Volume 12 · Issue 02 · 2023

Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL, Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections.

We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keyword Cryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance of C. neoformans to approved antifungal drugs.

There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden.

The rising threat of C. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.

Rabies continues to be a serious threat to global public health endangering people’s health and public health safety. In the People’s Republic of China, multi-sectoral and comprehensive prevention and control strategies have aimed to extensively curb human rabies transmission. Here, we examine the current state of rabies infection in China, explore strategic interventions put in place in response to WHO’s ambition of "Zero rabies deaths by 2030" and critically assess the constraints and feasibility of dog-mediated rabies elimination in China.

This study analyzed and evaluated the process towards dog-mediated rabies elimination in China from five perspectives: namely, human, dog, policy, challenge, and prospects. Evidence-based data on progress of dog-mediated rabies elimination in China was derived from a number of sources; a literature search was undertaken using PubMed, Web of Science and CNKI databases, distribution data for human rabies cases as derived from the Data-center of the China Public Health Science and policy and document data were obtained from official websites of the relevant China ministries and commissions.

The incidence of human rabies cases in China have shown a downward trend year-on-year since 2007. Implementation of a government-led, multi-sectoral "One Health" approach to combating rabies has driven down the total number of rabies deaths nationwide to around 200 in 2020. The number of provincial-level administrative divisions (PLADs) reporting human cases of rabies has also decreased to 21 in 2020, 13 of which reported less than 10 cases. Furthermore, the number of outpatient visits seeking rabies post-exposure prophylaxis has risen dramatically over the past two decades, with demand being 15 times higher than it was initially. There remain however, significant gaps in rabies elimination outcomes across the different regions of China. To date the target of achieving a canine rabies vaccination rate of > 75% has not been met. The challenges of rabies immunization of dogs and dog management in underdeveloped cities and rural areas need to be addressed together with more effective animal surveillance and rabies risk from and too wildlife and livestock.

The Chinese government-led, multi-sectoral "One Health" approach to combating rabies and has made significant progress over the past decade. Development and adoption of more cost-effective One Health strategies can achieve more nationally beneficial rabies elimination outcomes. The ambitious target of "Zero rabies deaths by 2030" can be met through establishment of long-lasting herd immunity in dogs by means of dog mass vaccination campaigns, dog population management, epidemiological surveillance and the application of large-scale oral rabies vaccine to eliminate rabies in wild animals coupled with deployment of cost-effective human post-exposure prophylaxis, and community education.

Global connectivity and environmental change pose continuous threats to dengue invasions from worldwide to China. However, the intrinsic relationship on introduction and outbreak risks of dengue driven by the landscape features are still unknown. This study aimed to map the patterns on source-sink relation of dengue cases and assess the driving forces for dengue invasions in China.

We identified the local and imported cases (2006–2020) and assembled the datasets on environmental conditions. The vector auto-regression model was applied to detect the cross-relations of source-sink patterns. We selected the major environmental drivers via the Boruta algorithm to assess the driving forces in dengue outbreak dynamics by applying generalized additive models. We reconstructed the internal connections among imported cases, local cases, and external environmental drivers using the structural equation modeling.

From 2006 to 2020, 81,652 local dengue cases and 12,701 imported dengue cases in China were reported. The hotspots of dengue introductions and outbreaks were in southeast and southwest China, originating from South and Southeast Asia. Oversea-imported dengue cases, as the Granger-cause, were the initial driver of the dengue dynamic; the suitable local bio-socioecological environment is the fundamental factor for dengue epidemics. The Bio8 [odds ratio (OR) = 2.11, 95% confidence interval (CI): 1.67–2.68], Bio9 (OR = 291.62, 95% CI: 125.63–676.89), Bio15 (OR = 4.15, 95% CI: 3.30–5.24), normalized difference vegetation index in March (OR = 1.27, 95% CI: 1.06–1.51) and July (OR = 1.04, 95% CI: 1.00–1.07), and the imported cases are the major drivers of dengue local transmissions (OR = 4.79, 95% CI: 4.34–5.28). The intermediary effect of an index on population and economic development to local cases via the path of imported cases was detected in the dengue dynamic system.

Dengue outbreaks in China are triggered by introductions of imported cases and boosted by landscape features and connectivity. Our research will contribute to developing nature-based solutions for dengue surveillance, mitigation, and control from a socio-ecological perspective based on invasion ecology theories to control and prevent future dengue invasion and localization.

The area of Oncomelania hupensis snail remains around 3.6 billion m², with newly emerging and reemergent habitats continuing to appear in recent years. This study aimed to explore the long-term dynamics of snail density before and after the operation of Three Gorges Dam (TGD).

Data of snail survey between 1990 and 2019 were collected from electronic databases and national schistosomiasis surveillance. Meta-analysis was conducted to estimate the snail density. Joinpoint model was used to identify the changing trend and inflection point. Inverse distance weighted interpolation (IDW) was used to determine the spatial distribution of recent snail density.

A total of 3777 snail survey sites with a precise location of village or beach were identified. For the down-stream area, snail density peaked in 1998 (1.635/0.11 m², 95% CI: 1.220, 2.189) and fluctuated at a relatively high level before 2003, then declined steadily from 2003 to 2012. Snail density maintained lower than 0.150/0.11 m² between 2012 and 2019. Joinpoint model identified the inflection of 2003, and a significant decreasing trend from 2003 to 2012 with an annual percentage change (APC) being −20.56% (95% CI: −24.15, −16.80). For the upstream area, snail density peaked in 2005 (0.760/0.11 m², 95% CI: 0.479, 1.207) and was generally greater than 0.300/0.11 m² before 2005. Snail density was generally lower than 0.150/0.11 m² after 2011. Snail density showed a significant decreasing trend from 1990 to 2019 with an APC being −6.05% (95% CI: −7.97, −7.09), and no inflection was identified. IDW showed the areas with a high snail density existed in Poyang Lake, Dongting Lake, Jianghan Plain, and the Anhui branch of the Yangtze River between 2015 and 2019.

Snail density exhibited a fluctuating downward trend in the Yangtze River basin. In the downstream area, the operation of TGD accelerated the decline of snail density during the first decade period, then snail density fluctuated at a relatively low level. There still exists local areas with a high snail density. Long-term control and monitoring of snails need to be insisted on and strengthened.

Non-pharmaceutical interventions (NPIs) have been implemented worldwide to suppress the spread of coronavirus disease 2019 (COVID-19). However, few studies have evaluated the effect of NPIs on other infectious diseases and none has assessed the avoided disease burden associated with NPIs. We aimed to assess the effect of NPIs on the incidence of infectious diseases during the COVID-19 pandemic in 2020 and evaluate the health economic benefits related to the reduction in the incidence of infectious diseases.

Data on 10 notifiable infectious diseases across China during 2010–2020 were extracted from the China Information System for Disease Control and Prevention. A two-stage controlled interrupted time-series design with a quasi-Poisson regression model was used to examine the impact of NPIs on the incidence of infectious diseases. The analysis was first performed at the provincial-level administrative divisions (PLADs) level in China, then the PLAD-specific estimates were pooled using a random-effect meta-analysis.

A total of 61,393,737 cases of 10 infectious diseases were identified. The implementation of NPIs was associated with 5.13 million [95% confidence interval (CI): 3.45‒7.42] avoided cases and USD 1.77 billion (95% CI: 1.18‒2.57) avoided hospital expenditures in 2020. There were 4.52 million (95% CI: 3.00‒6.63) avoided cases for children and adolescents, corresponding to 88.2% of total avoided cases. The top leading cause of avoided burden attributable to NPIs was influenza [avoided percentage (AP): 89.3%; 95% CI: 84.5‒92.6]. Socioeconomic status and population density were effect modifiers.

NPIs for COVID-19 could effectively control the prevalence of infectious diseases, with patterns of risk varying by socioeconomic status. These findings have important implications for informing targeted strategies to prevent infectious diseases.

Cryptosporidiosis is a zoonotic intestinal infectious disease caused by Cryptosporidium spp., and its transmission is highly influenced by climate factors. In the present study, the potential spatial distribution of Cryptosporidium in China was predicted based on ecological niche models for cryptosporidiosis epidemic risk warning and prevention and control.

The applicability of existing Cryptosporidium presence points in ENM analysis was investigated based on data from monitoring sites in 2011–2019. Cryptosporidium occurrence data for China and neighboring countries were extracted and used to construct the ENMs, namely Maxent, Bioclim, Domain, and Garp. Models were evaluated based on Receiver Operating Characteristic curve, Kappa, and True Skill Statistic coefficients. The best model was constructed using Cryptosporidium data and climate variables during 1986‒2010, and used to analyze the effects of climate factors on Cryptosporidium distribution. The climate variables for the period 2011‒2100 were projected to the simulation results to predict the ecological adaptability and potential distribution of Cryptosporidium in future in China.

The Maxent model (AUC = 0.95, maximum Kappa = 0.91, maximum TSS = 1.00) fit better than the other three models and was thus considered the best ENM for predicting Cryptosporidium habitat suitability. The major suitable habitats for human-derived Cryptosporidium in China were located in some high-population density areas, especially in the middle and lower reaches of the Yangtze River, the lower reaches of the Yellow River, and the Huai and the Pearl River Basins (cloglog value of habitat suitability > 0.9). Under future climate change, non-suitable habitats for Cryptosporidium will shrink, while highly suitable habitats will expand significantly (χ² = 76.641, P < 0.01; χ² = 86.836, P < 0.01), and the main changes will likely be concentrated in the northeastern, southwestern, and northwestern regions.

The Maxent model is applicable in prediction of Cryptosporidium habitat suitability and can achieve excellent simulation results. These results suggest a current high risk of transmission and significant pressure for cryptosporidiosis prevention and control in China. Against a future climate change background, Cryptosporidium may gain more suitable habitats within China. Constructing a national surveillance network could facilitate further elucidation of the epidemiological trends and transmission patterns of cryptosporidiosis, and mitigate the associated epidemic and outbreak risks.

Brucellosis is a common zoonotic infectious disease in China. This study aimed to investigate the incidence trends of brucellosis in China, construct an optimal prediction model, and analyze the driving role of climatic factors for human brucellosis.

Using brucellosis incidence, and the socioeconomic and climatic data for 2014–2020 in China, we performed spatiotemporal analyses and calculated correlations with brucellosis incidence in China, developed and compared a series of regression and Seasonal Autoregressive Integrated Moving Average X (SARIMAX) models for brucellosis prediction based on socioeconomic and climatic data, and analyzed the relationship between extreme weather conditions and brucellosis incidence using copula models.

In total, 327,456 brucellosis cases were reported in China in 2014–2020 (monthly average of 3898 cases). The incidence of brucellosis was distinctly seasonal, with a high incidence in spring and summer and an average annual peak in May. The incidence rate was highest in the northern regions’ arid and continental climatic zones (1.88 and 0.47 per million people, respectively) and lowest in the tropics (0.003 per million people). The incidence of brucellosis showed opposite trends of decrease and increase in northern and southern China, respectively, with an overall severe epidemic in northern China. Most regression models using socioeconomic and climatic data cannot predict brucellosis incidence. The SARIMAX model was suitable for brucellosis prediction. There were significant negative correlations between the proportion of extreme weather values for both high sunshine and high humidity and the incidence of brucellosis as follows: high sunshine, r = −0.59 and −0.69 in arid and temperate zones; high humidity, r = −0.62, −0.64, and −0.65 in arid, temperate, and tropical zones.

Significant seasonal and climatic zone differences were observed for brucellosis incidence in China. Sunlight, humidity, and wind speed significantly influenced brucellosis. The SARIMAX model performed better for brucellosis prediction than did the regression model. Notably, high sunshine and humidity values in extreme weather conditions negatively affect brucellosis. Brucellosis should be managed according to the "One Health" concept.

Malaria is caused by multiple parasitic species of the genus Plasmodium. Plasmodium vivax is the most geographically widespread and poses challenges in elimination due to its unique biological and epidemiological characteristics. The aim of study was to highlight the practices and experience targeting vivax malaria control and elimination in China.

P. vivax malaria was historically endemic in more than 70% of counties in China, with reported vivax malaria cases as high as 26 million a year. After around 70 years of effort, China was certified as malaria-free in June of 2021. The key insights into China’s vivax malaria control and elimination were offered, including radical cure strategies, comprehensive but adaptive strategies targeting species of Plasmodium and Anopheles, mass drug administration, and case-/focus-centred surveillance and response systems.

The complete global eradication of P. vivax and eventually malaria will be more difficult, and China’s practices and experience could be a valuable reference in this campaign.

A global surplus of coronavirus disease 2019 (COVID-19) vaccines exists as a result of difficulties in aligning the demand and supply for vaccine manufacturing and delivery. World leaders have accelerated vaccine development, approval, production and distribution as a pragmatic approach to addressing the immediate public health challenges of the first two and a half years of the pandemic.

The currently predominant, highly transmissible Omicron variant of severe acute respiratory syndrome coronavirus 2 has brought us closer to the threshold required to achieve herd immunity by greatly increasing rates of natural infection. Paradoxically, in parallel with rising vaccination levels in industrialized nations, this indirectly reduces the need for mass vaccine campaigns. Principal concerns that contribute to low vaccination rates which persist in several other countries, particularly of the Global South, are vaccine hesitancy and unequal access to vaccination. Social uncertainty fueled by fake news, misinformation, unfounded lay opinions and conspiracy theories has inevitably led to an erosion of public trust in vaccination.

To address the current mismatch between supply and demand of COVID-19 vaccines, there should be a focus on three principles: decelerating vaccine production, increasing distribution across communities, and optimizing cost-effectiveness of distribution logistics. Slowing down and switching from large-scale production to effectively 'made to order’ is a feasible option, which should be commensurate with management capacity. Transparent and evidence-based data should be widely and freely disseminated to the public through multimedia channels to mitigate miscommunication and conspiracy theories. Use of soon-to-expire stockpiles should be prioritized not only to enhance booster dose rollouts in adults but to expand immunization campaigns to children (especially those aged 5–11 years), subject to national approval. Future research should ideally aim to develop vaccines that only require basic, affordable storage and maintenance procedures as opposed to sophisticated and expensive protocols.