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IntroductionEbola virus disease (EVD) continues to be a significant public health problem in sub-Saharan Africa, especially in the Democratic Republic of the Congo (DRC). Large-scale vaccination during outbreaks may reduce virus transmission. We established a large population-based clinical trial of a heterologous, two-dose prophylactic vaccine during an outbreak in eastern DRC to determine vaccine effectiveness.Methods and analysisThis open-label, non-randomised, population-based trial enrolled eligible adults and children aged 1 year and above. Participants were offered the two-dose candidate EVD vaccine regimen VAC52150 (Ad26.ZEBOV, Modified Vaccinia Ankara (MVA)-BN-Filo), with the doses being given 56 days apart. After vaccination, serious adverse events (SAEs) were passively recorded until 1 month post dose 2. 1000 safety subset participants were telephoned at 1 month post dose 2 to collect SAEs. 500 pregnancy subset participants were contacted to collect SAEs at D7 and D21 post dose 1 and at D7, 1 month, 3 months and 6 months post dose 2, unless delivery was before these time points. The first 100 infants born to these women were given a clinical examination 3 months post delivery. Due to COVID-19 and temporary suspension of dose 2 vaccinations, at least 50 paediatric and 50 adult participants were enrolled into an immunogenicity subset to examine immune responses following a delayed second dose. Samples collected predose 2 and at 21 days post dose 2 will be tested using the Ebola viruses glycoprotein Filovirus Animal Non-Clinical Group ELISA. For qualitative research, in-depth interviews and focus group discussions were being conducted with participants or parents/care providers of paediatric participants.Ethics and disseminationApproved by Comité National d’Ethique et de la Santé du Ministère de la santé de RDC, Comité d'Ethique de l'Ecole de Santé Publique de l’Université de Kinshasa, the LSHTM Ethics Committee and the MSF Ethics Review Board. Findings will be presented to stakeholders and conferences. Study data will be made available for open access.Trial registration numberNCT04152486.

Objective: Lassa fever (LF), a hemorrhagic fever endemic to West Africa, has an incidence of approximately 500,000 cases per year. This study evaluated hearing loss and other sequelae following LF. Methods: This case–control study enrolled laboratory-confirmed LF survivors, non-LF febrile controls and matched-community controls with no history of LF or recent hospitalization for a febrile illness. Study participants completed a symptom questionnaire. Pure-tone audiometry was completed by a subset of participants. Results: A total of 147 subjects aged 3–66 years (mean, 23.3) were enrolled. LF survivors were significantly more likely to report balance difficulties (55% vs. 20%, p

Background Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago–the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. Methodology We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. Results A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. Conclusions This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level., Author summary Lassa fever (LF) is an acute viral haemorrhagic fever endemic to West Africa, causing an estimated 500,000 new infections and 10,000 deaths per year. At present, no treatment has been developed to specifically treat LF and only one prospective clinical trial has been conducted to evaluate the current treatment recommendation. Before a new era of LF clinical trials can begin, it is important to develop standardised methods and tools to ensure that trials are conducted in a consistent way and can generate reliable, comparable data. The aim of this project was initiate the first step to improve the comparability of LF studies by developing a standardised Phase III clinical trial methodology for LF therapeutics that could be applied in low-resource settings. Through multi-stakeholder consultation, we established a consensus position of clinicians and researchers on the core components of future Phase III clinical trials: Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV).

IntroductionCOVID-19 vaccines are now being distributed to low- and middle-income countries (LMICs), with global urgency surrounding national vaccination plans. LMICs have significant experience implementing vaccination campaigns to respond to epidemic threats but are often hindered by chronic health system challenges. We sought to identify transferable lessons for COVID-19 vaccination from the rollout of three vaccines that targeted adult groups in Africa and South America: MenAfriVac (meningitis A); 17D (yellow fever) and rVSV-ZEBOV (Ebola virus disease).MethodsWe conducted a rapid literature review and 24 semi-structured interviews with technical experts who had direct implementation experience with the selected vaccines in Africa and South America. We identified barriers, enablers, and key lessons from the literature and from participants’ experiences. Interview data were analysed thematically according to seven implementation domains.ResultsParticipants highlighted multiple components of vaccination campaigns that are instrumental for achieving high coverage. Community engagement is an essential and effective tool, requiring dedicated time, funding and workforce. Involving local health workers is a key enabler, as is collaborating with community leaders to map social groups and tailor vaccination strategies to their needs. Vaccination team recruitment and training strategies need to be enhanced to support vaccination campaigns. Although recognised as challenging, integrating vaccination campaigns with other routine health services can be highly beneficial if well planned and coordinated across health programmes and with communities.ConclusionAs supplies of COVID-19 vaccines become available to LMICs, countries need to prepare to efficiently roll out the vaccine, encourage uptake among eligible groups and respond to potential community concerns. Lessons from the implementation of these three vaccines that targeted adults in LMICs can be used to inform best practice for COVID-19 and other epidemic vaccination campaigns.

Purpose of review The COVID-19 pandemic is a global catastrophe that has led to untold suffering and death. Many previously identified policy challenges in planning for large epidemics and pandemics have been brought to the fore, and new ones have emerged. Here, we review key policy challenges and lessons learned from the COVID-19 pandemic in order to be better prepared for the future. Recent findings The most important challenges facing policymakers include financing outbreak preparedness and response in a complex political environment with limited resources, coordinating response efforts among a growing and diverse range of national and international actors, accurately assessing national outbreak preparedness, addressing the shortfall in the global health workforce, building surge capacity of both human and material resources, balancing investments in public health and curative services, building capacity for outbreak-related research and development, and reinforcing measures for infection prevention and control. Summary In recent years, numerous epidemics and pandemics have caused not only considerable loss of life, but billions of dollars of economic loss. The COVID-19 pandemic served as a wake-up call and led to the implementation of relevant policies and countermeasures. Nevertheless, many questions remain and much work to be done. Wise policies and approaches for outbreak control exist but will require the political will to implement them.

In response to the COVID-19 pandemic, in addition to the more routine public health measures, many countries have implemented “lockdowns”—closing borders, restricting international travel, and placing severe limitations on individual movement and group gatherings. While lockdowns may be an important tool to limit transmission, they come at a potentially great cost with regard to economic impact, mental health consequences, and increased morbidity and mortality from non–COVID-19 diseases. Furthermore, implementation of the required draconian measures may be difficult in some settings because of logistical, economic, and sociocultural impediments, especially in many low- and middle-income countries. Governments and health authorities must chart a course on how to “unlock” or control transmission where lockdowns are not feasible. “Precision physical distancing”—distancing tailored and optimized to specific physical, social, cultural, political, and economic contexts and to specific groups and settings—is proposed and discussed here as an important tool in the control of COVID-19. It has the advantages of being low cost, adaptable to diverse sociocultural and economic settings through community ownership and local action, and more easily monitored and potentially enforced than less precise measures. Precision physical distancing can be one important component of a sustainable long-term solution that is proportionate to the risk yet does not have a disproportionate impact on society and the economy, allowing a partial return to normal activities, with the community as an essential partner.

Dengue virus (DENV) affects more than 100 countries worldwide. Dengue virus infection has been increasing in the southern Peruvian Amazon city of Puerto Maldonado since 2000. We designed this study to describe the prevalence of past DENV infection and to evaluate risk factors. In 2012, we conducted a cross-sectional serosurvey and administered a knowledge, attitudes, and practices (KAP) questionnaire to members of randomly selected households. Sera were screened for antibodies to DENV by enzyme-linked immunosorbent assay and confirmed by plaque reduction neutralization test. We created indices for KAP (KAPi). We used SaTScan (Martin Kulldorff with Information Management Services Inc., Boston, MA) to detect clustering and created a multivariate model introducing the distance of households to potential vector and infection sources. A total of 505 participants from 307 households provided a blood sample and completed a questionnaire. Fifty-four percent of participants (95% confidence interval [CI]: 49.6; 58.5) had neutralizing antibodies to DENV. Higher values of KAPi were positively associated with having DENV antibodies in the multivariate analysis (odds ratio [OR(II)]: 1.6, 95% CI: 0.6, 2.4; OR(III): 2.7, 95% CI: 1.3, 5.5; and OR(IV): 2.4, 95% CI: 1.2, 5.0). Older groups had lower chances of having been exposed to DENV than younger people (OR(20–30): 0.5, 95% CI: 0.2, 0.8; OR(31–45): 0.5, 95% CI: 0.3, 0.9; and OR(>45): 0.6, 95% CI: 0.3, 1.3). Multivariate data analysis from the 270 households with location information showed male gender to have lower risk of past DENV infection (OR: 0.6, 95% CI: 0.4, 0.9). We conclude that risk of DENV infection in Puerto Maldonado is related to gender, age of the population, and location.

Background Large outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions. Methods We undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation. Results Of 389 cases, median presentation time was 6 days (IQR 4–10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13–17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0–4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5–12 and 13–17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5–9 days and 20–60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41–95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time. Conclusions Whilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes.

Background Following the West African Ebola virus disease (EVD) outbreak of 2013–2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. Methodology/Principal findings Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. Conclusions/Significance The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings.

COVID-19: Shining the Light on Africa.

Summary box Disease outbreaks and health emergencies cause substantial human suffering, death and economic loss. Such events push weak health systems to a breaking point, as witnessed during recent outbreaks of cholera, drug-resistant tuberculosis, Ebola virus disease and Zika virus disease.1–4 The current COVID-19 pandemic is testing the response and resilience of health systems worldwide, including well-resourced systems in Europe and North America, where health institutions and public health agencies are operating beyond capacity, diagnostics are lacking, triage systems are faltering, personal protective equipment are insufficient, and front-line health workers are facing risks of disease and death.5 Building responsive and resilient health systems is an imperative for the global health community. A resilient health system can absorb the shock of an emergency while continuing to provide regular health services.6–8 Most frameworks for building resilient health systems that effectively respond to disease outbreaks focus on enhancing preparedness or response capacity prior to an emergency9–11 or to strengthen health systems after the emergency, typically during the recovery phase. Indeed, many aspects of outbreak response lay the groundwork for health system strengthening (HSS), such as enhancing surveillance systems and training the health workforce.12 Over the last two …

Purpose of review Less than two decades into the 21st century, the world has already witnessed numerous large epidemics or pandemics. These events have highlighted inadequacies in both national and international capacity for outbreak prevention, detection, and response. Here, we review some of the major challenges from a policy perspective. Recent findings The most important challenges facing policymakers include financing outbreak preparedness and response in a complex political environment with limited resources, coordinating response efforts among a growing and diverse range of national and international actors, accurately assessing national outbreak preparedness, addressing the shortfall in the global biomedical workforce, building surge capacity of both human and material resources, balancing investments in public health and curative services, building capacity for outbreak-related research and development, and reinforcing measures for infection prevention and control. Summary In recent years, numerous epidemics and pandemics have caused not only considerable loss of life but also billions of dollars of economic loss. Although the events have served as a wake-up call and led to the implementation of relevant policies and counter-measures, such as the Global Health Security Agenda, many questions remain and much work to be done. Wise policies and approaches for outbreak control exist, but will require the political will to implement them.

Shifting the Paradigm As the treatment paradigm for patients with Ebola virus disease shifts from isolation to aggressive supportive care and antiviral therapy, the global health community can work...

Bausch is part of the UK Public Health Rapid Support Team, which is funded by the UK Department of Health and Social Care.

Rickettsia and Leptospira spp. are under-recognized causes of acute febrile disease worldwide. Rickettsia species are often placed into the spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR). We explored the antibody prevalence among humans for these two groups of rickettsiae in four regions of Peru (Lima, Cusco, Puerto Maldonado, and Tumbes) and for Leptospira spp. in Puerto Maldonado and Tumbes. We also assessed risk factors for seropositivity and collected serum samples and ectoparasites from peri-domestic animals from households in sites with high human seroprevalence. In total, we tested 2,165 human sera for antibodies (IgG) against SFGR and TGR by ELISA and for antibodies against Leptospira by a microscopic agglutination test. Overall, human antibody prevalence across the four sites was 10.6% for SFGR (ranging from 6.2% to 14.0%, highest in Tumbes) and 3.3% for TGR (ranging from 2.6% to 6.4%, highest in Puerto Maldonado). Factors associated with seroreactivity against SFGR were male gender, older age, contact with backyard birds, and working in agriculture or with livestock. However, exposure to any kind of animal within the household decreased the odds ratio by half. Age was the only variable associated with higher TGR seroprevalence. The prevalence of Leptospira was 11.3% in Puerto Maldonado and 5.8% in Tumbes, with a borderline association with keeping animals in the household. We tested animal sera for Leptospira and conducted polymerase chain reaction (PCR) to detect Rickettsia species among ectoparasites collected from domestic animals in 63 households of seropositive participants and controls. We did not find any association between animal infection and human serostatus.

Health workers infected with Ebola virus in Kenema, Sierra Leone, had potential virus exposure inside and outside of hospitals. Prevention measures must address a spectrum of risk factors both in formal and informal care settings as well as in the community., Background. Ebola virus disease (EVD) in health workers (HWs) has been a major challenge during the 2014–2015 outbreak. We examined factors associated with Ebola virus exposure and mortality in HWs in Kenema District, Sierra Leone. Methods. We analyzed data from the Sierra Leone National Viral Hemorrhagic Fever Database, contact tracing records, Kenema Government Hospital (KGH) staff and Ebola Treatment Unit (ETU) rosters, and burial logs. Results. From May 2014 through January 2015, 600 cases of EVD originated in Kenema District, including 92 (15%) HWs, 66 (72%) of whom worked at KGH. Among KGH medical staff and international volunteers, 18 of 62 (29%) who worked in the ETU developed EVD, compared with 48 of 83 (58%) who worked elsewhere in the hospital. Thirteen percent of HWs with EVD reported contact with EVD patients, while 27% reported contact with other infected HWs. The number of HW EVD cases at KGH declined roughly 1 month after implementation of a new triage system at KGH and the opening of a second ETU within the district. The case fatality ratio for HWs and non-HWs with EVD was 69% and 74%, respectively. Conclusions. The cluster of HW EVD cases in Kenema District is one of the largest ever reported. Most HWs with EVD had potential virus exposure both inside and outside of hospitals. Prevention measures for HWs must address a spectrum of infection risks in both formal and informal care settings as well as in the community.

SummaryThere is an increasing role for bioinformatic and phylogenetic analysis in tropical medicine research. However, scientists working in low- and middle-income regions may lack access to training opportunities in these methods. To help address this gap, a 5-day intensive bioinformatics workshop was offered in Lima, Peru. The syllabus is presented here for others who want to develop similar programs. To assess knowledge gained, a 20-point knowledge questionnaire was administered to participants (21 participants) before and after the workshop, covering topics on sequence quality control, alignment/formatting, database retrieval, models of evolution, sequence statistics, tree building, and results interpretation. Evolution/tree-building methods represented the lowest scoring domain at baseline and after the workshop. There was a considerable median gain in total knowledge scores (increase of 30%, p

Using a large, passive, febrile surveillance program in Iquitos, Peru, we retrospectively tested human blood specimens for scrub typhus group orientiae by ELISA, immunofluorescence assay, and PCR. Of 1,124 participants, 60 (5.3%) were seropositive, and 1 showed evidence of recent active infection. Our serologic data indicate that scrub typhus is present in the Peruvian Amazon.

Beginning in 2014, there has been significant progress in normalization of relations between Cuba and the United States. Herein, we discuss the history and recent progress in scientific collaboration between the two countries as well as the continued challenges. Science and global health diplomacy can be key tools in reestablishing a trusting and productive relationship of mutual and global benefit, bringing about better and healthier lives for people in both Cuba and the United States.

The interoceanic highway (IOH) in Madre de Dios, Peru has driven dramatic change in the Peruvian Amazon basin. We conducted a mixed methods study to examine the impact of these changes on the subjective well-being (SWB) of four communities on the IOH. Themes that emerged qualitatively included changing health threats, environmental degradation, and the impact of increased migration. To achieve a higher level of SWB, respondents emphasized the need for higher incomes, opportunities to learn new skills, and a better education for their children. Potential threats to SWB included marital problems and poorer health. Quantitative analyses suggested that social support and a sense of security impacted reported SWB scores based on life satisfaction, and the impact of income on life satisfaction was mediated by food security. Although long-term residents felt that specific determinants of SWB had both increased (food variety, transport and access to work) and decreased (access to natural resources and hunting), the majority reported that their lives had improved overall. Health had been affected by the IOH in both negative ways (increased dengue and road accidents) and positive ways (improved access to health services). Our results suggest that the rapidly-changing communities near the IOH link well-being to health, income, community, and the environment.

The massive outbreak of Ebola virus disease in west Africa between 2013 and 2016 resulted in intense efforts to evaluate the efficacy of several specific countermeasures developed through years of preclinical work, including the first clinical trials for therapeutics and vaccines. In this Review, we discuss how the experience and data generated from that outbreak have helped to advance the understanding of the use of these countermeasures for post-exposure prophylaxis against Ebola virus infection. In future outbreaks, post-exposure prophylaxis could play an important part in reducing community transmission of Ebola virus by providing more immediate protection than does immunisation as well as providing additional protection for health-care workers who are inadvertently exposed over the course of their work. We propose provisional guidance for use of post-exposure prophylaxis in Ebola virus disease and identify the priorities for future preparedness and further research.

Background Madre de Dios, a southern state in the Peruvian Amazon basin, has experienced rapid development as well as an influx of migrants since the construction of the Interoceanic Highway (IOH) connecting Brazil, Bolivia, and the Peruvian coast. We explored perceptions of migration and development in up to eight communities along the IOH in Madre de Dios following construction of the highway. Methods We conducted a multiple methods study involving focus group (FG) discussions and interviews with key informants (KIs) in eight communities in Madre de Dios. The data was used to develop and apply a survey on demographics, financial, personal, social, human, and physical capital in four communities between February 2014 and March 2015. Results We conducted 12 FGs and 34 KI interviews. A total of 522 people participated in the survey. Comparing migrants (those who had moved to the area after construction of the IOH) and non-migrants, we found no difference in food security or access to health services. The majority (67.6%) of respondents from both groups reported that illness was their primary threat to well-being. Non-migrants owned more land than migrants (p

Peru did not fit the source–sink model for the global spread of this virus., It remains unclear whether lineages of influenza A(H3N2) virus can persist in the tropics and seed temperate areas. We used viral gene sequence data sampled from Peru to test this source–sink model for a Latin American country. Viruses were obtained during 2010–2012 from influenza surveillance cohorts in Cusco, Tumbes, Puerto Maldonado, and Lima. Specimens positive for influenza A(H3N2) virus were randomly selected and underwent hemagglutinin sequencing and phylogeographic analyses. Analysis of 389 hemagglutinin sequences from Peru and 2,192 global sequences demonstrated interseasonal extinction of Peruvian lineages. Extensive mixing occurred with global clades, but some spatial structure was observed at all sites; this structure was weakest in Lima and Puerto Maldonado, indicating that these locations may experience greater viral traffic. The broad diversity and co-circulation of many simultaneous lineages of H3N2 virus in Peru suggests that this country should not be overlooked as a potential source for novel pandemic strains.

I will always remember 2014 as the year that Ebola virus took over west Africa and thus, much of my time and life. The epicenters of the outbreak in Guinea and Sierra Leone are areas that I have worked in since 1996 on projects to build capacity to combat another viral hemorrhagic disease, Lassa fever, with the Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), Tulane University, and others. I spent a lot time and made many friends and colleagues in the Forest Region of Guinea and the Kenema District of Sierra Leone, both at the heart of this Ebola outbreak. I have also responded to quite a few Ebola and Marburg virus outbreaks over the years. Therefore, it was natural that, when Ebola hit west Africa, I would get involved. Indeed, since April of 2014, it has pretty much been all Ebola all of the time, with me cycling constantly between my home in Lima, Peru and west Africa, Geneva, and Washington, consulting primarily with the WHO and the US Government.

The 2013 outbreak of Ebola virus disease (EVD) in West Africa constituted a major humanitarian crisis. The outbreak numbered over 28,500 cases, more than 10 times the number cumulatively registered from all previous EVD outbreaks combined, with at least 11,000 deaths, and resulted in billions of dollars of lost economic growth to an already impoverished region. The unprecedented scale of West Africa 2013 took the world by surprise and laid bare deficiencies in our response capacity to complex humanitarian disasters of highly infectious and lethal pathogens. However, the magnitude of West Africa 2013 also provided a unique opportunity and obligation to better understand not only the biology and epidemiology of EVD, but also the many scientific, economic, social, political, ethical, and logistical challenges in confronting emerging infectious diseases in the modern era.

BACKGROUND. Data on norovirus epidemiology among all ages in community settings are scarce, especially from tropical settings. METHODS. We implemented active surveillance in 297 households in Peru from October 2012 to August 2015 to assess the burden of diarrhea and acute gastroenteritis (AGE) due to norovirus in a lower-middle-income community. During period 1 (October 2012–May 2013), we used a “traditional” diarrhea case definition (≥3 loose/liquid stools within 24 hours). During period 2 (June 2013–August 2015), we used an expanded case definition of AGE (by adding ≥2 vomiting episodes without diarrhea or 1–2 vomiting episodes plus 1–2 loose/liquid stools within 24 hours). Stool samples were tested for norovirus by reverse-transcription polymerase chain reaction. RESULTS. During period 1, overall diarrhea and norovirus-associated diarrhea incidence was 37.2/100 person-years (PY) (95% confidence interval [CI], 33.2–41.7) and 5.7/100 PY (95% CI, 3.9–8.1), respectively. During period 2, overall AGE and norovirus-associated AGE incidence was 51.8/100 PY (95% CI, 48.8–54.9) and 6.5/100 PY (95% CI, 5.4–7.8), respectively. In both periods, children aged

Background:There are limited data on the burden of disease posed by influenza in low- and middle-income countries. Furthermore, most estimates of influenza disease burden worldwide rely on passive sentinel surveillance at health clinics and hospitals that lack accurate population denominators. Methods:We documented influenza incidence, seasonality, health-system utilization with influenza illness, and vaccination coverage through active community-based surveillance in 4 ecologically distinct regions of Peru over 6 years. Approximately 7200 people in 1500 randomly selected households were visited 3 times per week. Naso- and oropharyngeal swabs were collected from persons with influenza-like illness and tested for influenza virus by real-time reverse-transcription polymerase chain reaction. Results:We followed participants for 35353 person-years (PY). The overall incidence of influenza was 100 per 1000 PY (95% confidence interval [CI], 97-104) and was highest in children aged 2-4 years (256/1000 PY [95% CI, 236-277]). Seasonal incidence trends were similar across sites, with 61% of annual influenza cases occurring during the austral winter (May-September). Of all participants, 44 per 1000 PY (95% CI, 42-46) sought medical care, 0.7 per 1000 PY (95% CI, 0.4-1.0) were hospitalized, and 1 person died (2.8/100000 PY). Influenza vaccine coverage was 27% among children aged 6-23 months and 26% among persons aged ≥65 years. Conclusions:Our results indicate that 1 in 10 persons develops influenza each year in Peru, with the highest incidence in young children. Active community-based surveillance allows for a better understanding of the true burden and seasonality of disease that is essential to plan the optimal target groups, timing, and cost of national influenza vaccination programs.

Background\ud \ud Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014.\ud \ud Methods\ud \ud We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase–polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients.\ud \ud Results\ud \ud Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness (in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient.\ud \ud Conclusions\ud \ud The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.)

Background Limited data exist on transmission dynamics and effectiveness of control measures for influenza in confined settings. Objectives To investigate the transmission dynamics of a 2009 pandemic H1N1 influenza A outbreak aboard a Peruvian Navy ship and quantify the effectiveness of the implemented control measures. Methods We used surveillance data and a simple stochastic epidemic model to characterize and evaluate the effectiveness of control interventions implemented during an outbreak of 2009 pandemic H1N1 influenza A aboard a Peruvian Navy ship. Results The serological attack rate for the outbreak was 49·1%, with younger cadets and low-ranking officers at greater risk of infection than older, higher-ranking officers. Our transmission model yielded a good fit to the daily time series of new influenza cases by date of symptom onset. We estimated a reduction of 54·4% in the reproduction number during the period of intense control interventions. Conclusion Our results indicate that the patient isolation strategy and other control measures put in place during the outbreak reduced the infectiousness of isolated individuals by 86·7%. Our findings support that early implementation of control interventions can limit the spread of influenza epidemics in confined settings.

We report on and evaluate the process and findings of a real-time modeling exercise in response to an outbreak of measles in Lola prefecture, Guinea, in early 2015 in the wake of the Ebola crisis. Multiple statistical methods for the estimation of the size of the susceptible (i.e., unvaccinated) population were applied to weekly reported measles case data on seven subprefectures throughout Lola. Stochastic compartmental models were used to project future measles incidence in each subprefecture in both an initial and a follow-up iteration of forecasting. Measles susceptibility among 1- to 5-year-olds was estimated to be between 24% and 43% at the beginning of the outbreak. Based on this high baseline susceptibility, initial projections forecasted a large outbreak occurring over approximately 10 weeks and infecting 40 children per 1,000. Subsequent forecasts based on updated data mitigated this initial projection, but still predicted a significant outbreak. A catch-up vaccination campaign took place at the same time as this second forecast and measles cases quickly receded. Of note, case reports used to fit models changed significantly between forecast rounds. Model-based projections of both current population risk and future incidence can help in setting priorities and planning during an outbreak response. A swiftly changing situation on the ground, coupled with data uncertainties and the need to adjust standard analytical approaches to deal with sparse data, presents significant challenges. Appropriate presentation of results as planning scenarios, as well as presentations of uncertainty and two-way communication, is essential to the effective use of modeling studies in outbreak response.

Background Undifferentiated febrile illness (UFI) is one of the most common reasons for people seeking healthcare in low-income countries. While illness and death due to specific infections such as malaria are often well-quantified, others are frequently uncounted and their impact underappreciated. A number of high consequence infectious diseases, including Ebola virus, are endemic or epidemic in the Federal Republic of Sudan which has experienced at least 12 UFI outbreaks, frequently associated with haemorrhage and high case fatality rates (CFR), since 2012. One of these occurred in Darfur in 2015/2016 with 594 cases and 108 deaths (CFR 18.2%). The aetiology of these outbreaks remains unknown. Methodology/Principal findings We report a retrospective cohort study of the 2015/2016 Darfur outbreak, using a subset of 65 of 263 outbreak samples received by the National Public Health Laboratory which met selection criteria of sufficient sample volume and epidemiological data. Clinical features included fever (95.8%), bleeding (95.7%), headache (51.6%) and arthralgia (42.2%). No epidemiological patterns indicative of person-to-person transmission or health-worker cases were reported. Samples were tested at the Public Health England Rare and Imported Pathogens Laboratory using a bespoke panel of likely pathogens including haemorrhagic fever viruses, arboviruses and Rickettsia, Leptospira and Borrelia spp. Seven (11%) were positive for Crimean-Congo haemorrhagic fever virus (CCHFV) by real-time reverse transcription PCR. The remaining samples tested negative on all assays. Conclusions/Significance CCHFV is an important cause of fever and haemorrhage in Darfur, but not the sole major source of UFI outbreaks in Sudan. Prospective studies are needed to explore other aetiologies, including novel pathogens. The presence of CCHFV has critical infection, prevention and control as well as clinical implications for future response. Our study reinforces the need to boost surveillance, lab and investigative capacity to underpin effective response, and for local and international health security., Author summary The Federal Republic of Sudan has had at least 12 outbreaks of febrile illness of unknown cause associated with symptoms of haemorrhage and high case fatality rates since 2012. Outbreaks without clear diagnosis are concerning, particularly in countries such as Sudan where a range of high consequence diseases, including viral haemorrhagic fevers, are endemic or epidemic, and local laboratory capacity is limited. We transferred historical samples stored in the National Public Health Authority from one of these outbreaks that occurred in Darfur 2015–2016 to the Public Health England Laboratory at Porton, UK, and tested them against a wide range of infectious diseases to try to identify the cause, and to help the Sudanese Federal Ministry of Health to develop and target their limited laboratory capacity. We found that Crimean-Congo Haemorrhagic Fever was an important cause but not the only source of cases in this outbreak. This has implications for prevention and control as well as for treating cases. Our study also highlighted the need for future studies to explore other possible causes, including new pathogens, and reinforced the need to boost surveillance, lab and investigative capacity for more timely and complete outbreak response.

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.

We present findings describing the epidemiology of non-severe acute respiratory syndrome human coronavirus-associated influenza-like illness from a population-based active follow-up study in four different regions of Peru. In 2010, the prevalence of infections by human coronaviruses 229E, OC43, NL63, or HKU1 was 6.4% in participants with influenza-like illness who tested negative for influenza viruses. Ten of 11 human coronavirus infections were identified in the fall–winter season. Human coronaviruses are present in different regions of Peru and are relatively frequently associated with influenza-like illness in Peru.

Background The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community. Methods We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission. Findings Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission.

BACKGROUND: Madre de Dios is located in the southeastern Amazonian region of Peru. Rodents have been estimated to be the reservoirs for up to 50 % of emerging zoonotic pathogens, including a host of viruses, bacteria, and parasites. As part of a larger study involving both human and animal research, this study serves to obtain a broader understanding of the key challenges and concerns related to health and rodent-borne illnesses from the perspective of the people living in these communities. METHODS: We used a mixed methods approach, which comprised of 12 focus group discussions, 34 key informant interviews and the application of a survey (n = 522) in four communities along the Inter-Oceanic Highway (IOH) in Madre de Dios, Peru over a two-year period. RESULTS: Although 90 % of survey respondents answered that rodents can transmit diseases and had seen rodents in their homes and immediate surroundings, most could not name specific rodent-borne diseases and, when probed, described rodents as pests or nuisance animals, but were not concerned about acquiring illnesses from them. Key informant interview data suggests that there has been a perceived increase in the amount of rodents in the communities since the construction of the IOH, however this potential increase was not coupled with increased knowledge about diseases or perceived risks among these key informants. Health providers also mentioned a lack of diagnostic tools specific for rodent-borne illnesses. This may be related to the fact that although a common rodent-borne disease like leptospirosis is frequently detected in the region, it is not routinely and readily diagnosed, therefore the real burden of the disease and exposure risk can be underestimated. If rodent-borne diseases are not on the radar of health professionals, they may not consider presumptive treatment, which could result in unnecessary morbidity and mortality. CONCLUSION: Awareness of rodent-borne diseases is still lacking in the area, even among health care professionals within the communities, despite the known burden of diseases like leptospirosis. We expect to report further findings as we obtain more information from all the study components.

As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa. EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death. Males and females have been equally affected, with children (0–14 years of age) accounting for 19 %, young adults (15–44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40–90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission. While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1325-2) contains supplementary material, which is available to authorized users.

Using a large, passive, clinic-based surveillance program in Iquitos, Peru, we characterized the prevalence of rickettsial infections among undifferentiated febrile cases and obtained evidence of pathogen transmission in potential domestic reservoir contacts and their ectoparasites. Blood specimens from humans and animals were assayed for spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR) by ELISA and/or PCR; ectoparasites were screened by PCR. Logistic regression was used to determine associations between patient history, demographic characteristics of participants and symptoms, clinical findings and outcome of rickettsial infection. Of the 2,054 enrolled participants, almost 2% showed evidence of seroconversion or a 4-fold rise in antibody titers specific for rickettsiae between acute and convalescent blood samples. Of 190 fleas (Ctenocephalides felis) and 60 ticks (Rhipicephalus sanguineus) tested, 185 (97.4%) and 3 (5%), respectively, were positive for Rickettsia spp. Candidatus Rickettsia asemboensis was identified in 100% and 33% of the fleas and ticks tested, respectively. Collectively, our serologic data indicates that human pathogenic SFGR are present in the Peruvian Amazon and pose a significant risk of infection to individuals exposed to wild, domestic and peri-domestic animals and their ectoparasites., Author Summary Rickettsial infection remains relatively unexplored in South America compared to other regions of the world. For most regions of Peru (including the Amazon Basin), nothing more than broad serological characterization is available about circulating rickettsiae. Even less is known about the animal reservoirs and insect vectors involved in disease transmission. With this study we aimed to better characterize the circulating species of Rickettsia in humans in the Amazon Basin, as well as investigate their domestic animal reservoir and arthropod vectors. Out of 2054 fever patients enrolled we identified 38 individuals with serologic evidence for acute rickettsial infection. Their homes were visited in order to draw blood samples and collect ectoparasites from their domestic animals. Serology and molecular methods were used to test the animal blood samples as well as the ectoparasites. The information collected contributes to the understanding of the transmission dynamics of rickettsial diseases in Iquitos and leads to a better understanding of the exposure risk to rickettsial infection and it will guide approaches for prevention.

The outbreak of Ebola virus disease (EVD) that occurred from 2013 to 2016 in the West African countries of Guinea, Liberia, and Sierra Leone, with imported cases to three neighboring African countries as well as to the United States and Europe, constituted a major humanitarian disaster. The outbreak numbered over 28,500 cases, more than 10 times the number cumulatively registered from all previous EVD outbreaks combined, with at least 11,000 deaths, and resulted in billions of dollars of lost economic growth to an already impoverished region. The unprecedented scale of West Africa 2013 took the world by surprise and laid bare deficiencies in our response capacity to complex humanitarian disasters of highly infectious and lethal pathogens. However, the magnitude of West Africa 2013 also provided an, albeit unwelcome, unique opportunity and obligation to better understand the biology and epidemiology of EVD and, equally as important, the many scientific, economic, social, political, ethical, and logistical challenges in confronting emerging diseases in the modern era. Here we re-examine EVD, reviewing the unique challenges and scientific advances of West Africa 2013, contrasting them with the prior assumptions and classical teachings, identifying what they have taught us and what we still have to learn.

Here we describe clinicopathologic features of Ebola virus disease in pregnancy. One woman infected with Sudan virus in Gulu, Uganda, in 2000 had a stillbirth and survived, and another woman infected with Bundibugyo virus had a live birth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malarial parasite pigment-laden macrophages. These data suggest that trophoblast infection may be a mechanism of transplacental ebolavirus transmission.

Dengue virus (DENV) is thought to have emerged from a sylvatic cycle in Africa but has since become adapted to an urban-centric transmission cycle. These urban areas include villages in West Africa where DENV is not often routinely considered for patients presenting with febrile illnesses, as other endemic diseases (malaria, Lassa fever, e.g.) present with similar non-specific symptoms. Thus, dengue is likely under diagnosed in the region. These plaque reduction neutralization test-50 (PRNT50) screening results of patients presenting with fevers of unknown origin (FUO) at a clinic in Kenema, Sierra Leone indicate that all four serotypes of DENV likely circulate in areas surrounding Kenema. Using a more conservative PRNT80 cut-off value, our results still indicate the presence of antibody to all four serotypes in the region. Identifying alternate etiologies of FUOs in this region will assist clinicians in plan-of-care decisions as well as follow-up priorities. This is particularly relevant given the Ebola outbreak in the region, where diagnosis has a range of downstream effects ranging from correct allocation of medical resources, appropriate isolation of patients, and ultimately, a better informed public health sector., Author Summary Identifying the infectious diseases in developing nations could assist in clinical response, disaster response, and in assessing the need for specific public health infrastructure and therapeutics. Here we tested serum from patients in Sierra Leone who sought treatment for fever (and which remained undiagnosed) for immunological reaction to dengue viruses 1–4. We used a plaque reduction neutralization test, where patient antibodies will neutralize virus and reduce the number of plaques formed by virus. We report both the typical 50% reduction as well as a more stringent 80% reduction in our cohort. We show that over 77% of patients in this study had moderate reaction (PRNT50) to at least one dengue virus type and many patients reacted to more than one dengue virus. We conclude that dengue is circulating in the region and may be a thus far undiagnosed etiology of fevers of unknown origin in the region.

As the massive outbreak of Ebola virus disease (EVD) in west Africa wanes, it has become increasingly clear that thousands of survivors have many sequelae, some of which might be very severe, such as arthritis and vision-threatening uveitis. The mental health effects of EVD on survivors and other family and community members is similarly profound. Furthermore, it is increasingly being recognised that Ebola virus might persist for weeks or months in selected body compartments of survivors, most notably in the semen of men, bringing risk of renewed transmission where it has previously been eliminated. These challenges to EVD survivors constitute a new emergency in terms of addressing individual patient need and to control the disease spread. In this Review, we assess what is known regarding the sequelae of EVD, including possible delayed virus clearance. We discuss some of the key challenges regarding the provision of care to survivors and implementation of necessary future research.

Despite the slowing and eventual halting of the spread of Ebola virus disease (EVD) in West Africa,1,2 the battle for preventing and managing future outbreaks is still on. This is no time to be complacent. The scale of the outbreak, in which every few days during the early part of the outbreak about the same number of cases accrued as occurred during the entire 3-month outbreak in Gulu, Uganda, in 2000–2001 — previously the largest outbreak on record — prompted us to pull out all the stops, albeit after a slow start.3 Vaccines are a key weapon in our . . .

The filoviruses Marburg and Ebola cause severe hemorrhagic fever (HF) in humans. Beginning with the 1967 Marburg outbreak, 30 epidemics, isolated cases, and accidental laboratory infections have been described in the medical literature. We reviewed those reports to determine the basic clinical and laboratory features of filoviral HF. The most detailed information was found in descriptions of patients treated in industrialized countries; except for the 2000 outbreak of Ebola Sudan HF in Uganda, reports of epidemics in central Africa provided little controlled or objective clinical data. Other than the case fatality rate, there were no clear differences in the features of the various filovirus infections. This compilation will be of value to medical workers responding to epidemics and to investigators attempting to develop animal models of filoviral HF. By identifying key unanswered questions and gaps in clinical data, it will help guide clinical research in future outbreaks.