ABSTRACT
Helicobacter pylori infection is involved in development of diverse gastro-pathologies. Our aim is to investigate potential signature of cytokines-chemokine levels (IL-17A, IL-1ß, and CXCL-8) in H. pylori-infected patients and their impact on immune response in both corpus and antrum. Multivariate level analysis with machine learning model were carried out using cytokines/chemokine levels of infected Moroccan patients. In addition, Geo dataset was used to run enrichment analysis following CXCL-8 upregulation. Our analysis showed that combination of cytokines-chemokine levels allowed prediction of positive H. pylori density score with <5% of miss-classification error, with fundus CXCL-8 being the most important variable for this discrimination. Furthermore, CXCL-8 dependent expression profile was mainly associated to IL6/JAK/STAT3 signaling in the antrum, interferons alpha and gamma responses in the corpus and commonly induced transcriptional /proliferative activities. To conclude, CXCL-8 level might be a signature of Moroccan H. pylori-infected patients and an inducer of regional-dependent immune response at the gastric level. Larger trials must be carried out to validate the relevance of these results for diverse populations.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Cytokines/metabolism , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Helicobacter Infections/metabolism , Helicobacter Infections/pathology , Helicobacter pylori/metabolism , Immunity , Stomach/pathologyABSTRACT
The COVID-19 pandemic has caused millions of deaths and has resulted in disastrous societal and economic impacts worldwide. During SARS-CoV-2 infection, abnormal levels of pro-inflammatory cytokines have been observed and were associated to the severity of the disease. Type I (-α/ß) and Type III (IFN-λ) interferons are family members of cytokines that play an important role in fighting viral replication during the early phases of infection. The location and timing of the IFNs production have been shown to be decisive for the COVID-19 outcome. Despite the effectiveness of COVID-19 vaccines and with the emergence of new SARS-CoV-2 variants, a better understanding of the involvement of IFNs as players in antiviral immunity in the COVID-19 pathophysiology is necessary to implement additional potent prophylactic and/or therapeutic approaches. In this study, we investigated the role of type I and III IFN in COVID-19 pathophysiology. We first analyzed the IFN-α, IFN-ß and IFN- λ mRNA expression in nasopharyngeal swabs and blood samples from Moroccan patients infected with SARS-CoV-2 and secondly correlated these IFNs expressions with COVID-19 clinical and biological parameters. Our results showed that in the upper airways of patients with mild, non-severe, or severe COVID-19 manifestations, the IFN- α, - ß and - λ are expressed in the same manner as in controls. However, in blood samples their expression was downregulated in all groups. Univariate linear models with interferons as predictors to evaluate clinical-biological parameters highlighted that the main clinical-biological relations were found when testing: FiO2, Lymphocyte values and virus load. Furthermore, the multivariate models confirmed that quantifications of interferons during COVID-19 are good biological markers for tracking COVID-19 pathophysiology.
Subject(s)
COVID-19 , Interferon Type I , Humans , Interferons , COVID-19 Vaccines , Pandemics , SARS-CoV-2 , Antiviral Agents , Cytokines , Interferon-alpha , Interferon LambdaABSTRACT
Cutaneous leishmaniasis is an infectious disease, considered as a major public health problem in different regions of the world. The current treatments are limited due to their toxicity and treatment failures, which have increased the search for new substances of natural origin to control this infection. Capparis spinosa is an important medicinal plant, rich in biochemical compounds with a broad range of activities including antimicrobial effects. Nevertheless, more investigations are still needed to determine its effect on Leishmania parasites. This study aimed to evaluate the effect of C. spinosa' extracts on Leishmania major promastigotes and amastigotes growth as well as on L-arginine metabolic pathways, especially the production of leishmanicidal molecules such as nitric oxide. Our results showed that C. spinosa' methanolic and aqueous extracts contained polyphenols and flavonoids at different concentrations. The methanolic extract of C. spinosa, compared to the aqueous extract, showed significantly higher amounts of total polyphenols (21.23 ± 1.08) mg GAE/g of dw (P < 0.05), as well as a higher antioxidant activity evaluated respectively by Reducing Power and DPPH (EC50: 0.31 ± 0.02 and 7.69 ± 1.28) mg/ml. Both extracts significantly inhibited L. major promastigotes and intra-macrophagic amastigotes growth in vitro in a dose-dependent manner (P < 0.001) and induced NO production not only in Leishmania-infected macrophages but also in uninfected macrophages, without showing any cytotoxicity in vitro. Furthermore, in silico docking studies showed that C. spinosa compounds identified by RP-HPLC exhibited inhibitory activity against the arginase enzyme. The leishmanicidal effect of C. spinosa may be due to its phenolic content and its mechanism of action may be mediated by an increase in NO production and by the inhibition of arginase enzyme in silico. These findings support the hypothesis that C. spinosa might be a valuable source of new biomolecules for leishmaniasis treatment.
Subject(s)
Capparis , Leishmania major , Nitric Oxide/metabolism , Arginase/metabolism , Capparis/chemistry , Capparis/metabolism , Flavonoids/pharmacology , Polyphenols/pharmacology , Plant Extracts/pharmacology , Methanol/pharmacologyABSTRACT
Type 1 diabetes is characterized by insulin deficiency due to the destruction of pancreatic ß cells, leading to hyperglycemia, which in turn induces vascular complications. In the current study, we investigated the effect of intraperitoneal administration of clove essential oil (CEO: 20 mg/kg body weight) on certain oxidative stress and glucose metabolism enzymes, as well as the expression of proinflammatory mediators. Administration of CEO to diabetic rats showed a significant decline in blood glucose levels, total cholesterol, and xanthine oxidase, compared to the streptozotocin group. Furthermore, these treated rats elicited a notable attenuation in the levels of lipid peroxides, and thiols groups in both liver and brain tissues. The activities of antioxidant and metabolic enzymes were reverted to normality in diabetic upon CEO administration. In addition to its protective effects on red blood cell hemolysis, CEO is a potent α-amylase inhibitor with an IC50 =298.0±2.75â µg/mL. Also, treatment of diabetic rats with CEO significantly reduced the iNOS expression in the spleen. Our data showed that CEO has potential beneficial effects on diabetes, which can possibly prevent the pathogenesis of diabetic micro- and macrovascular complications.
Subject(s)
Diabetes Mellitus, Experimental , Oils, Volatile , Syzygium , Rats , Animals , Clove Oil/pharmacology , Clove Oil/therapeutic use , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Inflammation Mediators/metabolism , Inflammation Mediators/pharmacology , Oxidative Stress , Antioxidants/metabolism , Streptozocin , Hypoglycemic Agents/pharmacologyABSTRACT
Platelets play a major role in the processes of primary hemostasis and pathological inflammation-induced thrombosis. In the mid-2000s, several studies expanded the role of these particular cells, placing them in the "immune continuum" and thus changing the understanding of their function in both innate and adaptive immune responses. Among the many receptors they express on their surface, platelets express Toll-Like Receptors (TLRs), key receptors in the inflammatory cell-cell reaction and in the interaction between innate and adaptive immunity. In response to an infectious stimulus, platelets will become differentially activated. Platelet activation is variable depending on whether platelets are activated by a hemostatic or pathogen stimulus. This review highlights the role that platelets play in platelet modulation count and adaptative immune response during viral infection.
Subject(s)
Blood Platelets , Virus Diseases , Humans , Platelet Activation , Inflammation , Immune System , Immunity, InnateABSTRACT
Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease caused by Protozoa of the genus Leishmania. Clinical manifestations of this disease are the result of a complex interplay of diverse factors, including the genetic background and the immune status of the host. Understanding the impact of these factors on the CL pathology may provide new targets to manage the infection and improve clinical outcome. The NLRP3 inflammasome, an innate immune complex of several cell types, seems to be involved in the CL physiopathology. Current studies of its role show contradictory effects of this complex on the evolution of Leishmania infection in mice and humans. In this review, we discuss the data regarding different roles of the NLRP3 inflammasome in murine and human CL.
Subject(s)
Inflammasomes/metabolism , Leishmaniasis, Cutaneous/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Animals , Humans , Leishmania/pathogenicityABSTRACT
The outbreak of coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has emerged in China in December 2019 and rapidly spread to more than 196 countries worldwide. The physiopathology of human SARS-CoV-2 has not been completely understood, but its pathogenesis has been linked to a disproportionate response of the immune system. Just as described for SARS and MERS, an uncontrolled systemic inflammatory response, known as cytokine release syndrome (CRS) was observed in severe COVID-19 patients. It results from the release by immune and non-immune effector cells of substantial amounts of pro-inflammatory cytokines and appears to contribute to SARS-CoV-2 pulmonary inflammation and extensive lung damage. In addition, hyper-coagulation and thrombosis resulted from the important release of pro-inflammatory cytokines contribute to the lethality of subjects severely infected with SARS-CoV-2. It is therefore essential to have a deep understanding of the various cytokines involved in this exacerbated immune response, and that could be targeted by potential immunological treatments. The aim of this review was to gather the current knowledge about the role of pro-inflammatory cytokines, namely IL-1ß, IL-6, IL-8, IL-17 and TNFα in SARS-CoV-2 CRS, the probable causes and clinical outcomes of this phenomenon in severe cases of COVID-19.
Subject(s)
COVID-19/pathology , Cytokine Release Syndrome/pathology , Cytokines/blood , SARS-CoV-2/immunology , Cytokines/immunology , Humans , Macrophage Activation/immunology , Thrombosis/pathologyABSTRACT
INTRODUCTION: Helicobacter pylori induces acute gastritis that can progress to serious diseases such as gastric cancer. H. pylori interacts with host cells within the gastric mucosa, resulting in activation of multiple innate immune signalling pathways, leading to pro-inflammatory cytokines production and immune cells recruitment. Various studies have shown that there are ethnic- and population-related differences in the expression of these cytokines. Although the H. pylori infection is a major public health problem in Morocco, to our knowledge, no study has been carried out in gastric cytokine expression from H. pylori-infected Moroccan patients. Thus we aimed to (i) determine the IL-1ß, IL-8 and IL-17A gene expression in gastric biopsies from Moroccan patients infected with H. pylori, and (ii) to determine the cytokine signature of each pathological stages associated with this infection. MATERIAL AND METHODS: 71 patients with epigastralgic pain were included in this study. The H. pylori detection on gastric biopsies was performed by histopathological and PCR analysis. The IL-1ß, IL-8 and IL-17A mRNA expression in the antrun and fundus biopsies was performed by RT-qPCR. RESULTS: The histopathological and PCR analyses revealed that 87.32% of the patients were infected with H. pylori. IL-1ß mRNA expression was significantly lower in the antral mucosa of H. pylori-infected patients (pâ¯=â¯0.0038) than in the uninfected while there was no significant difference in the expression of IL-8 and IL-17A mRNA. The expression of the three cytokines was higher in the fundic mucosa of H. pylori-infected patients than in the uninfected patients, but only IL-8 and IL-17A expression reached statistical significance (pâ¯=â¯0.042 and pâ¯=â¯0.0179 respectively). Furthermore, the multivariate predictive analysis highlighted a cytokine signature that may predict metaplasia during the infection progression that involves a specific down-regulation of IL17A and an up-regulation of IL1ß in antral and fundic metaplasia respectively.
Subject(s)
Gastritis/pathology , Helicobacter Infections/pathology , Helicobacter pylori/immunology , Interleukin-17/analysis , Interleukin-1beta/analysis , Interleukin-8/analysis , Adult , Female , Gastric Mucosa/immunology , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/diagnosis , Gastritis/microbiology , Helicobacter Infections/diagnosis , Humans , Male , Middle Aged , Morocco , Signal Transduction/immunology , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathologyABSTRACT
Recent studies have shown that in individuals who have received two doses of COVID-19 vaccine, the level of IgG antibodies decreased over time. In addition, the resurgence of the epidemic due to variants has led the authorities in several countries, including Morocco, to extend the third dose to the entire adult population. In this study, we included 43 healthcare workers (HCWs) who were vaccinated with three doses. They were vaccinated with ChAdOx1 nCoV-19 for the first two doses and with BNT 162b2 or BBIBP-CorV vaccine for the third dose. Humoral response was assessed on the day of injection of the third dose of vaccine and one month after the third dose by measuring anti-receptor-binding domain (RBD) IgG levels. Seven months after the second dose, the median titer of anti-RBD IgG was higher in the group with a history of SARS-CoV-2 infection than in the group with no history of infection (1038 AU/mL vs. 76.05 AU/mL, respectively, p = 0.003). One month after the third dose, a significant increase in median level of anti-RBD in both groups was observed: from 76.05 AU/mL to 6127 AU/mL in the group with no history of infection and from 1038 AU/mL to 14,412 AU/mL in the group with history of infection. Notably, the BNT 162b2 vaccine elicits a high titer of anti-RBD antibody compared to the BBIBP-CorV vaccine. Median antibody titers were 21,991 AU/mL and 3640 AU/mL for BNT 162b2 and BBIBP-CorV vaccines, respectively (p = 0.0002). 23% of HCWs were infected with SARS-CoV-2 within the first two months after the third dose injection. However, all these patients developed mild symptoms and tested negative by RT-qPCR between 10 and 15 days after the onset of symptoms. Our findings support that the third dose of COVID-19 vaccine significantly improves the humoral response and protects against the severe disease.
ABSTRACT
Coronavirus 2019 (COVID-19) is a global health threat. The kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be assessed, as the long-term duration of these immunoglobulins remains largely controversial. The aim of this study was to assess the longitudinal dynamics of anti-SARS-CoV-2 antibodies against the nucleocapsid (N) protein and the receptor-binding domain (RBD) of the spike protein up to one year in a cohort of 190 COVID-19 patients. Between March and September 2021, we enrolled patients from two regional hospitals in Casablanca, Morocco. Blood samples were collected and analyzed for antibody levels. We used the commercial Euroimmun ELISA for the determination of anti-N IgM, the Abbott Architect™ SARS-CoV-2 IgG test for the detection of anti-RBD IgG, and an in-house kit for the assay of anti-N IgG and anti-N IgA. IgM and IgA antibodies were assessed 2-5, 9-12, 17-20 and 32-37 days after symptom onset. IgG antibodies were also assessed 60, 90, 120 and 360 days after symptom onset. One-third of patients developed IgM (32%), while two-thirds developed IgA (61%). One month of symptom onset, most patients developed IgG, with 97% and 93% positivity for anti-RBD IgG and anti-N IgG, respectively. The anti-RBD IgG positivity rate remained high up to one year of follow-up. However, the anti-N IgG positivity rate decreased over time, with only 41% of patients testing positive after one year's follow-up. IgG levels were significantly higher in older people (over 50 years) than in other study participants. We also found that patients who had received two doses of ChAdOx1 nCoV-19 vaccine prior to infection had a lower IgM response than unvaccinated patients. This difference was statistically significant two weeks after the onset of symptoms. We present the first study in Africa to measure the kinetics of antibody response (IgA, IgM and IgG) to SARS-CoV-2 over one year. Most participants remained seropositive for anti-RBD IgG after one year but showed a significant decline in antibody titers.
Subject(s)
COVID-19 , Humans , Aged , SARS-CoV-2 , Kinetics , Prospective Studies , ChAdOx1 nCoV-19 , Longitudinal Studies , Immunoglobulin M , Antibodies, Viral , Immunoglobulin G , MoroccoABSTRACT
Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious global public health problems. Characterization of the immune response, particularly antibodies to SARS-CoV-2, is important for establishing vaccine strategies. The purpose of this study was to evaluate longitudinally the kinetics of anti-SARS-CoV-2 antibodies against spike protein (S1) for up to 3 months in a cohort of 169 COVID-19 patients. We enrolled COVID-19 patients at two regional hospitals in Casablanca, Morocco, between March and September 2021. Blood samples were collected and N-specific IgM and S-specific IgG levels were measured by a commercial Euroimmun ELISA. IgM antibodies were assessed 2-5 (D00), 9-12 (D07), 17-20 (D15), and 32-37 (D30) days after symptom onset; IgG antibodies were assessed at these time points plus 60 (D60) and 90 (D90) days after symptom onset. We found that at 3 months after symptom onset, 79% of patients had detectable SARS-CoV-2-specific IgG antibodies, whereas their IgM seropositivity was 19% by 1 month after symptom onset. The IgM level decreased to 0.34 (interquartile range [IQR] 0.19-0.92) at 1 month after symptom onset, whereas the IgG level peaked at D30 (3.10; IQR 1.83-5.64) and remained almost stable at D90 (2.95; IQR 1.52-5.19). IgG levels were significantly higher in patients older than 50 years than in those younger than 50 at all follow-up time points (P < 0.05). Statistical analysis showed no significant difference in median anti-S1 antibody levels among infected patients based on gender or comorbidities. This study provides information on the longevity of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Immunoglobulin G , Antibodies, Viral , Immunoglobulin MABSTRACT
Genetic polymorphisms at the IL-1 cluster are associated with increased Helicobacter pylori (H. pylori)-associated disease risk in an ethnically dependent manner. Due to the corroborated role of IL-1ß in H. pylori infection progression, our aim is to depict the impact of IL1B rs1143627 and rs16944 as well as the IL1RN variable number of identical tandem repeats (VNTR) on the clinical and biological features of Moroccan H. pylori-infected patients. A total of 58 patients with epigastralgic pain were referred to the gastroenterology department for histopathological and clinical analysis. DNA extraction from antrum and fundus biopsies and PCR-RFLP were performed to detect polymorphisms. As a result, VNTR was significantly associated with IL-1ß antrum levels (p-value = 0.029), where the *1/*4 genotype showed a positive association with upregulated cytokine levels in the antrum and was clustered with H. pylori-infected patients' features and higher levels of IL-1ß in the antrum and fundus. Likewise, *1/*1 genotype carriers clustered with severe gastritis activity and H. pylori density scores along with low levels of IL-1ß in the antrum and fundus, while the *1/*2 genotype was clustered with non-infected-patient features and normal IL-1ß levels. In conclusion, VNTR might be an interesting predictor to identify patients at risk of developing H. pylori-associated pathologies.
ABSTRACT
BACKGROUND: Hepatitis A virus (HAV) is the common cause of acute hepatitis worldwide. Indeed, hepatitis A is endemic in developing countries such in Morocco and most residents are exposed in childhood. The characterisation of circulating strains of HAV remains crucial to understand the virological evolution and geo-temporal characteristics, which are essential for controlling infections and outbreaks. The purpose of the current study was the detection and characterisation of HAV strains circulating in Morocco by performing serological test, RT-PCR, sequencing and phylogenetic analysis. METHODS: In this cross-sectional study, 618 suspected acute hepatitis cases were examined by Architect HAV abIgM. Of the 162 positives, 64 underwent RNA extraction. None of the suspected cases was immune to HAV and none of them had received a blood transfusion. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and the VP1/VP3 capsid region of HAV were subjected to sequencing and phylogenetic analyses. RESULTS: HAV Acute infection rate was 26.2% [95% CI, 22.8-29.9], while viraemia reached 45% (29/64) after amplification of the VP3/VP1 region. Phylogenetic analysis of the VP1/2A segment revealed the presence of sub-genotypes IA and IB. Eighty-seven percent of the strains belonged to the subgenotype IA, while twelve percent to IB subgenotype. CONCLUSION: This first molecular study of acute hepatitis A in Morocco provided information about genetic diversity of HAV, revealing the co-circulating of only two subgenotypes (IA and IB). Notably, subgenotype IA was found to be the predominant subgenotype in Morocco.
Subject(s)
Hepatitis A virus , Hepatitis A , Humans , Hepatitis A/epidemiology , Cross-Sectional Studies , Phylogeny , Morocco/epidemiology , Hepatitis A virus/genetics , Genotype , Acute Disease , RNA, Viral/genetics , RNA, Viral/analysisABSTRACT
Cutaneous leishmaniasis (CL), a vector-borne parasitic disease caused by the Leishmania protozoan, is a serious public health problem in Morocco. The treatment of this disease is still based on pentavalent antimonials as the primary therapy, but these have associated side effects. Thus, the development of effective, risk-free alternative therapeutics based on natural compounds against leishmaniasis is urgent. Arginase, the key enzyme in the polyamine biosynthetic pathway, plays a critical role in leishmaniasis outcome and has emerged as a potential therapeutic target. The objective of this study was to test Cannabis sativa's phytochemical components (cannabinoids and terpenoids) through molecular docking against Leishmania and human arginase enzymes. Our results showed that delta-9-tetrahydrocannabinol (THC) possessed the best binding energies of -6.02 and -6.35 kcal/mol with active sites of Leishmania and human arginases, respectively. Delta-9-THC interacted with Leishmania arginase through various amino acids including His139 and His 154 and linked to human arginase via His 126. In addition to delta-9-THC, caryophyllene oxide and cannabidiol (CBD) also showed a good inhibition of Leishmania and human arginases, respectively. Overall, the studied components were found to inhibit both arginases active sites via hydrogen bonds and hydrophobic interactions. These components may serve as therapeutic agents or in co-administrated therapy for leishmaniasis.
ABSTRACT
The genus Leishmania comprises a wide range of species, some of which are pathogenic to humans and each of which has a different tissue preference, resulting in one of the three clinical forms of human leishmaniasis: visceral, cutaneous, or mucocutaneous. Although, all pathogenic species are deposited intradermally in the mammalian host upon an infectious sand fly bite, only the viscerotropic strains can leave the skin and reach the internal organs. We assume that Leishmania tissue tropism is not only the result of Leishmania genetic determinism but is also governed by the interaction of the parasite with different vectorial and human host elements. To shed light on these elements and key steps determining the course of the infection, we describe throughout this review the disease's progression from the early stages of infection taking place in the skin to the late stages succeeding in the parasite's visceral dissemination. Hence, we address the question of Leishmania tropism, through providing relevant hypotheses and answers gathered from the literature.
Subject(s)
Leishmania , Leishmaniasis, Cutaneous , Leishmaniasis, Visceral , Animals , Leishmania/genetics , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Visceral/parasitology , Mammals , Skin/pathology , TropismABSTRACT
Helicobacter pylori (H. pylori) infection is a causal factor of gastric cancer. Among the cytokines secreted during this infection, IL-1ß is highly associated with promotion and progression of gastric cancer. On the therapeutic front, eradication of H. pylori was thought to be efficient to restore gastric homeostasis. However, successful H. pylori eradication in patients with advanced stages (intestinal metaplasia) failed to diminish inflammation that is due to heightened Th17 response and elevated IL-1ß levels. In fact, association between these two components was established, suggesting that IL-1ß is a critical target in these cases. In this review, we will discuss the functional relevance of IL-1ß in advanced H. pylori infection and how its targeting may bring clinical benefit.
Helicobacter pylori (H. pylori) infection is a causal factor of gastric cancer. This disease is strongly associated to an inflammatory factor (interleukin 1ß). On the therapeutic front, eradication of H. pylori was thought to be efficient to restore gastric comfort. However, successful H. pylori eradication in patients with advanced stages of this infection failed to diminish inflammation, due to the inflammatory factor cited preciously, thereby exacerbating gastric tissue damage. In this review, we will discuss the functional relevance of IL-1ß in advanced H. pylori infection and how its targeting may bring clinical benefit.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Cytokines , Gastric Mucosa , Helicobacter Infections/complications , Helicobacter Infections/drug therapy , Humans , Interleukin-1beta , Stomach Neoplasms/drug therapy , Stomach Neoplasms/microbiologyABSTRACT
Data about the duration of antibodies after vaccination show that the protection against SARS-CoV-2 infection begins to decline over time. This study aims to determine anti-SARS-CoV-2 anti-S IgG levels in healthcare workers five months after the second vaccination dose. We collected samples from 82 participants who were fully vaccinated with ChAdOx1 nCoV-19 or BBIBP-CorV. We assessed anti-SARS-CoV-2 IgG antibodies using a Euroimmun ELISA and an Abbott Architect ™ SARS-CoV-2 IgG test. Of the 82 participants, 65.85% were seropositive for IgG using ELISA, and 86.59% were positive for IgG according to the Abbott Architect ™ test. Individuals vaccinated with the ChAdOx1 nCoV-19 vaccine had a median anti-S1 antibody level of 1.810 AU/mL [interquartile range (IQR), 1.080-3.7340] and 171.7 AU/mL [79.9-684.6] according to the Euroimmun ELISA and Abbott Architect test, respectively. These tests indicated that people vaccinated with BBIBP-CorV had a median anti-S1 antibody level of 1.840 AU/mL [0.810-2.960] and 126.7 AU/mL [54.9-474.3], respectively. Statistical analysis showed no significant difference between the positivity rates of the vaccinated individuals, either for gender or for age. In addition, we found no significant difference between the two vaccines. Our study provides information on the longevity of the anti-SARS-CoV-2 IgG antibodies in people at least five months after vaccination.
ABSTRACT
Cutaneous leishmaniasis (CL) occurring due to Leishmania tropica is a public health problem in Morocco. The distribution and incidence of this form of leishmaniasis have increased in an unusual way in the last decade, and the control measures put in place are struggling to slow down the epidemic. This study was designed to assess the impact of climatic and environmental factors on CL in L. tropica foci. The data collected included CL incidence and climatic and environmental factors across three Moroccan foci (Foum Jemaa, Imintanout, and Ouazzane) from 2000 to 2019. Statistical analyses were performed using the linear regression model. An association was found between the occurrence of CL in Imintanout and temperature and humidity (r2 = 0.6076, df = (1.18), p-value = 3.09 × 10-5; r2 = 0.6306, df = (1.18), p-value = 1.77 × 10-5). As a second objective of our study, we investigated the population structure of L.tropica in these three foci, using the nuclear marker internal transcribed spacer 1 (ITS1). Our results showed a low-to-medium level of geographic differentiation among the L.tropica populations using pairwise differentiation. Molecular diversity indices showed a high genetic diversity in Foum Jemaa and Imintanout; indeed, 29 polymorphic sites were identified, leading to the definition of 13 haplotypes. Tajima's D and Fu's F test statistics in all populations were not statistically significant, and consistent with a population at drift-mutation equilibrium. Further analysis, including additional DNA markers and a larger sample size, could provide a more complete perspective of L. tropica's population structure in these three regions. In addition, further research is needed to better understand the impact of climatic conditions on the transmission cycle of Leishmania, allowing both for the development of effective control measures, and for the development of a predictive model for this parasitosis.
ABSTRACT
In Morocco, leishmaniases are a major public health problem due to their genetic diversity and geographical distribution. Cutaneous leishmaniasis (CL) is an infectious disease caused by various species of Leishmania and transmitted typically by bite of phlebotomine sand flies. This study identifies sand fly fauna in Ibaraghen village, province of Azilal, which is a focus of CL, by combination of morphological and molecular methods (sequencing of COI gene, MALDI-TOF MS protein profiling). Nested-kDNA PCR was used to detect and identify Leishmania species within potential vector species. 432 CDC light traps were placed at different heights above ground level at four capture sites during a whole year. Traps at 1.5 m above the ground yielded capture of sand flies almost double compared to above ground level (29.33%), while the collection reached 55.09% when the traps were placed 2.5 m above ground. A total of 2,830 sand flies were collected, 2,213 unfed specimens were morphologically identified, 990 males (44.73%) and 1,223 females (55.26%) of 13 species; ten Phlebotomus species and three Sergentomyia species. Six species were analysed by MALDI-TOF MS protein profiling (4 Phlebotomus and 2 Sergentomiya species), and their identification was confirmed by COI sequencing. 1,375 unfed females were screened for the presence of Leishmania by nested-kDNA PCR in pools, 11/30 pools of P. sergenti showing a single band of 750 bp corresponding to L. tropica. Our results confirm the role of P. sergenti as a proven vector in Azilal focus of cutaneous leishmaniasis; however, the relative abundance of other species known as vectors of Leishmania species emphasizes the risk of introduction of L. infantum and L. major in this province. For the first time in Morocco, a combined approach to identify sand flies by both morphology and molecular methods based on DNA barcoding and MALDI-TOF MS protein profiling was applied.
Subject(s)
Leishmania , Leishmaniasis, Cutaneous , Phlebotomus , Psychodidae , Animals , DNA, Kinetoplast , Female , Insect Vectors , Leishmania/genetics , Leishmaniasis, Cutaneous/epidemiology , Leishmaniasis, Cutaneous/veterinary , Male , Morocco/epidemiology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/veterinaryABSTRACT
Polymorphonuclear neutrophils (PMNs) are the first phagocyte recruited and infected by Leishmania. They synthetize superoxide anions (O2-) under the control of the NADPH oxidase complex. In Morocco, Leishmania major and L. tropica are the main species responsible for cutaneous leishmaniasis (CL). The impact of these parasites on human PMN functions is still unclear. We evaluated the in vitro capacity of primary Moroccan strains of L. major and L. tropica to modulate PMN O2- production and p47phox phosphorylation status of the NADPH oxidase complex. PMNs were isolated from healthy blood donors, and their infection rate was measured by microscopy. O2- production was measured by superoxide dismutase-inhibitable reduction of cytochrome C. P47phox phosphorylation was analyzed by Western blot using specific antibodies against Ser328 and Ser345 sites. Whereas we did not observe any difference in PMN infectivity rate, our results indicated that only L. tropica promastigotes inhibited both fMLF- and PMA-mediated O2- production independently of p47phox phosphorylation. Leishmania soluble antigens (SLAs) from both species significantly inhibited O2- induced by fMLF or PMA. However, they only decreased PMA-induced p47phox phosphorylation. L. major and L. tropica modulated differently O2- production by human PMNs independently of p47phox phosphorylation. The inhibition of ROS production by L. tropica could be a mechanism of its survival within PMNs that might explain the reported chronic pathogenicity of L. tropica CL.