SERUM IMMUNOGLOBULIN PROFILE OF Trypanosoma congolense - INFECTED SHEEP IN RELATION TO PARASITAEMIA AND CHANGES IN CIRCULATING LEUCOCYTE AND ERYTHROCYTE MASS

Trypanosomiasis is a major problem in developing countries most especially Africa and the incriminating agents are T. congolense, T.vivax. T.brucei in small ruminants. It has high morbity  and mortality Rates of 70% and 20% respectively . The experimental animals were four Rams which were used as control and infected group, Parameters for this experiment were recorded before infection. Following inoculation with T.congolense, 2 mls of blood was collected from the sheep in vacutainers for serum biochemical assay. Enzyme linked immunosorbent assay was used to assay IGG and IGM concentrations and 1ml of blood was collected in vacutainers with anti coagulant to check leucocytic and erythrocytic index.This was done every day until day 6 and then every other day. Clinical signs observed post infection were , Anemia, Hematuria ,Rhinitis, dyspnea ,emaciation and paralysis of the fore and hind limbs and death .Statistical tables and charts were used for analyses. The  role of   Hypoprotenemia , IGG and IGM  in experimental infection with Trypanosoma congolense   were looked at. The anemia was Normocytic normochromic and later became Microcytic hypochromic, PCV Recorded on the first day prior to infection was 27%  and on the last day of  infection became 6% . Leucocytosis was Degenerative and Leucopenia was also observed Perhaps due to the antigenic nature of the parasite. On first day WBC count was 8.5 x109/L and Prior to death Leucocytosis of 6.1x 109 /L. Hypoproteneimia was also seen with Blood urea Nitrogen and Alanine aminotransferase falling to values below normal 55U/L and 155mg/dl respectively. There were also fluctuations in the values of IGG and IGM  with initial values of 1.4 and 0.71 µg/ML  and terminal values of 0.34 and 0.21 /L. The organs looked at Kidneys,Lungs,Heart and Liver were all in their initial stages of destruction , they were inflamed,edematous , congested and necrotic . Hypoprotenemia, , immune suppression,dyspnea ,Anemia and Leucopenia  may be the cause of death in Trypanosomiasis. Keywords:Leucopenea,Anemia,Trypanosoma,immunogobuins,Hypoprotenemia DOI: 10.7176/JBAH/11-6-06 Publication date:March 31st 202

Establishing convergent validity of a medication literacy assessment instrument for use within the Nigerian setting

Purpose: To establish convergent validity of a previously designed medication literacy instrument for use in Nigeria. Methods: A cross-sectional study was conducted in Zaria, Kaduna State from May to August 2021, with structured instruments administered to conveniently sampled members of the public via one-on-one interviews to collect data. These instruments included a previously designed medication literacy assessment instrument and the Newest Vital Sign United Kingdom version (NVS-UK) health literacy assessment questionnaire. Data obtained was reported using descriptive and inferential statistics. Results: Three hundred respondents were interviewed, majority of whom were females (51 %) and aged between 15 – 25 (76.6 %). The percentage of correct responses to the NVS-UK questions ranged from 22 to 58.3 %, while the total number of NVS-UK questions answered correctly by respondents ranged from 0 to 6 with a mean of 2.2 ± 1.7. Respondents’ NVS-UK scores were associated with their highest level of education completed (p = 0.001). The NVS-UK showed adequate internal consistency (Cronbach’s Alpha = 0.7) and validation of the developed medication literacy instrument against the NVS-UK demonstrated a Spearman’s rho correlation coefficient of 0.42. Conclusion: The designed instrument is valid and can be used to assess medication literacy within the country

Ecthyma gangrenosum on the face of a malnourished child with Pseudomonas sepsis: Simulating Cancrum oris

Introduction: Ecthyma gangrenosum (EG) is a cutaneous lesion commonly caused by Pseudomonas aeruginosa that involves mainly the lower limbs and gluteal region, seen more in immunosuppressed patients with neutropenia. Cancrum oris (Noma) is a gangrenous necrosis of the face that begins as a gingival ulcer and progresses rapidly to destroy contiguous tissues in malnourished children. Case Presentation: This article reports a case of facial EG which was similar to Noma in a malnourished child: a 16-month old girl with fever, cough, weight loss, watery stool and swelling on right cheek. She was febrile, pale, wasted with bilateral pitting pedal oedema. She had a solitary circumscribed round necrotic lesion, with surrounding hyperaemia on the right malar area which extended to destroy the right ala nasi. No intra-oral rashes but she had left ear discharge. She received blood transfusion, antibiotics, antiseptic wound care and nutritional rehabilitation. Management and Outcome: Swabs of the lesion and ear discharge both revealed Gram-negative bacilli and culture yielded P. aeruginosa. Retroviral, Mantoux and Gene Xpert tests were negative. She had moderate anaemia, normal white blood cell count, and neutropaenia. Parenteral ceftriazone was changed to ciprofloxacin based on sensitivity results and lack of clinical response. The wound healed with residual scarring and partial destruction of right ala nasi. Discussion: Although this patient had facial necrosis to suggest Noma, she did not have initial oral involvement, and clinical features such as Pseudomonas sepsis and neutropaenia suggested EG. Facial necrosis in malnourished children may be due to EG

Darunavir-Cobicistat versus Lopinavir-Ritonavir for COVID-19 Pneumonia: Qatar's Experience

Background: Coronavirus Disease 2019 (COVID-19) was first discovered in China and resulted in a pandemic crisis. 1,2 Many agents were investigated with inconclusive outcomes. 3 This study was conducted to compare the efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in the treatment of patients with COVID-19. Methods: This retrospective, multicenter, observational study was conducted on adult patients hospitalized in COVID-19 facilities in Qatar. Patients were included if they had pneumonia and received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatment. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Data were analyzed descriptively and inferential statistics were applied at alpha level of 0.05. Results: A total of 400 patients' medical records were analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. The majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (SD 4.89). Patients who received lopinavir-ritonavir had a significantly faster time to the primary composite endpoint of clinical improvement and/or virological clearance than patients who received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], p = 0.011) [Figure 1]. Patients who received lopinavir-ritonavir had a significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), p = 0.000), and slower time to virological clearance than those who received darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), p = 0.035) [Figure 2]. No significant difference in adverse events incidence or severity was observed. Conclusion: In patients with COVID-19, early treatment with lopinavir-ritonavir was associated with faster time to reach the primary composite endpoint of clinical improvement and/or virological clearance than treatment with darunavir-cobicistat. Future trials are warranted to confirm these findings.qscienc

Darunavir-cobicistat versus lopinavir-ritonavir in the treatment of COVID-19 infection (DOLCI): A multicenter observational study

Background Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. Methods and findings This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. Conclusion In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings.Scopu

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance

SARS-CoV-2 seroprevalence in pregnant women during the first three COVID-19 waves in The Gambia

OBJECTIVES: SARS-CoV-2 transmission in Sub-Saharan Africa has probably been underestimated. Population-based seroprevalence studies are needed to determine the extent of transmission in the continent. METHODS: Blood samples from a cohort of Gambian pregnant women were tested for SARS-CoV-2 total receptor binding domain (RBD) IgM/IgG before (Pre-pandemic: October-December 2019), and during the pandemic (Pre-wave1: February-June 2020; Post-wave1: October-December 2020, Post-wave2: May-June 2021; and Post-wave3: October-December 2021). Samples reactive for SARS-CoV-2 total RBD IgM/IgG were tested in specific S1- and nucleocapsid (NCP) IgG assays. RESULTS: SARS-CoV-2 total RBD IgM/IgG seroprevalence was 0.9% 95%CI (0.2, 4.9) in Pre-pandemic; 4.1% (1.4, 11.4) in Pre-wave1; 31.1% (25.2, 37.7) in Post-wave1; 62.5% (55.8, 68.8) in Post-wave2 and 90.0% (85.1, 93.5) in Post-wave3. S-protein IgG and NCP-protein IgG seroprevalence also increased at each Post-wave period. Although S-protein IgG and NCP-protein IgG seroprevalence was similar at Post-wave1, S-protein IgG seroprevalence was higher at Post-wave2 and Post-wave3, [prevalence difference (PD) 13.5 (0.1, 26.8) and prevalence ratio (PR) 1.5 (1.0, 2.3) in Post-wave2; and 22.9 (9.2, 36.6) and 1.4 (1.1, 1.8) in Post-wave3 respectively, p<0.001]. CONCLUSION: SARS-CoV-2 transmission in The Gambia during the first three COVID-19 waves was high, differing significantly from official numbers of COVID-19 cases reported. Our findings are important for policy makers in managing the near-endemic COVID-19

Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39–7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients’ subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.This study was funded by the Medical Research Center at Hamad Medical Corporation, Qatar (MRC-01-20-1095)

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Engineering Melon Plants with Improved Fruit Shelf Life Using the TILLING Approach

Background: Fruit ripening and softening are key traits that have an effect on food supply, fruit nutritional value and consequently, human health. Since ethylene induces ripening of climacteric fruit, it is one of the main targets to control fruit over ripening that leads to fruit softening and deterioration. The characterization of the ethylene pathway in Arabidopsis and tomato identified key genes that control fruit ripening. [br/] Methodology/Principal Findings: To engineer melon fruit with improved shelf-life, we conducted a translational research experiment. We set up a TILLING platform in a monoecious and climacteric melon line, cloned genes that control ethylene production and screened for induced mutations that lead to fruits with enhanced shelf life. Two missense mutations, L124F and G194D, of the ethylene biosynthetic enzyme, ACC oxidase 1, were identified and the mutant plants were characterized with respect to fruit maturation. The L124F mutation is a conservative mutation occurring away from the enzyme active site and thus was predicted to not affect ethylene production and thus fruit ripening. In contrast, G194D modification occurs in a highly conserved amino acid position predicted, by crystallographic analysis, to affect the enzymatic activity. Phenotypic analysis of the G194D mutant fruit showed complete delayed ripening and yellowing with improved shelf life and, as predicted, the L124F mutation did not have an effect. [br/] Conclusions/Significance: We constructed a mutant collection of 4023 melon M2 families. Based on the TILLING of 11 genes, we calculated the overall mutation rate of one mutation every 573 kb and identified 8 alleles per tilled kilobase. We also identified a TILLING mutant with enhanced fruit shelf life. This work demonstrates the effectiveness of TILLING as a reverse genetics tool to improve crop species. As cucurbits are model species in different areas of plant biology, we anticipate that the developed tool will be widely exploited by the scientific community