School of Medicine

Post-traumatic stress disorder and associated factors in patients with severe physical injuries at Jaramogi Oginga Odinga teaching and referral hospital, Kisumu, Kenya

Wed, 01 Jan 2025 00:00:00 GMT

Post-traumatic stress disorder and associated factors in patients with severe physical injuries at Jaramogi Oginga Odinga teaching and referral hospital, Kisumu, Kenya NAMUNYU, Michael Post-Traumatic Stress Disorder (PTSD) is a severe psychological condition that significantly impairs daily functioning and quality of life. It is brought about by exposure to traumatic experiences such as natural disasters, military warfare, sexual assault, or physical harm. Despite its high prevalence, PTSD is often underdiagnosed. Local information on how prevalent and associated attributes of this condition are deficient. The study aimed to assess how common post-traumatic stress disorder (PTSD) is and to identify the factors linked to its occurrence among individuals with severe physical injuries at Jaramogi Oginga Odinga Teaching and Referral Hospital. The research employed a cross-sectional study design to examine the variables, collecting data from 143 patients with severe physical injuries who were undergoing follow-up in the surgical and orthopaedic outpatient clinics at JOOTRH over a two-month period. A standardized PTSD assessment tool was used to evaluate all the patients for probable PTSD. The collected data were processed and analysed using SPSS version 25 statistical software. Descriptive statistics were summarized in tables and charts, while for inferential analysis, chi-square statistics were used to assess categorical associations. Independent risk factors for PTSD were ascertained through multiple logistic regression analysis, with statistical significance defined as p < 0.05 at a 95% confidence interval. The study found a PTSD prevalence of 16.8% among individuals with severe physical injuries (n = 24). Statistically significant factors associated with PTSD included male gender (P=0.005, OR=0.27), being in employment (P=0.001, OR=0.178), urban residency (P=0.006, OR=0.27), low social support (P=0.000, OR=0.55), and being married (P=0.018, OR=0.19). These factors were associated with lower prevalence. However, prior physical injury (P = 0.00, OR = 9.38) and a familial predisposition to mental illness (p = 0.001, OR = 12.9) exhibited a markedly higher prevalence of PTSD. In conclusion, compared to similar studies conducted in tertiary institutions across the region, this study reported a notably higher prevalence of PTSD. Gender, occupational status, prior physical trauma, residential setting, social support level, marital status, and a family history of mental health disorders were all identified as important predictors of PTSD. Given the higher prevalence of PTSD found in this study, the external validity of these findings warrants confirmation through replication studies with adequate statistical power so as to generalise the findings throughout other institutions and the wider region. Targeted screening of patients with increased risk factors should be done, specifically those with a history of prior physical injuries and individuals with familial predisposition to psychiatric disorders. Master's Thesis

Histological patterns of prostate specimens analyzed at Jaramogi Oginga Odinga teaching and referral Hospital

Sun, 01 Jan 2023 00:00:00 GMT

Histological patterns of prostate specimens analyzed at Jaramogi Oginga Odinga teaching and referral Hospital MUSUNGU, Vincent Sechere Prostate cancer is the fifth most prevalent cause of cancer-related death worldwide in men, accounting for an estimated 366,000 deaths and 6.3 million disability-adjusted life years. There is scarce information on prostate biology and histological characteristics of prostate tumors among men in western part of Kenya who are all exposed to factors that can alter the biology of prostate gland thus predisposing to prostate cancer variants that may be different from the conventional adenocarcinoma. Such scarcity of information could lead to assumptions that all prostate tumors are adenocarcinoma. While some prostate tumors are not aggressive, there are different types of prostate tumors and each prostate tumor type has unique clinical profile. Some prostate tumors have indolent course while others have aggressive course and therefore knowledge of tumor subtypes can help in clinical decision making based on patient profile. This purpose of the study was to investigate prostate histological patterns among patients whose prostate specimens were processed and reported at JOOTRH between 2017 and 2022 with a focus on improving prostate cancer diagnosis and histology reporting. The main objective was to determine histological patterns of prostate specimens at JOOTRH between 2017 and 2022. The specific objectives were to: find out the histomorphology of prostate specimens as reported at JOOTRH, to correlate the patient age and PSA level at the time of prostate specimen collection at JOOTRH and to determine the common prostate tumor type reported in men whose prostate specimens were analyzed at JOOTRH. This was a laboratory based cross sectional study design carried out in pathology laboratory at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) in Kisumu city. The target population in this study constituted prostate specimens which had PSA level, analyzed and reported at JOOTRH between 2017 and 2022. The study was carried out between December 2022 and February 2023. Using Yamane formula, the sample size was determined to be 80. Random sampling was used. A sampling frame consisted of pathology register of the histopathological reports of the prostate specimens analyzed at JOOTRH. Each name in the register was assigned serial numbers. All the numbers were fed in a computer program (randomizer application) to randomly sample 80 names. Data extraction form was used. The extraction form consisted of age of the patient, clinical notes (PSA and Age), macroscopic examination, microscopic examination of the prostate tissues and conclusion. Descriptive and inferential statistics was done by the SPSS version 29 for windows. The frequencies were tabulated in percentages, tables and graphs. Inferential statistics utilized chi-square, ANOVA, independent t test, one sample chi-square and linear regression. P value less than 0.05 was considered statistically significant. There was statistically significant variation (p 0.001) in prostate specimen color as reported in prostate histology at JOOTRH. The researcher could not demonstrate that the prostate specimen surfaces occur with equal changes (p<0.05, X2=23.275, df=2, 95% CI). The results reveal that there is no statistically significant difference in the prostate biopsy sizes in comparison to the mean (p=0.984, t=0.020, 95% CI). Prostate histology reports were divided into four groups based on the age of the patient (Group 1: 40–49 years, Group 2: 50–59 years, Group 3: 60–79 years, and Group 4: above 80 years). The ANOVA results suggest that the microscopic features of the groups did not differ significantly (F2, 34 = 1.469, p = 0.244, 95% CI). There is a statistically significant positive correlation between Gleason scores and PSA levels (p = 0.004, r = 0.474). The Pearson correlation between age and PSA levels was found to have a statistically significant positive correlation (r = 0.236, p = 0.035, 95% CI). Regarding the prostate tumor type, prostate adenocarcinoma was the predominant tumor type, accounting for all 100% of observed prostate cancer types. The tumor types reported were divided into four groups based on the age of the patient (Group 1: 40–49 years, Group 2: 50–59 years, Group 3: 60–79 years, and Group 4: above 80 years). The ANOVA results suggest that the types of prostate tumors in the groups did not differ significantly (F3,76 = 1.300, p = 0.28, 95% CI). Based on study results, the health workers should improve documentation of the prostate histology reporting to include core biopsies and gross morphological parameters like volume, description of cell details observed and Biopsies should be requested in cases where there is high likelihood of prostate cancer. Master's Thesis

The Histomorphological and biochemical hepatorestorative Effects of silymarin milk thistle on paracetamol induced Hepatotoxicity in adult albino rats (Rattus norvegicus)

Sun, 01 Jan 2023 00:00:00 GMT

The Histomorphological and biochemical hepatorestorative Effects of silymarin milk thistle on paracetamol induced Hepatotoxicity in adult albino rats (Rattus norvegicus) NGETICH, Davis Kiprono Liver toxicity has been on a steady rise worldwide and it is attributed to various causes including paracetamol-induced when taken singly in high dose or prolonged use. Paracetamol is a common, most preferred and widely tolerated first line analgesia for mild and moderate acute pain for all age groups. Since its cheap and easily accessible as an over-the-counter drug, it can be easily misused especially with increasing causes of pain in the society. Its long-term use causes liver toxicity and eventually liver failure. Most plant medicinal extracts have been found to either prevent or ameliorate the hepatotoxic effects either alcohol or drug induced. Silymarin milk thistle is a medicinal herb that grows widely in various climatic conditions, available locally and affordable to all. It has been used over time to prevent or treat liver diseases though there is inadequate data on its histo-morphologic restorative effects that occur on the liver following drug induced hepatotoxicity. This study aimed at evaluating the restorative histo-morphological changes of silymarin milk thistle on paracetamol induced hepatotoxicity. Specifically, the study determined; the histomorphological injurious effects that occur on the liver following toxicity, the restorative histomorphological effects of various doses of silymarin milk thistle on paracetamol hepatotoxicity and assessed the changes in liver biochemical parameters of Aspartate transaminase (AST), Alkaline phosphatase (ALP) and Alanine transaminase (ALT) following administration of silymarin milk thistle and paracetamol toxicity. A post-test only true experimental study design was used with a total of 24 adult albino rats randomly sampled into intervention and non-intervention groups. The non-intervention further into control of 3 rats received no drug interventions and 3 rats that received high dose of paracetamol (750 mg/kbwt) for 5 days. A total of 3 intervention groups each having 6 rats received same dose of paracetamol (750 mg/kbwt) for 5 days to induce hepatotoxicity and varying doses of silymarin (low dose- 200mg/kbwt, medium dose- 400 mg/kbwt and high dose- 600 mg/kbwt) to each group respectively for the remaining 16 days of the experimental process. Humane sacrificial was done on day 21 and liver tissues harvested and processed for both gross and histological examinations and stained using Hematoxylin & Eosin (H&E). Morphological data were entered into excel sheet, analyzed through Statistical Package for the Social Sciences (SPSS) version 26, and One-way Analysis of Variance (ANOVA) was used to test the mean groups and a post hoc was used to test the difference between the mean groups. The results showed that there was a significant reduction (P=0.0001) in length, width and volume in the control group as compared with the paracetamol only group. It also had areas of hemorrhagic necrosis, vacuolated hepatocytes and dilated sinusoids. Unlike the low dose and medium dose silymarin groups, there was a significant increase in all the parameters (volume, weight, length and width) in the high dose silymarin when compared with the control. In comparison with the control group the medium dose and low dose groups registered a significant difference in all the parameters while the high dose group showed no significant difference to signify some level of restoration. Histologically, the paracetamol only group liver had areas of hemorrhagic necrosis, pocket foci of hemorrhage and dilated sinusoids and compared with those of the low dose and medium dose silymarin groups. The high dose group had even distribution of normal hepatocytes and sinusoids and was similar with the control liver. The liver biochemical parameters were significantly (P=0.0001) elevated in the paracetamol only group, low dose and medium dose silymarin groups when compared with the control whose parameters presented no significant difference with those of the high dose silymarin group. In conclusion, high dose silymarin had hepato-restorative effects, therefore more studies should be done on the safe human dose and its pharmacokinetics so that it can be taken alongside those drugs causing hepatotoxicity and to treat liver related conditions, ultimately reducing liver related mortalities. Master's Thesis

Single dose versus extended dose antibiotics in prevention of surgical site infection in elective caesarean section at a tertiary hospital in Kisumu-Kenya: a randomized controlled trial

Sun, 01 Jan 2023 00:00:00 GMT

Single dose versus extended dose antibiotics in prevention of surgical site infection in elective caesarean section at a tertiary hospital in Kisumu-Kenya: a randomized controlled trial JUMA, Steven Odhiambo When compared to other surgical procedures overall, Caesarean section (CS) accounts for the most recorded cases of surgical site infection (SSI). Following CS, antibiotic prophylaxis usage has been proven to lower incidence of SSI in both high risk and low risk individuals. However, it is not obvious if either single dose (SD) or extended dose (ED) antibiotic prophylaxis make much difference in SSI prevention despite previous research emphasizing the importance of antibiotic prophylaxis in surgical procedures The main objective of this study was to compare the effectiveness of SD, and ED antibiotics in elective CS in prevention of SSI. This was an open label randomized control study carried out in 9 months period beginning March 2022 to December 2022 at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). 150 consenting patients were randomly distributed into control and intervention arms. Subjects in booth groups received intravenous (IV) ceftriaxone one gram 30 minutes before operation; subjects in control arm received additional IV ceftriaxone and metronidazole for 48 hours then amoxicillin 500mg every 8 hours and metronidazole 500mg tablets for 5 days. The participants were followed up for evidence of SSIs for 4 weeks. Data was collected and recorded into an abstraction form during the period of follow up by the investigator and research assistant. The completed forms were received, checked for completeness, and keyed into the computer. The data was analyzed using Statistical Package for Social Sciences (SPSS) Version 25. Rate of SSI was assessed and compared across study arms. Patients ‘factors associated with infection rate were analyzed at bivariate levels using Chi square and Fisher’s exact test. Multivariate logistic regression test was further done to determine factors associated with SSI. All covariates with p-value <=0.05 at bivariate analysis were included in multivariate logistic regression with 95% confidence intervals were reported. Out of the 75 on SD arm, 2 (2.6%) developed SSI, whereas of the 75 on ED arm, 1 (1.3%) developed SSI. Patient factors such as age, income status, parity, level of education, indication for CS, type of incision, amount of blood loss, random blood sugar level prior to operation, white blood cell level, type of anesthesia did not have significant influence in development of SSI in both the trial arms during the twenty-eight days of follow up. The findings showed that there was no statistically significant difference in occurrence of post elective caesarian SSI between the SD and ED groups with a p value of 0.567 at 1 degree of freedom (df) with a 95% confidence interval (CI) of 0.533044 – 5.559 with relative risk (RR) of 0.493. In conclusion, SD prophylaxis is equally effective as ED prophylaxis in prevention of SSI in elective CS. This study recommends that in the absence of evidence of SSI, there is no justification for ED of antibiotics as SD is sufficient. Master's Thesis

Perceptions of patients and clinicians on integration of human immunodeficiency virus and non- communicable diseases care in Jarmogi Oginga Odinga teaching and referral hospital, Kisumu- Kenya

Sat, 01 Jan 2022 00:00:00 GMT

Perceptions of patients and clinicians on integration of human immunodeficiency virus and non- communicable diseases care in Jarmogi Oginga Odinga teaching and referral hospital, Kisumu- Kenya LUATE, Richard The rising prevalence of non-communicable diseases (NCDs) among patients with HIV has led to the need to re-think of how best to manage the patient with both conditions in the HIV clinic. Despite the evidence suggesting system-wide and nation-wide benefits to integration, the patient and service level effects are undocumented. This study aimed to investigate patients and clinicians’ perception of challenges of NCDs-HIV care service integration. A descriptive crosssectional study was carried out in the Jaramogi Oginga Odinga Teaching and Referral Hospital HIV and MOPC clinics, involving 480 respondents from 2 groups; adult HIV patients and clinicians providing care for HIV patients and NCDs. The two groups of respondents were randomly and purposively sampled respectively. A structured questionnaire designed with a 4point Likert scale was used for data collection. A score of 1 was awarded for strongly disagree, 2 for disagree, 3 for agree and 4 for strongly agree. All scores were added to give an aggregate score for each domain and overall. The study found that most respondents strongly agreed that combining HIV and NCDs Clinic would improve care, decrease frequency of clinic visits be cost effective as resources are shared for HIV and NCDs, and integration could capitalize on the good foundations built for HIV to improve NCDs Care. 49.8% of patients strongly agreed the integration of HIV and NCDs care services improve HIV and NCDs care in the HIV outpatient clinics. 87% of clinicians strongly agreed that the integration of HIV and NCDs care services improve care in the HIV outpatient clinics. Concerns on funding and lack of policies and strategies on integration were expressed as possible problems to the implementation of an integrated approach. The study also confirmed the clinicians’ and patients’ willingness to work and be seen in the integrated clinic respectively. 83.6% of the patients agreed they would visit HIV and NCDs integrated outpatient clinics for HIV and NCDs care. On the other hand, all clinicians agreed they would attend and work in integrated outpatient clinics to provide care for HIV and NCDs patients. Most respondents perceived that the integration of HIV and NCDs care services would lower frequency of visiting clinics, improve care for both HIV and NCDs in the HIV outpatient clinic, and enhance cost effectiveness of accessing quality health care. On the challenges, it was apparent that the integration of HIV and NCDs care services would lead to crowding and workload for patients and clinicians respectively. Regardless of the challenges, both patients and clinicians were overwhelmingly interested in being seen and working in integrated HIV and NCDs outpatient clinics respectively

Nurses’ knowledge related to pain assessment for critically ill patients at a public sector Hospital in Johannesburg

Wed, 01 Jan 2014 00:00:00 GMT

Nurses’ knowledge related to pain assessment for critically ill patients at a public sector Hospital in Johannesburg Indrah G. M. Onwong'a Discrepancies exist between how pain is assessed in ICU patients able and unable to self report. There are pain assessment scales and guidelines that have been developed over the years for pain assessment. However, little is known regarding ICU nurses’ knowledge and current practices in the provision of pain management in the critically ill. The purpose of this study was to investigate intensive care nurses’ knowledge and practices related to pain assessment for critically ill patients. A quantitative non experimental, descriptive cross-sectional design was used to achieve the objectives. ICU nurse participants (n=79) were drawn from the five (5) adult ICUs in a public tertiary hospital. Data were collected using a self-administered questionnaire by Rose et al. 2011. Descriptive and inferential statistics were used to analyze the data. There was a significant difference in the nurses who used a formal pain assessment tool for patients able to self-report (mean percentage, 72.1%) compared to patients unable to self report (mean percentage, 52.0%) with a statistical significance (p=0.0027). However, there was no difference in the perceived importance of the use of pain scale. Nurses assessed pain frequently and were more confident in patients able to self-report than patients unable to self-report (p=0.0001). Behaviors most frequently considered indicative of pain were Restlessness (mean percentage 48.1%), and ventilator alarms (mean percentage, 47.4%). Pain assessment was considered extremely important for post-operative ICU patients and (mean percentage, 91.1%) and trauma ICU patients (mean percentage, 87.0%). Most frequently occurring barriers were unavailable pain assessment tools, lack of designated area for charting pain and hemodynamic instability. Enablers were pain prioritization in ICU and motivated staff. Most of the nurses had received pain education on various topics; however a few (29.7%) were extremely satisfied. Based on the research findings, despite participant’s perceived importance of pain assessment for patients who can self-report and those who cannot self-report, nurses were less familiar with formal pain assessment tools for patients unable to self-report and less confident in their pain assessment. Hence, a wide gap of the two groups of patients Master's Thesis, Donation

The Study of Drug Metabolism G In Children with Protein Energy, Malnutrition and Tuberculosis Using 'The caffeine Breath Test

Sun, 01 Jan 1995 00:00:00 GMT

The Study of Drug Metabolism G In Children with Protein Energy, Malnutrition and Tuberculosis Using 'The caffeine Breath Test NYATIGI, Paul Remington The purpose of this study was to determine the applicability of the ,saffeine breath test in assessing liver drug metabolism. , in children/with Kwashiorkor and those on anti-TB drugs. Seventeen children aged between 3-10 years were recruited into the study, of which 8 were cases of kwashiorkor and 9 on anti-TB treatment. Both groups were studied before commencing dietary rehabilitation or anti- TB treatment. Labelled caffeine was given orally at a dose of 3 mg kg -1 dissolved in distilled water. Breath samples were collected by requesting the child to blow into the mask at intervals of 15 minutes for a period of 2 hours. The collected sample were transferred into a labelled headspace analyzer vial for storage pending analysis. The procedure was repeated after 10-14 days of intervention. Breath samples were analyzed at the Scottish Universities Research Reactor Centre, Edinburgh. Unfortunately, due to faulty seal on some of the collection vials, only a limited number of specimens had adequate amount of isotope for analysis (~50). In the kwashiorkor group there were 4 sin{ille and 3 duplicate samples which had adequate amount of isotope labelled carbon dioxide for analysis. In the patients with duplicate samples a rise in level of labelled carbon dioxide recovered after nutritional rehabilitation, 'the mean (SO) percentage was 2.86 (1.3) before and 3.6 vii (1.39) after rehabilitation. In TB patients there were 3 single and 4 duplicate samples which had adequate amount of isotope labelled carbon dioxide for analysis. In these TB patients with duplicate samples, two had a notable rise and the other two had marginal decline in level of cumulative labelled carbon dioxide after commencement of treatment. The study showed that the caffeine breath test is a useful test of liver drug metabolizing enzymes in children with malnutrition. The study also demonstrates that the caffeine breath test can be used in children of three years of age or possibly younger. Further studies are required particularly to repeat the test when the children have recovered from malnutrition and tuberculosis.

Evaluation of serum thyroid hormones and lipid levels in HIV-infected patients on highly active antiretroviral therapy at the Jaramogi Oginga Odinga teaching and referral hospital in Kisumu county, western Kenya

Fri, 01 Jan 2021 00:00:00 GMT

Evaluation of serum thyroid hormones and lipid levels in HIV-infected patients on highly active antiretroviral therapy at the Jaramogi Oginga Odinga teaching and referral hospital in Kisumu county, western Kenya OMONDI, Alfred Juma While Highly Active Antiretroviral Therapy (HAART) has significantly reduced HIV-associated mortalities, they are not devoid of adverse effects including endocrine and metabolic disorders like thyroid dysfunctions and dyslipidemias. However, Alterations in serum thyroid hormones and lipid levels among HAART users in Sub-Saharan population like Kenya is yet to be elucidated. This study determined the serum lipid levels; Total cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL), Low Density Lipoproteins (LDL) and the serum Thyroid hormones levels; Thyroid Stimulating Hormone (TSH), Thyroxine (T4) and Triiodothyronine (T3) levels among the HAART-treated and HAART-naïve subjects. Using cross study design, patients (n=104) attending Jaramogi Oginga Teaching and Referral Hospital (JOOTRH) in Kisumu County, Western Kenya were recruited. The study participants were categorized into two groups; HAART-treated (84) and HAART-nave (20). Demographic, medical history and anthropometric data were collected after which fasting state blood was collected and centrifuged to obtain serum. Colorimetric method was used to determine the serum TC, TG, HDL, and LDL levels while immunofluorescence method was used to determine the serum TSH, T4 and T3 levels. The difference in serum lipid and thyroid hormones levels between HAART-treated and HAART-naïve groups were determined using Mann Whitney U test while Spearman correlation test was used to determine the association between serum lipids and serum thyroid hormones levels. Although the thyroid hormones were found to be within normal ranges in both groups, TSH levels were significantly higher among the HAART-treated patients than in HAART-naïve counterparts, [median (IQR) 1.72 (1.71) nmo/L vs median (IQR), 0.87 (1.07) nmo/L, P=0.001]. However, the serum T4 and T3 levels were similar in both the HAART-treated and HAART-naïve patients, [median (IQR) 144.39 (67.53.64) nmo/L vs median (IQR), 136.99 (134.22) nmo/L, P=0.426] and [median (IQR) 2.43 (2.73) nmo/L vs median (IQR) 3.10 (2.62) nmo/L, (P=0.147) respectively. The serum lipids levels, were all within normal ranges, and did not differ significantly between the HAART-treated patients and the HAART-naïve counterparts; TC, [median (IQR) 186.00 (91.50) mg/dl vs median (IQR) 149.50 (70.30) mg/dl, (P=0.092)]; HDL, [median (IQR) 52.50 (24.00) mg/dl vs median (IQR) 44.00 (34.00) mg/dl, (P=0.280)], LDL, [138.00 (86.30) vs 117.00(46.50), (P=0.476)] as well as TG [median (IQR) 82.00 (62.80) mg/dl vs median (IQR) 94.50 (55.80) mg/dl, (P=0.504)]. While a positive association was found between T4 and LDL levels, (ρ =0.240, P=0.014), no association was established between serum TSH as well as T3 levels and serum lipid profiles. This study shows that there is varying serum TSH levels HAART-treated and HAART-naive patients and that serum LDL levels increases with increase in serum T4 levels. Routine monitoring of serum lipids and thyroid hormones levels for the HIV-infected patients particularly those on HAART treatment is therefore recommended. Masters Thesis

Evaluation of The Actions of Diosmin – Hesperidin Combination On HIV- Protease Inhibitor-Induced Hyperglycemia in Rattusnorvegicusalbinus

Fri, 01 Jan 2021 00:00:00 GMT

Evaluation of The Actions of Diosmin – Hesperidin Combination On HIV- Protease Inhibitor-Induced Hyperglycemia in Rattusnorvegicusalbinus AKUNGA , Nahashon Gichana Glucose intolerance is impaired glucose uptake by peripheral tissues due to insulin resistance and is usually associated with chronic hyperglycemia. The condition often leads to overt diabetes mellitus [DM] - a metabolic disorder that is characterized by the body’s inability to lower blood glucose to normal levels. Available reports show that medication with HIV protease inhibitors [PIs] causes insulin resistance and hence glucose intolerance in HIV- positive patients. This study evaluated the actions of the flavonoids (Diosmin[DIOS] and Hesperidin[HES]) on HIV protease inhibitor (HIV-PIs) induced hyperglycemia in Rattusnorvegicusalbinus (wistar rats). Seventy two Wistar rats were randomly assigned into six groups of twelve rats each. Each group was given a specific treatment with HIV protease inhibitors and or flavonoids for 42 days. The blood glucose, HbA1c and insulin levels were measured analyzed.The Control and the ATV/RTV+DIOS/HES treated groups had a significant difference only once at the end of week one of the treatment period (diff. =0.625 mmol/L, p=0.014). The Control group, DIOS/HES and the ATV/RTV+DIOS/HES treated groups did not show any significant differences in their group mean blood glucose levels from the second week of treatment to the end of the study. The ATV/RTV (5.95±2.15 mmol/L on week 3), LPV/RTV (5.14±0.92 mmol/L on week 3) and LPV/RTV+DIOS/HES (5.30±1.72 mmol/L on week 3) treated groups had significantly elevated group mean blood glucose levels on the third week of the study compared to the control group (3.88±0.42 mmol/L on week3). The HIV-Protease inhibitor treatments increased blood insulin levels (grand mean of 3.58±2.27µIU/mL at baseline (day 0) to 20.32±2.27 µIU/mL on day 42, p<0.001). The HIV-protease inhibitors increased group mean HbA1c levels with the LPV/RTV treated group increasing from 4.67± 0.16 percent on day 0 to 5.45±0.77 percent on day 42 (p<0.01) and ATV/RTV treated group mean HbA1c level increasing from 4.52±0.16 percent on day 0 to 5.13±0.53 percent on day 42 (p<0.01) while the DIOS/HES group mean HbA1c levels decreased significantly (4.73±0.16 percent at day 0 to 3.35±0.48 percent on day 42, p<0.001). The results demonstrated that the co-administration of ATV/RTV with DIOS/HES significantly reduced the blood glucose elevating effects of the ATV/RTV combination. The co-administration of the flavonoids with HIV-PIs also reduced the blood HbA1c levels resulting from HIV-PIs treatment.

Analysis of Reactivity and Functionality of Serum Antibodies From Monovalent and Multivalent Shigella Bioconjugate Vaccinated Rabbits Against Shigella Isolates From Kenya

Fri, 01 Jan 2021 00:00:00 GMT

Analysis of Reactivity and Functionality of Serum Antibodies From Monovalent and Multivalent Shigella Bioconjugate Vaccinated Rabbits Against Shigella Isolates From Kenya ODUNDO , ELIZABETH AWINO Shigella species is a major cause of bacterial diarrheal mortalities and morbidities worldwide and second in Kenya, especially in children under five years. Antibiotics are needed in treatment of shigellosis however, increasing resistance necessitates other control measures such as Shigella vaccine but none has widely been approved. An immunogenic novel monovalent and multivalent bioconjugate vaccine (linking Shigella O-antigen (LPS) to Exoprotein A of Pseudomonas aeruginosa) against the four major Shigella serotypes responsible for 80% global morbidity; S. flexneri (Sf) 2a, 3a, 6 and S. sonnei is in development. The monovalent and quadrivalent bioconjugate vaccine constructs have been evaluated for immunogenicity in rabbit models and is planned for clinical trial in Kenya. Therefore, it is necessary to further understand the antibody response (reactivity and functionality (BA)) from the monovalent and quadrivalent (adjuvanted 4V-adj) and without an adjuvant (4V) Shigella bioconjugate vaccinated rabbit serum against Shigella isolates from Kenya. This retrospective laboratory-based study, nested within an ongoing parent diarrheal surveillance protocol in Kenya since 2009, was conducted to test the immunized rabbit serum against 129 archived Shigella strains from Kenyan. Specifically, this study assesses the specific reactivity of serum antibodies against the four major Shigella serotypes targeted; cross reactivity of the serum antibodies against Shigella serotypes (Sf 1b, 2b, 4a, 4b, Shigella spp, S. dysenteriae and S. boydii) not targeted by the formulation and the BA of the serum antibodies against a subset of reactive Shigella isolates. The 129 isolates were serotyped and screened for retention of the virulence factor O-antigen LPS by plating on Congo red (CR) culture plate. The specific and cross reactivity of the immunized rabbit serum to the virulent Shigella isolates was determined by colony blot assay. The BA of the serum antibodies against reactive Shigella isolates was assessed by a serum bactericidal assay (SBA) and analyzed using Nist Integrated Colony Enumerator and Opsititre software. Of the 129 Shigella isolates, 109 (85%) retained their virulence; 67 serotypes were targeted by the vaccine while 42 were not-targeted serotypes. From the virulent isolates, a subset of 22 isolates targeted by vaccine Sf 2a (4), 3a (10), 6 (4), S. sonnei form I (4) and 19 isolates not targeted by the vaccine Sf 1b (5), 2b (5), 4a (2), 4b (3), S boydii (2) and S. dysenteriae (3) were assessed for reactivity. Specific reactivity Serum from rabbits immunized with the 4V-Adj and the respective monovalent vaccines against the 22 target serotypes had 100% specific reactivity. The serum from 4V-Adj vaccinated rabbits cross-reacted with Sf 2b (75%), Sf 4a (100%), one Sf 1b (25%) and Sf 4b (33%). Serum from rabbits immunized with the Sf 2a monovalent vaccine cross-reacted with Shigella serotypes; one Sf 3a and three Sf 2b, while the Sf 3a monovalent serum cross-reacted with one Sf 2a. The surviving colonies were enumerated using excel based Nist Integrated Colony Counter and analyzed using the Opsititre software and presented in tables. There was ≥4-fold increase in BA between the pre and post vaccine rabbit sera with all the Shigella serotypes tested except one cross-reactive Sf 3a indicative that, the rabbit’s serum antibodies had functional activity. Collectively, these results demonstrate that the monovalent/ quadrivalent bioconjugate Shigella vaccine may be more broadly protective than designed offering a promising solution to reduced morbidity and mortalities associated with Shigella spp. These results strengthen the vaccine development strategies and lay a solid foundational basis for Shigella bioconjugate vaccine human challenge studies here in Kenya.