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Immune activation alters cellular and humoral responses to yellow fever 17D vaccine
Get PDFThis study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort.Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections.
This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort.
Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination.
Results. We showed that YF-17D–induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers.
Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D–neutralizing antibody titers after vaccination. Additionally, memory
T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination.
Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity.
Trial registration. Registration is not required for observational studies.
Funding. This study was funded by Canada’s Global Health Research Initiative, Defense Threat Reduction
Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United
States Agency for International Development
Mulongo Ni Namuunyu
Get PDFThe book narrates a story of domestic animals which loved to associate so much with the human beings.The book narrates a story of domestic animals which loved to associate so much with the human beings
Embuzi, Embwa ne Nte
Get PDFThis is a children's story book.This story is narrated to children on how animals like the Goat, Dog and Cow, which leave in our homes how they behave and relate to each other as well as to us the Human beings
Widespread Pyrethroid and DDT Resistance in the Major Malaria Vector Anopheles funestus in East Africa Is Driven by Metabolic Resistance Mechanisms
Get PDFThe study discusses Widespread Pyrethroid and DDT Resistance in the Major Malaria Vector Anopheles funestus in East Africa.Background
Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms.
Methodology/Principal Findings
Female An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin) and II (deltamethrin) pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance.
Conclusion
The extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management
Kumwikhoyo Kwe Khukhwiiyobula
Get PDFThis book narrates the story of enjoying leisure time as friendsThis book narrates the story of enjoying leisure time as friend
Knowledge of integrated management of childhood illnesses community and family practices (C-IMCI) and association with child undernutrition in Northern Uganda: a cross-sectional study
Get PDFThis study was done to address the prevalence of stunting and wasting and the association with the knowledge and practices of C-IMCI among caretakers in Gulu district, Northern Uganda.Background: Childhood undernutrition is a major challenge in Uganda with a prevalence of wasting and stunting at 5% and 33%, respectively. Community and family practices of the Integrated Management of Childhood Illnesses (C-IMCI) was introduced in sub-Saharan Africa early after the year 2000. C-IMCI was postulated to address major childhood morbidity and mortality challenges with nutrition as one of the outcomes. The association between knowledge patterns of C-IMCI and undernutrition has not been fully established especially in sub-Saharan Africa.
This study was done to address the prevalence of stunting and wasting and the association with the knowledge and practices of C-IMCI among caretakers in Gulu district, Northern Uganda.
Methods: This was a community-based cross-sectional study among 442 caretaker-child pairs. A standardized questionnaire was employed to assess the knowledge and practices of the C-IMCI among caretakers including four practices: breastfeeding, immunization, micronutrient supplementation and complementary feeding. Weight and height of children (6–60 months) were recorded. Wasting and stunting were defined as weight-for-height and height-for-age z-score, respectively, with a cut-off < −2 according to the World Health Organization growth standards. Logistic regression analysis reporting Odds Ratios (OR) with 95% confidence intervals (CI) was used to explore associations using SAS statistical software.
Results: The percentage of caretakers who had adequate knowledge on C-IMCI (basic knowledge within each pillar) was 13%. The prevalence of wasting and stunting were 8% and 21%, respectively. Caretakers’ lack of knowledge of C-IMCI was associated with both wasting (OR 24.5, 95% CI 4.2-143.3) and stunting (OR 4.0, 95% CI 1.3-12.4). Rural residence was also associated with both wasting (OR = 3.1, 95% CI 1.5-6.5) and stunting (OR = 1.7, 95% CI 1.0-2.7). Children younger than 25 months were more likely to be wasted (OR = 3.3, 95% CI 1.7-10.0).
Conclusion: We found a low level of overall knowledge of the C-IMCI of 13.3% (n = 59). There is also a high prevalence of childhood undernutrition in Northern Uganda. Caretakers’ limited knowledge of the C-IMCI and rural residence was associated with both wasting and stunting. Interventions to increase the knowledge of the C-IMCI practices among caretakers need reinforcement
Effectiveness of a Pre-treatment Snack on the Uptake of Mass Treatment for Schistosomiasis in Uganda: a cluster randomized trial
Get PDFThe the study was to examine the effectiveness of a pre-treatment snack on uptake of mass treatment.Background: School-based mass treatment with praziquantel is the cornerstone for schistosomiasis control in school-aged children. However, uptake of treatment among school-age children in Uganda is low in some areas. The objective of the study was to examine the effectiveness of a pre- treatment snack on uptake of mass treatment.
Methods and Findings:In a cluster randomized trial carried out in Jinja district, Uganda, 12 primary schools were randomized into two groups; one received education messages for schistosomiasis prevention for two months prior to mass treatment, while the other, in addition to the education messages, received a pre-treatment snack shortly before mass treatment. Four weeks after mass treatment, uptake of praziquantel was assessed among a random sample of 595 children in the snack schools and 689 children in the non-snack schools as the primary outcome. The occurrence of side effects and the prevalence and mean intensity of Schistosoma mansoni infection were determined as the secondary outcomes. Uptake of praziquantel was higher in the snack schools, 93.9% (95% CI 91.7%–95.7%), compared to that in the non-snack schools, 78.7% (95% CI 75.4%–81.7%) (p = 0.002). The occurrence of side effects was lower in the snack schools, 34.4% (95% CI 31.5%–39.8%), compared to that in the non-snack schools, 46.9% (95% CI 42.2%–50.7%) (p = 0.041). Prevalence and mean intensity of S. mansoni infection was lower in the snack schools, 1.3% (95% CI 0.6%–2.6%) and 38.3 eggs per gram of stool (epg) (95% CI 21.8–67.2), compared to that in the non-snack schools, 14.1% (95% CI 11.6%–16.9%) (p = 0.001) and 78.4 epg (95% CI 60.6–101.5) (p = 0.001), respectively.
Conclusions: Our results suggest that provision of a pre-treatment snack combined with education messages achieves a higher uptake compared to the education messages alone. The use a pre-treatment snack was associated with reduced side effects as well as decreased prevalence and intensity of S. mansoni infection
Namutosi Ni Butsuune Butaru
Get PDFThis book narrates a story of young girls who used to work together and one day they went to fetch fire wood near a river bank.This book narrates a story of young girls who used to work together and one day they went to fetch fire wood near a river bank
Eiŋaaŋa
Get PDFThis is a children's story book.This is a children's story narrating about the nature, different species of a wild birds and how they treat each other
Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression
Get PDFBioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: Mammalian-wide interspersed repeats (MIRs) are the most ancient family of transposable elements (TEs) in the human genome. The deep conservation of MIRs initially suggested the possibility that they had been exapted to play functional roles for their host genomes. MIRs also happen to be the only TEs whose presence in-and-around human genes is positively correlated to tissue-specific gene expression. Similar associations of enhancer prevalence within genes and tissue-specific expression, along with MIRs’ previous implication as providing regulatory sequences, suggested a possible link between MIRs and enhancers.
Results: To test the possibility that MIRs contribute functional enhancers to the human genome, we evaluated the relationship between MIRs and human tissue-specific enhancers in terms of genomic location, chromatin environment, regulatory function, and mechanistic attributes. This analysis revealed MIRs to be highly concentrated in enhancers of the K562 and HeLa human cell-types. Significantly more enhancers were found to be linked to MIRs than would be expected by chance, and putative MIR-derived enhancers are characterized by a chromatin environment highly similar to that of canonical enhancers. MIR-derived enhancers show strong associations with gene expression levels, tissue-specific gene expression and tissue-specific cellular functions, including a number of biological processes related to erythropoiesis. MIR-derived enhancers were found to be a rich source of transcription factor binding sites, underscoring one possible mechanistic route for the element sequences co-option as enhancers. There is also tentative evidence to suggest that MIR-enhancer function is related to the transcriptional activity of non-coding RNAs.
Conclusions: Taken together, these data reveal enhancers to be an important cis-regulatory platform from which MIRs can exercise a regulatory function in the human genome and help to resolve a long-standing conundrum as to the reason for MIRs’ deep evolutionary conservation