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Introduction:Diarrheal diseases and meningitis are among the first causes of death in the world. Objective:The aim of this study was to evaluate the follow-up of the epidemiological surveillance of diseases with epidemic potential at the laboratories of the National Hospital of Donka (LHND), the National Hospital of Ignace Deen (LHNID) and the National Institute of Public Health (LINSP). Material and Methods: This was a four years retrospective study, from May 1st, 2009 to May 1st, 2013. Data collection was made from the registers. Results:Only the LHND had notified cases of cholera (17 cases =100%). The frequency of proven cases by gender was respectively 52.94% men for 47.06% women. The most affected age groups were those of 21-40 years (41.18%) and 41-60 years (29.41%). The mean age was 21.59 ± 4.71 years. During this survey period, the LINSP notified more cases of meningitis (60%), followed by the LHND (21.88%) and the LHNID (18.12%). The age group from 0 to 5 years was the most affected by meningitis with 84.29% for LHND and 77.59% for LHNID. The mean age was 2.87 ± 0.63 year. TheHemophilus influenzaeb was the most encountered with 55.73% at the LINSP, 47.15% at the LHND and 27.59% at the LHNID. Five of twenty suspected samples for red diarrhea were positive forShigella dysenteriae. Conclusion: The epidemiological surveillance of diseases with epidemic potential is useful and necessary for the control, prevention and fight against these infectious bacterial diseases.

Background: Ebola virus emerged in West Africa in December 2013. The ease of mobility, porous borders, and lack of public health infrastructure led to the largest Ebola virus disease (EVD) outbreak to date. Intervention: The 2013 EVD outbreak signalled the need for laboratory diagnostic capabilities in areas without strong public health systems. As part of the United States’ Department of Defense response, MRIGlobal was contracted to design, fabricate, equip, deploy, and operate two mobile diagnostic laboratories (MDLs). The first laboratory analysed blood samples from patients in an adjacent Ebola Treatment Centre (ETC) and buccal swabs from the deceased in the community in Moyamba, Sierra Leone. The second laboratory was deployed to support an ETC in Conakry, Guinea. The Department of Defense provided real-time quantitative reverse transcription polymerase chain reaction assays that were deployed and validated on-site. Lessons Learnt: Prompt and accurate molecular diagnostics reduced sample turn-around times from over 24 h to under 4 h. Experienced laboratory staff tested up to 110 samples per day and on-site engineering proved necessary for MDL setup and operation. As the Ebola response slowed, the sustainment of the MDLs’ operations was prioritised, including staff training and the transition of the MDLs to local governments. Training programmes for local staff were prepared in Sierra Leone and Guinea. Recommendations: The MRIGlobal MDL team significantly contributed to establishing increased laboratory capacity during the EVD outbreak in West Africa. Using the MDLs for molecular diagnosis is highly recommended until more sustainable solutions can be provided.

Little is known about respiratory viruses infection in Guinea. Influenza surveillance has not been implemented in Guinea mainly because of the paucity of laboratory infrastructure and capacity. This paper presents the first influenza surveillance data in Guinea. Swabs were obtained from August 2018 through December 2019 at influenza sentinel sites and transported to the Institut National de Santé Publique for testing. Ribonucleic acid was extracted and tested for the presence of influenza A and B by real-time reverse transcription-polymerase chain reaction (RT-PCR). Positive samples were further characterised to determine the subtypes and lineages of influenza viruses. A total of 862 swabs were collected and tested. Twenty-three per cent of samples tested positive for influenza A and B viruses. Characterisation of positive specimens identified influenza A/H1N1pmd09 (2.5%), influenza A/H3N2 (57.3%), influenza B/Victoria lineage (36.7%) and 7 (3.5%) influenza B with undetermined lineage. Influenza B virus activity clustered in August through November while influenza A/H3N2 displayed two clusters of activities that appeared in May through August and November through December. For the first time in Guinea, the epidemiology, diversity and period of circulation of influenza viruses were studied. The results indicate the predominance and the periods of activities of influenza B Victoria lineage and influenza A/H3N2 which are important information for preventive strategies. It is warranted to extend the influenza surveillance to other parts of Guinea to better understand the epidemiology of the viruses and monitor the emergence of influenza strains with pandemic potential.

BackgroundThe 2013-16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus.MethodsIn this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for antibody quantification by ELISA, functional neutralising antibody analysis using live Zaire ebolavirus, and T cell phenotype studies. We report on the longitudinal cellular and humoral response among Ebola virus disease survivors and highlight potentially paucisymptomatic infection.FindingsWe recruited 117 survivors of Ebola virus disease, 66 contacts, and 23 negative controls. The mean neutralising antibody titre among the Ebola virus disease survivors 3-14 months after infection was 1/174 (95% CI 1/136-1/223). Individual results varied greatly from 1/10 to more than 1/1000 but were on average ten times greater than that induced after 1 month by single dose Ebola virus vaccines. Following reactivation with glycoprotein peptide, the mean T cell responses among 116 Ebola virus disease survivors as measured by ELISpot was 305 spot-forming units (95% CI 257-353). The dominant CD8+ polyfunctional T cell phenotype, as measured among 53 Ebola virus disease survivors, was interferon γ+, tumour necrosis factor+, interleukin-2-, and the mean response was 0·046% of total CD8+ T cells (95% CI 0·021-0·071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection.InterpretationThe continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection.FundingUS Food & Drug Administration, Horizon 2020 EU EVIDENT, Wellcome, UK Department for International Development.TranslationFor the French translation of the abstract see Supplementary Materials section.

During 2014, Africa reported more than half of the global suspected cholera cases. Based on the data collected from seven countries in the African Cholera Surveillance Network (Africhol), we assessed the sensitivity, specificity, and positive and negative predictive values of clinical cholera case definitions, including that recommended by the World Health Organization (WHO) using culture confirmation as the gold standard. The study was designed to assess results in real-world field situations in settings with recent cholera outbreaks or endemicity. From June 2011 to July 2015, a total of 5,084 persons with suspected cholera were tested for Vibrio cholerae in seven different countries of which 35.7% had culture confirmation. For all countries combined, the WHO case definition had a sensitivity = 92.7%, specificity = 8.1%, positive predictive value = 36.1%, and negative predictive value = 66.6%. Adding dehydration, vomiting, or rice water stools to the case definition could increase the specificity without a substantial decrease in sensitivity. Future studies could further refine our findings primarily by using more sensitive methods for cholera confirmation.

Clinical follow-up of Ebola virus disease (EVD) survivors revealed a persistence of clinical symptoms and higher risk of mortality. Long-term analyses of the immune and inflammatory profiles of EVD survivors are currently lacking. Here, we evaluate immune profile status and gene expression profiles in 35 Guinean EVD survivors (EBOV_S) from the last West African outbreak, a median of 23 months (IQR [18-25]) after discharge from the Ebola treatment center. We show a persistent increase of several biomarkers of inflammation, immune activation and gut tissue damage in EBOV_S compared to healthy donors living in the same area. These results are confirmed by phenotypic characterization of immune cell subsets revealing increases in activation marker expression and the frequencies of CD8+ T cells, exhausted B cells, non-classical NK cells and circulating dendritic cells. All survivors have EBOV-specific IgG antibodies and robust and polyfunctional EBOV-specific memory T-cell responses. Deep sequencing studies of the genes expressed in blood revealed a significant enrichment in genes associated with antiviral responses in EBOV_S. This study assess the long-term persistence of immunological dysfunction in survivors and identify a set of biological and genetic markers that could be used to define a signature of “chronic Ebola virus disease (CEVD)”.

In 2015, favipiravir was administered on a compassionate-use basis to patients with Ebola virus disease in Guinea. This study reveals a trend toward improved survival in favipiravir-treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time., Background In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus–specific reverse transcription–polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. Methods To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. Results The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. Conclusions Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

To guide One Health capacity building efforts in the Republic of Guinea in the wake of the 2014–2016 Ebola virus disease (EVD) outbreak, we sought to identify and assess the existing systems and structures for zoonotic disease detection and control. We partnered with the government ministries responsible for human, animal, and environmental health to identify a list of zoonotic diseases – rabies, anthrax, brucellosis, viral hemorrhagic fevers, trypanosomiasis and highly pathogenic avian influenza – as the country's top priorities. We used each priority disease as a case study to identify existing processes for prevention, surveillance, diagnosis, laboratory confirmation, reporting and response across the three ministries. Results were used to produce disease-specific systems “maps” emphasizing linkages across the systems, as well as opportunities for improvement. We identified brucellosis as a particularly neglected condition. Past efforts to build avian influenza capabilities, which had degraded substantially in less than a decade, highlighted the challenge of sustainability. We observed a keen interest across sectors to reinvigorate national rabies control, and given the regional and global support for One Health approaches to rabies elimination, rabies could serve as an ideal disease to test incipient One Health coordination mechanisms and procedures. Overall, we identified five major categories of gaps and challenges: (1) Coordination; (2) Training; (3) Infrastructure; (4) Public Awareness; and (5) Research. We developed and prioritized recommendations to address the gaps, estimated the level of resource investment needed, and estimated a timeline for implementation. These prioritized recommendations can be used by the Government of Guinea to plan strategically for future One Health efforts, ideally under the auspices of the national One Health Platform. This work demonstrates an effective methodology for mapping systems and structures for zoonotic diseases, and the benefit of conducting a baseline review of systemic capabilities prior to embarking on capacity building efforts. Keywords: Guinea, One Health, Zoonotic disease, Health systems assessment, Capacity building

In the wake of the 2014–2016, West Africa Ebola virus disease (EVD) outbreak, the Government of Guinea recognized an opportunity to strengthen its national laboratory system, incorporating capacity and investments developed during the response. The Ministry of Health (MOH) identified creation of a holistic, safe, secure, and timely national specimen referral system as a priority for improved detection and confirmation of priority diseases, in line with national Integrated Disease Surveillance and Response guidelines. The project consisted of two parts, each led by different implementing partners working collaboratively together and with the Ministry of Health: the development and approval of a national specimen referral policy, and pilot implementation of a specimen referral system, modeled on the policy, in three prefectures. This paper describes the successful execution of the project, highlighting the opportunities and challenges of building sustainable health systems capacity during and after public health emergencies, and provides lessons learned for strengthening national capabilities for surveillance and disease diagnosis.

International audience; To clarify the role of bats in the ecology of Ebola viruses, we assessed the prevalence of Ebola virus antibodies in a large-scale sample of bats collected during 2015-2017 from countries in Africa that have had previous Ebola outbreaks (Guinea, the Democratic Republic of the Congo) or are at high risk for outbreaks (Cameroon). We analyzed 4,022 blood samples of bats from >12 frugivorous and 27 insectivorous species; 2-37 (0.05%-0.92%) bats were seropositive for Zaire and 0-30 (0%-0.75%) bats for Sudan Ebola viruses. We observed Ebola virus antibodies in 1 insectivorous bat genus and 6 frugivorous bat species. Certain bat species widespread across Africa had serologic evidence of Zaire and Sudan Ebola viruses. No viral RNA was detected in the subset of samples tested (n = 665). Ongoing surveillance of bats and other potential animal reservoirs are required to predict and prepare for future outbreaks.

Background During the 2014–2016 Ebola epidemic in West Africa, a key epidemiological feature was disease transmission within healthcare facilities, indicating a need for infection prevention and control (IPC) training and support. Methods IPC training was provided to frontline healthcare workers (HCW) in healthcare facilities that were not Ebola treatment units, as well as to IPC trainers and IPC supervisors placed in healthcare facilities. Trainings included both didactic and hands-on components, and were assessed using pre-tests, post-tests and practical evaluations. We calculated median percent increase in knowledge. Results From October–December 2014, 20 IPC courses trained 1,625 Guineans: 1,521 HCW, 55 IPC trainers, and 49 IPC supervisors. Median test scores increased 40% (interquartile range [IQR]: 19–86%) among HCW, 15% (IQR: 8–33%) among IPC trainers, and 21% (IQR: 15–30%) among IPC supervisors (all P

International audience; Questions remain as to whether an unnoticed Ebola outbreak occurred in Guinea before the 2014-2016 epidemic. To address this, we used a highly sensitive and specific Luminex-based assay for Ebola virus (EBOV) antibody detection to screen blood samples collected in the framework of the Demographic Health Survey performed in 2012 in Guinea. One sample (GF069) of 1,483 tested was positive at very high immunoglobulin G titer to Zaire EBOV in Guinée Forestière. Thus, at least 2 years before the 2014 EVD outbreak in Guinea, Zaire EBOV was circulating in rural areas of this country.

Preventive measures and treatment guidelines are needed to address the sizeable prevalence of disease in this population., The prevalence and consequences of malaria among infants are not well characterized and may be underestimated. A better understanding of the risk for malaria in early infancy is critical for drug development and informed decision making. In a cross-sectional survey in Guinea, The Gambia, and Benin, countries with different malaria transmission intensities, the overall prevalence of malaria among infants

Background Human Ebola infection is characterized by a paralysis of the immune system. A signature of αβ T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014–2015 occurred in West Africa, and to assess their association with the clinical outcome. Methodology/Principal findings Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector Vδ2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56bright and CD56dim NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56neg NK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome. Conclusions/Significances Altogether, the data suggest that both effector Vδ2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of Vδ2 and NK cells., Author summary Human Ebola infection presents a high lethality rate and is characterized by a paralysis of the immune response. The definition of the protective immune profile during Ebola infection represents a main challenge useful in vaccine and therapy design. In particular, the protective/pathogenetic involvement of innate immune cells during Ebola infection in humans remains to be clarified. Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Center in Guinea, and the profiling of innate immunity was correlated with the clinical outcome. Our results show that both effector Vδ2 T-cells and NK cells were associated with survival, suggesting their involvement in the complex network of protective response to EBOV infection.

Background: Laboratory-enhanced surveillance is critical for rapidly detecting the potential re-emergence of Ebola virus disease. Rapid diagnostic tests (RDT) for Ebola antigens could expand diagnostic capacity for Ebola virus disease. Objectives: The Guinean National Coordination for Ebola Response conducted a pilot implementation to determine the feasibility of broad screening of patients and corpses with the OraQuick® Ebola RDT. Methods: The implementation team developed protocols and trained healthcare workers to screen patients and corpses in Forecariah prefecture, Guinea, from 15 October to 30 November 2015. Data collected included number of consultations, number of fevers reported or measured, number of tests performed for patients or corpses and results of confirmatory RT-PCR testing. Data on malaria RDT results were collected for comparison. Feedback from Ebola RDT users was collected informally during supervision visits and forums. Results: There were 3738 consultations at the 15 selected healthcare facilities; 74.6% of consultations were for febrile illness. Among 2787 eligible febrile patients, 2633 were tested for malaria and 1628 OraQuick® Ebola RDTs were performed. A total of 322 OraQuick® Ebola RDTs were conducted on corpses. All Ebola tests on eligible patients were negative. Conclusions: Access to Ebola testing was expanded by the implementation of RDTs in an emergency situation. Feedback from Ebola RDT users and lessons learned will contribute to improving quality for RDT expansion.

In March 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus (EBOV) as the causative agent. Full-length genome sequencing and phylogenetic analysis showed that EBOV from Guinea forms a separate clade in relationship to the known EBOV strains from the Democratic Republic of Congo and Gabon. Epidemiologic investigation linked the laboratory-confirmed cases with the presumed first fatality of the outbreak in December 2013. This study demonstrates the emergence of a new EBOV strain in Guinea.

International audience; An epidemic of Ebola virus disease of unprecedented scale has been ongoing for more than a year in West Africa. As of 29 April 2015, there have been 26,277 reported total cases (of which 14,895 have been laboratory confirmed) resulting in 10,899 deaths. The source of the outbreak was traced to the prefecture of Guéckédou in the forested region of southeastern Guinea. The virus later spread to the capital, Conakry, and to the neighbouring countries of Sierra Leone, Liberia, Nigeria, Senegal and Mali. In March 2014, when the first cases were detected in Conakry, the Institut Pasteur of Dakar, Senegal, deployed a mobile laboratory in Donka hospital to provide diagnostic services to the greater Conakry urban area and other regions of Guinea. Through this process we sampled 85 Ebola viruses (EBOV) from patients infected from July to November 2014, and report their full genome sequences here. Phylogenetic analysis reveals the sustained transmission of three distinct viral lineages co-circulating in Guinea, including the urban setting of Conakry and its surroundings. One lineage is unique to Guinea and closely related to the earliest sampled viruses of the epidemic. A second lineage contains viruses probably reintroduced from neighbouring Sierra Leone on multiple occasions, while a third lineage later spread from Guinea to Mali. Each lineage is defined by multiple mutations, including non-synonymous changes in the virion protein 35 (VP35), glycoprotein (GP) and RNA-dependent RNA polymerase (L) proteins. The viral GP is characterized by a glycosylation site modification and mutations in the mucin-like domain that could modify the outer shape of the virion. These data illustrate the ongoing ability of EBOV to develop lineage-specific and potentially phenotypically important variation.

During the pandemic 2009 episode, we conducted laboratory-based surveillance in four countries from West Africa: Senegal, Mauritania, Cape Verde, and Guinea. Specimens were obtained from 3,155 patients: 2,264 patients from Senegal, 498 patients from Cape Verde, 227 patients from Mauritania, and 166 patients from Guinea; 911 (28.9%) patients were positive for influenza, 826 (90.7%) patients were positive for influenza A, and 85 (9.3%) patients were positive for influenza B. Among the influenza A positives, 503 (60.9%) positives were H1N1pdm09, 314 (38.0%) positives were H3N2, and 9 (1.1%) positives were seasonal H1N1. The highest detection rate for seasonal influenza viruses (17.1%) occurred in the 5-14 years age group. However, for A(H1N1)pdm09, the detection rate was highest in the 15-24 years age group (35.8%). Based on the present study data, the timeline of detection of A(H1N1)pdm09 viruses in these four countries should be Cape Verde, Guinea, Mauritania, and finally, Senegal. Genetic and antigenic analyses were performed in some isolates.

This study aimed at reconstructing the spatial and temporal evolution of Lassa virus (LASV) in the natural host population. To this end, we generated 132 partial nucleoprotein sequences of LASV from M. natalensis trapped in 12 villages around Faranah, Upper Guinea, over a period of 12 years. This study reveals two main features of LASV evolution in M. natalensis. First, the virus evolves in the reservoir with a molecular clock rate of 9 (7–11) × 10–4 position–1 year–1 implying that contemporary LASV lineages circulate in the Faranah area since less than 100 years. Second, viruses circulating in a specific village are diverse and polyphyletic. We observed, however, there are monophyletic clusters at village and sub-village level at specific points in time. In conclusion, our data indicate that the temporal and spatial pattern of LASV evolution in the natural reservoir is characterized by a combination of stationary circulation within a village and virus movement between villages. The latter feature is relevant for rodent control strategies, as it implies that recurrence of the virus from neighbouring villages may occur in villages where the virus has previously been eradicated.

This assay provides results in less time than routine PCR and is equally sensitive., Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity.

Background The case fatality ratio (CFR) of Ebola virus disease (EVD) can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investigate whether viremia in EVD patients may be used to evaluate baseline EVD CFRs. Methods and Findings We analyzed the laboratory and epidemiological records of patients with EVD confirmed by reverse transcription PCR hospitalized in the Conakry area, Guinea, between 1 March 2014 and 28 February 2015. We used viremia and other variables to model the CFR. Data for 699 EVD patients were analyzed. In the week following symptom onset, mean viremia remained stable, and the CFR increased with viremia, V, from 21% (95% CI 16%–27%) for low viremia (V < 104.4 copies/ml) to 53% (95% CI 44%–61%) for intermediate viremia (104.4 ≤ V < 105.2 copies/ml) and 81% (95% CI 75%–87%) for high viremia (V ≥ 105.2 copies/ml). Compared to adults (15–44 y old [y.o.]), the CFR was larger in young children (0–4 y.o.) (odds ratio [OR]: 2.44; 95% CI 1.02–5.86) and older adults (≥45 y.o.) (OR: 2.84; 95% CI 1.81–4.46) but lower in children (5–14 y.o.) (OR: 0.46; 95% CI 0.24–0.86). An order of magnitude increase in mean viremia in cases after July 2014 compared to those before coincided with a 14% increase in the CFR. Our findings come from a large hospital-based study in Conakry and may not be generalizable to settings with different case profiles, such as with individuals who never sought care. Conclusions Viremia in EVD patients was a strong predictor of death that partly explained variations in CFR in the study population. This study provides baseline CFRs by viremia group, which allow appropriate adjustment when estimating efficacy in treatment studies. In randomized controlled trials, stratifying analysis on viremia groups could reduce sample size requirements by 25%. We hypothesize that monitoring the viremia of hospitalized patients may inform the ability of surveillance systems to detect EVD patients from the different severity strata., In a retrospective cohort study, Simon Cauchemez and colleagues find viral load can predict case fatality ratios among patients with Ebola Virus., Editors' Summary Background During the current outbreak of Ebola virus disease (EVD) in West Africa, which started in December 2013, there have been more than 28,000 confirmed, probable, and suspected cases of EVD and more than 11,000 deaths from the disease. Ebola virus is transmitted to people from wild animals and spreads in human populations through direct contact with the bodily fluids (including blood, saliva, and urine) or organs of infected people or through contact with bedding and other materials contaminated with bodily fluids. The symptoms of EVD, which start 2–21 days after infection, include fever, headache, vomiting, diarrhea, and internal and external bleeding. Infected individuals are not infectious until they develop symptoms but remain infectious as long as their bodily fluids contain virus. There is no proven treatment or vaccine for EVD, although several treatments are now being assessed in people following promising laboratory studies. Supportive care—given under strict isolation conditions to prevent the spread of the disease to other patients or to healthcare workers—improves survival. Why Was This Study Done? Ideally, the efficacy of a potential treatment for any disease is assessed in a randomized controlled trial, a study that compares outcomes among people chosen at random to receive the treatment with outcomes among people given a placebo (dummy treatment). However, because EVD is frequently fatal, randomized controlled trials of potential treatments are considered unethical. Instead, studies evaluating treatments for EVD usually compare the case fatality ratio (CFR; the number of deaths caused by a disease divided by the number of cases of that disease; a CFR of 100% indicates that everyone who develops the disease dies) among treated patients with a baseline CFR estimated from historical data. But the CFR of EVD varies markedly over time and space for poorly understood reasons (for example, changes in patient care or variations in the detection of people with disease of different severity might change the CFR). Thus, the CFR in the treatment group could differ from the baseline CFR for reasons that are independent of the treatment. To find a way around this problem, in this retrospective cohort study, the researchers investigate whether there is a relationship between viremia (the amount of virus in the blood) and the CFR among patients with EVD. What Did the Researchers Do and Find? The researchers used laboratory and epidemiological data (for example, patient age and date of symptom onset and death; epidemiology is the study of disease patterns in populations) to investigate the relationship between viremia and CFR among 699 patients with confirmed EVD hospitalized in the Conakry area of Guinea between March 2014 and February 2015. In the week following symptom onset, mean (average) viremia remained stable, and the CFR among the patients increased with the level of viremia. Thus, the CFRs for patients with low, intermediate, and high viremia (defined by the number of virus copies per milliliter of blood) were 21%, 53%, and 81%, respectively. Compared to adults aged 15–44 years, young children (aged less than five years) and older adults had a higher CFR, but children aged 5–14 years had a lower CFR. Notably, the CFR in the study population was 14% higher after July 2014 than in the months of March–July 2014, an increase that coincided with a ten-fold increase in the average level of viremia in the population. What Do These Findings Mean? These findings suggest that viremia is a strong predictor of death that can partly explain variations in the CFR of EVD. Because these findings are based on data collected from hospitalized patients, they may not be generalizable to other settings. Importantly, however, these findings provide estimates of CFR by viremia group that can now be used to adjust risk when undertaking clinical evaluations of EVD-specific treatments. That is, by allowing for differing levels of viremia, it will be possible to assess the efficacy of treatments for EVD more accurately in nonrandomized clinical trials. Moreover, the researchers calculate that stratification of patients by viremia group could reduce the sample size needed in any randomized trials that are undertaken (for example, comparisons of two potential treatments) by 25%. Finally, the researchers suggest that monitoring viremia among patients hospitalized for EVD might provide information about the ability of different surveillance systems to detect patients with different levels of disease severity (probability of death). Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001908. The World Health Organization (WHO) provides information about EVD, information about potential EVD therapies, and regular updates on the current EVD epidemic; a summary of the discussion of a WHO Ethics Working Group Meeting on the ethical issues related trials of EVD treatments is available; the WHO website also provides information about efforts to control Ebola in the field and personal stories from people who have survived EVD The UK National Health Service Choices website provides detailed information on EVD The US Centers for Disease Control and Prevention also provides information about http://www.cdc.gov/vhf/ebola/EVD

We recently reported increased prevalence of Lassa virus (LASV) infection in Mastomys natalensis during the rainy season in Guinea, West Africa. Here, the association of LASV prevalence with fecundity, fertility, and the age structure of the rodent population was analyzed using data from the previous study. The animals reproduced throughout the year, but highest fecundity was observed during the rainy season. Accordingly, the rodent population was aged at the beginning and young at the end of the rainy season. Lassa virus infection was observed in all age groups, including the very young, which is compatible with vertical transmission. However, since the prevalence of infection showed a trend with increasing age in the younger age groups, horizontal transmission by yet unknown mechanisms may also play a role in LASV transmission. Multivariate analysis did not show an association of LASV prevalence with any demographic variable studied. Rodent behavior influencing virus transmissibility and contaminated environment may therefore be responsible for spatial and seasonal variations in LASV prevalence in M. natalensis.

A nanopore DNA sequencer is used for real-time genomic surveillance of the Ebola virus epidemic in the field in Guinea; the authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection. This paper reports the use of nanopore DNA sequencers (known as MinIONs) for real-time genomic surveillance of the Ebola virus epidemic, in the field in Guinea. The authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection. The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths1. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10−3 and 1.42 × 10−3 mutations per site per year. This is equivalent to 16–27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic2,3,4,5,6,7. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions8. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities9. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15–60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.

In the absence of a vaccine or specific treatments for Ebola virus disease (EVD), early identification of cases is crucial for the control of EVD epidemics. We evaluated a new extraction kit (SpeedXtract (SE), Qiagen) on sera and swabs in combination with an improved diagnostic reverse transcription recombinase polymerase amplification assay for the detection of Ebola virus (EBOV-RT-RPA). The performance of combined extraction and detection was best for swabs. Sensitivity and specificity of the combined SE and EBOV-RT-RPA were tested in a mobile laboratory consisting of a mobile glovebox and a Diagnostics-in-a-Suitcase powered by a battery and solar panel, deployed to Matoto Conakry, Guinea as part of the reinforced surveillance strategy in April 2015 to reach the goal of zero cases. The EBOV-RT-RPA was evaluated in comparison to two real-time PCR assays. Of 928 post-mortem swabs, 120 tested positive, and the combined SE and EBOV-RT-RPA yielded a sensitivity and specificity of 100% in reference to one real-time RT-PCR assay. Another widely used real-time RT-PCR was much less sensitive than expected. Results were provided very fast within 30 to 60 min, and the field deployment of the mobile laboratory helped improve burial management and community engagement.

The commensal rodent Mastomys natalensis is the natural reservoir of Lassa arenavirus (LASV), which causes hemorrhagic fever in West Africa. To study a possible effect of the virus on phenotypic and genotypic variation of its persistently infected host, we compared LASV-positive and non-infected wild-caught M. natalensis. The LASV effects on the phenotypic variation were explored using standard external morphometric measurements, geometric morphometric analyses of the cranial size and shape, and brain case volume. The genetic variability of M. natalensis specimens was assessed using 9 polymorphic microsatellite markers. Independent of sex and age, LASV-infected animals had smaller external body measurements, reproductive organs, skull size and brain case volume. Cranial shape differences between the 2 groups are represented by a lateral constriction of the entire skull. The genetic variability revealed consanguinity only among the LASV-positive rodents. We hypothesize that growth impairment may result in a selective disadvantage for LASV-infected M. natalensis, leading to a preferably commensal lifestyle in areas where the LAVS is endemic and, thereby, increasing the risk of LASV transmission to humans.

West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a two-year-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak. ispartof: Nature vol:524 issue:7563 pages:97-101 ispartof: location:England status: published