Chronic Carriers Research Articles

C-reactive protein and high-sensitivity C-reactive protein levels in asymptomatic intestinal parasite carriers from urban and rural areas of Gabon.

Chronic carriage of intestinal parasitic infections (IPIs) can induce chronic inflammation and dysbiosis, which are risk factors for non-communicable diseases. The objective of this study was to determine the relationship between IPI carriage and inflammation in a population of volunteers living in Gabon. A cross-sectional study was conducted from September 2020 to November 2021 in asymptomatic volunteers aged 18 years old and over, residing in different areas of Gabon: Libreville (urban area) and Koula-Moutou and Bitam (rural areas). The detection of IPIs was carried out using four common microscopic techniques. C-reactive protein (CRP), and high-sensitivity C-reactive protein (hsCRP) were measured and levels were compared according to the presence or absence of IPI. Overall, 518 participants were included, 64.5% (n = 334) of whom resided in urban area and 35.5% (n = 184) in rural areas. The median age was 35 years (27; 46). The prevalence of asymptomatic IPIs was 29.9% (n = 155), with a significantly higher frequency in rural areas than in urban area (adjusted OR 6.6 (CI 3.2-13.8), p < 0.01). Protozoa were more frequent than soil-transmitted helminths (STHs) in both areas: 81.6% (n = 40) in urban area and 69.8% (n = 74) in rural areas. STHs were predominant in rural areas (48.1% vs 22.4% in urban area. In case of IPI, the median values of CRP (15 (13-15) mg/L vs 13.0 (11.1-14.9) mg/L) and hsCRP (4.2 (1.4-13.0) mg/L vs 2.2(0.4-6.1) mg/L) were higher (p<0.01). Elevated hsCRP and CRP were significantly more frequent in parasitized individuals (for hsCRP: 22.6%, n = 35; for CRP: 52.9%, n = 82); in particular among STH carriers (for hsCRP: 65.9%, n = 27, for CRP: 36.6%, n = 15) (p < 0.01). This first study showed that asymptomatic IPIs, particularly STH carriage are associated with high CRP and hsCRP levels. Further larger and longitudinal studies are needed to elucidate the global and specie-specific enteropathogens link with chronic inflammation.

Transmission of Hepatitis B in Newborn Mothers with Positive Hbs in the Csref of Commune V of the District of Bamako

The main cause of chronic HBsAg carriage is mother-to-child transmission. The aim of the study was to determine the epidemiological, clinical and biological aspects of mother-to-child transmission of the hepatitis B virus in newborns of HBsAg-positive mothers. Methodology: This was a descriptive cross-sectional study which took place from 1 March 2020 to 30 June 2021 at the CSREF in Commune V. Sampling was exhaustive, and all newborns whose mothers were carriers of hepatitis B were included in the study. Results: One hundred and twenty newborns out of 3197 referred from the maternity unit, representing a frequency of 3.7% of hepatitis B in pregnant women. Eighty newborns were included. The other 40 were not included because the mothers refused. Among the mothers, 11/80 tested positive for HBeAg and anti-HBs, with 2 positive results (18.18%). Twelve pregnant women had viral load tests, with two positive results (16.66%). Six of the 80 pregnant women had received tenofovir during pregnancy (7.5%), and all the newborns had negative HBsAg results at 4 months of age. Conclusion : Low realization of viral markers of hepatitis B and treatment during pregnancy.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.

Pathology of Chronic Mycoplasma ovipneumoniae Carriers in a Declining Bighorn Sheep (Ovis canadensis) Population.

Bighorn sheep (Ovis canadensis) across North America commonly experience population-limiting epizootics of respiratory disease. Although many cases of bighorn sheep pneumonia are polymicrobial, Mycoplasma ovipneumoniae is most frequently associated with all-age mortality events followed by years of low recruitment. Chronic carriage of M. ovipneumoniae by adult females serves as a source of exposure of naïve juveniles; relatively few ewes may be responsible for maintenance of infection within a herd. Test-and-remove strategies focused on removal of adult females with evidence of persistent or intermittent shedding (hereafter chronic carriers) may reduce prevalence and mitigate mortality. Postmortem confirmation of pneumonia in chronic carriers has been inadequately reported and the pathology has not been thoroughly characterized, limiting our understanding of important processes shaping the epidemiology of pneumonia in bighorn sheep. Here we document postmortem findings and characterize the lesions of seven ewes removed from a declining bighorn sheep population in Wyoming, USA, following at least two antemortem detections of M. ovipneumoniae within a 14-mo period. We confirmed that 6/7 (85.7%) had variable degrees of chronic pneumonia. Mycoplasma ovipneumoniae was detected in the lung of 4/7 (57.1%) animals postmortem. Four (57.1%) had paranasal sinus masses, all of which were classified as inflammatory, hyperplastic lesions. Pasteurella multocida was detected in all seven (100%) animals, while Trueperella pyogenes was detected in 5/7 (71.4%). Our findings indicate that not all chronic carriers have pneumonia, nor do all have detectable M. ovipneumoniae in the lung. Further, paranasal sinus masses are a common but inconsistent finding, and whether sinus lesions predispose to persistence or result from chronic carriage remains unclear. Our findings indicate that disease is variable in chronic M. ovipneumoniae carriers, underscoring the need for further efforts to characterize pathologic processes and underlying mechanisms in this system to inform management.

Longterm Outcome of Therapeutic Vaccination with a Third Generation Pre-S/S HBV Vaccine (PreHevbrioR) of Chronically HBV Infected Patients.

Several antiviral treatment regimens for chronic hepatitis B (CHB) virus infection have been shown to be effective in suppressing viral load and reducing the risk of hepatocellular injury and its complications. It has been hypothesized that high levels of circulating HBV surface antigen(s) may lead to immune tolerance against HBV and contribute to chronic carriership. Conversely, low-level HBsAg may create a window for the reconstitution of an HBV-specific immune response through vaccination and control of infection. Previous studies in non-responders to yeast-derived HBV vaccines, using a third-generation pre-S/S vaccine, have led to up to 95% anti-HBs seroconversion. This report evaluates the long-term outcome after experimental vaccination with a pre-S/S HBV vaccine intended as a therapeutic intervention in chronic HBV carriers. Four low-level HBsAg carriers (<500 IU/mL) were vaccinated three to seven times with 20 μg PreHevbrioR. Three out of four carriers eliminated HBsAg completely and seroconverted to anti-HBs. One patient seroconverted to anti-HBs but remained with a borderline HBsAg titer (10 IU/mL). Serum anti-HBs levels following repeated vaccination varied between 27 and >1000 IU/L, respectively. Long-term observation (>6 years) showed that after discontinuing NUC treatment for at least two years, HBsAg and HBV DNA remained negative with anti-HBs positive titers ranging between 80 and >1000 IU/L. Based on our preliminary observations, there is a rationale to further evaluate the role of this vaccine as a therapeutic agent.

Prospects for Controlling Hepatitis B Globally.

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.

A regular screening for hepatitis delta virus among chronic hepatitis B carriers improves the diagnostic of this infection and of subsequent cirrhosis development.

The prevalence of Hepatitis Delta Virus (HDV) is underestimated and the assessment of fibrosis is recommended for this infection. We tested the diagnostic impact of an annual screening for HDV serology in Hepatitis B Surface Antigen (HBs Ag) chronic carriers and followed the progression of fibrosis in these patients. Between January 2014 and October 2021, we annually tested all chronic HBs Ag-positive patients for HDV antibody (HDV Ab). Each HDV Ab positive patient underwent annually repeated elastometry. Patients with detectable HDV RNA levels (group 1) were compared to those with undetectable HDV RNA (group 2). We identified 610 chronic HBs Ag-positive patients, and repeated screening for HDV Ab was performed in 534 patients. Sixty (11%) patients were HDV Ab positive at baseline and were considered as "coinfected". Seven cases of HDV superinfection were diagnosed through repeated screening. In co-infected patients, cirrhosis was initially diagnosed in 12/60 patients and developed in six patients during follow-up. HDV RNA PCR was performed in 57/67 patients and 27 had detectable levels (group 1). Cumulative incidence of cirrhosis at 7years was 13.8% (95% CI 0-30) in group 1 and 0 (95% CI 0-0) in group 2 (p=0.026). A systematic screening for HDV in chronic HB Ag carriers revealed a high prevalence of HDV Ab. Repeated serological screening enables the diagnosis of superinfections in asymptomatic patients. Regular assessment of fibrosis using elastometry leads to the identification of incidental cirrhosis in patients with detectable HDV RNA.

Early host immune responses in a human organoid-derived gallbladder monolayer to Salmonella Typhi strains from patients with acute and chronic infections: a comparative analysis.

Salmonella enterica serovar Typhi (S. Typhi), a human-restricted pathogen, invades the host through the gut to cause typhoid fever. Recent calculations of the typhoid fever burden estimated that more than 10 million new typhoid fever cases occur in low and middle-income countries, resulting in 65,400-187,700 deaths yearly. Interestingly, if not antibiotic-treated, upon the resolution of acute disease, 1%-5% of patients become asymptomatic chronic carriers. Chronically infected hosts are not only critical reservoirs of infection that transmit the disease to naive individuals but are also predisposed to developing gallbladder carcinoma. Nevertheless, the molecular mechanisms involved in the early interactions between gallbladder epithelial cells and S. Typhi remain largely unknown. Based on our previous studies showing that closely related S. Typhi strains elicit distinct innate immune responses, we hypothesized that host molecular pathways activated by S. Typhi strains derived from acutely and chronically infected patients would differ. To test this hypothesis, we used a novel human organoid-derived polarized gallbladder monolayer model, and S. Typhi strains derived from acutely and chronically infected patients. We found that S. Typhi strains derived from acutely and chronically infected patients differentially regulate host mitogen-activated protein kinase (MAPK) and S6 transcription factors. These variations might be attributed to differential cytokine signaling, predominantly via TNF-α and IL-6 production and appear to be influenced by the duration the isolate was subjected to selective pressures in the gallbladder. These findings represent a significant leap in understanding the complexities behind chronic S. Typhi infections in the gallbladder and may uncover potential intervention targets.

Giardia intestinalis reshapes mucosal immunity toward a Type 2 response that attenuates inflammatory bowel-like diseases.

Diarrheal diseases are the second leading cause of death in children worldwide. Epidemiological studies show that co-infection with Giardia intestinalis decreases the severity of diarrhea. Here, we show that Giardia is highly prevalent in the stools of asymptomatic school-aged children. It orchestrates a Th2 mucosal immune response, characterized by increased antigen-specific Th2 cells, IL-25, Type 2-associated cytokines, and goblet cell hyperplasia. Giardia infection expanded IL-10-producing Th2 and GATA3 + Treg cells that promoted chronic carriage, parasite transmission, and conferred protection against Toxoplasma gondii -induced lethal ileitis and DSS-driven colitis by downregulating proinflammatory cytokines, decreasing Th1/Th17 cell frequency, and preventing collateral tissue damage. Protection was dependent on STAT6 signaling, as Giardia -infected STAT6 -/- mice no longer regulated intestinal bystander inflammation. Our findings demonstrate that Giardia infection reshapes mucosal immunity toward a Type 2 response, which confers a mutualistic protection against inflammatory disease processes and identifies a critical role for protists in regulating mucosal defenses.

Stat3 activation-triggered transcriptional networks govern the early stage of HBV-induced hepatic inflammation.

Until now, it remains a mystery that chronic hepatitis B virus (HBV)-infected patients in the "immune tolerance phase" will transition to the "immune activation phase" as they age. In this study, we reveal that Stat3 activation-triggered hepatic transcriptional alterations are distinctive characteristics of the early stage of immune/inflammation activation in chronic HBV infection. For the first time, we discover a mechanism that might trigger the transition from immune tolerance to immune activation in chronic HBV carriers.

Prevalence of Hepatitis D virus infection among Hepatitis B virus surface antigen positive children attending two selected Hospitals in Jos, Nigeria

Hepatitis B virus is a member of Hepadnaviridae family that cause liver infections in humans. These viral infections are characteristically linked with cirrhosis, chronic hepatitis, and hepatocellular carcinoma that are the leading cause of morbidity and mortality in the population of developing countries including Nigeria. Young children and newborns are more likely to have liver damage early in life and become chronic HBV carriers. This study identified the frequency of hepatitis B and D co-infection in children visiting the emergency pediatric units of Plateau State Specialist Hospital and Bingham University Teaching Hospital in Jos, Plateau State, Nigeria. The virus was screened using immunochromatographic Skytec® HBsAg test strips and Alere chase buffer for the qualitative detection of HBsAg in serum. HBsAg positive samples were confirmed using HBsAg Monolisa ELISA kit. Using an Italian HDV ELISA kit, samples that tested positive for HBsAg were further examined to evaluate the presence of HDV co-infection. The finding of this study revealed that 4.4% of children had HBsAg markers on their bodies. None of the children with HBV infection were co-infected with HDV. The HBV prevalence was found to be highest in children aged 6 to 10 years. Females had higher levels of HBV seropositivity (5.5%). Risk factors in children included birthplace (native households), failure to check children's HBV status after immunization, and history of jaundice. To properly manage and prevent this infection, it is advised that children should be promptly immunized at birth, their HBV status should be confirmed following immunization and they should be revaccinated if necessary.

Apparent prevalence of hemotropic mycoplasma in dairy calves and replacement heifers on Michigan farms

The bovine hemoplasmas include Mycoplasma wenyonii and Candidatus Mycoplasma hemobos which are increasingly recognized as infecting cattle throughout the world. Infection with hemotropic mycoplasma has been reported to be widespread in mature dairy cows, but little is known about prevalence in calves and heifers. The objective of this study was to investigate the prevalence and dynamics of infection with M. wenyonii and C.M. hemobos infections in calves and replacement heifers on Michigan dairy farms and assess potential associations between infection status and hematological values. The study was designed as a prospective cross-sectional study with a longitudinal component. A convenience sample of 11 farms agreed to participate and were visited twice between March and September 2022. During the first farm visit, researchers collected blood samples from up to 94 animals per farm distributed among newborn and pre-weaned calves (n ≤ 31), weaned calves (n = 21), pre-breeding heifers (n = 21), and pregnant heifers (n = 21). During the first visit, blood samples (n = 174) were also collected from a convenience sample of mature cows to confirm the herd infection status. The same calves and heifers were sampled again about 95 d (±3.0) later. During the first visit, blood samples were collected from 797 calves and replacement heifers, while 675 samples were collected during the second visit due to inability to locate some animals. Detection of M. wenyonii and C. M. hemobos were based on results of real time PCR. The hematocrit was determined using microcentrifugation and the concentration of leukocytes using an automated cell counter. In all herds, most mature cows that were sampled tested positive for infection. The within herd apparent prevalence of hemoplasma in calves and replacement heifers was 100% for both M. wenyonii and C. M. hemobos. The apparent prevalence of hemoplasma in youngstock was associated with age. In calves that were 1 to 6 mo old, the prevalence of infection was 6-8% but sharply increased to 31% by 8 mo of age. In older animals, the prevalence remained high, and was almost 100% in animals greater than 17 mo of age. Based on calves and heifers sampled twice, the cumulative incidence varied widely among herds ranging from 3.7% to 96.0% and increased with age of animals. There was no difference in hematocrit or number of lymphocytes, monocytes, neutrophils, or total leukocytes based on infection status. The number of eosinophils was greater in infected animals. This is the first study to report the prevalence of hemoplasmas in calves and replacement heifers in the US It indicates that young calves can be infected with hemoplasmas, but the rate of infection is low. The likelihood of infection increases as animals age, with a notable rise in the proportion of infected heifers occurring by 8 mo old and the prevalence eventually reaching nearly 100% of infection in older animals. Once infected, heifers appear to remain chronic carriers. Hemoplasma infection alone does not usually lead to the development of clinical signs and most of the animals remain apparently healthy.

TNF blockers alone and associated with Benznidazole impact in vitro cytokine dynamics in chronic Chagas disease.

Studies involving the immune response in Chagas disease suggest an imbalance in the immune response of symptomatic patients, with an inflammatory profile dominating in Chagas heart disease, mainly by tumour necrosis factor (TNF). TNF is considered a key cytokine in immunopathology in chronic carriers in several processes during the immune response. Our work aimed to evaluate regulatory (interleukin [IL]-4 and IL-10) and inflammatory (TNF, interferon-gamma [IFN-γ], IL-2 and IL-6) cytokines in peripheral blood mononuclear cells culture supernatants. of affected patients with undetermined clinical forms-IND (n = 13) mild heart form-CARD1 (n = 13) and severe cardiac form-CARD2 (n = 16), treated in vitro with two TNF blockers, Adalimumab (ADA) and Etanercept (ETA) alone or in association with Benznidazole (BZ). The results indicate that ADA was more competent in blocking TNF (compared to ETA) in all groups but with much lower levels in the CARD2 group. ETA statistically decreased TNF levels only in the CARD2 group. IFN-γ increased in the CARD2 group after treatment with ETA relative to ADA. IL-4 had its levels decreased when treated by both drugs. IL-2 was detected in cells from CARD2 carriers compared to the NEG group after treatment with both drugs. The association with BZ decreased levels of IL-2/TNF and increased IL-4. These data reinforce the participation of TNF in severe Chagas heart disease and bring perspectives on using these blockers in the immunological treatment of Chagas disease since the use of BZ is extremely limited in these patients.

Chronic Epstein-Barr viral load carriage after pediatric organ transplantation.

Epstein-Barr virus (EBV) infection and EBV-associated post-transplant lymphoproliferative disorder (EBV/PTLD) is one of the most devastating complications occurring in pediatric solid organ transplant (SOT) recipients. Observations of SOT recipients undergoing serial EBV monitoring to inform reduction of immune suppression to prevent EBV-/PTLD has identified patients who maintain chronic high EBV load (CHL) in their blood. The CHL carrier state has been seen more commonly in pediatric compared to adult transplant recipients. Some but not all CHL may progress to EBV/PTLD. However, little is known regarding the biology of this CHL carrier state and the optimal clinical approach to CHL has not been established. This review summarizes the current knowledge and evidence of chronic high EBV load and introduces commonly adopted approaches from experts in this field.

Asymptomatic Plasmodium falciparum carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia.

Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear. In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria. Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p < 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season. Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.

Prevalence of hepatitis B virus infection and its associated factors among students in N'Djamena, Chad.

Infection by hepatitis B virus (HBV) is a major issue in public health. The prevalence of HBV in Chad is 12.4%, all age groups considered. Here, we aimed to determine the prevalence of HBV and its associated factors among university students in N'Djamena, the country's capital. A cross-sectional survey of students at either the University of N'djamena or Emi Koussi University was conducted from 3 to 23 July 2021. All participating students provided signed, informed consent and were included in the study consecutively. Blood samples were collected, and serum tested for hepatitis B surface antigen (HBsAg) using the Determine HBsAg rapid test kit, with confirmation of positive tests on an Abbott Architect i1000SR analyzer. Descriptive analysis and logistic regression were used to determine associations between the outcome variable and independent/covariate variables. A total of 457 students with a median age of 24 years were included across different faculties. The prevalence of HBV infection was 14.87% (68/457). Most students (75%) were aged 25 years or less. Unprotected sex was reported by 64.9% of the students and multiple sexual partners by 53.6%. Furthermore, 45.7% of them reported having no knowledge of hepatitis B. Having an HBsAg-positive mother (AOR: 2.11), having a history of transcutaneous medical procedures (AOR: 2.97) and living with a family (AOR: 4.63) were significantly associated with HBV status. Age ≥26 years appeared as a protective factor (AOR = 0.41). Our study detected a high, 14.87% prevalence of HBV infection among students in N'djamena, Chad, and shed light on its associated factors. HBV prevention strategies should include raising awareness among students, making full hepatitis vaccination mandatory before children begin school, promoting mass screening to identify and treat chronic HBV carriers and reduce transmission, and reducing the cost of vaccination.

Detecting residual chronic Salmonella Typhi carriers on the road to typhoid elimination in Santiago, Chile, 2017-2019.

In Santiago, Chile, where typhoid had been hyperendemic (1977-1991), we investigated whether residual chronic carriers could be detected among household contacts of non-travel-related typhoid cases occurring 2017-2019. Culture-confirmed cases were classified as "autochthonous" (domestically-acquired) versus "travel/immigration-related". Household contacts of cases had stool cultures and serum Vi antibody measurements to detect chronic Salmonella Typhi carriers. Whole genome sequences of acute cases and their epidemiologically-linked chronic carrier isolates were compared. Five of 16 autochthonous typhoid cases (31.3%) were linked to four chronic carriers in case households; two cases (onsets 23 months apart) were linked to the same carrier. Carriers were women aged 69-79 years with gallbladder dysfunction and Typhi fecal excretion; three had highly elevated serum anti-Vi titers. Genomic analyses revealed close identity (≤11 core genome SNP [Single Nucleotide Polymorphism] differences) between case and epidemiologically-linked carrier isolates; all were genotypes prevalent in 1980s Santiago. A cluster of four additional autochthonous cases un-linked to a carrier was identified based on genomic identity (0-1 SNPs). Travel/immigration isolate genotypes were typical for the countries of travel/immigration. Although autochthonous typhoid cases in Santiago are currently rare, 5/16 such cases (31.3%) were linked to elderly chronic carriers identified among household contacts of cases.

Defying the odds: Determinants of the antimicrobial response of Salmonella Typhi and their interplay.

Salmonella Typhi, the invasive serovar of S. enterica subspecies enterica, causes typhoid fever in healthy human hosts. The emergence of antibiotic-resistant strains has consistently challenged the successful treatment of typhoid fever with conventional antibiotics. Antimicrobial resistance (AMR) in Salmonella is acquired either by mutations in the genomic DNA or by acquiring extrachromosomal DNA via horizontal gene transfer. In addition, Salmonella can form a subpopulation of antibiotic persistent (AP) cells that can survive at high concentrations of antibiotics. These have reduced the effectiveness of the first and second lines of antibiotics used to treat Salmonella infection. The recurrent and chronic carriage of S. Typhi in human hosts further complicates the treatment process, as a remarkable shift in the immune response from pro-inflammatory Th1 to anti-inflammatory Th2 is observed. Recent studies have also highlighted the overlap between AP, persistent infection (PI) and AMR. These incidents have revealed several areas of research. In this review, we have put forward a timeline for the evolution of antibiotic resistance in Salmonella and discussed the different mechanisms of the same availed by the pathogen at the genotypic and phenotypic levels. Further, we have presented a detailed discussion on Salmonella antibiotic persistence (AP), PI, the host and bacterial virulence factors that can influence PI, and how both AP and PI can lead to AMR.

Seroprevalence of Viral Hepatitis C on Donations of Blood at Moulay Ismail Military Hospital in Meknes

Introduction: Hepatitis C is an infection with hepatocellular tropism, transmitted by the hepatitis C virus via fecal-oral, parenteral or mother-to-child transmission. Her active chronic carriage may be the cause of cirrhosis. Objective: The purpose of this study was to determine the seroprevalence of HCV in blood donations collected at the Moulay Ismail military hospital in Meknes in order to protect the recipients. Material and Methods: This is a retrospective study of 8639 military blood donors. All donors have gone through a pre-screening stage involving an anamnesis and pre-donation clinical examination associated with a biological screening performed by the 4th generation recombinant ELISA and confirmed on the Abott Architect system. Result: The study is focused on 8639 blood donors, mostly male, with extreme ages of 18 to 56 years. We found an HCV seroprevalence of 0.17%. No case of co-infection has been recorded. Discussion and conclusion: The HCV seroprevalence rate in our series remains relatively low in comparison with the data of the literature, this could be related to the campaigns of sensitization, to the exposure of the preventive measures for the military population as well as to the success of the pre-selection stage at Moulay Ismail hospital in Meknes.

Differential responses of monocyte-derived macrophages from Theileria orientalis infected carrier cattle to Pasteruella multocida B:2 infection and latex beads: A preliminary study

This study aims to evaluate the responses of peripheral blood monocyte-derived macrophages (PBMDMs) from Theileria orientalis carrier cattle following exposure to Pasteruella multocida B:2 (PM B:2) and latex beads. Twenty-six male crossbred Kedah-Kelantan (KK) cattle were sampled for this study and quantitative PCR (qPCR) was employed in the detection of T. orientalis MPSP gene. Bactericidal assay using a 10:1 multiplicity of infection was performed to measure the phagocytosis and intracellular killing of PM B:2 by PBMDMs. The cell cultures were inoculated with 107 cfu/mL of PM B:2 and incubated in a humidified incubator. The absence of clinical signs, previous history of T. orientalis infection and an MPSP gene copy number below 15,000 GC/μL suggest that the cattle were asymptomatic chronic carriers. A non-significant phagocytic and mean cell death rates were observed in the PBMDMs of T. orientalis positive cattle relative to clinically healthy cattle (CHC) (p > 0.05). The PBMDMs of T. orientalis positive cattle had the lowest mean rate of intracellular killing relative to the CHC at the 30th minute post-infection only (p < 0.05). Exposure to latex beads caused an increase in the appearance of multinucleated macrophages following incubation of PBMDMs from T. orientalis positive cattle. Furthermore, the phagocytic index of PBMDMs of T. orientalis positive cattle were low or poor compared to that of CHC (p = 0.000). Therefore, our findings suggest that PBMDMs from cattle with chronic T. orientalis infection can efficiently phagocytise and kill PM: B2 but exhibited poor phagocytosis ability for foreign bodies despite appearance of multinucleated macrophages.