Ebola haemorrhagic fever outbreak in Masindi District, Uganda: outbreak description and lessons learned

Background

Prevention of diarrhea has presented indomitable challenges. A preventive strategy that has received significant interest is zinc supplementation. Existing literature including quantitative meta-analyses and systematic reviews tend to show that zinc supplementation is beneficial however evidence to the contrary is augmenting. We therefore conducted an updated and comprehensive meta-analytical synthesis of the existing literature on the effect of zinc supplementation in prevention of diarrhea.

Methods

EMBASE^®, MEDLINE ^® and CINAHL^® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. Effect of zinc supplementation on the following five outcomes was studied: incidence of diarrhea, prevalence of diarrhea, incidence of persistent diarrhea, incidence of dysentery and incidence of mortality. The published RCTs were combined using random-effects meta-analyses, subgroup meta-analyses, meta-regression, cumulative meta-analyses and restricted meta-analyses to quantify and characterize the role of zinc supplementation with the afore stated outcomes.

Results

We found that zinc supplementation has a modest beneficial association (9% reduction) with incidence of diarrhea, a stronger beneficial association (19% reduction) with prevalence of diarrhea and occurrence of multiple diarrheal episodes (28% reduction) but there was significant unexplained heterogeneity across the studies for these associations. Age, continent of study origin, zinc salt and risk of bias contributed significantly to between studies heterogeneity. Zinc supplementation did not show statistically significant benefit in reducing the incidence of persistent diarrhea, dysentery or mortality. In most instances, the 95% prediction intervals for summary relative risk estimates straddled unity.

Conclusions

Demonstrable benefit of preventive zinc supplementation was observed against two of the five diarrhea-related outcomes but the prediction intervals straddled unity. Thus the evidence for a preventive benefit of zinc against diarrhea is inconclusive. Continued efforts are needed to better understand the sources of heterogeneity. The outcomes of zinc supplementation may be improved by identifying subgroups that need zinc supplementation.     

关注新暴发的马尔堡出血热

马尔堡出血热（Marburg haemorrhagic fever）,又称为马尔堡病毒病,是一种以突然发病、发热、多脏器损害、出血、休克、皮疹及高病死率为特征的烈性传染病,其命名源自1967年秋,当时在西德的马尔堡、法兰克福以及南斯拉夫的贝尔格莱德的几所医学实验室的工作人员中,暴发了一起严重的类似出血热表现的疫情,先后共31人发病,7例死亡,这些患者大都接触过一批从乌干达运来的非洲绿猴。科学家们对患者的血液和组织细胞进行了培养,分离出一种以前没有见到过的病毒。根据发病地点,将这种病毒命名为马尔堡病毒（Marburgvirus,MBGV）。而感染此种病毒后,引起的以发热、出血症状为主的疾病被称为马尔堡出血热。     

埃博拉出血热医院感染预防与控制技术指南(第一版)

正为加强埃博拉出血热(Ebola hemorrhagic fever)医院感染预防与控制准备工作,最大限度减少医院感染风险,根据《传染病防治法》、《医院感染管理办法》等法律法规,制定本技术指南。一、埃博拉出血热防控的基本要求(一)埃博拉出血热是由埃博拉病毒(Ebola virus)引起的一种急性出血性传染病。主要通过接触患者或     

Management of viral haemorrhagic fever in the Netherlands

Two cases of Lassa fever have been reported in the Netherlands since viral haemorrhagic fevers became notifiable diseases in 1978. In 1980, an expatriate from Burkina Faso who was not seriously ill was confirmed by laboratory tests after his discharge from hospital. The second case occurred in 2000: the patient died on the 11th day of admission to hospital. The problems we faced in the management of this case and the contact investigation--more than one hundred contacts - highlighted the need for national recommendations in the Netherlands.     

Epidemiological aspects of an outbreak of dengue fever/dengue haemorrhagic fever in Singapore

A nation-wide outbreak of 260 cases of DF/DHF with 1 death occurred in Singapore from Apr-Sept 1986. The outbreak originated from 3 separate foci of transmission at the western, south-eastern and north-eastern parts of the island and then spread to other dengue receptive urban and suburban areas. The morbidity rate was highest in young male Chinese adults between 15 and 24 years of age. The outbreak was rapidly brought under control through destruction of adult Aedes mosquitoes, surveys and source reduction of larval breeding habitats, health education and to a certain extent law enforcement. The Aedes population was high in the main foci of transmission although the overall house index was only 1.1. Other factors which could have precipitated the outbreak included waning herd immunity of the human population and continuous introduction of dengue virus into the country.     

A clinical guide to viral haemorrhagic fevers: Ebola, Marburg and Lassa

The viral haemorrhagic fevers are a group of diseases that share many clinical features. Ebola, Marburg and Lassa are diseases that cause a relatively small number of deaths globally, but pose special risks to medical staff due to the ease of transmission, and can have a profound impact to the communities they affect. This article gives a brief overview of diseases caused by the Ebola, Marburg and Lassa viruses. It gives some practical advice to the clinician on the diagnosis and management of these diseases.     

Containing a haemorrhagic fever epidemic: the Ebola experience in Uganda (October 2000-January 2001).

INTRODUCTION: The Ebola virus, belonging to the family of filoviruses, was first recognized in 1976 when it caused concurrent outbreaks in Yambuku in the Democratic Republic of Congo (DRC), and in the town of Nzara in Sudan. Both countries share borders with Uganda. A total of 425 cases and 224 deaths attributed to Ebola haemorrhagic fever (EHF) were recorded in Uganda in 2000/01. Although there was delayed detection at the community level, prompt and efficient outbreak investigation led to the confirmation of the causative agent on 14 October 2000 by the National Institute of Virology in South Africa, and the subsequent institution of control interventions. CONTROL INTERVENTIONS: Public health interventions to contain the epidemic aimed at minimizing transmission in the health care setting and in the community, reducing the case fatality rate due to the epidemic, strengthening co-ordination for the response and building capacity for on-going surveillance and control. Co-ordination of the control interventions was organized through the Interministerial Committee, National Ebola Task Force, District Ebola Task Forces, and the Technical Committees at national and district levels. The World Health Organization (WHO) under the Global Outbreak Alert and Response Network co-ordinated the international response. The post-outbreak control interventions addressed weaknesses prior to outbreak detection and aimed at improving preparations for future outbreak detection and response. Challenges to control efforts included inadequate and poor quality protective materials, deaths of health workers, numerous rumors and the rejection of convalescent cases by members of the community. CONCLUSIONS: This was recognized as the largest reported outbreak of EHF in the world. Control interventions were very successful in containing the epidemic. The community structures used to contain the epidemic have continued to perform well after containment of the outbreak, and have proved useful in the identification of other outbreaks. This was also the first outbreak response co-ordinated by the WHO under the Global Outbreak Alert and Response Network, a voluntary organization recently created to co-ordinate technical and financial resources to developing countries during outbreaks.     

Vectors of dengue fever/dengue haemorrhagic fever with advances in their control

The most important vector of dengue in the Western Pacific Region is Ae. aegypti. On some occasions, Ae. albopictus, Ae. polynesiensis and several other species of the Ae. scutellaris complex have been suspected vectors in localities where Ae. aegypti was not found. Long-term vector control by the use of insecticides has been expensive and difficult to achieve. However, spray equipment and ULV insecticides have been obtained in many places for emergency use during outbreaks, and Abate larviciding also has been used in high-risk localities to help prevent outbreaks. Obtaining greater community participation supported by intensified health education and other acceptable measures is considered an important approach for achieving improved long-term control. Developing an acceptable and effective cover for domestic water storage containers is also recognized as a potentially important tool for suppressing vector populations.     

An outbreak of Ebola in Uganda

An outbreak of Ebola disease was reported from Gulu district, Uganda, on 8 October 2000. The outbreak was characterized by fever and haemorrhagic manifestations, and affected health workers and the general population of Rwot-Obillo, a village 14 km north of Gulu town. Later, the outbreak spread to other parts of the country including Mbarara and Masindi districts. Response measures included surveillance, community mobilization, case and logistics management. Three coordination committees were formed: National Task Force (NTF), a District Task Force (DTF) and an Interministerial Task Force (IMTF). The NTF and DTF were responsible for coordination and follow-up of implementation of activities at the national and district levels, respectively, while the IMTF provided political direction and handled sensitive issues related to stigma, trade, tourism and international relations. The international response was coordinated by the World Health Organization (WHO) under the umbrella organization of the Global Outbreak and Alert Response Network. A WHO/CDC case definition for Ebola was adapted and used to capture four categories of cases, namely, the 'alert', 'suspected', 'probable' and 'confirmed cases'. Guidelines for identification and management of cases were developed and disseminated to all persons responsible for surveillance, case management, contact tracing and Information Education Communication (IEC). For the duration of the epidemic that lasted up to 16 January 2001, a total of 425 cases with 224 deaths were reported countrywide. The case fatality rate was 53%. The attack rate (AR) was highest in women. The average AR for Gulu district was 12.6 cases/10 000 inhabitants when the contacts of all cases were considered and was 4.5 cases/10 000 if limited only to contacts of laboratory confirmed cases. The secondary AR was 2.5% when nearly 5000 contacts were followed up for 21 days. Uganda was finally declared Ebola free on 27 February 2001, 42 days after the last case was reported. The Government's role in coordination of both local and international support was vital. The NTF and the corresponding district committees harmonized implementation of a mutually agreed programme. Community mobilization using community-based resource persons and political organs, such as Members of Parliament was effective in getting information to the public. This was critical in controlling the epidemic. Past experience in epidemic management has shown that in the absence of regular provision of information to the public, there are bound to be deleterious rumours. Consequently rumour was managed by frank and open discussion of the epidemic, providing daily updates, fact sheets and press releases. Information was regularly disseminated to communities through mass media and press conferences. Thus all levels of the community spontaneously demonstrated solidarity and response to public health interventions. Even in areas of relative insecurity, rebel abductions diminished considerably.     

Management of patients in Germany with suspected viral haemorrhagic fever and other potentially lethal contagious infections

Patients suffering from viral haemorrhagic fevers must be handled specifically. The clinical diagnosis of these diseases in the initial stage is difficult because early symptoms are non specific. In Germany, specific diagnosis is available at two diagnostic centres with biosafety level 4 facilities. Five high security infectious disease isolation units for patient care are available in Munich, Leipzig, Hamburg, Berlin, and Frankfurt. In addition, a corresponding number of centres of competence are established to offer support and advice to the hospitals initially treating the patients and to the local public health officers. The decentralisation of these centres of competence is recommended to allow for more timely and reactive responses to VHF epidemic threats. The risk categorisation for contacts has proved to be very useful in practice.     

Bichat guidelines for the clinical management of haemorrhagic fever viruses and bioterrorism-related haemorrhagic fever viruses

Haemorrhagic fever viruses (HFVs) are a diverse group of viruses that cause a clinical disease associated with fever and bleeding disorder. HFVs that are associated with a potential biological threat are Ebola and Marburg viruses (Filoviridae), Lassa fever and New World arenaviruses (Machupo, Junin, Guanarito and Sabia viruses) (Arenaviridae), Rift Valley fever (Bunyaviridae) and yellow fever, Omsk haemorrhagic fever, and Kyanasur Forest disease (Flaviviridae). In terms of biological warfare concerning dengue, Crimean-Congo haemorrhagic fever and Hantaviruses, there is not sufficient knowledge to include them as a major biological threat. Dengue virus is the only one of these that cannot be transmitted via aerosol. Crimean-Congo haemorrhagic fever and the agents of haemorrhagic fever with renal syndrome appear difficult to weaponise. Ribavirin is recommended for the treatment and the prophylaxis of the arenaviruses and the bunyaviruses, but is not effective for the other families. All patients must be isolated and receive intensive supportive therapy.     

Effect of dengue-1 antibodies on American dengue-2 viral infection and dengue haemorrhagic fever

In Iquitos, Peru, no cases of dengue haemorrhagic fever have been recorded in individuals infected with dengue-1 virus followed by American genotype dengue-2 (American dengue-2) virus. We assayed serum samples collected in Iquitos that tested positive for antibodies of monotype dengue-1 and monotype dengue-2 using a plaque reduction neutralisation test to determine their ability to neutralise the infectivity of two dengue-1 viruses, two American dengue-2 viruses, and two Asian dengue-2 viruses. Sera positive for the dengue-1 antibody neutralised dengue-1 viruses and American dengue-2 viruses much more effectively than Asian dengue-2 viruses. Neutralisation of American dengue-2 virus by sera positive for dengue-1 antibodies may account for the absence of dengue haemorrhagic fever in individuals infected with dengue-1 in 1990-91 followed by American dengue-2 virus in 1995 in Iquitos, Peru.