Malaria cases in China acquired through international travel, 2013-2022.

BACKGROUND: Despite the World Health Organisation certifying China malaria-free in 2021, the risk of local transmission caused by imported malaria cases remains a significant clinical and public health issue. It is necessary to present the changing trends of malaria in China and discuss the role of travel medicine services in consolidating malaria elimination. METHODS: This study systematically reviewed articles and reports related to human malaria from 2013 to 2022 published in international and Chinese databases. Data on malaria (i.e. number of cases, Plasmodium spp., diagnostic method, country of acquisition, provinces with high risk of re-introduction and transmission) were collected and synthesised, then summarised using descriptive statistics. RESULTS: Overall, 24 758 cases of malaria (>99.5% laboratory confirmed, > 99.2% imported, 0.5% fatal) were reported in China from 2013 to 2022, with a downward trend over the years (4128 cases in 2013 compared to 843 cases in 2022; χ2 trend p-value = 0.005). The last locally acquired case was reported in 2017. P. falciparum (65.5%) was the most common species identified, followed by P. vivax (20.9%) and P. ovale (10.0%). Two Pheidole knowlesi cases were also identified in 2014 and 2017 in returned travellers from Malaysia and Indonesia, respectively. The most common countries of malaria acquisition were Ghana, Angola, and Myanmar. P. vivax was mainly detected in returned travellers from Myanmar, while P. falciparum and P. ovale were detected in travellers from Sub-Saharan Africa. Imported cases were mainly reported in Yunnan, Jiangsu, Sichuan, Guangxi, Shandong, Zhejiang, and Henan provinces, where large numbers of Chinese people travel overseas for work. CONCLUSION: Returned travellers from malaria-endemic countries pose a significant risk of malaria re-introduction to China. Travel medicine should be strengthened to improve the capacity and accessibility of both pre- and post-travel services, including malaria prophylaxis and prompt diagnosis of illness in returned travellers.

Use of Dengvaxia® in Australian Travellers: a case series.

Dengvaxia is the only licensed dengue vaccine in Australia, but rarely used. We report the experience of using Dengvaxia in seven Australian travellers. Main reasons for opting for vaccination were travel to dengue-endemic regions and severe symptoms during the prior dengue infection. The vaccine was well tolerated by all travellers.

Influence of lack of blinding on the estimation of medication-related harms: a retrospective cohort study of randomized controlled trials.

BACKGROUND: Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms. METHODS: We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI). RESULTS: We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P < 0.01) among 82 trials in 20 meta-analyses where blinding of participants was lacking. With regard to lack of blinding of healthcare providers or outcomes assessors, the RORs were 0.68 (95% CI: 0.53 to 0.87, P < 0.01 from 81 trials in 22 meta-analyses) and 1.00 (95% CI: 0.94 to 1.07, P = 0.94 from 858 trials among 155 meta-analyses) respectively. Sensitivity analyses indicate that these findings are applicable to both objective and subjective outcomes. CONCLUSIONS: Lack of blinding of participants and health care providers in randomized controlled trials may underestimate medication-related harms. Adequate blinding in randomized trials, when feasible, may help safeguard against potential bias in estimating the effects of harms.

A systematic review and meta-analysis of sexually transmitted infections and blood-borne viruses in travellers.

BACKGROUND: Sexually transmitted infections (STIs) and blood-borne viruses (BBVs) impose a global health and economic burden. International travellers facilitate the spread of infectious diseases, including STIs. Hence, this review assessed the prevalence/proportionate morbidity of travellers with STIs and sexually transmitted BBVs, and factors associated with the infection in this population. METHODS: PubMed, Scopus, Web of Science, CINHAL, Embase, and Cochrane Library were searched from inception of the databases until November 2022. Published analytical observational studies reporting the prevalence/proportionate morbidity of travellers with STIs and factors associated with STIs by type of traveller (i.e. tourists, business travellers, students, visiting friends or relatives [VFRs], international truck drivers, backpackers, expatriates, and men who have sex with men [MSM]) were included. The selection of articles, data extraction, and risk of bias assessment were conducted by two independent reviewers. Meta-analyses were conducted for each STI by clinical presentation and type of traveller. RESULTS: Thirty-two studies (n = 387 731 travellers) were included, 19 evaluated the proportionate morbidity of STIs among symptomatic travellers, while 13 examined the prevalence of STIs in asymptomatic travellers. The highest proportionate morbidity was found among VFRs (syphilis, 1.67%; 95%CI:1.03-2.81%), backpackers (chlamydia trachomatis, 6.58%; 95%CI: 5.96-7.25%), and MSM (HIV [2.50%;95%CI:0.44-12.88%], gonorrhoea [4.17%;95%CI:1.1.5-13.98%], lymphogranuloma venereum [4.17%;95%CI:1.1.5-13.98%], and HAV [20.0%; 95% CI: 14.99-26.17%]). The highest prevalence of STIs among asymptomatic were found in MSM (HIV [25.94%;95%CI:22.21-30.05%] and HBV [24.90%; 95%CI:21.23-28.96%]) and backpackers (chlamydia trachomatis, 3.92%;95% CI:2.72-5.32%). Short duration of the trip (<1 month), not having pre-travel consultation, travelling to Southeast Asia, and being unvaccinated for HBV were identified as risk factors for STIs. CONCLUSION: Strategies to prevent STIs and sexually transmitted BBVs should be discussed at pretravel consultations and recommendations should be prioritized in high-risk groups of travellers, such as backpackers, VFRs, and MSMs. Additionally, healthcare providers should tailor recommendations for safe sex practices to individual travellers' unique needs.

Sexual and reproductive health integration into pre-travel consultations: a scoping review.

BACKGROUND: Casual sex during travel is a major preventable factor in the global transmission of sexually transmissible infections (STI). Pre-travel consults present an excellent opportunity for practitioners to educate travellers about sexual and reproductive health (SRH) and safety. The scoping review aims to explore and understand the extent to which SRH is included in pre-travel consultations. METHODS: PubMed, Embase, CINAHL, Scopus, Medline and Web of Science were systematically searched for primary research articles exploring whether health care practitioners (HCP) included SRH in pre-travel consultations. Extracted findings were synthesised and presented in narrative form. RESULTS: Findings across 13 articles suggest HCP infrequently broached SRH in pre-travel consultations with HCP discomfort, and lack of time and resources presented as key barriers. Urban practice settings, HCP experience, training in travel medicine, and traveller characteristics such as sexual orientation were positively correlated with discussions about SRH. SRH advice reported was general in nature, primarily focusing on safer sex, condoms, or unspecified STI advice. Risk assessments based solely on age or stereotypes around sexual preferences led to key aspects of SRH care being missed for some (e.g. SRH was less likely to be discussed with older travellers). CONCLUSIONS: HCPs frequently miss opportunities to integrate SRH into pre-travel consultations. Strategies to promote HCP confidence and awareness present a promising means to boost the frequency and quality of SRH advice disseminated. Integrating culturally safe and responsive SRH history-taking and advice into pre-travel consultations may contribute to global reductions in STI transmission and promote traveller SRH well-being.

Comparison of bias adjustment in meta-analysis using data-based and opinion-based methods.

INTRODUCTION: Several methods exist for bias adjustment of meta-analysis results, but there has been no comprehensive comparison with unadjusted methods. We compare 6 bias-adjustment methods with 2 unadjusted methods to examine how these different methods perform. METHODS: We re-analyzed a meta-analysis that included 10 randomized controlled trials. Two data-based methods (Welton's data-based approach and Doi's quality effects model) and 4 opinion-informed methods (opinion-based approach, opinion-based distributions combined statistically with data-based distributions, numerical opinions informed by data-based distributions, and opinions obtained by selecting areas from data-based distributions) were used to incorporate methodological quality information into the meta-analytical estimates. The results of these 6 methods were compared with 2 unadjusted models: the DerSimonian-Laird random effects model and Doi's inverse variance heterogeneity model. RESULTS: The 4 opinion-based methods returned the random effects model estimates with wider uncertainty. The data-based and quality effects methods returned different results and aligned with the inverse variance heterogeneity method with some minor downward bias adjustment. CONCLUSION: Opinion-based methods seem to only add uncertainty rather than bias adjust.

The provision of sexual and reproductive health information and services to travellers: an exploratory survey of Australian travel medicine clinicians.

BACKGROUND: International travel can increase the risk of exposure to infectious diseases including sexually transmissible infections (STI). Pre-travel medical consultation provides an opportunity for travel-related health risk assessments and advice. This study explored how travel medicine clinicians integrate sexual and reproductive health (SRH) services into clinical practice. METHODS: A convenience sample of travel medicine clinicians completed a cross-sectional survey online or via hard-copy disseminated at an annual national Australian travel medicine conference. RESULTS: Of the 67 respondents, most (n , 51; 76.1%) had a postgraduate qualification relevant to travel medicine and 55.2% (n , 37) had worked in travel medicine for over 10years. Only 22.4% (n , 15) reported conducting a SRH history/STI risk assessment for all travel patients. STI testing pre-departure was conducted on patient request (48, 71.6%), if symptomatic (32, 47.8%) or based on risk history (28, 41.8%). SRH information pre-departure was most frequently provided if prompted by patient questions (n , 42; 62.7%), or based on the patient's history (n , 37; 55.2%). Over half the sample (n , 40; 59.7%) expressed interest in further training in SRH. CONCLUSION: Providing and engaging with additional training may assist travel medicine clinicians to take a more proactive approach to SRH consultations and STI testing. Additional research is needed to explore models of care that will allow comprehensive SRH and STI services to be integrated into standard pre- and post-travel care.

Pediatric Central Venous Access Device Lock Solutions: A Network Meta-analysis.

CONTEXT: Central venous access device (CVAD) locks are routine interventions used to prevent and treat complications, such as infection, thrombosis, and catheter occlusion. OBJECTIVE: To compare and rank lock-solutions for prevention or treatment of complications in pediatrics. Design Systematic review and network meta-analysis. DATA SOURCES: Five databases and 2 clinical trial registries were searched. STUDY SELECTION: Published and unpublished randomized controlled trials that enrolled pediatric patients with a CVAD and compared the effectiveness of lock-solutions. DATA EXTRACTION: Data extraction was conducted by 2 reviewers. Odds ratio (OR) for prevention or treatment of CVAD-associated bloodstream infection (BSI), thrombosis, occlusion, CVAD-failure, and mortality were calculated, with point estimates ranking lock-solutions. RESULTS: Twenty-nine studies were included. Chelating agents and antibiotic locks given as prevention were associated with lower odds (OR: 0.11; 95% confidence interval [CI]: 0.02-0.67; moderate-quality; OR: 0.19; 95% CI: 0.05-0.79, high-quality, respectively) of CVAD-associated BSI compared with heparinized saline (reference). Preventative thrombolytic agents had lower odds (OR: 0.64, 95% CI: 0.44-0.93; low-quality) of CVAD occlusion, whereas ethanol had higher odds (OR: 2.84, 95% CI: 1.31-6.16; high-quality) compared with heparinized saline (reference). No lock solution had effects on thrombosis prevention or treatment, CVAD-failure, CVAD-associated BSI treatment failure, or mortality. LIMITATIONS: There was substantial uncertainty around the point estimates because of the limited number of studies for outcomes and study heterogeneity. More high-quality studies are needed to confirm the efficacy of lock solutions. CONCLUSIONS: Chelating agents and antibiotic locks may be effective for CVAD-associated BSI prevention in pediatrics. Thrombolytic agents can be an option for CVAD occlusion prevention, whereas ethanol may not be recommended.

Mortality, hospital length of stay, and recurrent bloodstream infections associated with extended-spectrum beta-lactamase-producing Escherichia coli in a low prevalence region: A 20-year population-based large cohort study.

OBJECTIVES: This population-based study aimed to investigate the risk factors and effect of extended-spectrum beta-lactamase (ESBL) production on clinical outcomes in Escherichia coli bloodstream infection (BSI) patients. METHODS: The study population was defined as patients aged ≥15 years with E. coli BSI in Queensland, Australia, from 2000 to 2019. Outcomes were defined as 30-day case fatality, hospital length of stay (LOS), and recurrent E. coli BSI. RESULTS: A total of 27,796 E. coli BSIs were identified, of which 1112 (4.0%) were ESBL-producers. Patients with ESBL-Ec BSI were more frequently older, male, with comorbidity, recurrent E. coli BSI, and less likely with community-associated community-onset infections as compared to non-ESBL-Ec BSI patients. The standardized mortality rate of ESBL-Ec BSI increased 8-fold from 2000 to 2019 (1 to 8 per million residents) and case fatality was 12.8% (n = 142) at 30 days from positive blood culture. Patients with ESBL-Ec BSI were not at higher risk of 30-day case fatality (adjusted hazard ratio [HR] = 0.98, 95% CI: 0.83-1.17), but had higher risk of recurring episodes (adjusted subdistribution HR = 1.58, 95% CI: 1.29-1.92) and observed 14% longer LOS (adjusted incidence rate ratio = 1.14, 95% CI: 1.10-1.18) than non-ESBL-Ec BSI patients. CONCLUSION: In this large patient cohort, ESBL-Ec BSI did not increase case fatality risk but observed higher hospital LOS and recurrent E. coli BSI than non-ESBL-Ec BSI. Clinical resources are warranted to account for the higher morbidity risk associated with ESBL production and incidence.

Imported malaria into Australia: surveillance insights and opportunities.

BACKGROUND: Malaria continues to pose a significant burden in endemic countries, many of which lack access to molecular surveillance. Insights from malaria cases in travellers returning to non-endemic areas can provide valuable data to inform endemic country programmes. To evaluate the potential for novel global insights into malaria, we examined epidemiological and molecular data from imported malaria cases to Australia. METHODS: We analysed malaria cases reported in Australia from 2012 to 2022 using National Notifiable Disease Surveillance System data. Molecular data on imported malaria cases were obtained from literature searches. RESULTS: Between 2012 and 2022, 3204 malaria cases were reported in Australia. Most cases (69%) were male and 44% occurred in young adults aged 20-39 years. Incidence rates initially declined between 2012 and 2015, then increased until 2019. During 2012-2019, the incidence in travellers ranged from 1.34 to 7.71 per 100 000 trips. Cases were primarily acquired in Sub-Saharan Africa (n = 1433; 45%), Oceania (n = 569; 18%) and Southern and Central Asia (n = 367; 12%). The most common countries of acquisition were Papua New Guinea (n = 474) and India (n = 277). Plasmodium falciparum accounted for 58% (1871/3204) of cases and was predominantly acquired in Sub-Saharan Africa, and Plasmodium vivax accounted for 32% (1016/3204), predominantly from Oceania and Asia. Molecular studies of imported malaria cases to Australia identified genetic mutations and deletions associated with drug resistance and false-negative rapid diagnostic test results, and led to the establishment of reference genomes for P. vivax and Plasmodium malariae. CONCLUSIONS: Our analysis highlights the continuing burden of imported malaria into Australia. Molecular studies have offered valuable insights into drug resistance and diagnostic limitations, and established reference genomes. Integrating molecular data into national surveillance systems could provide important infectious disease intelligence to optimize treatment guidelines for returning travellers and support endemic country surveillance programmes.

Use of conditional estimates of effect in cancer epidemiology: An application to lung cancer treatment.

BACKGROUND: In oncology clinical trials, there is the assumption that randomization sufficiently balances confounding covariates and therefore average treatment effects are usually reported. This paper explores the wider benefits provided by conditioning on covariates for reasons other than mitigation of confounding. METHODS: We reanalyzed the data from primary randomized controlled trials listed in two meta-analyses to explore the significance of conditioning on smoking status in terms of the effect magnitude of treatment on progression free survival in non-small cell lung cancer. RESULTS: The reanalysis revealed that conditioning on smoking status using sub-group analyses provided the closest empiric estimate of individual treatment effect based on smoking status and significantly reduced the heterogeneity of treatment effect observed across studies. In addition, smoking status was determined to be a modifier of the effect of treatment. CONCLUSION: Conditioning on prognostic covariates in randomized trials in oncology helps generate the closest empiric estimates of individual treatment benefit, addresses heterogeneity due to varying covariate distributions across trials and facilitates future decision making as well as evidence synthesis. Conditioning using sub-group analyses also allows examination for effect modification in meta-analysis.

Causes of death among international travellers in Peru, 2017 to 2021.

BACKGROUND: The wellbeing and safety of international tourists is a paramount concern for governments and stakeholders. Mortality among travellers and the causes of death serve as a significant metric of destination safety. We describe the epidemiology and causes of death among international travellers in Peru. METHODS: Data retrieved from the Peruvian government's deaths certificates registry included all non-residents who died between January 2017 and December 2021. We analysed the national incidence and causes of death among international travellers in Peru. Causes of death were classified into non-communicable diseases (NCD), communicable diseases and injuries. We classified fatalities according to the existence of preventive measures that could be provided during the travel medicine consultation to decrease the risk. RESULTS: We obtained records from 1514 deaths among international travellers (973 males, 64%). The incidence increased from 0.2 deaths per 10 000 travellers in 2017 to 9.9 in 2021. NCDs were the most common causes of death (n = 560, 37%), followed by communicable diseases (n = 487, 32%), and injuries (n = 321, 21%). Causes of death were unknown in 9.7% of the records. The leading causes of death in these categories were cancer, cardiovascular disease, COVID-19 and trauma. We found similar sex distribution of NCDs in travellers aged >50 years and higher rates of communicable diseases among males across all ages. Injury-associated deaths were significantly higher among males aged 18-29 years (P < 0.001) compared with other sex-age groups. We estimated that for 57.7% of deaths risk could have been decreased through pre-travel advice. CONCLUSION: Rates of deaths among travellers to Peru increased over time. Most deaths were due to NCDs, followed by communicable diseases and injuries. Pre-travel medical optimization and effective advice focused on age-sex and destination specific risks could reduce risk among travellers. Increased awareness among travel medicine practitioners and improvement of emergency medical response systems in Peru could decrease mortality.

The SMART Safety: An empirical dataset for evidence synthesis of adverse events.

Evidence synthesis serves an important role to promote informed decision-making in healthcare practice. A key issue of evidence synthesis is the approach to deal with rare adverse events and the methods to address bias of harm effects. Empirical data is essential to help methodologists and statisticians to solve the issues in evidence synthesis of adverse events. For this reason, we have established SMART Safety dataset, the largest empirical dataset of meta-analyses of adverse events. The dataset contains 151 systematic reviews with 629 meta-analyses on safety outcomes, which covers more than 2,300 randomized controlled trials and 362 harm outcomes, with 10,069 rows and 45 columns of trial level information. All information was double- or even quadra-checked and further verified by referring the original source (e.g., the full-text of the included randomized trials) to ensure high validity of the data.

A Health Survey Revealing Prevalence of Vector-Borne Diseases and Tuberculosis in Papua New Guinea Defence Force Personnel and Families.

The Papua New Guinean Defence Force (PNGDF) and the Australian Defence Force (ADF) work and train closely. Infectious diseases pose a health threat to both forces, but recent knowledge about the risk at military bases in Papua New Guinea is limited. To improve understanding, a collaborative cross-sectional survey was conducted (March-April 2019) at Lombrum Naval base (Manus province) and Moem Army barracks (Wewak, East Sepik province) plus its Vanimo outpost (Sandaun province). Clinical data, venous blood, and sputum were collected from PNGDF personnel (DF) from the three sites, with point-of-care testing conducted for malaria (microscopy and rapid diagnostic test [RDT]), lymphatic filariasis (RDT), glucose-6-phosphate-dehydrogenase (G6PD) deficiency (RDT), tuberculosis (GeneXpert), and hemoglobin level. Finger prick blood collected from family members residing at the Wewak base was tested for malaria and hemoglobin level. Overall, 235 DF and 793 family members completed the survey. Microscopy revealed malaria prevalence as 0.4% Plasmodium falciparum and 3.1% Plasmodium vivax among DF and 3.5% P. falciparum, 14.3% P. vivax, and 0.3% mixed P. falciparum/P. vivax among family members. Among DF, 3.9% were G6PD deficient and none tested positive for tuberculosis or for lymphatic filariasis antigen. Anemia was present in 6.5% of DF and 47.3% of family members, predominantly females. Results suggest ongoing exposure to malaria, particularly P. vivax, at study sites, whereas infections of lymphatic filariasis and tuberculosis were not detected. Survey results will inform the PNGDF and the ADF regarding vector-borne disease risk for future sustainable health and disease control interventions.

A decision support tool for risk-benefit analysis of Japanese encephalitis vaccine in travellers.

BACKGROUND: During pre-travel consultations, clinicians and travellers face the challenge of weighing the risks verus benefits of Japanese encephalitis (JE) vaccination due to the high cost of the vaccine, low incidence in travellers (~1 in 1 million), but potentially severe consequences (~30% case-fatality rate). Personalised JE risk assessment based on the travellers' demographics and travel itinerary is challenging using standard risk matrices. We developed an interactive digital tool to estimate risks of JE infection and severe health outcomes under different scenarios to facilitate shared decision-making between clinicians and travellers. METHODS: A Bayesian network (conditional probability) model risk-benefit analysis of JE vaccine in travellers was developed. The model considers travellers' characteristics (age, sex, co-morbidities), itinerary (destination, departure date, duration, setting of planned activities) and vaccination status to estimate the risks of JE infection, the development of symptomatic disease (meningitis, encephalitis), clinical outcomes (hospital admission, chronic neurological complications, death) and adverse events following immunization. RESULTS: In low-risk travellers (e.g. to urban areas for <1 month), the risk of developing JE and dying is low (<1 per million) irrespective of the destination; thus, the potential impact of JE vaccination in reducing the risk of clinical outcomes is limited. In high-risk travellers (e.g. to rural areas in high JE incidence destinations for >2 months), the risk of developing symptomatic disease and mortality is estimated at 9.5 and 1.4 per million, respectively. JE vaccination in this group would significantly reduce the risk of symptomatic disease and mortality (by ~80%) to 1.9 and 0.3 per million, respectively. CONCLUSION: The JE tool may assist decision-making by travellers and clinicians and could increase JE vaccine uptake. The tool will be updated as additional evidence becomes available. Future work needs to evaluate the usability of the tool. The interactive, scenario-based, personalised JE vaccine risk-benefit tool is freely available on www.VaxiCal.com.

Data extraction error in pharmaceutical versus non-pharmaceutical interventions for evidence synthesis: Study protocol for a crossover trial.

Background: Data extraction is the foundation for research synthesis evidence, while data extraction errors frequently occur in the literature. An interesting phenomenon was observed that data extraction error tend to be more common in trials of pharmaceutical interventions compared to non-pharmaceutical ones. The elucidation of which would have implications for guidelines, practice, and policy. Methods and analyses: We propose a crossover, multicenter, investigator-blinded trial to elucidate the potential variants on the data extraction error rates. Eligible 90 participants would be 2nd year or above post-graduate students (e.g., masters, doctoral program). Participants will be randomized to one of the two groups to complete pre-defined data extraction tasks: 1) group A will contain 10 randomized controlled trials (RCTs) of pharmaceutical interventions; 2) group B will contain 10 RCTs of non-pharmaceutical interventions. Participants who finish the data extraction would then be assigned to the alternative group for another round of data extraction after a 30 min washout period. Finally, those participants assigned to A or B group will be further 1:1 randomly matched based on a random-sequenced number for the double-checking process on the extracted data. The primary outcome will be the data extract error rates of the pharmaceutical intervention group and non-pharmaceutical group, before the double-checking process, in terms of the cell level, study level, and participant level. The secondary outcome will be the data error rates of the pharmaceutical intervention group and non-pharmaceutical group after the double-checking process, again, in terms of the cell level, study level, and participant level. A generalized linear mixed effects model (based on the above three levels) will be used to estimate the potential differences in the error rates, with a log link function for binomial data. Subgroup analyses will account for the experience of individuals on systematic reviews and the time used for the data extraction. Discussion: This trial will provide useful evidence for further systematic review of data extraction practices, improved data extraction strategies, and better guidelines. Trial registration: Chinese Clinical Trial Register Center (Identifier: ChiCTR2200062206).

The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income settings and thus are not globally representative. This study quantifies the excess mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and economic costs associated with ARB BSIs, compared to antibiotic-sensitive bacteria (ASB), among adult inpatients in low- and middle-income countries (LMICs). METHODS AND FINDINGS: We conducted a systematic review by searching 4 medical databases (PubMed, SCIELO, Scopus, and WHO's Global Index Medicus; initial search n = 13,012 from their inception to August 1, 2022). We only included quantitative studies. Our final sample consisted of n = 109 articles, excluding studies from high-income countries, without our outcomes of interest, or without a clear source of bloodstream infection. Crude mortality, ICU admission, and LOS were meta-analysed using the inverse variance heterogeneity model for the general and subgroup analyses including bacterial Gram type, family, and resistance type. For economic costs, direct medical costs per bed-day were sourced from WHO-CHOICE. Mortality costs were estimated based on productivity loss from years of potential life lost due to premature mortality. All costs were in 2020 USD. We assessed studies' quality and risk of publication bias using the MASTER framework. Multivariable meta-regressions were employed for the mortality and ICU admission outcomes only. Most included studies showed a significant increase in crude mortality (odds ratio (OR) 1.58, 95% CI [1.35 to 1.80], p < 0.001), total LOS (standardised mean difference "SMD" 0.49, 95% CI [0.20 to 0.78], p < 0.001), and ICU admission (OR 1.96, 95% CI [1.56 to 2.47], p < 0.001) for ARB versus ASB BSIs. Studies analysing Enterobacteriaceae, Acinetobacter baumanii, and Staphylococcus aureus in upper-middle-income countries from the African and Western Pacific regions showed the highest excess mortality, LOS, and ICU admission for ARB versus ASB BSIs per patient. Multivariable meta-regressions indicated that patients with resistant Acinetobacter baumanii BSIs had higher mortality odds when comparing ARB versus ASB BSI patients (OR 1.67, 95% CI [1.18 to 2.36], p 0.004). Excess direct medical costs were estimated at $12,442 (95% CI [$6,693 to $18,191]) for ARB versus ASB BSI per patient, with an average cost of $41,103 (95% CI [$30,931 to $51,274]) due to premature mortality. Limitations included the poor quality of some of the reviewed studies regarding the high risk of selective sampling or failure to adequately account for relevant confounders. CONCLUSIONS: We provide an overview of the impact ARB BSIs in limited resource settings derived from the existing literature. Drug resistance was associated with a substantial disease and economic burden in LMICs. Although, our results show wide heterogeneity between WHO regions, income groups, and pathogen-drug combinations. Overall, there is a paucity of BSI data from LMICs, which hinders implementation of country-specific policies and tracking of health progress.

Immune response after rabies pre-exposure prophylaxis and a booster dose in Australian bat carers.

Periodic vaccination against rabies is essential for individuals at continuing risk of rabies exposure. There is limited evidence on long-term immunogenicity after a 3-dose intramuscular (3IM) pre-exposure prophylaxis (PrEP) and single IM booster dose, thus current guideline recommendations differ in the interval for serology tests following PrEP and boosters. This study investigated post-PrEP and post-booster persistence of antibodies in Australian bat carers. Bat carers who received 3IM PrEP/booster doses and had post-PrEP/booster serology test results were included. The proportion of antibody-negative (<0.5 EU/mL) individuals after PrEP/booster dose were examined. Three hundred and five participants (65.6% females, median age at PrEP 43.1 years) were included. The proportion who were antibody-negative varied depending on the time between 3IM PrEP and the serology test: 8.0% <1 year, 29.8% 1-2 years, 21.2% 2-3 years and 7.7% >3 years. Ninety-one participants receiving booster doses were further assessed. Only one participant was antibody-negative at >3 years after receiving one IM booster dose. Our findings support that a serology test should be performed 1 year after 3IM PrEP, followed by first booster if required. Rabies antibodies persist for many years after receiving the booster doses. The interval between subsequent serology tests and the first booster dose should be no longer than 3 years. Future studies are required to provide more insight into the most appropriate timing of subsequent boosters.