Development and Evaluation of Wild-Derived Rats as Potential Experimental Models for Research

Wild rodents have been used as animal models in experimental studies of cellular aging, cerebral malaria, schistosomiasis, and leishmaniasis. Since they are the reservoirs of these diseases, recent studies have shown that research involving wild rodents is more efficient in giving a mirror image of the disease progression outside the laboratory setting. The study design was an analytic experimental study where observations were made between two groups of animals i.e. the wild-derived and lab-bred rats. The outcome of the intervention was obtained by comparing the two groups. This study sought to determine the usability of wild-derived rats as potential experimental animal models for biomedical research. Wild rats were randomly captured in areas with high transmission of Schistosoma mansoni and Leishmania donovani in Kisumu and Kitui counties, in Kenya and maintained in the animal house at Kenya Medical Research Institute (KEMRI) in Nairobi. Breeding was carried out, and the subsequent generations were used to assess schistosomiasis and leishmaniasis disease progression between the wild-derived, and laboratory-bred rats. We further monitored behavior patterns and food consumption rate for 3 months in a total of 6 experimental trials. The results on feed consumption capacity indicated that consumption was significantly higher in laboratory-bred groups (p=0.001) compared to wild-derived rats. Overall, laboratory-bred rats were significantly heavier than wild rats. In the use of rats to assess schistosomiasis and leishmaniasis disease progression, the wild-derived rats were more susceptible to leishmaniasis and may be considered for S. mansoni compared to wild (worms recovered p=0.031). In conclusion, the study indicated that wild rats are potential reservoir hosts for both schistosomiasis and leishmaniasis and have the potential to maintain cycles of infection until after successful chemotherapeutic intervention. Therefore, wild rats may provide natural means for parasites like S. mansoni and L. donovani to re-infect humans in endemic areas.

Assessment of factors influencing adoption of tomato post-harvest loss-reduction technologies in Kaduna state, Nigeria

The Nigerian government\u27s policy on agriculture supports productivity enhancements, yet tomato production is constrained by post-harvest losses of up to over 45%. 420 tomato farmers were selected for study in Kaduna State, Nigeria. Multinomial Logit Model was used to determine factors influencing losses while factors influencing adoption and intensity were modelled using Tobit. The results showed the adoption rate of (new technologies) RP was 3.57%, CS = 0.47%, RT = 0.71%, MD =0.71%, CD = 100%. Adoption rate of (traditional method) raffia basket was 100%. For farmers, the highest source of losses was those in storage (70.5%), followed by farm level (14.5%). Results on factors influencing PHL showed that in transit, Modern Technology accentuated losses (p<0.10), while Car/truck ownership mitigated losses (p<0.01) In storage, Modern Technology (p<0.05), Farm Distance (p<0.05), Farm Size (p<0.10), and Own Car/truck ownership (p<0.10) mitigated losses, while only Multiple Cropping (p<0.05) accentuated losses. In marketing, education (p<0.05), modern technology (p<0.10), multiple cropping (P<0.10), and credit access (P<0.10) accentuated losses while age of farmer (p<0.10), years of technology adoption (p<0.10), farm size (p<0.10), and wealth status of farmer (p<0.05) mitigated losses. The results factors influencing adoption and adoption intensity of PHL-reducing technology show that Education (p<0.05), Age (p<0.10), Extension (p<0.10), CS_Information_Sources (p<0.01), RT_Information_Sources (p<0.01), MD_Information_Sources (p<0.05), Labour_sourcesT (p<0.01), Credit_sourcesT (p<0.10), and Farm_Size (p<0.01) were positive and had a significant influence. Education had a quadratic (Education2) negative influence on adoption of PHL reducing technologies. In conclusion, extension services exposure, large farm holding, and multiple information sources positively influenced adoption of post-harvest loss reduction technologies. The field survey also showed a 100% willingness of the farmers to adopt improved/modern technologies. The study recommended using PPP model to make these modern technologies and farm practices within the financial reach of farmers to mitigate post-harvest losses

Effects of selected drivers of information and communication on awareness and perception of tomato post-harvest loss-reduction technologies in Kaduna, Nigeria

The Nigerian government\u27s policy on agriculture has supported productivity enhancements among smallholder farmers, yet tomato production is constrained by post-harvest losses leading to over 45 % (750,000 metric tons) loss. Various initiatives are constantly being introduced to make technologies and practices available to reduce these losses. This study was carried out to determine the level of awareness and perception of four technologies. A total of 420 tomato farmers were selected in Kaduna State, Nigeria. Awareness and perception were modelled using the Multivariate Probit Model. The results showed that one or more of the independent variables including cooperative affiliation (p<0.001, for awareness of Reusable Plastic Crate {RP} technique), frequency of extension visit (p<0.001, for awareness of RP), and farm area cultivated (p<0.05, for awareness of Refrigerated Truck {RT}/ Machine Drying {MD}) were significant. For perception, some of the independent variables explored and found significant included multiple sources of information for CS/RT, losses through transit/storage (P<0.01) and the number of technologies adopted (P<0.001) for cheapness; credit access (P<0.001) and farm area (P<0.001) for availability; marital status (P<0.01) and losses through storage (P<0.021) for labour saving perceptions. The awareness and perception of the tomato PHL reduction technologies do not provide common determinants. The study concluded that the communication channels such as Farmer to Farmer, Radio and extension agents (57.9%, 9.3%, 33% for RP, respectively), among others, influenced awareness of the new technologies among farmers. The study recommends the need to drive farmers’ awareness using suitable advocacy channels. A better understanding of constraints that influence farmers\u27 perceptions is important while designing and rolling out technologies

Cystic echinococcosis in donkeys in eastern Africa

Cystic echinococcosis (CE) is endemic in humans and domestic animals in eastern Africa. All the species of the Echinococcus granulosus sensu lato complex have been reported in this region except for E. equinus, possibly due to the small number of studies involving equids. This study reports the frequency of different Echinococcus species in donkeys from eastern Africa. A total of 5961 donkeys were examined during meat inspection in 3 slaughterhouses in Kenya. Identification of Echinococcus spp. was achieved through polymerase chain reaction-restriction fragment-length polymorphism and sequencing of the mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 gene. The prevalence of CE was 5.7% (337/5961). The 263 genotyped cysts belonged to E. equinus (n = 163), E. granulosus sensu stricto (n = 70), E. canadensis (G6/7) (n = 26) and E. ortleppi (n = 4). One donkey harboured a metacestode of Spirometra theileri. All E. equinus cases, except 2, originated from southern Ethiopia, whereas the other species were more evenly distributed across the study area. Most of the cysts belonging to E. equinus were fertile (111/163), while those of the other species were non-fertile. This is the first report of Echinococcus spp. in donkeys from sub-Saharan Africa and the first confirmation of E. equinus in East Africa. The frequent fertility of E. equinus cysts in donkeys affirms their suitability as intermediate hosts of this species, while low frequency and cyst fertility suggest a marginal role of donkeys in the transmission of E. granulosus s. s., E. canadensis (G6/7) and E. ortleppi

Impact of Opioid Substitution Therapy on Antiretroviral Therapy Outcomes:A Systematic Review and Meta-Analysis

BACKGROUND: Human immunodeficiency virus (HIV)-infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID.METHODS: We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I(2) statistic.RESULTS: We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32-2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17-2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41-3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63-.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21-1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65-1.25).CONCLUSIONS: These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID.</p

The potential role of roaming dogs in establishing a geographically novel life cycle of taeniids (Echinococcus spp. and Taenia spp.) in a non-endemic area

Cystic Echinococcosis (CE) is endemic in humans and livestock in many pastoral communities in Kenya. The distribution of the disease is enhanced by several factors, including livestock trade, which has allowed for the spread of CE to non-endemic areas such as western Kenya. Dogs' roaming behaviour, with consequent contamination of the environment with intestinal parasites, could then lead to parasite establishment. This study examined dogs' infection levels with taeniid eggs and their potential role in contaminating the environment with intestinal parasites. Methodology: We selected sixteen ruminant slaughterhouses in Busia and Bungoma Counties, and around each slaughterhouse we identified ten homesteads owning free-roaming dogs. We administered a questionnaire on dog management practices to the homestead owner and collected a faecal sample from the dog's rectum. In homesteads around 8 of the 16 slaughterhouses, we collared dogs with a GPS tracker to assess their movement patterns. The faecal samples were examined microscopically following zinc-chloride sieving-floatation technique for the presence of taeniid eggs and other canine intestinal parasites. Polymerase Chain Reaction – Restriction Fragment Length Polymorphism of NADH dehydrogenase subunit 1 gene and sequencing were used to confirm taeniid eggs identified during microscopy. Additionally, the Coproantigen-ELISA was used to detect the presence of taeniid antigen in a sub-set of the faecal samples. Results: Helminths detected in the 155 dogs sampled included hookworms (n = 92; 59.4%), ascarids (n = 15; 9.7%), and taeniids (n = 1; 0.6%). Through Copro-PCR, 13 eggs extracted from the sample of the only taeniid infected dog were sequenced and identified as E. canadensis (G6/7) [n = 1], Taenia multiceps [n = 1], and Taenia serialis [n = 6]; the remaining were indeterminate. Of the 77 faecal samples tested for E. granulosus sensu lato (s. l.) with the Copro-ELISA, 64 (83.1%) were negative, 12 (15.6%) were positive, while 1 (1.3%) was suspicious. The dogs travelled a median of 13.5 km daily, and 28 dogs visited the slaughterhouses during the 5-day recording period. Conclusion: The results indicate a relatively high carriage of zoonotic parasites by free-roaming domestic dogs in western Kenya, which poses a risk to human and livestock populations. We report for the first time a domestic lifecycle of Echinococcus canadensis and Taenia multiceps in western Kenya, as well as a presumptive sylvatic cycle of coenurosis by T. serialis. We recommend an extensive and ongoing Copro-antigen survey of dog faeces, broader assessment of dog parasites with zoonotic potential, adherence to slaughterhouse management practices, and dog-ownership programmes to highlight the importance of deworming and restricted dog movements

Impact of opioid substitution therapy on the HIV prevention benefit of antiretroviral therapy for people who inject drugs

Objective: A recent meta-analysis suggested that opioid substitution therapy (OST) increased uptake of anti-retroviral treatment (ART) and HIV viral suppression. We modelled whether OST could improve the HIV prevention benefit achieved by ART amongst people who inject drugs (PWID). Methods: We modelled how introducing OST could improve the coverage of ART across a PWID population for different baseline ART coverage levels. Using existing data on how yearly HIV-transmission risk is related to HIV plasma viral load, changes in the level of viral suppression across the population were used to project the relative reduction in yearly HIV-transmission risk achieved by ART, with or without OST, compared to if there was no ART - defined here as the prevention effectiveness of ART. Results: Due to OST use increasing the chance of being on ART and achieving viral suppression if on ART, the prevention effectiveness of ART for PWID on OST (compared to PWID not on OST) increases by 44%, 31% or 20% for a low (20%), moderate (40%) or high (60%) baseline ART coverage, respectively. Improvements in the population-level prevention effectiveness of ART are also achieved across all PWID, compared to if OST was not introduced. For instance, if OST is introduced at 40% coverage, the population-level prevention effectiveness of ART could increase by 27%, 20% or 13% for a low (20%), moderate (40%) or high (60%) baseline ART coverage, respectively. Conclusions: OST could markedly improve the HIV prevention benefit of ART; supporting strategies that aim to concurrently scale-up OST with ART

Impact of opioid substitution therapy on the HIV prevention benefit of antiretroviral therapy for people who inject drugs

Objective: A recent meta-analysis suggested that opioid substitution therapy (OST) increased uptake of anti-retroviral treatment (ART) and HIV viral suppression. We modelled whether OST could improve the HIV prevention benefit achieved by ART amongst people who inject drugs (PWID). Methods: We modelled how introducing OST could improve the coverage of ART across a PWID population for different baseline ART coverage levels. Using existing data on how yearly HIV-transmission risk is related to HIV plasma viral load, changes in the level of viral suppression across the population were used to project the relative reduction in yearly HIV-transmission risk achieved by ART, with or without OST, compared to if there was no ART - defined here as the prevention effectiveness of ART. Results: Due to OST use increasing the chance of being on ART and achieving viral suppression if on ART, the prevention effectiveness of ART for PWID on OST (compared to PWID not on OST) increases by 44%, 31% or 20% for a low (20%), moderate (40%) or high (60%) baseline ART coverage, respectively. Improvements in the population-level prevention effectiveness of ART are also achieved across all PWID, compared to if OST was not introduced. For instance, if OST is introduced at 40% coverage, the population-level prevention effectiveness of ART could increase by 27%, 20% or 13% for a low (20%), moderate (40%) or high (60%) baseline ART coverage, respectively. Conclusions: OST could markedly improve the HIV prevention benefit of ART; supporting strategies that aim to concurrently scale-up OST with ART

The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the Clinical Validity of 111 Gene-Disease Relationships.

PURPOSE: The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels (GCEPs) have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders GCEP (SD-GCEP) was formed to address an unmet need. METHODS: The SD-GCEP applied ClinGen\u27s framework to evaluate the clinical validity of genes associated with rare syndromic disorders. 111 Gene-Disease Relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated. RESULTS: From April 2020 through March 2024, 38 precurations were performed on genes with multiple disease relationships and were reviewed to determine if the disorders were part of a spectrum or distinct entities. 14 genes were lumped into a single disease entity and 24 were split into separate entities, of which 11 were curated by the SD-GCEP. A full review of 111 GDRs for 100 genes followed, with 78 classified as Definitive, 9 as Strong, 15 as Moderate, and 9 as Limited highlighting where further data are needed. All diseases involved two or more organ systems, while the majority (88/111 GDRs, 79.2%) had five or more organ systems affected. CONCLUSION: The SD-GCEP addresses a critical gap in gene curation efforts, enabling inclusion of genes for syndromic disorders in clinical testing and contributing to keeping pace with the rapid discovery of new genetic syndromes