Homozygous mutation in SLO3 leads to severe asthenoteratozoospermia due to acrosome hypoplasia and mitochondrial sheath malformations

Background Potassium channels are important for the structure and function of the spermatozoa. As a potassium transporter, the mSlo3 is essential for male fertility as Slo3 knockout male mice were infertile with the series of functional defects in sperm cells. However, no pathogenic variant has been detected in human SLO3 to date. Here we reported a human case with homozygous SLO3 mutation. The function of SLO3 in human sperm and the corresponding assisted reproductive strategy are also investigated. Methods We performed whole-exome sequencing analysis from a large cohort of 105 patients with asthenoteratozoospermia. The effects of the variant were investigated by quantitative RT-PCR, western blotting, and immunofluorescence assays using the patient spermatozoa. Sperm morphological and ultrastructural studies were conducted using haematoxylin and eosin staining, scanning and transmission electron microscopy. Results We identified a homozygous missense variant (c.1237A > T: p.Ile413Phe) in the sperm-specific SLO3 in one Chinese patient with male infertility. This SLO3 variant was rare in human control populations and predicted to be deleterious by multiple bioinformatic tools. Sperm from the individual harbouring the homozygous SLO3 variant exhibited severe morphological abnormalities, such as acrosome hypoplasia, disruption of the mitochondrial sheath, coiled tails, and motility defects. The levels of SLO3 mRNA and protein in spermatozoa from the affected individual were reduced. Furthermore, the acrosome reaction, mitochondrial membrane potential, and membrane potential during capacitation were also afflicted. The levels of acrosome marker glycoproteins and PLCζ1 as well as the mitochondrial sheath protein HSP60 and SLO3 auxiliary subunit LRRC52, were significantly reduced in the spermatozoa from the affected individual. The affected man was sterile due to acrosome and mitochondrial dysfunction; however, intra-cytoplasmic sperm injection successfully rescued this infertile condition. Conclusions SLO3 deficiency seriously impact acrosome formation, mitochondrial sheath assembly, and the function of K+ channels. Our findings provided clinical implications for the genetic and reproductive counselling of affected families.

Nipah virus detection at bat roosts following spillover events in Bangladesh, 2012-2019

Knowledge of the dynamics and genetic diversity of Nipah virus circulating in bats and at the human-animal interface is limited by current sampling efforts, which produce few detections of viral RNA. We report on a series of investigations at bat roosts identified near human Nipah cases in Bangladesh between 2012 and 2019. Pooled bat urine samples were collected from 23 roosts; seven roosts (30%) had at least one sample with Nipah RNA detected from the first visit. In subsequent visits to these seven roosts, RNA was detected in bat urine up to 52 days after the presumed exposure of the human case, although the probability of detection declined rapidly with time. These results suggest that rapidly deployed investigations of Nipah virus shedding from bat roosts near human cases could increase the success of viral sequencing compared to background surveillance and enhance our understanding of Nipah virus ecology and evolution.

A Review of Zoonotic Babesiosis as an Emerging Public Health Threat in Asia

Zoonotic babesiosis poses a serious health risk in many parts of the world. Its emergence in Asia is thus a cause for significant concern, demanding that appropriate control measures are implemented to suppress its spread in this region. This study focuses on zoonotic Babesia species reported in Asia, offering an extensive review of those species reported in animals and humans. We reported 11 studies finding zoonotic Babesia species in animals and 16 in humans. In China, the most prevalent species was found to be Babesia microti, reported in both humans (n = 10) and wild and domesticated animals (n = 4). In Korea, only two studies reported human babesiosis, with a further two studies reporting Babesia microti in wild animals. Babesia microti was also reported in wild animal populations in Thailand and Japan, with evidence of human case reports also found in Singapore, Mongolia and India. This is the first review to report zoonotic babesiosis in humans and animals in Asia, highlighting concerns for future public health in this region. Further investigations of zoonotic species of Babesia in animal populations are required to confirm the actual zoonotic threat of babesiosis in Asia, as well as its possible transmission routes.

A Human Case of Lumbosacral Canal Sparganosis in China

In this study, we intended to describe a human case of lumbosacral canal sparganosis in People’s Republic of China (China). A 56-year-old man was admitted to Xiangya Hospital Central South University in Changsha, Hunan province, China after having an experience of perianal pain for a week. An enhancing mass, a tumor clinically suggested, was showed at the S1-S2 level of the lumbosacral spine by the examination of magnetic resonance imaging (MRI) with gadolinium contrast. The patient was received the laminectomy from S1 to S2, and an ivory-white living worm was detected in inferior margin of L5. In ELISA-test with cerebrospinal fluid (CSF) and serum samples, anti-sparganum antibodies were detected. He had a ingesting history of undercooked frog meat in his youth. By the present study, a human case of spinal sparganosis invaded in lumbosacral canal at the S1-S2 level was diagnosed in China. Although the surgical removal of larvae is known to be the best way of treatment for sparganosis, we administered the high-dosage of praziquantel, albendazole and dexamethasone to prevent the occurrence of another remain worms in this study.

Modelling to infer the role of animals in gambiense human African trypanosomiasis transmission and elimination in DRC

Gambiense human African trypanosomiasis (gHAT) has been targeted for elimination of transmission (EoT) to humans by 2030. Whilst this ambitious goal is rapidly approaching, there remain fundamental questions about the presence of non-human animal transmission cycles and their potential role in slowing progress towards, or even preventing, EoT. In this study we focus on the country with the most gHAT disease burden, the Democratic Republic of Congo (DRC), and use mathematical modelling to assess whether animals may contribute to transmission in specific regions, and if so, how their presence could impact the likelihood and timing of EoT. By fitting two model variants – one with, and one without animal transmission – to the human case data from 2000–2016 we estimate model parameters for 158 endemic health zones of DRC. We evaluate the statistical support for each model variant in each health zone and infer the contribution of animals to overall transmission and how this could impact predicted time to EoT. We conclude that there are 24/158 health zones where there is moderate or high statistical support for some animal transmission. However, – even in these regions – we estimate that animals would be extremely unlikely to maintain transmission on their own. Animal transmission could hamper progress towards EoT in some settings, with projections under continuing interventions indicating that the number of health zones expected to achieve EoT by 2030 reduces from 68 to 61 if animals are included in the model. With supplementary vector control (at a modest 60% tsetse reduction) added to medical screening and treatment interventions, the predicted number of health zones meeting the goal increases to 147/158 for the model including animals. This is due to the impact of vector reduction on transmission to and from all hosts.

Near infra-red fluorescence identification of the thoracic duct to prevent chyle leaks during oesophagectomy

Background Chyle leaks following oesophagectomy are a frustrating complication of surgery with considerable morbidity. The use of near infra-red (NIR) fluorescence in surgery is an emerging technology and the use of fluorescence to identify the thoracic duct has been demonstrated in animal work and early human case reports. This study evaluated the use mesenteric and enteral administration of indocyanine green (ICG) in humans to identify the thoracic duct during oesophagectomy. Methods Patients undergoing oesophagectomy were recruited to the study. Administration of ICG via an enteral route or mesenteric injection was evaluated. Fluorescence was assessed using a NIR fluorescence enabled laparoscope system with a visual scoring system and signal to background ratios. Visualisation of the thoracic duct under white light and NIR fluorescence was compared as well as any identification of active chyle leak. Patients were followed up post-operatively for adverse events and chyle leak. Results 20 patients received ICG and were included in the study. The enteral route failed to fluoresce the thoracic duct. Mesenteric injection (17 patients) identified the thoracic duct under fluorescence prior to white light in 70% of patients with a mean signal to background ratio of 5.35. In 6 participants, a possible active chyle leak was identified under fluorescence with 4 showing active chyle leak from what was identified as the thoracic duct. Conclusion This study demonstrates that ICG administration via mesenteric injection can highlight the thoracic duct during oesophagectomy and may be a potential technology to reduce chyle leak following surgery. Clinical trial registration Clinical trials.gov (NCT03292757).

Development of an Index to Measure West Nile Virus Transmission Risk in New Jersey Counties

ABSTRACT We developed an index for use by New Jersey counties to measure West Nile virus (WNV) transmission risk to the human population. We used a latent profile analysis to develop the index, identifying categories of environmental conditions associated with WNV transmission risk to humans. The final model included 4 indicators of transmission risk: mosquito abundance and minimum field infection rate, temperature, and human case count. We used data from 2004 to 2018 from all 21 New Jersey counties aggregated into 11 2-wk units per county per year (N = 3,465). Three WNV risk classes were identified. The Low Risk class had low levels of all variables. The Moderate Risk class had high abundance, average temperature levels, and low levels of the other variables. The High Risk class had substantially above average human case likelihood, average temperature, and high mosquito infection rates. These results suggest the presence of 3 distinct WNV risk profiles, which can be used to guide the development of public health actions intended to mitigate WNV transmission risk to the human population.

Use of Cervid Serosurveys to Monitor Eastern Equine Encephalitis Virus Activity in Northern New England, United States, 2009–2017

Vertebrate surveillance for eastern equine encephalitis virus (EEEV) activity usually focuses on three types of vertebrates: horses, passerine birds, and sentinel chicken flocks. However, there is a variety of wild vertebrates that are exposed to EEEV infections and can be used to track EEEV activity. In 2009, we initiated a pilot study in northern New England, United States, to evaluate the effectiveness of using wild cervids (free-ranging white-tailed deer and moose) as spatial sentinels for EEEV activity. In Maine, New Hampshire, and Vermont during 2009–2017, we collected blood samples from hunter-harvested cervids at tagging stations and obtained harvest location information from hunters. U.S. Centers for Disease Control and Prevention processed the samples for EEEV antibodies using plaque reduction neutralization tests (PRNTs). We detected EEEV antibodies in 6 to 17% of cervid samples in the different states and mapped cervid EEEV seropositivity in northern New England. EEEV antibody-positive cervids were the first detections of EEEV activity in the state of Vermont, in northern Maine, and northern New Hampshire. Our key result was the detection of the antibodies in areas far outside the extent of documented wild bird, mosquito, human case, or veterinary case reports of EEEV activity in Maine, New Hampshire, and Vermont. These findings showed that cervid (deer and moose) serosurveys can be used to characterize the geographic extent of EEEV activity, especially in areas with low EEEV activity or with little or no EEEV surveillance. Cervid EEEV serosurveys can be a useful tool for mapping EEEV activity in areas of North America in addition to northern New England.

Eastern Equine Encephalomyelitis in Michigan: Historical Review of Equine, Human, and Wildlife Involvement, Epidemiology, Vector Associations, and Factors Contributing to Endemicity

Eastern equine encephalomyelitis (EEE) is a mosquito-borne viral disease that is an emerging public health concern in the state of Michigan. Although Michigan has one of the highest incidence rates of EEE in the United States, much of the information known about cases in humans, equines, and other animals residing in Michigan is unpublished. This article summarizes such information and explores spatial trends in the historic distribution of EEE in Michigan. Outbreaks in Michigan have occurred over an 80-yr interval, involving only horses in 1942–1943 and 1973–1976, and then episodically from 1980 to 2020, and involving horses, humans, and wild and domestic animals. An estimated 1,036 equine cases (confirmed and suspected) and 36 confirmed human cases have occurred, including 10 in 2019 (6 deaths) and 4 in 2020 (2 deaths). Human cases ranged in age from 1 to 81 yr; 70% were male, and fatality rate of 34.3%. Equine and human cases occurred from July to October, peaked in August, and cluster in space in southwestern and southeastern lower Michigan. Cases occurred in glacial outwash and ice-contact landscapes in glacial interlobate zones. EEE virus (EEEV) was recovered from Culiseta melanura, Coquillettidia perturbans, five species of Aedes, and other mosquito species near horse and human case sites. Virus isolations or presence of neutralizing antibodies in several passerine species of birds suggest broad EEEV–bird associations. White-tailed deer and other wildlife were also affected. Geographic spread to northern areas of the state suggests expansion of this disease system into new and unsuspected foci.