Molecular characterization of the 2022 Sudan virus disease outbreak in Uganda.

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.

A health care professionals training needs assessment for oncology in Uganda.

BACKGROUND: Cancer incidence and mortality in sub-Saharan Africa are increasing and do account for significant premature death. The expertise of health care providers is critical to downstaging cancer at diagnosis and improving survival in low- and middle-income countries. We set out to determine the training needs of health care providers for a comprehensive oncology services package in selected hospitals in Uganda, in order to inform capacity development intervention to improve cancer outcomes in the East African region. METHODS: This was a cross-sectional survey using the WHO Hennessey-Hicks questionnaire to identify the training needs of health workers involved in cancer care, across 22 hospitals in Uganda. Data were captured in real time using the Open Data Kit platform from which the data was exported to Stata version 15 for analysis using the Wilcoxon signed-rank test and Somers-Delta. RESULTS: There were 199 respondent health professionals who were predominately female (146/199, 73.37%), with an average age of 38.97 years. There were 158/199 (79.40%) nurses, 24/199 (12.06%) medical doctors and 17/199 (8.54%) allied health professionals. Overall, the research and audit domain had the highest ranking for all the health workers (Somers-D = 0.60). The respondent's level of education had a significant effect on the observed ranking (P value = 0.03). Most of the continuing medical education (CME) topics suggested by the participants were in the clinical task-related category. CONCLUSION: The "research and audit" domain was identified as the priority area for training interventions to improve oncology services in Uganda. There are opportunities for addressing the identified training needs with an expanded cancer CME programme content, peer support networks and tailored training for the individual health care provider.

2022 Sudan Ebolavirus Outbreak in Uganda: Modelling Case Burden and Outbreak Duration.

In September 2022, an outbreak of Sudan virus (SUDV) was confirmed in Uganda. Following the first case report, we developed an individual based modelling platform (IBM-SUDV) to estimate the burden of cases and deaths, as well as the duration of the unfolding SUDV outbreak, using different scenarios. Modelled projections were within the range of cases and deaths ultimately observed.

Ebola disease outbreak caused by the Sudan virus in Uganda, 2022: a descriptive epidemiological study.

BACKGROUND: Uganda has had seven Ebola disease outbreaks, between 2000 and 2022. On Sept 20, 2022, the Ministry of Health declared a Sudan virus disease outbreak in Mubende District, Central Uganda. We describe the epidemiological characteristics and transmission dynamics. METHODS: For this descriptive study, cases were classified as suspected, probable, or confirmed using Ministry of Health case definitions. We investigated all reported cases to obtain data on case-patient demographics, exposures, and signs and symptoms, and identified transmission chains. We conducted a descriptive epidemiological study and also calculated basic reproduction number (Ro) estimates. FINDINGS: Between Aug 8 and Nov 27, 2022, 164 cases (142 confirmed, 22 probable) were identified from nine (6%) of 146 districts. The median age was 29 years (IQR 20-38), 95 (58%) of 164 patients were male, and 77 (47%) patients died. Symptom onsets ranged from Aug 8 to Nov 27, 2022. The case fatality rate was highest in children younger than 10 years (17 [74%] of 23 patients). Fever (135 [84%] of 160 patients), vomiting (93 [58%] patients), weakness (89 [56%] patients), and diarrhoea (81 [51%] patients) were the most common symptoms; bleeding was uncommon (21 [13%] patients). Before outbreak identification, most case-patients (26 [60%] of 43 patients) sought care at private health facilities. The median incubation was 6 days (IQR 5-8), and median time from onset to death was 10 days (7-23). Most early cases represented health-care-associated transmission (43 [26%] of 164 patients); most later cases represented household transmission (109 [66%]). Overall Ro was 1·25. INTERPRETATION: Despite delayed detection, the 2022 Sudan virus disease outbreak was rapidly controlled, possibly thanks to a low Ro. Children (aged <10 years) were at the highest risk of death, highlighting the need for targeted interventions to improve their outcomes during Ebola disease outbreaks. Initial care-seeking occurred at facilities outside the government system, showing a need to ensure that private and public facilities receive training to identify possible Ebola disease cases during an outbreak. Health-care-associated transmission in private health facilities drove the early outbreak, suggesting gaps in infection prevention and control. FUNDING: None.

Antiretroviral therapies in women after single-dose nevirapine exposure.

BACKGROUND: Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS: In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir­emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS: A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS: In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir­emtricitabine was superior to nevirapine plus tenofovir­emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.).

Continental concerted efforts to control the seventh outbreak of Ebola Virus disease in Uganda: The first 90 days of the response.

On 20th September 2022, Uganda declared the 7th outbreak of Ebola virus disease (EVD) caused by the Sudan Ebola strain following the confirmation of a case admitted at Mubende Regional Referral Hospital. Upon confirmation, the Government of Uganda immediately activated the national incident management system to initiate response activities. Additionally, a multi-country emergency stakeholder meeting was held in Kampala; convening Ministers of Health from neighbouring Member States to undertake cross-border preparedness and response actions. The outbreak spanned 69 days and recorded 164 cases (142 confirmed, 22 probable), 87 recoveries and 77 deaths (case fatality ratio of 47%). Nine out of 136 districts were affected with transmission taking place in 5 districts but spilling over in 4 districts without secondary transmission. As part of the response, the Government galvanised robust community mobilisation and initiated assessment of medical counter measures including therapeutics, new diagnostics and vaccines. This paper highlights the response actions that contributed to the containment of this outbreak in addition to the challenges faced with a special focus on key recommendations for better control of future outbreaks.

Acute hypoxaemic respiratory failure in a low-income country: a prospective observational study of hospital prevalence and mortality.

INTRODUCTION: Limited data exist on the epidemiology of acute hypoxaemic respiratory failure (AHRF) in low-income countries (LICs). We sought to determine the prevalence of AHRF in critically ill adult patients admitted to a Ugandan tertiary referral hospital; determine clinical and treatment characteristics as well as assess factors associated with mortality. MATERIALS AND METHODS: We conducted a prospective observational study at the Mulago National Referral and Teaching Hospital in Uganda. Critically ill adults who were hospitalised at the emergency department and met the criteria for AHRF (acute shortness of breath for less than a week) were enrolled and followed up for 90 days. Multivariable analyses were conducted to determine the risk factors for death. RESULTS: A total of 7300 patients was screened. Of these, 327 (4.5%) presented with AHRF. The majority (60 %) was male and the median age was 38 years (IQR 27-52). The mean plethysmographic oxygen saturation (SpO2) was 77.6% (SD 12.7); mean SpO2/FiO2 ratio 194 (SD 32) and the mean Lung Injury Prediction Score (LIPS) 6.7 (SD 0.8). Pneumonia (80%) was the most common diagnosis. Only 6% of the patients received mechanical ventilatory support. In-hospital mortality was 77% with an average length of hospital stay of 9.2 days (SD 7). At 90 days after enrolment, the mortality increased to 85%. Factors associated with mortality were severity of hypoxaemia (risk ratio (RR) 1.29 (95% CI 1.15 to 1.54), p=0.01); a high LIPS (RR 1.79 (95% CI 1.79 1.14 to 2.83), p=0.01); thrombocytopenia (RR 1.23 (95% CI 1.11 to 1.38), p=0.01); anaemia (RR 1.15 (95% CI 1.01 to 1.31), p=0.03) ; HIV co-infection (RR 0.84 (95% CI 0.72 to 0.97), p=0.019) and male gender (RR 1.15 (95% CI 1.01 to 1.31) p=0.04). CONCLUSIONS: The prevalence of AHRF among emergency department patients in a tertiary hospital in an LIC was low but was associated with very high mortality. Pneumonia was the most common cause of AHRF. Mortality was associated with higher severity of hypoxaemia, high LIPS, anaemia, HIV co-infection, thrombocytopenia and being male.

HIV subtypes induce distinct profiles of HIV-specific CD8(+) T cell responses.

CD8(+) T cells play an important role in controlling HIV infection and qualitative differences in HIV-specific CD8(+) responses may determine the degree of immune control. We studied 56 HIV-infected, ARV-naive Ugandans and examined the role of subtypes in modulating their HIV-specific T cell responses. Gag-specific responses were readily detectable in our study population. Interestingly, we found significantly decreased Gag-specific cytolysis (as measured by CD107 expression) in subtype D (n = 21) compared to subtype A (n = 35) HIV infection. Sequence analyses within identified epitopes suggest patterns of conservation that are subtype specific. We conclude that HIV subtypes may promote distinct profiles of T cells responses and immune control.

Therapeutic responses to AZT + 3TC + EFV in advanced antiretroviral naive HIV type 1-infected Ugandan patients.

Convenient, non-food-dependent dosing, low tablet volume, and relatively low cost have made nonnucleoside reverse transcriptase inhibitors a first choice for both clinicians and patients in Uganda. Concerns exist as to their efficacy in patients with viral loads (VL) above 100,000 copies/ml, a feature common to about 75% of HIV-1-infected patients presenting at the Joint Clinical Research Center (JCRC) in Uganda. Furthermore, there are few data on the response to such therapy of non-B subtypes, A and D, predominant in Uganda. Presented here is a retrospective analysis of therapeutic responses in 11 antiretroviral (ARV) naïve HIV-1-infected Ugandan patients who had been initiated on zidovudine (AZT), lamivudine (3TC), and efavirenz (EFV). Laboratory assessments subsequent to initiation of ARV therapy, done at 11.6 +/- 3.9 weeks and 30.6 +/- 5.9 weeks, showed 88.9 and 71.4% patients achieved undetectable viral load, respectively. Virological suppression to below detection occurred in 85.7% of patients at 11.6 weeks despite baseline VL >or= 100,000 copies/ml. At 31 weeks there was a median increment of +183 cells/mm(3) in CD4(+) T lymphocytes. These findings reflect significant efficacy in the use of AZT + 3TC + EFV in advanced ARV naive non-B subtype HIV-1-infected patients. The therapeutic responses were comparable to those previously described in the western world.

High prevalence of antiretroviral resistance in treated Ugandans infected with non-subtype B human immunodeficiency virus type 1.

This study examined the emergence and prevalence of drug-resistant mutations in reverse transcriptase and protease coding regions in human immunodeficiency virus type 1 (HIV-1)-infected Ugandans treated with antiretroviral drugs (ARV). Genotypic resistance testing was performed on 50 and 16 participants who were enrolled in a cross-sectional and longitudinal observational cohort, respectively. The majority of the 113 HIV-1 PR-RT sequences were classified as subtypes A and D. Drug resistance mutations were prevalent in 52% of ARV-experienced individuals, and 17 of 27 ARV-resistant isolates had three mutations or more in reverse transcriptase. Resistance mutations in protease were less prevalent but only 17 of the 50 patients were receiving a protease inhibitor upon sample collection. Mutations conferring drug resistance were also selected in 3 of 16 participants in the longitudinal cohort, i.e., less than 8 months after the initiation of ARV treatment. Rapid emergence of ARV resistance was associated with poor adherence to treatment regimens, which was related to treatment costs. ARV resistance did, however, appear at a slightly higher prevalence in HIV-1 subtype D (21 of 33) than subtype A (7 of 25) infected individuals. Overall, this observational study suggests that ARV-resistant HIV-1 isolates are emerging rapidly in ARV-treated individual in Uganda and possibly other developing countries.