The Lancet Regional Health - Western Pacific

BackgroundCOVID-19 non-pharmaceutical interventions (NPIs) disrupted transmission of many infectious diseases worldwide. While disruption patterns are well-documented, systematic analysis of post-pandemic recovery trajectories across diverse pathogens remains limited. We examined disruption and recovery of 47 nationally notifiable diseases in Australia from 2015 to 2025. MethodsWe analysed NNDSS surveillance data for 47 diseases across six transmission modes, quantifying disruption using observed-to-expected (O/E) ratios against 2015-2019 baselines. We applied difference-in-differences (DiD) to estimate causal NPI effects, Kaplan-Meier survival analysis for time-to-recovery, and bootstrap 95% confidence intervals for cumulative immunity debt. ResultsDuring 2020-2021, 28 diseases decreased (median O/E 0.51), with border-sensitive and vaccine-preventable diseases most affected. DiD analysis estimated that border closures were associated with significantly greater suppression among import-dependent diseases (coefficient -0.50, 95% CI -0.90 to -0.10, p=0.016). By 2025, recovery was heterogeneous: 17 diseases exceeded baseline levels, 12 returned to expected levels, 15 remained below baseline (9 partially recovered, 6 in sustained suppression), and 3 had insufficient data for trajectory classification. Five diseases showed suppression-then-overshoot trajectories suggestive of immunity debt, though bootstrap 95% confidence intervals confirmed statistically significant cumulative excess for only one (rotavirus); for influenza, high baseline variability precluded statistical confirmation despite a large absolute overshoot. ConclusionsPost-pandemic disease recovery in Australia is heterogeneous and incomplete. Fifteen of 47 diseases have not returned to baseline levels by 2025, while 17 exhibit overshoot. These findings argue for differentiated surveillance of still-suppressed diseases and targeted catch-up vaccination in pandemic birth cohorts. Article summaryWe analysed disruption and recovery of 47 nationally notifiable diseases in Australia from 2015 to 2025, finding that 15 diseases remain below pre-pandemic levels three years after NPI relaxation. Border closures caused disproportionate suppression of import-dependent diseases, and recovery trajectories varied by disease characteristics, with immunity debt statistically confirmed for only one of five candidate diseases.

IntroductionSporadic colorectal cancer (CRC) remains a significant driver of worldwide morbidity and mortality. Environmental factors associated with CRC are increasingly well-described and now include generalized colonic dysbiosis and individual enteric bacteria. Clostridioides difficile is one such species, with recent mouse model work suggesting prolonged exposure to C. difficile toxin B is conducive to colonic tumorigenesis. However, there is a dearth of real-world human evidence linking C. difficile infection and CRC. MethodsHerein, we analyzed a multicenter, longitudinal, Electronic Health Record (EHR)-based dataset to test the association between C. difficile test positivity and the risk for incident CRC utilizing unadjusted and multivariable (controlled for clinical conditions independently associated with CRC development) Cox proportional hazard modeling to compare C. difficile exposed and non-exposed cohorts ResultsWe found that individuals who tested recurrently positive for C. difficile had a significantly increased risk for incident CRC (aHR 2.05 [95% CI 1.27-3.29]) compared with those who tested positive only once (aHR 0.70 [0.45-1.10]) or never. Furthermore, we found potential trends that the effect of C. difficile test positivity on the risk for incident CRC was stronger amongst females compared with males. ImportanceThese findings help translate emerging mouse model work on C. difficile-influenced colorectal tumorigenesis and lay groundwork for more substantial human investigations into this connection. These findings also may begin to help guide the personalized deployment of novel fecal microbiota-based therapies designed to interrupt the life cycle of C. difficile within the gut of human hosts and, potentially, prevent long-term health sequelae of chronic C. difficile infection.

Introduction Heat waves are increasingly frequent and linked to higher mortality risks in Hong Kong. However, estimates of total excess mortality associated with heat waves remain unavailable. This study quantifies excess deaths associated with heat waves in Hong Kong from 2014 to 2023. Methods Daily age- and sex-specific mortality rates and population data were obtained from the Hong Kong Life Tables and Census and Statistics Department. Temperature data came from the Hong Kong Observatory, and relative risks were derived from local research. A Monte Carlo simulation was used to estimate heat-attributable deaths under different heat wave definitions, calculating total excess deaths and annualized death rates per 100,000 population. Results Between 2014 and 2023, heat exposure resulted in an estimated 1,455 (95% CI: 1,098-1,812) to 3,238 (95% CI: 3,234-3,242) excess deaths. In 2023, annualized excess death rates ranged from 2.95 (95% CI: 2.41-3.50) to 5.09 (95% CI: 5.07-5.12) per 100,000 people. Males and individuals aged 65 or older were disproportionately affected. Conclusion Over the 10-year study period, 1,455 to 3,238 excess deaths in Hong Kong were attributed to extreme heat. Heat waves now rank among the top ten causes of death in Hong Kong, with mortality rates comparable to diabetes. These findings underscore the need for urgent public health interventions to mitigate the impact of extreme heat.

BackgroundColorectal carcinoma (CRC) remains a significant cause of cancer morbidity and mortality worldwide. Right- and left-sided tumours differ in clinical, morphological, and molecular features. Microsatellite instability-high (MSI-H) tumours, often right-sided, are associated with distinct histopathological characteristics and prognostic implications. In Sri Lanka, molecular MSI testing is currently unavailable, highlighting the need for alternative predictive approaches. ObjectivesGeneral Objective: To describe the clinical and histopathological characteristics of right- and left-sided colorectal cancers in a Sri Lankan cohort and evaluate their usefulness in predicting MSI-H tumours. Specific ObjectivesTo compare clinicopathological features between right- and left-sided colorectal cancers. To predict MSI-H tumours based on clinicopathological features, including assessment of the MsPath score and histological parameters. To determine interobserver agreement for MsPath score application in selecting cases for MSI assessment. MethodsA retrospective analytical study was conducted on 156 colorectal carcinoma resections diagnosed between 2019 and 2021 at the National Hospital of Sri Lanka. Histopathological evaluation included tumour differentiation, mucinous and medullary features, tumour-infiltrating lymphocytes (TILs), and Crohn-like reaction. MsPath scores were calculated based on age, tumour site, and histological parameters. Immunohistochemistry (IHC) for PMS2 and MSH6 was performed on 46 selected cases to assess mismatch repair (MMR) status. ResultsOf 156 cases, 41 (26%) were right-sided and 115 (74%) left-sided. The majority were moderately differentiated adenocarcinomas (89%). Histological features suggestive of MSI-H including TILs (29%) and Crohn-like lymphoid reaction (23%) were more frequent in right-sided tumours. MsPath scores ranged from 0.0 to 5.9, with 50% of cases scoring below 1. Among the 46 cases evaluated by IHC, MMR deficiency was observed predominantly in higher MsPath score categories, and a significant association was found between MsPath score category and MMR status ({chi}{superscript 2} = 13.76, df = 2, p = 0.001). Interobserver agreement for MsPath scoring was substantial (Kappa = xx, indicating reproducibility). ConclusionRight-sided colorectal carcinomas in this Sri Lankan cohort more frequently exhibited histological features suggestive of MSI-H, including mucinous differentiation, TILs, and Crohn-like lymphoid reaction. MsPath scoring correlated with MMR deficiency in the IHC-tested subset, but its predictive value is limited without immunohistochemical confirmation. IHC using a two-antibody panel (PMS2 and MSH6) proved to be a feasible, cost-effective, and reliable method for MSI screening in resource-limited settings. This study is the first comprehensive evaluation of right-versus left-sided colorectal carcinomas and MsPath utility in Sri Lanka, underscoring the need for expanded IHC capacity, larger cohorts, and integration of molecular testing for MSI validation.

Dengue virus (DENV), comprising four distinct serotypes (DENV-1 to DENV-4), poses a major public health challenge in tropical regions. Infection with one serotype confers long-term immunity to that serotype alone, while subsequent heterologous infections are associated with increased risk of severe disease, necessitating vaccines that induce durable, balanced immunity across all serotypes. However, achieving such balance immunity remains a central challenge for dengue vaccine development. Using passive surveillance data from Kamphaeng Phet, Thailand (2004-2022), we characterized long-term serotype circulation and contributions to clinical dengue burden in a hyperendemic setting. We observed sustained co-circulation of all four serotypes over nearly two decades, with periodic shifts in dominant serotype. Among 6,840 PCR-confirmed dengue cases, the majority of which were hospitalized, DENV-1 through DENV-4 accounted for 32.8%, 25.9%, 24.8%, and 16.5% of detected dengue cases, respectively. Compared with DENV-1, clinically-apparent DENV-2 and DENV-4 infections were more likely to represent secondary infections (odds ratio 4.94 and 5.24, respectively) and occurred at older ages, underscoring the context-dependent clinical expression of different serotypes. Together, these findings demonstrate that all four dengue serotypes contribute meaningfully to clinical disease burden in Thailand and caution against de-emphasizing individual serotypes based on transient epidemiologic patterns. These results reinforce the importance of tetravalent vaccine strategies alongside continued evaluation of vaccine performance in evolving epidemiologic settings. Author SummaryDengue is a mosquito-borne disease that infects millions of people every year. The virus consists of four serotypes. Infection with one serotype does not provide full protection against the others, and a second infection with a different serotype can increase the likelihood of severe illness. For this reason, understanding which serotypes are circulating is important for designing and evaluating effective vaccines. Our analysis of nearly two decades of surveillance data from Kamphaeng Phet, Thailand demonstrates that all four serotypes were consistently present over time, each contributing a substantial number of cases. The serotypes showed distinct age- and immunity-dependent epidemiologic patterns. No single serotype could be considered unimportant. These findings highlight the complex nature of DENV transmission in Thailand and emphasize the need for vaccines that provide protection against all four serotypes. Continuous monitoring of circulating serotypes is essential to guide vaccine development and to ensure their effectiveness in real-world settings.

BackgroundThis study of Malawian children with rheumatic heart disease (RHD) sought to detect demographic, clinical, and echocardiographic risk factors for mortality. MethodsPediatric patients with RHD were recruited from March to October, 2018 from clinic rosters and inpatient consults in Lilongwe and Blantyre, Malawi. An echocardiogram was performed upon study enrollment. Cox regression analyses were performed to assess for factors associated with mortality over nearly 2 years of follow-up. ResultsOf 118 patients, nearly two-thirds were female (64.4%) and median age was 12 (IQR 10-14). Just under half (47.0%) lived >40km from a tertiary care center. There was a high prevalence of severe mitral regurgitation (65.3%), and pericardial effusion was present in 18.6%. Nearly a quarter (23.7%) died during follow-up. In univariable Cox regression, living >40km from tertiary care, living in a remote area, moderate or severe malnutrition, taking a beta blocker, severe mitral stenosis, any severe valve disease, severe left atrial enlargement, and presence of a pericardial effusion were statistically significant risk factors for mortality (p<0.05). In the adjusted model, living >40km from tertiary care (HR 2.66, CI 1.06-6.07, p=0.037), malnutrition (mild HR 3.92, CI 1.03-14.91, p=0.045); moderate HR 7.41, CI 1.92-28.54, p=0.004; severe HR 4.91, CI 1.44-16.71, p=0.011), beta blocker use (HR 4.62, CI 1.63-13.10, p=0.004), and presence of a pericardial effusion (HR 6.96, CI 3.00-16.13, p<0.001) remained independent risk factors for mortality. ConclusionsThis study of Malawian children emphasizes the dire prognosis of RHD in under-resourced settings and provides potential area of focus for targeted intervention.

Accurate quantification of individual exposure to air pollutants remains a major challenge in environmental health, as fixed-site monitoring fails to account for mobility, indoor environments, and physiological variability. We deployed TracMyAir, a smartphone-based digital health platform designed to generate time-resolved, personalized exposure and inhaled dose estimates for PM2.5 and ozone under real-world conditions. In an exploratory study of 18 adults contributing more than 1,500 participant-hours, the platform integrated smartphone geolocation, regulatory (AirNow) and community-based (PurpleAir) air quality data, building infiltration modeling, microenvironment classification, and wearable-derived physical activity metrics to compute eight tiers of hourly exposure estimates, culminating in individualized inhaled dose. Hourly dose estimates derived from smartphone-and smartwatch-based step counts were concordant (Spearman correlation p=0.97-0.98), while heart rate-based estimates yielded greater variability and higher mean values (p=0.82-0.92). Exposure explained 51-73% of variance in inhaled dose of PM2.5 and 68-84% of ozone, suggesting that physiological-based modeling approaches improve hyperlocal estimates of personal pollutant burden. Substantial inter-and intra-individual variability reflect dynamic microenvironmental transitions and activity patterns. Modeled doses based on regulatory and community sensor networks were strongly correlated (R=0.84), with community sensors located closer to participants on average, supporting the feasibility of integrating dense, low-cost monitoring networks. No consistent association was observed between outdoor pollutant levels and neighborhood socioeconomic status in this cohort. These findings demonstrate the feasibility of a scalable, smartphone-centered digital health approach for hyperlocal exposure and inhaled dose modeling. By leveraging ubiquitous consumer devices and existing air quality networks, TracMyAir enables personalized environmental exposure assessment with potential applications in epidemiology, population health, and precision environmental medicine.

BackgroundDengue fever is a major neglected tropical disease with a rapidly rising global burden, and localized outbreaks are increasingly reported in southern subtropical China. Fujian Province, a coastal subtropical region with favorable ecological conditions for Aedes albopictus breeding and frequent cross-border exchanges with dengue-endemic areas, has had continuous local dengue cases for over a decade, raising concerns about the establishment of a stable natural endemic focus. Sustained local dengue transmission is defined by four core criteria, but no systematic assessment of these criteria has been conducted for Fujian using long-term multi-dimensional surveillance data. We aimed to evaluate whether a natural endemic focus for sustained local dengue transmission has been established in Fujian Province from 2014 to 2024 using four core evidence dimensions. MethodsWe extracted data on imported and locally acquired dengue cases in Fujian from 2014 to 2024 from Chinas National Notifiable Disease Reporting System (NNDRS). Serological surveillance for dengue IgG antibodies and virological surveillance for dengue virus in Aedes albopictus were conducted at seven sentinel sites. The study period was stratified into three phases based on the impact of COVID-19 non-pharmacological interventions: pre-pandemic (2014-2019), pandemic(2020-2022), and post-pandemic(2023-2024). Descriptive epidemiological analysis and data visualization were performed using R software (version 4.4.1), with t-tests for continuous variables and {chi}{superscript 2} tests for categorical variables. ResultsA total of 3,606 dengue cases were reported in Fujian during the study period, including 1,229 imported and 2,377 locally acquired cases. Key findings were as follows: (1) Temporal distribution: Local dengue transmission was completely interrupted during the 2020-2022 COVID-19 pandemic (0 local cases, only 26 imported cases), and resumed at a low level in 2023-2024 (160 local cases). (2) Serology: The overall population dengue IgG antibody positivity rate was 4.2% (66/15,736), with no statistically significant difference between pre-epidemic (3.8%, 30/7,835) and post-epidemic seasons (4.5%, 36/7,901; P=0.48), and no year with a positivity rate exceeding 10%. (3) Vector surveillance: Only one dengue virus-positive sample was detected among 385,000 Aedes albopictus mosquitoes collected during routine surveillance (Taijiang District, Fuzhou, October 2017), with no viral nucleic acid detected in all other samples. (4) Age distribution: The mean age of locally acquired cases (46.1{+/-}19.8 years) was significantly higher than that of imported cases (35.8{+/-}11.2 years, P<0.001), and local cases were concentrated in the middle-aged group (40-60 years) with no child-dominant pattern observed. ConclusionsFujian Province has not established a stable natural endemic focus for sustained local dengue transmission, and imported cases are the primary driver of local outbreaks in the region. Strengthened surveillance and early management of imported cases, integrated vector control targeting Aedes albopictus, and targeted public health education are critical and essential strategies to prevent the establishment of a dengue natural endemic focus in Fujian and other subtropical coastal regions with similar epidemiological characteristics. Author SummaryDengue fever is a rapidly spreading neglected tropical disease worldwide, and southern China faces persistent threats of local transmission due to favorable ecological conditions for mosquito breeding and frequent cross-border travel. Fujian Province, a subtropical coastal region in southeastern China, has reported annual local dengue cases for over a decade, raising public health concerns about the potential establishment of a stable natural endemic focus--where the virus circulates sustainably without relying on imported cases. To address this critical question, we conducted a comprehensive 11-year assessment (2014-2024) of dengue transmission in Fujian using four key evidence dimensions defined for identifying dengue endemic foci: the continuity of local cases independent of imported sources, population antibody levels, dengue virus detection in local mosquitoes (Aedes albopictus), and the age distribution of infected patients. We also leveraged the COVID-19 pandemic(2020-2022) as a unique natural experiment, during which strict travel restrictions drastically reduced imported dengue cases, to test whether local transmission could persist on its own. Our findings showed that local dengue transmission in Fujian completely stopped during the COVID-19 pandemic and only resumed when cross-border travel and imported cases recovered, confirming local transmission is entirely dependent on imported virus sources. Additionally, the local population had a very low dengue antibody positivity rate (4.2%), dengue virus was detected in only one mosquito sample over 11 years of surveillance, and local cases were concentrated in middle-aged adults (not children--the typical group affected in endemic areas). Together, these results confirm that Fujian Province has not established a stable natural endemic focus for dengue fever. While no endemic focus exists yet, Fujian remains at high risk of imported-driven local outbreaks due to its climate and cross-border exchanges. Our study highlights three critical strategies to prevent the future establishment of a dengue endemic focus in Fujian and other similar subtropical coastal regions: strengthening surveillance and early response for imported dengue cases, implementing targeted mosquito control measures during peak transmission seasons, and conducting public health education to raise awareness of dengue prevention. These evidence-based interventions are key to blocking the formation of sustained local dengue transmission and protecting regional population health.

BackgroundSerotype 3 (S3) has remained a major cause of invasive pneumococcal disease (IPD) despite its inclusion in 13-valent pneumococcal conjugate vaccine (PCV). In October 2023, a 15-valent PCV (PCV15) including S3 was introduced into the Catalan universal childhood immunization program. MethodsWe conducted a retrospective pre-post surveillance study to compare pediatric IPD incidence in Catalonia during a pre-PCV15 period (October 1, 2022-September 30, 2023) and two post-PCV15 periods (October 1, 2023-September 30, 2024, and October 1, 2024-September 30, 2025). All IPD episodes in children <18 years attended in 34 hospitals were included. IPD was defined as detection of S. pneumoniae in a sterile site by culture or PCR. Results323 IPD episodes were identified in 319 children (mean age, 4.5 years). Overall IPD incidence declined from 13.0 to 9.4 episodes per 100,000 children in the first post-PCV15 period compared with the pre-PCV15 period (28% reduction; p=0.02), but returned to baseline in the second post-PCV15 period. S3-IPD incidence decreased significantly from 4.1 to 1.6 episodes per 100,000 (60% reduction; p=0.001) in the first post-PCV15 period and remained lower in the second period: 2.3 episodes per 100,000 (42% reduction compared with baseline; p=0.04). In contrast, IPD incidence caused by PCV7 serotypes increased from 0.3 in the pre-PCV15 and first post-PCV15 period to 2.7 episodes per 100,000 in the second post-PCV15 period (690% increase; p<0.001). ConclusionPCV15 introduction was associated with a sustained reduction in S3-IPD over two years. However, a marked increase in PCV7 serotypes offset overall gains in IPD incidence. SUMMARYPCV15 introduction in Catalonia achieved sustained reduction in serotype 3 invasive pneumococcal disease over two years, but a marked increase in PCV7 serotypes offset the overall disease reduction in the second post-vaccination year.

BackgroundAustralia is experiencing its worst syphilis epidemic in decades, driven by two distinct outbreaks -- a heterosexual epidemic disproportionately affecting Aboriginal and Torres Strait Islander communities in northern Australia, and a predominantly MSM-associated epidemic in urban centres. We examined the spatial dynamics of this dual epidemic, including geographic clustering, service accessibility associations, and COVID-19 impacts. MethodsWe analysed publicly available aggregate surveillance data (2013-2024). Spatial autocorrelation (Global/Local Morans I, Getis-Ord Gi*), spatial regression (OLS, spatial lag, spatial error), and geographically weighted regression (GWR) were applied to 74-75 Victorian local government areas (LGAs). Congenital syphilis vulnerability was mapped at SA3 level using composite proxy scoring. COVID-19 impact was assessed using interrupted time series (ITS) analysis. ResultsNational notifications rose 3.5-fold from 1,719 (2013) to 6,036 (2022). Strong spatial clustering was identified (Morans I=0.560, p<0.001), with 11 high-high clusters in inner Melbourne. The spatial lag model identified distance to sexual health clinic (coefficient: -0.225, p=0.050) and Indigenous population proportion (coefficient: 0.210, p=0.045) as significant predictors. Eleven SA3 areas were classified as high vulnerability for congenital syphilis, predominantly in remote northern Australia. Monthly NSW ITS found a non-significant 6% reduction in notifications during COVID restrictions (IRR=0.94, p=0.123). Comparing the COVID period (2020-2021) with pre-COVID means, remote area notifications increased 91% and female notifications increased 108% compared with 45% for males, reflecting the steep underlying epidemic trajectory. ConclusionsAustralias syphilis epidemic exhibits distinct spatial patterns shaped by service accessibility and sociodemographic factors. The concentration of high-vulnerability areas in remote northern Australia highlights the need for targeted service expansion, point-of-care testing, and culturally appropriate outreach. The acceleration of heterosexual transmission signals increasing congenital syphilis risk requiring urgent antenatal screening strengthening.

BackgroundTwo RSV immunisations products: a maternal vaccine, Abrysvo, and a long-acting monoclonal antibody, nirsevimab, both designed to prevent RSV illness in infants, have recently become available. Modelling evidence is required to inform how to optimally use these products in immunisation programs to reduce the burden of RSV in young children. MethodsWe extend a dynamic transmission model calibrated to RSV-hospitalisation data of children aged < 5 years in temperate Western Australia (WA) to simulate a range of potential RSV immunisation programs. Using our model, we estimate the impact of both single-product and hybrid RSV immunisation programs. The analysis considers timing of administration, coverage levels and targeting of high-risk groups. Impact on RSV burden is analysed in the context of the WA setting and the possible significant cost differences between the two products. ResultsAll programs analysed were effective in reducing RSV burden. Programs using nirsevimab for newborn infants at similar coverage levels to the Abrysvo programs, averted more RSV-hospitalisations annually. Seasonal programs that focused on protection during high RSV activity and programs targeting high-risk infants were the most efficient in reducing RSV burden. When dose cost is considered alongside program impact on RSV burden, we find evidence to support further economic analysis of hybrid programs as they could mitigate the cost differential between the two products while remaining highly effective in reducing RSV burden. ConclusionsOur study is the first to comprehensively analyse hybrid RSV immunisation programs that use Abrysvo and nirsevimab. RSV immunisation programs can substantially reduce the burden of RSV in young children. Our modelling analysis provides evidence on immunisation type, timing, coverage, high-risk groups and dosage cost that will support decision makers and can be used in economic evaluations.

BackgroundCervical cancer, generally induced by human papillomavirus (HPV) infection remains one of the most prevalent and deadly female cancers in sub-Saharan Africa (SSA). In Cameroon, the impact of prevention strategies is limited by systemic challenges, and insufficient evidence base to guide effective interventions. This study aimed to synthesize available evidence on the prevalence and key determinants of HPV infection among Cameroonian women. MethodsA comprehensive search was conducted across PubMed, Scopus, Web of Science, Embase, Cochrane electronic databases and local online publishers. Quality assessment of included studies was performed using the Joanna Briggs Institute (JBI) critical appraisal tool. The random effect model was used to pooled the estimates. Heterogeneity was evaluated using the I2 statistics. Statistical significance was set at p <0.05 and all analyses were conducted using R Statistics version 4.5.2. The protocol was registered on PROSPERO (CRD420261279093). ResultsThirty-six studies (20,033 participants) were included. The pooled prevalence of HPV infection 36.10 (95% CI: 27.28-45.97) with high heterogeneity (I2 = 98.4%). Higher estimates were observed among female sex workers 62.10% (95% CI: 58.08-66.00%, 1 study, n = 599) and women with pre-cancerous genital lesions 85.53% (95% CI: 61.72-95.59%, 4 studies, n = 673). Significant determinants of HPV infection included age below 40 (OR = 1.31; 95% CI: 1.14-1.49; 7 reports), unmarried status (OR = 1.43; 95% CI: 1.24-1.64; 15 reports), having five or more sexual partners (OR = 1.26; 95% CI: 1.05-1.51; 2 reports), parity below four (OR = 1.29; 95% CI: 1.09-1.52; 2 reports), HIV infection (OR = 1.92; 95% CI: 1.24-2.98; 6 reports), CD4 count below 500 cells/mm3 (OR = 2.00; 95% CI: 1.02-3.95; 2 reports), and viral load below 1000 copies/mL (OR = 2.12; 95% CI: 1.27-3.53; 2 reports). ConclusionsOur study demonstrates a high and persistent burden of HPV infection in Cameroon, with a greater impact on younger women and women living with HIV. These findings highlight an urgent public health need to strengthen and expand prevention strategies to effectively reduce and eliminate cervical cancer incidence in the country.

BackgroundOlder age is widely considered a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC), typically attributed to immunosenescence and inflammaging. However, whether this association reflects intrinsic biological ageing or accumulated comorbidity burden remains unclear, with implications for clinical risk stratification. MethodsWe conducted a retrospective cohort study using the Precision PASC Research Cohort (P2RC) from Mass General Brigham, comprising 133,792 COVID-19 patients from 12 hospitals and 20 community health centres in Massachusetts (March 2020-May 2024). PASC was ascertained using a validated computational phenotyping algorithm. We used generalised estimating equations with cluster-robust variance to model PASC risk, causal mediation analysis to decompose age effects through comorbidity burden and acute severity, and specification curve analysis across 768 analytical specifications to assess robustness. FindingsAfter adjustment for comorbidity burden, each decade of age was associated with 6% lower odds of PASC (OR 0.94; 95% CI 0.93-0.95). Causal mediation analysis revealed that comorbidities accounted for 145% of the total age effect, indicating inconsistent mediation wherein ages direct protective effect was masked by its indirect harm through chronic disease accumulation. This protection was age-dependent: adults younger than 65 years retained robust resilience independent of comorbidities (ADE:-0.0042, p<0.001), whereas adults 65 years and older showed complete loss of this protection (ADE: +0.0020, p=0.14). InterpretationLong COVID susceptibility is driven by physiological reserve rather than chronological age until approximately age 65, beyond which age-related protective mechanisms become exhausted. Risk stratification should prioritise comorbidity burden over birth year in younger adults. FundingNational Institute of Allergy and Infectious Diseases (NIAID).

BackgroundTyphoid fever incidence estimates are central to policy decisions on vaccine introduction and investments in non-vaccine prevention and control but are often unavailable. We explored whether prevalence metrics from sentinel studies of community-onset bloodstream infections could accurately predict local Salmonella Typhi (S. Typhi) incidence. MethodsUsing a previous systematic review (January 2018-December 2024), we identified studies reporting both typhoid incidence and prevalence of community-onset bloodstream infections from sentinel sites. From authors, we requested data on blood culture isolates and analysed four metrics: (i) S. Typhi prevalence among probable pathogens, (ii) S. Typhi rank order, (iii) S. Typhi to Escherichia coli ratio, and (iv) S. Typhi to stably endemic organisms ratio. Typhoid incidence was categorized as low (<10), medium (10-100) or high (>100) per 100,000 person-years. We used univariate ordinal regression to assess the association between each metric and typhoid incidence level. The model performance was evaluated by the c-statistic, sensitivity, and specificity. FindingsAnalysis of 29 study sites (20 Africa, 9 Asia) yielded 4,625 probable pathogens. The median (IQR) typhoid incidence was 140 (28-319) per 100,000 person-years. All metrics were associated with increased typhoid incidence level: for each 1% increase in S. Typhi prevalence OR 1.07 (95%CI 1.02-1.15); rank order OR 0.25 (95%CI 0.06-0.64); log S. Typhi to E. coli ratio OR 2.91 (95%CI 1.45-7.42); log S. Typhi to stably endemic organisms ratio OR 3.69 (95%CI 1.69-11.3). A parsimonious model using S. Typhi prevalence alone achieved c-statistics of 0.87 (0.58-0.97), 0.76 (0.51-0.91), and 0.88 (0.69-0.96) for low, medium, and high incidence, respectively. InterpretationSentinel prevalence metrics from bloodstream infections, particularly S. Typhi prevalence among probable pathogens, could be useful for inferring local typhoid fever incidence where direct data are unavailable. FundingGates foundation Research in contextO_ST_ABSEvidence before this studyC_ST_ABSGlobally, annual deaths from typhoid fever were estimated at 71,954 (95% uncertainty interval 38,051 to 118,560) in 2023. Typhoid conjugate vaccines (TCV) are recommended for regions with high typhoid incidence. Implementation, however, can be challenging due to a lack of local incidence data. Generating community incidence estimates requires expensive and time-consuming large prospective or hybrid surveillance studies, or novel techniques such as serology or environmental surveillance. Our previous study proposed that metrics from sentinel healthcare facilities such as the prevalence of Salmonella Typhi (S. Typhi) among all bloodstream pathogens or its rank order relative to other pathogens could serve as proxy for community incidence. However, contemporaneous incidence and prevalence data from the same time and location were limited in our previous study. To explore typhoid incidence estimation strategies, we searched PubMed and MEDLINE on January 8, 2026 with search terms including keywords of "typhoid fever", "incidence", and "prediction" without restrictions to language or publication date. Previous studies estimated incidence based on complex country-level covariates and disease modelling that lack ease of applicability for policy decisions. Recognising the need for pragmatic tools, we explored whether prevalence metrics from sentinel studies of community-onset bloodstream infections could accurately predict local S. Typhi incidence. Added value of this studyOur study was based on typhoid incidence studies that had available data for isolates of bloodstream infections. Of 29 sites across Africa and Asia with 4,625 probable pathogens, we found that all four sentinel metrics were significantly associated with typhoid incidence level. We demonstrated that a parsimonious model using S. Typhi prevalence alone achieved good discriminative performance in identifying high incidence settings. Implications of all the available evidenceWhen typhoid incidence estimates are unavailable, prevalence metrics from sentinel studies of community-onset bloodstream infections could help policymakers infer typhoid incidence and optimise resource allocation in water, sanitation, and hygiene, and TCV introduction.

BackgroundHelicobacter pylori infection accounts for 98% of gastric cancer (GC) cases in Japan. Since 2013, the nationwide expansion of H. pylori eradication therapy to chronic gastritis patients has created a unique opportunity to evaluate its population-level impact on GC primary prevention. However, short-term reductions in GC deaths are difficult to interpret given the long natural history of gastric carcinogenesis. This study aimed to assess the early impact of population-level eradication on GC deaths. MethodsWe applied a two-layer analytic framework consisting of a counterfactual analysis comparing observed GC deaths during 2013-2021 with expected GC deaths had eradication uptake remained at pre-2013 levels. This was combined with a structured, time-dependent, multilayer state-transition model to estimate GC deaths prevented by eradication using GC incidence integrated with age-dependent H. pylori prevalence. ResultsObserved GC deaths declined from 48,632 in 2013 to 41,624 in 2021, whereas counterfactual GC deaths declined more modestly, from 49,794 to 45,654. The divergence between observed and counterfactual GC deaths widened steadily from 1,162 in 2013 to 4,030 in 2021. Model-based estimates indicated that eradication prevented 1,427 GC deaths during 2013-2021, with annual GC deaths prevented increasing from 17 in 2015 to 417 in 2021, particularly among adults aged 50-79. ConclusionsThis study demonstrates that H. pylori eradication has already contributed to a 10.4% reduction in GC deaths in Japan by 2021, with annual expansion of primary prevention effects. This framework supports evidence-based evaluation of short-term reductions in GC deaths attributable to H. pylori eradication in high-prevalence settings.

IntroductionSequence-based typing (SBT) has been the standard molecular typing method for understanding Legionella pneumophila genetic relationships. However, genome-scale typing approaches, namely core-genome (cg) or whole-genome (wg) multilocus sequence typing (MLST), provide higher discriminatory power. To advance these capabilities, the Legionella International Typing (LIT) workgroup was established to develop, evaluate, and disseminate a novel cgMLST schema with enhanced wgMLST resolution for L. pneumophila investigations. MethodsWe created and populated the LIT cg/wgMLST schema with chewBBACA software using more than 9000 genome assemblies representative of the species diversity. We applied a multi-step refinement workflow, considering loci prevalence, diversity and presence/absence profile across the species tree, to select the final cg/wgMLST loci, and compared the performance of the LIT cgMLST schema with the previously used 1521-loci schema and assessed its congruence with SBT. ResultsThe LIT schema includes 2009 loci present in 98% of the dataset, forming the static cgMLST schema for routine genomic surveillance, plus 2698 accessory loci for an in-depth wgMLST analysis of clusters of interest. The LIT cgMLST schema maintains moderate agreement with SBT and presents high clustering congruence with the 1521-loci schema, while providing increased resolution. Analysis of epidemiologically related isolates using the LIT cgMLST schema for initial cluster delineation, followed by cluster-specific dynamic wgMLST analysis extending the cgMLST with accessory loci shared among isolates within each cluster, demonstrated increased confidence for outbreak investigation and source identification. ConclusionsThe LIT schema is expected to contribute to harmonizing genomic surveillance of Legionnaires disease at both local and global levels. The schema and associated resources for local implementation are available on Zenodo (https://doi.org/10.5281/zenodo.17871973).

The resurgence of measles in the United States, driven by declining childhood vaccination coverage, poses a substantial public health and economic threat. Using county-level MMR vaccine coverage data and spatial incidence models, we quantified the economic burden of measles in 2025 and projected the impact of continued declines in vaccine uptake. In 2025, the estimated cost per measles case was $104,629 (50% High-Density Interval [HDI]: $100,729-$110,140), yielding a national burden of $244.2 million (50% HDI: $69.9-$872.5 million). The cost per case varied widely across counties and was inversely correlated with local population immunity levels (Spearman correlation = -0.75, p < 0.001). We modeled a scenario in which coverage among children aged 0-6 years declined by 1% per year, reaching a 5% absolute reduction by year 5 relative to baseline. Under this scenario, we projected a nonlinear surge in cases, hospitalizations, and annual expenditures arising from outbreak response, direct medical costs, and productivity losses. This scenario produced 17,232 (50% HDI: 9,177-26,428), 4,085 (50% HDI: 2,184-6,210) hospitalizations, 36 (50% HDI: 19-54) deaths, and $1.50 (50% HDI: $0.90-$2.85) billion in annual costs in 2030, with a cumulative cost of $7.77 billion (50% HDI: $5.56-$11.58 billion) over 5 years. These findings demonstrate that even marginal reductions in MMR vaccine uptake can result in disproportionately large health and economic burdens. Significance StatementThe United States is experiencing a resurgence of measles amid recent declines in childhood MMR vaccination. Using mathematical modeling informed by spatially resolved data on vaccination coverage, incidence, and associated economic costs, we quantified both the current and projected financial burden of measles in the United States under continued declines in coverage. For 2025, we estimated that measles imposes a cost of $244.2 million nationwide, with substantial heterogeneity in cost per case across counties driven by gaps in population immunity. Even modest annual reductions in vaccine coverage among young children generate a nonlinear increase in cases and hospitalizations, with costs totaling $7.77 billion over a five-year period.

Embedding equity into vaccine eligibility is essential for reducing health inequalities. Yet, adult vaccine eligibility in most European countries is primarily based on fixed age thresholds, prioritising cost-effectiveness. This approach risks excluding the most vulnerable populations living in deprived communities with poorer health and shorter survival into older age. Extending eligibility based on clinical risk partially addresses this gap. Higher rates of underdiagnosis and delayed diagnosis in deprived populations limit the fairness of this approach, however, with the status quo of adult vaccine eligibility criteria likely doing active harm. In this perspective, we demonstrate the extent of this inequity in England. For example, the average male living in Hyde Park in the northern city of Leeds dies 9.5 years too early to ever receive the RSV vaccine offer at age 75. Meanwhile, a male living in Hyde Park, London, lives much longer and may receive the benefits of the RSV vaccine for 10 years or more. Drawing on lessons from the COVID-19 pandemic, we propose further evaluation of alternative eligibility models that incorporate local place-based disadvantage, which will inherently account for life expectancy and deprivation levels. These models will ensure earlier access to vaccines for communities with the greatest need and improve health equity without overwhelming health systems.

BackgroundMalawi has one of the highest incidences and mortality due to cervical cancer, which is caused by the human papillomavirus (HPV). Achieving high HPV vaccination coverage is critical for advancing the World Health Organization (WHO) cervical cancer elimination strategy. This study aims to describe the spatio-temporal uptake of the first and second doses of the HPV vaccine in Malawi and to investigate the covariates associated with the uptake. MethodsWe analysed HPV vaccination coverage data from routinely collected administrative data across 28 districts in Malawi from 2019 to 2024. We used spatio-temporal Bayesian models in R-INLA to investigate the association between environmental factors, such as urbanization and climatic conditions, and vaccination uptake. ResultsHPV vaccine uptake was 46.83% (95% Credible interval, CrI: 46.52%, 47.21%) for the first dose, and 32.44% (95% CrI: 32.09%, 32.96%) for the second dose, across the study period, with distinctive subnational heterogeneity. A negative relationship was observed between nighttime light intensity and vaccination coverage (first dose: posterior mean: -0.599, (95% CrI: -1.160, -0.040); second dose: posterior mean: -2.164, (95% CrI: -3.415, -0.967)). ConclusionsHPV vaccination uptake in Malawian districts remains below the WHO 90% vaccination target. These findings emphasise the need for decentralised planning to improve coverage. Targeted interventions, mobile outreach programmes, and strengthened community engagement, particularly in urban settings, may help close coverage gaps and accelerate progress toward cervical cancer elimination in Malawi.

BackgroundCervical cancer is one of the most common cancers in women, particularly among women living with HIV (WLWH). Persistent infection with High-risk oncogenic human papillomavirus (Hr-HPV) is the primary etiological factor. However, data on Hr-HPV prevalence among WLWH in Kinshasa, Democratic Republic of the Congo, remains poorly documented. This study aimed to determine the prevalence of Hr-HPV infection and identify associated risk factors in this population. MethodsA cross-sectional study was conducted on WLWH aged 25 to 65 years receiving antiretroviral therapy at the DREAM Centre in Kinshasa. Cervical sample were collected and analysing using multiplex PCR for detection of Hr-HPV genotypes. Sociodemographic data and risk factors were collected via questionnaires, and associations with Hr-HPV infection were assessed using multivariate logistic regression. ResultsA total of 436 women were included. The prevalence of Hr-HPV infection was 47.25%. HPV types 16 and 18 (alone or in co-infection) were detected in 23.79% of participants. In a multivariate logistic regression analysis, WHO clinical stage 3-4 (aOR 1.75; 95% CI 1.16-2.64; p=0.008) and HIV viral load [&ge;]1000 copies/mL (aOR 3.08; 95% CI 1.28-7.42; p=0.012) and Antiretroviral therapy duration <2 years (aOR 0.52; 95% CI 0.29-0.93; p=0.028) were significantly associated with Hr-HPV infection. ConclusionsNearly one in two WLWH in Kinshasa was infected with Hr-HPV, and one in four carried HPV-16/18 genotypes. Advanced HIV disease and uncontrolled viral replication were strongly associated with Hr-HPV infection. These findings underscore the urgent need to integrate systematic Hr-HPV screening into HIV care programs, particularly for women with advanced clinical stage or persistent viremia.