| 1. |
- Bwanga, Freddie
(författare)
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Rapid tests for multidrug resistant tuberculosis in low income settings
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis (TB) is at epidemic levels in the resource-limited settings (RLSs) due to HIV/AIDS, poverty and insufficient TB control programmes. These factors are also contributing to TB drug resistance. Patients with multidrug drug resistant tuberculosis (MDR-TB) do not respond to first line drugs. These patients require unique drug regimens, making it necessary to routinely screen for MDR-TB. Screening for MDR-TB with the Lowenstein-Jensen proportion method (LJPM), which is common in the RLSs is a very slow process taking 2-3 months. More rapid tests suitable for RLSs are urgently needed. In this thesis, a comparison of the technical and operational performance of several rapid tests for MDR-TB was done, and the most optimal tests for RLSs are proposed. In paper I, a meta-analysis of rapid tests for direct detection of MDR-TB was conducted. The direct nitrate reductase assay (NRA), microscopic observation drug susceptibility (MODS) and Genotype® MTBDRplus (GT-DRplus) were highly sensitive and specific, and far more rapid than the conventional indirect drug susceptibility testing (DST). In paper II, the NRA, MODS, Mycobacterium Growth Indicator Tube (MGIT 960), GT-DRplus, Alamar blue, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and resazurin assays were compared head-to-head for indirect detection of MDR-TB at the National Tuberculosis Reference Laboratory (NTRL) Kampala. The NRA, MGIT 960, GT-DRplus and MODS were the most sensitive and specific tests, with significantly shorter time to results compared to the LJPM. In paper III, the direct NRA and MODS assays were compared at the NTRL on sputum specimens from consecutive re-treatment TB patients. Interpretable results were obtained in over 90% of the samples with both assays. The median days to results were 10 with the NRA and 7 with MODS. The direct NRA was more sensitive and specific, and was cheaper. In paper IV, the sensitivity, specificity, time to results (TTR) and reproducibility of the direct GTDRplus against the MGIT 960 was assessed. Sensitivity and specificity were 100% and 96% for detection of rifampicin resistance; 81%, and 100% for isoniazid resistance; and 92%, and 96%, for MDR-TB, respectively. The TTR was 1-3 days, and concordance of results between the Molecular Laboratory at Makerere University and the FIND Diagnostics Laboratory was 98%. In paper V, we applied spoligotyping to study the clustering rate and predominant genotypic strains of 99 MDR-TB strains isolated from patients in Kampala. Eighty-three percent of the strains occurred in clusters, and the T2 lineage was the largest single cluster. Conclusion. The direct NRA and the GT-DRplus appear to be the most appropriate tests for MDR-TB in RLSs. The NRA being the cheapest test can be applied where resources are extremely limited, while the ultra rapid but commercially available GT-DRplus can be used where resources permit.
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| 2. |
- Lindstrand, Ann, et al.
(författare)
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Pneumococcal Carriage in Children under Five Years in Uganda-Will Present Pneumococcal Conjugate Vaccines Be Appropriate?
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs) are currently being implemented in many low-income countries. PCVs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission. In Uganda, PCV was launched in 2014, but baseline data is lacking for pneumococcal serotypes in carriage.OBJECTIVES: To study pneumococcal nasopharyngeal carriage and serotype distribution in children under 5 years of age prior to PCV introduction in Uganda.METHODS: Three cross-sectional pneumococcal carriage surveys were conducted in 2008, 2009 and 2011, comprising respectively 150, 587 and 1024 randomly selected children aged less than five years from the Iganga/Mayuge Health and Demographic Surveillance Site. The caretakers were interviewed about illness history of the child and 1723 nasopharyngeal specimens were collected. From these, 927 isolates of S. pneumoniae were serotyped.RESULTS: Overall, the carriage rate of S. pneumoniae was 56% (957/1723). Pneumococcal carriage was associated with illness on the day of the interview (OR = 1.50, p = 0.04). The most common pneumococcal serotypes were in descending order 19F (16%), 23F (9%), 6A (8%), 29 (7%) and 6B (7%). One percent of the strains were non-typeable. The potential serotype coverage rate for PCV10 was 42% and 54% for PCV13.CONCLUSION: About half of circulating pneumococcal serotypes in carriage in the Ugandan under-five population studied was covered by available PCVs.
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| 3. |
- Nabweyambo, Sheila, et al.
(författare)
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No association of a Vascular endothelial growth factor A (VEGFA) gene polymorphism with pre-eclampsia among pregnant women in Uganda
- 2023
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Ingår i: BMC Genomics. - : BioMed Central (BMC). - 1471-2164. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vascular endothelial growth factor A (VEGFA) is a major angiogenic factor that plays an important role in the formation of blood vessels during embryonic development. VEGFA has been implicated in the pathophysiology of pre-eclampsia (PE), since pre-eclamptic women present with reduced levels of free circulating VEGFA. The 3' untranslated region (3'-UTR) of the VEGFA gene consists of elements that regulate the transcription and hence expression of the VEGFA protein in circulation. Hence it is suggested that variations thereof could underlie the reduced VEGFA levels observed in pre-eclamptic women. The purpose of this study was to investigate presence of the + 936C/T polymorphism, a common single nucleotide polymorphism (SNP) in the 3'-UTR of the VEGFA gene, and determine its association with PE among pregnant women in Uganda.Results: There was no significant difference observed in the allele and genotype frequencies of the + 936C/T 3' UTR-VEGFA polymorphism between pre-eclamptic and normotensive pregnant women (P > 0.05). Additionally, there was no significant difference in the median plasma levels of free VEGFA among women with the wild type, CT and TT genotypes of the + 936C/T VEGFA polymorphism (median = 0.84 pg/mL (IQR = 0.39-1.41) Vs 1.05 (0.61-1.18) Vs 1.05 (1.05-1.05) respectively, p-value = 0.7161).Conclusions: These study findings indicate that the + 936C/T 3' UTR-VEGFA polymorphism had no significant association with increased susceptibility to PE among women in Uganda. Further studies with a larger sample size are recommended.
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| 4. |
- Ocheng, Francis, et al.
(författare)
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Antibacterial activities of extracts from Ugandan medicinal plants used for oral care
- 2014
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Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 155:1, s. 852-855
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Tidskriftsartikel (refereegranskat)abstract
- Ethnopharmacological relevance: Medicinal plants are widely used for treatment of oral/dental diseases in Uganda. Aim of the study: To investigate antibacterial activities of 16 commonly used medicinal plants on microorganisms associated with periodontal diseases (PD) and dental caries (DC). Materials and methods: Pulp juice and solvent extracts (hexane, methanol and water) from the plants were tested against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia associated with PD and Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus associated with DC. Tests were done using agar well-diffusion (pulp juice) and agar-dilution (Solvent extracts) assays. Results: Pulp juice from Zanthoxylum chalybeum and Euclea latidens showed activity against all the bacteria, Zanthoxylum chalybeum being most active. Hexane extract from aerial part of Helichrysum odoratissimum was most active (MIC: 0.125-0.5 mg/ml). Methanol extract from leaves of Lantana trifolia showed activity against all bacteria (MIC: 0.25-1 mg/ml). Conclusion: Several of the tested plants showed antibacterial activities against bacteria associated with PD and DC, meriting further investigations.
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| 5. |
- Ocheng, Francis, et al.
(författare)
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Essential Oils from Ugandan Aromatic Medicinal Plants : Chemical Composition and Growth Inhibitory Effects on Oral Pathogens
- 2015
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Ingår i: Evidence-based Complementary and Alternative Medicine. - : Hindawi Limited. - 1741-427X .- 1741-4288.
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Tidskriftsartikel (refereegranskat)abstract
- The study assessed the growth inhibitory effects of essential oils extracted from ten Ugandan medicinal plants (Bidens pilosa, Helichrysum odoratissimum, Vernonia amygdalina, Hoslundia opposita, Ocimum gratissimum, Cymbopogon citratus, Cymbopogon nardus, Teclea nobilis, Zanthoxylum chalybeum, and Lantana trifolia) used traditionally in the management of oral diseases against oral pathogens. Chemical compositions of the oils were explored by GC-MS. Inhibitory effects of the oils were assessed on periodontopathic Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and cariogenic Streptococcus mutans and Lactobacillus acidophilus using broth dilution methods at concentrations of 1%, 0.1%, and 0.01%. The most sensitive organism was A. actinomycetemcomitans. Its growth was markedly inhibited by six of the oils at all the concentrations tested. Essential oil from C. nardus exhibited the highest activity with complete growth inhibition of A. actinomycetemcomitans and P. gingivalis at all the three concentrations tested, the major constituents in the oil being mainly oxygenated sesquiterpenes. Most of the oils exhibited limited effects on L. acidophilus. We conclude that essential oils from the studied plants show marked growth inhibitory effects on periodontopathic A. actinomycetemcomitans and P. gingivalis, moderate effects on cariogenic S. mutans, and the least effect on L. acidophilus. The present study constitutes a basis for further investigations and development of certain oils into alternative antiplaque agents.
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| 6. |
- Ocheng, Francis, et al.
(författare)
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Essential Oils from Ugandan Medicinal Plants : In Vitro Cytotoxicity and Effects on IL-1 beta-Induced Proinflammatory Mediators by Human Gingival Fibroblasts
- 2016
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Ingår i: Evidence-based Complementary and Alternative Medicine. - : Hindawi Publishing Corporation. - 1741-427X .- 1741-4288.
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Tidskriftsartikel (refereegranskat)abstract
- The study investigated cytotoxicity of essential oils from four medicinal plants (Bidens pilosa, Ocimum gratissimum, Cymbopogon nardus, and Zanthoxylum chalybeum) on human gingival fibroblasts and their effects on proinflammatory mediators' secretion. Cytotoxicity of essential oils was investigated using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Effects of essential oils at subcytotoxicity concentrations on interleukin-(IL-) 6, IL-8, and prostaglandin E-2 (PGE(2)) secretions by gingival fibroblasts treated with IL-1 beta (300 pg/mL) were evaluated by ELISA and EIA. IC50 values of the essential oils ranged from 26 mu g/mL to 50 mu g/mL. Baseline and IL-1 beta-induced secretion of PGE(2) was inhibited by treatment with essential oil from O. gratissimum. Essential oils from B. pilosa and C. nardus had synergistic effects with IL-1 beta on PGE(2) seceretion. In conclusion, the study suggests that essential oil from O. gratissimum decreases gingival fibroblasts secretion of PGE(2), while essential oils from B. pilosa and C. nardus increase PGE(2) secretion. Essential oil from Z. chalybeum was the most cytotoxic, while oil from C. nardus was the least cytotoxic. Although the clinical significance of these findings remains to be determined, it may be suggested that essential oil from O. gratissimum, applied at subcytotoxicity concentrations, could reduce the participation of gingival fibroblasts in the gingival inflammation and tissue destruction associated with periodontitis.
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| 7. |
- Rutebemberwa, Elizeus, et al.
(författare)
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High prevalence of antibiotic resistance in nasopharyngeal bacterial isolates from healthy children in rural Uganda : A cross-sectional study
- 2015
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 120:4, s. 249-256
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Uganda, the main causes of death in children under 5 years of age are malaria and pneumonia-often due to delayed diagnosis and treatment. In preparation for a community case management intervention for pneumonia and malaria, the bacterial composition of the nasopharyngeal flora and its in vitro resistance were determined in children aged five or under to establish baseline resistance to commonly used antibiotics.METHODS: In a population-based survey in April 2008, nasopharyngeal specimens were collected from 152 randomly selected healthy children under 5 years of age in the Iganga/Mayuge Health and Demographic Surveillance Site (HDSS). Medical history and prior treatment were recorded. Demographic characteristics and risk factors for carriage of resistant strains were obtained from the HDSS census. Bacteria were isolated and analysed for antibiotic susceptibility using disk diffusion and E test.RESULTS: Streptococcus pneumoniae (S. pneumoniae) carriage was 58.6%, and, while most (80.9%) isolates had intermediate resistance to penicillin, none was highly resistant. Whereas no isolate was resistant to erythromycin, 98.9% were resistant to trimethoprim-sulphamethoxazole (co-trimoxazole).CONCLUSIONS: In vitro resistance in S. pneumoniae to co-trimoxazole treatment was high, and the majority of isolates had intermediate resistance to penicillin. To inform treatment policies on the clinical efficacy of current treatment protocols for pneumonia in health facilities and at the community level, routine surveillance of resistance in pneumonia pathogens is needed as well as research on treatment efficacy in cases with resistant strains. Improved clinical algorithms and diagnostics for pneumonia should be developed.
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