Schistosomiasis, soil transmitted helminthiasis, and malaria co-infections among women of reproductive age in rural communities of Kwale County, coastal Kenya.

BACKGROUND: Schistosoma haematobium, soil transmitted helminthes (STH), and malaria lead to a double burden in pregnancy that eventually leads to poor immunity, increased susceptibility to other infections, and poor pregnancy outcomes. Many studies have been carried out on pre-school and school aged children but very little has been done among the at risk adult population including women of reproductive age (WRA). Our current study sought to establish the risk factors and burden of co-infection with S. haematobium, STH, and Plasmodium sp. among WRA in Kwale County, Coastal Kenya. METHODS: A total of 534 WRA between the ages of 15-50 were enrolled in this cross-sectional study from four villages; Bilashaka and Mwaluphamba in Matuga sub-County, and Mwachinga and Dumbule in Kinango sub-County. Socio-demographic information was collected using a pre-tested standardized questionnaire. Parasitological examination was done using urine filtration method for Schistosoma haematobium, Kato Katz for STH (Ascaris lumbricoides, Hookworm, Trichuris trichiura), and standard slide microscopy for Plasmodium sp. Statistical analyses were carried out using STATA version 15.1. RESULTS: The overall prevalence of S. haematobium was 3.8% (95% CI: 2.6-5.4) while that for malaria was 4.9% (95% CI: 2.0-11.7). The prevalence of STH was 5.6% (95% CI: 2.8-11.3) with overall prevalence of 5.3% (95% CI: 2.5-10.9) for hookworm and 0.6% (95% CI: 0.2-1.9) for T. trichiura. The occurrence of co-infection was low and was recorded between S. haematobium and P. falciparum (0.6%), followed by S. haematobium and STH (0.4%). Among pregnant women, 2.6% had co-infection with S. haematobium and P. falciparum. Only 1.3% had co-infection with S. haematobium and hookworm or T. trichiura. Among non-pregnant women, co-infection with S. haematobium and P. falciparum was 0.2%. Similarly, co-infection with S. haematobium and hookworm or T. trichiura was 0.2%. Bed net ownership and usage among pregnant women was 87.8 and 96.6%, respectively. 66.3% of the women reported using improved water sources for drinking while 78.1% reported using improved sanitation facilities. CONCLUSION: The use of improved WASH activities might have contributed to the low prevalence of STHs and S. haematobium infections. Further, bed net ownership and usage might have resulted in the low prevalence of Plasmodium sp. infections observed.

Prevalence and risk factors associated with asymptomatic Plasmodium falciparum infection and anemia among pregnant women at the first antenatal care visit: A hospital based cross-sectional study in Kwale County, Kenya.

BACKGROUND: Prevalence of Prevalence of malaria in pregnancy (MiP) in Kenya ranges from 9% to 18%. We estimated the prevalence and factors associated with MiP and anemia in pregnancy (AiP) among asymptomatic women attending antenatal care (ANC) visits. METHODS: We performed a cross-sectional study among pregnant women attending ANC at Msambweni Hospital, between September 2018 and February 2019. Data was collected and analyzed in Epi Info 7. Descriptive statistics were calculated and we compared MiP and AiP in asymptomatic cases to those without either condition. Adjusted prevalence Odds odds ratios (aPOR) and 95% confidence intervals (CI) were calculated to identify factors associated with asymptomatic MiP and AiP. RESULTS: We interviewed 308 study participants; their mean age was 26.6 years (± 5.8 years), mean gestational age was 21.8 weeks (± 6.0 weeks), 173 (56.2%) were in the second trimester of pregnancy, 12.9% (40/308) had MiP and 62.7% had AiP. Women who were aged ≤ 20 years had three times likelihood of developing MiP (aPOR = 3.1 Cl: 1.3-7.35) compared to those aged >20 years old. The likelihood of AiP was higher among women with gestational age ≥ 16 weeks (aPOR = 3.9, CI: 1.96-7.75), those with parasitemia (aPOR = 3.3, 95% CI: 1.31-8.18), those in third trimester of pregnancy (aPOR = 2.6, 95% CI:1.40-4.96) and those who reported eating soil as a craving during pregnancy (aPOR = 1.9, 95%CI:1.15-3.29). CONCLUSIONS: Majority of the women had asymptomatic MiP and AiP. MiP was observed in one tenth of all study participants. Asymptomatic MiP was associated with younger age while AiP was associated with gestational age parasitemia, and soil consumption as a craving during pregnancy.

IL-21 Augments Rapamycin in Expansion of Alpha Fetoprotein Antigen Specific Stem-Cell-like Memory T Cells in vitro.

INTRODUCTION: Alloreactive tumor specific T cells are important arsenals of the adaptive immune system in the fight against tumors. However, stem cell-like memory T cells (Tscm) provide the key to effective elimination of tumor cells. Methods for generating these T cell subsets already exist. However, they could be made more efficient. Further, they are expensive and unattainable to the resource poor laboratories. In this regard, we are hereby describing a novel in vitro allogeneic co-culture method for raising allo-restricted tumor specific Tscm cells that we developed. METHODS: We started by obtaining PBLs that screened negative for HLA-A2 molecules from healthy donors followed by co-culture with T2/AFP cells to generate AFP peptide specific tumor-reactive T cells. Controls, IL-21 and/or rapamycin were applied to samples in 24 well plates. Samples were harvested and stained with anti-human CD3, CD8, CD44, CD62L, and HLA-A2/AFP dimer followed by flow cytometry analysis. Cell viability was measured by Trypan blue exclusion assay. One Way ANOVA and independent t test were used to compare the mean differences among and between groups where P values less than 0.05 were considered significant. RESULTS: Our results show that rapamycin arrests the differentiation of, and expands AFP specific Tscm cells. Further, the expansion of Tscm cells is augmented in the presence of IL-21. CONCLUSION: IL-21 and Rapamycin can be used concurrently to raise and maintain antigen specific Tscm cells in vitro for purposes of augmenting immunotherapy strategies against cancers.

CD8(low)CD28(-) T Cells: A Human CD8 T-Suppressor Subpopulation With Alloantigen Specificity Induced by Soluble HLA-A2 Dimer In Vitro.

CD8(+) suppressor T cells have been demonstrated to provide protection of allografts from rejection. We previously reported that soluble peptide/HLA-A2 dimer shows peptide-specific inhibitory effects on alloresponse in a coculture of peptide-pulsed T2 cells with HLA-A2 negative lymphocytes in vitro. Here we found a subset of CD8(low)CD28(-) T cells that was induced in the dimer-treated coculture. Importantly, this population showed hyporesponsiveness to the alloantigen restimulation as well as alloantigen-specific suppression on alloreactive T cells in a cell-cell contact-dependent fashion. The suppressive mechanisms of CD8(low)CD28(-) T cells involved an elevated expression of membrane-bound TGF-ß1, but not Foxp3, CTLA-4, or IL-10. Furthermore, an overrepresention of CD8(low)CD28(-) T cells was observed in the patients after allogeneic platelet transfusion and positively correlated with the elevated concentrations of plasma HLA class I antigens. Our findings demonstrated that soluble HLA-A2 dimer could efficiently induce the tolerant CD8(low)CD28(-) T cells with alloantigen-specific suppression on alloreactive T cells. This study might provide a new strategy for preparation of donor-specific suppressor T cells and represent an attractive alternative for induction of allograft tolerance.

L-ficolin binds to the glycoproteins hemagglutinin and neuraminidase and inhibits influenza A virus infection both in vitro and in vivo.

L-ficolin, one of the complement lectins found in human serum, is a novel pattern recognition molecule that can specifically bind to microbial carbohydrates, thereby activating the lectin complement pathway and mounting a protective innate immune response. However, little is known about the role of L-ficolin during viral infections in vivo. In the present study, we used a mouse model of influenza A virus infection to demonstrate that the administration of exogenous L-ficolin or ficolin A (FCNA - an L-ficolin-like molecule in the mouse) is protective against the virus. Furthermore, FCNA-null mice have a greatly increased susceptibility to infection with the influenza A virus. Moreover, we found recombinant human L-ficolin inhibited influenza A virus entry into Madin-Darby canine kidney cells. More importantly, L-ficolin can recognize and bind hemagglutinin (HA) and neuraminidase (NA) glycoproteins and different subtypes of influenza A virus, and these interactions can be competitively inhibited by N-acetyl-D-glucosamine. In addition, the binding of L-ficolin and FCNA may lead to the activation of the lectin complement pathway. To our knowledge, this is the first report demonstrating that L-ficolin can block influenza virus infections both in vitro and in vivo using FCNA-knockout mice, possibly by interacting with the carbohydrates of HA and NA. Therefore, these data may provide new immunotherapeutic strategies based on the innate immune molecule L-ficolin against the influenza A virus.

Salmonella typhi: from a human pathogen to a vaccine vector.

Salmonella (S.) typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector.

Type IVB pilus operon promoter controlling expression of the severe acute respiratory syndrome-associated coronavirus nucleocapsid gene in Salmonella enterica Serovar Typhi elicits full immune response by intranasal vaccination.

Attenuated Salmonella enterica serovar Typhi strains have been considered to be attractive as potential live oral delivery vector vaccines because of their ability to elicit the full array of immune responses in humans. In this study, we constructed an attenuated S. enterica serovar Typhi strain stably expressing conserved nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) by integrating the N gene into the pilV gene, which was under the control of the type IVB pilus operon promoter in S. enterica serovar Typhi. BALB/c mice were immunized with this recombinant strain through different routes: intranasally, orogastrically, intraperitoneally, and intravenously. Results showed that the intranasal route caused the highest production of specific immunoglobulin G (IgG), IgG2a, and secretory IgA, where IgG2a was imprinted as a Th1 cell bias. Moreover, this recombinant live vaccine induced significantly high levels of specific cytotoxic T-lymphocyte activities and increased gamma interferon-producing T cells compared with the parental strain. Our work provides insights into how the type IVB pilus operon promoter controlling SARS-CoV N gene expression in Salmonella might be attractive for a live-vector vaccine against SRAS-CoV infection, for it could induce mucosal, humoral, and cellular immune responses. Our work also indicates that the type IVB pilus operon promoter controlling foreign gene expression in Salmonella can elicit full immune responses by intranasal vaccination.