Ebola Treatment Unit Research Articles

Mother of All Labour: Vulnerability and Immunity in Times of Ebola

Wonkifong Ebola treatment unit was unique at the time of the outbreak that hit the Guinea in 2014. Contrary to other infrastructures run by Western workers, Wonkifong mainly employed personnel from Guinea, the Democratic Republic of Congo, and Cuba. Even so, the unit constituted a racialised landscape where proximity to white agencies granted privileges to certain groups of racialised people while excluding others. In a humanitarian infrastructure aimed at empowering knowledge of epidemics in the Global South, Black children were quarantined without their parents and left mostly unattended. After many months, former patients were hired as nannies to remedy the infrastructure’s blind spot. These women were employed to care for the children thanks to their immunity to the virus. Building on the concept of a ‘politics of life’ and exploring how these women were exploited as ‘medical superbodies’, my article sheds light on how the humanitarian infrastructure produced a gendered labour that mirrors other economies exploiting female Black bodies such as the colony or the plantation. Relying on an ethnography of practices of care and mobility within the unit, this piece underlines how the postcolonial segregation at play during the outbreak operated not strictly in terms of skin colour, but in terms of gender and closeness to white power.

Crimean-Congo hemorrhagic fever cases diagnosed during an outbreak of Sudan virus disease in Uganda, 2022-23.

In September 2022, Uganda experienced an outbreak of Sudan virus disease (SVD), mainly in central Uganda. As a result of enhanced surveillance activities for Ebola disease, samples from several patients with suspected viral hemorrhagic fever (VHF) were sent to the VHF Program at Uganda Virus Research Institute (UVRI), Entebbe, Uganda, and identified with infections caused by other viral etiologies. Herein, we report the epidemiologic and laboratory findings of Crimean-Congo hemorrhagic fever (CCHF) cases that were detected during the SVD outbreak response. Whole blood samples from VHF suspected cases were tested for Sudan virus (SUDV) by real-time reverse transcription-polymerase chain reaction (RT-PCR); and if negative, were tested for CCHF virus (CCHFV) by RT-PCR. CCHFV genomic sequences generated by metagenomic next generation sequencing were analyzed to ascertain strain relationships. Between September 2022 and January 2023, a total of 2,626 samples were submitted for VHF testing at UVRI. Overall, 13 CCHF cases (including 7 deaths; case fatality rate of 53.8%), aged 4 to 60 years, were identified from 10 districts, including several districts affected by the SVD outbreak. Four cases were identified within the Ebola Treatment Unit (ETU) at Mubende Hospital. Most CCHF cases were males engaged in livestock farming or had exposure to wildlife (n = 8; 61.5%). Among confirmed cases, the most common clinical symptoms were hemorrhage (n = 12; 92.3%), fever (n = 11; 84.6%), anorexia (n = 10; 76.9%), fatigue (n = 9; 69.2%), abdominal pain (n = 9; 69.2%) and vomiting (n = 9; 69.2%). Sequencing analysis showed that the majority of identified CCHFV strains belonged to the Africa II clade previously identified in Uganda. Two samples, however, were identified with greater similarity to a CCHFV strain that was last reported in Uganda in 1958, suggesting possible reemergence. Identifying CCHFV from individuals initially suspected to be infected with SUDV emphasizes the need for comprehensive VHF testing during filovirus outbreak responses in VHF endemic countries. Without expanded testing, CCHFV-infected patients would have posed a risk to health care workers and others while receiving treatment after a negative filovirus diagnosis, thereby complicating response dynamics. Additionally, CCHFV-infected cases could acquire an Ebola infection while in the ETU, and upon release because of a negative Ebola virus result, have the potential to spread these infections in the community.

Corneal and Conjunctival Abnormalities in a Cohort of Survivors from the Western African Ebola Virus Disease Outbreak

PurposeTo characterize corneal and conjunctival abnormalities (CCAs) and their impact on visual acuity in a cohort of survivors from the Western African Ebola virus disease (EVD) outbreak. DesignA post hoc analysis of 121 patients, who had previously undergone screening for the Ebola Virus Persistence in Ocular Tissues and Fluids study, was performed. MethodsPatients underwent a comprehensive ophthalmic exam at the Lowell and Ruth Gess Eye Hospital in Freetown, Sierra Leone. Demographic (including age, sex, and the number of days spent in the Ebola treatment unit and examination (such as visual acuity, and ocular complications) data were collected and used for the analysis. Visual acuity was either uncorrected or corrected with spectacles. Descriptive and inferential statistical analyses were performed, and a p-value < 0.05 was considered statistically significant. ResultsA total of 242 eyes (121 patients) were included in this study. The mean age was 31.5 ± 16.1 years, and 70% were female. Of 242 eyes, 28 (11.5%) eyes of 15 patients (12.4%) presented with at least one or more corneal or conjunctival abnormalities. Within eyes that demonstrated CCAs, the findings included dry eye (28.6% of eyes), band keratopathy (25% of eyes), and corneal scar (21.4% of eyes). Corneal edema was found in 14.3% of eyes, while pterygium and epithelial bullae were each found in 7.1% of affected eyes. Patients without CCAs had better visual acuity compared to patients with CCAs although the difference was not statistically significant (0.82 ± 1.17 vs 1.01 ± 1.29, p=0.4). A subset of patients with CCAs also reported ocular symptoms including eye pain, light sensitivity, excessive tearing, and blurry vision. ConclusionIn this post hoc analysis, we observed CCAs in 12% of EVD survivors. These findings highlight the potential for corneal and conjunctival sequelae during EVD survivorship and the need for ongoing ophthalmic care for this vulnerable population.

Factors associated with death in patients admitted with Ebola virus disease to Ebola Treatment Units in Guinea, Sierra Leone, and Liberia – December 2013 to March 2016

Background The 2013-2016 West African Ebola Virus Disease (EVD) outbreak resulted in 28,600 cases and 11,300 deaths officially reported to the World Health Organization. Previous studies investigating factors associated with death had conflicting findings, interventions showing promising outcomes had small sample sizes, studies were often single- or dual-country based and most focused on laboratory-confirmed EVD and not on clinically-suspected EVD. We used the Ebola data platform of the Infectious Disease Data Observatory (IDDO) to review individual patient records to assess factors associated with death, and particularly whether there were differences between laboratory-confirmed and clinically-suspected cases. Methods This was a cohort study involving analysis of secondary data in the IDDO database. The study population included all patients classified as having either clinically-suspected or laboratory-confirmed EVD, admitted to 22 Ebola Treatment Units (ETU) in Guinea, Liberia and Sierra Leone between December 2013 and March 2016. Baseline characteristics and treatments were documented along with ETU exit outcomes. Factors associated with death were investigated by multivariable modified Poisson regression. Results There were 14,163 patients, of whom 6,208 (43.8%) were laboratory-confirmed and 7,955 (56.2%) were clinically-suspected. Outcomes were not recorded in 2,889 (20.4%) patients. Of the 11,274 patients with known outcomes, 4,090 (36.3%) died: 2,956 (43.6%) with laboratory-confirmed EVD and 1,134 (18.8%) with clinically-suspected EVD. The strongest risk factor for death was confirmed disease status. Patients with laboratory-confirmed disease had 2.9 times higher risk of death compared to clinically-suspected patients, after adjusting for other co-variables. Other factors significantly associated with death included a higher risk for patients aged ≥60 years and a lower risk for patients in Sierra Leone. Conclusions Although laboratory-confirmed patients admitted to ETUs fared worse than clinically-suspected patients, the latter still had a substantial risk of death and more attention needs to be paid to this group in future EVD outbreaks.

Prevalence of somatic symptoms among Ebola Virus Disease (EVD) survivors in Africa: a systematic review and meta-analysis

BackgroundMany Ebola virus disease (EVD) survivors have reported somatic and neuropsychological symptoms after discharge from the Ebola Treatment Unit (ETU). Since the 2014–2016 Ebola epidemic in West Africa, various studies have investigated and identified these symptoms. Evidence on somatic symptoms is widely available in the literature, however, there is no concise overview of the prevalence across different time intervals.MethodsThis meta-analysis was conducted following the (PRISMA) guidelines. A database search was conducted to identify original studies that reported the prevalence of symptoms. The primary outcome measure was the prevalence rate of several somatic symptoms. Results were pooled, and prevalence rates were assessed over time, to elucidate any particular trends.ResultsWe included 23 studies (5,714 participants). The pooled prevalence was: arthralgia 50% (95% CI: 41%-59%); headache 44% (95% CI: 36%-52%); myalgia 32% (95% CI: 26%-38%); abdominal pain 27% (95% CI: 15%-39%); fatigue 25% (95% CI: 19%-31%); numbness of feet 16% (95% CI: 14%-18%); numbness of hands 12% (95% CI: 10%-14%) and hearing loss 9% (95% CI: 5%-12%). Prevalence across different time intervals revealed significant patterns. All the symptoms persisted for more than 2 years after discharge except for abdominal pain.ConclusionThe pooled prevalence rates of somatic symptoms are notably high. Arthralgia and headache are the most prevalent of the symptoms, with hearing loss and numbness in hands and feet being the least. We found that arthralgia, myalgia, and abdominal pain decreased over time. However, headache, fatigue, numbness of hands and feet, and hearing loss increased over time.

Sudan virus disease super-spreading, Uganda, 2022

BackgroundOn 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.MethodsIn 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.ResultsTwo 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.ConclusionExtended 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.

Assessment of health care workers preparedness to epidemics: A case of Ebola virus disease preparedness in private hospitals in Kampala, Uganda.

Unrecognized Ebola Virus Disease (EVD) can lead to multiple chains of transmissions if the first caretakers are not trained and prepared. This study aimed to assess healthcare workers (HCWs) preparedness in private hospitals located in Kampala, to detect, respond and prevent EVD. A descriptive cross-sectional study was carried out among HCWs in direct clinical care provision in four private hospitals, and in one Ebola Treatment Unit (ETU) using a self-administered questionnaire from March to June 2020. 222 HCWs agreed to participate aged from 19 to 64 years and with 6 months to 38 years of practice where most were nurses (44%). 3/5 hospitals did not have written protocols on EVD case management, and only one (ETU) had an exclusive emergency team. 59% were not sure whether contact tracing was taking place. Private hospitals were not included in EVD trainings organized by the Ministry of Health (MoH). In addition, HCWs in private hospitals were not empowered by the MoH to take part in EVD case management. Despite these shortcomings, only 66% of HCWs showed an interest to be immunized. Knowledge about potential Ebola vaccines was generally poor. In Kampala, Uganda, establishment of a more comprehensive preparedness and response strategy for EVD outbreaks is imperative for HCWs in private facilities, including a wide vaccination educational program on Ebola vaccination. The findings from this study if addressed will likely improve the preparedness and management of future Ebola outbreaks in Uganda.

Time to care and factors influencing appropriate Sudan virus disease care among case patients in Uganda, September to November 2022

ObjectivesEarly 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. MethodsWe 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. ResultsAmong 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 (crude risk ratio = 1.8, 95% confidence interval (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. ConclusionDelayed isolation was common early in the outbreak. Strong contact tracing and community engagement could expedite presentation to ETUs.

Infection prevention and control studies for care of patients with suspected or confirmed filovirus disease in healthcare settings, with focus on Ebola and Marburg: an integrative review

ObjectiveTo review evidence pertaining to methods for preventing healthcare-associated filovirus infections (including the survivability of filoviruses in clinical environments and the chlorine concentration required for effective disinfection), and to assess...

Keeping our Healthcare Workers Safe–Ebola and COVID-19

Introduction:Over the past decade, the world has wrestled with two major pandemics: Ebola and COVID-19. While Ebola revealed that we needed a strategy, Covid-19 showed we still didn't have one. Apart from ensuring that we isolate and contain the virus, one of the major concerns in responding to a pandemic is limiting transmission to healthcare personnel.Method:This presentation describes a clinician's experience with employing the same infection control strategies used for Ebola in a makeshift Ebola Treatment Unit in a school in Sierra Leone and at a COVID-19 alternate care facility built in a convention center in the US.Results:Transmission control strategies used for healthcare workers during Ebola were also successful for COVID-19. Both facilities, despite grossly different access to financial resources, ensured all clinicians didn’t break protocol of safety, due to rigorous donning and doffing entrances and exits, internalized individual risk, separated spaces with tape, and zoned areas.Conclusion:Two facilities with access to vastly different resources to treat two distinct infectious diseases used the same infection control measures for staff with success. Highlighting the priority of internalization of risk by healthcare workers alongside critical infection control measures proves to be the most valuable resource over multi-million dollar facilities erected during COVID.

Identification of Laboratory Biomarkers for Early Detection and Clinical Management of Post-Acute Syndrome Among Survivors of the 2013-2016 West Africa Ebola Outbreak in Sierra Leone.

The clinical management of persistent medical conditions affecting Ebola survivors, generally described as a post-Ebola syndrome, remains a public health concern. We aimed to analyze Ebola survivors' laboratory biomarkers as compared to their non-infected household relatives to identify biomarkers that could guide the identification of survivors at increased risk of developing severe at odds with the non-severe post-Ebola syndrome. Data were extracted from medical records of the Ebola survivors clinic, and we included only Ebola survivor's parameters recorded during the first baseline follow-up visit 2 weeks interval after their second negative PCR result. Moreover, household non-infected family contacts of survivors visiting the clinic during the same period were recruited as community control. The mean age of survivors was 32.65 (IQR: 15.5, 38.25) years, and Ebola IgG immunoglobulin was detected in all, thus confirming their status. The statistical significance (all p < 0.05) observed in monocyte percentage (MONO%), cluster of differentiation 4 percentage (CD4%), alanine aminotransferase (ALT), creatinine (CREA), and creatinine kinase (C-kinase) proved to be clinically significant as compared to the household relatives' group. Interestingly, the linear regression analysis indicated that the duration at ETU was negatively associated with lymphocyte percentage with a 5% lymphocyte decrease per day spent at ETU. Finally, there was a significant (p < 0.05) association between hematological (Hb, PCV, MCV, MCH), biochemical (ALT, CREA, C-kinase, T-cholesterol, triglycerides) parameters and the risk of developing severe complications. We recommend clinicians closely monitor Hb, PCV, MCV, MCH, ALT, CREA, C-kinase, T-cholesterol, triglycerides and lymphocytes as clinically relevant laboratory biomarkers to identify survivors at higher risk of developing severe post-acute syndrome upon discharge from Ebola treatment unit including headache, abdominal pain, chest pain, ocular complication, arthralgia, hearing difficulty and erectile dysfunction which can impact health-related quality of life among Ebola survivors.

Homage to Ebola Fighters: Black Labor and Humanitarian Media Campaigns.

During the Ebola outbreak that hit Guinea in 2014, most of the people employed at the Wonkifong Ebola treatment unit were from Africa or Cuba. Despite the recruitment of black personnel, the unit exposes how the humanitarian infrastructure exploited Guinean workers as if their lives were less vulnerable than those of the foreign personnel. The Africanization of aid reveals a post‐colonial segregation at the intersection of race, class, and locality. The article follows Guinean workers in the quarantine unit, as well as their enrolment in media campaigns. Their experience illuminates a triage at the core of Global Health according to which not only were local workers treated as expendable lives, but their stories were silenced. Yet how did Guinean workers inhabit this anti‐black world? The article unfolds the journey of workers during the outbreak and three years later, exploring the strategies they used to produce their own narratives through personal archives. [humanitarian aid, humanitarian media campaigns, race, Ebola, archives]

Risk Factors for Ebola Virus Persistence in Semen of Survivors in Liberia.

Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola virus disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within 1 year after discharge from the Ebola treatment unit or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR >1 year after discharge from the Ebola treatment unit or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical examinations and blood work. Compared with early clearers, late clearers were older (median, 42.5 years; P < .001) and experienced fewer severe clinical symptoms (median 2, P = .006). Late clearers had more lens opacifications (odds ratio, 3.9 [95% confidence interval, 1.1-13.3]; P = .03), after accounting for age, higher total serum immunoglobulin G3 (IgG3) titers (P = .005), and increased expression of the HLA-C*03:04 allele (0.14 [.02-.70]; P = .007). Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.

Evaluation of viral load in patients with Ebola virus disease in Liberia: a retrospective observational study

SummaryBackgroundViral load in patients with Ebola virus disease affects case fatality rate and is an important parameter used for diagnostic cutoffs, stratification in randomised controlled trials, and epidemiological studies. However, viral load in Ebola virus disease is currently estimated using numerous different assays and protocols that were not developed or validated for this purpose. Here, our aim was to conduct a laboratory-based re-evaluation of the viral loads of a large cohort of Liberian patients with Ebola virus disease and analyse these data in the broader context of the west Africa epidemic.MethodsIn this retrospective observational study, whole blood samples from patients at the Eternal Love Winning Africa Ebola treatment unit (Monrovia, Liberia) were re-extracted with an optimised protocol and analysed by droplet digital PCR (ddPCR) using a novel semi-strand specific assay to measure viral load. To allow for more direct comparisons, the ddPCR viral loads were also back-calculated to cycle threshold (Ct) values. The new viral load data were then compared with the Ct values from the original diagnostic quantitative RT-PCR (qRT-PCR) testing to identify differing trends and discrepancies.FindingsBetween Aug 28 and Dec 18, 2014, 727 whole blood samples from 528 individuals were collected. 463 (64%) were first-draw samples and 409 (56%) were from patients positive for Ebola virus (EBOV), species Zaire ebolavirus. Of the 307 first-draw EBOV-positive samples, 127 (41%) were from survivors and 180 (59%) were from non-survivors; 155 (50%) were women, 145 (47%) were men, and seven (2%) were not recorded, and the mean age was 29·3 (SD 15·0) years for women and 31·8 (SD 14·8) years for men. Survivors had significantly lower mean viral loads at presentation than non-survivors in both the reanalysed dataset (5·61 [95% CI 5·34–5·87] vs 7·19 [6·99–7·38] log10 EBOV RNA copies per mL; p<0·0001) and diagnostic dataset (Ct value 28·72 [27·97–29·47] vs 26·26 [25·72–26·81]; p<0·0001). However, the prognostic capacity of viral load increased with the reanalysed dataset (odds ratio [OR] of death 8·06 [95% CI 4·81–13·53], p<0·0001 for viral loads above 6·71 log10 EBOV RNA copies per mL vs OR of death 2·02 [1·27–3·20], p=0·0028 for Ct values below 27·37). Diagnostic qRT-PCR significantly (p<0·0001) underestimated viral load in both survivors and non-survivors (difference in diagnostic Ct value minus laboratory Ct value of 1·79 [95% CI 1·16–2·43] for survivors and 5·15 [4·43–5·87] for non-survivors). Six samples that were reported negative by diagnostic testing were found to be positive upon reanalysis and had high viral loads.InterpretationInaccurate viral load estimation from diagnostic Ct values is probably multifactorial; however, unaddressed PCR inhibition from tissue damage in patients with fulminant Ebola virus disease could largely account for the discrepancies observed in our study. Testing protocols for Ebola virus disease require further standardisation and validation to produce accurate viral load estimates, minimise false negatives, and allow for reliable epidemiological investigation.

Ebola Survivors are not at Increased Risk for Gynecologic Surgeries

As the result of multiple signs and symptoms, and complications observed among survivors of the Ebola virus disease (EVD), there is an assumption that survivors might experience perturbations within their clotting parameters. This may eventually lead to increased bleeding time, predisposing them to increased risk for surgical complications. This study aimed to comparatively review specific intra-operative parameters such as uterine fibroids and polyps among a number of EVD survivors and non survivors undergoing elective gynecologic surgeries at Redemption Hospital, a tertiary specialized referral hospital located within one of the EVD hotspots, in Liberia from January to October 2016. A case-control study was conducted wherein cases were referred from the Partnership for = Research on Vaccines and Infectious Diseases in Liberia (PREVAIL), an EVD clinical trial platform, while controls were sampled from the general patient population, at Redemption Hospital. The controls were matched based on age, employment status and parity. All surgeries were performed by single surgeon based on a surgical checklist that included designated intra- and post-operative parameters. Statistical analysis such as counts, percentiles, confidence intervals and relative risks were performed to assess the differences between the cases and controls, respectively. Survivors were between the ages of 42 years and 44 years for controls with an average interval between discharge from the Ebola Treatment Unit (ETU) and surgical intervention of greater than one year. The median duration of surgical procedure was 60 minutes and blood loss of 250 ml in both groups. Besides the relative risks (RR) of receiving antibiotics for more than 3 days of 1.5 (85.7% vs. 57.1%) and hospitalization of more than 7 days of 0.25 (14% vs. 57%) for survivors as compared to controls, most of the indicators were not significantly different. The findings revealed that EVD survivors who present with benign tumors such as uterine fibroids, polyps, or adenomyosis, requiring elective uterine surgery such as myomectomy and/or hysterectomy are generally not at increased risk of surgical complications because most of the indicators (hospitalization, blood loss, antibiotics, etc.) were not significantly different between the two groups. Findings from this study may potentially revise the approaches used by gynecologists and general surgeons during encounters and/or interventions with patient(s) concerning emerging infectious diseases (EIDs)

Association between oral antimalarial medication administration and mortality among patients with Ebola virus disease: a multisite cohort study

BackgroundEmpiric antimalarial treatment is a component of protocol-based management of Ebola virus disease (EVD), yet this approach has limited clinical evidence for patient-centered benefits.MethodsThis retrospective cohort study evaluated the association between antimalarial treatment and mortality among patients with confirmed EVD. The data was collected from five International Medical Corps operated Ebola Treatment Units (ETUs) in Sierra Leone and Liberia from 2014 through 2015. The standardized protocol used for patient care included empiric oral treatment with combination artemether and lumefantrine, twice daily for three days; however, only a subset of patients received treatment due to resource variability. The outcome of interest was mortality, comparing patients treated with oral antimalarials within 48-h of admission to those not treated. Analysis was conducted with logistic regression to generate adjusted odds ratios (aORs). Multivariable analyses controlled for ETU country, malaria rapid diagnostic test result, age, EVD cycle threshold value, symptoms of bleeding, diarrhea, dysphagia and dyspnea, and additional standard clinical treatments.ResultsAmong the 424 cases analyzed, 376 (88.7%) received early oral antimalarials. Across all cases, mortality occurred in 57.5% (244). In comparing unadjusted mortality prevalence, early antimalarial treated cases yielded 55.1% mortality versus 77.1% mortality for those untreated (p = 0.005). Multivariable analysis demonstrated evidence of reduced aOR for mortality with early oral antimalarial treatment versus non-treatment (aOR = 0.34, 95% Confidence Interval: 0.12, 0.92, p = 0.039).ConclusionEarly oral antimalarial treatment in an EVD outbreak was associated with reduced mortality. Further study is warranted to investigate this association between early oral antimalarial treatment and mortality in EVD patients.

Rapid establishment of a frontline field laboratory in response to an imported outbreak of Ebola virus disease in western Uganda, June 2019

The Democratic Republic of the Congo (DRC) declared an Ebola virus disease (EVD) outbreak in North Kivu in August 2018. By June 2019, the outbreak had spread to 26 health zones in northeastern DRC, causing >2,000 reported cases and >1,000 deaths. On June 10, 2019, three members of a Congolese family with EVD-like symptoms traveled to western Uganda’s Kasese District to seek medical care. Shortly thereafter, the Viral Hemorrhagic Fever Surveillance and Laboratory Program (VHF program) at the Uganda Virus Research Institute (UVRI) confirmed that all three patients had EVD. The Ugandan Ministry of Health declared an outbreak of EVD in Uganda’s Kasese District, notified the World Health Organization, and initiated a rapid response to contain the outbreak. As part of this response, UVRI and the United States Centers for Disease Control and Prevention, with the support of Uganda’s Public Health Emergency Operations Center, the Kasese District Health Team, the Superintendent of Bwera General Hospital, the United States Department of Defense’s Makerere University Walter Reed Project, and the United States Mission to Kampala’s Global Health Security Technical Working Group, jointly established an Ebola Field Laboratory in Kasese District at Bwera General Hospital, proximal to an Ebola Treatment Unit (ETU). The laboratory consisted of a rapid containment kit for viral inactivation of patient specimens and a GeneXpert Instrument for performing Xpert Ebola assays. Laboratory staff tested 76 specimens from alert and suspect cases of EVD; the majority were admitted to the ETU (89.3%) and reported recent travel to the DRC (58.9%). Although no EVD cases were detected by the field laboratory, it played an important role in patient management and epidemiological surveillance by providing diagnostic results in <3 hours. The integration of the field laboratory into Uganda’s National VHF Program also enabled patient specimens to be referred to Entebbe for confirmatory EBOV testing and testing for other hemorrhagic fever viruses that circulate in Uganda.

Risk Factors for Persistent Ebola Virus Infection in Semen Among Survivors From Liberia

Background: Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola Virus Disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to better understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. Methods: In 2017, a cohort of 131 male survivors of the 2014-2016 outbreak of EVD in Liberia were recruited from a national semen testing program into this case-case study. “Early clearers” were defined as those with two consecutive negative EBOV semen tests by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) at least two weeks apart within 1 year after discharge from the Ebola Treatment Unit (ETU). “Late clearers” had detectable EBOV RNA by rRT-PCR more than one year after ETU discharge. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical exams and blood work including chemistries, blood counts, hemoglobinopathies, human leukocyte antigen typing, and immunologic/inflammatory markers. Findings: Among 131 participants, 30 demonstrated long-term detection of EBOV RNA in semen by rRT-PCR, up to 852 days after ETU discharge. Compared to early clearers, late clearers were more likely to be older (median 42.5 years, p=0.0001) and reported having experienced fewer severe clinical symptoms (median 2, p=0.006). Late clearers were found to more frequently have lens opacifications (OR 3.9, 95%CI 1.1-13.3, p=0.03), after accounting for age. Finally, late clearers also exhibited elevated total serum IgG3 titers (p=0.007) and increased expression of the HLA-C*03:04 allele (OR 0.14, 95% CI 0.02-0.70, p=0.007). Interpretation: Older age and decreased illness severity may play a significant role in determining the clearance of EBOV from the semen of survivors. Immune and host genetic factors including total serum IgG3 and HLA-C*03:04 may mediate that interaction. In addition, our finding that late clearers were more likely to have lens opacifications after accounting for age suggests that individuals with EBOV persistence in semen may also have EBOV persistence in other immunologically protected sites, such as the eye. Identifying risk factors for viral persistence in semen among male survivors is critical to inform screening efforts and prevent recurrent outbreaks of EBOV. Funding Information: This was work was supported by funds from the CDC Foundation and the Centers for Disease Control and Prevention. This project has also been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. Declaration of Interests: The authors report no competing interests. Ethics Approval Statement: The study protocol was approved by the CDC and Liberia MoH Institutional Review Boards and Meharry Medical College (for hemoglobinopathy testing).

Establishing Healthcare Worker Performance and Safety in Providing Critical Care for Patients in a Simulated Ebola Treatment Unit: Non-Randomized Pilot Study.

Improving the provision of supportive care for patients with Ebola is an important quality improvement initiative. We designed a simulated Ebola Treatment Unit (ETU) to assess performance and safety of healthcare workers (HCWs) performing tasks wearing personal protective equipment (PPE) in hot (35 °C, 60% relative humidity) or thermo-neutral (20 °C, 20% relative humidity) conditions. In this pilot phase to determine the feasibility of study procedures, HCWs in PPE were non-randomly allocated to hot or thermo-neutral conditions to perform peripheral intravenous (PIV) and midline catheter (MLC) insertion and endotracheal intubation (ETI) on mannequins. Eighteen HCWs (13 physicians, 4 nurses, 1 nurse practitioner; 2 with prior ETU experience; 10 in hot conditions) spent 69 (10) (mean (SD)) minutes in the simulated ETU. Mean (SD) task completion times were 16 (6) min for PIV insertion; 33 (5) min for MLC insertion; and 16 (8) min for ETI. Satisfactory task completion was numerically higher for physicians vs. nurses. Participants’ blood pressure was similar, but heart rate was higher (p = 0.0005) post-simulation vs. baseline. Participants had a median (range) of 2.0 (0.0–10.0) minor PPE breaches, 2.0 (0.0–6.0) near-miss incidents, and 2.0 (0.0–6.0) health symptoms and concerns. There were eight health-assessment triggers in five participants, of whom four were in hot conditions. We terminated the simulation of two participants in hot conditions due to thermal discomfort. In summary, study tasks were suitable for physician participants, but they require redesign to match nurses’ expertise for the subsequent randomized phase of the study. One-quarter of participants had a health-assessment trigger. This research model may be useful in future training and research regarding clinical care for patients with highly infectious pathogens in austere settings.

Persistence of Ebola virus in semen among Ebola virus disease survivors in Sierra Leone: A cohort study of frequency, duration, and risk factors.

Sexual transmission chains of Ebola virus (EBOV) have been verified and linked to EBOV RNA persistence in semen, post-recovery. The rate of semen persistence over time, including the average duration of persistence among Ebola virus disease (EVD) survivors, is not well known. This cohort study aimed to analyze population estimates of EBOV RNA persistence rates in semen over time, and associated risk factors in a population of survivors from Sierra Leone. In this cohort study from May 2015 to April 2017 in Sierra Leone, recruitment was conducted in 2 phases; the first enrolled 100 male participants from the Western Area District in the capital of Freetown, and the second enrolled 120 men from the Western Area District and from Lungi, Port Loko District. Mean age of participants was 31 years. The men provided semen for testing, analyzed by quantitative reverse transcription PCR (qRT-PCR) for the presence of EBOV RNA. Follow-up occurred every 2 weeks until the endpoint, defined as 2 consecutive negative qRT-PCR results of semen specimen testing for EBOV RNA. Participants were matched with the Sierra Leone EVD case database to retrieve cycle threshold (Ct) values from the qRT-PCR analysis done in blood during acute disease. A purposive sampling strategy was used, and the included sample composition was compared to the national EVD survivor database to understand deviations from the general male survivor population. At 180 days (6 months) after Ebola treatment unit (ETU) discharge, the EBOV RNA semen positive rate was 75.4% (95% CI 66.9%-82.0%). The median persistence duration was 204 days, with 50% of men having cleared their semen of EBOV RNA after this time. At 270 days, persistence was 26.8% (95% CI 20.0%-34.2%), and at 360 days, 6.0% (95% CI 3.1%-10.2%). Longer persistence was significantly associated with severe acute disease, with probability of persistence in this population at 1 year at 10.1% (95% CI 4.6%-19.8%) compared to the probability approaching 0% for those with mild acute disease. Age showed a dose-response pattern, where the youngest men (≤25 years) were 3.17 (95% CI 1.60, 6.29) times more likely to be EBOV RNA negative in semen, and men aged 26-35 years were 1.85 (95% CI 1.04, 3.28) times more likely to be negative, than men aged >35 years. Among participants with both severe acute EVD and a higher age (>35 years), persistence remained above 20% (95% CI 6.0%-50.6%) at 1 year. Uptake of safe sex recommendations 3 months after ETU discharge was low among a third of survivors. The sample was largely representative of male survivors in Sierra Leone. A limitation of this study is the lack of knowledge about infectiousness. In this study we observed that EBOV RNA persistence in semen was a frequent phenomenon, with high population rates over time. This finding will inform forthcoming updated recommendations on risk reduction strategies relating to sexual transmission of EBOV. Our findings support implementation of a semen testing program as part of epidemic preparedness and response. Further, the results will enable planning of the magnitude of testing and targeted counseling needs over time.