The incubation period for mpox virus clade Ib could extend significantly longer than previously characterized variants, with a median of 14 days from exposure to rash onset, according to new research.
Investigators analyzed surveillance data from 37 polymerase chain reaction(PCR)-confirmed cases with high viral load (cycle threshold values less than 34) collected between June and October 2024 at the Mpox Treatment Center in the Uvira health zone in the Democratic Republic of the Congo. The median incubation period from exposure to rash was 13.6 days, with 5% of cases expected to develop rash within 3.1 days and 95% within 32.3 days.
The investigators revealed differential incubation periods by transmission route. Sexual transmission demonstrated a shorter median incubation of 10.3 days compared with nonsexual transmission at 13.5 days. For fever onset, the median was 14.5 days, whereas onset of any symptom occurred at a median of 11.6 days.
Among the 243 suspected cases with complete contact information, 48% were male, 30% were children younger than 5 years, and just 1% reported previous smallpox vaccination. Among cases with both complete contact information and valid laboratory results (n = 123/243), 72% were PCR-positive, with 40% of confirmed cases meeting high-confidence criteria based on low cycle threshold values.
Exposure patterns differed markedly from the predominantly sexually transmitted clade IIb outbreak. Most suspected cases reported nonsexual physical contact (95%) and respiratory contact (84%), with exposures occurring primarily within households (72%). Just 8% of cases reported sexual exposures, though this proportion increased to 16% among high-confidence confirmed cases.
The investigators employed Bayesian methods accounting for multiple reported contacts per case, censored times from exposure to symptom onset, and right-truncation of exposure windows limited to the previous 21 days per World Health Organization (WHO) recommendations. When contact pair information was unavailable, models used a maximum exposure window of 35 days prior to symptom onset, consistent with published estimates for clades I and II.
The results demonstrated sensitivity to PCR-based case definitions. Confirmed cases (cycle threshold less than 39) showed a median incubation of 18 days, while suspected cases yielded 17 days—both longer than high-confidence confirmed cases. However, median incubation periods for sexual exposure remained consistent across definitions: 12 days for confirmed cases and 12 days for suspected cases.
Temporal analysis revealed shorter incubation periods in the early epidemic phase (prior to September 1, 2024) with a median of 10 days vs 17 days in the later phase. This shift correlated with epidemiologic transition from predominantly sexual transmission in early weeks to mainly nonsexual community transmission, particularly affecting young children.
The study population came from the Uvira health zone in the South Kivu province, which reported its first mpox case on May 2, 2024, and became a clade Ib hotspot. An mpox treatment center opened on June 8, 2024, with free care provided from June 17, 2024. Two small-scale vaccination campaigns occurred by August 2025: a two-dose campaign in October and December 2024 targeting high-risk adults (approximately 14,000 doses) and a single-dose campaign in May to June 2025 (2,000 doses).
Lesion swabs were tested by quantitative PCR using GeneXpert (Xpert Mpox; Cepheid) or Radi Fast Mpox Kits (KH Medical), with test selection based on reagent availability rather than patient characteristics. As a result of deletion of the OPG032 gene in clade Ib viruses, GeneXpert assays yielded negative results for the mpox virus but positive results for orthopoxvirus (E9L target)—a pattern specific to clade Ib. A subsample of 49 Uvira cases underwent clade typing with TIB Molbiol qPCR kit, confirming all tested cases belonged to clade Ib.
Estimates proved robust across multiple distributional assumptions (log-normal, gamma, and Weibull) and different assumptions regarding probability of unreported community exposures. Median incubation period estimates for high-confidence confirmed cases remained stable when using cycle threshold cutoffs of 34 or less but increased with higher thresholds, suggesting potential false positives at elevated cycle threshold values.
Analysis of 50 contact pairs with available symptom onset dates for both case and contact (49 reporting nonsexual exposures) yielded median incubation estimates of 12 days for all contact pairs, similar to main estimates for nonsexual exposure. However, limited sample sizes precluded stratified analysis by exposure type within this subset.
The findings could carry implications for postexposure vaccination timing. Current WHO recommendations specify vaccination within 14 days of exposure based on estimates for non–clade Ib mpox virus and historical smallpox data. The extended incubation period observed for clade Ib suggested potential for longer vaccination windows, though vaccine effectiveness data for this application remain needed.
Study limitations included the lack of detailed exposure histories, absence of lower bounds on exposure periods, and implicit assumptions of person-to-person transmission without zoonotic infections. Estimates of the right tails of the incubation period carried greater uncertainty because of sensitivity to distributional assumptions. The analysis also couldn't definitively determine whether longer overall estimates vs previous clade characterizations reflected biological differences, methodologic corrections for downward bias, or shifts in predominant transmission modes over the epidemic course.
The research received funding from the Gates Foundation and the Geneva Centre for Emerging Viral Diseases, with data collected through public health surveillance activities approved by institutional review boards at Johns Hopkins Bloomberg School of Public Health and Université Catholique de Bukavu.
Source: Annals of Internal Medicine
