Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 88 Records) |
Query Trace: Ju J [original query] |
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Molecular characterizations of Cryptosporidium, Giardia, and Enterocytozoon in humans in Kaduna State, Nigeria.
Maikai BV , Umoh JU , Lawal IA , Kudi AC , Ejembi CL , Xiao L . Exp Parasitol 2012 131 (4) 452-6 The use of molecular diagnostic tools in epidemiological investigations of Cryptosporidium, Giardia, and Enterocytozoon has provided new insights into their diversity and transmission pathways. In this study, 157 stool specimens from 2-month to 70-year-old patients were collected, a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis of the small subunit (SSU) rRNA gene was used to detect and differentiate Cryptosporidium species, and DNA sequence analysis of the 60 kDa glycoprotein (gp60) gene was used to subtype Cryptosporidium hominis and Cryptosporidium parvum. Giardia duodenalis, and Enterocytozoon bieneusi in the specimens were detected using PCR and sequence analysis of the triosephosphate isomerase (tpi) gene and internal transcribed spacer (ITS), respectively. C. hominis and C. parvum were found in two (1.3%) and one (0.6%) specimen respectively, comprising of Ia and IIe (with 8 nucleotide substitutions) subtype families. The G. duodenalis A2 subtype was detected in five (3.2%) specimens, while four genotypes of E. bieneusi, namely A, type IV, D and WL7 were found in 10 (6.4%) specimens. Children aged two years or younger had the highest occurrence of Cryptosporidium (4.4%) and Enterocytozoon (13.0%) while children of 6 to 17 years had the highest Giardia infection rate (40.0%). No Cryptosporidium, Giardia, and Enterocytozoon were detected in patients older than 60 years. Enterocytozoon had high infection rates in both HIV-positive (3.3%) and HIV-negative (8.3%) patients. Results of the study suggest that anthroponotic transmission may be important in the transmission of Cryptosporidium spp. and G. duodenalis while zoonotic transmissions may also play a role in the transmission of E. bieneusi in humans in Kaduna State, Nigeria. |
A novel cold-chain free VCG-based subunit vaccine protects against Chlamydia abortus-induced neonatal mortality in a pregnant mouse model
Richardson S , Bell CR , Medhavi F , Tanner T , Lundy S , Omosun Y , Igietseme JU , Eko FO . Front Immunol 2023 14 1243743 Chlamydia abortus (Cab) causes spontaneous abortion and neonatal mortality in infected ruminants and pregnant women. Most Cab infections are asymptomatic, although they can be treated with antibiotics, signifying that control of these infections may require alternative strategies, including the use of effective vaccines. However, the limitations imposed by live attenuated and inactivated vaccines further suggest that employment of subunit vaccines may need to be considered. The efficacy of a newly generated Vibrio cholerae ghost (rVCG)-based subunit vaccine harboring the N-terminal portion of the Cab Pmp18D protein (rVCG-Pmp18.3) in preventing Cab-induced abortion or neonatal mortality was evaluated in pregnant mice. Mice were intranasally (IN) immunized and boosted twice, 2 weeks apart with the vaccine, and immunized and unimmunized mice were caged with males 4 weeks postimmunization. The mice were then infected either IN or transcervically (TC) 10 days after pregnancy, and the fertility rate was determined 7 days postpartum. Eight days after delivery, the mice were sacrificed, and Cab infectivity in the lungs and spleens was evaluated by culturing tissue homogenates in tissue culture. Our results demonstrated that the vaccine induced immune effectors that mediated complete clearance of infection in the lungs and significantly reduced Cab infectivity in the spleen following IN immunization. Vaccine immunization also afforded protection against Cab-induced upper genital tract pathology (uterine dilation). Furthermore, while there was no incidence of abortion in both immunized and unimmunized mice, immunized mice were completely protected against neonatal mortality compared to unimmunized infected controls, which lost a significant percentage of their litter 7 days postpartum. Our results establish the capability of the rVCG-Pmp18.3 vaccine to prevent infection in the lungs (mucosal) and spleen (systemic) and protect mice from Cab-induced tubal pathologies and neonatal mortality, a hallmark of Cab infection in ruminants. To advance the commercial potential of this vaccine, future studies will optimize the antigen dose and the number of vaccine doses required for protection of ruminants. |
An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus (preprint)
Shen WF , Galula JU , Liu JH , Liao MY , Huang CH , Wang YC , Wu HC , Liang JJ , Lin YL , Whitney MT , Chang GJ , Chen SR , Wu SR , Chao DY . bioRxiv 2018 351700 Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein we show for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction. Mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher cross reactive (CR) neutralization antibodies (NtAbs) and were protected against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. Our results revealed that a “epitope-resurfaced” mature-form dengue VLP has the potential to induce quaternary structure-recognizing broad CR NtAbs. |
A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus (preprint)
Chao DY , Shen WF , Galula JU , Liu JH , Liao MY , Huang CH , Wang YC , Wu HC , Liang JJ , Lin YL , Whitney MT , Chang GJ , Chen SR , Wu SR . bioRxiv 2018 275685 Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. The vaccine candidates under development require a tetravalent immunogen to induce a balanced immunity against all four serotypes of dengue virus. Herein we show that mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher and broader neutralization antibodies (NtAbs) against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. The cryo-electron microscopy reconstruction showed that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Most importantly, maternally transferred antibodies derived from mD2VLP-vaccinated female mice protected suckling mice from lethal challenge by all four serotypes of DENV. Our results support the fact that a universal dengue vaccine that protects against all four serotypes of dengue viruses can be achieved by using an immunogen such as mD2VLP. |
Genital tract microbiome dynamics are associated with time of Chlamydia infection (preprint)
Zhao L , Lundy SR , Eko FO , Igietseme JU , Omosun YO . bioRxiv 2022 19 Background: We have previously shown that the time of Chlamydia infection was crucial in determining the chlamydial infectivity and pathogenesis. This study aims to determine whether the time of Chlamydia infection affects the genital tract microbiome. This study analyzed mice vaginal, uterine, and ovary/oviduct microbiome with and without Chlamydia infection. The mice were infected with Chlamydia at either 10:00 am (ZT3) or 10:00 pm (ZT15). Result(s): The results showed that mice infected at ZT3 had higher Chlamydia infectivity than those infected at ZT15. There was more variation in the compositional complexity of the vaginal microbiome (alpha diversity) of mice infected at ZT3 than those mice infected at ZT15 throughout the infection within each treatment group, with both Shannon and Simpson diversity index values decreased over time. The analysis of samples collected four weeks post-infection showed that there were significant taxonomical differences (beta diversity) between different parts of the genital tract-vagina, uterus, and ovary/oviduct-and this difference was associated with the time of infection. Firmicutes and Proteobacteria were the most abundant phyla within the microbiome in all three genital tract regions for all the samples collected during this experiment. Additionally, Firmicutes was the dominant phylum in the uterine microbiome of ZT3 Chlamydia infected mice. Conclusion(s): The results show that the time of infection is associated with the microbial dynamics in the genital tract. And this association is more robust in the upper genital tract than in the vagina. This result implies that more emphasis should be placed on understanding the changes in the microbial dynamics of the upper genital tract over the course of infection. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Respiratory syncytial virus (RSV) disease and prevention products: Knowledge, attitudes, and preferences of Kenyan healthcare workers in two counties in 2021
Nyawanda BO , Opere VA , Nyiro JU , Vodicka E , Fleming JA , Baral R , Khan S , Pecenka C , Ayugi JO , Atito R , Ougo J , Bigogo G , Emukule GO , Otieno NA , Munywoki PK . Vaccines (Basel) 2023 11 (6) Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) among infants under 6 months of age. Yet, in Kenya, little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions around RSV disease and the prevention products under development. Between September and October 2021, we conducted a mixed methods cross-sectional survey to assess HCWs' knowledge, attitudes, and perceptions of RSV disease and RSV vaccinations in two counties. We enrolled HCWs delivering services directly at maternal and child health (MCH) departments in selected health facilities (frontline HCWs) and health management officers (HMOs). Of the 106 respondents, 94 (88.7%) were frontline HCWs, while 12 were HMOs. Two of the HMOs were members of the Kenya National Immunization Technical Advisory Group (KENITAG). Of the 104 non-KENITAG HCWs, only 41 (39.4%) had heard about RSV disease, and 38/41 (92.7%) felt that pregnant women should be vaccinated against RSV. Most participants would recommend a single-dose vaccine schedule (n = 62, 58.5%) for maximal adherence and compliance (n = 38/62, 61.3%), single dose/device vaccines (n = 50/86, 58.1%) to prevent wastage and contamination, and maternal vaccination through antenatal care clinics (n = 53, 50%). We found the need for increased knowledge about RSV disease and prevention among Kenyan HCWs. |
Genital tract microbiome dynamics are associated with time of Chlamydia infection in mice
Zhao L , Lundy SR , Eko FO , Igietseme JU , Omosun YO . Sci Rep 2023 13 (1) 9006 We have previously shown that the time of Chlamydia infection was crucial in determining the chlamydial infectivity and pathogenesis. This study aims to determine whether the time of Chlamydia infection affects the genital tract microbiome. This study analyzed mice vaginal, uterine, and ovary/oviduct microbiome with and without Chlamydia infection. The mice were infected with Chlamydia at either 10:00 am (ZT3) or 10:00 pm (ZT15). The results showed that mice infected at ZT3 had higher Chlamydia infectivity than those infected at ZT15. There was more variation in the compositional complexity of the vaginal microbiome (alpha diversity) of mice infected at ZT3 than those mice infected at ZT15 throughout the infection within each treatment group, with both Shannon and Simpson diversity index values decreased over time. The analysis of samples collected four weeks post-infection showed that there were significant taxonomical differences (beta diversity) between different parts of the genital tract-vagina, uterus, and ovary/oviduct-and this difference was associated with the time of infection. Firmicutes and Proteobacteria were the most abundant phyla within the microbiome in all three genital tract regions for all the samples collected during this experiment. Additionally, Firmicutes was the dominant phylum in the uterine microbiome of ZT3 Chlamydia infected mice. The results show that the time of infection is associated with the microbial dynamics in the genital tract. And this association is more robust in the upper genital tract than in the vagina. This result implies that more emphasis should be placed on understanding the changes in the microbial dynamics of the upper genital tract over the course of infection. |
Estimates of the national burden of respiratory syncytial virus in Kenyan children aged under 5years, 2010-2018
Nyawanda BO , Murunga N , Otieno NA , Bigogo G , Nyiro JU , Vodicka E , Bulterys M , Nokes DJ , Munywoki PK , Emukule GO . BMC Med 2023 21 (1) 122 BACKGROUND: Respiratory syncytial virus (RSV) is among the leading childhood causes of viral pneumonia worldwide. Establishing RSV-associated morbidity and mortality is important in informing the development, delivery strategies, and evaluation of interventions. METHODS: Using data collected during 2010-2018 from base regions (population-based surveillance studies in western Kenya and the Kilifi Health and Demographic Surveillance Study), we estimated age-specific rates of acute respiratory illness (ARI), severe acute respiratory illness (SARI-defined as hospitalization with cough or difficulty breathing with onset within the past 10 days), and SARI-associated deaths. We extrapolated the rates from the base regions to other regions of Kenya, while adjusting for risk factors of ARI and healthcare seeking behavior, and finally applied the proportions of RSV-positive cases identified from various sentinel and study facilities to the rates to obtain regional age-specific rates of RSV-associated outpatient and non-medically attended ARI and hospitalized SARI and severe ARI that was not hospitalized (non-hospitalized SARI). We applied age-specific RSV case fatality ratios to SARI to obtain estimates of RSV-associated in- and out-of-hospital deaths. RESULTS: Among Kenyan children aged < 5 years, the estimated annual incidence of outpatient and non-medically attended RSV-associated ARI was 206 (95% credible interval, CI; 186-229) and 226 (95% CI; 204-252) per 1000 children, respectively. The estimated annual rates of hospitalized and non-hospitalized RSV-associated SARI were 349 (95% CI; 303-404) and 1077 (95% CI; 934-1247) per 100,000 children respectively. The estimated annual number of in- and out-of-hospital deaths associated with RSV infection in Kenya were 539 (95% CI; 420-779) and 1921 (95% CI; 1495-2774), respectively. Children aged < 6 months had the highest burden of RSV-associated severe disease: 2075 (95% CI; 1818-2394) and 44 (95% CI 25-71) cases per 100,000 children for hospitalized SARI and in-hospital deaths, respectively. CONCLUSIONS: Our findings suggest a substantial disease burden due to RSV infection, particularly among younger children. Prioritizing development and use of maternal vaccines and affordable long-lasting monoclonal antibodies could help reduce this burden. |
A multicenter survey of asymptomatic cryptococcal antigenemia among patients with advanced HIV disease in Nigeria
Oladele RO , Jordan AM , Okaa JU , Osaigbovo II , Shettima SA , Shehu NY , Davies AA , Mohammed Y , Alex-Wele MA , Iliyasu G , Nwaokenye JC , Fayemiwo SA , Udoh UA , Gbajabiamila T , Denning DW , Chiller TM . PLOS Glob Public Health 2023 3 (1) e0001313 As of 2018, cryptococcal antigen (CrAg) screening in patients with advanced human immunodeficiency virus (HIV) disease (AHD) was not routinely implemented in Nigeria despite being recommended in the national HIV treatment guidelines. Our aim was to determine the prevalence and risk factors for asymptomatic cryptococcal antigenemia in adult people living with HIV (PLHIV) in Nigeria to advocate for the implementation of routine CrAg screening. A descriptive cross-sectional study and CrAg screening of consecutive adult PLHIV with CD4 counts ≤200 cells/μL was conducted from April 2018 to April 2019 at HIV clinics in eleven tertiary hospitals spread across Nigeria's six geopolitical regions. Prevalence of asymptomatic cryptococcal antigenemia was estimated by facility and geopolitical zone. Logistic regression was conducted to identify risk factors for cryptococcal antigenemia. In total, 1,114 patients with AHD were screened. The overall prevalence of asymptomatic cryptococcal antigenemia was 3.9% with wide variation across facilities (range: 0/75 [0%]- 15/122 [12.3%]) and geopolitical zones (range: 0/75 [0%]-19/279 [6.8%]). Prevalence of antigenemia was highest in the South-West (19/279 [6.8%]) and lowest in the North-East (0/75 [0%]). Prevalence was 5.2% (26/512) and 3.2% (18/561) in patients with CD4<100 and CD4 of 101-200, respectively. Of all patients with antigenemia, 50% were on antiretroviral therapy (ART) at the time of having a positive CrAg test. In adjusted analysis, cryptococcal antigenemia was significantly less in patients on ART and patients who had completed any formal education. The survey showed a high overall burden of cryptococcal antigenemia in Nigeria, with variable prevalence across geopolitical regions. We provided valuable evidence for implementing routine CrAg screening of AHD patients in Nigeria which has commenced in selected centres. |
The COVID-19 pandemic in sub-Saharan Africa: The significance of presumed immune sufficiency
Idowu AO , Omosun YO , Igietseme JU , Azenabor AA . Afr J Lab Med 2023 12 (1) 1964 A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China in 2019 and later ignited a global pandemic. Contrary to expectations, the effect of the pandemic was not as devastating to Africa and its young population compared to the rest of the world. To provide insight into the possible reasons for the presumed immune sufficiency to coronavirus disease 2019 (COVID-19) in Africa, this review critically examines literature published from 2020 onwards on the dynamics of COVID-19 infection and immunity and how other prevalent infectious diseases in Africa might have influenced the outcome of COVID-19. Studies characterising the immune response in patients with COVID-19 show that the correlates of protection in infected individuals are T-cell responses against the SARS-CoV-2 spike protein and neutralising titres of immunoglobin G and immunoglobin A antibodies. In some other studies, substantial pre-existing T-cell reactivity to SARS-CoV-2 was detected in many people from diverse geographical locations without a history of exposure. Certain studies also suggest that innate immune memory, which offers protection against reinfection with the same or another pathogen, might influence the severity of COVID-19. In addition, an initial analysis of epidemiological data showed that COVID‑19 cases were not severe in some countries that implemented universal Bacillus Calmette-Guerin (BCG) vaccination policies, thus supporting the potential of BCG vaccination to boost innate immunity. The high burden of infectious diseases and the extensive vaccination campaigns previously conducted in Africa could have induced specific and non-specific protective immunity to infectious pathogens in Africans. |
Food sensitivities in a diverse nationwide cohort of veterans with interstitial cystitis/bladder pain syndrome
Jarman A , Janes JL , Shorter B , Moldwin R , De Hoedt AM , Barbour KE , Kim J , Freedland SJ , Anger JT . J Urol 2022 209 (1) 101097ju0000000000002938 PURPOSE: Prior studies suggest that certain foods exacerbate interstitial cystitis/bladder pain syndrome symptoms. However, these studies were limited in size and demographics. We assessed the presence of diet sensitivities among patients with interstitial cystitis/bladder pain syndrome and compared them with patients with other pelvic pain conditions and healthy controls. MATERIALS AND METHODS: We identified Veterans Affairs patients nationwide by querying ICD-9/10 codes for interstitial cystitis/bladder pain syndrome. Patients were assigned to interstitial cystitis, other pelvic pain, or healthy control cohorts after chart review. We mailed all patients the Shorter-Moldwin Food Sensitivity Questionnaire to evaluate the self-perceived effects of specific foods/beverages on urinary symptoms and/or bladder pain. RESULTS: In the interstitial cystitis/bladder pain syndrome cohort, 70% had >/=1 food sensitivity vs 37% of the other pelvic pain cohort and 32% of healthy controls (P < .001). The average number of sensitivities were similar between other pelvic pain conditions and healthy control cohorts, which were significantly less than in interstitial cystitis/bladder pain syndrome patients. Interstitial cystitis/bladder pain syndrome patients were more sensitive to acidic, spicy foods, and certain beverages vs other cohorts (all P < .001). Within the interstitial cystitis/bladder pain syndrome cohort, Black patients had significantly higher sensitivity to alcoholic and noncaffeinated beverages than Whites. Black patients did report significantly worsened urinary urgency than Whites (P < .05). CONCLUSIONS: In a diverse population of veterans, interstitial cystitis/bladder pain syndrome patients had significantly more food sensitivities than those without interstitial cystitis/bladder pain syndrome. This suggests that food sensitivities could be suggestive of interstitial cystitis/bladder pain syndrome, which could make the Shorter-Moldwin Food Sensitivity Questionnaire a helpful diagnostic tool and aid in distinguishing interstitial cystitis/bladder pain syndrome from conditions often confused with interstitial cystitis/bladder pain syndrome. |
Toxigenic corynebacterium diphtheriae infection in cat, Texas, USA
Tyler RJr , Rincon L , Weigand MR , Xiaoli L , Acosta AM , Kurien D , Ju H , Lingsweiler S , Prot EY . Emerg Infect Dis 2022 28 (8) 1686-1688 We report a toxigenic strain of Corynebacterium diphtheriae isolated from an oozing dermal wound in a pet cat in Texas, USA. We also describe the epidemiologic public health efforts conducted to identify potential sources of infection and mitigate its spread and the molecular and genetic studies performed to identify the bacterium. |
Assessing Progress Toward the Vision of a Comprehensive, Shared Electronic Care Plan: Scoping Review.
Norton JM , Ip A , Ruggiano N , Abidogun T , Camara DS , Fu H , Hose BZ , Miran S , Hsiao CJ , Wang J , Bierman AS . J Med Internet Res 2022 24 (6) e36569 BACKGROUND: Care plans are central to effective care delivery for people with multiple chronic conditions. But existing care plans-which typically are difficult to share across care settings and care team members-poorly serve people with multiple chronic conditions, who often receive care from numerous clinicians in multiple care settings. Comprehensive, shared electronic care (e-care) plans are dynamic electronic tools that facilitate care coordination and address the totality of health and social needs across care contexts. They have emerged as a potential way to improve care for individuals with multiple chronic conditions. OBJECTIVE: To review the landscape of e-care plans and care plan-related initiatives that could allow the creation of a comprehensive, shared e-care plan and inform a joint initiative by the National Institutes of Health and the Agency for Healthcare Research and Quality to develop e-care planning tools for people with multiple chronic conditions. METHODS: We conducted a scoping review, searching literature from 2015 to June 2020 using Scopus, Clinical Key, and PubMed; we also searched the gray literature. To identify initiatives potentially missing from this search, we interviewed expert informants. Relevant data were then identified and extracted in a structured format for data synthesis and analysis using an expanded typology of care plans adapted to our study context. The extracted data included (1) the perspective of the initiatives; (2) their scope, (3) network, and (4) context; (5) their use of open syntax standards; and (6) their use of open semantic standards. RESULTS: We identified 7 projects for e-care plans and 3 projects for health care data standards. Each project provided critical infrastructure that could be leveraged to promote the vision of a comprehensive, shared e-care plan. All the e-care plan projects supported both broad goals and specific behaviors; 1 project supported a network of professionals across clinical, community, and home-based networks; 4 projects included social determinants of health. Most projects specified an open syntax standard, but only 3 specified open semantic standards. CONCLUSIONS: A comprehensive, shared, interoperable e-care plan has the potential to greatly improve the coordination of care for individuals with multiple chronic conditions across multiple care settings. The need for such a plan is heightened in the wake of the ongoing COVID-19 pandemic. While none of the existing care plan projects meet all the criteria for an optimal e-care plan, they all provide critical infrastructure that can be leveraged as we advance toward the vision of a comprehensive, shared e-care plan. However, critical gaps must be addressed in order to achieve this vision. |
Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya
Nyiro JU , Bukusi E , Mwaengo D , Nyaguara A , Nyawanda B , Otieno N , Bigogo G , Murunga N , Widdowson MA , Verani JR , Chaves SS , Mwangudza H , Odundo C , Berkley JA , Nokes DJ , Munywoki PK . Wellcome Open Res 2022 7 43 Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal titre ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06-0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07-0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting. |
Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion.
Zauche LH , Wallace B , Smoots AN , Olson CK , Oduyebo T , Kim SY , Petersen EE , Ju J , Beauregard J , Wilcox AJ , Rose CE , Meaney-Delman DM , Ellington SR . N Engl J Med 2021 385 (16) 1533-1535 Pregnant persons are at risk for severe coronavirus disease 2019 (Covid-19), and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is associated with increased risks of preterm birth and other adverse maternal and neonatal outcomes.1 Although spontaneous abortion (pregnancy loss occurring at less than 20 weeks of gestation) is a common pregnancy outcome affecting 11 to 22% of recognized pregnancies (see Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org),2-4 data to inform estimates of the risk of spontaneous abortion after receipt of an mRNA Covid-19 vaccine either before conception (30 days before the first day of the last menstrual period through 14 days after) or during pregnancy are limited. |
Cellular Basis for the Enhanced Efficacy of the Fms-Like Tyrosine Kinase 3 Ligand (FL) Adjuvanted VCG-Based Chlamydia abortus Vaccine.
Richardson S , Medhavi F , Tanner T , Lundy S , Omosun Y , Igietseme JU , Carroll D , Eko FO . Front Immunol 2021 12 698737 Efficacious vaccines are needed to control genital chlamydial diseases in humans and the veterinary industry. We previously reported a C. abortus (Cab) vaccine comprising recombinant Vibrio cholerae ghosts (rVCG) expressing the conserved and immunogenic N-terminal region of the Cab polymorphic membrane protein D (rVCG-Pmp18.1) protein that protected mice against intravaginal challenge. In this study, we investigated the immunomodulatory effect of the hematopoietic progenitor activator cytokine, Fms-like tyrosine kinase 3-ligand (FL) when co-administered with the rVCG-Pmp18.1 vaccine as a strategy to enhance the protective efficacy and the potential mechanism of immunomodulation. Groups of female C57BL/6J mice were immunized and boosted twice intranasally (IN) with rVCG-PmpD18.1 with and without FL or purified rPmp18.1 or rVCG-gD2 (antigen control) or PBS (medium) per mouse. The results revealed that co-administration of the vaccine with FL enhanced antigen-specific cellular and humoral immune responses and protected against live Cab genital infection. Comparative analysis of immune cell phenotypes infiltrating mucosal and systemic immune inductive tissue sites following immunization revealed that co-administration of rVCG-Pmp18.1 with FL significantly enhanced the number of macrophages, dendritic and NK cells, γδ and NK T cells in the spleen (systemic) and iliac lymph nodes (ILN) draining the genital tract (mucosal) tissues compared to rVCG-Pmp18.1 alone. Furthermore, FL enhanced monocyte infiltration in the ILN, while CD19+ B cells and CD4+ T cells were enhanced in the spleen. These results indicate that the immunomodulatory effect of FL is associated with its ability to mobilize innate immune cells and subsequent activation of robust antigen-specific immune effectors in mucosal and systemic lymphoid tissues. |
MiR-378b Modulates Chlamydia-Induced Upper Genital Tract Pathology.
Lundy SR , Abney K , Ellerson D , Igietseme JU , Carroll D , Eko FO , Omosun YO . Pathogens 2021 10 (5) Genital Chlamydia trachomatis infection causes severe reproductive pathologies such as salpingitis and pelvic inflammatory disease that can lead to tubal factor infertility. MicroRNAs (miRNAs) are evolutionarily conserved regulators of mammalian gene expression in development, immunity and pathophysiologic processes during inflammation and infection, including Chlamydia infection. Among the miRNAs involved in regulating host responses and pathologic outcome of Chlamydia infection, we have shown that miR-378b was significantly differentially expressed during primary infection and reinfection. In this study, we tested the hypothesis that miR-378b is involved in the pathological outcome of Chlamydia infection. We developed miR-378b knockout mice (miR-378b(-/-)) using Crispr/Cas and infected them along with their wild-type (WT) control with Chlamydia to compare the infectivity and reproductive pathologies. The results showed that miR-378b(-/-) mice were unable to clear the infection compared to WT mice; also, miR-378b(-/-) mice exhibited a relatively higher Chlamydia burden throughout the duration of infection. However, gross pathology results showed that miR-378b(-/-) mice had significantly reduced uterine dilatations and pathologic lesions after two infections compared to WT mice. In addition, the pregnancy and fertility rates for infected miR-378b(-/-) mice showed protection from Chlamydia-induced infertility with fertility rate that was comparable to uninfected WT mice. These results are intriguing as they suggest that miR-378b is important in regulating host immune responses that control Chlamydial replication and drive the inflammation that causes complications such as infertility. The finding has important implications for biomarkers of Chlamydial complications and targets for prevention of disease. |
Identification of Coronaviruses, Paramyxoviruses, Reoviruses, and Rotaviruses among Bats in Nigeria
Kia GSN , Tao Y , Umoh JU , Kwaga JKP , Tong S . Am J Trop Med Hyg 2021 104 (3) 1106-10 Bats are often consumed by some ethnic groups in Nigeria despite association of bats with many important emerging viruses. More than 300 bats representing eight species were captured during 2010-2011 in eight locations of northern Nigeria. Available fecal swabs (n = 95) were screened for the presence of arenaviruses, CoVs, paramyxoviruses (PMVs), reoviruses, rhabdoviruses, and influenza viruses using generic reverse transcription-polymerase chain reaction assays. Here, we document the detection of CoVs, PMVs, reoviruses, and rotaviruses (RVs) in Nigerian bats. The Nigerian bat CoVs are grouped within other bat SARS-CoV-like viruses identified from Ghana in a sister clade next to the human SARS-CoV clade. The phylogenetic analysis indicated a broad range of RVs present in Nigerian bats, some cluster with human RVs and some represent novel species. Our study adds that continuing global surveillance for viruses in bats to understand their origin, adaptation, and evolution is important to prevent and control future zoonotic disease outbreaks. |
Investigation of bacterial and fungal communities in indoor and outdoor air of elementary school classrooms by 16S rRNA gene and ITS region sequencing.
Lee BG , Yang JI , Kim E , Geum SW , Park JH , Yeo MK . Indoor Air 2021 31 (5) 1553-1562 The advent of high-throughput sequencing methods allowed researchers to fully characterize microbial community in environmental samples, which is crucial to better understand their health effects upon exposures. In our study, we investigated bacterial and fungal community in indoor and outdoor air of nine classrooms in three elementary schools in Seoul, Korea. The extracted bacterial 16S rRNA gene and fungal ITS regions were sequenced, and their taxa were identified. Quantitative polymerase chain reaction for total bacteria DNA was also performed. The bacterial community was richer in outdoor air than classroom air, whereas fungal diversity was similar indoors and outdoors. Bacteria such as Enhydrobacter, Micrococcus, and Staphylococcus that are generally found in human skin, mucous membrane, and intestine were found in great abundance. For fungi, Cladosporium, Clitocybe, and Daedaleopsis were the most abundant genera in classroom air and mostly related to outdoor plants. Bacterial community composition in classroom air was similar among all classrooms but differed from that in outdoor air. However, indoor and outdoor fungal community compositions were similar for the same school but different among schools. Our study indicated the main source of airborne bacteria in classrooms was likely human occupants; however, classroom airborne fungi most likely originated from outdoors. |
Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection.
Howard S , Richardson S , Benyeogor I , Omosun Y , Dye K , Medhavi F , Lundy S , Adebayo O , Igietseme JU , Eko FO . Front Immunol 2021 12 625318 Vaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after Chlamydia infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts >100 and p-values < 0.05 for further analysis. Interestingly, vaccine immunization and Chlamydia infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to Chlamydia infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live Chlamydia infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with Chlamydia infection and vaccination. |
Incidence of urinary tract infections in newborns with spina bifida: Is antibiotic prophylaxis necessary
Wallis MC , Paramsothy P , Newsome K , Williams T , Routh JC , Joseph DB , Cheng E , Tu D , Austin JC , Tanaka ST , Walker WO , Smith KA , Baum MA , Wiener JS . J Urol 2021 206 (1) 101097ju0000000000001690 PURPOSE: Urinary tract infections (UTI) commonly occur in patients with spina bifida (SB) and pose a risk for renal scarring. Routine antibiotic prophylaxis has been utilized in newborns with SB to prevent UTI. We hypothesized that prophylaxis can safely be withheld in newborns with SB until clinical assessment allows for risk stratification. MATERIALS AND METHODS: Newborns with myelomeningocele at nine institutions were prospectively enrolled in the UMPIRE study and managed by a standardized protocol with a strict definition for UTI. Patient data were collected regarding details of reported UTI, baseline renal ultrasound findings, vesicoureteral reflux, use of clean intermittent catheterization (CIC), and circumcision status in boys. Risk Ratios (RRs) and corresponding 95% confidence intervals (CIs) were calculated using log-binomial models. RESULTS: From 2/2015 through 8/2019, data were available on 299 newborns (50.5% male). During the first four months of life, 48 (16.1%) newborns were treated for UTI with 23 (7.7%) having positive cultures; however, only 12 (4.0%) met the strict UTI definition. Infants with grade 3-4 hydronephrosis had an increased risk of UTI compared to infants with no hydronephrosis (RR=10.1; 95%CI=2.8, 36.3). Infants on CIC also had an increased risk of UTI (RR=3.3; 95%CI=1.0, 10.5). CONCLUSIONS: The incidence of a culture-positive, symptomatic UTI among newborns with SB in the first 4 months of life was low. Patients with high grades of hydronephrosis or those on CIC had a significantly greater incidence of UTI. Our findings suggest that routine antibiotic prophylaxis may not be necessary for most newborns with SB. |
Loss of the virulence plasmid by Shigella sonnei promotes its interactions with CD207 and CD209 receptors
Wu BC , Olivia NA , Tembo JM , He YX , Zhang YM , Xue Y , Ye CL , Lv Y , Li WJ , Jiang LY , Huo XX , Sun ZY , Chen ZJ , Qin JC , Li AY , Park CG , Klena JD , Ding HH , Chen T . J Med Microbiol 2021 70 (3) Introduction. Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria. S. sonnei contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).Hypothesis/Gap Statement. S. sonnei by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.Aim. This study aimed to investigate if the S. sonnei rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of S. sonnei WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of S. sonnei WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Animal assays were used to observe the dissemination of S. sonnei.Results. S. sonnei did not express O-antigens after losing the virulence plasmid. The S. sonnei rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough S. sonnei. Expression of the O-antigen reduces the ability of the S. sonnei rough strain to be disseminated to mesenteric lymph nodes and spleens.Conclusion. This work demonstrated that S. sonnei rough strains - by losing the virulence plasmid - invaded APCs through interactions with CD209 and CD207 receptors. |
Evidence of SARS-CoV-2 Replication and Tropism in the Lungs, Airways and Vascular Endothelium of Patients with Fatal COVID-19: An Autopsy Case-Series.
Bhatnagar J , Gary J , Reagan-Steiner S , Estetter LB , Tong S , Tao Y , Denison AM , Lee E , DeLeon-Carnes M , Li Y , Uehara A , Paden CR , Leitgeb B , Uyeki TM , Martines RB , Ritter JM , Paddock CD , Shieh WJ , Zaki SR . J Infect Dis 2021 223 (5) 752-764 BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of SARS-CoV-2 tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case-patients (age range: 1 month to 84 years; COVID-19 confirmed n=21, suspected n=43) by SARS-CoV-2 RT-PCR. For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in-situ hybridization (ISH), subgenomic RNA RT-PCR, and whole genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case-patients (confirmed n=21 and suspected n=11). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case-patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes and macrophages of lungs, epithelial cells of airways, and in endothelial cells and vessels wall of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. D614G variant was detected in 9 RT-PCR-positive case-patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes. |
Bacterial community assemblages in classroom floor dust of 50 public schools in a large city: characterization using 16S rRNA sequences and associations with environmental factors.
Park JH , Lemons AR , Roseman J , Green BJ , Cox-Ganser JM . Microbiome 2021 9 (1) 15 Characterizing indoor microbial communities using molecular methods provides insight into bacterial assemblages present in environments that can influence occupants' health. We conducted an environmental assessment as part of an epidemiologic study of 50 elementary schools in a large city in the northeastern USA. We vacuumed dust from the edges of the floor in 500 classrooms accounting for 499 processed dust aliquots for 16S Illumina MiSeq sequencing to characterize bacterial assemblages. DNA sequences were organized into operational taxonomic units (OTUs) and identified using a database derived from the National Center for Biotechnology Information. Bacterial diversity and ecological analyses were performed at the genus level. We identified 29 phyla, 57 classes, 148 orders, 320 families, 1193 genera, and 2045 species in 3073 OTUs. The number of genera per school ranged from 470 to 705. The phylum Proteobacteria was richest of all while Firmicutes was most abundant. The most abundant order included Lactobacillales, Spirulinales, and Clostridiales. Halospirulina was the most abundant genus, which has never been reported from any school studies before. Gram-negative bacteria were more abundant and richer (relative abundance = 0.53; 1632 OTUs) than gram-positive bacteria (0.47; 1441). Outdoor environment-associated genera were identified in greater abundance in the classrooms, in contrast to homes where human-associated bacteria are typically more abundant. Effects of school location, degree of water damage, building condition, number of students, air temperature and humidity, floor material, and classroom's floor level on the bacterial richness or community composition were statistically significant but subtle, indicating relative stability of classroom microbiome from environmental stress. Our study indicates that classroom floor dust had a characteristic bacterial community that is different from typical house dust represented by more gram-positive and human-associated bacteria. Health implications of exposure to the microbiomes in classroom floor dust may be different from those in homes for school staff and students. Video abstract. |
Development and assessment of a pooled serum as candidate standard to measure influenza a virus group 1 hemagglutinin stalk-reactive antibodies
Carreño JM , McDonald JU , Hurst T , Rigsby P , Atkinson E , Charles L , Nachbagauer R , Behzadi MA , Strohmeier S , Coughlan L , Aydillo T , Brandenburg B , García-Sastre A , Kaszas K , Levine MZ , Manenti A , McDermott AB , Montomoli E , Muchene L , Narpala SR , Perera Rapm , Salisch NC , Valkenburg SA , Zhou F , Engelhardt OG , Krammer F . Vaccines (Basel) 2020 8 (4) The stalk domain of the hemagglutinin has been identified as a target for induction of protective antibody responses due to its high degree of conservation among numerous influenza subtypes and strains. However, current assays to measure stalk-based immunity are not standardized. Hence, harmonization of assay readouts would help to compare experiments conducted in different laboratories and increase confidence in results. Here, serum samples from healthy individuals (n = 110) were screened using a chimeric cH6/1 hemagglutinin enzyme-linked immunosorbent assay (ELISA) that measures stalk-reactive antibodies. We identified samples with moderate to high IgG anti-stalk antibody levels. Likewise, screening of the samples using the mini-hemagglutinin (HA) headless construct #4900 and analysis of the correlation between the two assays confirmed the presence and specificity of anti-stalk antibodies. Additionally, samples were characterized by a cH6/1N5 virus-based neutralization assay, an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and competition ELISAs, using the stalk-reactive monoclonal antibodies KB2 (mouse) and CR9114 (human). A "pooled serum" (PS) consisting of a mixture of selected serum samples was generated. The PS exhibited high levels of stalk-reactive antibodies, had a cH6/1N5-based neutralization titer of 320, and contained high levels of stalk-specific antibodies with ADCC activity. The PS, along with blinded samples of varying anti-stalk antibody titers, was distributed to multiple collaborators worldwide in a pilot collaborative study. The samples were subjected to different assays available in the different laboratories, to measure either binding or functional properties of the stalk-reactive antibodies contained in the serum. Results from binding and neutralization assays were analyzed to determine whether use of the PS as a standard could lead to better agreement between laboratories. The work presented here points the way towards the development of a serum standard for antibodies to the HA stalk domain of phylogenetic group 1. |
An evaluation of 6-month versus continuous isoniazid preventive therapy for M. tuberculosis in adults living with HIV/AIDS in Malawi
Hsieh YL , Jahn A , Menzies NA , Yaesoubi R , Salomon JA , Girma B , Gunde L , Eaton JW , Auld A , Odo M , Kiyiika CN , Kalua T , Chiwandira B , Mpunga JU , Mbendra K , Corbett L , Hosseinipour MC , Cohen T , Kunkel A . J Acquir Immune Defic Syndr 2020 85 (5) 643-650 BACKGROUND: To assist the Malawi Ministry of Health to evaluate two competing strategies for scale-up of isoniazid preventive therapy (IPT) among HIV-positive adults receiving ART. SETTING: Malawi. METHODS: We used a multi-district, compartmental model of the Malawi TB/HIV epidemic to compare the anticipated health impacts of 6-month versus continuous IPT programs over a 12-year horizon, while respecting a US$10.8 million constraint on drug costs in the first three years. RESULTS: The 6-month IPT program could be implemented nationwide while the continuous IPT alternative could be introduced in 14 (out of 27) districts. By the end of year 12, the continuous IPT strategy was predicted to avert more TB cases than the 6-month alternative, although not statistically significantly (2368 additional cases averted; 95%PI, -1459, 5023). The 6-month strategy required fewer person-years of IPT to avert a case of TB or death than the continuous strategy. For both programs, the mean reductions in TB incidence among PLHIV by year 12 were expected to be <10%, and the cumulative numbers of IPT-related hepatotoxicity to exceed the number of all-cause deaths averted in the first three years. CONCLUSION: With the given budgetary constraint, nationwide implementation of 6-month IPT would be more efficient and yield comparable health benefits than implementing continuous IPT program in fewer districts. The anticipated health effects associated with both IPT strategies suggested a combination of different TB intervention strategies would likely be required to yield greater impact on TB control in settings like Malawi, where ART coverage is relatively high. |
Shift work influences the outcomes of Chlamydia infection and pathogenesis
Lundy SR , Richardson S , Ramsey A , Ellerson D , Fengxia Y , Onyeabor S , Kirlin W , Thompson W , Black CM , DeBruyne JP , Davidson AJ , Immergluck LC , Blas-Machado U , Eko FO , Igietseme JU , He Q , Omosun YO . Sci Rep 2020 10 (1) 15389 Shift work, performed by approximately 21 million Americans, is irregular or unusual work schedule hours occurring after 6:00 pm. Shift work has been shown to disrupt circadian rhythms and is associated with several adverse health outcomes and chronic diseases such as cancer, gastrointestinal and psychiatric diseases and disorders. It is unclear if shift work influences the complications associated with certain infectious agents, such as pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility resulting from genital chlamydial infection. We used an Environmental circadian disruption (ECD) model mimicking circadian disruption occurring during shift work, where mice had a 6-h advance in the normal light/dark cycle (LD) every week for a month. Control group mice were housed under normal 12/12 LD cycle. Our hypothesis was that compared to controls, mice that had their circadian rhythms disrupted in this ECD model will have a higher Chlamydia load, more pathology and decreased fertility rate following Chlamydia infection. Results showed that, compared to controls, mice that had their circadian rhythms disrupted (ECD) had higher Chlamydia loads, more tissue alterations or lesions, and lower fertility rate associated with chlamydial infection. Also, infected ECD mice elicited higher proinflammatory cytokines compared to mice under normal 12/12 LD cycle. These results imply that there might be an association between shift work and the increased likelihood of developing more severe disease from Chlamydia infection. |
Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever.
Lan S , Shieh WJ , Huang Q , Zaki SR , Liang Y , Ly H . Virulence 2020 11 (1) 1131-1141 Arenaviruses, such as Lassa virus (LASV), can cause severe and fatal hemorrhagic fevers (e.g., Lassa fever, LF) in humans with no vaccines or therapeutics. Research on arenavirus-induced hemorrhagic fevers (AHFs) has been hampered by the highly virulent nature of these viral pathogens, which require high biocontainment laboratory, and the lack of an immune-competent small animal model that can recapitulate AHF disease and pathological features. Guinea pig infected with Pichinde virus (PICV), an arenavirus that does not cause disease in humans, has been established as a convenient surrogate animal model for AHFs as it can be handled in a conventional laboratory. The PICV strain P18, derived from sequential passaging of the virus 18 times in strain 13 inbred guinea pigs, causes severe febrile illness in guinea pigs that is reminiscent of lethal LF in humans. As inbred guinea pigs are not readily available and are difficult to maintain, outbred Hartley guinea pigs have been used but they show a high degree of disease heterogeneity upon virulent P18 PICV infection. Here, we describe an improved outbred guinea-pig infection model using recombinant rP18 PICV generated by reverse genetics technique followed by plaque purification, which consistently shows >90% mortality and virulent infection. Comprehensive virological, histopathological, and immunohistochemical analyses of the rP18-virus infected animals show similar features of human LASV infection. Our data demonstrate that this improved animal model can serve as a safe, affordable, and convenient surrogate small animal model for studying human LF pathogenesis and for evaluating efficacy of preventative or therapeutic approaches. |
Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States.
Martines RB , Ritter JM , Matkovic E , Gary J , Bollweg BC , Bullock H , Goldsmith CS , Silva-Flannery L , Seixas JN , Reagan-Steiner S , Uyeki T , Denison A , Bhatnagar J , Shieh WJ , Zaki SR , Covid-Pathology Working Group . Emerg Infect Dis 2020 26 (9) 2005-2015 An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection. |
Association of a province-wide intervention with salt intake and hypertension in Shandong Province, China, 2011-2016
Xu A , Ma J , Guo X , Wang L , Wu J , Zhang J , Bai Y , Xu J , Lu Z , Xu Z , Zhang X , Ding G , Hong Y , Du F , Wu Y , Yan L , Tang J , Cai X , Dong J , Xu C , Ren J , Chen X , Gao C , Zhang B , Yang Q , Moolenaar R , Cai Y , Jackson SL , Xie G , Yu S , Cui J , Wang Z , Zhao L , Ju L , Shen D , Yun S , Liang X , Bi Z , Wang Y . JAMA Intern Med 2020 180 (6) 877-86 IMPORTANCE: High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease. OBJECTIVE: To assess the association of a government-led, multisectoral, and population-based intervention with reduced salt intake and blood pressure in Shandong Province, China. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) program, a 5-year intervention to reduce sodium consumption in Shandong Province, China. Two representative samples of adults (aged 18-69 years) were surveyed in 2011 (15 350 preintervention participants) and 2016 (16 490 postintervention participants) to examine changes in blood pressure, and knowledge, attitudes, and behaviors related to sodium intake. Urine samples were collected from random subsamples (2024 preintervention participants and 1675 postintervention participants) for measuring sodium and potassium excretion. Data were analyzed from January 20, 2017, to April 9, 2019. INTERVENTIONS: Media campaigns, distribution of scaled salt spoons, promotion of low-sodium products in markets and restaurants, and activities to support household sodium reduction and school-based sodium reduction education. MAIN OUTCOMES AND MEASURES: The primary outcome was change in urinary sodium excretion. Secondary outcomes were changes in potassium excretion, blood pressure, and knowledge, attitudes, and behaviors. Outcomes were adjusted for likely confounders. Means (95% CIs) and percentages were weighted. RESULTS: Among 15 350 participants in 2011, 7683 (50.4%) were men and the mean age was 40.7 years (95% CI, 40.2-41.2 years); among 16 490 participants in 2016, 8077 (50.7%) were men and the mean age was 42.8 years (95% CI, 42.5-43.1 years). Among participants with 24-hour urine samples, 1060 (51.8%) were men and the mean age was 40.9 years (95% CI, 40.5-41.3 years) in 2011 and 836 (50.7%) were men and the mean age was 40.7 years (95% CI, 40.1-41.4 years) in 2016. The 24-hour urinary sodium excretion decreased 25% from 5338 mg per day (95% CI, 5065-5612 mg per day) in 2011 to 4013 mg per day (95% CI, 3837-4190 mg per day) in 2016 (P < .001), and potassium excretion increased 15% from 1607 mg per day (95% CI, 1511-1704 mg per day) to 1850 mg per day (95% CI, 1771-1929 mg per day) (P < .001). Adjusted mean systolic blood pressure among all participants decreased from 131.8 mm Hg (95% CI, 129.8-133.8 mm Hg) to 130.0 mm Hg (95% CI, 127.7-132.4 mm Hg) (P = .04), and diastolic blood pressure decreased from 83.9 mm Hg (95% CI, 82.6-85.1 mm Hg) to 80.8 mm Hg (95% CI, 79.4-82.1 mm Hg) (P < .001). Knowledge, attitudes, and behaviors associated with dietary sodium reduction and hypertension improved significantly. CONCLUSIONS AND RELEVANCE: The findings suggest that a government-led and population-based intervention in Shandong, China, was associated with significant decreases in dietary sodium intake and a modest reduction in blood pressure. The results of SMASH may have implications for sodium reduction and blood pressure control in other regions of China and worldwide. |
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