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We hypothesized that bighorn sheep ewes with chronic nasal Mycoplasma ovipneumoniae carriage are the source of infection that results in fatal lamb pneumonia. We tested this hypothesis in captive bighorn ewes at two study facilities over a 5-year period, by identifying carrier ewes and then comparing lamb fates in groups that did (exposed pens) or did not (non-exposed pens) include one or more carrier ewes. Most (23 of 30) lambs born in exposed pens, but none of 11 lambs born in non-exposed pens, contracted fatal pneumonia. In addition, surviving lambs in exposed pens showed obvious signs of respiratory disease while lambs in non-exposed pens did not. In crossover experiments, individual non-carrier ewes had lambs that experienced fatal pneumonia in years when housed in exposed pens, but not in years when housed in non-exposed pens. The results of these studies clearly associate lamb pneumonia to exposure to M. ovipneumoniae carrier ewes, consistent with a necessary role for this agent in epizootic pneumonia of bighorn sheep. These data specifically highlight the role of chronic M. ovipneumoniae carriage by some bighorn ewes in the epidemiology of this population-limiting wildlife disease.IMPORTANCEBighorn sheep populations, historically important in mountain and canyon ecosystems of western North America, declined precipitously following European settlement of North America and remain depressed today. One factor contributing to these declines and lack of recovery is epizootic pneumonia caused by the bacterium Mycoplasma ovipneumoniae . This pathogen arrived with settlers' domestic sheep and goats and spilled over to infect bighorn sheep, a process that continues to this day. Bighorn losses from this disease include high rates of mortality (median, approaching 50%) of all ages of bighorn sheep on initial exposure, followed in subsequent years to decades by mortality largely limited to young lambs. The source of infection causing persistent lamb losses is the focus of the research described here. Conducting these studies on groups of captive bighorn sheep enabled demonstration of clear linkage between largely asymptomatic nasal carriage of M. ovipneumoniae by ewes and outbreaks of fatal pneumonia in lambs.

Controlling persistent infectious disease in wildlife populations is an ongoing challenge for wildlife managers and conservationists worldwide, and chronic diseases in particular remain a pernicious problem.Here, we develop a dynamic pathogen transmission model capturing key features of Mycoplasma ovipneumoniae infection, a major cause of population declines in North American bighorn sheep Ovis canadensis. We explore the effects of model assumptions and parameter values on disease dynamics, including density‐ versus frequency‐dependent transmission, the inclusion of a carrier class versus a longer infectious period, host survival rates, disease‐induced mortality and recovery rates and the epidemic growth rate. Along the way, we estimate the basic reproductive ratio, R0, for M. ovipneumoniae in bighorn sheep to fall between approximately 1.36 and 1.74.We apply the model to compare efficacies across a suite of management actions following an epidemic, including test‐and‐remove, depopulation‐and‐reintroduction, range expansion, herd augmentation and density reduction.Our results suggest that test‐and‐remove, depopulation‐and‐reintroduction and range expansion could help persistently infected bighorn sheep herds recovery following an epidemic. By contrast, augmentation could lead to worse outcomes than those expected in the absence of management. Other management actions that improve host survival or reduce disease‐induced mortality are also likely to improve population size and persistence of chronically infected herds.Synthesis and applications. Dynamic transmission models like the one employed here offer a structured, logical approach for exploring hypotheses, planning field experiments and designing adaptive management. We find that management strategies that removed infected animals or isolated them within a structured metapopulation were most successful at facilitating herd recovery from a low‐prevalence, chronic pathogen. Ideally, models like ours should operate iteratively with field experiments to triangulate on better approaches for managing wildlife diseases. [ABSTRACT FROM AUTHOR]

Abstract Chronic pathogen carriage is one mechanism that allows diseases to persist in populations. We hypothesized that persistent or recurrent pneumonia in bighorn sheep (Ovis canadensis) populations may be caused by chronic carriers of Mycoplasma ovipneumoniae (Mo). Our experimental approach allowed us to address a conservation need while investigating the role of chronic carriage in disease persistence. We tested our hypothesis in two bighorn sheep populations in South Dakota, USA. We identified and removed Mo chronic carriers from the Custer State Park (treatment) population. Simultaneously, we identified carriers but did not remove them from the Rapid City population (control). We predicted removal would result in decreased pneumonia, mortality, and Mo prevalence. Both population ranges had similar habitat and predator communities but were sufficiently isolated to preclude intermixing. We classified chronic carriers as adults that consistently tested positive for Mo carriage over a 20‐month sampling period (n = 2 in the treatment population; n = 2 in control population). We failed to detect Mo or pneumonia in the treatment population after chronic carrier removal, while both remained in the control. Mortality hazard for lambs was reduced by 72% in the treatment population relative to the control (CI = 36%, 91%). There was also a 41% reduction in adult mortality hazard attributable to the treatment, although this was not statistically significant (CI = 82% reduction, 34% increase). Synthesis and Applications: These results support the hypothesis that Mo is a primary causative agent of persistent or recurrent respiratory disease in bighorn sheep populations and can be maintained by a few chronic carriers. Our findings provide direction for future research and management actions aimed at controlling pneumonia in wild sheep and may apply to other diseases.

Salmonella enterica serovar Typhi primarily persists in chronic carriers by forming biofilms on gallstones in the gallbladder. We have developed a gallstone mouse model to study chronic carriage. To better understand the infection timeline and differentiate between mice that have maintained long-term gallbladder carriage from those that have cleared infection, we utilized bioluminescent S . Typhimurium and in vivo imaging to detect and track the organ-specific presence of bacteria in living mice. The mice infected with our bioluminescent S . Typhimurium showed luminescence in the abdomen as early as 3 days in comparison to the mice infected with non-luminescent WT S . Typhimurium. With our methods, we achieve image resolution such that we can confidently identify the presence of S . Typhimurium in the gallbladder at >60 days post-infection. Using these methods, we have determined that the minimum number of bacteria necessary to detect luminescence in the mice is 10 3 c.f.u. and that one out of six initially infected mice will remain persistently infected for greater than 60 days, with gallbladder bacterial loads reaching upwards of 10 3 per milligram of tissue. Given that our limit of detection of luminescence is 10 3 c.f.u., our sensitivity is robust enough to identify the bacterial loads present in the average chronically infected mouse. The quantification of individual organs' bacterial c.f.u. and comparison of luminescence between WT and luminescent S . Typhimurium validate that our technique is specific and sensitive enough to detect organ-specific infection in our model of typhoidal chronic carriage., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors.)

Chronic pathogen carriage is one mechanism that allows diseases to persist in populations. We hypothesized that persistent or recurrent pneumonia in bighorn sheep (Ovis canadensis) populations may be caused by chronic carriers of Mycoplasma ovipneumoniae (Mo). Our experimental approach allowed us to address a conservation need while investigating the role of chronic carriage in disease persistence.We tested our hypothesis in two bighorn sheep populations in South Dakota, USA. We identified and removed Mo chronic carriers from the Custer State Park (treatment) population. Simultaneously, we identified carriers but did not remove them from the Rapid City population (control). We predicted removal would result in decreased pneumonia, mortality, and Mo prevalence. Both population ranges had similar habitat and predator communities but were sufficiently isolated to preclude intermixing.We classified chronic carriers as adults that consistently tested positive for Mo carriage over a 20‐month sampling period (n = 2 in the treatment population; n = 2 in control population).We failed to detect Mo or pneumonia in the treatment population after chronic carrier removal, while both remained in the control. Mortality hazard for lambs was reduced by 72% in the treatment population relative to the control (CI = 36%, 91%). There was also a 41% reduction in adult mortality hazard attributable to the treatment, although this was not statistically significant (CI = 82% reduction, 34% increase).Synthesis and Applications: These results support the hypothesis that Mo is a primary causative agent of persistent or recurrent respiratory disease in bighorn sheep populations and can be maintained by a few chronic carriers. Our findings provide direction for future research and management actions aimed at controlling pneumonia in wild sheep and may apply to other diseases. [ABSTRACT FROM AUTHOR]

ABSTRACT Typhoid fever, caused primarily by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening systemic disease responsible for significant morbidity and mortality worldwide. Three to 5% of individuals infected with S. Typhi become chronic carriers due to bacterial persistence in the gallbladder. We have demonstrated that Salmonella forms biofilms on gallstones to establish gallbladder carriage. However, an in-depth molecular understanding of chronic carriage in the gallbladder, from the perspective of both the pathogen and host, is poorly defined. To examine the dynamics of the gallbladder in response to Salmonella infection, we performed transcriptional profiling in the mouse gallbladder at early (7 days) and chronic (21 days) time points. Transcriptome sequencing (RNA-Seq) revealed a shift from a Th1 proinflammatory response at 7 days postinfection (dpi) toward an anti-inflammatory Th2 response by 21 dpi, characterized by increased levels of immunoglobulins and the Th2 master transcriptional regulator, GATA3. Additionally, bioinformatic analysis predicted the upstream regulation of characteristic Th2 markers, including interleukin-4 (IL-4) and Stat6. Immunohistochemistry and fluorescence-activated cell sorter (FACS) analysis confirmed a significant increase in lymphocytes, including T and B cells, at 21 dpi in mice with gallstones. Interestingly, the levels of Salmonella-specific CD4 T cells were 10-fold higher in the gallbladder of mice with gallstones at 21 dpi. We speculate that the biofilm state allows Salmonella to resist the initial onslaught of the Th1 inflammatory response, while yet undefined events influence a switch in the host immunity toward a more permissive type 2 response, enabling the establishment of chronic infection. IMPORTANCE The existence of chronic typhoid carriers has been in the public eye for over 100 years in part because of the publicity around Typhoid Mary. Additionally, it has been known for decades that the gallbladder is the main site of persistence and recently that gallstones play a key role. Despite this, very little is known about the physiological conditions that allow Salmonella enterica serovar Typhi to persist in the gallbladder. In this study, we analyze the transcriptional profile of the gallbladder in a mouse model of chronic carriage. We found a shift from an early proinflammatory immune response toward a later anti-inflammatory response, which could explain the stalemate that allows Salmonella persistence. Interestingly, we found a 10-fold increase in the number of Salmonella-specific T cells in mice with gallstones. This work moves us closer to understanding the mechanistic basis of chronic carriage, with a goal toward eradication of the disease.

Toxigenic strains of Corynebacterium diphtheriae cause the majority of respiratory diphtheria cases. However, nontoxigenic strains of C. diphtheriae can also cause diseases, and have become increasingly common. Infection that is limited to the anterior nares (nasal diphtheria) is a well-described but rare condition, even for toxigenic C. diphtheriae . We report a case involving chronic carriage of nasal diphtheria caused by nontoxigenic C. diphtheriae , as well as a review of other reported nontoxigenic C. diphtheriae cases in Japan. Mild or asymptomatic nasal diphtheria involving nontoxigenic strains, which can be the source of transmission, may be underrecognized. Our case highlights the importance of awareness regarding nontoxigenic diphtheria among clinicians, especially in the era of improved diphtheria vaccination coverage. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B (HB) infection is common in Mali. However, there is little information on molecular and biochemical characteristics of HB carriers.Methods: A group of 1466 adult volunteers was recruited in the district of Bamako. Confirmed HB carriers were tested for HB viral load by quantitative PCR and HBV was genotyped by sequencing of HBS. Fibrosis and hepatitis activity were measured using the Fibrotest-Actitest. A mutation of TP53 at codon 249 (R249S), specific for exposure to aflatoxin, was detected in cell-free DNA extracted from plasma.Results: Overall, 276 subjects were HBsAg-positive (18.8%). Among 152 subjects tested for HBV load, 49 (32.2%) had over 10(4) copies/mL and 16 (10.5%) had levels below the limit of detection. The E genotype was found in 91.1% of carriers. Fibrotest scores ≥ F2 were observed in 52 subjects (35.4%). Actitest scores ≥ A2 were detected in 15 subjects (10.2%) and were correlated with Fibrotest scores (p = 0.0006). Among 105 subjects tested, 60% had detectable levels of R249S copies (>40 copies/mL plasma).Conclusion: Chronic HB carriage in adults in Bamako district is well over epidemic threshold. About 1/3 of carriers have moderate to severe liver fibrosis and 60% have detectable aflatoxin-related TP53 R249S mutation. These results support introduction of anti-HB therapies to reduce the progression towards severe liver disease. [ABSTRACT FROM AUTHOR]

The hepatitis B vaccine has been part of the South African Expanded Program on Immunization since April 1995 but its long-term impact remains unknown. This study tested 1,206 sera collected from patients aged 1-25 years from various health facilities across the country for HBV serological markers and HBV DNA. Based on the year the vaccine was introduced, samples were stratified by age into pre- and post-vaccine introduction populations, which were then compared for evidence of immunity and chronic carriage using the Chi-square test. Where HIV status was known, subset analyses were performed. Immunity to HBV infection increased from 13.0% in the pre- to 57.0% in the post-vaccine introduction population ( P < 0.001). This decreased with increasing age within the post-vaccine introduction population (76.1% for 1-5 years, 50.0% for 6-10 years, and 46.3% for 11-16 years). In addition, HBV chronic carriage was significantly ( P = 0.003) reduced in the post- (1.4%) compared to the pre-vaccine introduction population (4.2%). The difference in prevalence of active HBV infection in the serologically exposed pre- and post-vaccine introduction populations was not statistically significant. Subset analyses showed that evidence of immunity was significantly ( P < 0.001) higher in the HIV negative compared to the HIV positive subset in both populations. Universal hepatitis B vaccination has been a remarkable success, with a significant increase in immunity to HBV infection. The observation that HBV chronic carriage increases as immunity wanes over time calls into question whether the time has come to consider a pre-adolescence vaccine booster dose policy. J. Med. Virol. 86:918-924, 2014. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: A population-based sero-epidemiological study enrolled 9486 volunteers in two governorates, Béja in the north and Tataouine in the south of Tunisia, in order to assess the magnitude of HBV transmission heterogeneity between the north and the south and within the same governorate, as well as the risk factors associated with infection and chronic carriage. Results: The overall prevalence of anti-HBc, HBsAg and chronic carriage was 28.5, 5.3 and 2.9%, respectively. Significant differences were observed between the two governorates according to anti-HBc (32.1% in Béja and 27.8% in Tataouine; p =0.005) and HBsAg prevalence (4.2% in Béja and 5.6% in Tataouine; p =0.001). Significant differences were noticed between districts revealing important heterogeneity in HBV transmission within the same governorate (HBsAg ranged from 12 to <2% within the same governorate). At the individual level, the presence of a family member infected with HBV, scarification practices, needle practices in the Primary Care Center and gender (male) significantly increased the risk of anti-Hbc, HBsAg positivity and chronic carriage of infection while existence of sanitation in the house was found to be protective. The basic reproductive number and the force of infection confirmed the heterogeneity of transmission. Horizontal transmission within the family explains hyperendemic clusters in Tunisia. [Copyright &y& Elsevier]

Summary: Most African countries do not initiate hepatitis B vaccination at birth. We conducted a non-randomized controlled trial comparing hepatitis B vaccination given at age 0, 6, and 14 weeks versus the current Côte d’Ivoire schedule of 6, 10, and 14 weeks. Pregnant women were enrolled at four health centers in Abidjan. At age 9 months, 0.5% of infants in both the birth and 6-week cohorts were positive for HBsAg and all were born to HBeAg-positive women. Among infants of HBeAg-positive mothers, 9 of 24 (37.5%) in the birth cohort and 10 of 17 (58.8%) in the 6-week cohort were HBsAg positive (adjusted OR, 2.7; 95% CI: 0.7–11.0). While both vaccine schedules prevented most cases of infant HBV transmission, both also had high failure rates among infants of HBeAg-positive mothers. African infants may benefit from a birth dose but additional studies are needed to verify this hypothesis. [Copyright &y& Elsevier]

Summary: An outbreak of staphylococcal bullous impetigo occurred over a period of five months in a maternity ward involving seven infected and two colonised neonates. The skin lesions were due to epidermolytic toxin A-producing Staphylococcus aureus. Infection control measures were implemented and a retrospective case–control study performed. Contact with an auxiliary nurse was the only risk factor for cases of bullous impetigo (P <0.01). The nurse cared for all seven cases and was an asymptomatic nasal carrier of the epidemic strain. Repeated courses of decontamination treatment failed to eradicate carriage. Nine months after the last case, another neonate developed a more severe form of bullous impetigo and the auxiliary nurse was reassigned to an adult ward. [Copyright &y& Elsevier]

In September 2021, a household cluster of three typhoid cases was investigated by Queensland public health authorities. Through case interviews and molecular typing, the investigation revealed chronic carriage of Salmonella Typhi persisting at least 12 years in the index case. This case report summarises the investigation and highlights the complexity of chronic pathogen carriage in the control and management of typhoid disease. Our findings raise considerations for prevention and treatment guidelines in Australia and demonstrate the beneficial role of molecular typing for complex case investigations., (© Commonwealth of Australia CC BY-NC-ND.)

Typhoid fever is caused primarily by Salmonella enterica serovar Typhi. Approximately 3% to 5% of individuals infected with S. Typhi become chronic carriers with the gallbladder (GB) as the site of persistence, as gallstones within the GB are a platform on which the bacteria form a biofilm. S. Typhi is a human-restricted pathogen; therefore, asymptomatic carriers represent a critical reservoir for further spread of disease. To examine the dynamics of the Salmonella biofilm during chronic carriage, the human gallstone (GS) environment was simulated by growing biofilms on cholesterol-coated surfaces in the presence of bile, and the transcriptional profile was determined. Some of the most highly activated genes corresponded to the curli fimbria operon, with the major structural component csgA upregulated >80-fold. The curli protein polymer is a major component of the extracellular matrix (ECM) in Salmonella biofilms. The upregulation of curli fimbriae by human bile was validated through reverse transcription-quantitative PCR (qRT-PCR), microscopy, and Western blotting. Interestingly, this activation appears human specific, as qRT-PCR showed repression of csgA in biofilms grown in mouse or ox bile. Comparative transcriptional studies of the two divergent csg operons suggest an early activation of both operons in minimal medium complemented with glucose that quickly diminishes as the biofilm matures. However, in the presence of human bile, there is a modest activation of both operons that steadily increases as the biofilm matures. Understanding the effect of the GB environment on key biofilm-associated factors can help target antibiofilm therapeutics or other preventative strategies to eradicate chronic carriage. [ABSTRACT FROM AUTHOR]

Typhoid fever, a human-specific disease, is primarily caused by the pathogen Salmonella enterica serovar Typhi. It is estimated that 3 to 5% of people infected with typhoid fever become chronic carriers. Studies have demonstrated that a mechanism of chronic carriage involves biofilm formation on gallstone surfaces. In the course of a previous study using a chronic carriage mouse model, a Salmonella enterica serovar Typhimurium isolate was recovered from a mouse gallstone that exhibited a 2-fold increase in biofilm formation over the wild type. In order to identify the gene(s) responsible for the phenotype, the genomic sequences of this isolate and others were determined and compared. These sequences identified single nucleotide polymorphisms (SNPs) in 14 genes. Mutations in the most promising candidates, envZ and rcsB, were created, but neither showed increased biofilm-forming ability separately or in combination. The hyperbiofilm isolate did, however, present variations in cellular appendages observable using different techniques and a preferential binding to cholesterol. The isolate was also examined for systemic virulence and the ability to colonize the gallbladder/gallstones in a mouse model of chronic infection, demonstrating a systemic virulence defect and decreased gallbladder/gallstone colonization. Finally, to determine if the appearance of hyperbiofilm isolates could be replicated in vitro and if this was a common event, wild-type Salmonella spp. were grown long term in vitro under gallbladder-mimicking conditions, resulting in a high proportion of isolates that replicated the hyperbiofilm phenotype of the original isolate. Thus, Salmonella spp. acquire random mutations under the gallbladder/gallbladder-simulating conditions that may aid persistence but negatively affect systemic virulence. [ABSTRACT FROM AUTHOR]

Two immunocompromised patients with relapsing gastrointestinal infection with relatively resistant Salmonella infantis were cured with prolonged ertapenem followed by encapsulated fecal transplant. [ABSTRACT FROM AUTHOR]