Association of nirmatrelvir-ritonavir with post-acute sequelae and mortality in patients admitted to hospital with COVID-19: a retrospective cohort study.

BACKGROUND: Studies have established the short-term efficacy of nirmatrelvir-ritonavir in managing COVID-19, yet its effect on post-COVID-19 condition, especially in patients admitted to hospital, remains understudied. This study aimed to examine the effect of nirmatrelvir-ritonavir on post-COVID-19 condition among patients admitted to hospital in Hong Kong. METHODS: This retrospective cohort study used real-world, territory-wide inpatient records, vaccination records, and confirmed COVID-19 case data from the Hong Kong Hospital Authority and Department of Health, The Government of the Hong Kong Special Administrative Region. Patients aged 18 years and older who tested positive for SARS-CoV-2 between March 11, 2022, and Oct 10, 2023, and who were admitted to hospital with COVID-19 were included. The treatment group included patients prescribed nirmatrelvir-ritonavir within 5 days of symptom onset, excluding those prescribed molnupiravir within 21 days, and the control group had no exposure to either nirmatrelvir-ritonavir or molnupiravir. The outcomes were post-acute inpatient death and 13 sequelae (congestive heart failure, atrial fibrillation, coronary artery disease, deep vein thrombosis, chronic pulmonary disease, acute respiratory distress syndrome, interstitial lung disease, seizure, anxiety, post-traumatic stress disorder, end-stage renal disease, acute kidney injury, and pancreatitis). These outcomes were evaluated starting at 21 days after the positive RT-PCR date in each respective cohort constructed for the outcome. Standardised mortality ratio weights were applied to balance covariates, and Cox proportional hazards regression was used to investigate the relationship between nirmatrelvir-ritonavir and outcomes. FINDINGS: 136 973 patients were screened for inclusion, among whom 50 055 were eligible and included in the analysis (24 873 [49·7%] were female and 25 182 [50·3%] were male). 15 242 patients were prescribed nirmatrelvir-ritonavir during acute COVID-19 and 23 756 patients were included in the control group; 11 057 patients did not meet our definition for the exposed and unexposed groups. Patients were followed up for a median of 393 days (IQR 317-489). In the nirmatrelvir-ritonavir group compared with the control group, there was a significantly lower hazard of post-acute inpatient death (hazard ratio 0·62 [95% CI 0·57-0·68]; p<0·0001), congestive heart failure (0·70 [0·58-0·85]; p=0·0002), atrial fibrillation (0·63 [0·52-0·76]; p<0·0001), coronary artery disease (0·71 [0·59-0·85]; p=0·0002), chronic pulmonary disease (0·68 [0·54-0·86]; p=0·0011), acute respiratory distress syndrome (0·71 [0·58-0·86]; p=0·0007), interstitial lung disease (0·17 [0·04-0·75]; p=0·020), and end-stage renal disease (0·37 [0·18-0·74]; p=0·0049). There was no evidence indicating difference between the groups in deep vein thrombosis, seizure, anxiety, post-traumatic stress disorder, acute kidney injury, and pancreatitis. INTERPRETATION: This study showed extended benefits of nirmatrelvir-ritonavir for reducing the risk of post-acute inpatient death as well as cardiovascular and respiratory complications among patients admitted to hospital with COVID-19. Further research is essential to uncover the underlying mechanisms responsible for these observed negative associations and to devise effective strategies for preventing the onset of post-acute sequelae. FUNDING: Health and Medical Research Fund, Research Grants Council theme-based research schemes, and Research Grants Council Collaborative Research Fund.

Association between meteorological variations and the superspreading potential of SARS-CoV-2 infections.

BACKGROUND: While many investigations examined the association between environmental covariates and COVID-19 incidence, none have examined their relationship with superspreading, a characteristic describing very few individuals disproportionally infecting a large number of people. METHODS: Contact tracing data of all the laboratory-confirmed COVID-19 cases in Hong Kong from February 16, 2020 to April 30, 2021 were used to form the infection clusters for estimating the time-varying dispersion parameter (kt), a measure of superspreading potential. Generalized additive models with identity link function were used to examine the association between negative-log kt (larger means higher superspreading potential) and the environmental covariates, adjusted with mobility metrics that account for the effect of social distancing measures. RESULTS: A total of 6,645 clusters covering 11,717 cases were reported over the study period. After centering at the median temperature, a lower ambient temperature at 10th percentile (18.2 °C) was significantly associated with a lower estimate of negative-log kt (adjusted expected change: -0.239 [95 % CI: -0.431 to -0.048]). While a U-shaped relationship between relative humidity and negative-log kt was observed, an inverted U-shaped relationship with actual vapour pressure was found. A higher total rainfall was significantly associated with lower estimates of negative-log kt. CONCLUSIONS: This study demonstrated a link between meteorological factors and the superspreading potential of COVID-19. We speculated that cold weather and rainy days reduced the social activities of individuals minimizing the interaction with others and the risk of spreading the diseases in high-risk facilities or large clusters, while the extremities of relative humidity may favor the stability and survival of the SARS-CoV-2 virus.

Geographic Targeting of COVID-19 Testing to Maximize Detection in Los Angeles County.

Background: Many severe acute respiratory syndrome coronavirus 2 infections have not been detected, reported, or isolated. For community testing programs to locate the most cases under limited testing resources, we developed and evaluated quantitative approaches for geographic targeting of increased coronavirus disease 2019 testing efforts. Methods: For every week from December 5, 2021, to July 23, 2022, testing and vaccination data were obtained in ∼340 cities/communities in Los Angeles County, and models were developed to predict which cities/communities would have the highest test positivity 2 weeks ahead. A series of counterfactual scenarios were constructed to explore the additional number of cases that could be detected under targeted testing. Results: The simplest model based on most recent test positivity performed nearly as well as the best model based on most recent test positivity and weekly tests per 100 persons in identifying communities that would maximize the average yield of cases per test in the following 2 weeks and almost as well as the perfect knowledge of the actual positivity 2 weeks ahead. In the counterfactual scenario, increasing testing by 1% 2 weeks ahead and allocating all tests to communities with the top 10% of predicted positivity would yield a 2% increase in detected cases. Conclusions: Simple models based on current test positivity can predict which communities may have the highest positivity 2 weeks ahead and hence could be allocated with more testing resources.

Effectiveness of BNT162b2 and Sinovac vaccines against the transmission of SARS-CoV-2 during Omicron-predominance in Hong Kong: A retrospective cohort study of COVID-19 cases.

BACKGROUND: In 2022, SARS-CoV-2 Omicron variants circulated globally, generating concerns about increased transmissibility and immune escape. Hong Kong, having an infection-naive population with a moderate 2-dose vaccine coverage (63% by the end of 2021), experienced a COVID-19 epidemic largely seeded by Omicron BA.2 variants that led to the greatest outbreak in the region to date. Little remains known about the protection of commonly-administered vaccines against transmission of Omicron BA.2 variants. METHODS: In this retrospective cohort study, we identified 17 535 laboratory-confirmed COVID-19 cases using contact tracing information during the Omicron-predominant period between January and June 2022 in Hong Kong. Demographic characteristics, time from positive test result to case reporting, isolation, or hospital admission, as well as contact tracing history and contact setting were extracted. Transmission pairs were reconstructed through suspected epidemiological links according to contact tracing history, and the number of secondary cases was determined for each index case as a measurement for risk of transmission. The effectiveness of mRNA vaccine (BNT162b2) and inactivated vaccine (Sinovac) against transmission of BA.2 variants was estimated using zero-inflated negative binomial regression models. RESULTS: Vaccine effectiveness against transmission for patients who received the 2-dose BNT162b2 vaccine was estimated at 56.2% (95% CI: 14.5, 77.6), 30.6% (95% CI: 13.0, 44.6), and 21.3% (95% CI: 2.9, 36.2) on 15 - 90, 91 - 180, and 181 - 270 days after vaccination, respectively, showing a significant decrease over time. For 3-dose vaccines, vaccine effectiveness estimates were 41.0% (95% CI: 11.3, 60.7) and 41.9% (95% CI: 6.1, 64.0) on 15 - 180 days after booster doses of Sinovac and BNT162b2, respectively. Although significant vaccine effectiveness was detected in household settings, no evidence of such protective association was detected in non-household settings for either Sinovac or BNT162b2. CONCLUSION: Moderate and significant protection against Omicron BA.2 variants' transmission was found for 2 and 3 doses of Sinovac or BNT162b2 vaccines. Although protection by 2-dose BNT162b2 may evidently wane with time, protection could be restored by the booster dose. Here, we highlight the importance of continuously evaluating vaccine effectiveness against transmission for emerging SARS-CoV-2 variants.

Relationship between antidepressants and severity of SARS-CoV-2 Omicron infection: a retrospective cohort study using real-world data.

Background: Few studies have used real-world data to evaluate the impact of antidepressant use on the risk of developing severe outcomes after SARS-CoV-2 Omicron infection. Methods: This is a retrospective cohort study using propensity-score matching to examine the relationship between antidepressant use and COVID-19 severity. Inpatient and medication records of all adult COVID-19 patients in Hong Kong during the Omicron-predominated period were obtained. Severe clinical outcomes including intensive care unit admission and inpatient death after the first positive results of reverse transcription polymerase chain reaction as well as a composite outcome of both were studied. Cox proportional hazard models were applied to estimate the crude and adjusted hazard ratios (HR). Findings: Of 60,903 hospitalised COVID-19 patients admitted, 40,459 were included for matching, among which 3821 (9.4%) were prescribed antidepressants. The rates of intensive care unit admission, inpatient death, and the composite event were 3.9%, 25.5%, and 28.3% respectively in the unexposed group, 1.3%, 20.0%, and 21.1% respectively in the exposed group, with adjusted HR equal to 0.332 (95% CI, 0.245-0.449), 0.868 (95% CI, 0.800-0.942), and 0.786 (95% CI, 0.727-0.850) respectively. The result was generally consistent when stratified by selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. Antidepressants with functional inhibition of acid sphingomyelinase activity, specifically fluoxetine, were also negatively associated with the outcomes. The effect of antidepressants was more apparent in female and fully vaccinated COVID-19 patients. Interpretation: Antidepressant use was associated with a lower risk of severe COVID-19. The findings support the continuation of antidepressants in patients with COVID-19, and provide evidence for the treatment potential of antidepressants for severe COVID-19. Funding: This research was supported by Health and Medical Research Fund [grant numbers COVID190105, COVID19F03, INF-CUHK-1], Collaborative Research Fund of University Grants Committee [grant numbers C4139-20G], National Natural Science Foundation of China (NSFC) [71974165], and Group Research Scheme from The Chinese University of Hong Kong.

Spatio-temporal estimates of HIV risk group proportions for adolescent girls and young women across 13 priority countries in sub-Saharan Africa.

The Global AIDS Strategy 2021-2026 identifies adolescent girls and young women (AGYW) as a priority population for HIV prevention, and recommends differentiating intervention portfolios geographically based on local HIV incidence and individual risk behaviours. We estimated prevalence of HIV risk behaviours and associated HIV incidence at health district level among AGYW living in 13 countries in sub-Saharan Africa. We analysed 46 geospatially-referenced national household surveys conducted between 1999-2018 across 13 high HIV burden countries in sub-Saharan Africa. Female survey respondents aged 15-29 years were classified into four risk groups (not sexually active, cohabiting, non-regular or multiple partner[s] and female sex workers [FSW]) based on reported sexual behaviour. We used a Bayesian spatio-temporal multinomial regression model to estimate the proportion of AGYW in each risk group stratified by district, year, and five-year age group. Using subnational estimates of HIV prevalence and incidence produced by countries with support from UNAIDS, we estimated new HIV infections in each risk group by district and age group. We then assessed the efficiency of prioritising interventions according to risk group. Data consisted of 274,970 female survey respondents aged 15-29. Among women aged 20-29, cohabiting (63.1%) was more common in eastern Africa than non-regular or multiple partner(s) (21.3%), while in southern countries non-regular or multiple partner(s) (58.9%) were more common than cohabiting (23.4%). Risk group proportions varied substantially across age groups (65.9% of total variation explained), countries (20.9%), and between districts within each country (11.3%), but changed little over time (0.9%). Prioritisation based on behavioural risk, in combination with location- and age-based prioritisation, reduced the proportion of population required to be reached in order to find half of all expected new infections from 19.4% to 10.6%. FSW were 1.3% of the population but 10.6% of all expected new infections. Our risk group estimates provide data for HIV programmes to set targets and implement differentiated prevention strategies outlined in the Global AIDS Strategy. Successfully implementing this approach would result in more efficiently reaching substantially more of those at risk for infections.

Estimated preventable COVID-19-associated deaths due to non-vaccination in the United States.

While some studies have previously estimated lives saved by COVID-19 vaccination, we estimate how many deaths could have been averted by vaccination in the US but were not because of a failure to vaccinate. We used a simple method based on a nationally representative dataset to estimate the preventable deaths among unvaccinated individuals in the US from May 30, 2021 to September 3, 2022 adjusted for the effects of age and time. We estimated that at least 232,000 deaths could have been prevented among unvaccinated adults during the 15 months had they been vaccinated with at least a primary series. While uncertainties exist regarding the exact number of preventable deaths and more granular data are needed on other factors causing differences in death rates between the vaccinated and unvaccinated groups to inform these estimates, this method is a rapid assessment on vaccine-preventable deaths due to SARS-CoV-2 that has crucial public health implications. The same rapid method can be used for future public health emergencies.

Comparing the incubation period, serial interval, and infectiousness profile between SARS-CoV-2 Omicron and Delta variants.

In January 2022, the SARS-CoV-2 Omicron variants initiated major outbreaks and dominated the transmissions in Hong Kong, displacing an earlier outbreak seeded by the Delta variants. To provide insight into the transmission potential of the emerging variants, we aimed to compare the epidemiological characteristics of the Omicron and Delta variants. We analyzed the line-list clinical and contact tracing data of the SARS-CoV-2 confirmed cases in Hong Kong. Transmission pairs were constructed based on the individual contact history. We fitted bias-controlled models to the data to estimate the serial interval, incubation period and infectiousness profile of the two variants. Viral load data were extracted and fitted to the random effect models to investigate the potential risk modifiers for the clinical viral shedding course. Totally 14 401 confirmed cases were reported between January 1 and February 15, 2022. The estimated mean serial interval (4.4 days vs. 5.8 days) and incubation period (3.4 days vs. 3.8 days) were shorter for the Omicron than the Delta variants. A larger proportion of presymptomatic transmission was observed for the Omicron (62%) compared to the Delta variants (48%). The Omicron cases had higher mean viral load over an infection course than the Delta cases, with the elder cases appearing more infectious than the younger cases for both variants. The epidemiological features of Omicron variants were likely an obstacle to contact tracing measures, imposed as a major intervention in settings like Hong Kong. Continuously monitoring the epidemiological feature for any emerging SARS-CoV-2 variants in the future is needed to assist officials in planning measures for COVID-19 control.

Estimation of Vaccine Effectiveness of CoronaVac and BNT162b2 Against Severe Outcomes Over Time Among Patients With SARS-CoV-2 Omicron.

Importance: Few studies have evaluated the waning of vaccine effectiveness against severe outcomes caused by SARS-CoV-2 Omicron infection. Hong Kong is providing inactivated and mRNA vaccines, but the population had limited protection from natural infections before the Omicron variant emerged. Objective: To examine the change in vaccine effectiveness against hospitalization and mortality due to the Omicron variant over time. Design, Setting, and Participants: This case-control study included adults with SARS-CoV-2 Omicron variant infection who died or were hospitalized in Hong Kong from January 1 to June 5, 2022 (ie, case participants), and adults with SARS-CoV-2 Omicron, sampled from the public health registry during the study period (ie, control participants), who were matched to case participants by propensity score. Exposures: Vaccination status of the individuals. Main Outcomes and Measures: Estimated vaccine effectiveness against death, death or hospitalization, and death among hospitalized patients. Vaccine effectiveness was calculated as 1 - adjusted odds ratio obtained by conditional logistic regression adjusted with covariates for each period following vaccination. Results: There were 32 823 case participants (25 546 [77.8%] ≥65 years; 16 930 [47.4%] female) and 131 328 control participants (100 041 [76.2%] ≥65 years; 66 625 [46.6%] female) in the sample analyzed for the death or hospitalization outcome. Vaccine effectiveness against death or hospitalization was maintained for at least 6 months after the second dose of both CoronaVac (74.0%; 95% CI, 71.8%-75.8%) and BNT162b2 (77.4%; 95% CI, 75.5%-79.0%) vaccines. Vaccine effectiveness against death in those aged 18 to 49 years was 86.4% (95% CI, 85.8%-87.0%) and 92.9% (95% CI, 92.6%-93.2%) for those receiving 2 doses of CoronaVac and BNT162b2, respectively, while for patients aged 80 years or older, it dropped to 61.4% (95% CI, 59.8%-63.2%) and 52.7% (95% CI, 50.2%-55.6%) for CoronaVac and BNT162b2, respectively. Nevertheless, overall vaccine effectiveness against death at 4 to 6 months after the third dose was greater than 90% for CoronaVac, BNT162b2, and the mixed vaccine schedule (eg, mixed vaccines: vaccine effectiveness, 92.2%; 95% CI, 89.2%-95.1%). Conclusions and Relevance: While vaccines were generally estimated to be effective against severe outcomes caused by SARS-CoV-2 Omicron infection, this analysis found that protection in older patients was more likely to wane 6 months after the second dose. Hence, a booster dose is recommended for older patients to restore immunity. This is especially critical in a setting like Hong Kong, where third-dose coverage is still insufficient among older residents.

Dining-Out Behavior as a Proxy for the Superspreading Potential of SARS-CoV-2 Infections: Modeling Analysis.

BACKGROUND: While many studies evaluated the reliability of digital mobility metrics as a proxy of SARS-CoV-2 transmission potential, none examined the relationship between dining-out behavior and the superspreading potential of COVID-19. OBJECTIVE: We employed the mobility proxy of dining out in eateries to examine this association in Hong Kong with COVID-19 outbreaks highly characterized by superspreading events. METHODS: We retrieved the illness onset date and contact-tracing history of all laboratory-confirmed cases of COVID-19 from February 16, 2020, to April 30, 2021. We estimated the time-varying reproduction number (Rt) and dispersion parameter (k), a measure of superspreading potential, and related them to the mobility proxy of dining out in eateries. We compared the relative contribution to the superspreading potential with other common proxies derived by Google LLC and Apple Inc. RESULTS: A total of 6391 clusters involving 8375 cases were used in the estimation. A high correlation between dining-out mobility and superspreading potential was observed. Compared to other mobility proxies derived by Google and Apple, the mobility of dining-out behavior explained the highest variability of k (ΔR-sq=9.7%, 95% credible interval: 5.7% to 13.2%) and Rt (ΔR-sq=15.7%, 95% credible interval: 13.6% to 17.7%). CONCLUSIONS: We demonstrated that there was a strong link between dining-out behaviors and the superspreading potential of COVID-19. The methodological innovation suggests a further development using digital mobility proxies of dining-out patterns to generate early warnings of superspreading events.

Risk scores for predicting HIV incidence among adult heterosexual populations in sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Several HIV risk scores have been developed to identify individuals for prioritized HIV prevention in sub-Saharan Africa. We systematically reviewed HIV risk scores to: (1) identify factors that consistently predicted incident HIV infection, (2) review inclusion of community-level HIV risk in predictive models and (3) examine predictive performance. METHODS: We searched nine databases from inception until 15 February 2021 for studies developing and/or validating HIV risk scores among the heterosexual adult population in sub-Saharan Africa. Studies not prospectively observing seroconversion or recruiting only key populations were excluded. Record screening, data extraction and critical appraisal were conducted in duplicate. We used random-effects meta-analysis to summarize hazard ratios and the area under the receiver-operating characteristic curve (AUC-ROC). RESULTS: From 1563 initial search records, we identified 14 risk scores in 13 studies. Seven studies were among sexually active women using contraceptives enrolled in randomized-controlled trials, three among adolescent girls and young women (AGYW) and three among cohorts enrolling both men and women. Consistently identified HIV prognostic factors among women were younger age (pooled adjusted hazard ratio: 1.62 [95% confidence interval: 1.17, 2.23], compared to above 25), single/not cohabiting with primary partners (2.33 [1.73, 3.13]) and having sexually transmitted infections (STIs) at baseline (HSV-2: 1.67 [1.34, 2.09]; curable STIs: 1.45 [1.17; 1.79]). Among AGYW, only STIs were consistently associated with higher incidence, but studies were limited (n = 3). Community-level HIV prevalence or unsuppressed viral load strongly predicted incidence but was only considered in 3 of 11 multi-site studies. The AUC-ROC ranged from 0.56 to 0.79 on the model development sets. Only the VOICE score was externally validated by multiple studies, with pooled AUC-ROC 0.626 [0.588, 0.663] (I2 : 64.02%). CONCLUSIONS: Younger age, non-cohabiting and recent STIs were consistently identified as predicting future HIV infection. Both community HIV burden and individual factors should be considered to quantify HIV risk. However, HIV risk scores had only low-to-moderate discriminatory ability and uncertain generalizability, limiting their programmatic utility. Further evidence on the relative value of specific risk factors, studies populations not restricted to "at-risk" individuals and data outside South Africa will improve the evidence base for risk differentiation in HIV prevention programmes. PROSPERO NUMBER: CRD42021236367.

Characterization of Unlinked Cases of COVID-19 and Implications for Contact Tracing Measures: Retrospective Analysis of Surveillance Data.

BACKGROUND: Contact tracing and intensive testing programs are essential for controlling the spread of COVID-19. However, conventional contact tracing is resource intensive and may not result in the tracing of all cases due to recall bias and cases not knowing the identity of some close contacts. Few studies have reported the epidemiological features of cases not identified by contact tracing ("unlinked cases") or described their potential roles in seeding community outbreaks. OBJECTIVE: For this study, we characterized the role of unlinked cases in the epidemic by comparing their epidemiological profile with the linked cases; we also estimated their transmission potential across different settings. METHODS: We obtained rapid surveillance data from the government, which contained the line listing of COVID-19 confirmed cases during the first three waves in Hong Kong. We compared the demographics, history of chronic illnesses, epidemiological characteristics, clinical characteristics, and outcomes of linked and unlinked cases. Transmission potentials in different settings were assessed by fitting a negative binomial distribution to the observed offspring distribution. RESULTS: Time interval from illness onset to hospital admission was longer among unlinked cases than linked cases (median 5.00 days versus 3.78 days; P<.001), with a higher proportion of cases whose condition was critical or serious (13.0% versus 8.2%; P<.001). The proportion of unlinked cases was associated with an increase in the weekly number of local cases (P=.049). Cluster transmissions from the unlinked cases were most frequently identified in household settings, followed by eateries and workplaces, with the estimated probability of cluster transmissions being around 0.4 for households and 0.1-0.3 for the latter two settings. CONCLUSIONS: The unlinked cases were positively associated with time to hospital admission, severity of infection, and epidemic size-implying a need to design and implement digital tracing methods to complement current conventional testing and tracing. To minimize the risk of cluster transmissions from unlinked cases, digital tracing approaches should be effectively applied in high-risk socioeconomic settings, and risk assessments should be conducted to review and adjust the policies.

Changes in Measles Seroprevalence in China After the Launch of Two Provincial Supplementary Immunization Activities During 2009 to 2013.

BACKGROUND: Supplementary immunization activities (SIAs) have been demonstrated being effective in reducing measles incidence within a short period of time in China, but the effects are short-lived if there is no follow-up SIA with high routine immunization coverage. OBJECTIVES: To assess the change in measles seroprevalence from 2009 to 2013 after the launch of 2 large-scale SIAs within the period. METHODS: Three population-based cross-sectional serologic surveys of measles antibodies were conducted in 2009, 2011 and 2013 in Zhejiang, a province in eastern China, with serologic samples collected from 1541, 896 and 1474 subjects, respectively. The serum levels of immunoglobulin G antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: We found that the seropositivity rate among infants 0-7 months of age, a group having no vaccination benefit, was below 80% throughout the study period. In addition, the seropositivity rate among adults 30-49 years of age decreased significantly from 96.0% (95% confidence interval: 93.7%-98.3%) in 2011 to 88.5% (95% confidence interval: 84.3%-92.8%) in 2013. CONCLUSION: We showed that large-scale SIAs were effective, but their effects were not long lasting. Given the drop in seropositivity among adults, their susceptibility should be carefully monitored. While older individuals could benefit from the immunization activities, children who were too young to be vaccinated still have a weak seropositivity profile and the optimal age for the administration of the first dose of vaccine should be reconsidered.

Epidemiological changes in measles infections in southern China between 2009 and 2016: a retrospective database analysis.

BACKGROUND: The incidence rate of measles in China reached a nadir in 2012 after 2 supplementary immunization activities (SIAs) were undertaken in 2009 and 2010. However, the disease began re-emerging in 2013, with a high prevalence rate observed in 2013-2014 in the southern province of Guangdong. In this study, we assessed the changes that occurred in measles epidemiology during 2009-2016, particularly between 2009 and 2011 (when the influence of the SIAs were in full effect) and between 2012 and 2016 (when this influence subsided). METHODS: Data from 22,362 patients with measles diagnosed between 2009 and 2016, and whose diagnoses were confirmed clinically and/or with laboratory testing, were extracted from the National Infectious Disease Monitoring Information System. Descriptive analyses were performed, and changes in epidemiological characteristics between 2009 and 2011 and 2012-2016 were compared. RESULTS: There was a substantial surge in 0-8-month-old patients after 2012; the incidence rate increased from 4.0 per 100,000 population in 2011 (10.3% of the total) to 280 per 100,000 population in 2013 (32.8% of the total). Patients aged 0-6 years represented 73.4% of the total increase between 2011 and 2013. Compared with 2009-2011, adults aged ≥25 years accounted for a higher proportion of patients in 2013 and after (p < 0.01), and were highest in 2016 (31% of the patient total). CONCLUSION: Despite the remarkable results achieved by SIAs in terms of providing herd immunity, the 2013 resurgence of measles revealed insufficient immunization coverage among children. Therefore routine immunization programs should be strengthened, and supplementary vaccinations targeting adults should also be contemplated.

Association between meteorological variations and activities of influenza A and B across different climate zones: a multi-region modelling analysis across the globe.

OBJECTIVE: To elucidate the effects of meteorological variations on the activity of influenza A and B in 11 sites across different climate regions. METHODS: Daily numbers of laboratory-confirmed influenza A and B cases from 2011-2015 were collected from study sites where the corresponding daily mean temperature, relative humidity, wind speed and daily precipitation amount were used for boosted regression trees analysis on the marginal associations and the interaction effects. RESULTS: Cold temperature was a major determinant that favored both influenza A and B in temperate and subtropical sites. Temperature-to-influenza A, but not influenza B, exhibited a U-shape association in subtropical and tropical sites. High relative humidity was also associated with influenza activities but was less consistent with influenza B activity. Compared with relative humidity, absolute humidity had a stronger association - it was negatively associated with influenza B activity in temperate zones, but was positively associated with both influenza A and B in subtropical and tropical zones. CONCLUSION: The association between meteorological factors and with influenza activity is virus type specific and climate dependent. The heavy influence of temperature on influenza activity across climate zones implies that global warming is likely to have an impact on the influenza burden.

Latitudes mediate the association between influenza activity and meteorological factors: A nationwide modelling analysis in 45 Japanese prefectures from 2000 to 2018.

BACKGROUND: Cold and dry conditions were well-documented as a major determinant of influenza seasonality in temperate countries but the association may not be consistent when the climate in temperate areas is closer to that in sub-tropical areas. We hypothesized latitudes may mediate the association between influenza activity and meteorological factors in 45 Japanese prefectures. METHODS: We used the weekly incidence of influenza-like illness of 45 prefectures from 2000 to 2018 as a proxy for influenza activity in Japan, a temperate country lying off the east coast of Asia. A combination of generalized additive model and distributed lag nonlinear model was adopted to investigate the associations between meteorological factors (average temperature, relative humidity, total rainfall, and actual vapour pressure, a proxy for absolute humidity) and the influenza incidence. Kendall's tau b (τ) and Spearman correlation coefficient (rs) between latitude and the adjusted relative risk (ARR) of each meteorological factor were also assessed. RESULTS: A higher vapour pressure was significantly associated with a lower influenza risk but the ARR strongly weakened along with a lower latitude (τ = -0.23, p-value = 0.02; rs = -0.33, p-value = 0.03). Lower temperature and lower relatively humidity were significantly associated with higher influenza risks in over 65% and around 40% of the prefectures respectively but the strength and significance of the correlations between their ARRs and latitude were weaker than that from vapour pressure. CONCLUSION: Even though the range of latitudes in Japan is small (26°N-43°N), the relationships between meteorological factors and influenza activity were mediated by the latitude. Our study echoed absolute humidity played a more important role in relating influenza risk, but we on the other hand showed its effect on influenza activity could be hampered in a low-latitude temperate region, which have a warmer climate. These findings thus offer a high-resolution characterization of the role of meteorological factors on influenza seasonality.

Early Waning of Maternal Measles Antibodies in Infants in Zhejiang Province, China: A Comparison of Two Cross-Sectional Serosurveys.

In China, children aged <8 months, who were expected to be protected by maternal antibodies before receiving the first dose of measles vaccine, were the age group with the greatest risk of infection in recent years. In this study, we evaluated whether infants yet to be age-eligible for measles vaccine had a sufficient seropositive level of maternal measles antibodies in 2009 and 2013. Blood samples were collected from infants aged <8 months through population-based serological surveys conducted in Zhejiang, China. Serum levels of immunoglobulin G measles antibodies were quantified using enzyme-linked immunosorbent assay. In 2013, the mean geometric mean titres (GMTs) of infants aged 4 to 8 months were below the seropositivity threshold (<200 mIU/mL), decreasing from 118.6 mIU/mL (95% confidence interval [CI] 83.0, 169.3 mIU/mL) at 4 months to 28.6 mIU/mL (95% CI 15.6, 52.3 mIU/mL) at 7 months. Antibody levels were significantly lower in 2013 than in 2009 starting from 5 months of age. In conclusion, infants aged 4 to 8 months are susceptible to measles due to low levels of maternal measles antibodies. It is thus suggested to provide infants with a supplementary dose on top of the routine schedule, and/or launch catch-up vaccination campaigns among young women.

Mathematical modelling of the impact of treating latent tuberculosis infection in the elderly in a city with intermediate tuberculosis burden.

Hong Kong is a high-income city with intermediate tuberculosis (TB) burden primarily driven by endogenous reactivations. A high proportion of remote latently infected people, particularly elderly, hinders the effectiveness of current strategies focusing on passive TB detection. In this study, we developed a mathematical model to evaluate the impact of treating latent TB infection (LTBI) in the elderly in addition to current TB control strategies. The model was calibrated using the annual age-stratified TB notifications from 1965-2013 in Hong Kong. Our results showed that at present, approximately 75% of annual new notifications were from reactivations. Given the present treatment completion rate, even if only a low to moderate proportion (approximately 20% to 40%) of elderly people were screened and treated for LTBI, the overall TB incidence could be reduced by almost 50%, to reach the 2025 milestone of the global End TB Strategy. Nevertheless, due to a high risk of hepatotoxicity in elderly population, benefit-risk ratios were mostly below unity; thus, intervention programs should be carefully formulated, including prioritising LTBI treatment for high-risk elderly groups who are closely monitored for possible adverse side effects.