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    Abdominal sonographic changes among HIV-TB co-infected adult patients initiating highly active antiretroviral therapy at Mulago Hospital Complex.
    (Makerere University, 2014) Jabo, Christian Roy Thomas
    Human immunodeficiency virus (HIV) infection increases the risk for infection with Mycobacterium tuberculosis (TB). In HIV-TB co-infected patients, abdominal tuberculosis accounts for 11-16% of extra pulmonary cases. Abdominal sonographic changes following initiation of Highly Active Antiretroviral Therapy (HAART) in these patients may be due to the response to anti-Tuberculous drugs and HAART, due to adverse reactions to these treatments or due to other associated co-morbidities. The changes may show improvement of abdominal features during treatment or worsening as a result of paradoxical TB-IRIS. They may also be new findings due to other opportunistic infections. Ultrasound imaging is a useful auxiliary investigative modality in the management of HIV-TB co-infected patients initiating HAART and it can demonstrate these abdominal sonographic changes. However, there is no recent research on its role in the management of HIV-TB co-infection in Uganda. Objective The study aimed at describing the abdominal sonographic findings among HIV-TB co-infected adult patients initiating HAART at Mulago Hospital Complex. Methodology A prospective descriptive study design was used. This study was nested in a prospective observational cohort study whose aim was to determine the incidence and predictors of clinical and immunological outcomes in adult patients co-infected with TB-HIV. It was conducted in the Department of Radiology at Mulago Hospital, the national referral hospital. Adults with HIV-TB co infection eligible for HAART were enrolled in the study. Serial abdominal ultrasound scans using low frequency (2-5MHZ) and high frequency probes (7-12MHZ) were performed. Data were collected on structured questionnaires, entered into a computer using Epi data version 3.1 and analysed using Stata version 11 with the help of a statistician. Results Eighty nine patients were enrolled and had a baseline ultrasound scan, 70 (78.7%) patients had a scheduled follow up scan and 10 (11.2%) had an ultrasound scan during an unscheduled visit. 9 patients (10.1%) were lost to follow up of whom 6 patients died (66.7%) while 3 (33.3%) did not return for the scheduled scan. 65.2% were males and 34.8 % were females giving a male to female ratio of 1.9:1. The age range was from 20-62 years and the median age was 32 years. There was no statistically significant difference in the abdominal sonographic findings at base line and 4 weeks after initiating HAART. Clinical features of abdominal pain and abdominal distention were significantly associated with development of abdominal sonographic changes while abdominal pain was the only symptom significantly associated with worsening of the abdominal sonographic changes (a OR=6.0, 95% CI=1.106-13.552 and a p value=0.038) on follow up or on development of symptoms of TB-IRIS. Fourteen patients had normal abdominal scans while 75 had features suggestive of abdominal TB on baseline scan like lymphadenopathy, hepatosplenomegaly and splenic nodules. Fourteen patients had features suggestive of TB-IRIS on the follow up and unscheduled scans. Co-morbidities like nephropathy, splenic candidiasis and carvenous hemangiomas were diagnosed. Sonographic changes observed in the abdomen were resolution of splenic infarction, regression of splenic abscesses, appendicitis, prostatic abscess, ascites, lymphadenopathy, cholecystitis, splenomegaly and hepatomegaly. Conclusions There is an increased incidence of HIV-TB co-infected patients with sonographic features which may be suggestive of abdominal tuberculosis at baseline scan. Worsening abdominal sonographic changes within 4 weeks of initiating HAART tend to be associated with paradoxical TB-IRIS. Abdominal pain and distention are associated with development of abdominal sonographic changes. Abdominal pain is significantly associated with worsening of abdominal sonographic features on follow up visits. There is no statistically significant difference between abdominal sonographic features at baseline and follow up 4 weeks after initiating HAART. Recommendations A study designed to establish the clinico-sonographic-pathological correlation and the schedule for follow up scans is highly recommended. Follow up abdominal sonography should be delayed beyond 4 weeks unless patients develop new symptoms or worsened symptoms. A screening ultrasound examination for TB-IRIS should be performed in all HIV-TB co-infected on treatment who develop abdominal pain.
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    Acceptance of routine testing for HIV among adult patients at the medical emergency unit at a national referral hospital in Kampala, Uganda
    ( 2006) Nakanjako, Damalie ; Kamya, Moses ; Kyabayinze, Daniel ; Mayanja-Kizza, Harriet ; Freers, Jurgen ; Whalen, Christopher ; Katabira, Elly
    HIV testing is an entry point to comprehensive HIV/AIDS prevention and care. In Uganda, Routine Testing and Counseling for HIV (RTC) is not widely offered as part of standard medical care in acute care settings. This study determined the acceptance of RTC in a medical emergency setting at Mulago national referral hospital. We interviewed 233 adult patients who were offered HIV testing. Overall, 83% were unaware of their HIV serostatus and 88% of these had been to a health unit in the previous six months. Of the 208 eligible for HIV testing, 95% accepted to test. Half the patients were HIV infected and 77% of these were diagnosed during the study. HIV testing was highly acceptable and detected a significant number of undiagnosed HIV infections. We recommend adoption of RTC as standard of care in the medical emergency unit in order to scale HIV diagnosis and linkage to HIV/AIDS care.
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    Accuracy of the M-kit absolute concentration method for detection of drug-resistant mycobacterium tuberculosis in Uganda
    (Makerere University, 2024) Orena, Beatrice
    With an increasing incidence of multidrug-resistant tuberculosis (MDR-TB), accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis to first-line and second-line plus new individualized anti-TB drugs has become crucial for proper patient management. Diagnosis of DR-TB is mainly performed using Lowenstein Jensen (LJ) and BACTEC MGIT 960 phenotypic DST methods at the Uganda National TB Reference Laboratory (NTRL). These methods have high skills demand and some require 4-6 weeks to report results with high contamination rates. Although WHO recently recommended molecular DST assays like GeneXpert and Hein MDRplus and MDRsl Line Probe Assay, these methods also present performance challenges with low coverage for drug-resistance-conferring mutations and few anti-TB agents tested. This study evaluated the diagnostic accuracy of the Multiplexing Kit (M-Kit) absolute concentration method in the detection of Drug-Resistant Mycobacterium Tuberculosis in Uganda, against the conventional LJ proportion phenotypic DST methods. A total of 212 freshly grown MTB Isolates from Tuberculosis patients referred to NTRL, were tested for drug resistance for Isoniazid, Rifampicin, Ethambutol, Moxifloxacin, Levofloxacin, Amikacin and P-Nitro Benzoic acid, on M-Kit and LJ proportion DST assay. Data obtained was entered in Microsoft Excel-2010 and statistical data analyzed using SPSS version 27 software; whereas inferential statistics, sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) and Kappa value for M-Kit with respect to the gold standard method(s) were calculated using the MedCalc software. The sensitivity and specificity findings of the M-Kit assay for different studied drugs was; Isoniazid 98.3%, 97.9%, Rifampicin 94.8%, 96.9%, Ethambutol 68.6%, 96.7%, Moxifloxacin 100%, 99.6%, Levofloxacin 100%, 99.0% respectively, and Amikacin with specificity of 100%. The accuracy for various drugs studied ranged between 87.9 % to 99.9%, with an excellent concordance between the two methods showed by kappa values ranging from 0.806 to 0.962. The M-kit absolute concentration method was found to be highly accurate in susceptibility testing of M. tuberculosis against various first and second line drugs; Isoniazid, Rifampicin, Moxifloxacin, Levofloxacin, and Amikacin, with suboptimal performance for Ethambutol, when compared with the LJ proportion method in Uganda.
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    Activation of the gab Operon in an RpoS-Dependent Manner by Mutations That Truncate the Inner Core of Lipopolysaccharide in Escherichia coli
    (American Society for Microbiology, 2004-12) Joloba, Moses L. ; Clemmer, Katy M. ; Sledjeski, Darren D. ; Rather, Philip N.
    The gab operon (gabDTPC) in Escherichia coli functions in the conversion of -aminobutyrate to succinate. One component of gab operon regulation involves the RpoS sigma factor, which mediates activation at high cell density. Transposon mutagenesis was used to identify new genes that regulate gab operon expression in rich media. A Tn5tmp insertion in the hldD (formerly rfaD) gene increased gabT::lacZ expression 12-fold. The hldD gene product, an ADP-L-glycerol-D-mannoheptose-6-epimerase, catalyzes the conversion of ADP-D-glycerol-D-mannoheptose to ADP-L-glycerol-D-mannoheptose, a precursor for the synthesis of inner-core lipopolysaccharide (LPS). Defined mutations in hldE, required for heptose synthesis, and waaF, required for the addition of the second heptose to the inner core, also resulted in high-level gabT::lacZ expression. The hldD, hldE, and waaF mutants exhibited a mucoid colony phenotype due to production of a colanic acid capsule. However, in the hldD::cat background, the high-level expression of gabT::lacZ was independent of the regulatory components for colanic acid synthesis (rcsA, rcsB, and rcsC) and also independent of manC (cpsB), a structural gene for colanic acid synthesis. Activation of gabT::lacZ in the hldD::cat background was dependent on the RpoS sigma factor. The hldD::cat mutation resulted in a sixfold increase in the levels of a translational RpoS-LacZ fusion and had a marginal effect on a transcriptional fusion. This study reveals a stress-induced pathway, mediated by loss of the LPS inner core, that increases RpoS translation and gab operon expression in E. coli.
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    Activity and dermal safety of Citrus limon (L.) Burm. f oil from Soroti, Uganda against selected Gram positive and Gram-negative bacteria.
    (Makerere University, 2018-08-02) Mpaata, Peter
    Background: Essential oils are widely used for culinary and nonculinary purposes like nutraceuticals, traditional medicine, aromatherapy and cosmetics. Genus citrus of the Rutaceae family has several plants including Citrus limon (C. limon) that are rich in essential oils known to have strong antibacterial activity. Citrus limon extracts are locally used in Uganda as astringent, to treat skin and mucocutaneous conditions. However, composition of essential oils varies with geographical origin of the plant and this may compromise their efficacy and safety. The main aim of this study was to evaluate activity of C. limon on both gram-negative and gram-positive bacteria and assess its dermal safety. Methodology: Citrus limon peel oil was extracted from fresh peels by hydro distillation using Clevenger’s apparatus for 6 hours and phytochemicals were identified by gas chromatography. Antibacterial activity was evaluated using Agar well diffusion and broth dilution methods, while dermal safety was evaluated using Draize’s method. Results: Yield of peel oil was 0.20%, D-limonene, terpineol and sabinene were the major chemical components identified. Only the gram-positive bacteria were susceptible to C. limon peel oil, the largest zones of inhibition were observed with Staphylococcus aureus and its minimum inhibitory concentration (MIC) was 105mg/ml. C. limon peel oil caused mild dermal irritation with no oedema in albino rabbits on a single exposure. Conclusion: Citrus limon oil has antibacterial activity on Staphylococcus aureus and Streptococcus pyogenes. When applied on albino rabbit skin, C. limon oilcauses hyper sensitivity reaction at a dose of 210 mg/ml and above.
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    Adolescent motherhood in Uganda: Dilemmas, health seeking behaviour and coping responses
    ( 2008) Atuyambe, Lynn Muhimbuura
    Introduction: Maternal mortality remains one of the most daunting public health problems in resource limited settings. Maternal health services play a critical role in the improvement of sexual and reproductive health and rights, especially for adolescent mothers. Adolescence is a time of rapid change and transition that can be stressful and difficult; pregnancy can further complicate this period. In Uganda, morbidity and mortality among adolescent mothers and their children are high. In order to better understand this situation, studies (I-IV) were conducted with the following objectives: to describe experiences and problems of pregnant adolescents (I); to describe health seeking behaviour (II) and analyze coping responses (III) of adolescents during pregnancy, delivery and early motherhood; and to compare health seeking practices of adolescents and adult mothers during pregnancy and early motherhood (IV). Methods: Qualitative (I-III) and quantitative (IV) studies were carried out in Wakiso district, Uganda. In study I, six focus group discussions (FGDs) were held with adolescent mothers and pregnant adolescents, and six key informant interviews (KIIs) were conducted with community leaders, persons in-charge of health units, and traditional birth attendants. In study II, 13 FGDs were conducted with married pregnant adolescents (5), unmarried pregnant adolescents (3) and married or unmarried adolescents with children (5). Semi-structured interviews were held with six KIs who were in-charge of maternity units. In study III we prospectively followed 24 pregnant adolescents (married and unmarried). Qualitative interviews about their experiences and coping responses were conducted at six months of pregnancy, one week post partum and at six months after delivery. All qualitative interviews and FGDs were tape-recorded. Content analysis (I-II) and narrative analysis (III) were done. In study IV, we conducted a cross sectional study in which 762 women (442 adolescents and 320 adults) were interviewed using a structured questionnaire. We assessed odds ratios (with 95% CI) for health care seeking during antenatal and postnatal periods, comparing adolescents to adult first-time mothers. Results: In study I, results revealed that pregnant adolescents faced domestic physical violence. Furthermore, they were psychologically violated by parents and partners as well as the community. Pregnant adolescents were treated inhumanely, overworked with household chores and had inadequate food to eat. Adolescents experienced stigma and, as a result, some carried out unsafe abortions. Both KIs and FGDs revealed that health workers were rude and unsympathetic to pregnant adolescents, which contributed to delays in seeking healthcare. Two main themes emerged in study II; 'feeling exposed and powerless‘, and 'seeking safety and empathy‘. The categories identified in the first theme were 'the dilemma of becoming an adolescent mother' and 'lack of decision making power'. In the second theme the following categories were identified: 'cultural practices and beliefs about birth', 'expectations and experiences', 'transport, a key determinant to health seeking', and 'dealing with constraints'. Adolescents felt exposed and powerless due to the dilemma of early motherhood and lack of decision-making power. The adolescent mothers seemed to be in continuous quest for safety and empathy. In study III, two narrative types and one narrative case emerged from the data: 'dealing with problems‘ (DWP), 'avoidance and shame‘ (AS) and 'violence and grief‘ (VG). The DWP type was characterized by wanting to solve her problems e.g. seeking healthcare, social support or initiating innovative ways to earn a living. Married adolescents seemed to cope better. The AS type was more resigned and helpless, avoiding realities, while the VG case was in crisis reaction and grief, and did not see any future. The first narrative type can be classified as 'problem-focused coping‘ and the last two narrative types as 'emotion-focused coping‘. Lastly, study IV revealed that adolescent mothers were significantly more disadvantaged in terms of healthcare seeking for reproductive health services and faced more challenges during pregnancy and early motherhood compared to adult mothers. Adolescent mothers were more likely to have dropped out of school due to pregnancy (OR=3.61, 95% CI: 2.40-5.44), less likely to earn a salary (OR=0.43, 95% CI: 0.24-0.76), and less likely to attend antenatal care (OR=1.52, 95% CI: 1.12-2.07) compared to adult mothers. Adolescents were also more likely to experience violence from parents (OR=2.07, 95% CI: 1.39-3.08) and to be stigmatized by the community (CI=1.58, 95% CI: 1.09-2.59). In early motherhood, adolescent mothers were less likely to seek second and third vaccine doses for their infants [Polio2 (OR=0.73, 95% CI: 0.55-0.98), Polio3 (OR=0.70: 95% CI: 0.51-0.95), DPT2 (OR=0.71, 95% CI: 0.53-0.96), DPT3 (OR=0.68, 95% CI: 0.50-0.92)] compared to adult mothers. Conclusions: Pregnant adolescents often lack basic needs like shelter, food and security. They also face relational problems with families, partners and the community (I). In search of safety and empathy, pregnant adolescents seek healthcare both in the modern and the traditional health sectors. They are in dilemma as they feel ashamed to meet their peers and also fear to visit health facilities (II). Married adolescents or those in committed relationships seem to cope better (problem-focused) with stressors during pregnancy and early motherhood than unmarried adolescents (III). Adolescents show poorer health seeking behaviour for themselves and their children, and increased community stigmatization and violence compared to adult mothers. This suggests bigger challenges to the adolescent mothers in terms of social support (IV). Adolescent friendly interventions such as pregnancy groups targeting pregnant adolescents with information of pregnancy, delivery and early childhood care could be introduced and implemented to improve adolescent mothers‘ health and that of their infants. Key words: Adolescent, motherhood, health seeking behaviour, coping responses, qualitative, narratives, Uganda.
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    Adrogenic effects of crude aqueous leaf extracts of citropsis articulata and mystroxylon aethiopicum and their safety profile in male albino rats.
    (Makerere University, 2014-05) Gakunga, Ndukui James
    Background: Erectile dysfunction is the inability of the male to attain or maintain an erection sufficient for satisfactory sexual intercourse. Many plants extracts are traditionally used to improve sexual performance in the world and Uganda in particular. Citropsis articulata (Rutaceae) locally known as Omuboro/Akatimbolo is prepared as an infusion for men in management of erectile dysfunction in western part of Uganda. M. aethiopicum (Celastraceae) commonly known as spike thorn and locally as Esasi is used for the management of helminthosis, erectile dysfunction, Black water in sheep and magic portion to keep communities together. Despite the wide use of C. articulata and M. aethiopicum by communities around the world, there is inadequate scientific information available on the actual pharmacological effects of aqueous leaves extracts on sex hormones, their safety profile and phytochemical composition. Study Objectives: The aim of this study was to determine the androgenic effects of crude aqueous leaf extracts of Citropsis articulata and Mystroxylon aethiopicum, their safety profile and phytochemical composition. Methodology: This was an experimental design whereby disease free adult male rats were randomly divided into eight groups (n=6) and kept in separate cages. The rats from group i-vii were orally dosed daily with 5mg/kg of flutamide to induce erectile dysfunction one hour prior to the administration of the extracts at doses of 150, 300 and 450 mg/kg body weight respectively of each extract. Group 7 rats received 100µg/kg bodyweight of testosterone intraperitoneally while those in group 8 were administered with 10mg/kg of normal saline (normal control). On days 0, 7, 14 and 21 the males from different groups were subjected to estrus induced females in separate cages. The sexual behavior of the rats i.e. mounting and intromission frequencies and body weights were recorded. Serum levels of sex hormones, biochemical and hematological parameters, organ weights and the histopathology were determined on day 22 with 18 hrs post last treatment. Acute toxicity used 8 weeks old Swiss mice (18-24g) that were divided into 4 groups (n=4) doses ranging from 7,500-12000mg/kg and 15,000-22,500mg/kg for both aqueous extracts respectively. Results: The phytochemical screening revealed strong presence of catechol tannins in both aqueous extracts of study plants. Rats treated with 450mg/kg of C. articulata and M. aethiopicum had a significant increase in serum testosterone levels (p<0.01 and P<0.001) respectively when compared to both normal and positive control. There was also a significant increase (p<0.01) in luteinizing hormone levels in rats treated with 450mg/kg of M. aethiopicum. Furthermore, a dose dependent increase in mounting and intromission frequencies, body weight, testis, liver, lungs and heart weight of animals treated with both aqueous extracts in all treatment groups. The LD50 value of C. articulata and M. aethiopicum were 18,985 and 9,708 mg/kg bodyweight respectively. Both aqueous extracts caused a significant dose dependent reduction (p<0.001) in Monocytes in al treatment groups. In serum biochemical parameters both aqueous extracts caused a significant reduction (p<0.05) in levels of Serum Alanine transferase enzyme. Histological examination of testis leydig cells revealed increased series of spermatogenesis and leydig cells proliferation at high doses of both extracts. Lastly, the Histopathological examination revealed no significant patho- physiological changes in the kidney and intestines in all treatment groups. However, the higher dose (450mg/kg) of M.aethiopicum caused pneumonitis and edema of lungs, focal areas of hepatic and perivascular degenerations with lymphocytes infiltration of the liver tissues. Conclusion: The study demonstrated the androgenic effects of both aqueous leaf extracts, which probably can be explained by the increase levels of serum testosterone and luteinizing hormone in all treated group. These results of the study may explain the use of these plants in the management of erectile dysfunction attributed to hypogonadism in local communities of Uganda. In addition, the extracts were found to be of less limited toxicity exonerated by the high LD50 values which is classified to be experimentally safe under OECD guidelines. However, prolonged use of higher doses of both extracts could result to Heamatological, biochemical and Histopathological changes in the living system, this implies the extracts potential to cause chronic toxicity.
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    Aetiology, risk factors and immediate outcome of bacteriologically confirmed neonatal septicaemia in Mulago hospital, Uganda
    ( 2006-06) Mugalu, J. ; Nakakeeto, M. K. ; Kiguli, S. ; Kaddu-Mulindwa, Deo H.
    Background: Neonatal septicaemia remains a major cause of morbidity and mortality. The aetiology, risk factors and outcome of this problem need to understood. Objective: To determine the aetiology, risk factors and immediate outcome of bacteriologically confirmed neonatal septicaemia in Mulago hospital. Methods: Blood cultures were aseptically obtained from neonates presenting with clinical sepsis by WHO criteria to Mulago during a five month period between July and November 2002. Blood was placed in Brain Heart Infusion media and incubated within 30 minutes. Subcultures were plated daily up to 7 days on blood, chocolate and MacConkey agar and incubated in aerobic and 5% carbon dioxide conditions. Pure colonies were identified by Gram stain and biochemical tests and antibiotic sensitivities were obtained. Results: Gram positive organisms were predominant (69.2%) followed by E. coli (17%) and Group B Streptococci (GBS) (7%). Staphylococcus aureus and E. coli dominated isolates in early and late onset sepsis. S. aureus was more sensitive to gentamicin than to cloxacillin. The sensitivity of E. coli to ceftriaxone was 94.1%. Factors significantly associated with neonatal septicaemia were male sex, history of convulsions, hypoglycaemia, lack of antenatal care, late onset sepsis and umbilical pus discharge. Mortality in sepsis cases was 18.1%, and 84% of deaths occurred in the first 2 days of admission. Hypoglycaemia was significantly associated with death (p < 0.01). Conclusion: S. aureus predominates the aetiology of neonatal septicaemia followed by E.coli. Most deaths occur in the first 48 hours of admission and hypoglycaemia is significantly associated with death.
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    African human variants that potentially impact the outcome of SARS-CoV-2 infection
    (Makerere University, 2023-11-15) Okwir, Julius
    Introduction: The SARS-CoV-2 pandemic has had an unprecedented global impact, resulting in millions of confirmed cases and deaths. However, the severity and death rates varied among different ethnicities and geographical regions, suggesting associations between host genetics and infection outcomes as reported in SARS-CoV-2 Genome-Wide Association Studies (GWAS). These studies predominantly focused on non-African populations, leaving a significant knowledge gap regarding genetic variants influencing SARS-CoV-2 infection outcomes in African populations whose allele frequencies may significantly differ from those of non-African populations. This study aimed to address this gap by identifying human variants impacting SARS-CoV-2 infection outcomes primarily using GWAS-identified variants from non-African populations and analyzing their frequencies and potential impact in African populations. Methods: Using the Genome Aggregation Database (gnomAD) as a reference, allele frequency estimates were retrieved for GWAS-identified SNPs from SARS-CoV-2 GWAS databases. Common and rare variants that potentially impact SARS-CoV-2 susceptibility and infection outcomes within African population were identified using the allele frequency information and a pairwise fixation index test (FST test) was conducted to assess the extent of genetic differentiation of these variants between African and non-African populations. Missense variants associated with COVID-19 outcomes were further identified, and linkage disequilibrium (LD) analyses of these variants were performed. Additionally, Gene Ontology (GO) pathway enrichment analysis was conducted to explain pathways relevant to infection outcomes. Results: Only a subset (40%) of SNPs identified were common and rare within the African population. FST tests indicated significant genetic differentiation between African and non-African populations. 29 missense variants associated with COVID-19 outcomes were present in 17 genes and associated with infection, critical illness, and hospitalization. High LD (R2 > 0.8) was observed with the common missense variants. GO pathway enrichment analysis unveiled 34 biological pathways linked to COVID-19 outcomes, with 2'-5'-Oligoadenylate Synthetase (OAS) activity and Cytokine-Mediated Signaling Pathway being particularly significant. Conclusion: These findings offer valuable insights into the possible genetic determinants of COVID-19 outcomes in African populations. The study underscores the need for further research to explain the precise mechanisms underlying these associations and paves the way for personalized therapies targeted at individual genetic profiles. This knowledge could be pivotal in combating not only existing but also future coronavirus infections, thereby contributing to public health preparedness.
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    Analysis of HIV-1 sub types among blood donors in Uganda using a multi-region hybridization assay.
    ( 2008-04) Bagaya, Bernard Ssentalo
    BACKGROUND: Uganda has been a focus of HIV/AIDS intervention efforts, including vaccine clinical trials. HIV-1 genetic diversity poses challenges for design of efficacious vaccines. Data on HIV-1 genetic diversity is crucial for design of an effective vaccine in Uganda. Some previous studies have reported discrepant results probably due to varied sensitivity of different sub typing methods and different study populations. Also no study sampled HIV-1 across the entire country. STUDY OBJECTIVES: I. To determine the HIV-1 prevalence, II. HIV-1 sub type distribution among blood donors attending donation centres located in five different regions of Nakasero / Kampala (Central), Mbale (Eastern), Fort Portal (Western), Mbarara (Southern) and Gulu (Northern region). METHODOLOGY: 6, 192 samples were collected from anonymous blood donors in five regional blood banks of Uganda. All samples were tested for HIV-1 using MUWRP laboratory algorithm. HIV-1 viral load and HIV-1 sub typing was performed on HIV-1 positive samples using Roche Amplicor HIV-1 monitor test v1.5 and MHA acd respectively. RESULTS: HIV-1 prevalence among blood donors was 1.3% but was highest in kampala at 1.8% and Gulu 1.5% and was lowest in Fort portal and Mbarara at 0.9% and 1.0% respectively. Prevalence increased with increasing age being 3.2% among the 34-39 and 3.4% in the 50+ age groups. HIV-1 subtypes A accounted for 50% of cases, 25% subtype D, 2% subtype C and recombinants AD made up 20% and 3% for AC. Subtype A was dominant in 4 out of 5 regional blood banks while subtype D predominated in Fort Portal. Sub type distribution was comparable across gender but the HIV-1 prevalence was higher in female (1.6%) blood donors than in males (1.3%) CONCLUSIONS: This study adds information to the HIV-1 sub type distribution in Uganda and informs vaccine design and clinical trials. HIV-1 pure sub type A was the most predominant sub type among blood donors in Uganda and the proportion of pure sub type C was very low in this study. Recombinant HIV strains being responsible for almost a quarter of cases among blood donors, a low risk population further depicts the increasing role of recombinants and dynamic nature of the HIV/AIDS pandemic HIV-1 subtype distribution was comparable with respect to gender. The study also demonstrates development of the capacity to genotype HIV-1 using the Real- Time PCR based MHAacd technique for the first time in Uganda.
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    Anatomical variations in the course of the sciatic nerve among ugandans.
    ( 2008-05) Kukiriza, John
    BACKGROUND: The sciatic nerve is the biggest nerve in the body and supplies most of the lower limb except the anterior compartment of the thigh and the skin of the medical aspect of the leg. It is commonly injured during the application of intragluteal injections. OBJECTIVES: To determine the course of the sciatic nerve in the thigh and how it varies in different individuals. METHODS: This was a descriptive cross sectional study which was carried out in the anatomy dissection laboratory, Makerere medical school and the mortuary at mulago hospital. RESULTS: 80 Limbs were dissected among which 56 (70%) were male and 24 (30%) were female. The height of the specimens ranged from 145 cm to 182 cm. In all cases the nerve was located in the lower medical quadrant of the gluteal region. The nerve entered the gluteal region in an intact state in 62 (77.5%) individuals and in a bifurcated state in 18 (22.5%) individuals. Among the 62 intact cases, the level of bifurcation of the nerve was found at an average vertical distance above the transverse popliteal crease of 8.5cm. Height of an individual and level of bifurcation of the nurve are not related. The common peroneal nerve passed above and the tibial nerve below the superior piriformis in 2 cases (2.5%) and the common peroneal nerve pierced piriformis and the tibial nerve passed below piriformis in 1 case (1.3%). In 4(5%) cases, the nerve which entered the gluteal region. 89.4% of sciatic nerve main trunks bifurcate between 3.8 and 12 cm above the transverse popliteal crease. Height of an individual is independent of the level of bifurcation of the nerve above the transverse popliteal crease. The sciatic nerve enters the gluteal region when intact in 77.5 % and when bifurcated and fuses again in 5% of individuals. RECOMMENDATIONS: Health workers should avoid the lower medial quadrant when administering intragureal injections and also put sciatic nurve variations into consideration when investigating sciatica. Popliteal block of the sciatic nerve above the transverse popliteal crease should be done above 12 cm.
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    Anatomical Variations of Gall bladder and Bile ducts-An MRI study
    (Makerere University, 2023-11-04) Kigundu, Yason
    Introduction: The Anatomy of the biliary tree is complex and is characterized by the frequent presence of Anatomical variations which can be found in ~50% of the general population. Accurate knowledge of the bile duct system anatomy is critical to properly diagnose hepatobiliary pathologies and minimize postoperative complications. Methods: This was a cross-sectional study at the Kampala MRI Centre. This study involved a retrospective analysis of Magnetic Resonance Cholangio-Pancreatography images of patients investigated from January 2017 to December 2022. Results: Out of the 231 patient MRCP images, we found out that the majority (57%) were female. In addition, the majority (43.3%) were 51 years and above. The commonest Gallbladder shape observed was the pear shape in 56.3% of cases. External gallbladder variations included Phrygian cap (16.5%) and Hartman pouch in 11.3% of the cases. All patients (231) had sub hepatic gallbladders. The majority of patients (53.2%) had the typical cystic duct course and insertion with a high entry in 24.2%, low entry in 18.2%, and medial entry in 4.4% of the cases. A majority 118 (51%) of the patients had Type 1 variation of intrahepatic ducts, 29.9% had type A2, 14.7% had type A3, 4% had type A5 while less than 1% had a very rare type of variation. Furthermore, this study showed that the mean Common Bile Duct (CBD) diameter was 4.7mm, the standard deviation was 1.4mm and a range of (1.6-8.5) mm. It was noted that for every unit increase in the average age, there is an increase in the average CBD diameter.
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    Anti-mycobacterial activity and acute toxicity of Erythrina abyssinica, Cryptolepis sanguinolenta and Solanum incanum
    (Makerere University, 2010-10) Bunalema, Lydia
    Tuberculosis (TB) kills approximately two million people annually. Efforts to treat the disease have been made much more difficult due to development of drug resistant TB strains (MDR and XDR TB) and co-infection with HIV AIDS. There is an urgent need therefore, to search for and develop new, inexpensive and effective anti-TB drugs. Extracts from three plants, Solanum incanum, Cryptolepis sanguinolenta and Erythrina abyssinica used in traditional medicine to treat TB symptoms were screened for anti-mycobacterial properties against a Rifampicin resistant, pan sensitive and Mycobacteria avium strains. In addition, the acute toxicity profile and phytochemistry of the active extracts were studied. The chloroform extract of E. abyssinica was the most active on M. avium wild strain and the rifampicin resistant strain (MIC= 0.3 and 0.39 mg/ml respectively). Against the pansensitive strain the methanol total crude extract was most active (MIC= 0.2 mg/ml). C. sanguinolenta total crude methanol extract was also active against the three strains of mycobacteria; however S. incanum did not show activity on any of the strains. Toxicity studies showed that the two plants had an LD50 of more than 500mg/kg body weight and thus considered to be safe. E. abyssinica extracts and C. sanguinolenta total crude extract contained alkaloids, terpenoids, tannins and flavones. Saponins and phenols were not detected in all extracts. C. sanguinolenta and E. abyssinica have potential to be developed into new anti-TB drugs. The results have also validated traditional knowledge from the local people regarding the use of these species to treat TB.
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    Antibody responses to Mycobacterial glycans and glycolipids as potential correlates of protection from mycobacterium tuberculosis infection in BCG vaccinated children
    (Makerere University, 2021-04-01) Ssejjoba, Martin
    Background: Globally, tuberculosis (TB) has remained the main cause of death from a single infectious pathogen. The only licensed TB vaccine to date, BCG, has variable efficacy. We need to understand the mechanism underlying the protection of BCG mediated immunity against TB to develop more efficacious vaccines. This study aimed to evaluate antibody responses to mycobacterial glycoconjugate antigens in BCG vaccinated children as potential correlates of protection from M.tb infection. Methodology: A retrospective case-control study design was used to determine the relationship between antibody responses to mycobacterial glycoconjugate antigens and M.tb infection in BCG vaccinated children. Cases were defined by positive T-SPOT.TB test while controls tested negative on this test. The cases and controls were matched based on cofounders; age, sex, BCG scar and area of residence. Enzyme-linked Immunosorbent Assays (ELISA) were used to measure antibody responses in archived children’s samples. Initial investigations were conducted to determine optimal arabinogalactan (AG), lipoarabinomannan (LAM) and Ag85 complex antigen concentration and plasma dilutions for IgG antibody ELISA assays. Anti-AG, anti-LAM and anti Ag85 complex IgG antibody responses were then measured in 88 cases and 176 matched controls from birth to 5 years of age. Results: Optimisation assays indicated that the optimal antigen concentration was 2.5µg/ml for Anti-AG, anti-LAM and anti-Ag85 complex IgG antibody ELISA assays. On the other hand, 1 in 25 was the optimal sample dilution for detection of anti-Ag85 Complex and anti-AG antibodies whereas 1 in 50 was optimal for detection of anti-LAM antibodies. Following ELISA testing of the samples it was found that anti-LAM antibodies were strongly associated with an increased likelihood of M.tb infection at the 1-year time point (adjusted odds ratio=6.302, 95% confidence interval (CI): 1.970, 20.165 p=0.002) whereas anti-Ag85 complex antibodies were weakly associated with a reduced likelihood of M.tb infection at only the 4-year (adjusted odds ratio=0.35, 95% confidence interval (CI): 0.101, 1.206, p=0.096) and 5-year time points (adjusted odds ratio=0.285, 95% confidence interval (CI): 0.069, 1.185, p=0.084). However, we found no evidence of association between anti-AG antibodies and M.tb infection at all the time points investigated. Conclusion: Our findings suggest that anti-LAM antibodies at the 1st year of childhood are associated with increased risk of M.tb infection rather than protection whereas anti-Ag85 complex antibodies at the 4th and 5th years of childhood have are weakly associated with protection. On the other hand, anti-AG antibodies are not associated to M.tb infection in children. These associations should be further investigated using in vitro assays to determine if these antibodies enhance or inhibit M.tb cellular infection.
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    Antifungal susceptibility patterns of vulvovaginal candida species among women attending antenatal clinic at Mbarara Regional Referral Hospital, South Western Uganda.
    (SCIENCEDOMAIN International, 2014) Kiguli, James Mukasa ; Itabangi, Herbert ; Atwine, Daniel ; Kibuka, Livingstone Sserunkuma ; Bazira, Joel ; Byarugaba, Frederick
    Aims: To identify the Candida species that cause vulvovaginal candidiasis and determine their antifungal susceptibility patterns. Study Design: This was a cross-sectional study. Place and Duration of Study: The study was conducted at the antenatal clinic of Mbarara Regional Referral Hospital in Mbarara Municipality, between December 2012 and February 2013. Methods: High vaginal swabs from 456 pregnant women were subjected to microscopy and culture on Sabouraud Dextrose Agar. Candida isolates were identified by the germ tube and Analytical profile index (API® Candida) tests. Susceptibility to fluconazole, itraconazole and voriconazole was determined by the Etest strips and for clotrimazole and nystatin by the disc diffusion method on Mueller Hinton agar supplemented with 2%w/v glucose and 0.5μg/ml methylene blue dye. Results: Of the 456 High vaginal swabs cultured, 207 grew Candida species. Species distribution was as follows: C. albicans (78.95%), C. glabrata (14.35%), C. krusei (3.35%), C. tropicalis (1.44%), C. famata (0.96%), C. parapsilosis (0.48%) and C. lusitaniae (0.48%). Resistance to nystatin was only observed in 0.61% of C.albicans. Resistance to clotrimazole was observed in 50%, 36.67% and 0.61% of C. famata, C. glabrata and C. albicans respectively. C. krusei showed a high resistance of 71.43% to fluconazole. C. glabrata, C. krusei, C. famata and C. lusitaniae exhibited 100% resistance to itraconazole. Resistance to voriconazole of less than 11% was exhibited by only C. albicans and C. glabrata. Conclusion: C.albicans was susceptible to most antifungal agents tested except itraconazole and voriconazole. All isolates were susceptible to nystatin except less than 1% of Candida albicans. Non-albicans demonstrated resistance to some drugs especially itraconazole. We recommend use of Nystatin for empirical management of vulvovaginal candidiasis among pregnant women.
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    Antimalarial susceptibility of plasmodium falciparum isolates from patients presenting with uncomplicated malaria at mulago hospital.
    ( 2007-10) Nakaziba, Rebecca
    INTRODUCTION AND OBJECTIVES: Malaria remains the greatest cause of morbidity and mortality in sub-saharan Africa. This work was done to determine the sensitivity of plasmodium falciparum isolates to the currently used antimalarial drugs (Chloroquine diphosphate, Artemether, quinine sulphate, Amodiaquine, Lumefantrine) and drug combinations (Artemether-Lumefantrine, Artemether-Amodiaquine, Artemether-Quinine sulphate) in Uganda, particulary in Mulago hospital. METHOD: Wild strains of P. falci[parum obtained from patients attending the out patient departemtn of mulago hospital, kampala, Uganda, were screened for sensitivity to the above antimalarial drugs using the parasite lactate dehydrogenase assay described by Makler et al, 1993 in which parasite growth and thus density is determined by the amount of the enzyme (which reduces APAD causing it to turn blue with the NBT dye) produced by the parasites. The parasite sensitivity to the drugs was described by the IC50 i.e the drug concentration added to an in vitro culture of parasites that reduces parasite growth by 50%. RESULTS: Most of the test samples were sensitive to quinine sulphate among the sinlge drugs followed by Artemether, the least being lumefantirc. Artemether- lumefantric was among the most active among the combined drugs and Artemether- Quinine was the least active. CONCLUSION: Quinine was the most active single drug and arthemether-lumefantric was the most active among the combined drugs.
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    Antimicrobial resistance among helicobacter bacteria isolates from patients attending the gastroenterology unit at Nsambya hospital Kampala, Uganda
    (Makerere University, 2024-09) Opolot, Aedeke Emmanuel
    Background: It is confirmed that 95% of duodenal and 80% of gastric ulcers are due to Helicobacter infections. Helicobacter diagnosis is mainly by urea breath test, blood antibody test, stool antigen test, gastric biopsy and culture. In Western Europe the prevalence of Helicobacter infection is estimated to be 34.3%, North America 37.1% and Africa 70.1% with Nigeria leading with 87.7% and Uganda 68%. Despite wide use of these combination therapies in Uganda which includes a combination of a proton inhibitor, amoxicillin, metronidazole or omeprazole with the second line drugs being fluoroquinolones and tetracycline, antimicrobial resistance to isolates of Helicobacter is becoming a major clinical problem undermining the efficacy of eradication regimens which had shown good effects in the past. In this study we determined the proportion of Helicobacter antigen positive and negative specimens giving a positive Helicobacter culture result, the prevalence of resistance to amoxicillin, clarithromycin, levofloxacin, tetracycline, metronidazole and rifampicin among the Helicobacter isolates and the factors associated with drug resistant Helicobacter in Uganda. Methods and materials: This was a cross-sectional study that recruited 146 participants with peptic ulcer disease from Nsambya hospital, Uganda. Stool and gastric biopsy samples were collected and tested for Helicobacter antigen using a rapid diagnostic test. Helicobacter isolates were cultured using selective agar media and antimicrobial susceptibility testing was performed using Ezy MICTM strips (HiMedia, India). Minimum inhibitory concentration breakpoints were interpreted according to EUCAST guidelines. Data was analyzed using IBM SPSS. Results and conclusion: A total of 146 participants clinically diagnosed with peptic ulcer disease were recruited. Gastric biopsy samples collected from endoscopy by the surgeon were 143/146 (97.9%).81/146 (55.5%) females recruited into the study. The median age was 42 and SD 17.6 years. A total of 53/143 (37.1%) gastric biopsy samples tested positive for Helicobacter antigen, 44/143 (31.0%) were culture positive, 22/143 (15.4%) gastric biopsy samples were both Helicobacter antigen and culture positive. Resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline and rifampicin was 45/46 (97.8%), 44/46 95.7%, 44/46 95.7%, 35/46 76.1%, 32/46 69.6% and 24/46 52.2% respectively History of treatment (p-value = 0.03). Duration of illness (p-value = 0.034), and bloating (p-value = 0.045). Antimicrobial resistance among Helicobacter isolates in Kampala, Uganda is very high and amoxicillin is the most resistant drug with over 90% resistance and rifampicin is the most susceptible drug for treating Helicobacter infection.
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    Antimicrobial Resistance Patterns and Molecular Characterization of Klebsiella pneumoniae in Clinical Isolates at Mbarara Regional Referral Hospital
    (Scientific Research Publishing, 2019) Joseph, Turugurwa ; James, Mwesigye ; Kennedy, Kassaza ; Fredrick, Byarugaba ; Taseera, Kabanda ; Benson, Musinguzi
    Background: Klebsiella pneumoniae is one of the most frequent opportunistic pathogens causing a range of infections and being resistant for beta-lactamases (ESBL) and Carbapenemases. Aim: The aim of the present study was to determine the antimicrobial resistance patterns and molecular characterization establishing the phenotypes and genotypes associated with drug resistance, an antibiogram of genotypically positive isolates for resistance of Klebsiella pneumoniae in clinical isolates at MRRH. Materials and Methods: A laboratory-based descriptive cross-sectional study that was conducted from September 2018 to May 2019 at MRRH. Klebsiella pneumoniae was identified by cultural and biochemical methods. Antibiotic sensitivity test was performed by modified Kirby-Bauer disc diffusion technique. ESBL production in Klebsiella pneumoniae was tested by double-disc synergy test, Carbapenemase production by MHT, Boronic Acid or EDTA test using Meropenem phenotypically and both resistance confirmed genotypically by Multiplex PCR. Results: Out of 1055 clinical isolates, 298 (28.2%) were found positive for Klebsiella.spp, 175 isolates were subcultured among which 22 (12.57%) were K. pneumoniae based on API 20E. Overall Sensitivity patterns of these Klebsiella pneumoniae isolates to Ceftriaxone, (Amoxicillin/Clavulanate), Gentamicin, Cefepime, Ciprofloxacin, Cefoxitin, Nitrofurantoin, Cefuroxime, piperacillin/tazobactam, Meropenem, Ceftazidime and cefotaxime were 72.7%, 63.7%, 54.5%, 45.5%, 31.8%, 31.8%, 27.3%, 27.3%, 22.7%, 22.7%, 18.2%, 9.1%, 9.1% respectively. ESBL producing K. pneumoniae was found at 68.18% (15/22) phenotypically. Genotypically; the ESBL genes were blaCTX-M (100%), blaSHV (80%) and blaTEM (100; 47%); 8/15 (73.3%) had CTX-M, SHV, TEM, 4/15 (26.67%) CTX-M, TEM, 3/15 (20.00%) CTX-M and SHV. Carbapenemase producing K. pneumoniae was found at 31.82% (7/22) phenotypically; 1/7 (14.28%) by MHT, 4/7 (57.14%) Boronic acid test and 2/7 (28.58%) EDTA test. Genotypically; 3/4 [(75%) 42.86%] had OXA-48, 1/4 [(25%) 14.28%] OXA-48 and KPC gene, 1/2 [(50%) 14.28%] KPC and VIM, 1/2 [(50%) 14.28%] KPC and KPC gene [(100%) 14.28%]. Conclusion/Recommendations: DDS to be used for ESBL production, MHT, Boronic Acid test and EDTA tests using Meropenem/or Imipenem for Carbapenemase-production routinely.
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    Antimicrobial stewardship practices and quality of antibacterial use in children under five and women in labour with obstetric risk factors in selected health facilities in Uganda
    (Makerere University, 2024) Kimbowa, Isaac Magulu
    Introduction Bacterial infections are a leading cause of morbidity and mortality in Ugandan hospitalised children under the age of five. Disparities exist in using antibacterial agents to treat bacterial infections at various health facilities in Uganda, resulting in various clinical outcomes that may be appropriate or inappropriate, compromising the quality of antibacterial usage in children under the age of five. The World Health Organisation and Ministry of Health have recommended implementing multifaceted interventions like (Medicine and Therapeutic committees (MTCs) and antimicrobial stewardship programmes (ASPs) to improve the quality of antibacterial use from birth to five years if child survival is to be achieved in health facilities low and middle-income countries. However, the extent of implementation of the multifaceted intervention) has remained undetermined amidst practices of off-label antibacterial use and inappropriate intrapartum antibacterial prophylaxis (IAP) during maternal labour in different health facilities in Uganda. Nevertheless, there is little evidence about the impact of these variables on the use of antibacterial medication in children under the age of five. Aim The study aimed to investigate antimicrobial stewardship practices and the quality of antibacterial use in children under five and women in labour with obstetric risk factors in selected health facilities in Uganda. Methods Sub-study I was an explanatory sequential mixed-method study conducted from August 2019 to February 2020 in a two-stage approach to determine the structure and functional role of MTCs in supporting optimal antibacterial use in selected health facilities. Sub-study II was conducted in three parts to determine antimicrobial stewardship practices to optimise antibacterial use in selected health facilities in Uganda. It was a cross-sectional study conducted using an interviewer-administered questionnaire among healthcare providers in selected health facilities in Uganda from October 2019 to February 2020. Sub-study III was a concurrent mixed-method design to investigate the extent of off-label antibacterial use among hospitalised children with suspected bacterial infections from May to October 2019 in seven tertiary hospitals in Uganda. Lastly, Sub-study IV was a cross-sectional study conducted to examine the extent of maternal intrapartum antibacterial exposure among women in labour with obstetric risk factors in selected health facilities in Uganda from May to October 2019. A retrospective review of medical records for one year (2018 to 2019) was conducted in seven tertiary hospitals. Results In this study, MTCs were more established in tertiary health facilities (RRH (n=10) and PNFPs (n=3) than in general hospitals (n=3). The most notable structure in the 16 MTCs that supported optimising antibacterial use included a membership ranging from 7 to 14 (median 10), and the mean (standard deviation) of subcommittees was 4 (+ 1.03) with the most frequent subcommittees as supply chain and logistics (14/16, 88%), antimicrobial stewardship (13/16, 81%), and infection control (12/16,75%) subcommittees. The most frequent activities supporting optimising antibacterial use included evaluating and selecting an antibacterials list (n=14, 88%) and conducting an antimicrobial stewardship activities list (n=15, 94) (substudy I). Of the 582 healthcare providers interviewed, 87% acknowledged the importance of antibacterial resistance in their hospitals, and 92% acknowledged its importance nationally. Furthermore, 91% of healthcare providers agreed that antibacterial resistance impacted their choices of antibacterial agents, while 85% agreed that it affected patients' clinical outcomes. The three top-ranked causes of antibacterial resistance, as determined by the relative importance index (RII) analysis, were prescribing an antibacterial when not needed (RII=0.879) and poor adherence of patients to prescribed antibacterial courses (RII=0.865), prescribing the wrong antibacterial (RII=0.833). Only 11% of healthcare providers had a high perception that their hospitals had effectively adopted hospital policy action to combat antibacterial resistance. The most perceived adopted policy actions were standard treatment guidelines, infection prevention and control, and distribution of high-quality antibacterials. Furthermore, within the 32 health facilities, 58% (340/582) of the healthcare providers had a high AMS attitude level. The AMS attitude levels were significantly associated with the sex of the female (aOR: 0.66, 95% CI: 0.47–0.92, P < 0.016), as well as with having a degree of bachelor's (aOR: 1.81, 95% CI: 1.24–2.63, P < 0.002) and master's degree (aOR: 2.06, 95% CI: 1.13–3.75, P < 0.018). Pharmacists among all interviewed healthcare providers had the highest mean AMS attitude scores. Conversely, 46% ( 261 / 582) of the healthcare providers had fair AMS practices. Medical officers had the highest mean AMS practice scores compared to other healthcare providers. Healthcare providers in western Uganda were significantly less likely to score high AMS practices (aOR: 0.52, 95% CI 0.34–0.79, P < 0.002). Lastly, despite the limited adoption of ASP (n=14, 44%), 30 of 32 healthcare institutions used at least one AMS strategy to support optimal antibacterial use. The core AMS strategy that was most implemented to optimise antibacterial use was preauthorization and approval, while combinational therapy was the most implemented supplemental AMS strategy (Substudy II). In the seven tertiary institutions, 88% (CI 86% to 89%) of 968 children under five had used off-label antibacterials. The age groups with the highest rates of off-label antibacterial use were newborns (94%; 97/103), hospitalised children (91%; 381/421), and those receiving ampicillin (91%; 384/420). The most common factors influencing off-label antibacterial usage were healthcare providers, hospitals and drug-related drivers (Sub-study III). The prevalence of inappropriate maternal intrapartum antibacterial prophylaxis exposure was 54.9% (95% Cl 51.5-58.1). The most frequent reason for inappropriate maternal intrapartum antibacterial prophylaxis was inappropriate timing of IAP (n=589, 67.5%), inappropriate dosing (618/873, 70.8%), and inappropriate antibacterial agent (n=479, 54.9%). Factors associated with inappropriate maternal intrapartum antibacterial exposure were mothers delivering from PNFP (PR 1.59 (95% CI 1.40-1.82), mothers being divorced or separated (PR1.38 ( 95% CI 1.11-1.71), mothers not referred to a health facility (PR 1.24(95% CI 1.08-1.42), mothers admitted before labour (PR 1.26(95% CI 1.06-1.36), mothers with no reported peripartum fever (PR 0.54( 95% CI 0.46-0.64) (Sub-study IV). Conclusion The implementation of multifaceted interventions (MTCs and antimicrobial stewardship programmes) to support optimal antibacterial use in children under five and women in labour with obstetric risk factors is still low in Uganda. MTC structures were more developed in tertiary hospitals than in general hospitals, they supported the formulary management and establishment of antimicrobial stewardship practices. Despite health facilities' low implementation of antimicrobial stewardship programmes, they adopted preauthorization and approval as a core AMS technique to optimise antibacterials in children underfive. Most healthcare providers have a high antimicrobial stewardship attitude and fair practice scores, and few perceived their hospitals to be effective in adopting policy actions to support the establishment of antimicrobial stewardship programmes in health facilities in Uganda. The low implementation of multifaceted interventions has not rendered improvement in the quality of antibacterial use in hospitalised children under five and women in labour with obstetric risk factors. The high prevalence of off-label antibacterial administration in children under five, along with high inappropriate maternal intrapartum antibacterial prophylaxis exposure among women in labour with obstetric risk factors, indicatied a low improvement in the quality of antibacterial use in children under five and women in labour.
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    Antimicrobial Susceptibility and Plasmid Genes Conferring Multi-Drug Resistance among Klebsiella Pneumoniae Isolated from patients attending Mulago National Referral Hospital from 2017 to 2018.
    (Makerere University, 2019-11-25) Eyapu, Christopher
    Introduction: Antimicrobial Resistance results from exposure of microorganisms to antimicrobial substances, consequently with the ineffectiveness of treatments and exacerbating the risk of spread to others. Klebsiella pneumoniae is one of the carbapenem-resistant, ESBL-producing Enterobacteriaceae listed among the Priority 1 critical pathogens in the world by 2017 WHO report on the global status of antibacterial resistance. The dissemination of antimicrobial resistance in numerous gram-negative bacteria has majorly been attributed to inter- and intra-specific DNA exchange by horizontal transfer of plasmid-located antimicrobial resistance genes. Plasmids are extra-chromosomal elements of DNA present in bacteria that replicate independently of the host genome. Methodology: This was a laboratory-based cross-sectional study in which the susceptibility profiles and conjugative genes of all the Multidrug-resistant Klebsiella pneumoniae isolates previously obtained from individuals attending Mulago National Referral Hospital were used. Recovery of stored isolates from January 2017 to December 2018 for re-identification by biochemical methods as Klebsiella pneumoniae, was performed. Susceptibility profiles of Klebsiella pneumoniae isolated in the selected study period were generated to determine Multi-Drug resistance by using the Kirby Bauer disc diffusion method. The Imipenem-EDTA double-disk synergy test was then performed to detect carbapenemase production. Conjugation experiments on L.B broth media using E. coli J53 as a recipient strain was done. Plasmid DNA from transconjugants was then extracted for PCR before gel Electrophoresis. Results: 63/67 of the test isolates were ESBL producers. Increasing resistance rates were observed, 83.3% of the MDR isolates were resistant to Ceftazidime, 99% to cefotaxime, 80.3% to amoxicillin-clavulanic acid and 84.9% to Cefepime. blaCTX-M was the most predominant gene in this setting although it was not readily disseminated by conjugation. A novel efflux pump in this setting OQX-AB was identified in 12/24 of the isolates tested that is responsible for multi-drug resistance. PCR detected the presence of blaTEM and QNR-s, blaTEM and OXA-1, blaTEM and aac(3)-IIa variants being disseminated by plasmids in combination from the same isolates after conjugation experiments. These isolates were majorly from patients admitted to the ICU of Mulago National Referral Hospital (71.4%). Conclusion: There was a high prevalence of plasmid associated conjugative genes in this setting specifically blaTEM, OXA-1, QEP, QNR-s, QNR-b and aac(3)-IIa gene. These findings elucidate the need for an active surveillance network for gram negative bacteria in Uganda.