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August 25, 2005
As of August 23, 2005, the Ministry of Health in Angola reported a total of 374 cases, including 329 deaths countrywide from the Marburg Hemorrhagic Fever. Of these, 368 cases, including 323 deaths, were reported in the Uige Province. A total of 158 cases were laboratory confirmed.
Fifty-two contacts are still being monitored in the Uige Province and clinical specimens from alerts continue to be shipped to the Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, for diagnostic testing.
The last confirmed case of Marburg died on 21 July 2005 in Songo municipality, Uige Province. There have been no laboratory confirmed cases since then.
Assessment of the
Outbreak
The international response to the outbreak in Angola began one month ago, on 22 March. The features of Marburg hemorrhagic fever, and the conditions in Angola, have been an extreme test of international capacity to hold emerging diseases at bay. The outbreak in Angola is the largest and deadliest on record for this rare disease, which is presently showing a case fatality rate higher than 90%. For comparison, outbreaks of the closely related Ebola hemorrhagic fever have shown mortality rates ranging, according to the virus strain involved, from 53% to 88%. The only other large outbreak of Marburg, in the Democratic Republic of Congo from 1998 through 2000, had a case fatality of 83%.
Two factors make the rapid detection of outbreaks of Marburg hemorrhagic fever difficult: the extreme rarity of this disease and its similarity to other diseases seen in countries where deaths from infectious diseases are common. Neither the source nor the date of the initial cases in Angola can be presently identified with any certainty.
The number of cases began increasing in February and then, more dramatically, in March. On 21 March, Marburg virus was detected in patient samples sent to the Centers for Disease Control and Prevention in Atlanta (USA), and WHO assistance was requested by the Ministry of Health in Angola. The operational response began the following day. As known from extensive experience with outbreaks of other viral hemorrhagic fevers, including Ebola, outbreaks of Marburg can be brought to an end using classic public health interventions. In theory, the measures needed to end the Angolan outbreak are few in number and straightforward in nature. Rapid detection and isolation of patients, tracing and management of their close contacts, infection control in hospitals and protective clothing for staff work to interrupt chains of transmission and thus seal off opportunities for further spread.
Such straightforward measures are complicated by the distinct features of this disease. The sudden onset, dramatic symptoms, and rapid deterioration of patients, and the absence of a vaccine and effective treatment, invariably incite great anxiety in affected populations. This anxiety, in turn, can interfere with control operations, especially when communities begin hiding cases and bodies because of suspicions about the safety of hospitals.
In the current outbreak, such suspicions are understandable. Very few patients with laboratory-confirmed Marburg hemorrhagic fever have survived; most hospitalized patients have died within a day or two following admission. For affected communities, staff from the mobile teams, fully suited in protective gear, are seen as taking away relatives and loved ones who may never again be seen alive.
WHO staff in Uige have today reported further signs that community attitudes are improving, though hostility towards the mobile teams remains of concern in one area known to have recent cases and deaths. Efforts to sensitize affected communities are continuing, with local volunteers supported by Portuguese-speaking experts from Brazil and Mozambique.
Conditions in Angola – a country weakened by almost three decades of civil unrest – have presented additional challenges. Supplies of water and electricity are intermittent, also in health care facilities. Weakened infrastructures, including those for communications and transportation, are another problem. Yesterday, the WHO office in Uige was informed of a death in another municipality, but was unable to collect the body for safe burial because of poor road conditions.
Fortunately, spread of the disease beyond Uige Province, located in the interior of the country, has been limited. Of the 266 cases and 244 deaths, 197 cases and 183 deaths occurred in Uige municipality. Other municipalities in Uige Province account for an additional 56 cases and 50 deaths.
WHO believes that the risk of international spread is low. No foreign nationals, with the exception of those involved in the direct care of patients, have been infected. There is no evidence that people can spread the virus before the onset of symptoms. Shortly after symptom onset, patients become rapidly and visibly very ill.
WHO is optimistic that the outbreak can be controlled if present activities continue with sufficient vigor. All the essential containment measures are being applied with extensive international support, including more than 60 international staff drawn from institutions in the Global Outbreak Alert and Response Network, and the cooperation of national authorities and experts.
Tools and methods developed during international responses to outbreaks of other diseases have all been brought to bear on the present outbreak, and the success of this collaborative effort has surpassed initial expectations. Needs, which have ranged from satellite telephones and hand-held radio sets to vehicles, protective equipment, disinfectants, and specialized staff, have been rapidly communicated and immediately met.
WHO and its partners are nonetheless prepared and organized to continue the outbreak response for several additional months, if this is needed. An important present goal is to transfer skills and responsibilities for outbreak response to national staff, and training efforts are under way with this goal in mind.
Advice for
Travelers
All currently available data indicate that casual contact plays no role in the spread of Marburg hemorrhagic fever. Transmission requires extremely close contact involving exposure to blood or other bodily fluids from a patient who will most likely be showing visible signs of illness. The disease can also be transmitted following exposure to items, including bedding and clothing, recently contaminated by a patient.
Transmission can occur in hospitals lacking adequate equipment and supplies for infection control and training in their proper use. The hospital system in Angola has suffered from almost three decades of civil unrest, and several cases of Marburg hemorrhagic fever have occurred in health care staff exposed during the treatment of patients in
Uige.
To date, WHO is not aware of any cases of Marburg that have occurred in foreign nationals other than those involved in the care of cases in
Uige.
WHO does not recommend restrictions on travel to any destination within Angola, but does advise some precautions. Travelers to Angola should be aware of the outbreak of Marburg hemorrhagic fever and of the need to avoid close contact with ill persons. Persons with existing medical conditions who might require hospitalization should consider deferring non-essential travel to Angola, particularly to Uige Province.
Those traveling to Angola for the purpose of working in health care settings should be fully informed regarding the outbreak of Marburg hemorrhagic fever, equipped with effective personal protective equipment, and trained in the procedures to prevent transmission in such settings.
Travelers leaving Angola should be advised to seek medical attention should any illness with fever develop within 10 days of their departure. Information about recent travel to Angola should be included when symptoms are reported.
Health care workers and health authorities in countries neighboring Angola should be aware of the symptoms of Marburg hemorrhagic fever and maintain vigilance for cases. Countries having close ties with Angola, necessitating frequent travel there by their citizens, may want to consider the introduction of measures to increase vigilance for potential symptoms in persons returning from Angola. In some cases, the introduction of screening procedures to identify potentially infected persons may be considered. WHO recommends that travelers with a clear exposure history be treated as contacts and placed under surveillance for 21 days, during which time their temperature should be monitored daily.
International appeal
Specialized international staff and equipment have been deployed rapidly and measures are beginning to have an impact. Control of the outbreak will require intensified and sustained technical support from multidisciplinary teams, and additional materials and supplies. Provision of adequate personal protective equipment is a particularly urgent need. Increased field coordination of technical, operational and logistic support is likewise needed.
Today, WHO has launched an appeal, through the United Nations, for funding to support the emergency response to this outbreak. WHO needs US$ 2.4 million to support the Ministry of Health, Angola to intensify ongoing operations in the field.
To reduce the risk of transmission in the community, priority activities include intensive social mobilization and health education in the towns and villages of Uige Province. To reduce the risk of transmission in health care facilities, priorities include the provision of personal protective equipment for front-line staff and essential supplies for infection control, including disinfectants. Additional activities that urgently need to be strengthened include the early detection and isolation of cases and the tracing and follow up of contacts.
International diagnostic and laboratory support
For laboratory work, Marburg virus has been classified as an extremely hazardous pathogen and can be handled safely only in specialized high-containment laboratories. WHO has established an international network of expert laboratories for the diagnosis of Marburg and other viral hemorrhagic fevers. Within this network, laboratories in Canada, Germany, South Africa, and the USA are providing diagnostic support for the Angolan outbreak. All have experience in working with Marburg virus.
Scientists from these laboratories are sharing test results and information on laboratory techniques in a virtual network and during weekly teleconferences. To ensure accurate tracking of the outbreak, members of the network are also standardizing methods for sample collection, testing, and the interpretation of results. The various diagnostic tests for Marburg hemorrhagic fever require skilled technical interpretation, as findings can vary according to the phase of the patient’s illness, the way in which samples were taken, and the type of test used.
In Angola, a portable field laboratory is now operating in Uige and a second one should be operational in Luanda shortly. Field laboratories provide rapid and sufficiently reliable results for use during an outbreak, when decisions about appropriate case management and contact tracing need to be made quickly. The laboratory network is providing backup support for situations in which exceptionally precise diagnostic results are important because of the implications for control measures. Such situations include the possible exportation of a case to another country, and a suspected case in a person who may have placed numerous other people at unusually high risk.
Sophisticated laboratory studies of the virus may help shed some light on certain unusual features of the outbreak, including the high fatality rate and the overwhelming concentration of initial cases in children under the age of five years. In this regard, comparisons of the virus with strains from previous outbreaks may be instructive.
A longer-term objective, whose achievement has long proved elusive, is to determine where Marburg virus hides in nature between outbreaks. Studies of viruses from Angola may offer some clues. Prior to the present outbreak, Angola was not considered to fall within the geographical “hot zone”, thought to be in central and eastern Africa, for outbreaks and sporadic cases of this rare disease.
Recommendations for Travelers
Before you leave
- Assemble a travel health kit containing basic first aid and medical supplies. Be sure to include a thermometer, household disinfectant, and alcohol-based hand rubs for hand hygiene.
- Inform yourself and others who may be traveling with you about Marburg virus. For information about this illness,
see CDC's Marburg Web site or contact MedAire.
- Be sure you are up to date with all your immunizations, and see your health-care provider at least 4-6 weeks before travel to get any additional immunizations, medications, or information you may need. For information on CDC health recommendations for international travel, see
CDC's Travelers' Health site.
- You may wish to check your health insurance plan or get additional insurance that covers medical evacuation in the event of illness. Information about medical evacuation services can be found at this
U.S. Department of State page.
- Identify in-country health-care resources in advance of your trip.
During travel
- As with other infectious illnesses, one of the most important preventive practices is careful and frequent hand washing. Cleaning your hands often, using soap and water (or waterless alcohol-based hand rubs when soap is not available), removes potentially infectious materials from your skin and helps prevent disease transmission. When wearing gloves, wash the gloves with soap and water before removing them, and then wash your hands.
- Avoid contact with ill or dead animals, especially primates.
- Do not eat “bushmeat” (wild animals, including primates, sold for consumption as food in local markets).
- If you or your family members become ill with fever or develop other symptoms such as chills, muscle aches, nausea, vomiting, or rash, visit a health-care provider immediately. You are encouraged to identify these resources in advance. When traveling to a health-care provider, limit your contact with others. All other travel should be avoided.
After you return
- Persons returning from the affected area should monitor their health for 10 days. Any traveler who becomes ill, even if only a fever, should consult a health-care provider immediately and tell him or her about their recent travel and potential contacts. Tell the provider about your symptoms prior to going to the office or emergency room so arrangements can be made, if necessary, to prevent transmission to others in the health-care setting.
What is Marburg hemorrhagic fever?
Marburg hemorrhagic fever is a rare, severe type of hemorrhagic fever which affects both humans and non-human primates. Caused by a genetically unique zoonotic (that is, animal-borne) RNA virus of the filovirus family, its recognition led to the creation of this virus family. The four species of Ebola virus are the only other known members of the filovirus family.
Marburg virus was first recognized in 1967, when outbreaks of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, Germany and in Belgrade, Yugoslavia (now Serbia). A total of 37 people became ill; they included laboratory workers as well as several medical personnel and family members who had cared for them. The first people infected had been exposed to African green monkeys or their tissues. In Marburg, the monkeys had been imported for research and to prepare polio vaccine.
Recorded cases of the disease are rare, and have appeared in only a few locations. While the 1967 outbreak occurred in Europe, the disease agent had arrived with imported monkeys from Uganda. No other case was recorded until 1975, when a traveler most likely exposed in Zimbabwe became ill in Johannesburg, South Africa – and passed the virus to his traveling companion and a nurse. 1980 saw two other cases, one in Western Kenya not far from the Ugandan source of the monkeys implicated in the 1967 outbreak. This patient’s attending physician in Nairobi became the second case. Another human Marburg infection was recognized in 1987 when a young man who had traveled extensively in Kenya, including western Kenya, became ill and later died. In 1998, an outbreak occurred in Durba, Democratic Republic of the Congo. Cases were linked to individuals working in a gold mine. After the outbreak subsided, there were still some sporadic cases that occurred in the region.
Where is Marburg virus found?
Marburg hemorrhagic fever is caused by a virus that is believed to primarily inhabit countries in East and Central Africa. Although the disease is rare, it has the potential to spread to other people, especially health-care staff and family members who care for the patient. Transmission to humans may occur through direct contact with the body fluids (i.e., blood, saliva, urine) of an infected person or infected animal, or through contact with objects that have been contaminated with infectious material. Spread of the virus between human has occurred in settings of close contact, such as hospitals.
How do humans get Marburg hemorrhagic fever?
Just how the animal host first transmits Marburg virus to humans is unknown. However, as with some other viruses which cause viral hemorrhagic fever, humans who become ill with Marburg hemorrhagic fever may spread the virus to other people. This may happen in several ways. Persons who have handled infected monkeys and have come in direct contact with their fluids or cell cultures, have become infected. Spread of the virus between humans has occurred in a setting of close contact, often in a hospital. Droplets of body fluids, or direct contact with persons, equipment, or other objects contaminated with infectious blood or tissues are all highly suspect as sources of disease.
What are the symptoms of the disease?
After an incubation period of 5-10 days, the onset of the disease is sudden and is marked by fever, chills, headache, and myalgia. Around the fifth day after the onset of symptoms, a maculopapular rash, most prominent on the trunk (chest, back, stomach), may occur. Nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea then may appear. Symptoms become increasingly severe and may include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhaging, and multi-organ dysfunction.
Because many of the signs and symptoms of Marburg hemorrhagic fever are similar to those of other infectious diseases, such as malaria or typhoid fever, diagnosis of the disease can be difficult, especially if only a single case is involved.
What is the recovery period?
Recovery from Marburg hemorrhagic fever may be prolonged and accompanied by orchititis, recurrent hepatitis, transverse myelitis or uvetis. Other possible complications include inflammation of the testis, spinal cord, eye, parotid gland, or by prolonged hepatitis.
What is the fatality rate?
The case-fatality rate for Marburg hemorrhagic fever is between 23-25%.
What is the treatment for Marburg hemorrhagic fever?
A specific treatment for this disease is unknown. However, supportive hospital therapy should be utilized. This includes balancing the patient’s fluids and electrolytes, maintaining their oxygen status and blood pressure, replacing lost blood and clotting factors and treating them for any complicating infections.
Sometimes treatment also has used transfusion of fresh-frozen plasma and other preparations to replace the blood proteins important in clotting. One controversial treatment is the use of heparin (which blocks clotting) to prevent the consumption of clotting factors. Some researchers believe the consumption of clotting factors is part of the disease process.
Who is at risk?
People who have close contact with a human or non-human primate infected with the virus are at risk. Such persons include laboratory or quarantine facility workers who handle non-human primates that have been associated with the disease. In addition, hospital staff and family members who care for patients with the disease are at risk if they do not use proper barrier nursing techniques.
Can this disease be prevented?
Due to our limited knowledge of the disease, preventive measures against transmission from the original animal host have not yet been established. Measures for prevention of secondary transmission are similar to those used for other hemorrhagic fevers. If a patient is either suspected or confirmed to have Marburg hemorrhagic fever, barrier nursing techniques should be used to prevent direct physical contact with the patient. These precautions include wearing of protective gowns, gloves, and masks; placing the infected individual in strict isolation; and sterilization or proper disposal of needles, equipment, and patient excretions.
What needs to be done to address the threat of Marburg hemorrhagic fever?
Marburg hemorrhagic fever is a very rare human disease. However, when it does occur, it has the potential to spread to other people, especially health care staff and family members who care for the patient. Therefore, increasing awareness among health-care providers of clinical symptoms in patients that suggest Marburg hemorrhagic fever is critical. Better awareness can help lead to taking precautions against the spread of virus infection to family members or health-care providers. Improving the use of diagnostic tools is another priority. With modern means of transportation that give access even to remote areas, it is possible to obtain rapid testing of samples in disease control centers equipped with Biosafety Level 4 laboratories in order to confirm or rule out Marburg virus infection.
A fuller understanding of Marburg hemorrhagic fever will not be possible until the ecology and identity of the virus reservoir are established. In addition, the impact of the disease will remain unknown until the actual incidence of the disease and its endemic areas are determined.
Source: Centers for
Disease Control (CDC) and World Health Organization (WHO)
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