The devastating COVID-19 pandemic over the past three years has made One Health a trending philosophy not only as a regional and national initiative but also as transboundary efforts calling for multilateral cooperations. Mwatondo et al. presented One Health Networks in a recent article published in The Lancet, calling for further promotion of the One Health approach[1]. Likewise, recent studies in developing countries described the rapid adoption of One Health concepts globally and the major advances in practice of One Health in the past two decades[2-4]. In this perspective, we highlight a pilot One Health program China spearheaded by the World Bank and the provincial government of Hainan. This pilot program aims to boost our awareness of preventing and combating emerging infectious diseases using the One Health approach[5]. Hainan, the southernmost province in China of tropical climate, has recently been designated by the Central Government as an province-wide free trade port, similar to Hong Kong and Singapore, and is expected to rapidly transition from a dormant tourist attraction to an international hub of commerce. The World Bank Hainan initiative will fund collaborative scientific projects on emerging infectious disease surveillance and prevention including sentinel surveillance of zoonotic diseases, active surveillance of antibiotic resistance patterns, monitoring and mitigating the impacts of climate change on health, and food security. The initiative also facilitates government interagency coordination, and reform of existing governance mechanisms in pursuit of One Health objectives. The efforts are also supported by the World Health Organization, Food and Agriculture Organization of the United Nations, and the World Organization for Animal Health. Presently, Hainan Province is building a "One Health" system in institutional and mechanism innovation, interdisciplinary collaborative research, talent training, and international cooperation. Hainan has by far conducted various cooperation projects with domestic and international universities, and established a think tank of more than 100 renowned experts across the globe, and two cooperation organizations of One Health. As part of the World Bank Hainan initiative and the first academic journal in the field of One Health in China, One Health Bulletin was launched with an aim to expand interdisciplinary collaboration and communication on human, animal and environmental health. We intend to disseminate the latest research findings on public health policies, emerging infectious diseases, antimicrobial resistance, food safety and security, biosafety and biosecurity, environmental health, management and early warning, etc. As mapped out in the One Health initiative, research platforms on animal-derived food safety, full-chain bacterial resistance, new drug creation technology and product research and development are to be set up by 2025. A risk-based monitoring system for zoonotic diseases and other health threats, and a One Health data collecting and exchanging platform will also be established. Concurrently, the initiative will continue to strengthen the emergency response capacity of medical institutions, establish a control mechanism for antibiotics misuse and overuse as well as One Health environmental programs, and prevent the cross-border spread of epidemics. As a demonstrative area of One Health practice, Hainan will share the stories of One Health solutions and best practices nationwide and worldwide.
The steady decline in malaria cases and deaths in recent years is a step ahead toward elimination; however, an increasing number of reports of antimalarial and insecticide resistance highlight the importance of having newer approaches to achieve the goal in the stipulated time frame. Therefore, having an effective and durable malaria vaccine is extremely crucial, which can complement the tools currently in use. Although the malaria vaccine development efforts initiated in the 1910’s with the first attempts to develop a malaria vaccine involved inoculating humans with live, attenuated strains of the malaria parasite but the efforts have been intensified over the previous decade, resulting in several significant developments. Based on the field implementation trial in three African countries (Ghana, Kenya, and Malawi), the World Health Organization (WHO) in 2021 recommended the RTS,S vaccine for use in moderate-high transmission settings for malaria prevention and control. RTS,S vaccine, administered in 4 doses, demonstrated vaccine efficacy of 36% after 48 months of follow-up among 5-17 months old children[1]. RTS,S vaccine demonstrated the feasibility of use of malaria vaccine in the endemic areas; however, certain points needed consideration: reduction in the concentration and representation of HBsAg (currently 4:1) in virus-like particle (VLP); a mechanism to reduce the high antigenic competition with HBsAg, and thus high seroconversion rates for HBsAg, and finally having a vaccine with improved efficacy to meet the WHO goal of having a malaria vaccine with an efficacy of 70% or more in preventing clinical malaria by 2030[2]. Thus, the need for improvement in the existing vaccine was realized, and it is always preferable having multiple vaccines against malaria for meeting the demands. The R21 vaccine, an improved version of the RTS vaccine, was designed and developed at the Jenner Institute in 2012, at the University of Oxford. It consists of a circumsporozoite protein (CSP) C-terminus fused with the HBsAg N-terminus. Unlike RTS,S, R21 used an advanced vector system ( Pichia pastoris) for expressing fused CSP-HBsAg proteins. The expressed R21 VLP is ~22 nm in size. A preclinical study by Collins et al. tested the immunogenicity of R21 with a range of adjuvants in mice[2]. The accessibility of CSP and HBsAg was tested, and the study confirmed CSP as fairly accessible and HBsAg as having decreased accessibility, and the low antibody titter to HBsAg echoed this finding. Thus, R21 has the potential to generate a greater immune response towards malaria antigen, in contrast to RTS/AS01, as anti-NANP (part of CSP) is an immune correlate of protection against malaria. Further, anti-NANP, being an immune correlate of protection, should lead to greater efficacy of the vaccine. Matrix-M (MM), a saponin-based adjuvant manufactured by Novavax and recently used in COVID-19 and influenza vaccines, is the adjuvant for R21[3]. The R21 vaccine Phase 1a study was conducted from October 2015 to January 2017 among 31 healthy adults at the University of Oxford. The study participants were randomized to four groups and received either 2/10/50 mcg of R21 alone or mixed with MM. Based on the interim findings of Phase 1a, the Phase 1b study was initiated in Burkina Faso in August 2016 and enrolled 13 participants who were randomized to receive either 10 mcg R21 along with MM or placebo[4]. The anti-NANP responses to the R21 (10 mcg each) dose were similar to the response attained by three RTS (50 mcg each) doses, highlighting the requirement of a relatively lower antigen dose in the case of R21, thus being cost-effective for vaccine production. Based on Phase 1 results, Phase 2b was initiated in May 2019 in Burkina Faso, before the onset of the malaria season[3]. In this, 450 children aged 5-17 months were randomized to either group 1 (5 mcg R21 and 25 mcg MM) or group 2 (5 mcg R21 and 50 mcg MM) or the control group. The children received 3 doses of vaccine 4 weeks apart. The anti-NANP titters were assessed using ELISA before the 1st dose of the vaccine and at frequent intervals thereafter. The vaccine efficacy was 74% in group 1 at 6 months and 71% at 12 months, and 77% in group 2 both at 6 months and 12 months[3]. Thereafter, the booster dose was administered to 409 children in 2020. Group 2 (higher adjuvant dose) retained an efficacy of 77%. The geometric mean of antibody titters increased till 28 days after 3rd dose and then decline, however, the levels again rose after the fourth dose (booster dose). Further, anti-NANP antibodies showed a negative correlation with malaria episodes, thus it can be considered as a correlate of protection for the R21 vaccine. Phase 3 trial was initiated in Burkina Faso, Kenya, Mali, and Tanzania with a sample size of 4 800 children[5] and the investigators have submitted the results for regulatory approvals, though the results are not available in public in the form of scientific literature. The immunobridging study can be conducted in malaria-endemic areas for generating evidence for the safety and immunogenicity of the R21 vaccine[5]. For vaccines showing effectiveness in one setting, immunobridging studies are mainly conducted to infer effectiveness in another setting. In immunobridging studies, an immune correlate of protection, i.e., seroconversion rate or antibody titters are compared between two settings using appropriate statistical tests. The immunobridging studies have been conducted earlier for COVID-19 vaccines. It is an effective approach for generating relevant data in a shorter time period. R21, an improved version of the RTS,S vaccine has shown promising results in Phase 2 trial, and Phase 3 trial results are awaited. Now, Ghana and Nigeria's governments in April 2023 have provided the regulatory clearance and approved its use for malaria control. In the WHO, the prequalification process for the R21 vaccine is being undertaken. There are some impending questions: 1) How the vaccine will perform in areas of low transmission? 2) Will it be cost-effective? 3) How the vaccine will perform if administered around the year or irrespective of the season, as currently, the vaccine efficacy results are available for the seasonal administration of the vaccine? 4) If approved by the WHO, do countries still need to test the vaccine in a trial setting or immunobridging studies will suffice? 5) Long-term safety data of the vaccine; 6) Need of booster doses, if yes, the interval and age till which booster should be given? 7) Impact of human and parasite genetic diversity on the effectiveness of the vaccine. In addition, Phase 4, i.e., post-marketing surveillance should be prioritized, by strengthening pharmacovigilance in the countries opting for wider use of the vaccine in public health settings. Despite some unanswered questions, the R21 vaccine with efficacy exceeding 75%, the WHO’s target, has the potential to revolutionize malaria prevention, thus reducing malaria morbidity and mortality, and finally eliminating malaria. For effectively eliminating a disease, or for efficient control and prevention, as has been shown for COVID and polio, the role of vaccine is prominent. For mass-scale use in a field setting, an uninterrupted supply of vaccines is very crucial and, being manufactured by the Serum Institute of India, has assured delivery of 200 million doses of R21 vaccine per year which may meet the demands. With the commitment towards eliminating malaria, it is hoped that the vaccine may be instrumental for this in malaria-endemic communities globally.
Objective: To identify the knowledge and awareness level of human mpox viral infection among healthcare workers in southwestern Nigeria. Methods: A cross-sectional study was conducted in Ekiti State, southwest Nigeria among 316 healthcare workers that were selected through a systematic random sampling. Data were collected with the aid of a semi-structured, self-administered questionnaire. The Chi-square test and binary logistic regression were used to find the association between the independent and dependent variables. The significance level was set at P-value <0.05. Results: Two hundred and twenty-two (70.3%) of the respondents were aged ≤40 years, mean age (36±9) years, 189 (59.8%) were female, 306 (96.8%) were Christians, and 203 (64.2%) were married. Three hundred and fourteen (99.4%) of the respondents were aware of mpox infection. Main sources of information about mpox were medical education (44.0%), radio/television (32.0%) and newspaper (21.0%). However, among those aware of the disease, 209 (67.0%) demonstrated poor knowledge levels. Longer than 5 years’ experience of medical practice was the only significant predictor of higher knowledge level of the disease (OR 1.76, 95% CI 1.01-3.06; P=0.046). Conclusions: Despite the high awareness level of mpox infection among healthcare workers, there still exists a huge knowledge gap. It is recommended that targeted intervention could be directed towards continuous medical education and simulation exercises on re-emerging infectious diseases like mpox to improve the knowledge of the healthcare workers.
Objective: To investigate the perception of antibiotics, the frequency of inappropriate antibiotic use, and the factors that lead to inappropriate antibiotic use by parents who apply to primary healthcare organizations. Methods: This cross-sectional study included 973 parents who applied to primary healthcare centers. We analyzed basic concepts related to antibiotics prescribed for their children, antibiotic administration, and antibiotic resistance, as well as parents' knowledge and attitudes towards antibiotic use, and their experiences, practices, and perceptions related to purchasing antibiotics without prescription. Results: In the past one year, 78.9% of the parents gave antibiotics to their children at least once, and 39.1% gave antibiotics three or more times. Some of the participants (7.1%) reported having forced the physician to prescribe antibiotics and purchased antibiotics without a prescription (13.2%). The knowledge about antibiotics and awareness about antibiotic resistance were found to be more frequent; among parents who had university degrees, higher income levels, two or fewer children, social insurance and negative behaviours were lower in those who received information about antibiotics from healthcare professionals. The probability of taking antibiotics without prescription was lower in that of with higher income level (OR 0.460; 95% CI 0.219-0.965), and the probability of forcing antibiotic prescription was higher in those with 3 or more children (OR 6.94; 95% CI 2.37-20.26). The score obtained from the awareness of antibiotic resistance sub-dimension was found to negatively affect the behavior of forcing antibiotic prescription (OR 0.852; 95% CI 0.732-0.993) but the score obtained from the behaviour sub-dimension was positively affect this behaviour (OR 1.136; 95% CI 1.011-1.276). Conclusions: Inappropriate antibiotic use appears to be a problem with negative perception, lack of knowledge and socioeconomic dimension. Studies should be conducted to increase antibiotic knowledge in parents and to expand the scope of social insurance.
Objective: To make evidence-based decisions based on broad mortality trends for Razavi Khorasan province, Iran. Methods: In order to determine the baseline number of deaths, we used univariate time series analyses for monthly data from the monthly vital statistics reports (From April 2015 to March 2022). For excess mortalities, these baselines were subtracted from reported deaths with a 95% prediction interval. To compare time and causes, a P-score was calculated. Results: From March 2020 to March 2022, there were 61 949 registered deaths, and the estimated deaths with a 95% confidence interval (CI) were 43 246.16 (35 718.28, 50 774.05). So, in 2020-2021 and 2021-2022, the death counts were 35.15% and 51.33% higher than projected. A total of 18 666 cardiovascular diseases were reported and a total of 15 704.46 (12 006.95, 19 401.96) was estimated. The P-score for this duration was 14.49% and 23.23% higher than expected. Infectious and parasitic diseases plus COVID-19 were 16 633 and estimated to be 1 044.87 (456.77, 1 632.96). A total of 4 420 diseases of the respiratory system were reported, and 4 564.94 deaths were predicted (2 277.43, 6 852.43). In the first year of the pandemic, the P-score dropped to -35.28% and in the second year, it jumped sharply to 22.38%. Conclusions: Excess mortality, along with cause-specific mortality, can be helpful for monitoring trends and developing public health policies at the local, national, and international levels.
Objective: To investigate the clinical and epidemiological features and outcome of Chryseobacterium and Elizabethkingia spp. infections in children, together with antimicrobial susceptibilities. Methods: This retrospective study was conducted at a tertiary pediatric hospital in Turkey. All patients infected with Chryseobacterium/Elizabethkingia spp. among those presenting to Ankara City Hospital between March 2014 and March 2022 were included. Results: A total of 49 cases were included and 29 cases were identified as Elizabethkingia. The median age was 14 (0.2-185.0) months. The majority (89.8%) of these patients had an underlying disease, including malignancy (42.9%). Bacteremia (46.9%) and central line-associated bloodstream infection (28.6%) were the most common infections. The thirty-day all-cause mortality rate was 12.2%. The most commonly used antibiotics were ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX). Forty-five (91.8%) isolates were susceptible to ciprofloxacin, 44 (91.6%) to TMP-SMX, and 21 (87.5%) to levofloxacin. Conclusions: Chryseobacterium and Elizabethkingia spp. are emergent, nosocomial pathogens and the majority of cases were older than the neonatal period. They were mainly seen in patients with long hospital stays, indwelling devices, and those who have received antibiotics within the last month, especially carbapenems. In addition, they were associated with bloodstream infection and malignancy. The most commonly useful antibiotics according to the resistance patterns were ciprofloxacin and TMP-SMX.
Objective: To evaluate the radiological features of IgG4-related disease (IgG4-RD) in the head and neck region. Methods: In this radiology-based study, radiological features, clinical, laboratory, pathological findings, and prognosis of nine patients with head and neck involvement diagnosed with IgG4-RD were investigated retrospectively. Results: The median age of the patients was 38 years (range: 2.5-79 years), and there were six males and three females. The most common symptoms and clinical findings of the patients were eyelid and lacrimal gland swelling, painless exophthalmos, and ophthalmoplegia. The most common site of involvement on MRI was the orbit. Orbital involvement was followed by branches of the trigeminal nerve, sinonasal cavity, cervical lymph nodes, and dural involvement. The most common and remarkable imaging features were T2 hypointensity and diffuse homogeneous contrast enhancement. Conclusions: Head and neck involvement of the IgG4-RD, has specific imaging features that can help with diagnosis. Thus, early diagnosis and better outcomes can be achieved with increasing awareness of these features of this relatively new pathology.
Rationale: Disseminated tuberculosis involves the central nervous system in up to a third of cases. However, meningitis and spondylodiscitis due to miliary tuberculosis rarely occur together, particularly in the immuno-competent population. Patient concerns: A 37-year-old immunocompetent male presented with altered level of consciousness for one week and lower back pain with evening pyrexia for one month. Examination revealed spastic paraplegia and left hemiparesis. Diagnosis: Disseminated tuberculosis presenting with meningitis and spondylodiscitis. Interventions: Category I anti-tuberculous therapy with a tapering regimen of intravenous dexamethasone was administered. Outcomes: There was clinical improvement after nine months of treatment. Lessons: Tuberculosis may present with atypical clinical manifestations. Contrast enhanced computed tomography scan or magnetic resonance imaging combined with histopathological features, a high index of suspicion and clinical improvement with anti-tuberculous treatment can confirm the diagnosis in the absence of microbiological evidence, especially in extrapulmonary tuberculosis.
Public health strategies have resulted in declines in some respiratory infectious viruses during the COVID-19 pandemic[1], while the way to assess the extent of public health measures and their impacts on respiratory infectious diseases varies[2-4]. During the pandemic, Thailand has implemented a strong and rapid governmental response according to its incidence rate[3], and we attempted to investigate the association between the extent of public health measures and other respiratory infectious diseases cases amidst the COVID-19 pandemic in Thailand. In this way, the level of public health measures and their impacts on other kinds of non-SARS-CoV-2 respiratory infections will help the government formulate more efficient policies. Containment and Health Index (CHI), a composite measure of the response metrics such as school closures, cancellation of public events and wearing masks, is calculated by the Oxford COVID-19 Government Response Tracker Project in January 2020, to record containment and health system policies[5]. The data spanned from 2020 to 2021 to represent the time when public health measures were put in place in Thailand. The monthly CHI data was an average of daily CHI from Oxford COVID-19 Government Response Tracker in the corresponding month[6]. The reported cases of respiratory infectious diseases such as influenza, tuberculosis, measles, scarlet fever, pneumonia, pertussis, were obtained from the national database for disease surveillance repository provided by Bureau of Epidemiology, Department of Disease Control, Ministry of Public Health, Thailand[7]. These concerned respiratory infectious diseases have been reported with a significant drop in the incidence by an average of 61% in a recent review[3]. However, the influences brought by differenet extents of public health measures were unsure. To further explore their association, regression analysis, Shapiro-Wilk test was used to test the normality of data distribution and scatterplot was used to illustrate their trend. Spearman Correlation Analysis was used to detect the correlation between monthly CHI and reported cases of respiratory infectious diseases in 2020-2021 because of their skewed distribution and negative trend. We found negative correlations between CHI and the notification of the above six respiratory infectious diseases (-1< r <-0.5) in moderate/strong extent using a non-parametric Spearman Correlation Analysis at a significance level of 0.01 (Table 1). However, after using the seasonal autoregressive integrated moving average model to compare with the hospitalization of tuberculosis cases when no public health measures are in place, it underwent an insignificant reduction in the backdrop of public health measures[3]. In contrast to other infectious viruses or bacteria, the transmission of tuberculosis is more multifactorial for its features of incubation period, and reactivation infections[3]. Its high correlation coefficient still suggested that the public health measures taken by governments to curb the spread of SARS-CoV-2 played a significant role in reducing tuberculosis incidence. The reduction in community transmission of Mycobacterium tuberculosis by movement of asymptomatic tuberculosis patients, less access to public transportation, health care facilities and testing and confirming diagnosis services for high-risk tuberculosis population were indispensable reasons[8]. Overall, our study showed that public health measures would impact incidence of respiratory infectious diseases in different extents by employing a COVID-19 response metric. It is crucial for the government to explore a more proper way to investigate the impact of public health measures.