Atypical clinical presentation of Ebola virus disease in pregnancy: Implications for clinical and public health management

Background Between December 2013 and June 2016, West Africa experienced the largest Ebola virus disease (EVD) outbreak in history. Understanding EVD in pregnancy is important for EVD clinical screening and infection prevention and control. Methods We conducted a review of medical records and EVD investigation reports from three districts in Sierra Leone. We report the clinical presentations and maternal and fetal outcomes of six pregnant women with atypical EVD, and subsequent transmission events from perinatal care. Results The six women (ages 18–38) were all in the third trimester. Each presented with signs and symptoms initially attributed to pregnancy. None met EVD case definition; only one was known at presentation to be a contact of an EVD case. Five women died, and all six fetuses/neonates died. These cases resulted in at least 35 additional EVD cases. Conclusions These cases add to the sparse literature focusing on pregnant women with EVD, highlighting challenges and implications for outbreak control. Infected newborns may also present atypically and may shed virus while apparently asymptomatic. Pregnant women identified a priori as contacts of EVD cases require special attention and planning for obstetrical care

A challenging response to a Lassa fever outbreak in a non endemic area of Sierra Leone in 2019 with export of cases to The Netherlands.

INTRODUCTION: On November 20, 2019, the Sierra Leone International Health Regulations (IHR) National Focal Point was notified of an exported case of Lassa fever in The Netherlands, by a Dutch doctor who previously practiced in a rural hospital in Sierra Leone. This report describes the extent of the outbreak, possible sources of infection, and the outbreak response measures taken. METHODS: Response measures implemented to control the outbreak included coordination across multiple countries and cities, outbreak investigation, active case finding, contact tracing and monitoring, laboratory investigation, and isolation and treatment of cases. RESULTS: We report a hospital-associated outbreak that resulted in 3 confirmed cases (health workers) and 2 probable cases (patients). The case fatality rate was 60%, whereas the secondary attack rate was 14%. Two cases involved exportations to The Netherlands. Failure to detect the index case and poor adherence to infection prevention and control (IPC) protocols contributed to disease spread. Pregnancy status and nonspecific signs and symptoms of the index case contributed to failure in early case detection. CONCLUSIONS: Rapid activation of national and subnational incident management systems resulted in rapid outbreak control. We recommend regular training for clinicians on surveillance and IPC protocols and strengthening in-country Lassa virus diagnostic capacity

New filovirus disease classification and nomenclature.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Clinical features of patients isolated for suspected Ebola virus disease at Connaught Hospital, Freetown, Sierra Leone: a retrospective cohort study.

BACKGROUND: The size of the west African Ebola virus disease outbreak led to the urgent establishment of Ebola holding unit facilities for isolation and diagnostic testing of patients with suspected Ebola virus disease. Following the onset of the outbreak in Sierra Leone, patients presenting to Connaught Hospital in Freetown were screened for suspected Ebola virus disease on arrival and, if necessary, were admitted to the on-site Ebola holding unit. Since demand for beds in this unit greatly exceeded capacity, we aimed to improve the selection of patients with suspected Ebola virus disease for admission by identifying presenting clinical characteristics that were predictive of a confirmed diagnosis. METHODS: In this retrospective cohort study, we recorded the presenting clinical characteristics of suspected Ebola virus disease cases admitted to Connaught Hospital's Ebola holding unit. Patients were subsequently classified as confirmed Ebola virus disease cases or non-cases according to the result of Ebola virus reverse-transcriptase PCR (EBOV RT-PCR) testing. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of every clinical characteristic were calculated, to estimate the diagnostic accuracy and predictive value of each clinical characteristic for confirmed Ebola virus disease. RESULTS: Between May 29, 2014, and Dec 8, 2014, 850 patients with suspected Ebola virus disease were admitted to the holding unit, of whom 724 had an EBOV RT-PCR result recorded and were included in the analysis. In 464 (64%) of these patients, a diagnosis of Ebola virus disease was confirmed. Fever or history of fever (n=599, 83%), intense fatigue or weakness (n=495, 68%), vomiting or nausea (n=365, 50%), and diarrhoea (n=294, 41%) were the most common presenting symptoms in suspected cases. Presentation with intense fatigue, confusion, conjunctivitis, hiccups, diarrhea, or vomiting was associated with increased likelihood of confirmed Ebola virus disease. Three or more of these symptoms in combination increased the probability of Ebola virus disease by 3·2-fold (95% CI 2·3-4·4), but the sensitivity of this strategy for Ebola virus disease diagnosis was low. In a subgroup analysis, 15 (9%) of 161 confirmed Ebola virus disease cases reported neither a history of fever nor a risk factor for Ebola virus disease exposure. INTERPRETATION: Discrimination of Ebola virus disease cases from patients without the disease is a major challenge in an outbreak and needs rapid diagnostic testing. Suspected Ebola virus disease case definitions that rely on history of fever and risk factors for Ebola virus disease exposure do not have sufficient sensitivity to identify all cases of the disease. FUNDING: None

Epidemiology of ebola virus disease transmission among health care workers in sierra leone, may to december 2014: a retrospective descriptive study

Background: Anecdotal evidence suggests that much of the continuing infection of health care workers (HCWs) with Ebola virus during the current outbreak in Sierra Leone has occurred in settings other than Ebola isolation units, and it is likely that some proportion of acquisition by HCWs occurs outside the workplace. There is a critical need to define more precisely the pathways of Ebola infection among HCWs, to optimise measures for reducing risk during current and future outbreaks. Methods: We conducted a retrospective descriptive study of Ebola acquisition among health workers in Sierra Leone during May-December 2014. The data used were obtained mainly from the national Ebola database, a cross-sectional survey conducted through administration of a structured questionnaire to infected HCWs, and key informant interviews of select health stakeholders. Results: A total of 293 HCWs comprising 277 (95 %) confirmed, 6 (2 %) probable, and 10 (3 %) suspected cases of infection with Ebola virus were enrolled in the study from nine districts of the country. Over half of infected HCWs (153) were nurses; others included laboratory staff (19, 6.5 %), doctors (9, 3.1 %), cleaners and porters (9, 3.1 %), Community Health Officers (8, 2.7 %), and pharmacists (2, 0.7 %). HCW infections were mainly reported from the Western Area (24.9 %), Kailahun (18.4 %), Kenema (17.7 %), and Bombali (13.3 %) districts. Almost half of the infected HCWs (120, 47.4 %) believed that their exposure occurred in a hospital setting. Others believed that they were exposed in the home (48, 19 %), at health centres (45, 17.8 %), or at other types of health facilities (13, 5.1 %). Only 27 (10.7 %) of all HCW infections were associated with Ebola virus disease (EVD) isolation units. Over half (60 %, 150) of infected HCWs said they had been trained in infection prevention and control prior to their infection, whereas 34 % (85) reported that they had not been so trained. Conclusions: This study demonstrated the perception that most HCW infections are associated with general health care and home settings and not with dedicated EVD settings, which should provide substantial reassurance to HCWs that measures in place at dedicated EVD facilities generally provide substantial protection when fully adhered to

Epidemiology of ebola virus disease transmission among health care workers in sierra leone, may to december 2014: a retrospective descriptive study

Background: Anecdotal evidence suggests that much of the continuing infection of health care workers (HCWs) with Ebola virus during the current outbreak in Sierra Leone has occurred in settings other than Ebola isolation units, and it is likely that some proportion of acquisition by HCWs occurs outside the workplace. There is a critical need to define more precisely the pathways of Ebola infection among HCWs, to optimise measures for reducing risk during current and future outbreaks. Methods: We conducted a retrospective descriptive study of Ebola acquisition among health workers in Sierra Leone during May-December 2014. The data used were obtained mainly from the national Ebola database, a cross-sectional survey conducted through administration of a structured questionnaire to infected HCWs, and key informant interviews of select health stakeholders. Results: A total of 293 HCWs comprising 277 (95 %) confirmed, 6 (2 %) probable, and 10 (3 %) suspected cases of infection with Ebola virus were enrolled in the study from nine districts of the country. Over half of infected HCWs (153) were nurses; others included laboratory staff (19, 6.5 %), doctors (9, 3.1 %), cleaners and porters (9, 3.1 %), Community Health Officers (8, 2.7 %), and pharmacists (2, 0.7 %). HCW infections were mainly reported from the Western Area (24.9 %), Kailahun (18.4 %), Kenema (17.7 %), and Bombali (13.3 %) districts. Almost half of the infected HCWs (120, 47.4 %) believed that their exposure occurred in a hospital setting. Others believed that they were exposed in the home (48, 19 %), at health centres (45, 17.8 %), or at other types of health facilities (13, 5.1 %). Only 27 (10.7 %) of all HCW infections were associated with Ebola virus disease (EVD) isolation units. Over half (60 %, 150) of infected HCWs said they had been trained in infection prevention and control prior to their infection, whereas 34 % (85) reported that they had not been so trained. Conclusions: This study demonstrated the perception that most HCW infections are associated with general health care and home settings and not with dedicated EVD settings, which should provide substantial reassurance to HCWs that measures in place at dedicated EVD facilities generally provide substantial protection when fully adhered to