A secondary analysis of the MORDOR cluster-randomized trial in 30 rural Niger communities found that biannual azithromycin mass drug administration (MDA) to children aged 1–59 months did not significantly reduce enteric fever seroincidence over five years. Using IgA/IgG antibodies against Hemolysin E measured via kinetic ELISA in 1,417 dried blood spot samples, seroincidence approximately doubled in both arms — from ~69 to 145 per 100 person-years in placebo communities and ~75 to 135 in azithromycin communities. A difference-in-differences of −16.2 per 100 person-years was non-significant. A borderline-significant attenuation emerged only in children under 2 years (DiD −43.7; 95% CI −88.8 to 0.02).
This preprint, not yet peer-reviewed, carries important public health weight. Azithromycin MDA has demonstrated consistent all-cause child mortality reductions in sub-Saharan Africa, yet this analysis reveals that broad antibiotic distribution does not translate into meaningful typhoid control — a finding consistent with growing concerns about MDA's narrow mechanistic reach against Salmonella Typhi specifically. The dramatic doubling of seroincidence in both arms over five years signals worsening transmission dynamics independent of the intervention, possibly tied to climate, water infrastructure, or demographic shifts. The under-2 signal is biologically plausible given immature immunity but remains statistically marginal. Critically, seroincidence is an indirect surrogate — not clinical disease confirmation — and the 1,417-sample size limits subgroup power. The authors' emphasis on Niger's recent typhoid conjugate vaccine rollout as the appropriate tool is well-placed: antibiotics treat infection; vaccines prevent it.