|Ebola and Marburg hemorrhagic fevers: neglected tropical diseases?|
|Jump to Full Text|
|PMID: 22761967 Owner: NLM Status: MEDLINE|
|Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the "classic" NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease.|
|Adam MacNeil; Pierre E Rollin|
Related Documents :
|19527367 - Multiple bilateral spinal nerve root calcifications in charcot-marie-tooth disease.
14652447 - X-linked charcot-marie-tooth disease with myokymia: report of a family.
11096587 - Gallstones.
2827487 - Dietary factors and risk of trophoblastic disease.
21576577 - Fox-fordyce disease following axillary laser hair removal.
15790527 - Parkinson's disease: in vivo assessment of disease progression using positron emission ...
|Type: Journal Article; Research Support, U.S. Gov't, P.H.S.; Review Date: 2012-06-26|
|Title: PLoS neglected tropical diseases Volume: 6 ISSN: 1935-2735 ISO Abbreviation: PLoS Negl Trop Dis Publication Date: 2012 Jun|
|Created Date: 2012-07-04 Completed Date: 2012-10-15 Revised Date: 2013-07-12|
Medline Journal Info:
|Nlm Unique ID: 101291488 Medline TA: PLoS Negl Trop Dis Country: United States|
|Languages: eng Pagination: e1546 Citation Subset: IM|
|Viral Special Pathogens Branch, the Centers for Disease Control and Prevention, Atlanta, GA, USA. firstname.lastname@example.org|
|APA/MLA Format Download EndNote Download BibTex|
Ebola Vaccines / administration & dosage
Hemorrhagic Fever, Ebola / epidemiology, prevention & control*
Marburg Virus Disease / epidemiology, prevention & control*
Neglected Diseases / epidemiology, prevention & control*
Journal ID (nlm-ta): PLoS Negl Trop Dis
Journal ID (iso-abbrev): PLoS Negl Trop Dis
Journal ID (publisher-id): plos
Journal ID (pmc): plosntds
Publisher: Public Library of Science, San Francisco, USA
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
collection publication date: Month: 6 Year: 2012
Electronic publication date: Day: 26 Month: 6 Year: 2012
Volume: 6 Issue: 6
E-location ID: e1546
PubMed Id: 22761967
Publisher Id: PNTD-D-11-00942
|Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases?|
|Pierre E. Rollin|
|Viral Special Pathogens Branch, the Centers for Disease Control and
Prevention, Atlanta, Georgia, United States of America
|University of Texas Medical Branch, United States of America
|Correspondence: * E-mail: email@example.com
Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are two similar clinical diseases caused by viruses of the genera Ebolavirus (EBOV) and Marburgvirus (MARV), respectively, both of the family Filoviridae . Owing to largely sensationalist accounts of outbreaks , these diseases are widely recognized, despite the overall rarity of their occurrence . However, EBOV and MARV are highly pathogenic, and have traditionally been associated with devastating outbreaks, with case fatality ranging from 25% to 90% . Additionally, EBOV and MARV are considered potential bioweapons agents , and as such are classified as class A select agents. While the ability to conduct research on infectious EBOV and MARV is limited to a small number of high containment laboratories, extensive funding has been applied to primary research in the past decade, and progress has been made in understanding the biology of these viruses, as well as toward development of potential therapies , . However, from the perspective of those at most risk of disease, this progress has not been experienced. Large outbreaks of EHF in the Democratic Republic of Congo (DRC) in 2007 and 2008, and in Uganda in 2007 –, have demonstrated the continued potential for prolonged virus transmission in impoverished rural communities. We will discuss the epidemiology and control of EHF and MHF, relative to the concepts of neglected tropical diseases (NTDs).
EBOV and MARV are zoonotic viruses, and outside of outbreaks, do not persist in human populations. Current data suggest fruit bats as the reservoir of EBOV and MARV, and the distribution of both viruses appears to be limited to sub-Saharan Africa – (with the exception of Reston ebolavirus (REBOV), identified in the Philippines, and not recognized to be associated with human disease , ). Clusters and outbreaks are primarily the result of person-to-person transmission of these viruses, which occurs through direct contact with the body, bodily fluids (commonly to health care workers), or contaminated clothes or linens of an infected person –. The level of viremia, and thus presumptively the risk of transmission, corresponds with disease severity, with highest concentrations of the virus during later stages of disease , .
Three distinct contact modalities account for virus transmission during outbreaks (summarized in Table 1): 1) transmission between family members, close contacts, and care givers of sick individuals; 2) contact with dead bodies during preparation and funeral proceedings; and 3) transmission in health care settings from sick patients to medical staff or to other hospitalized patients by breaches in barrier nursing and reusing medical equipment , , –. As a result, outbreak response involves three major components: 1) daily observation of all contacts of sick individuals, so that upon onset of illness, persons can be transported to medical facilities and avoid further transmission in the community; 2) ensuring safe burials of deceased individuals; and 3) establishment of patient isolation wards, with medical staff equipped with and trained in usage of personal-protective equipment, to block health care–associated transmission of the virus , –.
While logistically challenging, the above interventions are not technologically difficult. These have consistently been applied in outbreaks, and are effective in stopping the chains of transmission. So why do large EHF and MHF outbreaks continue to occur? Response activities are contingent on identification of the outbreak. A common occurrence among large outbreaks is the large lag, often in the range of months, between initial cases and actual detection of EBOV or MARV . Typical symptoms of EHF and MHF, such as fever, vomiting, diarrhea, fatigue, headache, and myalgia , , , , , can be mistaken for other more frequent endemic tropical infections. However, the fact that outbreaks occur most commonly in resource-limited settings should not be overlooked. Other important aspects include limited capacity of medical and public health staff to conduct disease surveillance and the inability to rapidly perform diagnostic testing.
Additionally, while the zoonotic source of exposure is not always identified in outbreaks, introductions of these viruses to human populations have been associated with entering caves and mines (for MARV) and hunting for or processing bushmeat (for EBOV) –. Educational interventions aimed at discouraging these activities (or potentially directly blocking physical access to caves or mines) have the potential to limit introduction of EBOV and MARV into human populations. For instance, education outreach was performed in the border region of Republic of the Congo (RoC) and Gabon after a series of EHF outbreaks occurred over numerous years, starting in 1994; however, no outbreaks have occurred since 2005 . Similarly, introduction of MARV occurred for numerous years among miners in Watsa Zone of DRC , and cases of MHF ceased only following flooding of the mine . Finally, among routes of filovirus transmission to humans, it may be important to consider the role of other potential secondary hosts. REBOV, and its association with primates from the Philippines, was identified previously . While serologic evidence indicated that humans exposed to infectious primates may be infected, REBOV does not appear to cause overt disease in humans , . Interestingly, REBOV was recently identified in commercial swine in the Philippines, and similarly, evidence of seropositive humans exposed to these animals was observed . Recent laboratory studies have demonstrated that REBOV, as well as ZEBOV, not only infects, but also may be transmitted among swine , . The scenario that either a pathogenic filovirus may enter (and be transmitted among swine) or that mutations in REBOV may result in a virus pathogenic to humans should continue to be considered in global surveillance efforts. In addition to the direct impact on human health, the potential economic impact on agricultural production, if swine (or other livestock) are a direct or perceived threat for transmission of filoviruses, would likely be devastating to a local or regional economy.
Currently there is no standardized definition of an NTD , , and various groups have applied differing standards in the classification of NTDs. Liese et al. summarized two district approaches to characterizing NTDs, the first as “neglect as the defining characteristic”, and the second as “the diseases' shared features and their effects on poverty and development” . The latter of these two approaches has focused on a group of 13 specific protozoan, helminth, and bacterial infections that have a large global burden of disease and strong poverty-promoting effect, and persist as chronic infections despite effective medical treatments available , . (Recently, proposals have expanded this list of NTDs to a total of 17 specific infectious agents ). Focusing on the former approach, an important aspect is the direct role of neglect as a contributing factor to NTDs. Previous reviews have described the impact of NTDs on the “bottom billion”, i.e., the portion of the human population living in the most impoverished conditions . Similarly, the “vicious cycle” of interrelatedness between poverty and infectious diseases has been noted by the World Health Organization (WHO) .
A major component of the “13 NTDs” is the underlying high burden of disease, both from a morbidity and mortality standpoint, as well as from an economic standpoint. One estimate suggests more than 500,000 deaths annually as a result of these diseases . The burden of EHF and MHF globally is substantially lower (and in comparison to the economic impact of the 13 NTDs , the overall economic impact of EHF and MHF would be marginal in comparison). To date, approximately 2,300 total EHF and MHF cases have been recognized , . There are some data to suggest this number to be a substantial underestimate. Serosurveys in central Africa have reported the prevalence of reactive antibodies to EBOV in human populations to range from 5% to 15%, implying a much high burden of infection –. Since 1976, in large outbreaks of EHF and MHF, the time from initial cases to outbreak confirmation has typically taken months , ; thus, it is likely that smaller, brief outbreaks or isolated cases frequently go unrecognized, especially in remote areas. During an intense prospective surveillance program from 1981 to 1985 in the Sud-Ubangi region of northwestern DRC, Jezek et al. identified a total of 21 EHF cases, indicating a possible ongoing occurrence of sporadic EBOV infections in this population . Similarly, during an investigation of MHF in Watsa Zone of northeastern DRC, which involved multiple zoonotic introductions in miners working in gold mines (and some subsequent secondary transmissions) between 1998 and 2000, medical staff reported the disease as a locally recognized clinical entity in miners, occurring as far back as possibly the 1980s . Regardless, the overall burden of disease due to EHF and MHF is clearly dwarfed in comparison to those of the 13 NTDs.
In contrast, when EHF and MHF are examined from a bottom billion viewpoint, there are multiple factors supporting the notion that disease, and particularly outbreaks, are components of impoverished conditions. From a geographic standpoint, the bulk of human disease has occurred in rural, and often highly remote, locations in the central African countries of Angola, Gabon, RoC, DRC, Sudan, and Uganda  (Figure 1), some of the least developed locations in the world (for instance, see Table 2). As an example of remoteness, 71.3% of the Gulu, Uganda (site of the 2000 EHF outbreak), population live more than 5 km from the nearest health facility, while this percentage is only 0.7% in the capital, Kampala . Although the global distribution of NTDs is more geographically widespread, multiple NTDs also have a high prevalence across this region of Africa , .
Further defining the association between EHF and MHF and impoverished conditions is the observation that amplification of EBOV and MARV transmission commonly occurs in resource-limited health care settings. In addition to transmission associated with re-used medical equipment, many outbreaks involve transmission (sometimes with high frequency) to medical staff caring for patients –. Because EBOV and MARV transmission occurs through direct physical contact with an infected person, bodily fluids, or through contact with contaminated clothes or linens, transmission to health care staff and patients can largely be controlled through implementation of barrier nursing practices for individuals with hemorrhagic symptoms and ensuring that needles or other medical equipment that may contain contaminated fluids are not reused.
Although EHF and MHF may not have the regional or national poverty-promoting effects as some NTDs, the local effects of an outbreak on a village, town, or region can be devastating. Tens to hundreds of deaths have occurred in previous outbreaks. Additionally, these conditions are highly stigmatizing –. Sick patients, medical staff, as well as those who have recovered, commonly face fear and rejection or stigmatization from the local community. Furthermore, the long-term health and psychosocial impacts of EHF and MHF on survivors can be challenging; studies demonstrate post-infection sequelae, as well as prolonged poor health, among those who survived EBOV or MARV infection –.
The impact of EHF or MHF on local health systems can be similarly devastating, particularly for individuals in needs of standard medical care not associated with hemorrhagic fever. In the series of Durba-Watsa MHF cases associated with the Durba mine in northwest DRC, the only physician available at Watsa (district) hospital died of presumed MHF in 1994 and no physician was available in the district from 1994 to 1996. A second physician died of MHF in 1999, again leaving the hospital with no available physician. Similarly, the medical director and 11 staff members for a major hospital died of EHF in the Gulu, Uganda, outbreak in 2000 , . Beyond the deaths of specific individuals, outbreaks have also had severe effects on the actual functioning of medical services. For instance, the Kikwit, DRC, EHF outbreak in 1995 resulted in the infection of 80 health care workers and the closure of Kikwit General Hospital for non-EHF related activities, severely limiting the availability of medical care to the population of Kikwit (200,000), as well as surrounding areas , .
An additional defining characteristic of the 13 NTDs is the absence of an available vaccine . Moran et al. previously noted that funding for development of pharmaceutical tools for prevention or treatment is limited for many of the NTDs. For instance, of 2.5 billion US dollars devoted to research and development of new neglected disease products, almost 80% was applied to HIV, tuberculosis, and malaria, with approximately 2% devoted to helminths, and less than 0.1% devoted to Buruli ulcer or trachoma . Regardless, pharmaceutical treatments and cost effective control measures are available for most NTDs , , underscoring a need for improved implementation of treatment and control efforts. Even in the absence of a vaccine, cases of dracunculiasis (guinea worm disease) have drastically declined through basic public health measures, and guinea-worm eradication is anticipated in the near future . Similarly, no currently licensed vaccines or therapeutics are available for EHF or MHF (discussed further below). While the available funding for research and development of these products may contrast most NTDs, the fact that effective public health measures to prevent or control EHF and MHF are already known is consistent with the above observation for other NTDs.
As noted above, a common characteristic of large EHF and MHF outbreaks is the break-down (or absolute lack of) public health surveillance, resulting in long periods of time before identification of the outbreak by public health authorities. With improved surveillance, early chains of transmission can be identified and outbreak response efforts rapidly applied. As an example, during the recent reemergence of EHF in Luwero district, Uganda (May 2011), viral hemorrhagic fever was immediately suspected in the index (and only case) by clinicians at the hospital. While in a rural area, Luwero is located less than 2 hours by vehicle from the capital of Uganda (Kampala). A confirmatory laboratory diagnosis was acquired in less than a week, and outbreak response activities commenced within 24 hours . While contacts of this EHF case fortunately did not develop disease, the ability to identify and follow-up all contacts would have resulted in prevention of further spread of the virus, should secondary cases have developed.
Public health approaches for NTDs have traditionally focused on vertical drug-based treatment strategies , . However, the importance of integration of NTD control into broad health systems is now being recognized , . Moreover, technical guidelines by the WHO Regional Office for Africa (AFRO) and Member States were recently released for the Integrated Disease Surveillance and Response (IDSR) strategy . The IDSR recommends integrated surveillance of multiple infectious diseases to broaden the ability to detect and respond to infectious diseases of epidemic potential or those targeted for eradication or elimination. Priority diseases included in the 2010 IDSR guidelines include EHF and MHF, as well as a number of other NTDs, including Buruli ulcer, dracunculiasis, leprosy, lymphatic filariasis, onchocerciasis, trachoma, and trypanosomiasis. While public health resources are limited across sub-Saharan Africa, and challenges still exist in its integration, studies have demonstrated tangible improvement of surveillance as a result of IDSR implementation .
Laboratory diagnostics are a crucial component of public health surveillance, and efforts need to be made to ensure capacity for rapid diagnostic testing for EHF and MHF across sub-Saharan Africa, as well as the ability to rule out other tropical infections. In the above noted EHF case in Uganda in May 2011, in-country laboratory capacity was available, and a rapid diagnosis was made on the index case, allowing for an immediate public health response .
Of additional importance to the control of EHF and MHF is the prevention of health care–associated spread of the viruses. The fact that basic contact precautions (gowns and gloves) can largely block spread of EHF and MHF in health care settings underscores the effect of poverty on the spread of these diseases. Efforts to provide greater availability of basic medical supplies to rural health care settings in central Africa would help minimize the risk of large outbreaks of EHF and MHF, as well as have the broad benefit of preventing non-related health care–associated infections in patients and health care workers, and ensure greater patient safety. A recent report by Marchal et al. stressed potential linkages between NTD control and improvement of health systems . While infection control during medical care is only one aspect of the entire health system, renewed focus on improving health systems may have a direct impact on prevention of initial spread, and ultimately outbreaks, of EHF and MHF.
Extensive research efforts over the past decade have focused on development of vaccines and anti-viral therapies for EHF and MHF, and currently there are numerous promising products in development –. This evidence suggests there may be an optimistic picture for future licensing of efficacious biologic-based measures for EHF and MHF. But are these applicable for those most at risk for disease? There are two scenarios to consider: vaccines that are administered before the exposure, which prevent disease, and vaccines or anti-viral therapies that can be administered after the exposure (either before or possibly after onset of disease) to prevent or improve the clinical prognosis of illness. From an occupation-based risk standpoint, prophylactic vaccination will be clearly a valuable preventive measure, both for individuals with potential exposure in the laboratory or through ecological work, as well as medical and public health personal involved in hands-on outbreak response activities.
When we consider those at risk of endemic exposure to EBOV or MARV—the bottom billion—the potential value of prophylactic vaccination becomes murky. A scenario in which one envisions applying vaccine across the entire endemic population in sub-Saharan Africa is unrealistic. Given the total burden of filovirus disease (∼2,300 total cases identified since 1967), attempting the administration of millions of doses of vaccine has limited justification, particularly considering the current ongoing challenge of establishing high levels of coverage of routine immunizations in many endemic areas. For instance, estimated coverage of polio and measles among 1-year-olds in Uganda in 2009 was 59% and 68%, respectably .
A second prophylactic vaccination strategy would be to apply a targeted or mass vaccination campaign to an entire region, in the event of an outbreak. Given the nature of the spread of EBOV and MARV in outbreak settings (chains of person-to-person transmission), the efficacious outbreak control measure already developed (contact tracing, isolation, and safe burials), and the scope of even the largest outbreaks (Gulu, Uganda in 2000 with 425 EHF cases is the largest known outbreak), the application of mass vaccination would not be an efficient or cost effective control mechanism, and would likely draw resources and public personnel away from outbreak control activities. Additionally, if vaccine is administered to an exposed individual during the incubation period and disease subsequently develops, there is a risk that those administering the vaccine will be perceived by the local population as spreading the disease, which would undermine efforts to further implement vaccination or other control methods.
A final strategy, in the instance of a vaccine or anti-viral drug with the potential to prevent or minimize severity of disease, would be to apply these measures to high risk contacts of suspected or confirmed EHF or MHF cases, as well as to those who are already ill (and in isolation). This activity, if measures can be administered early enough to be effective, would inevitably save lives and would be an incentive for suspected patients to enter isolation. However, from an outbreak control standpoint, a symptomatic individual tracked through contact tracing activities is in essence removed from the “transmitter pool”, and shortly after onset of symptoms (and infectiousness) will be placed under safe isolation for proper medical care. Similarly, sick individuals, already in properly managed isolation, would not further propagate the virus. Thus, while having potential therapeutic value, post-exposure biologics may have limited impact on the scope of EHF or MHF outbreaks.
Finally, it worth reiterating in the broad context of vaccines or anti-viral therapies for outbreak settings, that any application is contingent on identification of the outbreak. Since traditionally in large outbreaks, a high proportion of cases occur before outbreak identification, biologic-based prevention measures would have no impact on these cases. With effective surveillance, initial cases can be identified rapidly, minimizing the overall impact of the outbreak through classic outbreak control measures. Thus, while not a stand-alone intervention for outbreak control, application of anti-viral therapies may help lower the overall impact of fatalities in EHF and MHF outbreaks.
Those most at risk for EHF and MHF are residents of rural central Africa, many of whom are among the bottom billion. Outbreaks of EHF and MHF are commonly associated with limited public health surveillance and inadequate medical preventive measures, both partially the result of impoverished conditions. Effective methods to prevent and control EHF and MHF are well understood. While challenging, efforts to combine control of these diseases with other NTDs, through mechanisms such as integrated surveillance and improvement of health systems, would provide a combined benefit to populations in rural central Africa. While multiple candidate vaccines and anti-viral therapies against EBOV and MARV are currently in development, classical public health surveillance and outbreak control guidelines will likely remain the cornerstone of disease control. However, modern therapies have the potential to minimize the number of EHF and MHF deaths in outbreak settings.
Key Learning Points
The authors have declared that no competing interests exist.
All funding was provided by the Centers for Disease Control and Prevention. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
We thank Craig Manning for mapping and graphical assistance.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
|1.||Sanchez A,Geisbert TW,Feldmann H. Year: 2007Filoviridae: Marburg and Ebola viruses.Knipe DM,Howley PM Fields Virology: Lippincott Williams&Wilkins.|
|2.||Semmler IA. Year: 1998Ebola goes pop: the filovirus from literature into film.Lit Med171491749604849|
|3.||Leroy EM,Gonzalez JP,Baize S. Year: 2011Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa.Clin Microbiol Infect1796497621722250|
|4.||Feldmann H,Geisbert TW. Year: 2011Ebola haemorrhagic fever.Lancet37784986221084112|
|5.||Borio L,Inglesby T,Peters CJ,Schmaljohn AL,Hughes JM,et al. Year: 2002Hemorrhagic fever viruses as biological weapons: medical and public health management.JAMA2872391240511988060|
|6.||Dias MB,Reyes-Gonzalez L,Veloso FM,Casman EA. Year: 2010Effects of the USA PATRIOT Act and the 2002 Bioterrorism Preparedness Act on select agent research in the United States.Proc Natl Acad Sci U S A1079556956120457912|
|7.||Burki TK. Year: 2011USA focuses on Ebola vaccine but research gaps remain.Lancet37838921809495|
|8.||Leroy EM,Epelboin A,Mondonge V,Pourrut X,Gonzalez JP,et al. Year: 2009Human Ebola outbreak resulting from direct exposure to fruit bats in Luebo, Democratic Republic of Congo, 2007.Vector Borne Zoonotic Dis972372819323614|
|9.||MacNeil A,Farnon EC,Wamala J,Okware S,Cannon DL,et al. Year: 2010Proportion of deaths and clinical features in Bundibugyo Ebola virus infection, Uganda.Emerg Infect Dis161969197221122234|
|10.||Wamala JF,Lukwago L,Malimbo M,Nguku P,Yoti Z,et al. Year: 2010Ebola hemorrhagic fever associated with novel virus strain, Uganda, 2007–2008.Emerg Infect Dis161087109220587179|
|11.||Leroy EM,Kumulungui B,Pourrut X,Rouquet P,Hassanin A,et al. Year: 2005Fruit bats as reservoirs of Ebola virus.Nature43857557616319873|
|12.||Pourrut X,Delicat A,Rollin PE,Ksiazek TG,Gonzalez JP,et al. Year: 2007Spatial and temporal patterns of Zaire ebolavirus antibody prevalence in the possible reservoir bat species.J Infect Dis196Suppl 2S176S18317940947|
|13.||Towner JS,Pourrut X,Albarino CG,Nkogue CN,Bird BH,et al. Year: 2007Marburg virus infection detected in a common African bat.PLoS ONE2e764 doi:10.1371/journal.pone.0000764. 17712412|
|14.||Towner JS,Amman BR,Sealy TK,Carroll SA,Comer JA,et al. Year: 2009Isolation of genetically diverse Marburg viruses from Egyptian fruit bats.PLoS Pathog5e1000536 doi:10.1371/journal.ppat.1000536. 19649327|
|15.||Barrette RW,Metwally SA,Rowland JM,Xu L,Zaki SR,et al. Year: 2009Discovery of swine as a host for the Reston ebolavirus.Science32520420619590002|
|16.||Taniguchi S,Watanabe S,Masangkay JS,Omatsu T,Ikegami T,et al. Year: 2011Reston ebolavirus antibodies in bats, the Philippines.Emerg Infect Dis171559156021801651|
|17.||Baron RC,McCormick JB,Zubeir OA. Year: 1983Ebola virus disease in southern Sudan: hospital dissemination and intrafamilial spread.Bull World Health Organ6199710036370486|
|18.||Roels TH,Bloom AS,Buffington J,Muhungu GL,Mac Kenzie WR,et al. Year: 1999Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: risk factors for patients without a reported exposure.J Infect Dis179Suppl 1S92S979988170|
|19.||Dowell SF,Mukunu R,Ksiazek TG,Khan AS,Rollin PE,et al. Year: 1999Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidemies a Kikwit.J Infect Dis179Suppl 1S87919988169|
|20.||Francesconi P,Yoti Z,Declich S,Onek PA,Fabiani M,et al. Year: 2003Ebola hemorrhagic fever transmission and risk factors of contacts, Uganda.Emerg Infect Dis91430143714718087|
|21.||Bausch DG,Towner JS,Dowell SF,Kaducu F,Lukwiya M,et al. Year: 2007Assessment of the risk of Ebola virus transmission from bodily fluids and fomites.J Infect Dis196Suppl 2S142S14717940942|
|22.||Ksiazek TG,Rollin PE,Williams AJ,Bressler DS,Martin ML,et al. Year: 1999Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995.J Infect Dis179Suppl 1S177S1879988182|
|23.||Towner JS,Rollin PE,Bausch DG,Sanchez A,Crary SM,et al. Year: 2004Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome.J Virol784330434115047846|
|24.||AnonymousYear: 1978Ebola haemorrhagic fever in Zaire, 1976.Bull World Health Organ56271293307456|
|25.||AnonymousYear: 1978Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International Study Team.Bull World Health Organ56247270307455|
|26.||Khan AS,Tshioko FK,Heymann DL,Le Guenno B,Nabeth P,et al. Year: 1999The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidemies a Kikwit.J Infect Dis179Suppl 1S76S869988168|
|27.||Tomori O,Bertolli J,Rollin PE,Fleerackers Y,Guimard Y,et al. Year: 1999Serologic survey among hospital and health center workers during the Ebola hemorrhagic fever outbreak in Kikwit, Democratic Republic of the Congo, 1995.J Infect Dis179Suppl 1S98S1019988171|
|28.||CDCYear: 2001Outbreak of Ebola hemorrhagic fever Uganda, August 2000-January 2001.MMWR Morb Mortal Wkly Rep50737711686289|
|29.||Kerstiens B,Matthys F. Year: 1999Interventions to control virus transmission during an outbreak of Ebola hemorrhagic fever: experience from Kikwit, Democratic Republic of the Congo, 1995.J Infect Dis179Suppl 1S2632679988193|
|30.||Guimard Y,Bwaka MA,Colebunders R,Calain P,Massamba M,et al. Year: 1999Organization of patient care during the Ebola hemorrhagic fever epidemic in Kikwit, Democratic Republic of the Congo, 1995.J Infect Dis179Suppl 1S268S2739988194|
|31.||Ndambi R,Akamituna P,Bonnet MJ,Tukadila AM,Muyembe-Tamfum JJ,et al. Year: 1999Epidemiologic and clinical aspects of the Ebola virus epidemic in Mosango, Democratic Republic of the Congo, 1995.J Infect Dis179Suppl 1S8S109988156|
|32.||Lamunu M,Lutwama JJ,Kamugisha J,Opio A,Nambooze J,et al. Year: 2004Containing a haemorrhagic fever epidemic: the Ebola experience in Uganda (October 2000-January 2001).Int J Infect Dis8273714690778|
|33.||Jeffs B,Roddy P,Weatherill D,de la Rosa O,Dorion C,et al. Year: 2007The Medecins Sans Frontieres intervention in the Marburg hemorrhagic fever epidemic, Uige, Angola, 2005. I. Lessons learned in the hospital.J Infect Dis196Suppl 2S154S16117940944|
|34.||Roddy P,Weatherill D,Jeffs B,Abaakouk Z,Dorion C,et al. Year: 2007The Medecins Sans Frontieres intervention in the Marburg hemorrhagic fever epidemic, Uige, Angola, 2005. II. lessons learned in the community.J Infect Dis196Suppl 2S162S16717940945|
|35.||MacNeil A,Farnon EC,Morgan OW,Gould P,Boehmer TK,et al. Year: 2011Filovirus outbreak detection and surveillance: lessons from Bundibugyo.J Infect Dis204Suppl 3S761S76721987748|
|36.||Bwaka MA,Bonnet MJ,Calain P,Colebunders R,De Roo A,et al. Year: 1999Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients.J Infect Dis179Suppl 1S1S79988155|
|37.||Colebunders R,Tshomba A,Van Kerkhove MD,Bausch DG,Campbell P,et al. Year: 2007Marburg hemorrhagic fever in Durba and Watsa, Democratic Republic of the Congo: clinical documentation, features of illness, and treatment.J Infect Dis196Suppl 2S148S15317940943|
|38.||Smith DH,Johnson BK,Isaacson M,Swanapoel R,Johnson KM,et al. Year: 1982Marburg-virus disease in Kenya.Lancet18168206122054|
|39.||Bausch DG,Nichol ST,Muyembe-Tamfum JJ,Borchert M,Rollin PE,et al. Year: 2006Marburg hemorrhagic fever associated with multiple genetic lineages of virus.N Engl J Med35590991916943403|
|40.||Pourrut X,Souris M,Towner JS,Rollin PE,Nichol ST,et al. Year: 2009Large serological survey showing cocirculation of Ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus.BMC Infect Dis915919785757|
|41.||Timen A,Koopmans MP,Vossen AC,van Doornum GJ,Gunther S,et al. Year: 2009Response to imported case of Marburg hemorrhagic fever, the Netherland.Emerg Infect Dis151171117519751577|
|42.||Georges AJ,Leroy EM,Renaut AA,Benissan CT,Nabias RJ,et al. Year: 1999Ebola hemorrhagic fever outbreaks in Gabon, 1994–1997: epidemiologic and health control issues.J Infect Dis179Suppl 1S65S759988167|
|43.||Leroy EM,Rouquet P,Formenty P,Souquiere S,Kilbourne A,et al. Year: 2004Multiple Ebola virus transmission events and rapid decline of central African wildlife.Science30338739014726594|
|44.||Nkoghe D,Kone ML,Yada A,Leroy E. Year: 2011A limited outbreak of Ebola haemorrhagic fever in Etoumbi, Republic of Congo, 2005.Trans R Soc Trop Med Hyg10546647221605882|
|45.||Adjemian J,Farnon EC,Tschioko F,Wamala JF,Byaruhanga E,et al. Year: 2011Outbreak of Marburg hemorrhagic fever among miners in Kamwenge and Ibanda Districts, Uganda, 2007.J Infect Dis204Suppl 3S796S79921987753|
|46.||Swanepoel R,Smit SB,Rollin PE,Formenty P,Leman PA,et al. Year: 2007Studies of reservoir hosts for Marburg virus.Emerg Infect Dis131847185118258034|
|47.||Miranda ME,Miranda NL. Year: 2011Reston ebolavirus in humans and animals in the Philippines: a review.J Infect Dis204Suppl 3S75776021987747|
|48.||Miranda ME,Ksiazek TG,Retuya TJ,Khan AS,Sanchez A,et al. Year: 1999Epidemiology of Ebola (subtype Reston) virus in the Philippines, 1996.J Infect Dis179Suppl 1S115S1199988174|
|49.||Kobinger GP,Leung A,Neufeld J,Richardson JS,Falzarano D,et al. Year: 2011Replication, pathogenicity, shedding, and transmission of Zaire ebolavirus in pigs.J Infect Dis20420020821571728|
|50.||Marsh GA,Haining J,Robinson R,Foord A,Yamada M,et al. Year: 2011Ebola Reston virus infection of pigs: clinical significance and transmission potential.J Infect Dis204Suppl 3S804S80921987755|
|51.||Liese B,Rosenberg M,Schratz A. Year: 2010Programmes, partnerships, and governance for elimination and control of neglected tropical diseases.Lancet375677620109865|
|52.||Molyneux DH. Year: 2010Neglected tropical diseases–beyond the tipping point?Lancet3753420109840|
|53.||Molyneux DH,Hotez PJ,Fenwick A. Year: 2005“Rapid-impact interventions”: how a policy of integrated control for Africa's neglected tropical diseases could benefit the poor.PLoS Med2e336 doi:10.1371/journal.pmed.0020336. 16212468|
|54.||Hotez PJ,Molyneux DH,Fenwick A,Kumaresan J,Sachs SE,et al. Year: 2007Control of neglected tropical diseases.N Engl J Med3571018102717804846|
|55.||Year: 2011Working to overcome the global impact of neglected tropical diseases - summary.Wkly Epidemiol Rec8611312021438440|
|56.||Hotez PJ,Fenwick A,Savioli L,Molyneux DH. Year: 2009Rescuing the bottom billion through control of neglected tropical diseases.Lancet3731570157519410718|
|57.||TDR/WHOYear: 2007Ten year vision strategy. Fostering an effective global research effort on infectious diseases of poverty in which disease endemic countries play a pivotal roleGenevaTDR/World Health Organization|
|58.||Hotez PJ,Molyneux DH,Fenwick A,Ottesen E,Ehrlich Sachs S,et al. Year: 2006Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria.PLoS Med3e102 doi:10.1371/journal.pmed.0030102. 16435908|
|59.||Mathers CD,Ezzati M,Lopez AD. Year: 2007Measuring the burden of neglected tropical diseases: the global burden of disease framework.PLoS Negl Trop Dis1e114 doi:10.1371/journal.pntd.0000114. 18060077|
|60.||Kuhn JH,Calisher CH. Year: 2008Filoviruses: a compendium of 40 years of epidemiological, clinical, and laboratory studiesNew YorkSpringer|
|61.||Busico KM,Marshall KL,Ksiazek TG,Roels TH,Fleerackers Y,et al. Year: 1999Prevalence of IgG antibodies to Ebola virus in individuals during an Ebola outbreak, Democratic Republic of the Congo, 1995.J Infect Dis179Suppl 1S102S1079988172|
|62.||Gonzalez JP,Nakoune E,Slenczka W,Vidal P,Morvan JM. Year: 2000Ebola and Marburg virus antibody prevalence in selected populations of the Central African Republic.Microbes Infect2394410717539|
|63.||Becquart P,Wauquier N,Mahlakoiv T,Nkoghe D,Padilla C,et al. Year: 2010High prevalence of both humoral and cellular immunity to Zaire ebolavirus among rural populations in Gabon.PLoS ONE5e9126 doi:10.1371/journal.pone.0009126. 20161740|
|64.||MacNeil A,Farnon EC,Morgan OW,Gould P,Boehmer TK,et al. Year: 2011Filovirus outbreak detection and surveillance: lessons from Bundibugyo.J Infect Dis204Suppl 3S761S76721987748|
|65.||Jezek Z,Szczeniowski MY,Muyembe-Tamfum JJ,McCormick JB,Heymann DL. Year: 1999Ebola between outbreaks: intensified Ebola hemorrhagic fever surveillance in the Democratic Republic of the Congo, 1981–1985.J Infect Dis179Suppl 1S60S649988166|
|66.||Accorsi S,Fabiani M,Lukwiya M,Ravera M,Costanzi A,et al. Year: 2001Impact of insecurity, the AIDS epidemic, and poverty on population health: disease patterns and trends in Northern Uganda.Am J Trop Med Hyg6421422111442220|
|67.||Hewlett BS,Epelboin A,Hewlett BL,Formenty P. Year: 2005Medical anthropology and Ebola in Congo: cultural models and humanistic care.Bull Soc Pathol Exot9823023616267966|
|68.||Hewlett BL,Hewlett BS. Year: 2005Providing care and facing death: nursing during Ebola outbreaks in central Africa.J Transcult Nurs1628929716160191|
|69.||De Roo A,Ado B,Rose B,Guimard Y,Fonck K,et al. Year: 1998Survey among survivors of the 1995 Ebola epidemic in Kikwit, Democratic Republic of Congo: their feelings and experiences.Trop Med Int Health38838859855400|
|70.||Kalongi Y,Mwanza K,Tshisuaka M,Lusiama N,Ntando E,et al. Year: 1999Isolated case of Ebola hemorrhagic fever with mucormycosis complications, Kinshasa, Democratic Republic of the Congo.J Infect Dis179Suppl 1S15S179988159|
|71.||Kibadi K,Mupapa K,Kuvula K,Massamba M,Ndaberey D,et al. Year: 1999Late ophthalmologic manifestations in survivors of the 1995 Ebola virus epidemic in Kikwit, Democratic Republic of the Congo.J Infect Dis179Suppl 1S13S149988158|
|72.||Rowe AK,Bertolli J,Khan AS,Mukunu R,Muyembe-Tamfum JJ,et al. Year: 1999Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidemies a Kikwit.J Infect Dis179Suppl 1S28S359988162|
|73.||Wendo C. Year: 2001Caring for the survivors of Uganda's Ebola epidemic one year on.Lancet358135011684230|
|74.||Borchert M,Mulangu S,Swanepoel R,Libande ML,Tshomba A,et al. Year: 2006Serosurvey on household contacts of Marburg hemorrhagic fever patients.Emerg Infect Dis1243343916704781|
|75.||Bausch DG. Year: 2001The Ebola Virus …… and the Challenges to Health Research in Africa.United Nations Chronicle38613|
|76.||Accorsi S,Fabiani M,Nattabi B,Corrado B,Iriso R,et al. Year: 2005The disease profile of poverty: morbidity and mortality in northern Uganda in the context of war, population displacement and HIV/AIDS.Trans R Soc Trop Med Hyg9922623315653126|
|77.||Bethony JM,Cole RN,Guo X,Kamhawi S,Lightowlers MW,et al. Year: 2011Vaccines to combat the neglected tropical diseases.Immunol Rev23923727021198676|
|78.||Moran M,Guzman J,Ropars AL,McDonald A,Jameson N,et al. Year: 2009Neglected disease research and development: how much are we really spending?PLoS Med6e30 doi:10.1371/journal.pmed.1000030. 19192946|
|79.||Centers for Disease Control and Prevention (CDC)Year: 2011Progress toward global eradication of dracunculiasis, January 2010-June 2011.MMWR Morb Mortal Wkly Rep601450145322031217|
|80.||WHOYear: 2011Outbreak news. Ebola, Uganda.Wkly Epidemiol Rec8622121661270|
|81.||Baker MC,Mathieu E,Fleming FM,Deming M,King JD,et al. Year: 2010Mapping, monitoring, and surveillance of neglected tropical diseases: towards a policy framework.Lancet37523123820109924|
|82.||Marchal B,Van Dormael M,Pirard M,Cavalli A,Kegels G,et al. Year: 2011Neglected tropical disease (NTD) control in health systems: the interface between programmes and general health services.Acta Trop120Suppl 1S177S18521439930|
|83.||WHO/CDCYear: 2010Technical guidelines for integrated disease surveillance and response in the African regionBrazzaville, Republic of Congo, and Atlanta, USAWHO and CDC|
|84.||Nsubuga P,Brown WG,Groseclose SL,Ahadzie L,Talisuna AO,et al. Year: 2010Implementing Integrated Disease Surveillance and Response: Four African countries' experience, 1998–2005.Glob Public Health536438019916090|
|85.||Feldmann H. Year: 2010Are we any closer to combating Ebola infections?Lancet3751850185220511001|
|86.||Geisbert TW,Bausch DG,Feldmann H. Year: 2010Prospects for immunisation against Marburg and Ebola viruses.Rev Med Virol2034435720658513|
|87.||Falzarano D,Geisbert TW,Feldmann H. Year: 2011Progress in filovirus vaccine development: evaluating the potential for clinical use.Expert Rev Vaccines10637721162622|
|88.||WHO Global Health Observatory Data RepositoryWorld Health Organization. Available: http://apps.who.int/ghodata/. Accessed 30 May 2012.|
[Figure ID: pntd-0001546-g001]
Figure 1 Location of Ebola hemorrhagic fever (red circles) and Marburg hemorrhagic fever (green squares) outbreaks.
Table 1 Common routes of EHF and MHF spread, and interventions to stop transmission during outbreaks.
|Route of Spread||Intervention|
|Community transmission to family members and other close contacts of EHF or MHF cases||Daily monitoring of all contacts of EHF and MHF cases and rapid transfer of sick contacts to medical facility for evaluation|
|Contact with deceased EHF or MHF cases during preparation of the body or funeral proceedings||Implementation of safe burial practices for all deceased individuals|
|Transmission in the health care setting from EHF or MHF cases to medical staff by direct contact or contact with bodily fluids, or to other patients through contaminated medical equipment||Establishment of isolation ward and provide clinical care by medical staff with training specific to EHF and MHF outbreaks|
Table 2 Select economic and health indicators for countries with previous large outbreaks of Ebola or Marburg hemorrhagic fever (total number of countries which rank is based on).
|Per Capita Income (228a)||Infant Mortality per 1,000 Live Births (223a)||Life Expectancy in Years, at Birth (222a)||Physicians per 1,000 Population (192a)|
|Angola||US$8,200 (121)||175.9 (1)||38.76 (222)||0.08 (169)|
|Democratic Republic of Congo||US$300 (227)||78.43 (14)||55.33 (199)||0.11 (163)|
|Gabon||US$14,500 (80)||49.95 (49)||52.49 (207)||0.29 (141)|
|Republic of Congo||US$4,100 (158)||76.05 (15)||54.91 (200)||0.10 (166)|
|Sudan||US$2,300 (184)||102.00 (6)b||55.42 (198)||0.28 (143)|
|Uganda||US$1,300 (204)||62.47 (29)||53.24 (204)||0.12 (161)|
Data from The World Factbook, CIA (accessed December 15, 2011).
aAvailable number of countries, which rank is based on.
bData is specific to South Sudan.
Previous Document: The haptic recognition of geometrical shapes in congenitally blind and blindfolded adolescents: is t...
Next Document: Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic "power station".