Ebola disease survivors often experience stigma in multiple forms, including felt (perceived) stigma, enacted (action-based) stigma, and institutional stigma. On September 20, 2022, Uganda declared a Sudan Virus Disease (species orthoebolavirus sudanense) outbreak after a patient with confirmed Sudan virus (SUDV) infection was identified in Mubende District. The outbreak led to 142 confirmed and 22 probable cases over the next two months. We examined the types of stigma experienced by survivors and their household members and its effect on their well-being. We conducted a qualitative study during January 2023 in Mubende and Kassanda Districts. We conducted in-depth and key informant interviews with ten SUDV disease survivors, ten household members of SUDV disease survivors, and ten key informants (district officials and health workers in the affected communities). Interviews were recorded, translated, transcribed, and analyzed thematically. Survivors reported experiencing isolation and rejection by community members and loss of work. They reported being denied purchases at shops or having their money collected in a basket and disinfected (enacted stigma), which led to self-isolation (felt stigma). Educational institutions denied admission to some students from affected homes, while parents of children in some affected families stopped sending children to school due to verbal abuse from students and teachers (structural stigma). Prolonged SUDV disease symptoms and additional attention to survivors from responders (including home visits by health workers, public distribution of support items, and conspicuous transport from home to the survivor's clinic) were perceived as aggravating both felt and enacted stigma. Even after the outbreak had been declared over, survivors felt that they were still considered a threat to the community. Survivors experienced mainly enacted stigma which was aggravated by the outbreak response and control activities such as additional attention to survivors from responders. Strengthening community engagement to counteract stigma, rethinking response activities that aggravate stigma, integrated response interventions by partners, private distribution of support items, and increasing awareness and sensitization could reduce stigma among the Ebola disease survivors in future responses.

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

BACKGROUND: Early detection of outbreaks requires robust surveillance and reporting at both community and health facility levels. Uganda implements Integrated Disease Surveillance and Response (IDSR) for priority diseases and uses the national District Health Information System (DHIS2) for reporting. However, investigations after the first case in the 2022 Uganda Sudan virus outbreak was confirmed on September 20, 2022 revealed many community deaths among persons with Ebola-like symptoms as far back as August. Most had sought care at private facilities. We explored possible gaps in surveillance that may have resulted in late detection of the Sudan virus disease (SVD) outbreak in Uganda. METHODS: Using a standardized tool, we evaluated core surveillance capacities at public and private health facilities at the hospital level and below in three sub-counties reporting the earliest SVD cases in the outbreak. Key informant interviews (KIIs) were conducted with 12 purposively-selected participants from the district local government. Focus group discussions (FGDs) were conducted with community members from six villages where early probable SVD cases were identified. KIIs and FGDs focused on experiences with SVD and Viral Hemorrhagic Fever (VHF) surveillance in the district. Thematic data analysis was used for qualitative data. RESULTS: Forty-six (85%) of 54 health facilities surveyed were privately-owned, among which 42 (91%) did not report to DHIS2 and 39 (85%) had no health worker trained on IDSR; both metrics were 100% in the eight public facilities. Weak community-based surveillance, poor private facility engagement, low suspicion index for VHF among health workers, inability of facilities to analyze and utilize surveillance data, lack of knowledge about to whom to report, funding constraints for surveillance activities, lack of IDSR training, and lack of all-cause mortality surveillance were identified as gaps potentially contributing to delayed outbreak detection. CONCLUSION: Both systemic and knowledge-related gaps in IDSR surveillance in SVD-affected districts contributed to the delayed detection of the 2022 Uganda SVD outbreak. Targeted interventions to address these gaps in both public and private facilities across Uganda could help avert similar situations in the future.

In 2022, the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state health and regulatory partners investigated an outbreak of Salmonella enterica serovar Typhimurium infections linked to cantaloupes from southwest Indiana, resulting in 87 ill persons and 32 hospitalizations reported in 11 states. Epidemiologic and traceback evidence confirmed cantaloupe as the vehicle for these infections. Based on records collected by FDA, traceback of cantaloupe exposures for 14 ill people converged on a packing house in southwest Indiana, which supplied cantaloupe to eight of the 11 points of service where ill people purchased cantaloupe. Salmonella isolates were recovered from environmental samples collected by FDA from three growers and a packing house in southwest Indiana. Whole genome sequencing analyses of these isolates found that isolates collected from one grower matched the Salmonella Typhimurium outbreak strain, and samples collected from the other two growers and the packing house matched a 2020 Salmonella Newport outbreak strain. State and federal public health and agricultural partners identified potential conditions and practices that could have possibly resulted in the contamination of cantaloupe, including the presence of Salmonella spp. in on-farm, post-harvest, and off-farm environments. This is the third outbreak of salmonellosis confirmed to be linked to melons, sourced from southwest Indiana in the last decade. The 2012, 2020, and 2022 outbreaks of reoccurring and persisting strains of Salmonella illustrate the need for additional efforts to determine the source and extent of environmental contamination in the melon growing region of southwest Indiana and for outreach and education to help promote practices to reduce contamination of melons. © 2024

RATIONALE: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/ACTG A5349 represents the largest Phase 3 randomized controlled therapeutic trial to date for such investigation. OBJECTIVES: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure with efficacy and safety outcomes. We aimed to determine pyrazinamide dosing strategies that optimize risks and benefits. METHODS: We analyzed pyrazinamide steady-state pharmacokinetic data using population nonlinear mixed-effects models. We evaluated the contribution of pyrazinamide exposure to long-term efficacy using parametric time-to-event models and safety outcomes using logistic regression. We evaluated optimal dosing with therapeutic windows targeting ≥95% durable cure and safety within the observed proportion of the primary safety outcome. MEASUREMENTS AND MAIN RESULTS: Among 2255 participants with 6978 plasma samples, pyrazinamide displayed 7-fold exposure variability (151-1053 mg·h/L). Body weight was not a clinically relevant predictor of drug clearance and thus did not justify the need for weight-banded dosing. Both clinical and safety outcomes were associated with pyrazinamide exposure, resulting in a therapeutic window of 231-355 mg·h/L for the control and 226-349 mg·h/L for the rifapentine-moxifloxacin regimen. Flat dosing of pyrazinamide at 1000 mg would have permitted an additional 13.1% (n=96) participants allocated to the control and 9.2% (n=70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared to the current weight-banded dosing. CONCLUSIONS: Flat dosing of pyrazinamide at 1000 mg daily would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772.

Introduction: Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). TB preventive treatment (TPT) can prevent active TB infection in PLHIV for several years after it is completed. During 2019–2021, the six-month course of TPT (using isoniazid) was the most readily available in Uganda; however, program data indicated a TPT program loss to follow-up (LTFU) rate of 12 % during this period. We evaluated factors associated with TPT LTFU among PLHIV in four regional referral hospitals (RRHs) in Uganda from 2019 to 2021. Methods: We abstracted program data from TPT registers on patient LTFU at Masaka, Mbale, Mubende, and Jinja RRHs. Additional data collected included client demographics, duration on HIV antiretroviral therapy (ART), year of TPT initiation, adherence, and point of entry. LTFU was defined as the failure to finish six consecutive months of isoniazid without stopping for more than two months at a time. We conducted bivariate analysis using the chi-square test for independence. Variables with p < 0.05 in bivariate analysis were included in a logistic regression model to establish independent factors associated with LTFU. Results: Overall, 24,206 clients were started on TPT in the four RRHs. Their median age was 40 years (range, 1–90 years), and 15,962 (66 %) were female. A total of 22,260 (92 %) had TPT adherence >95 %. Independent factors associated with LTFU included being on ART for <3 months (AOR: 3.1, 95 % CI: 2.1–4.5) and 20–24 years (AOR: 4.7, 95 % CI: 1.9–12) or 25–29 years (AOR: 3.3, 95 % CI: 1.3–8.2) compared to 15–19 years. Conclusions: PLHIV just starting ART and young adults had higher odds of being LTFU from TPT during 2019–2021 in the four RRHs. Close follow-up of PLHIV aged 20–29 years and those newly initiated on ART could improve TPT completion. © 2024 The Author(s)

BACKGROUND: On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this outbreak was 1.25. We described persons who were exposed to the virus, became infected, and they led to the infection of an unusually high number of cases during the outbreak. METHODS: In this descriptive cross-sectional study, we defined a super-spreader person (SSP) as any person with real-time polymerase chain reaction (RT-PCR) confirmed SVD linked to the infection of ≥ 13 other persons (10-fold the outbreak R). We reviewed illness narratives for SSPs collected through interviews. Whole-genome sequencing was used to support epidemiologic linkages between cases. RESULTS: Two SSPs (Patient A, a 33-year-old male, and Patient B, a 26-year-old male) were identified, and linked to the infection of one probable and 50 confirmed secondary cases. Both SSPs lived in the same parish and were likely infected by a single ill healthcare worker in early October while receiving healthcare. Both sought treatment at multiple health facilities, but neither was ever isolated at an Ebola Treatment Unit (ETU). In total, 18 secondary cases (17 confirmed, one probable), including three deaths (17%), were linked to Patient A; 33 secondary cases (all confirmed), including 14 (42%) deaths, were linked to Patient B. Secondary cases linked to Patient A included family members, neighbours, and contacts at health facilities, including healthcare workers. Those linked to Patient B included healthcare workers, friends, and family members who interacted with him throughout his illness, prayed over him while he was nearing death, or exhumed his body. Intensive community engagement and awareness-building were initiated based on narratives collected about patients A and B; 49 (96%) of the secondary cases were isolated in an ETU, a median of three days after onset. Only nine tertiary cases were linked to the 51 secondary cases. Sequencing suggested plausible direct transmission from the SSPs to 37 of 39 secondary cases with sequence data. CONCLUSION: Extended time in the community while ill, social interactions, cross-district travel for treatment, and religious practices contributed to SVD super-spreading. Intensive community engagement and awareness may have reduced the number of tertiary infections. Intensive follow-up of contacts of case-patients may help reduce the impact of super-spreading events.

BACKGROUND: Uganda Ministry of Health (MOH) recommends a first HIV DNA-PCR test at 4-6 weeks for early infant diagnosis (EID) of HIV-exposed infants (HEI) and immediate return of results. WHO recommends initiating antiretroviral therapy (ART) ≤ 7 days from HIV diagnosis. In 2019, MOH introduced point-of-care (POC) whole-blood EID testing in 33 health facilities and scaled up to 130 facilities in 2020. We assessed results turnaround time and ART linkage pre-POC and during POC testing. METHODS: We evaluated EID register data for HEI at 10 health facilities with POC and EID testing volume of ≥ 12 infants/month from 2018 to 2021. We abstracted data for 12 months before and after POC testing rollout and compared time to sample collection, results receipt, and ART initiation between periods using medians, Wilcoxon, and log-rank tests. RESULTS: Data for 4.004 HEI were abstracted, of which 1.685 (42%) were from the pre-POC period and 2.319 (58%) were from the period during POC; 3.773 (94%) had a first EID test (pre-POC: 1.649 [44%]; during POC: 2.124 [56%]). Median age at sample collection was 44 (IQR 38-51) days pre-POC and 42 (IQR 33-50) days during POC (p < 0.001). Among 3.773 HEI tested, 3.678 (97%) had test results. HIV-positive infants' (n = 69) median age at sample collection was 94 (IQR 43-124) days pre-POC and 125 (IQR 74-206) days during POC (p = 0.04). HIV positivity rate was 1.6% (27/1.617) pre-POC and 2.0% (42/2.061) during POC (p = 0.43). For all infants, median days from sample collection to results receipt by infants' caregivers was 28 (IQR 14-52) pre-POC and 1 (IQR 0-25) during POC (p < 0.001); among HIV-positive infants, median days were 23 (IQR 7-30) pre-POC and 0 (0-3) during POC (p < 0.001). Pre-POC, 4% (1/23) HIV-positive infants started ART on the sample collection day compared to 33% (12/37) during POC (p < 0.001); ART linkage ≤ 7 days from HIV diagnosis was 74% (17/23) pre-POC and 95% (35/37) during POC (p < 0.001). CONCLUSION: POC testing improved EID results turnaround time and ART initiation for HIV-positive infants. While POC testing expansion could further improve ART linkage and loss to follow-up, there is need to explore barriers around same-day ART initiation for infants receiving POC testing.

BACKGROUND: Early isolation and care for Ebola Disease patients at Ebola Treatment Units (ETU) curb outbreak spread. We evaluated time to ETU entry and associated factors during the 2022 Sudan virus disease (SVD) outbreak in Uganda. METHODS: We included persons with RT-PCR-confirmed SVD with onset September 20-November 30, 2022. We categorized days from symptom onset to ETU entry ('delays') as short (≤2), moderate (3-5), and long (≥6); the latter two were 'delayed isolation'. We categorized symptom onset timing as 'earlier' or 'later,' using October 15 as a cut-off. We assessed demographics, symptom onset timing, and awareness of contact status as predictors for delayed isolation. We explored reasons for early vs late isolation using key informant interviews. RESULTS: Among 118 case-patients, 25 (21%) had short, 43 (36%) moderate, and 50 (43%) long delays. Seventy-five (64%) had symptom onset later in the outbreak. Earlier symptom onset increased risk of delayed isolation [cRR=1∙8, 95%CI (1∙2-2∙8)]. Awareness of contact status and SVD symptoms, and belief that early treatment-seeking was lifesaving facilitated early care-seeking. Patients with long delays reported fear of ETUs and lack of transport as contributors. CONCLUSION: Delayed isolation was common early in the outbreak. Strong contact tracing and community engagement could expedite presentation to ETUs.

Given its enhanced genetic stability, novel oral poliovirus vaccine type 2 was deployed for type 2 poliovirus outbreak responses under World Health Organization Emergency Use Listing. We evaluated the safety profile of this vaccine. No safety signals were identified using a multipronged approach of passive and active surveillance.

BACKGROUND: The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the Phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes. METHODS: We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months, TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models, and all trial-defined safety outcomes using logistic regression. RESULTS: Our model derived rifampicin exposure ranged from 4.57 mg·h/L to 140.0 mg·h/L with a median of 41.8 mg·h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to weight-banded dose. Exposure-efficacy analysis (N=680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared to those with exposure above the median. Exposure-safety analysis (N=722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events, or serious adverse events. CONCLUSIONS: Flat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard of care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation.

INTRODUCTION: acute flaccid paralysis (AFP) surveillance is the gold standard of the Global Polio Eradication Initiative (GPEI) for detecting cases of poliomyelitis and tracking poliovirus transmission. Nigeria's AFP surveillance performance indicators are among the highest in countries of the World Health Organization (WHO) African Region. The primary AFP surveillance performance indicators are the rate of non-polio AFP among children and the proportion of timely, adequate specimen collection. The surveillance working group of the National Emergency Operations Centre assessed the quality of AFP surveillance data in some reportedly high-performing states. METHODS: we conducted a retrospective review of AFP surveillance performance indicators in Nigeria for 2010-2019. We also reviewed data in reports from four groups of surveillance peer reviews and validation visits (conducted by in-country GPEI partners) during August 2017-May 2019 in 16 states with high primary AFP surveillance indicators; the validation visits reviewed clinical information and the dates of specimen collection and onset of paralysis with caretakers. RESULTS: there were consistently increasing AFP surveillance primary performance indicators during 2010-2016, followed by declines during 2017-2019. From the data for 16 states with peer reviews conducted from August 2017-May 2019, overall concordance of reported and "true" (validated) AFP indicator data in peer review investigations was highly variable. True AFP concordance ranged from 58%-100%, and stool timeliness concordance ranged from 56%-95%. The most common clinical causes of reported AFP cases that were not true AFP were spastic paralysis, malaria, sickle cell disease, and malnutrition. All the states that participated in peer reviews developed surveillance improvement plans based on the gaps identified. CONCLUSION: Nigeria has highly sensitive AFP surveillance according to reported primary AFP performance indicators. The findings of peer reviews indicate that the AFP surveillance system needs to be strengthened and well-supervised to enhance data quality.

In 2011, a dedicated consortium of experts commenced work on the development of the novel oral poliovirus vaccine type 2 (nOPV2). After careful and rigorous analysis of data to enable early, targeted use of the vaccine, World Health Organization´s (WHO´s) Strategic Advisory Group of Experts on Immunization (SAGE) reviewed data from accelerated clinical development of nOPV2 and endorsed entering assessment under WHO´s Emergency Use Listing (EUL) procedure. In November 2020, nOPV2 received an interim recommendation for use under EUL to enable rapid field availability and potential wider rollout of the vaccine. In December 2020, Nigeria initiated preparation to meet all criteria for initial use of nOPV2 in the country and the documentation process to verify meeting them. The process entailed addressing the status of meeting 25 readiness criteria in nine categories for nOPV2 use in Nigeria for response efforts to ongoing cVDPV2 outbreaks. During January-February 2021, Nigeria submitted the required documentation for all required indicators for nOPV2 initial use. In February 2021, the country obtained approval from the GPEI nOPV2 Readiness Verification Team to introduce nOPV2 and in March 2021, rolled out the novel vaccine in mass vaccination campaigns for outbreak response in Bayelsa, Delta, Niger, Sokoto and Zamfara states, and one area council in the Federal Capital Territory (FCT). The lessons learned from this rollout experience in Nigeria are being applied as the country streamlines and strengthens the nOPV2 rollout process across the remaining states.

INTRODUCTION: in August 2020, the World Health Organization African Region was certified free of wild poliovirus (WPV) when Nigeria became the last African country to interrupt wild poliovirus transmission. The National Polio Emergency Operations Center instituted in 2012 to coordinate and manage Nigerian polio eradication efforts reviewed the epidemiology of WPV cases during 2000-2020 to document lessons learned. METHODS: we analyzed reported WPV cases by serotype based on age, oral poliovirus vaccine immunization history, month and year of reported cases, and annual geographic distribution based on incidence rates at the Local Government Area level. The observed trends of cases were related to major events and the poliovirus vaccines used during mass vaccination campaigns within the analysis period. RESULTS: a total of 3,579 WPV type 1 and 1,548 WPV type 3 laboratory-confirmed cases were reported with onset during 2000-2020. The highest WPV incidence rates per 100,000 population in Local Government Areas were 19.4, 12.0, and 11.3, all in 2006. Wild poliovirus cases were reported each year during 2000-2014; the endemic transmission went undetected throughout 2015 until the last cases in 2016. Ten events/milestones were highlighted, including insurgency in the northeast which led to a setback in 2016 with four cases from children previously trapped in security-compromised areas. CONCLUSION: Nigeria interrupted WPV transmission despite the challenges faced because of the emergency management approach, implementation of mass vaccination campaigns, the commitment of the government agencies, support from global polio partners, and special strategies deployed to conduct vaccination and surveillance in the security-compromised areas.

INTRODUCTION: in Nigeria, supportive supervision of Supplementary Immunization Activities (SIA) is a quality improvement strategy for providing support to vaccination teams administering the poliovirus vaccines to children under 5 years of age. Supervision activities were initially reported in paper forms. This had significant limitations, which led to Open Data Kit (ODK) technology being adopted in March 2017. A review was conducted to assess the impact of ODK for supervision reporting in place of paper forms. METHODS: issues with paper-based reporting and the benefits of ODK were recounted. We determined the average utilization of ODK per polio SIA rounds and assessed the supervision coverage over time based on the proportion of local government areas with ODK geolocation data per round. RESULTS: a total of 17 problematic issues were identified with paper-based reporting, and ODK addressed all the issues. Open Data Kit-based supervision reports increased from 3,125 in March 2017 to 51,060 in February 2020. Average ODK submissions for national rounds increased from 84 in March 2017 to 459 in February 2020 and for sub-national rounds increased from 533 in July 2017 to 1,596 in October 2019. Supportive supervision coverage improved from 42.5% in March 2017 to 97% in February 2020. CONCLUSION: the use of digital technologies in public health has comparative advantages over paper forms, and the adoption of ODK for supervision reporting during polio SIAs in Nigeria experienced the advantages. The visibility and coverage of supportive supervision improved, consequentially contributing to the improved quality of polio SIAs.

The Nigeria Polio Emergency Operations Centre (EOC) was established in October 2012 to strengthen coordination, provide strategic direction based on real-time data analysis, and manage all operational aspects of the polio eradication program. The establishment of seven state-level polio EOCs followed. With success achieved in the interruption of wild poliovirus (WPV) transmission as certified in 2020, the future direction of the polio EOC is under consideration. This paper describes the role of the polio EOC in other emergencies and perspectives on future disease control initiatives. A description of the functionality and operations of the polio EOC and a review of documentation of non-polio activities supported by the EOC was done. Key informant insights of national and state-level stakeholders were collected through an electronic questionnaire to determine their perspectives on the polio EOC's contributions and its future role in other public health interventions. The polio EOC structure is based on an incident management system with clear terms of reference and accountability and with full partner coordination. A decline in WPV1 cases was observed from 122 cases in 2012 to 0 in 2015; previously undetected transmission of WPV1 was confirmed in 2016 and all transmission was interrupted under the coordination of the EOCs at national and state levels. During 2014-2019, the polio EOC infrastructure and staff expertise were used to investigate and respond to outbreaks of Ebola, measles, yellow fever, and meningitis and to oversee maternal and neonatal tetanus elimination campaigns. The EOC structure at the national and state levels has contributed to the positive achievements in the polio eradication program in Nigeria and further in the coordination of other disease control and emergency response activities. The transition of the polio EOCs and their capacities to support other non-polio programs will contribute to harnessing the country's capacity for effective coordination of public health initiatives and disease outbreaks.

BACKGROUND: Widespread COVID-19 vaccine uptake can facilitate epidemic control. A February 2021 study in Uganda suggested that public vaccine uptake would follow uptake among leaders. In May 2021, Baylor Uganda led community dialogue meetings with district leaders from Western Uganda to promote vaccine uptake. We assessed the effect of these meetings on the leaders' COVID-19 risk perception, vaccine concerns, perception of vaccine benefits and access, and willingness to receive COVID-19 vaccine. METHODS: All departmental district leaders in the 17 districts in Western Uganda, were invited to the meetings, which lasted approximately four hours. Printed reference materials about COVID-19 and COVID-19 vaccines were provided to attendees at the start of the meetings. The same topics were discussed in all meetings. Before and after the meetings, leaders completed self-administered questionnaires with questions on a five-point Likert Scale about risk perception, vaccine concerns, perceived vaccine benefits, vaccine access, and willingness to receive the vaccine. We analyzed the findings using Wilcoxon's signed-rank test. RESULTS: Among 268 attendees, 164 (61%) completed the pre- and post-meeting questionnaires, 56 (21%) declined to complete the questionnaires due to time constraints and 48 (18%) were already vaccinated. Among the 164, the median COVID-19 risk perception scores changed from 3 (neutral) pre-meeting to 5 (strong agreement with being at high risk) post-meeting (p < 0.001). Vaccine concern scores reduced, with medians changing from 4 (worried about vaccine side effects) pre-meeting to 2 (not worried) post-meeting (p < 0.001). Median scores regarding perceived COVID-19 vaccine benefits changed from 3 (neutral) pre-meeting to 5 (very beneficial) post-meeting (p < 0.001). The median scores for perceived vaccine access increased from 3 (neutral) pre-meeting to 5 (very accessible) post-meeting (p < 0.001). The median scores for willingness to receive the vaccine changed from 3 (neutral) pre-meeting to 5 (strong willingness) post-meeting (p < 0.001). CONCLUSION: COVID-19 dialogue meetings led to district leaders' increased risk perception, reduced concerns, and improvement in perceived vaccine benefits, vaccine access, and willingness to receive the COVID-19 vaccine. These could potentially influence public vaccine uptake if leaders are vaccinated publicly as a result. Broader use of such meetings with leaders could increase vaccine uptake among themselves and the community.

BACKGROUND: The COVID-19 pandemic overwhelmed the capacity of health facilities globally, emphasizing the need for readiness to respond to rapid increases in cases. The first wave of COVID-19 in Uganda peaked in late 2020 and demonstrated challenges with facility readiness to manage cases. The second wave began in May 2021. In June 2021, we assessed the readiness of health facilities in Uganda to manage the second wave of COVID-19. METHODS: Referral hospitals managed severe COVID-19 patients, while lower-level health facilities screened, isolated, and managed mild cases. We assessed 17 of 20 referral hospitals in Uganda and 71 of 3,107 lower-level health facilities, selected using multistage sampling. We interviewed health facility heads in person about case management, coordination and communication and reporting, and preparation for the surge of COVID-19 during first and the start of the second waves of COVID-19, inspected COVID-19 treatment units (CTUs) and other service delivery points. We used an observational checklist to evaluate capacity in infection prevention, medicines, personal protective equipment (PPE), and CTU surge capacity. We used the "ReadyScore" criteria to classify readiness levels as > 80% ('ready'), 40-80% ('work to do'), and < 40% ('not ready') and tailored the assessments to the health facility level. Scores for the lower-level health facilities were weighted to approximate representativeness for their health facility type in Uganda. RESULTS: The median (interquartile range (IQR)) readiness scores were: 39% (IQR: 30, 51%) for all health facilities, 63% (IQR: 56, 75%) for referral hospitals, and 32% (IQR: 24, 37%) for lower-level facilities. Of 17 referral facilities, two (12%) were 'ready' and 15 (88%) were in the "work to do" category. Fourteen (82%) had an inadequate supply of medicines, 12 (71%) lacked adequate supply of oxygen, and 11 (65%) lacked space to expand their CTU. Fifty-five (77%) lower-level health facilities were "not ready," and 16 (23%) were in the "work to do" category. Seventy (99%) lower-level health facilities lacked medicines, 65 (92%) lacked PPE, and 53 (73%) lacked an emergency plan for COVID-19. CONCLUSION: Few health facilities were ready to manage the second wave of COVID-19 in Uganda during June 2021. Significant gaps existed for essential medicines, PPE, oxygen, and space to expand CTUs. The Uganda Ministry of Health utilized our findings to set up additional COVID-19 wards in hospitals and deliver medicines and PPE to referral hospitals. Adequate readiness for future waves of COVID-19 requires additional support and action in Uganda.

BACKGROUND: Uganda conducted its third mass long-lasting insecticidal net (LLIN) distribution campaign in 2021. The target of the campaign was to ensure that 100% of households own at least one LLIN per two persons and to achieve 85% use of distributed LLINs. LLIN ownership, use and associated factors were assessed 3 months after the campaign. METHODS: A cross-sectional household survey was conducted in 14 districts from 13 to 30 April, 2021. Households were selected using multistage sampling. Each was asked about LLIN ownership, use, duration since received to the time of interview, and the presence of LLINs was visually verified. Outcomes were having at least one LLIN per two household members, and individual LLIN use. Modified Poisson regression was used to assess associations between exposures and outcomes. RESULTS: In total, 5529 households with 27,585 residents and 15,426 LLINs were included in the analysis. Overall, 95% of households owned ≥ 1 LLIN, 92% of the households owned ≥ 1 LLIN < 3 months old, 64% of households owned ≥ 1 LLIN per two persons in the household. Eighty-seven per cent could sleep under an LLIN if every LLIN in the household were used by two people, but only 69% slept under an LLIN the night before the survey. Factors associated with LLIN ownership included believing that LLINs are protective against malaria (aPR = 1.13; 95% CI  1.04-1.24). Reported use of mosquito repellents was negatively associated with ownership of LLINs (aPR = 0.96; 95% CI 0.95-0.98). The prevalence of LLIN use was 9% higher among persons who had LLINs 3-12 months old (aPR = 1.09; 95% CI  1.06-1.11) and 10% higher among those who had LLINs 13-24 months old (aPR = 1.10; 95% CI  1.06-1.14) than those who had LLINs < 3 months old. Of 3,859 LLINs identified in the households but not used for sleeping the previous night, 3250 (84%) were < 3 months old. Among these 3250, 41% were not used because owners were using old LLINs; 16% were not used because of lack of space for hanging them; 11% were not used because of fear of chemicals in the net; 5% were not used because of dislike of the smell of the nets; and, 27% were not used for other reasons. CONCLUSION: The substantial difference between the population that had access to LLINs and the population that slept under LLINs indicates that the National Malaria Control Programme (NMCP) may need to focus on addressing the main drivers or barriers to LLIN use. NMCP and/or other stakeholders could consider designing and conducting targeted behaviour change communication during subsequent mass distribution of LLINs after the mass distribution campaign to counter misconceptions about new LLINs.

BACKGROUND: Semuto Subcounty reported rubella/measles outbreaks in January 2020 and June-August 2021. This study investigated the outbreak in 2021 to determine the scope, and the factors associated with transmission. METHODS: A probable case was defined as a resident of Semuto Subcounty with acute onset of fever and a generalized maculopapular rash with either cough/cold or red eyes from 1 June to 31 August 2021. A confirmed case was defined as a probable case with a blood sample positive for measles-specific IgM. A village-matched case-control study was conducted with 30 cases and 122 controls (1:4 ratio). A control was defined as an individual aged 6 months-9 years, sampled at random, with no signs or symptoms of measles from 1 June to 31 August 2021, residing in the same village as the matched case. Adjusted Mantel-Haenszel odds ratios (OR(MH)) and confidence intervals (CIs) were calculated. RESULTS: Of the 30 cases (27 probable and three confirmed), 16 (53%) were male. The subcounty attack rate (AR) was 3.2/1000. Children aged 5-9 years were the most affected (AR 5.0/1000). Twenty-two (79%) cases and 116 (97%) controls had ever received measles vaccine (OR(MH) 0.13, 95% CI 0.03-0.52). Interaction with symptomatic persons at water collection points (OR(MH) 4.4, 95% CI 1.6-12) and playing at community playgrounds (OR(MH) 4.2, 95% CI 1.7-11) increased the odds of infection. CONCLUSIONS: Socializing/congregating at water collection points and community playgrounds facilitated the transmission of measles in this outbreak.

Globally, hepatitis A virus (HAV) is one of the most common agents of acute viral hepatitis and causes approximately 1.4 million cases and 90,000 deaths annually despite the existence of an effective vaccine. In 2019, federal, state, and local partners investigated a multi-state outbreak of HAV infections linked to fresh blackberries sourced from multiple suppliers in Michoacn, Mexico. A total of 20 individuals with outbreak-related HAV infection were reported in seven states, including 11 hospitalizations, and no deaths. The Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and Nebraska State and Douglas County Health Departments conducted a traceback investigation for fresh blackberries reportedly purchased by 16 ill persons. These individuals reported purchasing fresh blackberries from 11 points of service from September 16 through 29, 2019 and their clinical isolates assessed through next-generation sequencing and phylogenetic analysis were genetically similar. The traceback investigation did not reveal convergence on a common grower or packing house within Mexico, but all of the blackberries were harvested from growers in Michoacn, Mexico. FDA did not detect the pathogen after analyzing fresh blackberry samples from four distributors, one consumer, and from nine importers at the port of entry as a result of increased screening. Challenges included gaps in traceability practices and the inability to recover the pathogen from sample testing, which prohibited investigators from determining the source of the implicated blackberries. This multi-state outbreak illustrated the importance of food safety practices for fresh produce that may contribute to foodborne illness outbreaks.

In early 2018, we investigated a large national multiple-serotype Salmonella outbreak linked to contaminated kratom, a raw minimally processed botanical substance. Kratom is a plant consumed for its stimulant effects and as an opioid substitute. A case was defined as a laboratory-confirmed Salmonella infection with one of the outbreak strains (serotypes I 4,[5],12:b:-, Heidelberg, Javiana, Okatie, Weltevreden, or Thompson) with illnesses onset during January 11, 2017-May 8, 2018. State and local officials collected detailed information on product consumption and sources. Suspected products were tested for Salmonella and traceback was conducted to determine product distribution chains and suppliers. We identified 199 cases from 41 states; 54 patients were hospitalized. Early interviews indicated kratom was an exposure of interest. Seventy-six (74%) of 103 people interviewed reported consuming kratom in pills, powders, or teas. Multiple serotypes of Salmonella were detected in samples of kratom collected from the homes of the patients and from retail locations. Several companies issued recalls of kratom products due to Salmonella contamination. To the authors' knowledge, this investigation is the first to establish kratom as a vehicle for Salmonella infection. Our findings underscore the serious safety concerns regarding minimally processed botanical substances intended for oral consumption and the challenges in investigating outbreaks linked to novel outbreak vehicles.

During the spring of 2018, the U.S. Food and Drug Administration (FDA), U.S. Centers for Disease Control and Prevention (CDC), states and local public health agencies responded to a multistate outbreak of gastrointestinal illnesses caused by multiple   Salmonella   serovars and associated with consumption of kratom, a product harvested from a tropical tree native to Southeast Asia. The outbreak included 199 case-patients reported by 41 U.S. states, with illness onset dates ranging from January 11, 2017 to May 8, 2018, leading to 54 hospitalizations, and no deaths. Case-patients reported purchasing kratom products from physical and online retail points of service (POS). Products distributed to 16 POS where 24 case-patients from 17 states purchased kratom were selected for traceback investigation. Traceback revealed that the kratom was imported from several countries, the most common being Indonesia. Local and state officials collected product samples from case-patients and retail POS. The FDA collected 76 product samples from POS and distributors, of which 42 (55%) tested positive for   Salmonella  . The positive samples exhibited a wide range of pulsed field gel electrophoresis (PFGE) patterns and whole genome sequence (WGS) genetic heterogeneity, and a total 25 of 42 (60%) yielded at least one isolate indistinguishable from one or more outbreak-related clinical isolates. While it does not exclude a possibility of a single contamination source, the extent of genetic diversity exhibited by the   Salmonella   isolates recovered from product samples and a lack of traceback convergence, suggested that kratom was widely contaminated across multiple sites from which it was grown, harvested, and packaged. As a result of the contamination, kratom products were recalled by numerous firms (both voluntarily and mandatory). Epidemiologic, traceback, and laboratory evidence supported the conclusion that kratom products were associated with illnesses.

The identification of sensitive, specific and reliable biomarkers that can be quantified in the early phases of tuberculosis treatment and predictive of long-term outcome is key for the development of an effective short-course treatment regimen. Time-to-positivity (TTP), a biomarker of treatment outcome against Mycobacterium tuberculosis, measures longitudinal bacterial growth in Mycobacteria Growth Indicator Tube broth culture and may be predictive of standard time-to-stable-culture-conversion (TSCC). In two randomized phase 2b trials investigating dose-ranging rifapentine (Study 29 and 29x), 662 participants had sputum collected over six months where TTP, TSCC and time-to-culture-conversion were quantified. The goals of this post hoc study were to characterize longitudinal TTP profiles and to identify individual patient characteristics associated with delayed time to culture conversion. In order to do so, a nonlinear mixed-effects model describing longitudinal TTP was built. Independent variables associated with increased bacterial clearance (increased TTP), assessed by subject-specific and population-level trajectories, were higher rifapentine exposure, lower baseline grade of sputum acid-fast bacilli smear, absence of productive cough, and lower extent of lung infiltrates on radiographs. Importantly, sensitivity analysis revealed that major learning milestones in phase 2b trials, such as significant exposure-response and covariate relationships, could be detected using truncated TTP data as early as 6 weeks from start of treatment, suggesting alternative phase 2B study designs. The TTP model built depicts a novel phase 2B surrogate endpoint that can inform early assessment of experimental treatment efficacy and treatment failure or relapse in patients treated with shorter and novel TB treatment regimens, improving efficiency of phase 2 clinical trials.

INTRODUCTION: Efficient management of study drug inventory shipments is critical to keep research sites enrolling into multisite clinical treatment trials. A standard manual drug-management process used by the Tuberculosis Trials Consortium (TBTC), did not accommodate import permit approval timelines, shipment transit-times and time-zone differences. We compared a new web-based solution with the manual process, during an international 34-site clinical trial conducted by the TBTC and the AIDS Clinical Trials Group (ACTG); TBTC Study 31/ACTG A5349. MATERIAL AND METHODS: We developed and implemented a technological solution by integrating logistical and regulatory requirements for drug importation with statistical simulations that estimated stock-out times in an online Drug Management Module (DMM). We measured the average shipment-related drug stock-outs and time to drug availability, to assess the efficiency of the DMM compared to the manual approach. RESULTS: An Interrupted Time-Series (ITS) analysis showed a 15% [p-value = 0.03; 95% C.I. (-28.8%, -2.0%)] reduction in average shipment-related study drug stock-out after DMM implementation. The DMM streamlined the restocking process at study sites, reducing median transit-time for sites associated with a depot by 2 days [95% C.I. (-3.0, -1.0)]. Under the DMM, study drugs were available for treatment assignment on the day received, compared to one day after receipt under the manual process. DISCUSSION: The DMM provided TBTC's Data and Coordinating Center and site staff with more efficient procedures to manage and consistently maintain study drug inventory at enrolling sites. This DMM framework can improve efficiency in future multicenter clinical trials. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (Identifier: NCT02410772) on April 8, 2015.

BACKGROUND: Rifapentine exposure is associated with bactericidal activity against Mycobacterium tuberculosis, but high interindividual variation in plasma concentrations is encountered. OBJECTIVES: To investigate a genomic association with interindividual variation of rifapentine exposure, SNPs of six human genes involving rifamycin metabolism (AADAC, CES2), drug transport (SLCO1B1, SLCO1B3) and gene regulation (HNF4A, PXR) were evaluated. METHODS: We characterized these genes in 173 adult participants in treatment trials of the Tuberculosis Trials Consortium. Participants were stratified by self-identified race (black or non-black), and rifapentine AUC from 0 to 24 h (AUC0-24) was adjusted by analysis of covariance for SNPs, rifapentine dose, sex, food and HIV coinfection. This study was registered at ClinicalTrials.gov under identifier NCT01043575. RESULTS: The effect on rifapentine least squares mean AUC0-24 in black participants overall decreased by -10.2% for AADAC rs1803155 G versus A allele (Wald test: P = 0.03; false discovery rate, 0.10). Black participants with one G allele in AADAC rs1803155 were three times as likely to have below target bactericidal rifapentine exposure than black participants with the A allele (OR, 2.97; 95% CI: 1.16, 7.58). With two G alleles, the OR was greater. In non-black participants, AADAC rs1803155 SNP was not associated with rifapentine exposure. In both black and non-black participants, other evaluated genes were not associated with rifapentine exposure (P > 0.05; false discovery rate > 0.10). CONCLUSIONS: Rifapentine exposure in black participants varied with AADAC rs1803155 genotype and the G allele was more likely to be associated with below bactericidal target rifapentine exposure. Further pharmacogenomic study is needed to characterize the association of the AADAC rs1803155 with inadequate rifapentine exposure in different patient groups.

INTRODUCTION: in 2015, a cholera outbreak was confirmed in Nairobi county, Kenya, which we investigated to identify risk factors for infection and recommend control measures. METHODS: we analyzed national cholera surveillance data to describe epidemiological patterns and carried out a case-control study to find reasons for the Nairobi county outbreak. Suspected cholera cases were Nairobi residents aged >2 years with acute watery diarrhea (>4 stools/≤12 hours) and illness onset 1-14 May 2015. Confirmed cases had Vibrio cholerae isolated from stool. Case-patients were frequency-matched to persons without diarrhea (1:2 by age group, residence), interviewed using standardized questionaires. Logistic regression identified factors associated with case status. Household water was analyzed for fecal coliforms and Escherichia coli. RESULTS: during December 2014-June 2015, 4,218 cholera cases including 282 (6.7%) confirmed cases and 79 deaths (case-fatality rate [CFR] 1.9%) were reported from 14 of 47 Kenyan counties. Nairobi county reported 781 (19.0 %) cases (attack rate, 18/100,000 persons), including 607 (78%) hospitalisations, 20 deaths (CFR 2.6%) and 55 laboratory-confirmed cases (7.0%). Seven (70%) of 10 water samples from communal water points had coliforms; one had Escherichia coli. Factors associated with cholera in Nairobi were drinking untreated water (adjusted odds ratio [aOR] 6.5, 95% confidence interval [CI] 2.3-18.8), lacking health education (aOR 2.4, CI 1.1-7.9) and eating food outside home (aOR 2.4, 95% CI 1.2-5.7). CONCLUSION: we recommend safe water, health education, avoiding eating foods prepared outside home and improved sanitation in Nairobi county. Adherence to these practices could have prevented this protacted cholera outbreak.

Introduction: Following a declaration by the World Health Organization that Liberia had successfully interrupted Ebola virus transmission on May 9th, 2015; the country entered a period of enhanced surveillance. The number of cases had significantly reduced prior to the declaration, leading to closure of eight out of eleven Ebola testing laboratories. Enhanced surveillance led to an abrupt increase in demand for laboratory services. We report interventions, achievements, lessons learned and recommendations drawn from enhancing laboratory capacity. Methods: Using archived data, we reported before and after interventions that aimed at increasing laboratory capacity. Laboratory capacity was defined by number of laboratories with Ebola Virus Disease (EVD) testing capacity, number of competent staff, number of specimens tested, specimen backlog, daily and surge testing capacity, and turnaround time. Using Stata 14 (Stata Corporation, College Station, TX, USA), medians and trends were reported for all continuous variables. Results: Between May and December 2015, interventions including recruitment and training of eight staff, establishment of one EVD laboratory facility, implementation of ten Ebola GeneXpert diagnostic platforms, and establishment of working shifts yielded an 8-fold increase in number of specimens tested, a reduction in specimens backlog to zero, and restoration of turn-around time to 24 hours. This enabled a more efficient surveillance system that facilitated timely detection and containment of two EVD clusters observed thereafter. Conclusion: Effective enhancement of laboratory services during high demand periods requires a combination of context-specific interventions. Building and ensuring sustainability of local capacity is an integral part of effective surveillance and disease outbreak response efforts.

Globalization has opened many fronts for disease outbreaks because of the quick movement of people and porous borders around the world. The emergence of zoonotic diseases and other communicable diseases highlights the need for implementation of the Global Health Security Agenda packages if countries are to achieve compliance with International Health Regulations (IHR 2005). Health workforce development is one of the critical components that must be addressed with utmost urgency if gaps in early disease detection and response are to be addressed. In this regard, this case study is based on a measles outbreak investigation in Uganda simulating a real-life outbreak investigation by field epidemiologists and seeks to demonstrate the principles of applied epidemiology outlining the critical steps in outbreak investigations and generation of evidence for decision making. It aims to shore up the health workforce capacity by providing practical training for field epidemiology students and professionals that builds their skills in outbreak investigation. This case study can be completed in less than three hours.

During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.