Puerperal Sepsis Zero: Stepped-Wedge Implementation of WHO IPC Bundles in Rural Maternity Services

Puerperal Sepsis Zero” (PS-0) is a Geneva-led, multicountry stepped-wedge trial designed to reduce maternal sepsis in rural maternity services. Coordinated by HUG/Unige with African co-PIs and Ministries of Health, the study rolls out a WHO-aligned infection-prevention bundle across ~100 primary/district facilities in Uganda, Benin, Cameroon, DRC, and Zimbabwe. Clusters cross over to the intervention every 8 weeks during an 18-month rollout, followed by 6 months of stabilization, encompassing ~120,000 births.

Puerperal Sepsis Zero: Stepped-Wedge Implementation of WHO IPC Bundles in Rural Maternity Services

The PS-0 bundle integrates five components: (1) hand- and environmental-hygiene readiness (point-of-care alcohol rub, nudges, monthly audits); (2) peri-caesarean prevention (single-dose prophylactic antibiotic 30–60 minutes pre-incision, preoperative skin prep, and immediate pre-CS vaginal antisepsis); (3) standardized clean birth/suture kits; (4) obstetric early-warning triggers (e.g., MEOWS/mSIRS) to prompt timely review, cultures when indicated, and first-dose antibiotics; and (5) a day-3 (48–72 h) postnatal contact to detect evolving infections. An embedded stewardship thread tracks antibiotic days of therapy and aligns choices with WHO AWaRe; sentinel sites report resistance data to GLASS.

The primary outcome is maternal sepsis within 7 days postpartum. Secondary outcomes include caesarean SSI, timeliness indicators (antibiotic timing, vaginal antisepsis), hand-hygiene compliance, day-3 contact completion, antibiotic use, microbiology, cost-effectiveness (ICERs per sepsis and per DALY averted), and implementation outcomes (Proctor taxonomy). Mixed-effects models, ITS, and mediation analyses will estimate effect and mechanisms. Findings are designed to be policy-ready for WHO/EU scale-up.

Background and rationale

Maternal sepsis is a life-threatening condition arising from infection during pregnancy, childbirth, post-abortion or the postpartum period and remains a leading cause of preventable maternal morbidity and mortality (World Health Organization [WHO], n.d.; Bonet et al., 2017). The Global Maternal Sepsis Study (GLOSS) and subsequent analyses underscore the substantial burden of infection-related severe maternal outcomes across regions, especially where essential resources and infection prevention and control (IPC) capacity are inconsistent (Bonet et al., 2020; Baguiya et al., 2024). Fundamental enablers—water, sanitation, hygiene, waste and reliable electricity (WASH/E)—are frequently deficient: global monitoring shows persistent gaps in basic water and hygiene services in health-care facilities, particularly in low-resource settings (WHO & UNICEF, 2023; UNICEF, 2024).

Evidence-based, programmatic guidance exists. WHO’s core components for IPC programmes provide a systems blueprint for facilities and countries (WHO, 2016). WHO recommendations on prevention and treatment of maternal peripartum infections (with 2021 updates) specify key practices, including timely single-dose prophylactic antibiotics for caesarean section, preoperative skin preparation, and vaginal antiseptic cleansing before caesarean delivery (WHO, 2015; WHO, 2021a, 2021b, 2021c). Complementary hand-hygiene guidance and the multimodal improvement strategy emphasise point-of-care alcohol-based hand rub and supply reliability (WHO, 2009; WHO, 2021). For postnatal care, WHO recommends routine contacts at 48–72 hours, 7–14 days, and 6 weeks—windows that can capture evolving puerperal infections early (WHO, 2022).

Randomised and quasi-experimental studies show that peri-caesarean bundles (antibiotic timing, skin and vaginal preparation, theatre discipline, and postoperative wound care) reduce surgical site infections (SSIs) (Gan et al., 2024; Mahomed et al., 2022), while systematic reviews support preoperative vaginal antisepsis to lower endometritis and wound infection after caesarean (Haas et al., 2020; Liu et al., 2023). Yet adoption is uneven where staffing is stretched, and WASH/E is unreliable. Implementation science indicates that coherent bundles, supported by strong IPC programmes, can close know-do gaps at scale (WHO, 2016).

Objective

To evaluate the effectiveness, implementation, and cost-effectiveness of a simplified, WHO-aligned IPC bundle to reduce maternal sepsis within 7 days postpartum across rural and district maternity facilities, using a pragmatic, multicountry stepped-wedge cluster trial coordinated by Geneva University Hospitals/University of Geneva (HUG/Unige) with African co-principal investigators and Ministries of Health.

Intervention: The Puerperal Sepsis Zero (PS-0) bundle

Five integrated components, each mapped to WHO guidance:

1. Hand hygiene and environmental hygiene readiness Continuous availability of alcohol-based hand rub at the point of care; soap, water, and functional sinks; nudges (posters/floor markings) following WHO multimodal strategy; monthly micro-audits (WHO, 2009; WHO, 2021).
2. Peri-caesarean infection prevention (a) Antibiotic prophylaxis: single-dose agent given 30–60 minutes pre-incision (timing tracked) (WHO, 2021a; Rubin et al., 2021). (b) Preoperative skin prep per WHO recommendation (WHO, 2021b). (c) Vaginal antiseptic cleansing immediately before caesarean (WHO, 2021c; Haas et al., 2020; Liu et al., 2023).
3. Clean birth/suture kits Standardised kits for vaginal birth and caesarean wound closure to reduce variability and stock-outs (WHO, 2015).
4. Early-warning triggers for infection Vital-sign–based obstetric early-warning charts (e.g., MEOWS/mSIRS) to prompt timely review, cultures when indicated, and first-dose antibiotics for suspected sepsis (Chimwaza et al., 2024; Singhal et al., 2023).
5. Day-3 postnatal contact (48–72 h) Facility or community contact aligned with WHO postnatal guidance to assess fever, wound status, urinary and genital tract symptoms, and provide care/referral as needed (WHO, 2022).

An embedded antimicrobial stewardship thread tracks antibiotic days of therapy per 100 deliveries and aligns selections with WHO AWaRe principles, while linking microbiology (where available) to WHO GLASS reporting (WHO, 2021d; WHO, 2022b).

Trial design

Design. Stepped-wedge cluster randomized trial (facility = cluster). All clusters start in control (usual care) and cross over to the PS-0 bundle in randomly assigned waves every 8 weeks over 18 months, followed by a 6-month stabilization phase. The design enables causal inference while ensuring eventual access for all facilities and accommodates secular trends (Hemming et al., 2015 rationale applies analogously to service-delivery SW-CRTs).

Setting and sites. ~100 primary/district facilities across Uganda, Benin, Cameroon, the Democratic Republic of Congo, and Zimbabwe, selected with Ministries of Health to represent rurality, electricity reliability, and delivery volume.

Participants. All women delivering in participating facilities during the study period. Analytic cohorts: (a) all births for process and SSI outcomes; (b) clinically suspected maternal infections within 7 days postpartum for sepsis outcomes, using the WHO maternal sepsis construct (Bonet et al., 2017; WHO, n.d.).

Sample size (illustrative). Assuming ~120,000 births across 100 clusters, baseline maternal sepsis incidence of ~4–6 per 1,000 births (context-dependent), and an intra-cluster correlation coefficient of 0.002–0.01, the trial is powered (>80%, α=0.05) to detect a 25–30% relative reduction in maternal sepsis. Power will be refined using pre-trial facility data; SSI reductions are expected to be more readily detectable.

Outcomes

Primary clinical outcome

• Maternal sepsis within 7 days postpartum, defined per WHO consensus (infection + organ dysfunction) and adapted to feasible organ-dysfunction proxies (Bonet et al., 2017; Bonet et al., 2020).

Key secondary outcomes

• Caesarean SSI within 30 days (CDC definition), endometritis, wound complications.
• Timeliness indicators: proportion receiving CS prophylactic antibiotic 30–60 minutes pre-incision; proportion with documented vaginal antisepsis before CS.
• Hand hygiene availability and compliance: ABHR at point of care; observed compliance using WHO methodology.
• Postnatal day-3 contact completion rate.
• Antibiotic use and stewardship: days of therapy/100 deliveries; AWaRe mix (Access/Watch/Reserve) (WHO, 2021d).
• Microbiology (where feasible): culture yield and resistance patterns reported to GLASS or national systems (WHO, 2022b).
• Economic outcomes: incremental cost per sepsis case averted and per disability-adjusted life-year (DALY) averted (health-system perspective).
• Implementation outcomes (acceptability, adoption, fidelity, feasibility, penetration, sustainability, and implementation cost) following Proctor’s taxonomy (Proctor et al., 2011).

Measurement and data systems

• Case detection: triage triggers (temperature, heart rate, respiratory rate, blood pressure, oxygen saturation, mental status) on an obstetric early-warning chart; urgent review thresholds adapted from MEOWS/mSIRS evidence (Chimwaza et al., 2024; Singhal et al., 2023).
• Peri-caesarean practices: timestamped anaesthesia charting for antibiotic timing; pre-incision check for skin and vaginal preparation.
• Hand hygiene: monthly point-prevalence observations using WHO “My 5 Moments” methodology; supply readiness audits (WHO, 2009; WHO, 2021).
• Postnatal day-3 contact: brief symptom screen and wound check (in person or phone) consistent with WHO schedules (WHO, 2022).
• Microbiology: “clinical-indication only” sampling (blood/urine/wound) at sentinel sites, EUCAST/CLSI AST, and GLASS-compatible reporting where capacity exists (WHO, 2022b).
• Costing: micro-costing of bundle inputs (ABHR, kits, training/time), sepsis management (labs, drugs, bed-days), and referral.

Analysis plan

• Primary analysis: mixed-effects regression for stepped-wedge designs with fixed effects for step (time) and random intercepts for clusters; adjustment for a priori covariates (delivery mode, referral status, baseline facility volume, WASH/E reliability).
• Secondary analyses: cluster-level interrupted time series; mediation of effect via fidelity indices (e.g., antibiotic-timing adherence, hand-hygiene availability).
• Economic evaluation: incremental cost-effectiveness ratios (ICERs) per maternal sepsis averted and per DALY averted, probabilistic sensitivity analyses; scenario analyses varying WASH/E reliability and ABHR pricing.
• Implementation outcomes: measured with validated instruments aligned to Proctor’s taxonomy; barriers/facilitators coded using the Consolidated Framework for Implementation Research (CFIR) (Damschroder et al., 2009; Damschroder et al., 2022; Proctor et al., 2011).

Implementation strategy

Governance. HUG/Unige coordinates; national public academic partners serve as country PIs; Ministries of Health quality/IPC units co-implement to enable policy uptake.

Training and mentorship. Short, simulation-based sessions on CS prophylaxis timing, skin/vaginal preparation, asepsis, and hand-hygiene technique; quarterly supportive supervision.

Supply and WASH/E actions. ABHR production or procurement plans; dispenser placement at points of care; minimal plumbing fixes where feasible; escalation of structural issues to district health authorities using the 2023 WASH progress framework (WHO & UNICEF, 2023).

Data use for improvement. Simple dashboards (facility and district) track antibiotic-timing adherence, ABHR availability, day-3 contact completion, and early-warning trigger performance.

Stewardship and surveillance. Antibiotic choice guided by national EMLs and AWaRe; quarterly antibiogram feedback at sentinel sites; contribution to GLASS where operational (WHO, 2021d; WHO, 2022b).

Ethical considerations

All women receive guideline-concordant care; equipoise concerns the organisational bundle’s impact on timeliness and outcomes. The stepped-wedge approach ensures eventual access to the intervention and supports systems learning. Community engagement includes mothers’ groups and midwifery councils; consent processes follow local regulations for service-delivery research.

Anticipated impact and policy relevance

PS-0 addresses proven, actionable levers: hand-hygiene availability and behaviour; antibiotic prophylaxis timing; skin and vaginal preparation; early recognition; and early postnatal review. Each is directly tied to WHO guidance and feasible in rural settings. By combining clinical outcomes with implementation and cost data, the study aims to generate policy-ready evidence for national IPC and maternal health programmes, WHO guideline panels, and EU global-health funders. Given persistent WASH/E gaps and infection burdens, even modest relative reductions in maternal sepsis and CS SSI could translate into substantial DALYs averted and cost savings (WHO & UNICEF, 2023; Bonet et al., 2020).

References

• Baguiya, A., Faye, A., Kpozehouen, A., et al. (2024). Infection-related severe maternal outcomes and case fatality across WHO regions: Analyses from the GLOSS study. BMC Pregnancy and Childbirth, 24, 317. 

• Bonet, M., Nogueira Pileggi, V., Rijken, M. J., et al. (2017). Towards a consensus definition of maternal sepsis. BMJ Global Health, 2(6), e000734. 

• Bonet, M., Brizuela, V., Abalos, E., et al. (2020). Frequency and management of maternal infection in health facilities in 52 countries (GLOSS). The Lancet Global Health, 8(5), e661–e671. 

• Chimwaza, Y., Alabi, O., Olufemi-Tawi, O., et al. (2024). Early warning systems for identifying severe maternal outcomes related to infection. BMC Pregnancy and Childbirth, 24, 480. 

• Damschroder, L. J., Aron, D. C., Keith, R. E., Kirsh, S. R., Alexander, J. A., & Lowery, J. C. (2009). A consolidated framework for advancing implementation science. Implementation Science, 4, 50. 

• Damschroder, L. J., Reardon, C. M., Opra Widerquist, M. A., & Lowery, J. (2022). The updated Consolidated Framework for Implementation Research (CFIR). Implementation Science, 17, 75. 

• Gan, A., et al. (2024). The impact of an evidence-based bundle on caesarean surgical-site infection. Maternal-Fetal Medicine, 6(2), 227–236.

• Haas, D. M., Morgan, S., Contreras, K., & Enders, S. (2020). Vaginal preparation before caesarean section for preventing postoperative infections. Cochrane Database of Systematic Reviews, 7, CD007892. 

• Mahomed, K., et al. (2022). Implementation of an evidence-based bundle to reduce caesarean SSI. American Journal of Infection Control, 50(12), 1337–1343. 

• Proctor, E., Silmere, H., Raghavan, R., et al. (2011). Outcomes for implementation research. Administration and Policy in Mental Health and Mental Health Services Research, 38(2), 65–76. 

• Rubin, H., Pollak, Y., Rokach, A., et al. (2021). Timing of antimicrobial prophylaxis before caesarean. Scientific Reports, 11, 9138. 

• Singhal, S., et al. (2023). Use of the modified early obstetric warning system chart as a predictor of maternal morbidity. Journal of Family Medicine and Primary Care, 12(3), 565–571. 

• UNICEF. (2024). WASH in health care facilities: Data portal. 

• WHO. (2009). WHO guidelines on hand hygiene in health care. 

• WHO. (2015). WHO recommendations for prevention and treatment of maternal peripartum infections. 

• WHO. (2016). Guidelines on core components of infection prevention and control programmes. 

• WHO. (2021). Resource considerations for investing in hand hygiene improvement in health care facilities. 

• WHO. (2021a). WHO recommendation on prophylactic antibiotics for women undergoing caesarean section. 

• WHO. (2021b). WHO recommendation on choice of antiseptic agent and method of application for preoperative skin preparation for caesarean section. (See guideline updates page.) 

• WHO. (2021c). WHO recommendation on vaginal preparation with antiseptic agents for women undergoing caesarean section. (See guideline updates page.) 

• WHO. (2021d). 2021 AWaRe classification. 

• WHO. (2022). WHO recommendations on maternal and newborn care for a positive postnatal experience. 

• WHO. (2022b). Global antimicrobial resistance and use surveillance system (GLASS): 2022 report. 

• WHO. (n.d.). Maternal sepsis. 

• WHO & UNICEF. (2023). Water, sanitation, hygiene, waste and electricity services in health care facilities: Progress on the fundamentals – 2023 global report. 

• Liu, G., Xie, H., Zhao, H., et al. (2023). Different methods of vaginal preparation before caesarean: A network meta-analysis. AJOG MFM, 5(5), 100966.