Toward tuberculosis elimination by understanding epidemiologic characteristics and risk factors in Hainan Province, China

Background The disease burden of tuberculosis(TB)was heavy in Hainan Province,China,and the information on transmission patterns was limited with few studies.This atudy aims to further explore the epidemiological charac-teristics and influencing factors of TB in Hainan Province,and thereby contribute valuable scientific evidences for TB elimination in Hainan Province.Methods The TB notification data in Hainan Province from 2013 to 2022 were collected from the Chinese National Disease Control Information System Tuberculosis Surveillance System,along with socio-economic data.The spatial-temporal and population distributions were analyzed,and spatial autocorrelation analysis was conducted to explore TB notification rate clustering.In addition,the epidemiological characteristics of the cases among in-country migrants were described,and the delay pattern in seeking medical care was investigated.Finally,a geographically and tem-porally weighted regression(GTWR)model was adopted to analyze the relationship between TB notification rate and socio-economic indicators.The tailored control suggestions in different regions for TB elimination was provided by understanding epidemiological characteristics and risk factors obtained by GTWR.Results From 2013 to 2022,64,042 cases of TB were notified in Hainan Province.The estimated annual percent-age change of TB notification rate in Hainan Province from 2013 to 2020 was-6.88%[95%confidence interval(CI):-5.30%,-3.69%],with higher rates in central and southern regions.The majority of patients were males(76.33%)and farmers(67.80%).Cases among in-country migrants primarily originated from Sichuan(369 cases),Heilongjiang(267 cases),Hunan(236 cases),Guangdong(174 cases),and Guangxi(139 cases),accounting for 53%.The majority(98.83%)of TB cases were notified through passive case finding approaches,with delay in seeking care.The GTWR analysis showed that gross domestic product per capita,the number of medical institutions and health personnel per 10,oo0 people were main factors affecting the high TB notification rates in some regions in Hainan Province.Dif-ferent regional tailored measures such as more TB specialized hospitals were proposed based on the characteristics of each region.Conclusions The notification rate of TB in Hainan Province has been declining overall but still remained high in central and southern regions.Particular attention should be paid to the prevalence of TB among males,farmers,and outof-province migrant populations.The notification rate was also influenced by economic development and medical conditions,indicating the need of more TB specialized hospitals,active surveillance and other tailored prevention and control measures to promote the progress of TB elimination in Hainan Province.

Epidemiological features and temporal trends of the co-infection between HIV and tuberculosis, 1990-2021: findings from the Global Burden of Disease Study 2021

Background The co-infection of human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)and tuberculosis(TB)poses a significant clinical challenge and is a major global public health issue.This study aims to elucidate the disease burden of HIV-TB co-infection in global,regions and countries,providing critical informa-tion for policy decisions to curb the HIV-TB epidemic.Methods The ecological time-series study used data from the Global Burden of Disease(GBD)Study 2021.The data encompass the numbers of incidence,prevalence,mortality,and disability-adjusted life year(DALY),as well as age-standardized incidence rate(ASIR),prevalence rate(ASPR),mortality rate(ASMR),and DALY rate for HIV-infected drug-susceptible tuberculosis(HIV-DS-TB),HIV-infected multidrug-resistant tuberculosis(HIV-MDR-TB),and HIV-infected extensively drug-resistant tuberculosis(HIV-XDR-TB)from 1990 to 2021.from 1990 to 2021.The estimated annual percentage change(EAPC)of rates,with 95%confidence intervals(C/s),was calculated.Results In 2021,the global ASIR for HIV-DS-TB was 11.59 per 100,000 population(95%UI:0.37-13.05 per 100,000 population),0.55 per 100,000 population(95%UI:0.38-0.81 per 100,000 population),for HIV-MDR-TB,and 0.02 per 100,000 population(95%UI:0.01-0.03 per 100,000 population)for HIV-XDR-TB.The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71(95%CI:1.92-7.59)and 13.63(95%CI:9.44-18.01),respectively.The global ASMR for HIV-DS-TB was 2.22 per 100,000 population(95%UI:1.73-2.74 per 100,000 population),0.21 per 100,000 population(95%UI:0.09-0.39 per 100,000 population)for HIV-MDR-TB,and 0.01 per 100,000 population(95%UI:0.00-0.03 per 100,000 population)for HIV-XDR-TB in 2021.The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78(95%CI:1.32-8.32)and 10.00(95%Cl:6.09-14.05),respectively.Conclusions The findings indicate that enhancing diagnostic and treatment strategies,strengthening healthcare infrastructure,increasing access to quality medical care,and improving public health education are essential to combat HIV-TB co-infection.

Towards an actionable One Health approach

Background Despite the increasing focus on strengthening One Health capacity building on global level,challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region.Recognizing these gaps,the One Health Action Commission(OHAC)was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact.Main text This viewpoint describes the agenda of,and motivation for,the recently formed OHAC.Recognizing the urgent need for evidence to support the formulation of necessary action plans,OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses,antimicrobial resistance,addressing food safety,and to enhance capacity building for context-sensitive One Health implementation.Conclusions By promoting broader engagement and connection of multidisciplinary stakeholders,OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge,distilled practical experience and actionable policy advice,guided by strong ethical principles of One Health.

Promoting higher-valent pediatric combination vaccines in China: challenges and recommendations for action

Many countries have adopted higher-valent pediatric combination vaccines to simplify vaccination schedules and minimize health expenditures and social costs.However,China is conservative in the use of pediatric combina-tion vaccines.By reviewing and synthesizing quantitative and qualitative data,in this commentary we identify gaps and challenges to combination vaccine use and make recommendations for promoting use of higher-valent pediatric combination vaccines in China.Challenges are in four dimensions:(1)legislation and regulation,(2)immunization schedule design,(3)vaccine awareness and price,and(4)research and development capacity.To optimize the use of combination vaccines to reduce vaccine-preventable disease burden,we make recommendations that address key challenges:(1)develop policies and regulations to strengthen enforcement of the Vaccine Administration Law and remove regulatory hurdles that hinder combination vaccine research and development,(2)establish an evi-dence-informed policy-making mechanism for combination vaccines,(3)resolve immunization schedule conflicts between monovalent and combination vaccines,and(4)implement effective interventions to increase vaccine awareness and reduce price.

Epidemiological characteristics of tuberculosis incidence and its macro-influence factors in Chinese mainland during 2014-2021

Background Tuberculosis(TB)remains a pressing public health issue,posing a significant threat to individuals'well-being and lives.This study delves into the TB incidence in Chinese mainland during 2014-2021,aiming to gain deeper insights into their epidemiological characteristics and explore macro-level factors to enhance control and prevention.Methods TB incidence data in Chinese mainland from 2014 to 2021 were sourced from the National Notifiable Disease Reporting System(NNDRS).A two-stage distributed lag nonlinear model(DLNM)was constructed to evaluate the lag and non-linearity of daily average temperature(℃,Atemp),average relative humidity(%,ARH),average wind speed(m/s,AWS),sunshine duration(h,SD)and precipitation(mm,PRE)on the TB incidence.A spatial panel data model was used to assess the impact of demographic,medical and health resource,and economic factors on TB incidence.Results A total of 6,587,439 TB cases were reported in Chinese mainland during 2014-2021,with an average annual incidence rate of 59.17/100,000.The TB incidence decreased from 67.05/100,000 in 2014 to 46.40/100,000 in 2021,notably declining from 2018 to 2021(APC=-8.87%,95%CI:-11.97,-6.85%).TB incidence rates were higher among males,farmers,and individuals aged 65 years and older.Spatiotemporal analysis revealed a significant cluster in Xinjiang,Qinghai,and Xizang from March 2017 to June 2019(RR=3.94,P<0.001).From 2014 to 2021,the proportion of etiologically confirmed cases increased from 31.31%to 56.98%,and the time interval from TB onset to diagnosis shortened from 26 days(IQR:10-56 days)to 19 days(IQR:7-44 days).Specific meteorological conditions,including low temperature(<16.69℃),high relative humidity(>71.73%),low sunshine duration(<6.18 h)increased the risk of TB incidence,while extreme low wind speed(<2.79 m/s)decreased the risk.The spatial Durbin model showed positive associations between TB incidence rates and sex ratio(β=1.98),number of beds in medical and health institutions per 10,000 population(β=0.90),and total health expenses(β=0.55).There were negative associations between TB incidence rates and population(β=-1.14),population density(β=-0.19),urbanization rate(β=-0.62),number of medical and health institutions(β=-0.23),and number of health technicians per 10,000 population(β=-0.70).Conclusions Significant progress has been made in TB control and prevention in China,but challenges persist among some populations and areas.Varied relationships were observed between TB incidence and factors from meteorological,demographic,medical and health resource,and economic aspects.These findings underscore the importance of ongoing efforts to strengthen TB control and implement digital/intelligent surveillance for early risk detection and comprehensive interventions.

Integrated Eco-Health approach significantly reduces helminth infections in endemic Khong islands with emphasis on Schistosoma mekongi

Background Helminth infections,including Opisthorchis viverrini,hookworm,and Trichuris trichiura,are prevalent in Khong district,Champasack province,southern Lao People's Democratic Republic(PDR).Schistosomiasis caused by Schistosoma mekongi is of public health concern on the islands of the Khong district.This study aimed to assess the impact of an Eco-Health/One-Health approach in combination with mass drug administration(MDA)to reduce these helminth infections.Methods We conducted a community intervention using a stepped-wedge trial approach on two endemic islands(Donsom and Donkhone)of the Khong district,Champasack province,Lao PDR,between April 2012 and March 2013.In each study village,30-40 households were randomly selected.All members of selected households,who were at home during the study period were invited to participate in the study.A baseline study was conducted to assess helminth infections,knowledge attitudes and practices toward Schistosoma mekongi infection,behavior of open defecation and availability of latrine at home.After the baseline(TO),the Eco-Health/One-Health approach was imple-mented on Donsom(intervention)and Donkhone island(control).An assessment was conducted in 2014(T1),one year after the completion of intervention implementation,to assess the short-term impact of the Eco-Health/One-Health approach on helminth infections and compare intervention and control islands.Later in 2015,the Eco-Health/One-Health approach was implemented on control island(Donkhone).After the implementation of intervention,the parasitological assessments were conducted annually in humans in 2015(T2),in 2016(T3)and in 2017(T4),and in dogs in 2017(T4)to evaluate the long-term impact of the intervention on helminth infections.Frequency was used to describe the prevalence of helminth infections.Logistic regression was applied to associate the KAP(knowledge,attitudes,and practices and open defecation behavior)and the reduction of helminth infections between intervention and control islands.The reduction in prevalence pre-and post-intervention was associated using a McNemar test.A two-independent sample t-test was applied to compare the mean eggs per gram(EPG)of helminth infections between control and intervention islands.A paired t-test test was used to compare the mean EPG of stool samples before(baseline)and after(follow-up)interventions for the two islands separately.A P-value lower than 0.05 was considered statistically significant.Results Eco-Health/One-Health approach appears to be associated with reduction in prevalence of S.mekongi by 9.0%[odds ratio(OR)=0.49,P=0.003]compared to the use of mass drug administration alone(control island).Additionally,this intervention package significantly reduced O.viverrini infection by 20.3%(OR=1.92,P<0.001)and hookworm by 17.9%(OR=0.71,P=0.045),respectively.Annual parasitological assessments between 2012 and 2017 showed that the Eco-Health/One-Health approach,coupled with MDA,steadily reduced the prevalence of S.mekongi on the intervention island from 29.1%to 1.8% and on the control island from 28.4%to 3.1%,respectively.Conclusions The study findings suggest that the Eco-Health/One-Health approach appears to be associated with a significant reduction in prevalence of S.mekongi and helminth co-infections,particularly hookworm and T.trichiura.Therefore,implementing the Eco-Health/One-Health approach in schistosomiasis-endemic areas could accelerate the achievement of national goals for transmission interruption by 2025 and elimination by 2030.

Need for operational simplicity and timely disbursal of benefits—a qualitative exploration of the implementation of a direct benefit transfer scheme for persons with tuberculosis in India

Background Ni-kshay Poshan Yojana(NPY)is a direct benefit transfer scheme of the Government of India introduced in 2018 to support the additional nutritional requirements of persons with TB(PwTB).Our recent nationwide evaluation of implementation and utilization of NPY using programmatic data of PwTB from nine randomly selected Indian states,reported a 70%coverage and high median delay in benefit credit.We undertook a qualitative study between January and July 2023,to understand the detailed implementation process of NPY and explore the enablers and barriers to effective implementation and utilization of the NPY scheme.Methods We followed a grounded theory approach to inductively develop theoretical explanations for social phenomena through data generated from multiple sources.We conducted 36 in-depth interviews of national,district and field-level staff of the National Tuberculosis Elimination Programme(NTEP)and NPY beneficiaries from 30 districts across nine states of India,selected using theoretical sampling.An analytical framework developed through inductive coding of a set of six interviews,guided the coding of the subsequent interviews.Categories and themes emerged through constant comparison and the data collection continued until theoretical saturation.Results Stakeholders perceived NPY as a beneficial initiative.Strong political commitment from the state administration,mainstreaming of NTEP work with the district public healthcare delivery system,availability of good geographic and internet connectivity and state-specific grievance redressal mechanisms and innovations were identified as enablers of implementation.However,the complex,multi-level benefit approval process,difficulties in accessing banking services,perceived inadequacy of benefits and overworked human resources in the NTEP were identified as barriers to implementation and utilization.Conclusion The optimal utilization of NPY is enabled by strong political commitment and challenged by its lengthy implementation process and delayed disbursal of benefits.We recommend greater operational simplicity in NPY implementation,integrating NTEP activities with the public health system to reduce the burden on the program staff,and revising the benefit amount more equitably.

Forecasting and mapping dengue fever epidemics in China: a spatiotemporal analysis

Background Dengue fever(DF)has emerged as a significant public health concern in China.The spatiotemporal patterns and underlying influencing its spread,however,remain elusive.This study aims to identify the factors driving these variations and to assess the city-level risk of DF epidemics in China.Methods We analyzed the frequency,intensity,and distribution of DF cases in China from 2003 to 2022 and evalu-ated 11 natural and socioeconomic factors as potential drivers.Using the random forest(RF)model,we assessed the contributions of these factors to local DF epidemics and predicted the corresponding city-level risk.Results Between 2003 and 2022,there was a notable correlation between local and imported DF epidemics in case numbers(r=0.41,P<0.01)and affected cities(r=0.79,P<0.01).With the increase in the frequency and intensity of imported epidemics,local epidemics have become more severe.Their occurrence has increased from five to eight months per year,with case numbers spanning from 14 to 6641 per month.The spatial distribution of city-level DF epidemics aligns with the geographical divisions defined by the Huhuanyong Line(Hu Line)and Qin Mountain-Huai River Line(Q-H Line)and matched well with the city-level time windows for either mosquito vector activity(83.59%)or DF transmission(95.74%).The RF models achieved a high performance(AUC=0.92)when considering the time windows.Importantly,they identified imported cases as the primary influencing factor,contributing significantly(24.82%)to local DF epidemics at the city level in the eastern region of the Hu Line(E-H region).Moreover,imported cases were found to have a linear promoting impact on local epidemics,while five climatic and six socioeconomic factors exhibited nonlinear effects(promoting or inhibiting)with varying inflection values.Additionally,this model demonstrated outstanding accuracy(hitting ratio=95.56%)in predicting the city-level risks of local epidemics inChina.Conclusions China is experiencing an increasing occurrence of sporadic local DF epidemics driven by an unavoida-bly higher frequency and intensity of imported DF epidemics.This research offers valuable insights for health authori-ties to strengthen their intervention capabilities against this disease.

Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae among healthy children under 5 years of age in Hainan Province, China

Background The thirteen-valent pneumococcal conjugate vaccine(PCV13)is not included in the national immu-nization program and is administered voluntarily with informed consent in China.In preparation for assessing the impact of pilot introduction in Hainan Province,we conducted a carriage study among children under 5 years of age from four locations in Hainan Province,China.Methods From March to June 2022,nasopharyngeal(NP)swabs,collected from healthy children aged younger than 59 months who lived in the 4 different locations(Haikou,Wanning,Baisha and Qiongzhong)in Hainan Province,were tested for pneumococcus using conventional culture.Pneumococcal isolates were serotyped using the Quel-lung reaction.Risk factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age,daycare attendance and other factors.Results Pneumococcus was isolated in 710(30.4%)of the 2333 children enrolled.Of 737 pneumococci,29 serotypes were identifed;60.9%were PCV13 serotypes;the most common vaccine serotypes were 6B(20.4%),19F(13.0%),6A(11.9%)and 23F(6.1%);and the most common nonvaccine serotypes were 23A(12.9%),34(6.1%)and nontypeable(NT)pneumococci(5.6%).Children vaccinated with PCV13 had lower carriage(17.7%vs 32.5%;P=0.0001)and fewer PCV13 serotypes(41.9%vs 62.7%;P=0.0017)compared to unimmunized children.After adjustment,NP carriage Was higher among children attending daycare(aOR=2.3,95%CI:1.7-3.2),living in rural areas(aOR=1.4,95%CI:1.1-1.8),living with siblings(aOR=1.3,95%CI:1.0-1.6)and whose mothers had completed senior high/technical sec-ondary school(aOR=1.5,95%CI:1.1-2.0).In contrast,completion of 3-4 doses of PCV13 were associated with a lower carriage rate(aOR=0.6,95%CI:0.4-0.9).Conclusions We established the baseline of pneumococcal carriage,serotype distribution and PCV13 immuni-zation rates among healthy children under 5 years of age in Hainan Province,prior to the introduction of PCV13 into the national immunization program.The high proportion of PCV13 serotypes suggests that PCV13 introduction will likely have a substantial impact on pneumococcal carriage in Hainan Province.

The risk of mpox importation and subsequent outbreak potential in Chinese mainland: a retrospective statistical modelling study

Background The 2022-2023 mpox(monkeypox)outbreak has spread rapidly across multiple countries in the non-endemic region,mainly among men who have sex with men(MSM).In this study,we aimed to evaluate mpox's importation risk,border screening effectiveness and the risk of local outbreak in Chinese mainland.Methods We estimated the risk of mpox importation in Chinese mainland from April 14 to September 11,2022 using the number of reported mpox cases during this multi-country outbreak from Global.health and the international air-travel data from Official Aviation Guide.We constructed a probabilistic model to simulate the effectiveness of a border screening scenario during the mpox outbreak and a hypothetical scenario with less stringent quarantine requirement.And we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men,considering different transmissibility,population immunity and population activity.Results We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations respectively.Under the quarantine policy,15-19% of imported infections would remain undetected.Once a case of mpox is introduced into active MSM population with almost no population immunity,the risk of triggering local transmission is estimated at 42%,and would rise to>95% with over six cases.Conclusions Our study demonstrates that the reduced international air-travel volume and stringent border entry policy during the COvID-19 pandemic reduced mpox importations prominently.However,the risk could be sub-stantially higher with the recovery of air-travel volume to pre-pandemic level.Mpox could emerge as a public health threat for Chinese mainland given its large MSM community.

Molecular epidemiology and phylogenetic analysis of influenza viruses A (H3N2) and B/ Victoria during the COVID-19 pandemic in Guangdong, China

Background Non-pharmaceutical measures and travel restrictions have halted the spread of coronavirus disease 2019(COVID-19)and influenza.Nonetheless,with COVID-19 restrictions lifted,an unanticipated outbreak of the influ-enza B/Nictoria virus in late 2021 and another influenza H3N2 outbreak in mid-2022 occurred in Guangdong,southern China.The mechanism underlying this phenomenon remains unknown.To better prepare for potential influenza out-breaks during COVID-19 pandemic,we studied the molecular epidemiology and phylogenetics of influenza A(H3N2)and BNictoria that circulated during the COVID-19 pandemic in this region.Methods From January 1,2018 to December 31,2022,we collected throat swabs from 173,401 patients in Guang-dong who had acute respiratory tract infections.Influenza viruses in the samples were tested using reverse tran-scription-polymerase chain reaction,followed by subtype identification and sequencing of hemagglutinin(HA)and neuraminidase(NA)genes.Phylogenetic and genetic diversity analyses were performed on both genes from 403 samples.A rigorous molecular clock was aligned with the phylogenetic tree to measure the rate of viral evolution and the root-to-tip distance within strains in different years was assessed using regression curve models to determine the correlation.Results During the early period of COVID-19 control,various influenza viruses were nearly undetectable in respiratory specimens.When control measures were relaxed in January 2020,the influenza infection rate peaked at 4.94%(39/789)in December 2021,with the influenza B/Victoria accounting for 87.18%(34/39)of the total influenza cases.Six months later,the influenza infection rate again increased and peaked at 11.34%(255/2248)in June 2022;influenza A/H3N2 accounted for 94.51%(241/255)of the total influenza cases in autumn 2022.The diverse geographic distribution of HA genes of B/Nictoria and A/H3N2 had drastically reduced,and most strains originated from China.The rate of B/Victoria HA evolution(3.11×10^(-3),P<0.05)was 1.7 times faster than before the COVID-19 outbreak(1.80×10^(-3),P<0.05).Likewise,the H3N2 HA gene's evolution rate was 7.96×10^(-3)(P<0.05),which is 2.1 times faster than the strains'pre-COVID-19 evolution rate(3.81×10^(-3),P<0.05).Conclusions Despite the extraordinarily low detection rate of influenza infection,concealed influenza transmission may occur between individuals during strict COVID-19 control.This ultimately leads to the accumulation of viral mutations and accelerated evolution of H3N2 and BVictoria viruses.Monitoring the evolution of influenza may provide insights and alerts regarding potential epidemics in the future.

Chromosome-level genome assembly of Oncomelania hupensis: the intermediate snail host of Schistosoma japonicum

Background Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China, the Philippines and Indonesia.Oncomelania hupensis (Gastropoda: Pomatiopsidae) is the unique intermediate host ofS. japonicum. A complete genome sequence ofO. hupensis will enable the fundamental understanding of snail biology as well as its co-evolution with theS. japonicum parasite. Assembling a high-quality reference genome ofO. hupehensis will provide data for further research on the snail biology and controlling the spread ofS. japonicum.Methods The draft genome was de novo assembly using the long-read sequencing technology (PacBio Sequel II) and corrected with Illumina sequencing data. Then, using Hi-C sequencing data, the genome was assembled at the chromosomal level. CAFE was used to do analysis of contraction and expansion of the gene family and CodeML module in PAML was used for positive selection analysis in protein coding sequences.Results A total length of 1.46 Gb high-qualityO. hupensis genome with 17 unique full-length chromosomes (2n = 34) of the individual including a contig N50 of 1.35 Mb and a scaffold N50 of 75.08 Mb. Additionally, 95.03% of these contig sequences were anchored in 17 chromosomes. After scanning the assembled genome, a total of 30,604 protein-coding genes were predicted. Among them, 86.67% were functionally annotated. Further phylogenetic analysis revealed thatO. hupensis was separated from a common ancestor ofPomacea canaliculata andBellamya purificata approximately 170 million years ago. Comparing the genome ofO. hupensis with its most recent common ancestor, it showed 266 significantly expanded and 58 significantly contracted gene families (P < 0.05). Functional enrichment of the expanded gene families indicated that they were mainly involved with intracellular, DNA-mediated transposition, DNA integration and transposase activity.Conclusions Integrated use of multiple sequencing technologies, we have successfully constructed the genome at the chromosomal-level ofO. hupensis. These data will not only provide the compressive genomic information, but also benefit future work on population genetics of this snail as well as evolutional studies betweenS. japonicum and the snail host.

Global, regional, and national burden of HIV-negative tuberculosis, 1990-2021: findings from the Global Burden of Disease Study 2021

Background Tuberculosis(TB)is a major infectious disease with significant public health implications.Its widespread transmission,prolonged treatment duration,notable side effects,and high mortality rate pose severe challenges.This study examines the epidemiological characteristics of TB globally and across major regions,providing a scientific basis for enhancing TB prevention and control measures worldwide.Methods The ecological study used data from the Global Burden of Disease(GBD)Study 2021.It assessed new incidence cases,deaths,disability-adjusted life years(DALYs),and trends in age-standardized incidence rates(ASIRs),mortality rates(ASMRs),and DALY rates for drug-susceptible tuberculosis(DS-TB),multidrug-resistant tuberculosis(MDR-TB),and extensively drug-resistant tuberculosis(XDR-TB)from 1990 to 2021.A Bayesian age-period-cohort model was applied to project ASIR and ASMR.Results In 2021,the global ASIR for all HIV-negative TB was 103.00 per 100,000 population 95%uncertainty interval(UI):92.21,114.91 per 100,000 populationl,declining by 0.40%(95%UI:-0.43,-0.38%)compared to 1990.The global ASMR was 13.96 per 100,000 population(95%UI:12.61,15.72 per 100,000 population),with a decline of 0.44%(95%UI:-0.61,-0.23%)since 1990.The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population(95%UI:522.37,649.82 per 100,000 population),showing a decrease of 0.65%(95%UI:-0.69,-0.57 per 100,000 population)from 1990.The global ASIR of MDR-TB has not decreased since 2015,instead,it has shown a slow upward trend in recent years.The ASIR of XDR-TB has exhibited significant increase in the past 30 years.The projections indicate MDR-TB and XDR-TB are expected to see signifcant increases in both ASIR and ASMR from 2022 to 2035,highlighting the growing challenge of drug-resistant TB.Conclusions This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years.To reduce the TB burden,it is essential to enhance health infrastructure and increase funding in low-SDl regions.Developing highly efficient,accurate,and convenient diagnostic reagents,along with more effective therapeutic drugs,and improving public health education and community engagement,are crucial for curbing TB transmission.

Incidence and warning signs for complications of human brucellosis: a multi-center observational study from China

Background Brucellosis is a severe zoonotic disease that is often overlooked, particularly in impoverished countries. Timely identification of focal complications in brucellosis is crucial for improving treatment outcomes. However, there is currently a lack of established indicators or biomarkers for diagnosing these complications. Therefore, this study aimed to investigate potential warning signs of focal complications in human brucellosis, with the goal of providing practical parameters for clinicians to aid in the diagnosis and management of patients.Methods A multi-center cross-sectional study was conducted in China from December 2019 to August 2021. The study aimed to investigate the clinical characteristics and complications of patients with brucellosis using a questionnaire survey and medical record system. The presence of warning signs for complications was assessed using univariate and multivariate logistic regression models. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used for variable screening and model evaluation.Results A total of 880 participants diagnosed with human brucellosis were enrolled. The median age of the patients was 50 years [interquartile range (IQR): 41.5-58.0], and 54.8% had complications. The most common organ system affected by complications was the osteoarticular system (43.1%), with peripheral arthritis (30.0%), spondylitis (16.6%), paravertebral abscess (5.0%), and sacroiliitis (2.7%) being the most prevalent. Complications in other organ systems included the genitourinary system (4.7%), respiratory system (4.7%), and hematologic system (4.6%). Several factors were found to be associated with focal brucellosis. These factors included a long delay in diagnosis [odds ratio (OR) = 3.963, 95% confidence interval(CI): 1.906-8.238 for > 90 days], the presence of underlying disease (OR = 1.675, 95%CI: 1.176-2.384), arthralgia (OR = 3.197, 95%CI: 1.986-5.148), eye bulging pain (OR = 3.482, 95%CI: 1.349-8.988), C-reactive protein (CRP) > 10 mg/L (OR = 1.910, 95%CI: 1.310-2.784) and erythrocyte sedimentation rate (ESR) elevation (OR = 1.663, 95%CI: 1.145-2.415). The optimal cutoff value in ROC analysis was > 5.4 mg/L for CRP (sensitivity 73.4% and specificity 51.9%) and > 25 mm/h for ESR (sensitivity 47.9% and specificity 71.1%).Conclusions More than 50% of patients with brucellosis experienced complications. Factors such as diagnostic delay, underlying disease, arthralgia, eye pain, and elevated levels of CRP and ESR were identified as significant markers for the development of complications. Therefore, patients presenting with these conditions should be closely monitored for potential complications, regardless of their culture results and standard tube agglutination test titers.

MODELS:a six-step framework for developing an infectious disease model

Since the COVID-19 pandemic began,a plethora of modeling studies relatedto COVID-19 have been released.While some models stand out due to their innovative approaches,others are flawed in their methodology.To assist novices,frontline healthcare workers,and public health policymakers in navigating the complex landscape of these models,we introduced a structured framework named MODELS.This framework is designed to detail the essential steps and considerations for creating a dependable epidemic model,offering direction to researchers engaged in epidemic modeling endeavors.

Treatment and prevention of epilepsy in onchocerciasis-endemic areas is urgently needed

Background There is increasing epidemiological evidence supporting the association between onchocerciasis and seizures, reinforcing the concept of onchocerciasis-associated epilepsy (OAE). The aim of this paper is to provide an update on the new knowledge about OAE and to propose recommendations to the World Health Organization how to address this public health problem.Main text During the 2nd International Workshop on OAE held on 19-21 September, 2023, in Antwerp, Belgium, participants recognised OAE as a substantial yet neglected public health problem, particularly in areas of sub-Saharan Africa where onchocerciasis remains hyperendemic. Evidence from prospective population-based studies suggest that strengthening onchocerciasis elimination efforts leads to a significant reduction of OAE incidence. There is a need to validate an OAE case definition to estimate the burden of disease and identify onchocerciasis-endemic areas requiring intensification of onchocerciasis elimination programmes and integration of epilepsy care. It is expected that raising awareness about OAE will boost the population uptake of ivermectin. The implementation of a community-based epilepsy treatment programme offering free anti-seizure medications (ASMs) has shown high effectiveness in reducing the frequency of seizures and improving the overall quality of life of people with epilepsy.Conclusions To reduce OAE burden, enhanced collaboration between onchocerciasis and mental health programmes at community, national, and international levels is required. Urgent efforts are needed to ensure the uninterrupted provision of free ASMs in onchocerciasis-endemic areas. Furthermore, OAE should be included in the quantification of the onchocerciasis disease burden.

Assessing intersectional gender analysis in Nepal’s health management information system:a case study on tuberculosis for inclusive health systems

Background Tuberculosis(TB)remains a major public health problem in Nepal,high in settings marked by prevalent gender and social inequities.Various social stratifiers intersect,either privileging or oppressing individuals based on their characteristics and contexts,thereby increasing risks,vulnerabilities and marganilisation associated with TB.This study aimed to assess the inclusiveness of gender and other social stratifiers in key health related national policies and the Health Management Information System(HMIS)of National Tuberculosis Programme(NTP)by conducting an intersectional analysis of TB cases recorded via HMIS.Methods A desk review of key policies and the NTP’s HMIS was conducted.Retrospective intersectional analysis utilized two secondary data sources:annual NTP report(2017-2021)and records of 628 TB cases via HMIS 6.5 from two TB centres(2017/18-2018/19).Chi-square test and multi-variate analysis was used to assess the association between social stratifers and types of TB,registration category and treatment outcome.Results Gender,social inclusion and concept of intersectionality are incorporated into various health policies and strategies but lack effective implementation.NTP has initiated the collection of age,sex,ethnicity and location data since 2014/15 through the HMIS.However,only age and sex disaggregated data are routinely reported,leaving recorded social stratifiers of TB patients static without analysis and dissemination.Furthermore,findings from the intersectional analysis using TB secondary data,showed that male more than 25 years exhibited higher odds[adjusted odds ratio(a OR)=4.95,95%confidence interval(CI):1.60-19.06,P=0.01]of successful outcome compared to male TB patients less than 25 years.Similarly,sex was significantly associated with types of TB(P<0.05)whereas both age(P<0.05)and sex(P<0.05)were significantly associated with patient registration category(old/new cases).Conclusions The results highlight inadequacy in the availability of social stratifiers in the routine HMIS.This limitation hampers the NTP’s ability to conduct intersectional analyses,crucial for unveiling the roles of other social determinants of TB.Such limitation underscores the need for more disaggregated data in routine NTP to better inform policies and plans contributing to the development of a more responsive and equitable TB programme and effectively addressing disparities.

Mutations and intron polymorphisms in voltage-gated sodium channel genes of different geographic populations of Culex pipiens pallens/Culex pipiens quinquefasciatus in China

Background Culex pipiens pallens and Culex pipiens quinquefasciatus are the dominant species of Culex mosquitoes in China and important disease vectors.Long-term use of insecticides can cause mutations in the voltage-gated sodium channel(vgsc)gene of mosquitoes,but little is known about the current status and evolutionary origins of vgsc gene in different geographic populations.Therefore,this study aimed to determine the current status of vgsc genes in Cx.p.pallens and Cx.p.quinquefasciatus in China and to investigate the evolutionary inheritance of neighboring downstream introns of the vgsc gene to determine the impact of insecticides on long-term evolution.Methods Sampling was conducted from July to September 2021 in representative habitats of 22 provincial-level administrative divisions in China.Genomic DNA was extracted from 1308 mosquitoes,the IIS6 fragment of the vgsc gene on the nerve cell membrane was amplified using polymerase chain reaction,and the sequence was used to evaluate allele frequency and knockdown resistance(kdr)frequency.MEGA 11 was used to construct neighborjoining(NJ)tree.PopART was used to build a TCS network.Results There were 6 alleles and 6 genotypes at the L1014 locus,which included the wild-type alleles TTA/L and CTA/L and the mutant alleles TTT/F,TTC/F,TCT/S and TCA/S.The geographic populations with a kdr frequency less than 20.00%were mainly concentrated in the regions north of 38°N,and the geographic populations with a kdr frequency greater than 80.00%were concentrated in the regions south of 30°N.kdr frequency increased with decreasing latitude.And within the same latitude,the frequency of kdr in large cities is relatively high.Mutations were correlated with the number of introns.The mutant allele TCA/S has only one intron,the mutant allele TTT/F has three introns,and the wild-type allele TTA/L has 17 introns.Conclusions Cx.p.pallens and Cx.p.quinquefasciatus have developed resistance to insecticides in most regions of China.The neighboring downstream introns of the vgsc gene gradually decreased to one intron with the mutation of the vgsc gene.Mutations may originate from multiple mutation events rather than from a single origin,and populations lacking mutations may be genetically isolated.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry traces the geographical source of Biomphalaria pfeifferi and Bulinus forskali,involved in schistosomiasis transmission

Background Freshwater snails of the genera Bulinus spp.,Biomphalaria spp.,and Oncomelania spp.are the main intermediate hosts of human and animal schistosomiasis.Identification of these snails has long been based on mor-phological and/or genomic criteria,which have their limitations.These limitations include a lack of precision for the morphological tool and cost and time for the DNA-based approach.Recently,Matrix-Assisted Laser Desorp-tion/lonization Time-Of-Flight(MALDI-TOF)mass spectrometry,a new tool used which is routinely in clinical microbi-ology,has emerged in the field of malacology for the identification of freshwater snails.This study aimed to evaluate the ability of MALDI-TOF MS to identify Biomphalaria pfeifferi and Bulinus forskali snail populations according to their geographicalorigin.Methods This study was conducted on 101 Bi.pfeifferi and 81 Bu.forskali snails collected in three distinct geo-graphical areas of Senegal(the North-East,South-East and central part of the country),and supplemented with wild and laboratory strains.Specimens which had previously been morphologically described were identified by MALDl-TOF MS[identification log score values(LSV)≥1.7],after an initial blind test using the pre-existing database.After DNA-based identification,new reference spectra of Bi.pfeiferi(n=10)and Bu.forskali(n=5)from the geographical areas were added to the MALDI-TOF spectral database.The final blind test against this updated database was per-formed to assess identification at the geographic source level.Results MALDI-TOF MS correctly identified 92.1%of 101 Bi.pfeifferi snails and 98.8%of 81 Bu.forskali snails.At the final blind test,88%of 166 specimens were correctly identified according to both their species and sampling site,with LSVs ranging from 1.74 to 2.70.The geographical source was adequately identified in 90.1%of 91 Bi.pfeifferi and 85.3%of 75 Bu.forskalii samples.Conclusions Our findings demonstrate that MALDI-TOF MS can identify and differentiate snail populations according to geographical origin.It outperforms the current DNA-based approaches in discriminating laboratory from wild strains.This inexpensive high-throughput approach is likely to further revolutionise epidemiological studies in areas which are endemic for schistosomiasis.

Discrepancies between self-reported Checkf update medication in adherence and indirect measurement adherence among patients undergoing antiretroviral therapy:a systematic review

Background Given the critical importance of medication adherence in HIV/AIDS treatment,this study aims to com-pare medication adherence measured by self-report(SR)and indirect measurement among antiretroviral therapy(ART)patients,exploring the differences of adherence results measured by different tools.Methods We systematically searched PubMed,Embase,and the Cochrane Library to identify all relevant literature published up to November 22,2023,without language restrictions,reporting adherence to ART measured by both SR and indirect measurement methods,while also analyzing individual and group adherence separately.Discrepancies between SR and indirect measurement results were assessed using the Mann-Whitney U test or Wilcoxon signed-rank test,with correlations evaluated using the Pearson correlation coefficient.Following one-to-one comparisons,meta-epidemiological one-step analysis was conducted,and network meta-analysis techniques were applied to compare results obtained through specific adherence assessment tools reported in the identified articles.Results The analysis encompassed 65 original studies involving 13,667 HIV/AIDS patients,leading to 112 one-to-one comparisons between SR and indirect measurement tools.Statistically significant differences were observed between SR and indirect measurement tools regarding both individual and group adherence(P<0.05),with Pear-son correlation coeffcients of 0.843 for individual adherence and 0.684 for group adherence.During meta-epide-miological one-step analysis,SR-measured adherence was determined to be 3.94%(95%Cl:-4.48-13.44%)higher for individual adherence and 16.14%(95%Cl:0.81-18.84%)higher for group adherence compared to indirectly measured results.Subgroup analysis indicated that factors such as the year of reporting and geographic region appeared to influence the discrepancies between SR and indirect measurements.Furthermore,network meta-analysis revealed that for both individual and group adherence,the results obtained from most SR and indirect measurement tools were higher than those from electronic monitoring devices,with some demonstrating statistical significance(P<0.05).Conclusions The findings underscored the complexity of accurately measuring medication adherence among ART patients.Significant variability was observed across studies,with self-report methods showing a significant tendency towards overestimation.Year of reporting,geographic region,and adherence measurement tools appeared to influence the differences between SR and indirect measurements.Future research should focus on developing and validating integrated adherence measurements that can combine SR data with indirect measures to achieve a more comprehensive understanding of adherence behaviors.