Azithromycin and measles-rubella/polio vaccination during Nigeria´s integrated 2025-2026 campaign: practical guidance

¹Gates Foundation, Nigeria Country Office, Abuja, Nigeria, ²Department of Medical Microbiology and Parasitology, Usman Danfodiyo University, Sokoto, Nigeria

^&Corresponding author
Mohammed Yahaya, Department of Medical Microbiology and Parasitology, Usman Danfodiyo University, Sokoto, Nigeria

Brief     

Background and campaign context

Nigeria, through the National Primary Health Care Development Agency (NPHCDA), with support from partners including WHO AFRO, the Gates Foundation, Gavi, the U.S. Centers for Disease Control and Prevention (US CDC), UNICEF, and other implementing partners, is strengthening measles program quality. The country plans to introduce the Measles-Rubella (MR) vaccine in late 2025 to early 2026 through a phased approach, representing one of the largest campaigns globally [1]. Many states are considering integrated delivery with other interventions, including polio vaccination, Neglected Tropical Diseases (NTDs), particularly trachoma Mass Drug Administration (MDA) programs, seasonal malaria chemoprevention (SMC), insecticide-treated nets (ITNs), malaria vaccine, vitamin A, and nutrition services. The NPHCDA and Federal Ministry of Health and Social Welfare (FMoH&SW) will lead implementation, with partner support to ensure high coverage and effective delivery [2]. This article is an evidence-based practice guidance/commentary developed in response to an operational question arising during campaign planning; it does not report primary research or newly collected participant-level data.

Operational question

Field teams asked whether children receiving azithromycin for trachoma should delay MR or polio vaccination during the 2025/2026 integrated campaign activities.

Approach to evidence identification

To inform this practice guidance, we reviewed authoritative immunization guidance and relevant published literature addressing concomitant antibiotic use and vaccination. Guidance documents from the World Health Organization and the United States Centres for Disease Control and Prevention were prioritised, together with Nigerian immunization and integrated-campaign guidance where applicable. PubMed was also searched up to October 31^st 2025, using combinations of terms including 'azithromycin', 'antibiotics', 'vaccination', 'vaccine immunogenicity', 'measles', 'rubella', 'polio', 'microbiome', and 'mass drug administration' written only in English. Priority was given to clinical studies, randomized trials, systematic reviews, and programmatically relevant evidence in children. Because no studies were identified that directly evaluated simultaneous azithromycin administration with MR and polio vaccination during an integrated Nigerian campaign, recommendations were based primarily on established immunization guidance and indirect evidence from relevant antibiotic and vaccine studies.

Synthesis of guidance

Current immunization guidance indicates that systemic antibacterial therapy, including azithromycin, does not impair responses to inactivated vaccines (e.g., Penta or DTP-containing, HepB, Hib, PCV, IPV, HPV) or to most parenteral/live vaccines used in expanded program on Immunization (EPI), particularly measles-containing vaccines and oral polio vaccination (OPV) [3,4]. Therefore, co-administration or on-schedule vaccination is appropriate in children on azithromycin. The principal exceptions-Ty21a oral typhoid and oral cholera vaccines-can have reduced "uptake" with concurrent systemic antibiotics; a short interval, e.g., about three (3) days before/after antibiotics [3,4]. These exceptions are not part of Nigeria's MR/Polio/NTD 2025/2026 campaign package.

Evidence from mass azithromycin programmes

Direct evidence evaluating concurrent azithromycin administration with MR or polio vaccines during integrated mass campaigns remains limited. Large mass-azithromycin trials, including MORDOR, demonstrate the feasibility of repeated administration in young children. In MORDOR, 1,533 communities across Malawi, Niger, and Tanzania received twice-yearly azithromycin or placebo, with an overall 13.5% reduction in childhood mortality in azithromycin-treated communities [5]. However, the trial was designed to assess mortality rather than vaccine immunogenicity or effectiveness and did not measure vaccine-specific antibody responses [5]. Therefore, the recommendation not to delay MR or polio vaccination because of azithromycin is based principally on established immunization guidance, supported by indirect biological and programmatic evidence rather than direct evidence from integrated MR/Polio/NTD campaigns.

Potential antibiotic-vaccine interactions

Emerging evidence suggests that antibiotic exposure, particularly during early infancy, may influence immune responses to selected vaccines through alterations in the intestinal microbiome [6]. In a prospective cohort of 191 healthy term infants, Ryan et al. found that direct neonatal antibiotic exposure was associated with lower antibody titres to selected pneumococcal, Haemophilus influenzae type b and diphtheria vaccine antigens, accompanied by reduced abundance of Bifidobacterium species at the time of vaccination [7]. However, this study did not evaluate azithromycin administered during mass drug administration or immune responses to MR or oral polio vaccines. Therefore, while biologically plausible antibiotic-microbiome-vaccine interactions warrant consideration, current evidence does not demonstrate that short-course azithromycin administered during an integrated campaign clinically impairs MR or polio vaccine responses.

Operational implications for integrated campaign delivery

For implementation, the guidance should be translated into simple, consistent instructions for vaccination and NTD teams. Pre-campaign training should explicitly state that receipt of azithromycin alone does not require postponement of MR or polio vaccination. The same message should be incorporated into campaign job aids, frequently asked questions, supervisor checklists, and caregiver communication materials. Supervisors should monitor adherence during supportive supervision and promptly correct unnecessary deferrals. Where a child is not vaccinated, teams should document the specific clinical reason rather than recording azithromycin exposure as a contraindication. Evidence has shown that clear caregiver communication is important to prevent misconceptions that simultaneous medicines and vaccines are unsafe and to minimise missed opportunities for vaccination [8].

Mechanistic note

Azithromycin is a macrolide and not an immunosuppressive agent. While it has mild immunomodulatory and microbiome effects, these have not been shown to meaningfully impair vaccine-induced immune responses in clinical or programmatic settings [6].

Programmatic guidance for Azithromycin use in Nigeria 2025-2026 campaign

The practical guidance for azithromycin use during the integrated MR/Polio/NTD campaign is summarized in Table 1. i) Do not delay MR or polio vaccination: because of azithromycin treatment. ii) Apply standard live-vaccine cautions: only to children on genuine immunosuppression (chemotherapy, high-dose systemic corticosteroids), not to those on antibiotics alone. iii) Exceptions not in scope: if Ty21a oral typhoid or oral cholera vaccines are ever considered in separate activities, schedule them with short spacing from systemic antibiotics.

Implications for MR/Polio/NTD integrated delivery

Clear and consistent communication that azithromycin is not a contraindication to MR or polio vaccination will help prevent missed opportunities, especially in high zero-dose settings, thereby strengthening overall campaign effectiveness. This approach will sustain momentum for MR vaccine introduction and facilitate more efficient operational micro-planning in contexts where multiple interventions (polio, NTDs/SMC, ITNs, vitamin A, and nutrition services) are delivered concurrently.

When vaccination may still need to be deferred

Azithromycin use alone is not a reason to postpone MR or polio vaccination. However, vaccination decisions should continue to follow standard contraindications and precautions. Children with mild illness, including those receiving antibiotics, can generally be vaccinated as scheduled. Temporary deferral may be appropriate in children with moderate or severe acute illness, with or without fever, until the acute condition improves. Measles-Rubella vaccination, as a live attenuated vaccine, should also not be administered to individuals with recognised contraindications such as severe immunosuppression or a history of severe allergic reaction to a previous dose or vaccine component. Recent receipt of certain blood products may also require adjustment of the timing of measles-containing vaccines. These situations should be distinguished clearly from antibiotic exposure itself [4].

Limitations

The present guidance specifically addresses azithromycin administered as part of NTD activities and its relationship with MR and polio vaccination. It should not be interpreted as blanket guidance for all interventions delivered during integrated campaigns. Other interventions, including seasonal malaria chemoprevention, malaria vaccination, vitamin A supplementation, nutrition services, and distribution of insecticide-treated nets, should follow their respective eligibility criteria, contraindications, dosing schedules, and national implementation guidance. Operational integration does not necessarily imply pharmacological co-administration, and potential interactions should be assessed separately for each intervention.

Conclusion     

Azithromycin administration alone does not warrant delaying MR or polio vaccination during Nigeria's integrated MR/Polio/NTD campaign. Current immunization guidance supports vaccination on schedule in children receiving antibacterial therapy, provided no independent contraindication or precaution is present. This distinction should be incorporated into campaign training, job aids, supervision, and caregiver communication to minimise missed opportunities for vaccination. However, direct evidence from campaigns in which azithromycin, MR vaccine, and polio vaccine are delivered concurrently remains limited. Prospective operational research during future integrated campaigns-including documentation of co-administration, adverse events, missed opportunities, and selected immunization outcomes-would strengthen the evidence base and inform future national guidance.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Abdulmumin Saad conceived this guidance, coordinated the overall work, and contributed to the development of the manuscript. Yahaya Mohammed contributed to the conceptual framing, literature synthesis, and drafting of the manuscript, and provided critical technical input on immunization and programmatic guidance. Laila Umar supported the review of evidence and contributed to manuscript development. Yusuf Alhaji Yusufari contributed to the interpretation of findings, provided technical oversight, and critically reviewed the manuscript for important intellectual content.

Acknowledgments     

The authors acknowledge the contributions of government, donors, and partners supporting Nigeria's integrated immunization and public health campaigns, including the National Primary Health Care Development Agency (NPHCDA), Federal Ministry of Health and Social Welfare (FMoH&SW), Gavi, United States - Centers for Disease Control and Prevention (US-CDC), World Health Organization (WHO), UNICEF, and all other stakeholders involved in implementation and technical guidance in Nigeria.

Table     

Table 1: evidence-based practical guidance for azithromycin administration and vaccination during Nigeria’s 2025-2026 integrated MR/Polio/NTD campaign

References