Global Incidence of Diarrheal Diseases-An Update Using an Interpretable Predictive Model Based on XGBoost and SHAP: A Systematic Analysis.

BACKGROUND: Diarrheal disease remains a significant public health issue, particularly affecting young children and older adults. Despite efforts to control and prevent these diseases, their incidence continues to be a global concern. Understanding the trends in diarrhea incidence and the factors influencing these trends is crucial for developing effective public health strategies. OBJECTIVE: This study aimed to explore the temporal trends in diarrhea incidence and associated factors from 1990 to 2019 and to project the incidence for the period 2020-2040 at global, regional, and national levels. We aimed to identify key factors influencing these trends to inform future prevention and control strategies. METHODS: The eXtreme Gradient Boosting (XGBoost) model was used to predict the incidence from 2020 to 2040 based on demographic, meteorological, water sanitation, and sanitation and hygiene indicators. SHapley Additive exPlanations (SHAP) value was performed to explain the impact of variables in the model on the incidence. Estimated annual percentage change (EAPC) was calculated to assess the temporal trends of age-standardized incidence rates (ASIRs) from 1990 to 2019 and from 2020 to 2040. RESULTS: Globally, both incident cases and ASIRs of diarrhea increased between 2010 and 2019. The incident cases are expected to rise from 2020 to 2040, while the ASIRs and incidence rates are predicted to slightly decrease. During the observed (1990-2019) and predicted (2020-2040) periods, adults aged 60 years and above exhibited an upward trend in incidence rate as age increased, while children aged < 5 years consistently had the highest incident cases. The SHAP framework was applied to explain the model predictions. We identified several risk factors associated with an increased incidence of diarrhea, including age over 60 years, yearly precipitation exceeding 3000 mm, temperature above 20 °C for both maximum and minimum values, and vapor pressure deficit over 1500 Pa. A decreased incidence rate was associated with relative humidity over 60%, wind speed over 4 m/s, and populations with above 80% using safely managed drinking water services and over 40% using safely managed sanitation services. CONCLUSIONS: Diarrheal diseases are still serious public health concerns, with predicted increases in the incident cases despite decreasing ASIRs globally. Children aged < 5 years remain highly susceptible to diarrheal diseases, yet the incidence rate in the older adults aged 60 plus years still warrants additional attention. Additionally, more targeted efforts to improve access to safe drinking water and sanitation services are crucial for reducing the incidence of diarrheal diseases globally.

Exosomes mediate horizontal transmission of viral pathogens from insect vectors to plant phloem.

Numerous piercing-sucking insects can horizontally transmit viral pathogens together with saliva to plant phloem, but the mechanism remains elusive. Here, we report that an important rice reovirus has hijacked small vesicles, referred to as exosomes, to traverse the apical plasmalemma into saliva-stored cavities in the salivary glands of leafhopper vectors. Thus, virions were horizontally transmitted with exosomes into rice phloem to establish the initial plant infection during vector feeding. The purified exosomes secreted from cultured leafhopper cells were enriched with virions. Silencing the exosomal secretion-related small GTPase Rab27a or treatment with the exosomal biogenesis inhibitor GW4869 strongly prevented viral exosomal release in vivo and in vitro. Furthermore, the specific interaction of the 15-nm-long domain of the viral outer capsid protein with Rab5 induced the packaging of virions in exosomes, ultimately activating the Rab27a-dependent exosomal release pathway. We thus anticipate that exosome-mediated viral horizontal transmission is the conserved strategy hijacked by vector-borne viruses.

A Neuron-Specific Antiviral Mechanism Modulates the Persistent Infection of Rice Rhabdoviruses in Leafhopper Vectors.

Many plant rhabdoviruses are neurotropic and can persistently infect the central nervous system (CNS) of their insect vectors without causing significant cytopathology. The mechanisms by which the insect CNS resists infection by plant rhabdoviruses are largely unknown. Here, we report that the neural factor Hikaru genki homolog of the leafhopper Nephotettix cincticeps (NcHig) limits the spread of the nucleorhabdovirus rice yellow stunt virus (RYSV) in vector CNS. NcHig is predominantly expressed in the CNS of N. cincticeps, and the knockdown of NcHig expression by RNA interference enhances RYSV infection of the CNS. Furthermore, immuno-blockade of NcHig function by microinjection of N. cincticeps with NcHig antibody also enhances viral infection of the CNS. Thus, we conclude that the neuron-specific factor NcHig can control RYSV propagation in the CNS. Interestingly, we find the Hig homolog of the leafhopper Recilia dorsalis also has antiviral activity during the persistent infection of the cytorhabdovirus rice stripe mosaic virus (RSMV) in vector CNS. We further determine that RYSV and RSMV matrix proteins specifically interact with the complement control protein (CCP) domains of Higs. Thus, the matrix protein-binding ability of Hig is potentially essential for its antiviral activity in rice leafhoppers. Our results demonstrate an evolutionarily conserved antiviral mechanism for Hig to mediate the persistent infection of rice rhabdoviruses in the CNS of leafhopper vectors.