 50 reports met inclusion criteria. Overall, testing for HIV was well-established within antenatal care but limited for syphilis and HBV due to poor political support, inadequate funding, and insufficient operational guidance on how to deliver integrated testing within maternal and child health care. MTCT of syphilis and HBV appears to be impeded by lack of integrated systems to enable test-and-treat approaches with same-day test results and immediate treatment initiation, gaps in linkage to care, frequent stockouts of essential drugs and other commodities, prohibitive user fees, and limited clinical familiarity and training of staff in managing syphilis and HBV positive cases. To achieve triple EMTCT, co-strategies that leverage success of HIV programs to gain momentum towards prevention of congenital syphilis and MTCT of HBV, that break down siloed programs by co-delivery of testing, treatment, and training and that are supported through political will, advocacy, policy and funding are critical. INTRODUCTION Triple elimination of [vertical] mother-to-child transmission (EMTCT) of HIV, syphilis, and hepatitis B virus (HBV) is a global public health priority. All three infections are key drivers of maternal and infant morbidity and mortality. 1 – 4 Sequelae of perinatal infections can include immunosuppression and poor growth and development during early childhood following HIV infection, stillbirths and central nervous system abnormalities resulting from congenital syphilis, and chronic liver disease resulting from neonatal HBV. Substantial progress has been made towards EMTCT of HIV, with transmission rates as low as 2-4% in some sub-Saharan African countries, the region most impacted by the HIV. 5 As of 2024, 16 countries have been validated for elimination of HIV and/or syphilis by the World Health Organization (WHO), one for EMTCT of HIV alone, one for syphilis alone 6 , and 14 countries have achieved dual EMTCT of HIV and syphilis; but no countries have achieved elimination of congenital HBV. 6 – 10 Furthermore, no sub-Saharan country has achieved EMTCT for any of these three infections, despite the majority of infections occurring in this region. However, two countries have achieved the path to elimination designation for triple elimination, Botswana in 2021 11 and Namibia in 2023. 12 The rationale to combine efforts to achieve elimination for HIV, syphilis, and HBV infections is strong since these infections are all sexually and vertically transmitted, may present as asymptomatic in women or may have a long latency period, and can be identified and treated through “test-and-treat” approaches during pregnancy and breastfeeding to prevent vertical transmission. 13 With recent funding cuts impacting services globally, integration of services is more vital than ever. Prevention of congenital syphilis and HBV may leverage successful strategies used to reduce vertical HIV transmission rates, largely focused on testing and treating pregnant and postpartum women for HIV. Siloed approaches focused on preventing vertical HIV, syphilis, or HBV transmission independently fail to harness the potential of synergistic prevention efforts and are more costly. Identifying strategies that leverage existing systems, infrastructure, and resources—which largely exist for HIV—to achieve cross-cutting goals for the triple elimination of vertical transmission of HIV, hepatitis B, and syphilis can be cost-effective and will be critical for its success. Yet, recognizing that unique aspects of the prevention, diagnosis, and management of each infection also add complexity. Novel and innovative strategies will also be necessary to achieve triple elimination. We conducted a scoping review to gather ideas and perspectives about challenges and strategies for triple elimination. METHODS Search strategy, selection process, and data extraction We reviewed records published in PubMed between January 1, 2013, and April 27, 2023, to identify strategies that are, or could be, used to achieve dual or triple EMTCT, as well as identify challenges and gaps. We used the following combinations of search terms: ‘(eliminate OR prevent OR testing OR diagnose OR immunization OR treat) AND (vertical transmission OR mother-to-child transmission OR infectious pregnancy complication) AND HIV AND (syphilis OR hepatitis B)’ and applied filters to restrict publications between 2013 and 2023. Additionally, we included one guidance document and one publication recently released that the authors were previously aware of which presented strategies toward triple elimination. This approach was designed not to holistically identify all prevention strategies individually for HIV, syphilis, and HBV, but rather publications that were focused on strategies and challenges for dual and triple elimination, specifically. Publications could include commentaries, editorials, reviews, briefs, guidance documents, or original research. One reviewer (FK) screened titles and abstracts from selected titles on elimination of HIV syphilis, and/or HBV. Records were eligible for full-text review if they included information on strategies or challenges with EMTCT of HIV and at least one other infection (syphilis or HBV) and had titles and abstracts in English. Publications without abstracts (commentaries, research letters, editorials, correspondence, and research papers) were reviewed in full-text for eligibility. Full-text records were excluded from this scoping review if they reported on 1) the prevalence of HIV, syphilis, and/or HBV in pregnant women without strategies or challenges used for preventing vertical transmission; or 2) individual-level risk factors for prevention, testing, treatment, or linkage to care for of HIV, syphilis, and/or HBV. We used a standardized form to extract data on strategies and challenges to vertical transmission, stratified by intervention categories (primary prevention, testing, treatment, and linkage to care) and population (pregnant women, infants, and partners) (Supplementary File 1). One independent reviewer (FK) reviewed the full-text articles for inclusion and exclusion and extracted relevant data into relevant categories, and a second independent reviewer (ALD) reviewed the extracted data and categorization ( Supplementary Tables 1 -4).Two reviewers (ALD and AMW) conducted a content analysis of the extraction sheet, and classified findings based on themes of vertical transmission strategies and missed opportunities, and created a consolidated summary as shown in Table 1 . View this table: View inline View popup Table 4: General challenges, strategies, and progress in EMTCT View this table: View inline View popup Supplementary Table 1: Challenges, strategies, and progresses in testing to achieve triple EMTCT View this table: View inline View popup Download powerpoint Supplementary Table 2: Challenges, strategies, and progress in treatment and linkage to care to achieve EMTCT View this table: View inline View popup Download powerpoint Supplementary Table 3: Challenges, strategies, and progress in prevention View this table: View inline View popup Table 1: Strategies and missed opportunities for triple elimination RESULTS Out of 549 unique citations identified, 50 were included in this review ( Figure 1 ). Overall, 37 represented reports from specific geographical locations [the Americas (26%, 13/50), Africa (24%, 12/50), Asia (Western Pacific: 20%, 10/50 and South-East Asia: <1%, 2/50)], while the remaining 13 reports were either cross-regional, reviews, or expert opinions. Publications broadly focused on challenges, missed opportunities, and strategies in the following eight domains: 1) access and demand; 2) capacity building; 3) testing services, laboratory capacity, and infrastructure; 4) advocacy, policy, and funding; 5) supplies and supply chain; 6) prevention services; 7) treatment services; and 8) reporting and monitoring ( Table 1 ). Download figure Open in new tab Figure 1: Flow diagram for record selection Access and demand Challenges & missed opportunities While timely presentation to care promotes early detection, treatment, and initiation of interventions to maximize efforts to prevent MTCT of HIV, syphilis and HBV, delays in care occur for several reasons. Late first ANC attendance is one challenge. 14 In addition to limited access to ANC services, lack of awareness among pregnant women about the risks associated with MTCT of HIV, syphilis, and HBV infections during pregnancy; the perception of testing as costly, complex, and time-consuming; 15 and fear of encountering stigma upon receiving positive HIV or syphilis results 16 also pose substantial barriers to testing acceptance at ANC visits. Anxiety about receiving positive test results, particularly for HIV, due to concerns about stigma, societal prejudice, or abandonment by male partners was also identified as a critical barrier to accept HIV/syphilis testing. 14 , 16 – 18 Other aspects of partnerships that hinder testing coverage included the need for women to seek partner or spousal approval before HIV/syphilis testing in cultures considered patriarchal, and financial dependence on male partner. 16 For HBV, challenges reported in sub-Saharan Africa extend beyond awareness into lack of testing for HBeAg and HBV DNA tests. 19 Tests are largely too expensive and unavailable. HBV birth dose may be available in some settings, but similar to testing for HBV, lack of familiarity of HBV is compounded by the lack of availability of HBV birth doses at facilities where women deliver, as well as no clear distribution plan for women who deliver outside healthcare facilities. 19 Strategies Targeted educational campaigns to raise community awareness about the need and health benefits of early ANC visits; risks of MTCT of HIV, HBV, and syphilis; and available services to prevent MTCT of these infections have been proposed as a potential strategy that could improve rates of early ANC testing. 20 Improving ANC access and affordability at community- and primary-care levels of healthcare systems and promoting rapid diagnostic tests (RDTs) as a strategy to facilitate same-day testing and support task-shifting might help prevent delays in seeking ANC due long distance to healthcare facilities. 20 Capacity building Challenges & missed opportunities Understaffing, high staff turnover, lack of familiarity of HCWs about triple elimination, and unwelcoming attitudes of healthcare providers toward pregnant women (often as a result of heavy patient loads) are also barriers to achieving EMTCT targets. 16 , 18 – 24 Training for PMTCT of HIV has been complemented with implementation of programs that have integrated HIV testing and treatment into routine MCH services; however, providers lack knowledge and familiarity with clinical algorithms for testing and treating maternal syphilis and HBV. Strategies Broadening service provisions through task-shifting 20 and refresher courses for HCWs 14 have been proposed as a mechanism to improve efforts at dual HIV/syphilis elimination; however, adding content related to HBV could also help prevention efforts focus on triple elimination. 25 Other proposed strategies to augment capacity to deliver triple EMTCT include improving equitable access to point of care testing for pregnant women (particularly in remote settings) through community healthcare workers and task shifting; 26 increasing the proportion of deliveries with a skilled birth attendant; 21 , 25 and making EMTCT services readily available to all levels of healthcare facilities, including health centers. 20 Testing services, laboratory capacity, and infrastructure Challenges & missed opportunities Several challenges to achieving high test coverage for HIV, syphilis, and HBV in ANC settings have been identified. The lack of availability of dual HIV/syphilis RDTs has been identified as a common challenge to achieving high syphilis test coverage, and HBsAg RDTs to detect maternal HBV infections are not widely available, making uptake at the country-level low. 19 Additional testing is recommended for both HBV and syphilis infection after initial positive RDT results (DNA viral load or HBV envelope antigen (HBeAg) testing for HBV, and treponemal (FTA, TP-PA, EIA) testing for syphilis), and centralized laboratories are often used for these tests. However, the cost and laboratory infrastructure required to conduct these assays are significant barriers to testing; therefore, routine implementation is uncommon. 15 19 Furthermore, the time required for confirmatory testing can be an additional barrier to linkage to care and treatment. Additionally, the absence of a WHO-prequalified HBeAg RDT product and lack of access to HBV DNA testing may contribute to low uptake of additional testing prior to antiviral prophylaxis. 19 For both HBV and syphilis testing, out-of-pocket expenses are additional barriers to testing in some settings. 19 For HIV-exposed infants (HEI), early infant diagnosis (EID) programs aimed at testing infants at 4-6 weeks of age can aid in identification and rapid initiation of life-saving treatment for infants who acquire HIV. Yet, loss to follow-up, inadequate health systems, testing delays, and poor social support may contribute to low EID rates among HEI, particularly in African settings where HIV prevalence is higher. 19 14 Strategies The dual HIV/syphilis RDT has been proposed as one strategy to overcome limitations with laboratory capacity and infrastructure, healthcare provider burden to administer separate tests, and to close the gap in syphilis test coverage by leveraging HIV testing infrastructure. The dual RDT has excellent clinical performance, 21 , 27 is cost-effective, saves providers and patients time, 28 – 31 and results in higher acceptability and test coverage compared to separate tests for HIV and syphilis. 32 It has been recommended as a first-line HIV test in ANC by WHO since 2019 and is increasingly available in many contexts and settings. Funding for the dual RDT is covered under programs that support HIV services, which reduces barriers to financing syphilis testing in many countries,. 19 Incorporating testing for all three infections into existing MCH programs, ideally with a single RDT, could improve antenatal testing coverage for syphilis and HBV. 33 – 37 Triple HIV/syphilis/HBV RDTs are available and could be a significant intervention to improve coverage, but the quality of existing tests varies and the absence of a WHO prequalified test creates procurement challenges for countries, which limits accessibility. To improve coverage of early EID for HIV, specialized postnatal clinics, diagnostic tests with faster turnaround times, active follow-up through advocates or health workers, and integration of testing into routine child health programs have all been proposed. 14 Many HCWs operating within HIV PMTCT programs are aware of the benefits of referring male partners of pregnant women for HIV testing, either as individuals or couples, and treating partners who test positive for HIV. However, HCWs are less familiar with male partner testing and treatment for syphilis, making these practices more uncommon. 38 Refresher courses for HCWs have been proposed to raise awareness about the role of partner testing and treatment for congenital syphilis prevention. 14 Switching from an HIV RDT to a dual RDT to test male partners for both HIV and syphilis could be a strategy to build upon partner testing services for HIV and gain test coverage for partners. While some LMICs have free and universal access to syphilis treatment, including treatment of partners as an integral component of triple EMTCT, 35 out-of-pocket fees for syphilis treatment remain as a barrier to treating partners. Advocacy, policy, and funding Challenges & missed opportunities Strong levels of advocacy, normative guidance, and financial support for HIV EMTCT interventions have significantly helped countries advance towards achieving EMTCT for HIV. In contrast, financial and political support for preventing congenital syphilis has been relatively lower, 16 , 18 , 21 a and the national and global efforts to support EMTCT of HBV are substantially weaker. 19 Specific reasons for lack of funding for syphilis and HBV EMTCT include competing health priorities, financial diversion for public health emergencies such as the COVID-19 pandemic, 39 , 40 and siloed funding. 41 , 19 , 20 , 42 Despite the promise of enhanced support and policies for prevention of congenital syphilis, implementation is still comparatively weak compared to PMTCT of HIV. 19 , 20 , 42 , 43 Sub-optimal advocacy for congenital syphilis at national and global levels 21 , 24 , 44 also pose threats to achieving EMTCT. In addition, triple EMTCT efforts can also be hindered by punitive laws that limit access to sexual and reproductive healthcare services for certain populations (i.e., youth and immigrants). 40 Therefore, avoidance of coercion and legal restrictions on EMTCT service utilization may improve EMTCT efforts. 25 Strategies Political commitment and financial support are pillars to achieve EMTCT targets. For example, Cuba’s strong political commitment and dedicated national funding have been cited as enabling factors in achieving EMTCT targets for HIV and syphilis. 25 In addition, in randomly selected health facilities that introduced an “Early Essential Newborn Care in eight countries in the Western Pacific Region, national and concerted efforts to address all three infections by leveraging existing MNCH care and integrated care, offering free testing and treatment/prophylaxis for HIV, syphilis, and HBV resulted in in HBV birth-dose coverage exceeding 80% in all but one country. 47 However, antenatal HIV test coverage remained low (<40%) for six countries. 47 China, however, was able to achieve 100% coverage for both maternal HIV and syphilis testing in ANC, as well as 100% coverage for HBV birth-dose and found MTCT of HIV fell over four years from 8.1% to 6.7% with strong governmental leadership and support. 33 , 47 The adoption of national programs and policies, which recommend the integration of HIV/STI services within the package of ANC services, 45 along with the commitment of several countries to adopt strategies and guidelines for eliminating congenital syphilis, has allowed countries to substantially increase syphilis testing without adversely impacting HIV testing among pregnant women in primary care facilities, and address procurement issues necessary for massive programmatic scale-up. 21 , 46 Similar strategies could be employed to increase policy adoption and political support for HBV EMTCT. Supplies and supply chain Challenges & missed opportunities Overarching challenges affecting testing, treatment, and prevention for all three infections limit capacity to achieve EMTCT. These include siloed programs 14 , 24 , 41 that are less efficient and lack the ability to capitalize on shared resources and prevention strategies, limited laboratory capacity, and challenges with managing separate supply chains for separate EMTCT programs. Complex supply chain management is also a challenge with the dual RDT as algorithms are required to identify women who would be ineligible to test with the dual RDT, including WLWH and/or women with a recent syphilis diagnosis, creating difficulties with forecasting for the quantity of supplies required for each test. 41 Strategies Programs could benefit from streamlining service delivery through integrated testing and treatment, overcoming problematic silos that add time, complexity, and human resource demands. 33 , 34 , 47 Supply chains can be easier to monitor and track if they are cohesive and channeled through a universal triple elimination program, which would include factoring in complex procurement needs to test for all infections in a triple RDT, a dual test for HIV/syphilis, and multiple tests for each infection tests based on eligibility for triple or dual RDTs. This approach would help monitor inventory more closely though one program and avoid stockouts of test kits and supplies. For HBV, support from GAVI to supply the HBV birth dose is the key strategy to make meaningful inroads towards expanding access in settings where it is not available 19 . Prevention services Challenges & missed opportunities Oral tenofovir (TDF) is not only an effective HBV treatment but can also be used for maternal prophylaxis to prevent PMTCT. Limited availability of TDF monotherapy in LMICs has previously been shown to be problematic for HBV treatment, but is also a challenge for expanding coverage of for HB PMTCT. 19 Furthermore, HIV programs fail to fund TDF monotherapy further hindering availability. 19 High coverage of HBV birth dose vaccination contributes to elimination of vertical HBV transmission, but coverage remains very low in most LMICs. 19 In a survey conducted in 16 high-burden countries in sub-Saharan Africa, only six reported providing the HBV birth dose vaccine within 24 hours of birth. 19 HBV birth dose vaccinations are even more challenging for infants born outside of health care facilities. Few countries have policies supporting HBV birth dose vaccinations, and policy changes are necessary to incorporate HBV birth dose vaccination into national guidelines. 43 Furthermore, Although GAVI has endorsed introducing the HBV birth dose vaccine, implementation delays and lack of availability of supplies necessary to offer these vaccines underscore the importance of improving coordination between international entities and governments to ensure a prompt and efficient rollout; and GAVI will only cover costs of implementation - not commodities. 19 Additionally, confusion between HBV birth dose and the HBV vaccine provided as part of a 3-dose pentavalent or hexavalent vaccine series available to infants at 4-6 weeks of age have also created challenges to HBV birth dose coverage. 19 , 43 Notably, our search did not return results for challenges or missed opportunities for maternal PrEP, likely due to the nature of the search which only included challenges and strategies for dual infections—HIV and syphilis, or HIV and HBV. Strategies Oral TDF is already included in first-line ART regimens for HIV treatment, and in some formulations of oral PrEP for HIV prevention (typically co-formulated with emtricitabine (TDF/FTC)), but is not included in long-acting PrEP, nor second-line ART regimens used when first-line regimens fail, or when HIV drug resistance is detected. 19 HIV PrEP formulations that include oral TDF are commonly utilized for treating HBV infections even among HIV-negative women as it is more widely available. 19 Policies supporting community health workers to administer the vaccine during home births could help increase HBV birth dose coverage, particularly in settings where facility delivery rates are low. 19 Co-administration of the HBV birth dose with other birth dose vaccines, such as coupling BCG and OPV with the HBV birth dose as an integrated vaccination campaigns, has the potential to improve HBV birth dose vaccination coverage. 19 However, while the timing of administration is at birth the mode of administration differs for all three of these vaccines (oral, intradermal, and intramuscular injection), which require different service delivery and HCW training requirements, which could present additional challenges to co-administration. Allocation of specific funding within national budgets to HBV birth dose vaccination would also augment coverage, as acknowledgement of HBV birth dose vaccination within national priorities can make vaccination very inexpensive. 19 Finally, providing hepatitis B immunoglobulin (HBIG) to infants born to HBsAg positive mothers with high viremia is an alternative intervention available to protect infants against HBV infection, and has been shown in a modeling study to significantly lower transmission. 34 However, HBIG is expensive, requires adequate cold chain capacity and an efficient procurement system 34 , which might limit its accessibility. Although our review did not include results for maternal HIV PrEP implementation, many opportunities for integration exist both for HIV PrEP implementation within ANC settings, as well as within other prevention or harm reduction services. Treatment services Challenges & missed opportunities Delayed linkage to care following diagnosis, often due to needs for confirmatory testing, presents a significant barrier to early treatment for all three infections. Reasons for delays in linkages can also be attributed to siloed delivery of healthcare services, personnel, funding, data reporting systems, and program funding. 15 Insufficient numbers of trained staff, 15 as well as lack of familiarity with care and treatment of pregnant women infected with HBV and/or syphilis also contribute to these delays. 23 , 48 Despite high ART coverage in many communities affected by HIV, there is limited access and uptake to benzathine penicillin G treatment for syphilis, and TDF for women with HBV who require prophylaxis or treatment. 19 While benzathine penicillin G is inexpensive, stockouts hinder prompt treatment. 19 Similarly, TDF monotherapy for HBV treatment is also limited in many LMICs, but is substantially more costly. 19 Strategies To overcome challenges in prompt treatment initiation and linkage to care, potential strategies may include consolidating testing and treatment services for all three infections at a common point of service delivery, financial and human resource mobilization, and providing staff training in the management of pregnant women with these infections. 20 Reporting and monitoring Challenges & missed opportunities Finally, strong systems for monitoring and evaluating appropriate indicators that span the triple EMTCT continuum for women, infants, and partners is imperative to measure progress and barriers to success. 35 , 43 Programs with overstretched HCWs, or lack of funding to support dedicated staff for reporting, may hinder data collection and monitoring, as time and human resources to enter and monitor data may be insufficient with existing resources. Strategies Programs can invest in developing integrated information systems, supporting monitoring and evaluation activities, including surveillance as well as specific reporting systems to capture key indicators to measure progress and impact of incorporating dual testing. One strategy to improve congenital syphilis reporting that utilizes existing infrastructure without the need to develop novel systems, and improve monitoring and evaluation efforts, is the inclusion of congenital syphilis in the Global AIDS Response Progress Reporting System; this strategy could also be effective for HBV. DISCUSSION Progress towards achieving triple EMTCT is inconsistent across HIV, syphilis, and HBV, with the most substantial success in reducing vertical HIV transmission. High coverage of HIV testing during routine ANC and subsequent treatment and prevention interventions have led to marked reductions in new pediatric HIV infections. 32 , 34 – 36 , 49 However, gaps in testing and treatment for syphilis persist, lagging behind HIV, making dual elimination of HIV and syphilis elusive. Efforts to eliminate vertical HBV transmission also remain even more difficult, as HBV is frequently excluded in national guidelines, with subsequent low coverage of testing and treatment of pregnant women and uptake of the hepatitis B vaccine birth dose. Global reductions in funding threaten progress for elimination of vertical transmission of both syphilis and hepatitis B, and opportunities to employ cost-effective integration of services are more important than ever. Despite evidence that integrated EMTCT services can be effective for the prevention of congenital infections, programs tasked with EMTCT of HIV, syphilis, and HBV are often fragmented and not optimized for joint planning and service integration across healthcare programs, leading to inefficiencies and higher costs. Funding disparities exist, with HIV receiving substantially more financial support than syphilis and HBV programs. Without programmatic funding to support services, expenses for syphilis and HBV EMTCT interventions are passed on to women and their families, hindering programmatic integration of care for all three infections. Political will and technical support to prioritize MTCT of HIV led to the expansion of PMTCT programs, while integration of syphilis and HBV interventions into routine ANC services and guidelines have lagged behind. Providing integrated EMTCT services for all three infections has the potential to not only help ensure streamlining of supply chains, but may also be cost-effective and efficient to implement—characteristics that are pivotal in the current funding climate. 34 Future efforts to accelerate progress towards EMTCT of syphilis and HBV may find momentum by mirroring and/or leveraging successes from EMTCT of HIV. Community awareness, and prioritization by national governments and health care providers are necessary components of elimination efforts and help catalyze testing early in ANC. Achieving high levels of test coverage is critical to maximize subsequent elements of the treatment and prevention cascade, as demonstrated by the testing and treatment metrics used to validate EMTCT. 50 Aggressive programs to combat HIV in areas where the epidemic was generalized have been successful, including Thailand, the first country to be validated for EMTCT by WHO in Asia, 51 and Botswana, the first high HIV burden country to both test and treat >90% of pregnant women. 52 Developing similar strategies as used for HIV to raise awareness, and support for testing, treatment, and prevention of congenital syphilis and HBV infection, particularly if coupled with HIV EMTCT services, has potential to accelerate triple elimination progress. Recent reductions in global public health funding, particularly for HIV and other infectious diseases, will present an additional, and significant, hurdle for countries to make strides in activities towards triple elimination. In the face of these new challenges, countries will need to develop creative financing models to simultaneously continue to support HIV prevention and treatment programs, win addition to financial support for prevention of congenital syphilis and HBV infection. De-siloed systems under universal health care and co-delivery of services could be one cost-reducing approach to move closer to these goals. However, while funding for prevention is necessary, it is not sufficient, as policies supporting procurement of commodities and resources to effectively implement programs is also essential. Investments in infrastructure for monitoring and evaluation systems to track progress towards EMTCT have previously been cited as contributing factors to achieving EMTCT of HIV, 51 but systems will require capture and assessment of indicators specific for triple EMCT as lack of indicators have been shown to be barriers to EMTCT of HIV. 53 Strong policies and programs supporting integration, or co-delivery of services, in ANC was one of the most influential factors contributing to dual EMTCT in Cuba, Thailand, and Belarus. 50 Breaking down programmatic siloes to coordinate and streamline services is efficient, and momentum from one program, such as PMTCT of HIV, can help improve efforts for other integrated programs. The dual RDT has enormous potential to improve syphilis test coverage by using a single point-of-care test. However, availability remains limited, which hinders widespread use. In addition, while WHO universally recommends the dual RDT as a first line test during pregnancy, women living with HIV and those with a prior history of syphilis infection are not advised to test with the dual RDT. Therefore, providers are required to assess eligibility for the dual test and procurement plans need to address an adequate supply of multiple types of tests to meet the diverse testing needs of women, and providers need training to gain competencies in determining which test(s) to use for diagnosis for specific populations. Provider training would also assist with improving comfort and familiarity with managing syphilis and HBV infections. The addition of a triple test would likely require similar challenges with multiple procurement streams based on test eligibility but would be expected to make significant gains in HBV test coverage and overall gains towards implementation of elimination efforts. Although strategies addressing HBV family and partner testing strategies were not found in this scoping review, these would also improve case-finding for HBV and could be integrated with family and household testing for HIV and syphilis. Furthermore, testing coverage for HBV in ANC lags behind both HIV and syphilis in many areas (however in parts of Asia HBV testing surpasses syphilis testing) 15 ; however, we did not find any reports in our search addressing specific issues for HIV and HBV testing. However, we did find support for additional training on HBV for HCW to improve testing. In addition to training for HBV testing and treatment, improvements in diagnostics and access to maternal and infant HBV prevention would be strategic investments to promote uptake. While point-of-care WHO-prequalified HBsAg RDTs exist, availability within ANC programmes is even more limited than the dual RDT. Triple RDTs are available, but they are not WHO-prequalified, and countries may only be supported in purchasing WHO pre-qualified tests under funding agreements or may lack confidence in the quality of these tests as they have not been rigorously evaluated and tested according to WHO standards. Bundling HBsAg RDTs with dual RDTs, or prequalifying multiplex RDTs that include HBsAg, has the potential to sustain progress for HIV, continue the momentum for syphilis, and catalyze prevention efforts for HBV. Advancements in rapid diagnostics that replicate desirable qualities of high quality RDTs for new triple RDT, potentially including construction of a target product profile to maximize desirable attributes across all three infections, would be expected to have high utility to advance the triple elimination agenda. Expanding funding to holistically view and support triple EMTCT as a global health priority is worth the investment and it would be beneficial to invest in prevention interventions, such as TDF monotherapy for maternal HBV prophylaxis, BPG for maternal treatment and congenital syphilis prevention, and HBV birth dose vaccination. Although PEPFAR and The Global Fund have indicated openness to funding treatment of HBV-HIV co-infected patients, funding dedicated to TDF prophylaxis in antenatal settings is minimal. Adopting WHO recommendations to include TDF in the essential medicines list for HBV treatment within national guidelines could significantly enhance prophylactic and therapeutic options. Furthermore, considering adding TDF into long-acting PrEP formulations holds potential to provide dual protection against both HIV and HBV infection. Similarly, the addition of TDF to second-line ART regimens could prevent HBV acquisition among pregnant women living with HIV As stockouts of BPG remain a significant barrier, funding to maintain and monitor supply chains could improve access to this important prevention intervention. For infants, national immunization campaigns and policies recommending HBV birth dose administration concurrently with Bacillus Calmette-Guérin (BCG) and/or oral polio vaccines at birth could significantly bolster HBV birth dose coverage in LMICs. Finally, inclusive policies that reduce barriers to treatment initiation, including recent WHO guidelines on initiating treatment for syphilis and HBV prior to additional testing, or if additional testing is not available, can effectively reduce barriers to EMTCT. 54 , 55 Many overarching challenges across the care cascade have impeded progress towards achieving triple EMTCT targets by 2030. Countries that have been validated for dual elimination of HIV and syphilis have common qualities, including equitable and universal access to healthcare, strong political commitment and increased domestic funding for programs, and efficient integrated service delivery models. Synchronizing EMTCT interventions for all three infections within maternal and child health (MCH) platforms has high potential to enhance efficiencies in providing comprehensive EMTCT services, which is key to propel countries closer to achieving triple EMTCT. Our review has many strengths. It provides a contemporary view of the current strategies and missed opportunities towards triple EMTCT in LMIC settings. We included scientific research as well as commentaries and editorials with perspectives and recommendations of where future efforts could be directed to achieve triple EMTCT. In addition, our review focused on articles examining elimination of at least two infections rather than PMTCT of individual infections to examine synergistic strategies and missed opportunities across infections. Our review is also subject to some limitations. We restricted our search based on language, geographic location, and only included records from the last ten years, which may bias our results or omit relevant findings. In addition, several records included did not clearly define “integration,” and limited our ability to clearly summarize findings and recommendations. Furthermore, we did not review the grey literature where reports, guidance documents, or programmatic findings may have been presented. In addition, there were insufficient numbers of articles to adequately to compare and contrast findings across different contexts and settings, and findings are presented with limited reference to geographic setting despite the potential for there to be key differences in different settings. Finally, we may have missed strategies or challenges towards EMTCT of individual infections by excluding articles that were limited to only one infection. For example, some highly effective prevention interventions, such as HIV PrEP were notably absent in our search as most of the HIV PrEP literature is focused on HIV alone, rather than dual or triple EMTCT. In conclusion, implementation and scale-up of several interventions aimed at preventing MTCT of HIV have shown remarkable progress in global efforts towards elimination of MTCT of HIV: yet, significant challenges remain for EMTCT of syphilis and HBV within the changing global health landscape. Success and progress in the EMTCT cascade for HIV for prevention, testing, treatment, and linkage to care should be leveraged to include similar strategies for syphilis and HBV. International and national organizations should intensify their political, funding, and technical support to accelerating progress towards global triple EMTCT goals, including investments in technologies such as a triple RDT that can simultaneously test for all three infections. Data Availability All data produced in the present study are available upon reasonable request to the authors Authors’ contributions FK developed and implemented the search. FK and ALD extracted data. FK, ALD, and CQ designed the protocol. FK, AMW, and ALD synthesized the data. FK, ALD, AMW wrote the manuscript. FK, ALD, MNO, CQ, MB, OL, NL, CM, PMAS, AC, AI, EO, CMM, DG, KL, CCJ, and AMW all provided substantial input and edits to the manuscript. Funding Statement This study was funded by the World Health Organization (WHO) 2023/1353715-0. Collaborators from WHO were involved in study design, interpretation of results, and manuscript development; no other funders had a role in design, analysis, or interpretation. All collaborators had full access to all the data in the study. ALD had final responsibility for the decision to submit for publication, with concurrence from all authors. Competing interest The authors declare that they have no competing interests. Acknowledgments We acknowledge support from the University of Washington’s Global Center for Integrated Health of Women, Adolescents, and Children (Global WACh). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the World Health Organization. REFERENCES 1. ↵ Korenromp EL , Rowley J , Alonso M , et al. 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Share Strategies and missed opportunities in achieving triple elimination of mother-to-child transmission (EMTCT) of HIV, syphilis, and hepatitis B virus: a scoping review Fikir Kibret , Morkor Newman Owiredu , Caitlin Quinn , Magdalena Barr-DiChiara , Olufunmilayo Lesi , Niklas Luhmann , Chelsea Morroni , Agnes Chetty , Akudo Ikpeazu , Casimir Manzengo Mingiedi , Deyer Gopinath , Cheryl C. Johnson , Aliza Monroe-Wise , Alison L. Drake medRxiv 2025.06.26.25330370; doi: https://doi.org/10.1101/2025.06.26.25330370 Share This Article: Copy Citation Tools Strategies and missed opportunities in achieving triple elimination of mother-to-child transmission (EMTCT) of HIV, syphilis, and hepatitis B virus: a scoping review Fikir Kibret , Morkor Newman Owiredu , Caitlin Quinn , Magdalena Barr-DiChiara , Olufunmilayo Lesi , Niklas Luhmann , Chelsea Morroni , Agnes Chetty , Akudo Ikpeazu , Casimir Manzengo Mingiedi , Deyer Gopinath , Cheryl C. Johnson , Aliza Monroe-Wise , Alison L. 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