NRU :: Browsing by Author "Wampande, Eddie M."

Browsing by Author "Wampande, Eddie M."

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Carbapenem Resistance Profiles of Pathogenic Escherichia coli in Uganda
(2020) Ssekatawa, Kenneth; Byarugaba, Denis K.; Nakavuma, Jesca L.; Kato, Charles D.; Ejobi, Francis; Tweyongyere, Robert; Wampande, Eddie M.
Escherichia coli has been implicated as one of the main etiological agents of diarrhea, urinary tract infections, meningitis and septicemia worldwide. The ability to cause diseases is potentiated by presence of virulence factors. The virulence factors influence the capacity of E. coli to infect and colonize different body systems. Thus, pathogenic E. coli are grouped into DEC strains that are mainly clustered in phylogenetic group B1 and A; ExPEC belonging to A, B2 and D. Coexistence of virulence and beta-lactamase encoding genes complicates treatment outcomes. Therefore, this study aimed at presenting the CR profiles among pathogenic E. coli. Methods: This was a retrospective cross-sectional study involving use of archived E. coli clinical isolates collected in 2019 from four Ugandan tertiary hospitals. The isolates were subjected to antibiotics sensitivity assays to determine phenotypic resistance. Four sets of multiplex PCR were performed to detect CR genes, DEC pathotypes virulent genes, ExPEC PAI and the E. coli phylogenetic groups. Results: Antibiotic susceptibility revealed that all the 421 E. coli isolates used were MDR as they exhibited 100% resistance to more than one of the first-line antibiotics. The study registered phenotypic and genotypic CR prevalence of 22.8% and 33.0% respectively. The most predominant gene was blaOXA-48 with genotypic frequency of 33.0%, then blaVIM(21.0%), blaIMP(16.5%), blaKPC(14.8%) and blaNDM(14.8%). Spearman’s correlation revealed that presence of CR genes was highly associated with phenotypic resistance. Furthermore, of 421 MDR E. coli isolates, 19.7% harboured DEC virulent genes, where EPEC recorded significantly higher prevalence (10.8%) followed by S-ETEC(3.1%), STEC(2.9%), EIEC (2.0%) and L-ETEC(2.0%). Genetic analysis characterized 46.1% of the isolates as ExPEC and only PAI IV536(33.0%) and PAI IICFT073(13.1%) were detected. Phylogenetic group B2 was predominantly detected (41.1%), followed by A(30.2%), B1(21.6%), and D(7.1%). Furthermore, 38.6% and 23.1% of the DEC and ExPEC respectively expressed phenotypic resistance. Conclusion: Our results exhibited significant level of CR carriage among the MDR DEC and ExPEC clinical isolates belonging to phylogenetic groups B1 and B2 respectively. Virulence and CR genetic factors are mainly located on mobile elements. Thus, constitutes a great threat to the healthcare system as it promotes horizontal gene transfer.
Chemical tick control practices in southwestern and northwestern Uganda
(Ticks and tick-borne diseases, 2018) Vudriko, Patrick; Okwee-Acai, James; Byaruhanga, Joseph; Tayebwaa, Dickson S.; Okech, Samuel G.; Tweyongyere, Robert; Wampande, Eddie M.; Ademun Okurut, Anna R.; Mugabi, Kenneth; Muhindo, Jeanne B.; Nakavuma, Jesca L.; Umemiya-Shirafuji, Rika; Xuan, Xuenan
Tick acaricide failure is one of the leading challenges to cattle production in Uganda. To gain an understanding into the possible drivers of acaricide failure, this study characterized the current chemical tick control practices in the southwestern (Mbarara, Mitooma and Rukungiri districts) and northwestern (Adjumani district) regions of Uganda. A total of 85 farms participated in a survey that utilized a semi-structured questionnaire. Moreover, ticks were collected to determine the most common species on the farms. Tick acaricide failure was mainly encountered in the districts where 95% (60/63) of the farms reared exotic cattle (dairy cross-breeds) under a paddocking (fenced) system. In the northwestern region, local cattle were reared in communal grazing areas. All farms used chemical acaricides for tick control, predominantly amidine (amitraz) (48%, 41/85) and co-formulated organophosphates and pyrethroids (38%, 32/85). The spraying method was the most common (91%, 77/85) acaricide application technique, with cattle crush (81%, 69/85) as a common means of physical restraint. Less than optimal tick control practices encountered included use of substandard equipment for spraying, inappropriate dilutions, frequent interaction between animals in neighboring farms despite lack of synchronized chemical tick control and malpractices in acaricide rotation. Only Rhipicephalus appendiculatus and R. (Boophilus) decoloratus ticks were found in the southwestern region, where 51% (32/63) of the farmers used high acaricide concentrations above the manufacturers’ recommendation. Farmers in the northwestern region used 2.2 times less acaricide volume per cattle than those in the southwestern region, and more diverse tick species were encountered. Toxic effects of acaricide to cattle and workers were reported by 13% (11/85) and 32% (27/85) of the respondents, respectively. All 27 cases of human acaricide toxicity reported were from the southwestern region. Overall, our findings may inform strategies for more prudent chemical tick control and safe acaricide handling to benefit animal welfare, food safety and public health.
Distribution and transmission of Mycobacterium tuberculosis complex lineages among children in peri-urban Kampala, Uganda
(BMC pediatrics, 2015) Wampande, Eddie M.; Mupere, Ezekiel; Jaganath, Devan; Nsereko, Mary; Mayanja, Harriet K.; Eisenach, Kathleen; Boom, W. Henry; Gagneu, Sebastien; Joloba, Moses L.
To gain insight into the transmission of tuberculosis (TB) in peri-urban Kampala-Uganda, we performed a household contact study using children as a surrogate for recent transmission of Mycobacterium tuberculosis (MTB). Using this approach, we sought to understand M. tuberculosis complex (MTBC) lineage diversity, distribution and how these relate to TB transmission to exposed children. Method: MTBC isolates from children aged ≤ 15 years, collected from 2002 to 2010 in a household-contact study, were analyzed using a LightCycler RT-PCR SNP genotyping assay (LRPS). The resultant genotypic data was used to determine associations between MTBC lineage and the children’s clinical and epidemiological characteristics. Results and discussion: Of the 761 children surveyed, 9 % (69/761) had culture-positive TB an estimate in the range of global childhood TB; of these 71 % (49/69) were infected with an MTBC strain of the “Uganda family”, 17 % (12/69) infected with MTBC lineage 4 strains other than MTBC Uganda family and 12 % (8/69) infected with MTBC lineage 3, thereby disproportionately causing TB in the study area. Overall the data showed no correlation between the MTBC lineages studied and transmission (OR = 0.304; P-value = 0.251; CI: 95 %; 0.039-2.326) using children a proxy for TB transmission. Conclusions: Our findings indicate that MTBC Uganda family strains are the main cause of TB in children in peri-urban Kampala. Furthermore, MTBC lineages did not differ in their transmissibility to children.
Green Strategy–Based Synthesis of Silver Nanoparticles for Antibacterial Applications
(Frontiers in Nanotechnology, 2021) Ssekatawa, Kenneth; Byarugaba, Denis K.; Kato, Charles D.; Wampande, Eddie M.; Ejobi, Francis; Nakavuma, Jesca L.; Maaza, Malik; Sackey, Juliet; Nxumalo, Edward; Kirabira, John B.
Antibiotics have been the nucleus of chemotherapy since their discovery and introduction into the healthcare system in the 1940s. They are routinely used to treat bacterial infections and to prevent infections in patients with compromised immune systems and enhancing growth in livestock. However, resistance to last-resort antibiotics used in the treatment of multidrug-resistant infections has been reported worldwide. Therefore, this study aimed to evaluate green synthesized nanomaterials such as silver nanoparticles (AgNPs) as alternatives to antibiotics. UV-vis spectroscopy surface plasmon resonance peaks for AgNPs were obtained between 417 and 475 nm. An X-ray diffraction analysis generated four peaks for both Prunus africana extract (PAE) and Camellia sinensis extract (CSE) biosynthesized AgNPs positioned at 2θ angles of 38.2°, 44.4°, 64.5°, and 77.4° corresponding to crystal planes (111), (200), (220), and (311), respectively. A dynamic light-scattering analysis registered the mean zeta potential of +6.3mV and +0.9 mV for PAE and CSE biosynthesized nanoparticles, respectively. Fourier transform infrared spectroscopy spectra exhibited bands corresponding to different organic functional groups confirming the capping of AgNPs by PAE and CSE phytochemicals. Field emission scanning electron microscopy imaging showed that AgNPs were spherical with average size distribution ranging from 10 to 19 nm. Biosynthesized AgNPs exhibited maximum growth inhibitory zones of 21mm with minimum inhibitory concentration and minimum bactericidal concentration of 125 and 250 μg/ml, respectively, against carbapenem-resistant bacteria
Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: Evidence for coevolution?
(PLoS genetics, 2020) McHenry, Michael L.; Bartlett, Jacquelaine; Igo, Robert P.; Wampande, Eddie M.; Mayanja-Kizza, Harriet; Hall, Noemi B.; Tishkoff, Sarah A.; Stein, Catherine M.
Genetic studies of both the human host and Mycobacterium tuberculosis (MTB) demonstrate independent association with tuberculosis (TB) risk. However, neither explains a large portion of disease risk or severity. Based on studies in other infectious diseases and animal models of TB, we hypothesized that the genomes of the two interact to modulate risk of developing active TB or increasing the severity of disease, when present. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which there were 3 MTB lineages of which L4-Ugandan (L4.6) is the most recent. TB severity, measured using the Bandim TBscore, was modeled as a function of host SNP genotype, MTB lineage, and their interaction, within two independent cohorts of TB cases, N = 113 and 121. No association was found between lineage and severity, but association between multiple polymorphisms in IL12B and TBscore was replicated in two independent cohorts (most significant rs3212227, combined p = 0.0006), supporting previous associations of IL12B with TB susceptibility. We also observed significant interaction between a single nucleotide polymorphism (SNP) in SLC11A1 and the L4-Ugandan lineage in both cohorts (rs17235409, meta p = 0.0002). Interestingly, the presence of the L4-Uganda lineage in the presence of the ancestral human allele associated with more severe disease. These findings demonstrate that IL12B is associated with severity of TB in addition to susceptibility, and that the association between TB severity and human genetics can be due to an interaction between genes in the two species, consistent with host-pathogen coevolution in TB.
Long-term dominance of Mycobacterium tuberculosis Uganda family in peri-urban Kampala-Uganda is not associated with cavitary disease
(BMC Infectious Diseases, 2013) Wampande, Eddie M.; Mupere, Ezekiel; Debanne, SaraM; Asiimwe, Benon B.; Nsereko, Mary; Mayanja, Harriet; Eisenach, Kathleen; Kaplan, Gilla; Boom, Henry W.; Gagneux, Sebastien; Joloba, Moses L.
Previous studies have shown that Mycobacterium tuberculosis (MTB) Uganda family, a sub-lineage of the MTB Lineage 4, is the main cause of tuberculosis (TB) in Uganda. Using a well characterized patient population, this study sought to determine whether there are clinical and patient characteristics associated with the success of the MTB Uganda family in Kampala. A total of 1,746 MTB clinical isolates collected from1992-2009 in a household contact study were genotyped. Genotyping was performed using Single Nucleotide Polymorphic (SNP) markers specific for the MTB Uganda family, other Lineage 4 strains, and Lineage 3, respectively. Out of 1,746 isolates, 1,213 were from patients with detailed clinical data. These data were used to seek associations between MTB lineage/sub-lineage and patient phenotypes.
Molecular epidemiology of Babesia species, Theileria parva, and Anaplasma marginale infecting cattle and the tick control malpractices in central and eastern Uganda
(Ticks and tick-borne diseases, 2018) Tayebwa, Dickson Stuart; Vudriko, Patrick; Tuvshintulga, Bumduuren; Guswanto, Azirwan; Budiman Nugraha, Arifin; Gantuya, Sambuu; El-Saber Batiha, Gaber; Musinguzi, Simon Peter; Komugisha, Mariam; Bbira, Jonh Son; Okwee-Acai, James; Tweyongyere, Robert; Wampande, Eddie M.; Byaruhanga, Joseph; Adjou Moumouni, Paul Franck; Sivakumar, Thillaiampalam; Yokoyama, Naoaki; Igarashi, Ikuo
East Coast fever, babesiosis, and anaplasmosis are the major tick-borne diseases affecting cattle productivity in Uganda. The emergence of acaricide-resistant ticks is suspected to have caused a rise in hemoparasites. This study sought to detect and characterize hemoparasites among farms in acaricide-failure hotspots of central as compared to the acaricide-failure naïve areas in eastern Uganda. Nested PCR assays were performed to determine the prevalences of Babesia bovis, Babesia bigemina, Theileria parva, and Anaplasma marginale in cattle blood samples sourced from randomly selected farms. Randomly selected isolates were sequenced to determine the genetic diversity of the parasites using the following marker genes: B. bovis spherical body protein 4, B. bigemina rhoptry-associated protein 1a, T. parva 104 kDa microneme-rhoptry antigen, and A. marginale major surface protein 5. Furthermore, partially and fully engorged adult ticks were collected for taxonomy, and tick-control practices were assessed using a semi-structured questionnaire. The prevalences of B. bigemina, T. parva, and A. marginale in cattle were 17.2, 65.1, and 22.0%, and 10.0, 26.5, and 3% in the central and eastern region, respectively. Whilst, B. bovis was not detected in the farms involved. The sequences for B. bigemina, T. parva, and A. marginale from the central region showed 99% identity with those from the eastern region. Of the 548 ticks collected, 319, 147, 76, and 6 were Rhipicephalus (Boophilus) decoloratus, Rhipicephalus appendiculatus, Amblyomma variegatum, and Rhipicephalus evertsi evertsi, respectively. The Rhipicephalus ticks were more abundant in the central, whereas A. variegatum ticks were more abundant in the eastern region. Tick control malpractices were found in both central and eastern Uganda, and 42 of the 56 surveyed farms lacked appropriate restraining facilities and so they utilized either ropes or a ‘boma’ (enclosure). In summary, B. bigemina, T. parva, A. marginale and their co-infections were more prevalent in the central than eastern region; even though, tick control malpractices were observed in both regions. Therefore, an urgent tick and TBD control strategy is needed.
Nanotechnological Solutions For Controlling Transmission And Emergence Of Antimicrobial-Resistant Bacteria, Future Prospects, And Challenges: A Systematic Review
(Journal of Nanoparticle Research, 2020) Ssekatawa, Kenneth; Byarugaba, Dennis K.; Kato, Charles D.; Ejobi, Francis; Tweyongyere, Robert; Lubwama, Michael; Kirabira, John Baptist; Wampande, Eddie M.
Globally, a high prevalence of multi-drug-resistant (MDR) bacteria, mostly methicillin-resistant Staphylococcus aureus and carbapenem-resistant Enterobacteriaceae, has been reported. Infections caused by such bacteria are expensive and hard to treat due to reduced efficient treatment alternatives. Centered on the current rate of antibiotics production and approvals, it is anticipated that by 2050 up to 10 million people could die annually due to MDR pathogens. To this effect, alternative strategies such as the use of nanotechnology to formulate nanobactericidal agents are being explored. This systematic review addresses the recent approaches, future prospects, and challenges of nanotechnological solutions for controlling transmission and emergence of antibiotic resistance. A comprehensive literature search of PubMed and BioMed Central databases from June 2018 to January 2019 was performed. The search keywords used were “use of nanotechnology to control antibiotic resistance” to extract articles published only in English encompassing all research papers regardless of the year of publication. PubMed and BioMed Central databases literature exploration generated 166 articles of which 49 full-text research articles met the inclusion guidelines. Of the included articles, 44.9%, 30.6%, and 24.5% reported the use of inorganic, hybrid, and organic nanoparticles, respectively, as bactericidal agents or carriers/enhancers of bactericidal agents. Owing to the ever-increasing prevalence of antimicrobial resistance to old and newly synthesized drugs, alternative approaches such as nanotechnology are highly commendable. This is supported by in vitro, ex vivo, and in vivo studies assessed in this review as they reported high bactericide efficacies of organic, inorganic, and hybrid nanoparticles.
Prevalence of pathogenic Klebsiella pneumoniae based on PCR capsular typing harbouring carbapenemases encoding genes in Uganda tertiary hospitals
(Antimicrobial Resistance & Infection Control, 2021) Ssekatawa, Kenneth; Byarugaba, Denis K.; Nakavuma, Jesca L.; Kato, Charles D.; Ejobi, Francis; Tweyongyere, Robert; Wampande, Eddie M.
Background: Klebsiella pneumoniae is an opportunistic pathogen that has been implicated as one of commonest cause of hospital and community acquired infections. The K. pneumoniae infections have considerably contributed to morbidity and mortality in patients with protracted ailments. The capacity of K. pneumoniae to cause diseases depends on the presence of an array virulence factors. Coexistence and expression of virulence factors and genetic determinants of antibiotic resistance complicates treatment outcomes. Thus, emergence of pathogenic MDR K. pneumoniae poses a great threat to the healthcare system. However, the carriage of antibiotic resistance among pathogenic K. pneumoniae is yet to be investigated in Uganda. We sought to investigate the carbapenem resistance profiles and pathogenic potential based on capsular serotypes of K. pneumoniae clinical isolates. Methods: This was a cross sectional study involving use of archived Klebsiella pneumoniae isolates collected between January and December, 2019 at four tertiary hospitals in Uganda. All isolates were subject to antimicrobial susceptibility assays to determine phenotypic antibiotic resistance, pentaplex PCR to detect carbapenemases encoding genes and heptaplex PCR to identify capsular serotypes K1, K2, K3, K5, K20, K54 and K57. Results: The study found an overall phenotypic carbapenem resistance of 23.3% (53/227) and significantly higher genotypic resistance prevalence of 43.1% (98/227). Over all, the most prevalent gene was blaOXA-48-like (36.4%), followed by blaIMP-type (19.4%), blaVIM-type (17.1%), blaKPC-type (14.0%) and blaNDM-type (13.2%). blaVIM-type and blaOXA-48-like conferred phenotypic resistance in all isolates and 38.3% of isolates that harbored them respectively. Capsular multiplex PCR revealed that 46.7% (106/227) isolates were pathogenic and the predominantly prevalent pathotype was K5 (18.5%) followed by K20 (15.1%), K3 (7.1%), K2 (3.1%) and K1 (2.2%). Of the 106 capsular serotypes, 37 expressed phenotypic resistance; thus, 37 of the 53 carbapenem resistant K. pneumoniae were pathogenic. Conclusion: The high prevalence of virulent and antibiotic resistant K. pneumoniae among clinical isolates obtained from the four tertiary hospital as revealed by this study pose a great threat to healthcare. Our findings underline the epidemiological and public health risks and implications of this pathogen.
A review of phage mediated antibacterial applications
(Alexandria Journal of Medicine, 2021) Ssekatawa, Kenneth; Byarugaba, Denis K.; Kato, Charles D.; Wampande, Eddie M.; Ejobi, Francis; Tweyongyere, Robert; Nakavuma, Jesca L.
For over a decade, resistance to newly synthesized antibiotics has been observed worldwide. The challenge of antibiotic resistance has led to several pharmaceutical companies to abandon the synthesis of new drugs in fear of bacteria developing resistance in a short period hence limiting initial investment return. To this effect, alternative approaches such as the use of bacteriophages to treat bacterial infections are being explored. This review explores the recent advances in phage-mediated antibacterial applications and their limitations. Methods: We conducted a comprehensive literature search of PubMed, Lib Hub and Google Scholar databases from January 2019 to November 2019. The search key words used were the application of bacteriophages to inhibit bacterial growth and human phage therapy to extract full-text research articles and proceedings from International Conferences published only in English. Results: The search generated 709 articles of which 95 full-text research articles fulfilled the inclusion guidelines. Transmission Electron Microscopy morphological characterization conducted in 23 studies registered Myoviruses, Siphoviruses, Podoviruses, and Cytoviruses phage families while molecular characterization revealed that some phages were not safe to use as they harbored undesirable genes. All in vivo phage therapy studies in humans and model animals against multidrug-resistant (MDR) bacterial infection provided 100% protection. Ex vivo and in vitro phage therapy experiments exhibited overwhelming results as they registered high efficacies of up to 100% against MDR clinical isolates. Phage-mediated bio-preservation of foods and beverages and bio-sanitization of surfaces were highly successful with bacterial growth suppression of up to 100%. Phage endolysins revealed efficacies statistically comparable to those of phages and restored normal ethanol production by completely eradicating lactic acid bacteria in ethanol fermenters. Furthermore, the average multiplicity of infection was highest in ex vivo phage therapy (557,291.8) followed by in vivo (155,612.4) and in vitro (434.5).
Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana
(The American Journal of Human Genetics, 2018) Retshabile, Gaone; Mlotshwa, Busisiwe C.; Williams, Lesedi; Mwesigwa, Savannah; Mboowa, Gerald; Huang, Zhuoyi; Rustagi, Navin; Swaminathan, Shanker; Katagirya, Eric; Kyobe, Samuel; Wayengera, Misaki; Kisitu, Grace P.; Kateete, David P.; Wampande, Eddie M.; Maplanka, Koketso; Kasvosve, Ishmael; Pettitt, Edward D.; Matshaba, Mogomotsi; Nsangi, Betty; Marape, Marape; Tsimako-Johnstone, Masego; Brown, Chester W.; Yu, Fuli; Kekitiinwa, Adeodata; Joloba, Moses; Mpoloka, Sununguko W.; Mardon, Graeme; Anabwani, Gabriel; Hanchard, Neil A.
Large-scale, population-based genomic studies have provided a context for modern medical genetics. Among such studies, however, African populations have remained relatively underrepresented. The breadth of genetic diversity across the African continent argues for an exploration of local genomic context to facilitate burgeoning disease mapping studies in Africa.We sought to characterize genetic variation and to assess population substructure within a cohort of HIV-positive children from Botswana—a Southern African country that is regionally underrepresented in genomic databases. Using whole-exome sequencing data from 164 Batswana and comparisons with 150 similarly sequenced HIV-positive Ugandan children, we found that 13%–25% of variation observed among Batswana was not captured by public databases. Uncaptured variants were significantly enriched (p ¼ 2.2 3 10 16) for coding variants with minor allele frequencies between 1% and 5% and included predicted-damaging non-synonymous variants. Among variants found in public databases, corresponding allele frequencies varied widely, with Botswana having significantly higher allele frequencies among rare (<1%) pathogenic and damaging variants. Batswana clustered with other Southern African populations, but distinctly from 1000 Genomes African populations, and had limited evidence for admixture with extra-continental ancestries. We also observed a surprising lack of genetic substructure in Botswana, despite multiple tribal ethnicities and language groups, alongside a higher degree of relatedness than purported founder populations from the 1000 Genomes project. Our observations reveal a complex, but distinct, ancestral history and genomic architecture among Batswana and suggest that disease mapping within similar Southern African populations will require a deeper repository of genetic variation and allelic dependencies than presently exists.

Browsing by Author "Wampande, Eddie M."

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