Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-8 (of 8 Records) |
Query Trace: Aceng JR[original query] |
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Molecular characterization of the 2022 Sudan virus disease outbreak in Uganda
Balinandi S , Whitmer S , Mulei S , Nassuna C , Pimundu G , Muyigi T , Kainulainen M , Shedroff E , Krapiunaya I , Scholte F , Nyakarahuka L , Tumusiime A , Kyondo J , Baluku J , Kiconco J , Harris JR , Ario AR , Kagirita A , Bosa HK , Ssewanyana I , Nabadda S , Mwebesa HG , Aceng JR , Atwine D , Lutwama JJ , Shoemaker TR , Montgomery JM , Kaleebu P , Klena JD . J Virol 2023 97 (10) e0059023 Uganda experienced five Ebola disease outbreaks caused by Bundibugyo virus (n = 1) and Sudan virus (SUDV) (n = 4) from 2000 to 2021. On 20 September 2022, Uganda declared a fifth Sudan virus disease outbreak in the Mubende district, resulting in 142 confirmed and 22 probable cases by the end of the outbreak declaration on 11 January 2023. The earliest identified cases, through retrospective case investigations, had onset in early August 2022. From the 142 confirmed cases, we performed unbiased (Illumina) and SUDV-amplicon-specific (Minion) high-throughput sequencing to obtain 120 SUDV genome-and coding-complete sequences, representing 95.4% (104/109) of SVD-confirmed individuals within a sequence-able range (Ct ≤30) and 10 genome sequences outside of this range and 6 duplicate genome sequences. A comparison of the nucleotide genetic relatedness for the newly emerged Mubende variant indicated that it was most closely related to the Nakisamata SUDV sequence from 2011, represented a likely new zoonotic spillover event, and exhibited an inter- and intra-outbreak substitution rate consistent with previous outbreaks. The most recent common ancestor for the Mubende variant was estimated to have occurred in October and November 2021. The Mubende variant glycoprotein amino acid sequences exhibited 99.7% similarity altogether and a maximum of 96.1% glycoprotein similarity compared to historical SUDV strains from 1976. Integrating the genetic sequence and epidemiological data into the response activities generated a broad overview of the outbreak, allowing for quick fact-checking of epidemiological connections between the identified patients. IMPORTANCE Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013-2016 Western Africa outbreak demonstrated how devastating EBOD can be when it reaches an urban population. Here, the 2022 Sudan virus disease (SVD) outbreak in Mubende District, Uganda, is summarized, and the genetic relatedness of the new variant is evaluated. The Mubende variant exhibited 96% amino acid similarity with historic SUDV sequences from the 1970s and a high degree of conservation throughout the outbreak, which was important for ongoing diagnostics and highly promising for future therapy development. Genetic differences between viruses identified during the Mubende SVD outbreak were linked with epidemiological data to better interpret viral spread and contact tracing chains. This methodology should be used to better integrate discrete epidemiological and sequence data for future viral outbreaks. |
Genomic analysis, immunomodulation and deep phenotyping of patients with nodding syndrome.
Soldatos A , Nutman TB , Johnson T , Dowell SF , Sejvar JJ , Wilson MR , DeRisi JL , Inati SK , Groden C , Evans C , O'Connell EM , Toliva BO , Aceng JR , Aryek-Kwe J , Toro C , Stratakis CA , Buckler AG , Cantilena C , Palmore TN , Thurm A , Baker EH , Chang R , Fauni H , Adams D , Macnamara EF , Lau CC , Malicdan MCV , Pusey-Swerdzewski B , Downing R , Bunga S , Thomas JD , Gahl WA , Nath A . Brain 2022 146 (3) 968-976 The etiology of Nodding Syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with Nodding Syndrome, investigate potential contributors to disease etiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for Nodding Syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had Nodding Syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography, and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. Cerebrospinal fluid (CSF) was non-inflammatory, and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members, and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding Syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal etiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention. |
Uganda National Institute of Public Health: Establishment and experiences, 2013-2021
Ario AR , Makumbi I , Kadobera D , Bulage L , Ocom F , Kwesiga B , Jarvis DF , Nabatanzi S , Homsy J , Banage F , Brown V , Harris JR , Boore AL , Nelson LJ , Binder S , Mwebesa HG , Aceng JR . Glob Health Sci Pract 2022 10 (4) Uganda is an ecological hot spot with porous borders that lies in several infectious disease transmission belts, making it prone to disease outbreaks. To prepare and respond to these public health threats and emergencies in a coordinated manner, Uganda established the Uganda National Institute of Public Health (UNIPH) in 2013.Using a step-by-step process, Uganda's Ministry of Health (MOH) crafted a strategy with a vision, mission, goal, and strategic objectives, and identified value additions and key enablers for success. A regulatory impact assessment was then conducted to inform the drafting of principles of the bill for legislation on the Institute.Despite not yet attaining legal status, the UNIPH has already achieved faster, smarter, and more efficient and effective prevention, detection, and response to public health emergencies. Successes include a more coordinated multisectoral, disciplined, and organized response to emergencies; appropriate, timely, and complete information receipt and sharing; a functional national lab sample and results transportation network that has enabled detection and confirmation of public health events within 48 hours of alert; appropriate response to a confirmed public health event in 24-48 hours; and real-time surveillance of endemic- and epidemic-prone diseases.In this article, we document success stories, lessons learned, and challenges encountered during the unique staged process used to develop the components of the UNIPH. The creation of an integrated disease control center has proven to yield better collaboration and synergies between different arms of epidemic preparedness and response. |
Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019
Aceng JR , Ario AR , Muruta AN , Makumbi I , Nanyunja M , Komakech I , Bakainaga AN , Talisuna AO , Mwesigye C , Mpairwe AM , Tusiime JB , Lali WZ , Katushabe E , Ocom F , Kaggwa M , Bongomin B , Kasule H , Mwoga JN , Sensasi B , Mwebembezi E , Katureebe C , Sentumbwe O , Nalwadda R , Mbaka P , Fatunmbi BS , Nakiire L , Lamorde M , Walwema R , Kambugu A , Nanyondo J , Okware S , Ahabwe PB , Nabukenya I , Kayiwa J , Wetaka MM , Kyazze S , Kwesiga B , Kadobera D , Bulage L , Nanziri C , Monje F , Aliddeki DM , Ntono V , Gonahasa D , Nabatanzi S , Nsereko G , Nakinsige A , Mabumba E , Lubwama B , Sekamatte M , Kibuule M , Muwanguzi D , Amone J , Upenytho GD , Driwale A , Seru M , Sebisubi F , Akello H , Kabanda R , Mutengeki DK , Bakyaita T , Serwanjja VN , Okwi R , Okiria J , Ainebyoona E , Opar BT , Mimbe D , Kyabaggu D , Ayebazibwe C , Sentumbwe J , Mwanja M , Ndumu DB , Bwogi J , Balinandi S , Nyakarahuka L , Tumusiime A , Kyondo J , Mulei S , Lutwama J , Kaleebu P , Kagirita A , Nabadda S , Oumo P , Lukwago R , Kasozi J , Masylukov O , Kyobe HB , Berdaga V , Lwanga M , Opio JC , Matseketse D , Eyul J , Oteba MO , Bukirwa H , Bulya N , Masiira B , Kihembo C , Ohuabunwo C , Antara SN , Owembabazi W , Okot PB , Okwera J , Amoros I , Kajja V , Mukunda BS , Sorela I , Adams G , Shoemaker T , Klena JD , Taboy CH , Ward SE , Merrill RD , Carter RJ , Harris JR , Banage F , Nsibambi T , Ojwang J , Kasule JN , Stowell DF , Brown VR , Zhu BP , Homsy J , Nelson LJ , Tusiime PK , Olaro C , Mwebesa HG , Woldemariam YT . Global Health 2020 16 (1) 24 BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies. |
Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus .
Johnson TP , Tyagi R , Lee PR , Lee MH , Johnson KR , Kowalak J , Elkahloun A , Medynets M , Hategan A , Kubofcik J , Sejvar J , Ratto J , Bunga S , Makumbi I , Aceng JR , Nutman TB , Dowell SF , Nath A . Sci Transl Med 2017 9 (377) Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies. |
Notes from the field: Tetanus cases after voluntary medical male circumcision for HIV prevention - Eastern and Southern Africa, 2012-2015
Grund JM , Toledo C , Davis SM , Ridzon R , Moturi E , Scobie H , Naouri B , Reed JB , Njeuhmeli E , Thomas AG , Benson FN , Sirengo MW , Muyenzi LN , Lija GJ , Rogers JH , Mwanasalli S , Odoyo-June E , Wamai N , Kabuye G , Zulu JE , Aceng JR , Bock N . MMWR Morb Mortal Wkly Rep 2016 65 (2) 36-7 Voluntary medical male circumcision (VMMC) decreases the risk for female-to-male HIV transmission by approximately 60% (1), and the President's Emergency Plan for AIDS Relief (PEPFAR) is supporting the scale-up of VMMC for adolescent and adult males in countries with high prevalence of human immunodeficiency virus (HIV) and low coverage of male circumcision (2). As of September 2015, PEPFAR has supported approximately 8.9 million VMMCs (3). |
Multidistrict outbreak of Marburg virus disease - Uganda, 2012
Knust B , Schafer IJ , Wamala J , Nyakarahuka L , Okot C , Shoemaker T , Dodd K , Gibbons A , Balinandi S , Tumusiime A , Campbell S , Newman E , Lasry E , DeClerck H , Boum Y , Makumbi I , Bosa HK , Mbonye A , Aceng JR , Nichol ST , Stroher U , Rollin PE . J Infect Dis 2015 212 Suppl 2 S119-28 In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection. |
Safer countries through global health security
Frieden TR , Tappero JW , Dowell SF , Hien NT , Guillaume FD , Aceng JR . Lancet 2014 383 (9919) 764-6 Countries around the world face a perfect storm of converging threats that might substantially increase the risk from infectious disease epidemics, despite improvements in technologies, communication, and some health systems. New pathogens emerge each year, some of which have high mortality and the potential for efficient transmission—eg, severe acute respiratory syndrome (SARS),1 Middle East respiratory syndrome coronavirus,2 and avian influenza A H7N9.3 Existing pathogens are becoming resistant to available antibiotics and several are now resistant to virtually all available treatment.4 There is also the potential threat of intentional release of biological agents, which can be developed or synthesised biologically and disseminated at low cost and with little scientific expertise. Moreover, the accelerated pace of globalisation amplifies these risks: a disease is just a plane trip away, and an outbreak anywhere is a threat everywhere. | One of the primary responsibilities of any government is to protect the health and safety of its people. There are three key elements of health security: prevention wherever possible, early detection, and timely and effective response. Although many countries are now better able to manage infectious disease threats than in the past, these improvements have often been small in scale and limited in scope. The International Health Regulations (IHR), revised by WHO in 2005 to more directly address new and emerging epidemic threats,5 require all 194 signatory countries to improve capacity in these and other areas as part of their commitment to protecting health.6 Yet, at least 80% of countries did not report full IHR compliance by the 2012 deadline.7 |
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