Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing t...Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome.Here,we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models.In addition,we assessed the pathogenicity of AIVs in ferret models.Moreover,we compared the ability of viruses to replicate in mammalian cells,as well as the receptor-binding preferences of AIV isolates.Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation.Of the 24 AIV isolates tested,A/Mallard/South Korea/KNU2019-34/2019(KNU19-34;H1N1)caused severe bodyweight loss and high mortality in mice.The virus replicated in the lungs,kidneys,and heart.Importantly,KNU19-34-infected ferrets showed high viral loads in both nasal washes and lungs.KNU19-34 replicated rapidly in A549 and bound preferentially to human likeα2,6-linked sialic acids rather than to avian-likeα2,3-linked sialic acids,similar to the pandemic A/California/04/2009(H1N1)strain.Gene segments of KNU19-34 were distributed in Egypt and Asia lineages from 2015 to 2018,and the virus had several amino acid substitutions compared to H1N1 AIV isolates that were non-pathogenic in mice.Collectively,the data suggest that KNU19-34 has zoonotic potential and the possibility of new mutations responsible for mammalian adaptation.展开更多
There are some Indications thtt herpes aimplex virus (HSV) may be mutagenic. Specific chromosomal changes have also been demonstrated In cultured cells infected with HSV. To further Investigate the mutagenic activity ...There are some Indications thtt herpes aimplex virus (HSV) may be mutagenic. Specific chromosomal changes have also been demonstrated In cultured cells infected with HSV. To further Investigate the mutagenic activity of HSV type 2 (HSV-2) we used mouse skin as a model system for cardnogenetls. Inoculation of the back skin of 4-week-old Sencar mke with live virus twice per week for one week or with Inactivated virus twice per week for two weeks was used to Initiate the mouse akin. After Initiation with HSV-2, 12-O-tetradecanoylphorbol-13-acetale(TPA) was applied twice weekly for 50 weeks as a promoter. During a period of 52 weeks, no skin carcinoma was found In the experimental groups, whereas 55% of control mice treated with 9, 10-dlmethy1-1, 2- benzanthracene (DMBA ) and then with TPA-developed skin carcinoma. The results demonstrate that HSV-2 could not substitute for DMBA in this animal model of two-stage skin carcinogenesis.展开更多
The isolation of influenza viruses in Madin Darby Canine Kidney (MDCK) cells has shown preferential isolation of a great percentage of Influenza B strains at the first passage than Influenza A strains. During in vitro...The isolation of influenza viruses in Madin Darby Canine Kidney (MDCK) cells has shown preferential isolation of a great percentage of Influenza B strains at the first passage than Influenza A strains. During in vitro isolation of Influenza viruses, majority of type A viruses are not confirmed as positive isolates by Hemagglutination (HA) assay despite having higher virulence and pathogenicity versus influenza B viruses. This study investigated the differences in IFN-γ and IL-10 cytokines secreted by MDCK cells upon exposure to the viruses and thus provided possible answers as to why influenza type B can easily be isolated from MDCK cells compared to influenza A. Positive influenza viruses were inoculated onto MDCK cells. IFN-γ and IL-10 cytokines stimulated by the viruses in MDCK cells were measured by indirect ELISA at 1 hour, 12 hours, 48 hours and 72 hours post inoculation (pi). A total of 46 specimens, with 23 specimens from each virus type were analyzed. IFN-γ was significantly higher at 1 hour pi in MDCK cells for influenza type A at p value of 0.024 than type B. No statistical significance was observed in means of cytokine IL-10 between influenza type A and type B. The study may show that IFN-γ is correlated to the preferential isolation of influenza type B over type A viruses. Anti-inflammatory cytokines may not necessarily be playing a role in the preferential growth of influenza type B, a less virulent type over influenza type A in MDCK cells.展开更多
Sludge contains organic and inorganic compounds including traces of heavy metals such as lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), chromium (Cr) and others. These metals restrict the use of sludge in agricult...Sludge contains organic and inorganic compounds including traces of heavy metals such as lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), chromium (Cr) and others. These metals restrict the use of sludge in agriculture because their accumulation is harmful to the environment and particularly the food chain. Cadmium and lead are among the most common heavy metals found in municipal wastewater treatment plant sludge. They are capable of bioaccumulation in plant tissues like roots and leaves and are non-biodegradable and therefore they remain in the sludge which is disposed on land or used as fertilizers on farms. The presence of heavy metal pollutants serves as a great threat to soils and also makes plants grown on such soils unfit for animal and human consumption as they may have detrimental effects to animal and human life. For instance, Pb and Cd are known to be human carcinogens. This study therefore aimed to investigate the levels of Cd and Pb in the treated dry sludge from Lubigi Feacal Sludge and Wastewater treatment plant located in Kawempe division, Kampala city, Uganda so as to ascertain its safety for use on agricultural lands. Two batches of samples were collected and analyzed at Government Analytical laboratory in Wandegeya, Uganda. The acid digested sludge samples were analyzed using Atomic Absorption Spectroscopy (AAS) method. The average concentrations of Pb found in collected sludge samples, batch 1 (11.912 mg/kg dm) and batch 2 (5.304 mg/kg dm) were far below the Environment Protection Agency (EPA) maximum permissible concentration (840 mg/kg) for any land application. Cadmium was not detected in all the sludge samples collected;there is an implication that it is either completely absent in the sludge generated by the plant or present but far below detectable levels. The sludge generated from Lubigi fecal sludge and wastewater treatment plant is therefore safe for application on agricultural lands as far as Pb and Cd concentrations are concerned.展开更多
Aflatoxin contamination and rancidity in locally processed commercial fish feeds and ingredients along value chains is a Public and Animal health hazard. The study established the level of aflatoxin contamination, per...Aflatoxin contamination and rancidity in locally processed commercial fish feeds and ingredients along value chains is a Public and Animal health hazard. The study established the level of aflatoxin contamination, peroxide value (PV), Anisidine value (AnV), and their associated factors at storage areas among farmers, processors, traders, factories, and landing sites in the Wakiso and Kampala districts. The value chain actors were purposively selected in a cross-sectional study based on access to the feed store and the use of locally processed commercial fish feeds on farms. Data collected were statistically analyzed in SPSS version 20. All the samples (45) were positive for aflatoxin contamination and PV with 51% (23/45) of samples being contaminated with “above acceptable” aflatoxin levels and 66.6% (30/45) of samples with “above acceptable” PV. The overall percentage of “above acceptable” AnV was 11/29 (37.9%). Samples from factories were within acceptable contamination levels. Multivariate logistic regression analysis revealed no significant difference between aflatoxin contamination, peroxide, and Anisidine value with storage factors for locally processed commercial fish feeds and ingredients. The study recommended the purchase of fish feeds from factories and a larger study on storage factors responsible for aflatoxin contamination and rancidity in fish feeds in Uganda.展开更多
Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease...Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.展开更多
The demand for safe vaccines that ensure long-term and broad protection against multiple viral variants has dramatically increased after the emergence of catastrophic infectious diseases such as COVID-19.To ensure lon...The demand for safe vaccines that ensure long-term and broad protection against multiple viral variants has dramatically increased after the emergence of catastrophic infectious diseases such as COVID-19.To ensure long-term and broad protection against heterologous virus variants,antigen-specific polyfunctional T cells should be orchestrated with the activation of follicular helper T(TFH)cells and germinal center(GC)B cells.Herein,we suggest a novel engineered nanoadjuvant(SE(Trojan-TLR7/8a))that enhances the migration of nonexhausted antigen-presenting cells(APCs)into lymph nodes and elicits the activation of TFH cells,the generation of GC B cells,and polyfunctional T cells via multiscale dynamic immunomodulation through squalene nanoemulsion(SE)-mediated macroscopic control of vaccine delivery and Trojan-TLR7/8a-enabled dynamic and sustained activation of APCs at the cellular level.SE(Trojan-TLR7/8a)can be lyophilized,reduce systemic toxicity,and outperform current commercial vaccine adjuvants(Alum or AS03)and mRNA vaccines.SE(Trojan-TLR7/8a)ensures cross-protection against diverse influenza and SARS-CoV-2 variants,providing 100%protection while maintaining a healthy state.SE(Trojan-TLR7/8a)also sustains a potent T-cell response in an aged ferret model of SFTSV infection.SE(Trojan-TLR7/8a)suggested herein provides a novel vaccine design principle for dynamic modulation at the multiscale level and demonstrates long-term and broad protective immunity against emerging pandemic and endemic infectious viruses.展开更多
Monkeypox,a zoonotic disease caused by the monkeypox virus(MPXV),has significant global public health implications.Inflammasomes serve as crucial components of the innate immune system,detecting pathogens and triggeri...Monkeypox,a zoonotic disease caused by the monkeypox virus(MPXV),has significant global public health implications.Inflammasomes serve as crucial components of the innate immune system,detecting pathogens and triggering cell death in infected cells to eliminate harmful agents.However,the precise molecular mechanisms governing the activation of inflammasomes during MPXV infection remain largely unclear.Using CRISPR-knockout cytosolic innate immune sensor screening,we identified AIM2 as the sensor for MPXV within the inflammasome,a trigger for inflammatory cell death.Mechanistically,AIM2 forms a complex with essential cell death molecules,including ASC and caspase-1(CASP1),without interacting with RIPK3 or CASP8.Loss of ASC,CASP1,or gasdermin D(GSDMD)reduced cell death following MPXV infection,whereas loss of GSDME,CASP3,CASP6,CASP7,CASP9,RIPK3,or MLKL did not.Pyroptotic cell death was predominantly observed in infected cells,whereas apoptotic and necroptotic signaling pathways were primarily activated in uninfected bystander cells.Furthermore,we found that the transcription factor IRF1 serves as an upstream regulator of AIM2,controlling AIM2-dependent cell death.In experiments involving AIM2-deficient mice infected with MPXV,we observed a decrease in proinflammatory cytokines,multiple inflammatory cell death pathways,and leukocyte migration,culminating in increased viral spread.CAST/EiJ mice succumbed to high-dose MPXV infection within 8 days,whereas AIM2 inhibition increased survival,with 10%of the mice treated with an AIM2 inhibitor surviving the infection.In a low-dose infection model,AIM2 inhibition reduced IL-1βand IL-18 production,LDH release,and tissue pathology.These findings highlight the critical role of AIM2-mediated inflammasome activation,along with multiple programmed cell death pathways,in shaping the innate immune response to MPXV infection,offering valuable insights for developing therapeutic strategies targeting AIM2 and the broader innate immune response against monkeypox.展开更多
In November 2021,the Omicron variant(B.1.1.529)emerged and was designated a variant of concern(VOC)by the World Health Organization.Recently,Omicron was reported to extensively escape neutralizing antibodies elicited ...In November 2021,the Omicron variant(B.1.1.529)emerged and was designated a variant of concern(VOC)by the World Health Organization.Recently,Omicron was reported to extensively escape neutralizing antibodies elicited by COVID-19 vaccination or natural infection[1,2,3].However,whether Omicron evades the T cell immunity elicited by COVID-19 vaccination or natural infection remains to be elucidated.To address this issue,we analyzed the amino acid sequences of T cell epitopes identified from the original SARS-CoV-2 strain(Wuhan-Hu-1)in the Omicron variant(hCoV-19/South Africa/CERI-KRISP-K032284/2021).展开更多
Phagocytic ingestion of foreign substrates plays an important role in host protective immunity. In vitro, the foreign substrates phagocytosed such as erythrocytes,polystyrene latex beads, and microbes can be observed ...Phagocytic ingestion of foreign substrates plays an important role in host protective immunity. In vitro, the foreign substrates phagocytosed such as erythrocytes,polystyrene latex beads, and microbes can be observed by light microscopy. Therefore, the function of phagocytes has been investigated by means of phagocytosis. How-展开更多
Background:Rabies is a neglected disease despite being responsible for more human deaths than any other zoonosis.A lack of adequate human and dog surveillance,resulting in low prioritization,is often blamed for this p...Background:Rabies is a neglected disease despite being responsible for more human deaths than any other zoonosis.A lack of adequate human and dog surveillance,resulting in low prioritization,is often blamed for this paradox.Estimation methods are often employed to describe the rabies burden when surveillance data are not available,however these figures are rarely based on country-specific data.Methods:In 2013 a knowledge,attitudes,and practices survey was conducted in Uganda to understand dog population,rabies vaccination,and human rabies risk factors and improve in-country and regional rabies burden estimates.Poisson and multi-level logistic regression techniques were conducted to estimate the total dog population and vaccination coverage.Results:Twenty-four villages were selected,of which 798 households completed the survey,representing 4375 people.Dog owning households represented 12.9%of the population,for which 175 dogs were owned(25 people per dog).A history of vaccination was reported in 55.6%of owned dogs.Poverty and human population density highly correlated with dog ownership,and when accounted for in multi-level regression models,the human to dog ratio fell to 47:1 and the estimated national canine-rabies vaccination coverage fell to 36.1%.This study estimates there are 729486 owned dogs in Uganda(95%CI:719919-739053).Ten percent of survey respondents provided care to dogs they did not own,however unowned dog populations were not enumerated in this estimate.89.8%of Uganda’s human population was estimated to reside in a community that can support enzootic canine rabies transmission.Conclusions:This study is the first to comprehensively evaluate the effect of poverty on dog ownership in Africa.These results indicate that describing a dog population may not be as simple as applying a human:dog ratio,and factors such as poverty are likely to heavily influence dog ownership and vaccination coverage.These modelled estimates should be confirmed through further field studies,however,if validated,canine rabies elimination through mass vaccination may not be as difficult as previously considered in Uganda.Data derived from this study should be considered to improve models for estimating the in-country and regional rabies burden.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is more likely to progress to severe disease in the elderly,and the rates of hospitalization for coronavirus disease 2019(COVID-19)incre...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is more likely to progress to severe disease in the elderly,and the rates of hospitalization for coronavirus disease 2019(COVID-19)increase with age.1,2 Herein,we comprehensively compared adaptive and innate immune responses between children and adults infected with SARS-CoV-2.展开更多
Background:New insecticides with a novel mode of action such as neonicotinoids have recently been recommended for public health by WHO.Resistance monitoring of such novel insecticides requires a robust protocol to mon...Background:New insecticides with a novel mode of action such as neonicotinoids have recently been recommended for public health by WHO.Resistance monitoring of such novel insecticides requires a robust protocol to monitor the development of resistance in natural populations.In this study,we comparatively used three different solvents to assess the susceptibility of malaria vectors to neonicotinoids across Africa.Methods:Mosquitoes were collected from May to July 2021 from three agricultural settings in Cameroon(Njombe-Penja,Nkolondom,and Mangoum),the Democratic Republic of Congo(Ndjili-Brasserie),Ghana(Obuasi),and Uganda(Mayuge).Using the CDC bottle test,we compared the effect of three different solvents(ethanol,acetone,MERO)on the efficacy of neonicotinoids againstAnopheles gambiae s.l.In addition,TaqMan assays were used to genotype key pyrethroid-resistant markers inAn.gambiae and odds ratio based on Fisher exact test were used to evaluate potential cross-resistance between pyrethroids and clothianidin.Results:Lower mortality was observed when using absolute ethanol or acetone alone as solvent for clothianidin(11.4-51.9% mortality in Nkolondom,31.7-48.2% in Mangoum,34.6-56.1% in Mayuge,39.4-45.6% in Obuasi,83.7-89.3% in Congo and 71.1-95.9% in Njombe pendja)compared to acetone+MERO for which 100% mortality were observed for all the populations.Similar observations were done for imidacloprid and acetamiprid.Synergist assays(PBO,DEM and DEF)with clothianidin revealed a significant increase of mortality suggesting that metabolic resistance mechanisms are contributing to the reduced susceptibility.A negative association was observed between the L1014F-kdr mutation and clothianidin resistance with a greater frequency of homozygote resistant mosquitoes among the dead than among survivors(OR=0.5;P=0.02).However,the I114T-GSTe2 was in contrast significantly associated with a greater ability to survive clothianidin with a higher frequency of homozygote resistant among survivors than other genotypes(OR=2.10;P=0.013).Conclusions:This study revealed a contrasted susceptibility pattern depending on the solvents with ethanol/acetone resulting to lower mortality,thus possibly overestimating resistance,whereas the MERO consistently showed a greater efficacy of neonicotinoids but it could prevent to detect early resistance development.Therefore,we recommend monitoring the susceptibility using both acetone alone and acetone+MERO(4μg/ml for clothianidin)to capture the accurate resistance profile of the mosquito populations.展开更多
Background:Pathogenic water dwelling protozoa such as Acanthamoeba spp.,Hartmannella spp.,Naegleria spp.,Cryptosporidium spp.and Giardia spp.are often responsible for devastating illnesses especially in children and i...Background:Pathogenic water dwelling protozoa such as Acanthamoeba spp.,Hartmannella spp.,Naegleria spp.,Cryptosporidium spp.and Giardia spp.are often responsible for devastating illnesses especially in children and immunocompromised individuals,yet their presence and prevalence in certain environment in sub-Saharan Africa is still unknown to most researchers,public health officials and medical practitioners.The objective of this study was to establish the presence and prevalence of pathogenic free-living amoeba(FLA),Cryptosporidium and Giardia in Queen Elizabeth Protected Area(QEPA).Methods:Samples were collected from communal taps and natural water sites in QEPA.Physical water parameters were measured in situ.The samples were processed to detect the presence of FLA trophozoites by xenic cultivation,Cryptosporidium oocysts by Ziehl-Neelsen stain and Giardia cysts by Zinc Sulphate floatation technique.Parasites were observed microscopically,identified,counted and recorded.For FLA,genomic DNA was extracted for amplification and sequencing.Results:Both natural and tap water sources were contaminated with FLA,Cryptosporidium spp.and Giardia spp.All protozoan parasites were more abundant in the colder rainy season except for Harmannella spp.and Naegleria spp.which occurred more in the warmer months.The prevalence of all parasites was higher in tap water than in natural water samples.There was a strong negative correlation between the presence of Acanthamoeba spp.,Hartmannella spp.,Cryptosporidium spp.and Giardia spp.with Dissolved Oxygen(DO)(P<0.05).The presence of Cryptosporidium spp.showed a significant positive correlation(P<0.05)with conductivity,pH and Total Dissolved Solids(TDS);whereas the presence of Giardia spp.had only a strong positive correlation with TDS.Molecular genotyping of FLA produced 7 Acanthamoeba,5 Echinamoeba,2 Hartmannella,1 Bodomorpha,1 Nuclearia and 1 Cercomonas partial sequences.Conclusions:All water collection sites were found to be contaminated with pathogenic protozoa that could possibly be the cause of a number of silent morbidities and mortalities among rural households in QEPA.This implies that water used by communities in QEPA is of poor quality and predisposes them to a variety of protozoan infections including the FLA whose public health importance was never reported,thus necessitating adoption of proper water safety measures.展开更多
基金funded by grants from the National Research Foundation of Korea(NRF)grant funded by the Korea government(2018M3A9H4055203 and 2023R1A2C2003679)from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HV23C1857)from KRIBB Research Initiative Program(KGM9942421).
文摘Influenza,a highly contagious respiratory infectious disease caused by an influenza virus,is a threat to public health worldwide.Avian influenza viruses(AIVs)have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome.Here,we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models.In addition,we assessed the pathogenicity of AIVs in ferret models.Moreover,we compared the ability of viruses to replicate in mammalian cells,as well as the receptor-binding preferences of AIV isolates.Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation.Of the 24 AIV isolates tested,A/Mallard/South Korea/KNU2019-34/2019(KNU19-34;H1N1)caused severe bodyweight loss and high mortality in mice.The virus replicated in the lungs,kidneys,and heart.Importantly,KNU19-34-infected ferrets showed high viral loads in both nasal washes and lungs.KNU19-34 replicated rapidly in A549 and bound preferentially to human likeα2,6-linked sialic acids rather than to avian-likeα2,3-linked sialic acids,similar to the pandemic A/California/04/2009(H1N1)strain.Gene segments of KNU19-34 were distributed in Egypt and Asia lineages from 2015 to 2018,and the virus had several amino acid substitutions compared to H1N1 AIV isolates that were non-pathogenic in mice.Collectively,the data suggest that KNU19-34 has zoonotic potential and the possibility of new mutations responsible for mammalian adaptation.
文摘There are some Indications thtt herpes aimplex virus (HSV) may be mutagenic. Specific chromosomal changes have also been demonstrated In cultured cells infected with HSV. To further Investigate the mutagenic activity of HSV type 2 (HSV-2) we used mouse skin as a model system for cardnogenetls. Inoculation of the back skin of 4-week-old Sencar mke with live virus twice per week for one week or with Inactivated virus twice per week for two weeks was used to Initiate the mouse akin. After Initiation with HSV-2, 12-O-tetradecanoylphorbol-13-acetale(TPA) was applied twice weekly for 50 weeks as a promoter. During a period of 52 weeks, no skin carcinoma was found In the experimental groups, whereas 55% of control mice treated with 9, 10-dlmethy1-1, 2- benzanthracene (DMBA ) and then with TPA-developed skin carcinoma. The results demonstrate that HSV-2 could not substitute for DMBA in this animal model of two-stage skin carcinogenesis.
文摘The isolation of influenza viruses in Madin Darby Canine Kidney (MDCK) cells has shown preferential isolation of a great percentage of Influenza B strains at the first passage than Influenza A strains. During in vitro isolation of Influenza viruses, majority of type A viruses are not confirmed as positive isolates by Hemagglutination (HA) assay despite having higher virulence and pathogenicity versus influenza B viruses. This study investigated the differences in IFN-γ and IL-10 cytokines secreted by MDCK cells upon exposure to the viruses and thus provided possible answers as to why influenza type B can easily be isolated from MDCK cells compared to influenza A. Positive influenza viruses were inoculated onto MDCK cells. IFN-γ and IL-10 cytokines stimulated by the viruses in MDCK cells were measured by indirect ELISA at 1 hour, 12 hours, 48 hours and 72 hours post inoculation (pi). A total of 46 specimens, with 23 specimens from each virus type were analyzed. IFN-γ was significantly higher at 1 hour pi in MDCK cells for influenza type A at p value of 0.024 than type B. No statistical significance was observed in means of cytokine IL-10 between influenza type A and type B. The study may show that IFN-γ is correlated to the preferential isolation of influenza type B over type A viruses. Anti-inflammatory cytokines may not necessarily be playing a role in the preferential growth of influenza type B, a less virulent type over influenza type A in MDCK cells.
文摘Sludge contains organic and inorganic compounds including traces of heavy metals such as lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), chromium (Cr) and others. These metals restrict the use of sludge in agriculture because their accumulation is harmful to the environment and particularly the food chain. Cadmium and lead are among the most common heavy metals found in municipal wastewater treatment plant sludge. They are capable of bioaccumulation in plant tissues like roots and leaves and are non-biodegradable and therefore they remain in the sludge which is disposed on land or used as fertilizers on farms. The presence of heavy metal pollutants serves as a great threat to soils and also makes plants grown on such soils unfit for animal and human consumption as they may have detrimental effects to animal and human life. For instance, Pb and Cd are known to be human carcinogens. This study therefore aimed to investigate the levels of Cd and Pb in the treated dry sludge from Lubigi Feacal Sludge and Wastewater treatment plant located in Kawempe division, Kampala city, Uganda so as to ascertain its safety for use on agricultural lands. Two batches of samples were collected and analyzed at Government Analytical laboratory in Wandegeya, Uganda. The acid digested sludge samples were analyzed using Atomic Absorption Spectroscopy (AAS) method. The average concentrations of Pb found in collected sludge samples, batch 1 (11.912 mg/kg dm) and batch 2 (5.304 mg/kg dm) were far below the Environment Protection Agency (EPA) maximum permissible concentration (840 mg/kg) for any land application. Cadmium was not detected in all the sludge samples collected;there is an implication that it is either completely absent in the sludge generated by the plant or present but far below detectable levels. The sludge generated from Lubigi fecal sludge and wastewater treatment plant is therefore safe for application on agricultural lands as far as Pb and Cd concentrations are concerned.
文摘Aflatoxin contamination and rancidity in locally processed commercial fish feeds and ingredients along value chains is a Public and Animal health hazard. The study established the level of aflatoxin contamination, peroxide value (PV), Anisidine value (AnV), and their associated factors at storage areas among farmers, processors, traders, factories, and landing sites in the Wakiso and Kampala districts. The value chain actors were purposively selected in a cross-sectional study based on access to the feed store and the use of locally processed commercial fish feeds on farms. Data collected were statistically analyzed in SPSS version 20. All the samples (45) were positive for aflatoxin contamination and PV with 51% (23/45) of samples being contaminated with “above acceptable” aflatoxin levels and 66.6% (30/45) of samples with “above acceptable” PV. The overall percentage of “above acceptable” AnV was 11/29 (37.9%). Samples from factories were within acceptable contamination levels. Multivariate logistic regression analysis revealed no significant difference between aflatoxin contamination, peroxide, and Anisidine value with storage factors for locally processed commercial fish feeds and ingredients. The study recommended the purchase of fish feeds from factories and a larger study on storage factors responsible for aflatoxin contamination and rancidity in fish feeds in Uganda.
文摘Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.
基金supported by National Research Foundation(NRF)grants funded by the Korean government(grant numbers RS-2025-00513566 and RS-2023-00218648),Republic of Korea(Prof.Yong Taik Lim)supported by NRF grants funded by Korean government(grant number 2021R1A6A1A03045495),Republic of Korea(Prof.Jong-Soo Lee)supported by the Institute for Basic Science(grant number IBS-R801-D1),Republic of Korea(Director Young Ki Choi).
文摘The demand for safe vaccines that ensure long-term and broad protection against multiple viral variants has dramatically increased after the emergence of catastrophic infectious diseases such as COVID-19.To ensure long-term and broad protection against heterologous virus variants,antigen-specific polyfunctional T cells should be orchestrated with the activation of follicular helper T(TFH)cells and germinal center(GC)B cells.Herein,we suggest a novel engineered nanoadjuvant(SE(Trojan-TLR7/8a))that enhances the migration of nonexhausted antigen-presenting cells(APCs)into lymph nodes and elicits the activation of TFH cells,the generation of GC B cells,and polyfunctional T cells via multiscale dynamic immunomodulation through squalene nanoemulsion(SE)-mediated macroscopic control of vaccine delivery and Trojan-TLR7/8a-enabled dynamic and sustained activation of APCs at the cellular level.SE(Trojan-TLR7/8a)can be lyophilized,reduce systemic toxicity,and outperform current commercial vaccine adjuvants(Alum or AS03)and mRNA vaccines.SE(Trojan-TLR7/8a)ensures cross-protection against diverse influenza and SARS-CoV-2 variants,providing 100%protection while maintaining a healthy state.SE(Trojan-TLR7/8a)also sustains a potent T-cell response in an aged ferret model of SFTSV infection.SE(Trojan-TLR7/8a)suggested herein provides a novel vaccine design principle for dynamic modulation at the multiscale level and demonstrates long-term and broad protective immunity against emerging pandemic and endemic infectious viruses.
文摘Monkeypox,a zoonotic disease caused by the monkeypox virus(MPXV),has significant global public health implications.Inflammasomes serve as crucial components of the innate immune system,detecting pathogens and triggering cell death in infected cells to eliminate harmful agents.However,the precise molecular mechanisms governing the activation of inflammasomes during MPXV infection remain largely unclear.Using CRISPR-knockout cytosolic innate immune sensor screening,we identified AIM2 as the sensor for MPXV within the inflammasome,a trigger for inflammatory cell death.Mechanistically,AIM2 forms a complex with essential cell death molecules,including ASC and caspase-1(CASP1),without interacting with RIPK3 or CASP8.Loss of ASC,CASP1,or gasdermin D(GSDMD)reduced cell death following MPXV infection,whereas loss of GSDME,CASP3,CASP6,CASP7,CASP9,RIPK3,or MLKL did not.Pyroptotic cell death was predominantly observed in infected cells,whereas apoptotic and necroptotic signaling pathways were primarily activated in uninfected bystander cells.Furthermore,we found that the transcription factor IRF1 serves as an upstream regulator of AIM2,controlling AIM2-dependent cell death.In experiments involving AIM2-deficient mice infected with MPXV,we observed a decrease in proinflammatory cytokines,multiple inflammatory cell death pathways,and leukocyte migration,culminating in increased viral spread.CAST/EiJ mice succumbed to high-dose MPXV infection within 8 days,whereas AIM2 inhibition increased survival,with 10%of the mice treated with an AIM2 inhibitor surviving the infection.In a low-dose infection model,AIM2 inhibition reduced IL-1βand IL-18 production,LDH release,and tissue pathology.These findings highlight the critical role of AIM2-mediated inflammasome activation,along with multiple programmed cell death pathways,in shaping the innate immune response to MPXV infection,offering valuable insights for developing therapeutic strategies targeting AIM2 and the broader innate immune response against monkeypox.
基金This study was supported by the National Research Foundation Grant NRF-2018M3A9D3079498the Institute for Basic Science(IBS),Korea,under project code IBS-R801-D2.
文摘In November 2021,the Omicron variant(B.1.1.529)emerged and was designated a variant of concern(VOC)by the World Health Organization.Recently,Omicron was reported to extensively escape neutralizing antibodies elicited by COVID-19 vaccination or natural infection[1,2,3].However,whether Omicron evades the T cell immunity elicited by COVID-19 vaccination or natural infection remains to be elucidated.To address this issue,we analyzed the amino acid sequences of T cell epitopes identified from the original SARS-CoV-2 strain(Wuhan-Hu-1)in the Omicron variant(hCoV-19/South Africa/CERI-KRISP-K032284/2021).
文摘Phagocytic ingestion of foreign substrates plays an important role in host protective immunity. In vitro, the foreign substrates phagocytosed such as erythrocytes,polystyrene latex beads, and microbes can be observed by light microscopy. Therefore, the function of phagocytes has been investigated by means of phagocytosis. How-
基金This study was conducting with USAID funding.The funding agency had no role in study design,analysis,or interpretation of the data.
文摘Background:Rabies is a neglected disease despite being responsible for more human deaths than any other zoonosis.A lack of adequate human and dog surveillance,resulting in low prioritization,is often blamed for this paradox.Estimation methods are often employed to describe the rabies burden when surveillance data are not available,however these figures are rarely based on country-specific data.Methods:In 2013 a knowledge,attitudes,and practices survey was conducted in Uganda to understand dog population,rabies vaccination,and human rabies risk factors and improve in-country and regional rabies burden estimates.Poisson and multi-level logistic regression techniques were conducted to estimate the total dog population and vaccination coverage.Results:Twenty-four villages were selected,of which 798 households completed the survey,representing 4375 people.Dog owning households represented 12.9%of the population,for which 175 dogs were owned(25 people per dog).A history of vaccination was reported in 55.6%of owned dogs.Poverty and human population density highly correlated with dog ownership,and when accounted for in multi-level regression models,the human to dog ratio fell to 47:1 and the estimated national canine-rabies vaccination coverage fell to 36.1%.This study estimates there are 729486 owned dogs in Uganda(95%CI:719919-739053).Ten percent of survey respondents provided care to dogs they did not own,however unowned dog populations were not enumerated in this estimate.89.8%of Uganda’s human population was estimated to reside in a community that can support enzootic canine rabies transmission.Conclusions:This study is the first to comprehensively evaluate the effect of poverty on dog ownership in Africa.These results indicate that describing a dog population may not be as simple as applying a human:dog ratio,and factors such as poverty are likely to heavily influence dog ownership and vaccination coverage.These modelled estimates should be confirmed through further field studies,however,if validated,canine rabies elimination through mass vaccination may not be as difficult as previously considered in Uganda.Data derived from this study should be considered to improve models for estimating the in-country and regional rabies burden.
基金This work was supported by the Institute for Basic Science(IBS),Republic of Korea,under project code IBS-R801-D2(E.-C.S.)and Korea Disease Control and Prevention Agency(KDCA),Republic of Korea,under grant number 2020ER533100(J.-P.C.).
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection is more likely to progress to severe disease in the elderly,and the rates of hospitalization for coronavirus disease 2019(COVID-19)increase with age.1,2 Herein,we comprehensively compared adaptive and innate immune responses between children and adults infected with SARS-CoV-2.
文摘Background:New insecticides with a novel mode of action such as neonicotinoids have recently been recommended for public health by WHO.Resistance monitoring of such novel insecticides requires a robust protocol to monitor the development of resistance in natural populations.In this study,we comparatively used three different solvents to assess the susceptibility of malaria vectors to neonicotinoids across Africa.Methods:Mosquitoes were collected from May to July 2021 from three agricultural settings in Cameroon(Njombe-Penja,Nkolondom,and Mangoum),the Democratic Republic of Congo(Ndjili-Brasserie),Ghana(Obuasi),and Uganda(Mayuge).Using the CDC bottle test,we compared the effect of three different solvents(ethanol,acetone,MERO)on the efficacy of neonicotinoids againstAnopheles gambiae s.l.In addition,TaqMan assays were used to genotype key pyrethroid-resistant markers inAn.gambiae and odds ratio based on Fisher exact test were used to evaluate potential cross-resistance between pyrethroids and clothianidin.Results:Lower mortality was observed when using absolute ethanol or acetone alone as solvent for clothianidin(11.4-51.9% mortality in Nkolondom,31.7-48.2% in Mangoum,34.6-56.1% in Mayuge,39.4-45.6% in Obuasi,83.7-89.3% in Congo and 71.1-95.9% in Njombe pendja)compared to acetone+MERO for which 100% mortality were observed for all the populations.Similar observations were done for imidacloprid and acetamiprid.Synergist assays(PBO,DEM and DEF)with clothianidin revealed a significant increase of mortality suggesting that metabolic resistance mechanisms are contributing to the reduced susceptibility.A negative association was observed between the L1014F-kdr mutation and clothianidin resistance with a greater frequency of homozygote resistant mosquitoes among the dead than among survivors(OR=0.5;P=0.02).However,the I114T-GSTe2 was in contrast significantly associated with a greater ability to survive clothianidin with a higher frequency of homozygote resistant among survivors than other genotypes(OR=2.10;P=0.013).Conclusions:This study revealed a contrasted susceptibility pattern depending on the solvents with ethanol/acetone resulting to lower mortality,thus possibly overestimating resistance,whereas the MERO consistently showed a greater efficacy of neonicotinoids but it could prevent to detect early resistance development.Therefore,we recommend monitoring the susceptibility using both acetone alone and acetone+MERO(4μg/ml for clothianidin)to capture the accurate resistance profile of the mosquito populations.
基金The researchers would like to thank WaterNet,SIG-RISE and CARNEGIE-Next Generation of African Academics(NGAA-Carnegie),for supporting and funding this research,and Molecular Biology Laboratory,Makerere University for the equipment used in the diagnostics.
文摘Background:Pathogenic water dwelling protozoa such as Acanthamoeba spp.,Hartmannella spp.,Naegleria spp.,Cryptosporidium spp.and Giardia spp.are often responsible for devastating illnesses especially in children and immunocompromised individuals,yet their presence and prevalence in certain environment in sub-Saharan Africa is still unknown to most researchers,public health officials and medical practitioners.The objective of this study was to establish the presence and prevalence of pathogenic free-living amoeba(FLA),Cryptosporidium and Giardia in Queen Elizabeth Protected Area(QEPA).Methods:Samples were collected from communal taps and natural water sites in QEPA.Physical water parameters were measured in situ.The samples were processed to detect the presence of FLA trophozoites by xenic cultivation,Cryptosporidium oocysts by Ziehl-Neelsen stain and Giardia cysts by Zinc Sulphate floatation technique.Parasites were observed microscopically,identified,counted and recorded.For FLA,genomic DNA was extracted for amplification and sequencing.Results:Both natural and tap water sources were contaminated with FLA,Cryptosporidium spp.and Giardia spp.All protozoan parasites were more abundant in the colder rainy season except for Harmannella spp.and Naegleria spp.which occurred more in the warmer months.The prevalence of all parasites was higher in tap water than in natural water samples.There was a strong negative correlation between the presence of Acanthamoeba spp.,Hartmannella spp.,Cryptosporidium spp.and Giardia spp.with Dissolved Oxygen(DO)(P<0.05).The presence of Cryptosporidium spp.showed a significant positive correlation(P<0.05)with conductivity,pH and Total Dissolved Solids(TDS);whereas the presence of Giardia spp.had only a strong positive correlation with TDS.Molecular genotyping of FLA produced 7 Acanthamoeba,5 Echinamoeba,2 Hartmannella,1 Bodomorpha,1 Nuclearia and 1 Cercomonas partial sequences.Conclusions:All water collection sites were found to be contaminated with pathogenic protozoa that could possibly be the cause of a number of silent morbidities and mortalities among rural households in QEPA.This implies that water used by communities in QEPA is of poor quality and predisposes them to a variety of protozoan infections including the FLA whose public health importance was never reported,thus necessitating adoption of proper water safety measures.
