Browsing by Author "Lutwama, Julius Julian"
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Item Correspondence of Neutralizing Humoral Immunity and CD4 T Cell Responses in Long Recovered Sudan Virus Survivors(Viruses, 2016) Sobarzo, Ariel; Herbert, Andrew S.; Ochayon, David E.; Eskira, Yael; Egesa, Moses; Cose, Stephen; Lutwama, Julius Julian; Dye, John M.; Lobel, LeslieRobust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. However, the interplay between these two arms of immunity is poorly understood. To address this, we examined residual immune responses in survivors of the Sudan virus (SUDV) outbreak in Gulu, Uganda (2000–2001). Cytokine and chemokine expression levels in SUDV stimulated whole blood cultures were assessed by multiplex ELISA and flow cytometry. Antibody and corresponding neutralization titers were also determined. Flow cytometry and multiplex ELISA results demonstrated significantly higher levels of cytokine and chemokine responses in survivors with serological neutralizing activity. This correspondence was not detected in survivors with serum reactivity to SUDV but without neutralization activity. This previously undefined relationship between memory CD4 T cell responses and serological neutralizing capacity in SUDV survivors is key for understanding long lasting immunity in survivors of filovirus infections.Item High insecticide resistances levels in Anopheles gambiaes s.l. in northern Uganda and its relevance for future malaria control(BMC research notes, 2020) Echodu, Richard; Iga, Julius; Oyet, William Samuel; Mireji, Paul; Anena, Juliet; Onanyang, David; Iwiru, Tereza; Lutwama, Julius Julian; Auma Opiyo, ElizabethThe aim of the study was to determine the level of insecticide resistance and diversity in Anopheles mosquitoes in northern Uganda. Standard WHO insecticide susceptibility test assays were used to test for susceptibility to 0.5% malathion, 0.1% bendiocarb, 0.05% deltamethrin and 0.75% permethrin on 3–5 day old generation one progeny. We also screened for species diversity and knockdown resistance using PCR assay. Results: Anopheles gambiae s.s. is the predominant malaria vector in northern Uganda followed by An. arabiensis. An. gambiae s.s. was susceptible to malathion and bendiocarb with the observed mortality rate of 100% and 98–100% observed respectively while very high resistance was observed with deltamethrin and permethrin. Minimal KDReastern variant homozygous forms of 8.3% in An. gambiae s.s. were detected in Oyam district. In conclusion, this study confirms that An. gambiae s.s. females are susceptible to malathion and bendiocarb while high intensity of resistance was observed with deltamethrin and permethrin in the same area. Use of carbamate and organophosphate insecticides bendiocarb and malathion for indoor residual spraying activities in northern Uganda is highly recommended since high levels of pyrethroids resistance (deltamethrin and permethrin) was detected in the area.Item Household Predictors of Incidence of Malaria in Northern Uganda: Its Implication for Future Malaria Control(Research Square, 2020) Echodu, Richard; Oyet, William Sam; Iwiru, Tereza; Apili, Felister; Lutwama, Julius Julian; Auma Opiyo, Elizabeth; Otim, OchanUse of indoor residual spraying (IRS), long-lasting insecticidal nets (LLINS) and treatment with artemisinin-based combination therapy (ACT) have been greatly promoted in northern Uganda but the region still records highest number of malaria cases with prevalence up to 63%. This study assesses household predicators of malaria in the region and its impact on incidence of malaria at household levels. Methods: A cross-sectional study was conducted in four districts of Gulu, Oyam, Kitgum and Agago covering sixteen known hyper-endemics villages with high malaria burden in northern Uganda. In total, 193 households were surveyed. Data was collected through pre-tested structured questionnaires and systematically coded and analyzed using R software. Results: Women headed 58% of the 193 households surveyed. Six hundred and five (605) individuals were declared to have spent a night in the 193 households surveyed. Nighttime is when mosquitoes mostly gain access to victims in the study area. On average, there were two bed nets per household and out of the 605 individuals declared, 502 502 (86%) spent the night prior to interview under a bed net. Despite this effort, these households still reported malaria incidences in the last three months. Overall, children were prone to malaria more than adults by a ratio of 3:2, and in general, malaria incidences were strongly related to lack of bed nets or use thereof, and also linked directly to the number of individuals in a house. Households without bed nets controlled malaria by means of IRS in combination with closing doors (with the hope of keeping mosquitos at bay), draining stagnant water pool where mosquitos lay their eggs, trimming mosquito covers (grass) around homestead and/or receiving treatment after malaria incidences. When given a choice between insecticides (IRS) and treated bed nets, 1 in 3 households preferred treated bed nets. At the same time, bed nets were perceived unnecessary once IRS was applied. If true, the driving force to spraying insecticides indoor then becomes lack of a bed net. Conclusions: Household predicators of incidence of malaria in northern Uganda includes bed nets, use of treated bed nets, and indoor residual spraying with households not practicing any of these bearing the heaviest burden of malaria. Hierarchical clustering on principal components (HCPC) clusters households into four types in northern Uganda, 1) household that use bed nets and sleep in houses sprayed with insecticides; 2) households that use bed nets but no indoor residual spraying with insecticides; 3) households that have no bed nets and no indoor residual spraying; and 4) test bed nets before use. An opportunity therefore arises for tailoring malaria messages to fit each cluster of households given that clustering here appears not to be random. Malaria incidence was higher in children as compared to the adults that necessities having guidelines for management of interventions in local community setting.Item Household Predictors of Malaria Episode in Northern Uganda: Its Implication for Future Malaria Control(Research Square, 2021) Echodu, Richard; Oyet, William Sam; Iwiru, Tereza; Apili, Felister; Lutwama, Julius Julian; Auma Opiyo, Elizabeth; Otim, OchanUses of indoor residual spraying (IRS), long-lasting insecticidal nets (LLINS) and treatment with artemisinin-based combination therapy (ACT) are greatly promoted in northern part of Uganda as mitigating strategies for malaria episodes. Unfortunately, the region still records the highest malaria prevalence of 63%. This study assesses household predicators of malaria in the region and their impact on malaria episodes at the household levels. Methods: A cross-sectional study was conducted in four districts of Gulu, Oyam, Kitgum and Agago covering sixteen villages in northern Uganda. In total, 193 households were surveyed. Data was collected through pre-tested structured questionnaire and systematically coded for analysis using R software. Results: Women headed 58% of the 193 households surveyed. Six hundred and five (605) individuals were declared to have spent the previous night in these households. On average, there were two bed nets per household and 502 (86%) spent the night prior to interview under a bed net. Overall, malaria episodes were strongly related to lack of bed nets or lack of use thereof, and directly linked to the number of individuals in a household. Children were prone to malaria more than adults by a ratio of 2:1. When given a choice between insecticides (IRS) and treated bed nets, 1 in 3 households preferred treated bed nets. At the same time, data suggests that bed nets were perceived unnecessary once IRS was applied. If true, the driving force to spraying insecticides indoor then becomes lack of a bed net. Conclusions: Household predicators of incidence of malaria in northern Uganda includes bed nets, use of treated bed nets, and indoor residual spraying with households not practicing any of these bearing the heaviest burden of malaria. Hierarchical clustering on principal components (HCPC) clusters households into four types in northern Uganda, 1) household that use bed nets and sleep in houses sprayed with insecticides; 2) households that use bed nets but no indoor residual spraying with insecticides; 3) households that have no bed nets and no indoor residual spraying; and 4) test bed nets before use. Malaria incidence was higher in children as compared to the adults.Item Marburg Virus Survivor Immune Responses are Th1 Skewed with Limited Neutralizing Antibody Responses(Journal of Experimental Medicine, 2017) Stonier, Spencer W.; Herbert, Andrew S.; James, Rebekah M.; Egesa, Moses; Cose, Stephen; Lutwama, Julius Julian; Dye, John M.Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunityItem Phylogenomic analysis of Uganda influenza type-A viruses to assess their relatedness to the vaccine strains and other Africa viruses: a molecular epidemiology study(bioRxiv, 2021) Nabakooza, Grace; Owuor, David Collins; Laurent, Zaydah R. de; Owor, Nicholas; Kayiwa, John Timothy; Jjingo, Daudi; Nyaigoti Agoti, Charles; Nokes, David James; Kateete, David Patrick; Mulindwa Kitayimbwa, John; Frost, Simon David William; Lutwama, Julius JulianGenetic characterisation of circulating influenza viruses is essential for vaccine selection and mitigation of viral transmission. The current scantiness of viral genomic data and underutilisation of advanced molecular analysis methods on influenza viruses circulating in Africa has limited their extensive study and representation in the global influenza ecology. We aimed to sequence influenza type-A viruses (IAVs) that previously circulated in Uganda and characterised their genetic relatedness to the vaccine viruses and publicly available Africa IAVs. Methods: This was an observational study nested to the Uganda national influenza surveillance programme. We used Next-generation sequencing to locally generate genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) viruses collected between 2010 and 2018 from 7 districts across Uganda. A total of 206 hemagglutinin (HA), 207 neuraminidase (NA), and 213 matrix protein (MP) sequences were genetically compared to the WHO-recommended vaccines and other viruses isolated from Africa since 1994. Viral temporal and spatial divergence and circulating genetic clades were characterised using phylogenetic methods. Findings: We successfully generated gene sequences for 91·9% (215/234) viruses. Uganda A(H1N1)pdm09 and A(H3N2) virus HA, NA, and MP proteins had 96·36-99·09%, 96·49-99·39%, and 97·48-99·95% amino acid similarity, respectively, to vaccines recommended from 2010 through 2020. The local viruses incorporated amino acid substitutions (AAS) in their antigenic, receptor binding, and glycosylation sites each year causing them to antigenically drift away from vaccines. For seasons when vaccine formulations differed, Uganda IAV antigenic sites had 1-2 extra AAS relative to the Southern than Northern hemisphere vaccine viruses. All Uganda IAVs carried the adamantine-resistance marker S31N but not the neuraminidase inhibitor (NAI) resistance markers H274Y and H275Y. However, some A(H1N1)pdm09 viruses had permissive substitutions V234I, N369K, and V241I typical of NAI-resistant viruses.Item Retrospective in silico mutation profiling of SARS-CoV-2 structural proteins circulating in Uganda by July 2021: Towards refinement of COVID-19 disease vaccines, diagnostics, and therapeutics(Plos one, 2022) Odongo, Steven; Okella, Hedmon; Ndekezi, Christian; Okee, Moses; Namayanja, Monica; Mujuni, Brian; Sterckx, Yann G. J.; Kizito, Dennison; Mwiine, Frank Nobert; Lutwama, Julius Julian; Ibingira, CharlesThe SARS-CoV-2 virus, the agent of COVID-19, caused unprecedented loss of lives and economic decline worldwide. Although the introduction of public health measures, vaccines, diagnostics, and therapeutics disrupted the spread of the SARS-CoV-2, the emergence of variants poses substantial threat. This study traced SARS-CoV-2 variants circulating in Uganda by July 2021 to inform the necessity for refinement of the intervention medical products. A comprehensive in silico analysis of the SARS-CoV-2 genomes detected in clinical samples collected from COVID-19 patients in Uganda revealed occurrence of structural protein variants with potential of escaping detection, resisting antibody therapy, or increased infectivity. The genome sequence dataset was retrieved from the GISAID database and the open reading frame encoding the spike, envelope, membrane, or nucleocapsid proteins was translated. The obtained protein sequences were aligned and inspected for existence of variants. The variant positions on each of the four alignment sets were mapped on predicted epitopes as well as the 3D structures. Additionally, sequences within each of the sets were clustered by family. A phylogenetic tree was constructed to assess relationship between the encountered spike protein sequences and Wuhan-Hu-1 wild-type, or the Alpha, Beta, Delta and Gamma variants of concern. Strikingly, the frequency of each of the spike protein point mutations F157L/Del, D614G and P681H/R was over 50%. The furin and the transmembrane serine protease 2 cleavage sites were unaffected by mutation. Whereas the Delta dominated the spike sequences (16.5%, 91/550), Gamma was not detected. The envelope protein was the most conserved with 96.3% (525/545) sequences being wild-type followed by membrane at 68.4% (397/580). Although the nucleocapsid protein sequences varied, the variant residue positions were less concentrated at the RNA binding domains. The dominant nucleocapsid sequence variant was S202N (34.5%, 205/595). These findings offer baseline information required for refining the existing COVID-19 vaccines, diagnostics, and therapeutics.Item Sporadic outbreaks of crimean-congo haemorrhagic fever in Uganda, July 2018- January 2019(PLoS neglected tropical diseases, 2019) Mirembe, Bernadette Basuta; Musewa, Angella; Kadobera, Daniel; Kisaakye, Esther; Birungi, Doreen; Eurien, Daniel; Nyakarahuka, Luke; Balinandi, Stephen; Tumusiime, Alex; Kyondo, Jackson; Mbula Mulei, Sophia; Baluku, Jimmy; Kwesiga, Benon; Ndugwa Kabwama, Steven; Zhu, Bao-Ping; Harris, Julie R.; Lutwama, Julius Julian; Alex, Riolexus ArioCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne, zoonotic viral disease that causes haemorrhagic symptoms. Despite having eight confirmed outbreaks between 2013 and 2017, all within Uganda’s ‘cattle corridor’, no targeted tick control programs exist in Uganda to prevent disease. During a seven-month-period from July 2018-January 2019, the Ministry of Health confirmed multiple independent CCHF outbreaks. We investigated to identify risk factors and recommend interventions to prevent future outbreaks. We defined a confirmed case as sudden onset of fever (�37.5 ̊C) with �4 of the following signs and symptoms: anorexia, vomiting, diarrhea, headache, abdominal pain, joint pain, or sudden unexplained bleeding in a resident of the affected districts who tested positive for Crimean-Congo haemorrhagic fever virus (CCHFv) by RT-PCR from 1 July 2018–30 January 2019. We reviewed medical records and performed active case-finding. We conducted a case-control study and compared exposures of case-patients with age-, sex-, and sub-county-matched control-persons (1:4). We identified 14 confirmed cases (64% males) with five deaths (case-fatality rate: 36%) from 11 districts in the western and central region. Of these, eight (73%) case patients resided in Uganda’s ‘cattle corridor’. One outbreak involved two case-patients and the remainder involved one. All case-patients had fever and 93% had unexplained bleeding. Case-patients were aged 6–36 years, with persons aged 20–44 years more affected (AR: 7.2/1,000,000) than persons �19 years (2.0/1,000,000), p = 0.015. Most (93%) case-patients had contact with livestock �2 weeks before symptom onset. Twelve (86%) lived <1 km from grazing fields compared with 27 (48%) controls (OR M-H = 18, 95% CI = 3.2-1) and 10 (71%) of 14 case-patients found ticks attached to their bodies �2 weeks before symptom onset, compared to 15 (27%) of 56 control-persons (OR M-H = 9.3, 95%CI = 1.9–46). CCHF outbreaks occurred sporadically during 2018–2019, both within and outside the ‘cattle corridor’ districts of Uganda. Most cases were associated with tick exposure. The Ministry of Health should partner with the Ministry of Agriculture, Animal Industry, and Fisheries to develop joint nationwide tick control programs and strategies with shared responsibilities through a One Health approach.