A Comparative Analysis of Distribution and Allocation of Covid-19 Vaccines Between Two Administrations

The pandemic of COVID-19 is a life-threatening disease that entailed all governments but especially the U.S government, to quickly prevent methods of spreading the virus while strategically putting in place a plan for biological testing for a vaccine for immunity. The purpose was to determine how effective the formulation of a COVID-19 vaccine and the distribution would impact the mortality with efficacy rates. Besides, this research paper underlines the principles for ethical and equitable distribution for mass immunization. A comparative analysis between the Trump Administration and the Biden Administration will be presented regarding the funding stream, distribution of vaccinations, and prioritization efforts against morbidity and mortality. We will determine how the resources and funding were utilized to provide Covid-19 vaccines rapidly enough for mass immunization

Predictors of recurrent TB in sputum smear and culture positive adults: a prospective cohort study

Objective: To explore simple inexpensive non-culture based predictors of recurrent pulmonary tuberculosis (PTB). Setting and study population: HIV-infected and uninfected adults with the first episode of smear positive, culture-confirmed pulmonary tuberculosis in a high tuberculosis burden country.Design: A nested prospective cohort study of participants with pulmonary tuberculosis (PTB) presenting to a hospital out-patient clinic.Results: A total of 630 TB culture confirmed participants were followed up for eighteen months of which 57 (9%) developed recurrent recurrent TB. On univariate analysis,4.7% low grade(1+) pre-treatment sputum smear participants developed recurrent tuberculosis Vs 8.8% with high grade(3+) smears (OR=0.31,95%CI: 0.10-0.93, p=0.037).On multivariate analysis:participants with extensive fibro-cavitation had a high risk of recurrent TB Vs minimal end of treatment fibro-cavitation (18%Vs12%,OR=2.3,95%CI:1.09-4.68, p=0.03).Weight gain with HIV infection was assosciated with a high risk of recurrentTB Vs weight gain with no HIV infection(18%Vs 6%,OR=6.8,95%CI:165-27.83,p=0.008) where as weight gain with a low pre-treatment high bacillary burden was assosciated with a low risk of recurrent TB Vs weight gain with a high pre-treatmentbacillary burden(6.5%Vs7.9%,OR=0.2,95%CI:0.05-0.79,p=0.02).Conclusion: Extensive end of treatment pulmonary fibro-cavitation, high pre-treatment bacillary burden with no weight gain and HIV infection could be reliable predictors of recurrent tuberculosis.Keywords: Grade, fibrosis, cavities, weight

Missed Study Visits and Subsequent HIV Incidence Among Women in a Predominantly Sex Worker Cohort Attending a Dedicated Clinic Service in Kampala, Uganda

BACKGROUND: There is limited evidence on the relationship between sustained exposure of female sex workers (FSWs) to targeted HIV programmes and HIV incidence. We investigate the relationship between the number of missed study visits (MSVs) within each episode of 2 consecutively attended visits (MSVs) and subsequent HIV risk in a predominantly FSW cohort. // METHODS: Women at high risk of HIV are invited to attend an ongoing dedicated clinic offering a combination HIV prevention intervention in Kampala, Uganda. Study visits are scheduled once every 3 months. The analysis included HIV-seronegative women with ≥1 follow-up visit from enrollment (between April 2008 and May 2017) to August 2017. Cox regression models were fitted adjusted for characteristics on sociodemographic, reproductive, behavioral, and sexually transmitted infections (through clinical examination and serological testing for syphilis). // FINDINGS: Among 2206 participants, HIV incidence was 3.1/100 (170/5540) person-years [95% confidence interval (CI): 2.6 to 3.5]. Incidence increased from 2.6/100 person-years (95% CI: 2.1 to 3.2) in episodes without a MSV to 3.0/100 (95% CI: 2.2 to 4.1) for 1-2 MSVs and 4.3/100 (95% CI: 3.3 to 5.6) for ≥3 MSVs. Relative to episodes without a MSV, the hazard ratios (adjusted for confounding variables) were 1.40 (95% CI: 0.93 to 2.12) for 1-2 MSVs and 2.00 (95% CI: 1.35 to 2.95) for ≥3 MSVs (P-trend = 0.001). // CONCLUSION: Missing study visits was associated with increased subsequent HIV risk. Although several factors may underlie this association, the finding suggests effectiveness of targeted combination HIV prevention. But exposure to targeted interventions needs to be monitored, facilitated, and sustained in FSWs

Building sustainable market linkages through innovations platforms for technology adoption: Case studies from Uganda, Kenya and Tanzania.

Finding and sustaining markets for Orange-fleshed sweetpotatoes is a challenge in many parts of East Africa. Farmers face numerous difficulties in identifying credible business partners, while traders and other market chain actors are frustrated by inconsistencies in supply. In the Dissemination of New Agricultural Technology in Africa (DONATA) OFSP project, Innovation Platforms for Technology Adoption (IPTAs) in Ethiopia, Kenya, Rwanda, Tanzania and Uganda have brought together relevant value chain stakeholders to develop institutional mechanisms which have supported the up-scaling of OFSP technologies (e.g. new varieties, agronomic practices, and post-harvest activities) and marketing strategies. This paper presents key strides attained in accessing equitable markets by IPTAs in three DONATA project countries. While some IPTAs have segmented the market and differentiated the producer groups along product lines, others have supported various chain actors to strengthen their businesses thus increasing throughput to the markets. Hence in the former case, groups are classified along major OFSP products marketed (vines, roots and processed products), while in the latter, specialized actors take on these functions. Successes include firm contracts for supply of OFSP flour to supermarkets in Kenya, supply of roots to urban markets in Uganda, and sale of vines to individuals and organizations in Tanzania. The major challenges include aligning production to demand for consistent supply, poor market infrastructure and low consumer awareness of the benefits of OFSP. Future prospects lie with newly established relations with big buyers and also working closely with other initiatives to consolidate gains achieved to date

Predictors of recurrent TB in sputum smear and culture positive adults: a prospective cohort study

Objective: To explore simple inexpensive non-culture based predictors of recurrent pulmonary tuberculosis (PTB). Setting and study population: HIV-infected and uninfected adults with the first episode of smear positive, culture-confirmed pulmonary tuberculosis in a high tuberculosis burden country. Design: A nested prospective cohort study of participants with pulmonary tuberculosis (PTB) presenting to a hospital out-patient clinic. Results: A total of 630 TB culture confirmed participants were followed up for eighteen months of which 57 (9%) developed recurrent recurrent TB. On univariate analysis,4.7% low grade(1+) pre-treatment sputum smear participants developed recurrent tuberculosis Vs 8.8% with high grade(3+) smears (OR=0.31,95%CI: 0.10-0.93, p=0.037).On multivariate analysis:participants with extensive fibro-cavitation had a high risk of recurrent TB Vs minimal end of treatment fibro-cavitation (18%Vs12%,OR=2.3,95%CI:1.09-4.68, p=0.03).Weight gain with HIV infection was assosciated with a high risk of recurrent TB Vs weight gain with no HIV infection(18%Vs 6%,OR=6.8,95%CI:165-27.83,p=0.008) where as weight gain with a low pre-treatment high bacillary burden was assosciated with a low risk of recurrent TB Vs weight gain with a high pre-treatment-bacillary burden(6.5%Vs7.9%,OR=0.2,95%CI:0.05-0.79,p=0.02). Conclusion: Extensive end of treatment pulmonary fibro-cavitation, high pre-treatment bacillary burden with no weight gain and HIV infection could be reliable predictors of recurrent tuberculosis. DOI: https://dx.doi.org/10.4314/ahs.v19i2.33 Cite as: Muzanyi G, Mulumba Y, Mubiri P, Mayanja H, Johnson JL, Mupere E. Predictors of recurrent TB in sputum smear and culture positive adults: a prospective cohort study. Afri Health Sci.2019;19(2): 2091-2099. https://dx.doi.org/10.4314/ahs.v19i2.3

Predictors of loss to follow up among patients with type 2 diabetes mellitus attending a private not for profit urban diabetes clinic in Uganda : a descriptive retrospective study

BACKGROUND: Although the prevalence of type 2 diabetes mellitus is increasing in Uganda, data on loss to follow up (LTFU) of patients in care is scanty. We aimed to estimate proportions of patients LTFU and document associated factors among patients attending a private not for profit urban diabetes clinic in Uganda. METHODS: We conducted a descriptive retrospective study between March and May 2017. We reviewed 1818 out-patient medical records of adults diagnosed with type 2 diabetes mellitus registered between July 2003 and September 2016 at St. Francis Hospital - Nsambya Diabetes clinic in Uganda. Data was extracted on: patients' registration dates, demographics, socioeconomic status, smoking, glycaemic control, type of treatment, diabetes mellitus complications and last follow-up clinic visit. LTFU was defined as missing collecting medication for six months or more from the date of last clinic visit, excluding situations of death or referral to another clinic. We used Kaplan-Meier technique to estimate time to defaulting medical care after initial registration, log-rank test to test the significance of observed differences between groups. Cox proportional hazards regression model was used to determine predictors of patients' LTFU rates in hazard ratios (HRs). RESULTS: Between July 2003 and September 2016, one thousand eight hundred eighteen patients with type 2 diabetes mellitus were followed for 4847.1 person-years. Majority of patients were female 1066/1818 (59%) and 1317/1818 (72%) had poor glycaemic control. Over the 13 years, 1690/1818 (93%) patients were LTFU, giving a LTFU rate of 34.9 patients per 100 person-years (95%CI: 33.2-36.6). LTFU was significantly higher among males, younger patients (< 45 years), smokers, patients on dual therapy, lower socioeconomic status, and those with diabetes complications like neuropathy and nephropathy. CONCLUSION: We found high proportions of patients LTFU in this diabetes clinic which warrants intervention studies targeting the identified risk factors and strengthening follow up of patients

Successful Shortening of Tuberculosis Treatment Using Adjuvant Host-Directed Therapy with FDA-Approved Phosphodiesterase Inhibitors in the Mouse Model

Global control of tuberculosis (TB), an infectious disease that claims nearly 2 million lives annually, is hindered by the long duration of chemotherapy required for curative treatment. Lack of adherence to this intense treatment regimen leads to poor patient outcomes, development of new or additional drug resistance, and continued spread of M.tb. within communities. Hence, shortening the duration of TB therapy could increase drug adherence and cure in TB patients. Here, we report that addition of the United Stated Food and Drug Administration-approved phosphodiesterase inhibitors (PDE-Is) cilostazol and sildenafil to the standard TB treatment regimen reduces tissue pathology, leads to faster bacterial clearance and shortens the time to lung sterilization by one month, compared to standard treatment alone, in a murine model of TB. Our data suggest that these PDE-Is could be repurposed for use as adjunctive drugs to shorten TB treatment in humans

Genome Scan of M. tuberculosis Infection and Disease in Ugandans

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes. First, we analyzed culture confirmed TB disease compared to latent Mtb infection (LTBI) or lack of Mtb infection. Second, we analyzed resistance to Mtb infection in the face of continuous exposure, defined by a persistently negative tuberculin skin test (PTST-); this outcome was contrasted to LTBI. Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha (TNFα) expression in response to soluble Mtb ligands enriched with molecules secreted from Mtb (culture filtrate). We conducted a full microsatellite genome scan, using genotypes generated by the Center for Medical Genetics at Marshfield. Multipoint model-free linkage analysis was conducted using an extension of the Haseman-Elston regression model that includes half sibling pairs, and HIV status was included as a covariate in the model. The analysis included 803 individuals from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs. Suggestive linkage (p<10−3) was observed on chromosomes 2q21-2q24 and 5p13-5q22 for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel and the chromosome 7 region contains the IL6 gene. In addition, we replicated recent linkage findings on chromosome 20q13 for TB (p = 0.002). We also observed linkage at the nominal α = 0.05 threshold to a number of promising candidate genes, SLC11A1 (PTST- p = 0.02), IL-1 complex (TB p = 0.01), IL12BR2 (TNFα p = 0.006), IL12A (TB p = 0.02) and IFNGR2 (TNFα p = 0.002). These results confirm not only that genetic factors influence the interaction between humans and Mtb but more importantly that they differ according to the outcome of that interaction: exposure but no infection, infection without progression to disease, or progression of infection to disease. Many of the genetic factors for each of these stages are part of the innate immune system

Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi

© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Pathogens 5 (2009): e1000261, doi:10.1371/journal.ppat.1000261.Enterocytozoon bieneusi is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia, E. bieneusi is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of E. bieneusi have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for E. bieneusi. Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in E. bieneusi, of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of Encephalitozoon cuniculi proteins. Only one E. bieneusi protein with assigned function had no E. cuniculi homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the E. bieneusi genome, all traits consistent with genomic compaction. Our findings suggest that E. bieneusi is a likely model for extreme genome reduction and host dependence.This research was supported by National Institutes of Health (NIH) grants R21 AI064118 (DEA) and R21 AI52792 (ST). HGM was supported in part by NIH contracts HHSN266200400041C and HHSN2662004037C (Bioinformatics Resource Centers) and by the G. Unger Vetlesen Foundation

Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses

Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vaccines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vaccination serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4(+) T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1 & beta;, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abrogated vaccine responses in communities with endemic infections.Author summarySchistosomiasis drives host immune responses for optimal pathogen survival, potentially altering host responses to vaccine-related antigen. Chronic schistosomiasis and co-infection with hepatotropic viruses are common in countries where schistosomiasis is endemic. We explored the impact of Schistosoma mansoni (S. mansoni) worm burden on Hepatitis B (HepB) vaccination of individuals from a fishing community in Uganda. We demonstrate that higher schistosome-specific antigen (circulating anodic antigen, CAA) concentration pre-vaccination, is associated with lower HepB antibody titers post-vaccination at month 7. We show higher pre-vaccination levels of CCL17 in instances of high CAA that negatively associate with HepB antibody titers month 12 post-vaccination and coincided with lower frequencies of circulating T follicular helper cell populations (cTfh), proliferating antibody secreting cells (ASCs), and higher frequencies of regulatory T cells (Tregs). We also show that monocyte function is important in HepB vaccine responses, and high CAA is associated with alterations in the early innate cytokine/chemokine microenvironment. Our findings suggest that in individuals with high CAA and likely high worm burden, schistosomiasis can create an environment that is polarized against optimal host immune responses to the vaccine, which puts many endemic communities at risk for infection against HepB and other diseases that are preventable by vaccines.Cancer Signaling networks and Molecular Therapeutic