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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

Summary: Background: Lassa fever (LF) is a viral haemorrhagic fever endemic in West Africa. Lassa virus is maintained in and spread to humans from rodents, with occasional secondary human-to-human transmission. Present recommendations for personal protective equipment (PPE) for care of patients with LF generally follow those for filovirus diseases. However, the need for such high-level PPE for LF, which is thought to be considerably less transmissible between humans than filoviruses, is unclear. Aim: In Nigerian Lassa Treatment Centres (LTCs) we aimed to describe current PPE practices, identify barriers and facilitators to implementation of existing guidance, and assess healthcare workers' understanding. This would inform the development of future PPE guidelines for LF. Methods: We performed a mixed-methods study, including short cross-sectional surveys of PPE used in LTCs, observations of practice, and in-depth interviews with key informants. We described the quantitative data and we conducted a thematic analysis of qualitative data. Findings: Our survey of 74 HCWs found that approximately half reported problems with recommended PPE. In three LTCs PPE was used highly variably. Full PPE, as recommended in Nigeria CDC guidelines, was used in less than a quarter (21%) of interactions. In-depth interviews suggested this was based on availability and HCWs' own risk assessments. Conclusion: Without specific guidance on Lassa, the current approach is both resource and labour-intensive, where these are both limited. This has led to low adherence by health care workers, whose own experience indicates lower risk. The evidence-base to inform PPE required for LF must be improved to inform a more tailored approach.

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.

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.

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.

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.

Background Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. Methods We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). Findings We screened 137 EVD survivors from June 2016 – August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0 years (IQR 17–35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 – Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19 months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34 months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P, Highlights • Ebola virus disease (EVD) survivors are at-risk for severe vision impairment due to uveitis and subsequent cataract development. • Fifty EVD survivors underwent ocular fluid sampling and tested negative for Ebola virus by RT-PCR. • Thirty-four survivors underwent cataract surgery with excellent safety measures and vision restorative outcomes. Ebola virus disease (EVD) survivors are at high risk for uveitis, an inflammatory condition affecting the eye that may lead to severe vision impairment, often from cataract. Because persistent Ebola virus (EBOV) has been identified within the immune privileged eye, understanding the prevalence of intraocular EBOV persistence is significant for patients, providers, and public health policy. In this study, 50 EVD survivors tested negative for EBOV by RT-PCR of their intraocular fluid. Thirty-four underwent cataract surgery with vision restorative outcomes. These findings improve our ability to impact vision care and quality-of-life for thousands of EVD survivors at-risk for eye disease.

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...

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.

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.

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.

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.)

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. 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.

World Health Organization retains copyright in the manuscript and provides Elsevier the permission to publish the manuscript as a chapter in this book.

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.

Author(s): Rosenthal, Philip; Rosenthal, PJ; Hill, DR; Bausch, DG; Goraleski, KA; Higgs, S; Walker, PF; Plowe, CV

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 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 Kenema Government Hospital Lassa Fever Ward in Sierra Leone, directed since 2005 by Dr. Sheikh Humarr Khan, is the only medical unit in the world devoted exclusively to patient care and research of a viral hemorrhagic fever. When Ebola virus disease unexpectedly appeared in West Africa in late 2013 and eventually spread to Kenema, Khan and his fellow healthcare workers remained at their posts, providing care to patients with this devastating illness. Khan and the chief nurse, Mbalu Fonnie, became infected and died at the end of July, a fate that they have sadly shared with more than ten other healthcare workers in Kenema and hundreds across the region. This article pays tribute to Sheik Humarr Khan, Mbalu Fonnie and all the healthcare workers who have acquired Ebola virus disease while fighting the epidemic in West Africa. Besides the emotional losses, the death of so many skilled and experienced healthcare workers will severely impair health care and research in affected regions, which can only be restored through dedicated, long-term programs.

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.

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.

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.

Lassa fever is an acute viral hemorrhagic illness; the virus is endemic in West Africa and also of concern with regard to bioterrorism. Transmission of Lassa virus between humans may occur through direct contact with infected blood or bodily secretions. Oral administration of the antiviral drug ribavirin is often considered for postexposure prophylaxis, but no systematically collected data or uniform guidelines exist for this indication. Furthermore, the relatively low secondary attack rates for Lassa fever, the restriction of the area of endemicity to West Africa, and the infrequency of high-risk exposures make it unlikely that controlled prospective efficacy trials will ever be possible. Recommendations for postexposure use of ribavirin can therefore be made only on the basis of a thorough understanding and logical extrapolation of existing data. Here, we review the pertinent issues and propose guidelines based on extensive review of the literature, as well as our experience in this field. We recommend oral ribavirin postexposure prophylaxis for Lassa fever exclusively for definitive high-risk exposures. These guidelines may also serve for exposure to other hemorrhagic fever viruses susceptible to ribavirin.

Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region.

Unlike many viral hemorrhagic fevers (VHFs), Lassa fever (LF) is not a rare disease that emerges only as sporadic cases or in outbreak form. Although surveillance is inadequate to determine the true incidence, up to 300,000 infections and 5000 deaths from LF are estimated to occur yearly. The highest incidence is in the "Mano River Union (MRU) countries" of Sierra Leone, Liberia, and Guinea. Although civil unrest in this region over the past two decades has impeded capacity building and research, new-found peace in recent years presents new opportunities. In 2004, the Mano River Union Lassa Fever Network (MRU LFN) was established to assist MRU countries in the development of national and regional surveillance, diagnosis, treatment, control, and prevention of LF. Here, we review the present literature on treatment and pathogenesis of LF and outline priorities for future research in the field made possible by the improved research capacity of the MRU LFN.

The filoviruses, Marburg and Ebola, have the dubious distinction of being associated with some of the highest case-fatality rates of any known infectious disease--approaching 90% in many outbreaks. In recent years, laboratory research on the filoviruses has produced treatments and vaccines that are effective in laboratory animals and that could potentially drastically reduce case-fatality rates and curtail outbreaks in humans. However, there are significant challenges in clinical testing of these products and eventual delivery to populations in need. Most cases of filovirus infection are recognized only in the setting of large outbreaks, often in the most remote and resource-poor areas of sub-Saharan Africa, with little infrastructure and few personnel experienced in clinical research. Significant political, legal, and socio-cultural barriers also exist. Here, we review the present research priorities and environment for field study of the filovirus hemorrhagic fevers and outline a strategy for future prospective clinical research on treatment and vaccine prevention.

Blood samples from patients infected with the Sudan species of Ebola virus (EBOV), obtained during an outbreak of disease in Uganda in 2000, were tested for a panel of analytes to evaluate their clinical condition and to compare values obtained for patients with fatal and nonfatal cases and for uninfected (hospitalized control) patients. Liver function tests showed higher levels of aspartate aminotransferase (AST) in blood samples from patients with fatal cases than in samples from patients with nonfatal cases, whereas alanine aminotransferase levels were comparable and only slightly increased in all patients, suggesting that increased blood AST levels are due to a greater degree of injury in tissues other than the liver. Significantly higher levels of amylase, urea nitrogen, and creatinine suggest that acute pancreatitis and renal dysfunction develop in fatal cases, whereas reduced albumin and calcium levels may be linked to these conditions or to liver damage. d-Dimer levels in blood specimens were drastically increased in patients with fatal and nonfatal infections but were 4 times higher in patients with fatal cases than in patients who survived (180,000 vs. 44,000 ng/mL), during the most acute period of the infection (6-8 days after onset). These results indicate that disseminated intravascular coagulation is an early and important component of EBOV disease. This study has identified levels of analytes with prognostic value, which can also be used to target therapeutic interventions, and expands on the findings of prior blood tests conducted on this group of patients.

While studying respiratory infections of unknown etiology we detected Saffold virus in an oropharyngeal swab collected from a two-year-old female suffering from diarrhea and respiratory illness. The full viral genome recovered by deep sequencing showed 98% identity to a previously described Saffold strain isolated in Japan. Phylogenetic analysis confirmed the Peruvian Saffold strain belongs to genotype 3 and is most closely related to strains that have circulated in Asia. This is the first documented case report of Saffold virus in Peru and the only complete genomic characterization of a Saffold-3 isolate from the Americas.

Summary Background Limited data are available on the prevalence and predictors of clinical sequelae in survivors of Ebola virus disease (EVD). The EVD Survivor Clinic in Port Loko, Sierra Leone, has provided clinical care for 603 of 661 survivors living in the district. We did a cross-sectional study to describe the prevalence, nature, and predictors of three key EVD sequelae (ocular, auditory, and articular) in this cohort of EVD survivors. Methods We reviewed available clinical and laboratory records of consecutive patients assessed in the clinic between March 7, 2015, and April 24, 2015. We used univariate and multiple logistic regression to examine clinical and laboratory features of acute EVD with the following outcomes in convalescence: new ocular symptoms, uveitis, auditory symptoms, and arthralgias. Findings Among 277 survivors (59% female), median age was 29 years (IQR 20–36) and median time from discharge from an EVD treatment facility to first survivor clinic visit was 121 days (82–151). Clinical sequelae were common, including arthralgias (n=210, 76%), new ocular symptoms (n=167, 60%), uveitis (n=50, 18%), and auditory symptoms (n=67, 24%). Higher Ebola viral load at acute EVD presentation (as shown by lower cycle thresholds on real-time RT-PCR testing) was independently associated with uveitis (adjusted odds ratio [aOR] 3·33, 95% CI 1·87–5·91, for every five-point decrease in cycle threshold) and with new ocular symptoms or ocular diagnoses (aOR 3·04, 95% CI 1·87–4·94). Interpretation Clinical sequelae during early EVD convalescence are common and sometimes sight threatening. These findings underscore the need for early clinical follow-up of survivors of EVD and urgent provision of ocular care as part of health systems strengthening in EVD-affected west African countries. Funding Canadian Institutes of Health Research.

In an active diarrhea surveillance study of children aged 12-24 months in Lima, Peru, norovirus was the most common pathogen identified. The percentage of mixed (bacterial and noroviral) infections was significantly higher among norovirus-positive samples (53%) than among norovirus-negative samples (12%). The combination of norovirus with the most common bacterial pathogens was associated with increased clinical severity over that of either single-pathogen norovirus or single-pathogen bacterial infections.

An unprecedented epidemic of Ebola virus disease (EVD) unfolded in West Africa in 2014. The epidemic has been well described in the popular press and in regular reports from public health authorities. The medical literature has necessarily been slower in describing the epidemic, but comprehensive reports are now appearing, offering valuable accounts of the clinical features, epidemiology, and public health consequences of this terrifying disease. The American Society of Tropical Medicine and Hygiene (ASTMH) has been deeply involved with the EVD outbreak. Numerous ASTMH members have played major roles in addressing the epidemic, including clinicians and epidemiologists working at the front lines of the epidemic at great personal risk, public health authorities guiding control efforts in Africa and elsewhere, and drug and vaccine experts working to rush effective products to the field. The annual meeting of the ASTMH served as a forum for timely expert discussions on EVD, but also highlighted the political challenges of this particular crisis, as some experts were prevented from attending the ASTMH meeting as a result of ill-founded concerns about the consequences of their recent travel to West Africa. In this issue of the American Journal of Tropical Medicine and Hygiene (AJTMH) we offer a series of Perspectives from individuals active in addressing the EVD epidemic. As with other large disasters, the full toll of the EVD epidemic is difficult to fathom. The numbers are clear. As of the end of 2014, nearly 20,000 cases of EVD and 7,000 deaths have been reported to the World Health Organization (WHO). These numbers are likely underestimates caused by underreporting. Furthermore, although these numbers are much lower than those seen for our greatest tropical medicine challenges, the impact of the epidemic can easily be underappreciated. EVD is quite unique, even among severe infectious diseases, in causing massive disruption to societies, and in particular to the healthcare infrastructure. In affected areas of Africa, in addition to the huge direct toll of EVD, all aspects of healthcare have been torn apart. Management and control of the most important serious infectious diseases, including neonatal infections, human immunodeficiency virus (HIV) infection, tuberculosis, malaria, and other neglected diseases have been greatly disrupted. “Band-aid” solutions, such as widespread distribution of artemisinin-based combination therapies to decrease the incidence of non-Ebola febrile illnesses, have unknown efficacy, and may cause new problems, such as selection of drug resistance and loss of community confidence in the healthcare system. Outside of Africa, responses to the EVD epidemic have often been driven by fear, misguided estimates of risk, and political considerations. Most often, we in the scientific community appropriately focus on the data—the numbers of cases, the epidemiologic characteristics, and the efficacies of new interventions. In this process we may lose sight of the fact that a crisis such as the EVD epidemic is inherently personal. People are getting infected, suffering, and dying. In the case of this epidemic, much more so than in most humanitarian disasters, many of the victims are the healthcare workers and scientists who have willingly put themselves in harm's way to help alleviate the suffering of others. In this issue of the AJTMH we offer Perspectives focusing on the personal side of the epidemic, considering in particular the points of view of health workers as caregivers at risk, as patients, and as those working to improve our ability to manage and control this epidemic. Two perspectives, from Adaora Igonoh and Will Pooley, offer accounts from those who put themselves at personal risk caring for patients with EVD, and then contracted the disease themselves. Another, from Lewis Rubinson, offers an account of a potential Ebola virus exposure that led to complex consequences. Susan McClellan offers an account from one of the many non-African healthcare providers who eagerly put themselves at risk. Perspectives addressing an improved response to EVD include a discussion of how, despite some steps in the right direction, the public health community failed to best prepare for a potential hemorrhagic fever outbreak by Daniel Bausch, a consideration of rethinking discharge policy in seriously stressed EVD clinics by Tim O'Dempsey and others, and a comprehensive commentary on clinical preparedness for those providing EVD care from David Brett-Major and many others. Considering the political consequences of responses to the epidemic outside Africa, perspectives from groups led by Ramin Asgary and Piero Olliaro detail the consequences of the misguided effort of the State of Louisiana to protect public health by preventing attendance at the annual meeting of the ASTMH in New Orleans by anyone who had recently traveled to affected countries in West Africa. The West African EVD epidemic is still unfolding. This enormous disaster is likely to have long-range consequences, with impacts on efforts to control all tropical diseases in addition to specific effects on viral hemorrhagic fever preparedness and far-reaching impacts on the affected countries. Regardless of the future overall course, the epidemic will remain deeply personal, with obvious consequences on affected patients and families, but also on health workers. We hope that the Perspectives in this issue of the AJTMH will help readers to appreciate the personal side of this epidemic, both as a major humanitarian disaster and as a formidable challenge for the international public health community.

BACKGROUND: In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. METHODS: From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. RESULTS: Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). CONCLUSIONS: Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.

Dengue virus (DENV) was reintroduced to Peru in the 1990s and has been reported in Puerto Maldonado (population ~65,000) in the Peruvian southern Amazon basin since 2000. This region also has the highest human migration rate in the country, mainly from areas not endemic for DENV. The objective of this study was to assess the proportion of household income that is diverted to costs incurred because of dengue illness and to compare these expenses between recent migrants (RMs) and long-term residents (LTRs). We administered a standardized questionnaire to persons diagnosed with dengue illness at Hospital Santa Rosa in Puerto Maldonado from December 2012 to March 2013. We compared direct and indirect medical costs between RMs and LTRs. A total of 80 participants completed the survey, of whom 28 (35%) were RMs and 52 (65%) were LTRs. Each dengue illness episode cost the household an average of US$105 (standard deviation [SD] = 107), representing 24% of their monthly income. Indirect costs were the greatest expense (US$56, SD = 87), especially lost wages. The proportion of household income diverted to dengue illness did not differ significantly between RM and LTR households. The study highlights the significant financial burden incurred by households when a family member suffers dengue illness.