Outbreak of Marburg Virus reported in Rwanda.

On 27 September 2024 the  Rwanda Ministry of Health confirmed that an outbreak of Marburg Virus Disease was present in the country, following the detection of the Virus in the blood of two patients by real-time reverse transcription polymerase chain reaction analysis at the National Reference Laboratory of the Rwanda Biomedical Center, according to a press release issued by the World Health Organization on 30 September 2024.

As of 29 September 2024, 26 cases of the disease have been reported in seven of the country's thirty districts (Gasabo, Gatsibo, Kamonyi, Kicukiro, Nyagatare, Nyarugenge and Rubavu), with eight people having died of the disease, a case fatality rate of 31%. The majority of the patients are healthcare workers from two health facilities in Kigali; this is not uncommon with outbreaks of the Marburg and Ebola viruses, with the highly transmittable nature of these diseases often resulting in aa high mortality rate in healthcare workers around the initial locus of the outbreak.

Contract tracing has led to the screening of about 300 contacts of diagnosed patients, one of whom had travelled to Belgium, with all found to be healthy and not a threat to public health. The initial source of the outbreak is still under investigation.

Marburg Virus Disease is a haemorrhagic fever, similar to the closely related Ebola Virus Disease. Both are caused by single-strand negative-sense RNA viruses of the Filoviridae family. Both are easily spread though contact with bodily fluids, and can also spread by contaminated clothing and bedding. 

Negative stained transmission electron micrograph of a number of filamentous Marburg Virions, which had been cultured on Vero cell cultures, and purified on sucrose, rate-zonal gradients. Erskine Palmer/Russell Regnery/Centers for Disease Control and Prevention/Wikimedia Commons.

Marburg Virus has an incubation period of between two and 21 days, manifesting at first as a high fever, combined with a severe headache and a strong sense of malaise. This is typically followed after about three days by severe abdominal pains, with watery diarrhoea and vomiting. In severe cases the disease develops to a haemorrhagic stage after five-to-seven days, manifesting as bleeding from some or all bodily orifices. This typically leads to death on day eight or nine, from severe blood loss and shock. There is currently no treatment or vaccine available for Marburg Virus, although a number of teams are working on trying to develop vaccines. 

Previous outbreaks of Marburg Virus have been reported in Rwanda, as well as the neighbouring Democratic Republic of Congo and Tanzania. The Virus has also been reported in a number of other African countries, including Angola, Equatorial Guinea, Ghana, Guinea, Kenya, and South Africa. The most recent outbreaks occurred in January 2023, with unrelated epidemics in Tanzania and Equatorial Guinea. 

The high rate of infection of healthcare workers seen in Marburg Virus is particularly alarming, as this tends to weaken communities ability to resist the Virus. The Virus can spread quickly in healthcare settings, infecting people whose immune systems are already stressed by other conditions, and creating aa reserve which can feed infections in the wider community. This makes it important to screen all people potentially infected with the disease as quickly as possible, and to arrange for patients to be treated in isolation, as well as quickly tracing all known contacts of any cases, and screening them for infection too.

Marburg Virus is a zoonotic infection (disease transferred from Animals to Humans), with a wild-reserve of the Virus known to be present in Egyptian Fruit Bats, Rousettus aegyptiacus, which are found across much of Africa, the Mediterranean region, the Middle East, and South Asia. These Bats form large colonies in caves or sometimes mines. They are frugivores, and can be major pests of farmed fruits, bringing them into conflict with Humans, and are sometimes hunted for food, all of which create potential avenues for the Marburg Virus to pass from a Bat host to a Human one.

A colony of Egyptian Rousette Bats, Rousettus aegyptiacus. Giovanni Mari/Flikr/iNaturalist.

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The epidemiology of the 2020 Ebola outbreak in Équateur Province, Democratic Republic of the Congo.

On 1 June 2020 medical authorities in Équateur Province, Democratic Republic of the Congo, reported an outbreak of Ebolavirus Disease in Mbandaka, the capital of Équateur Province. This was the eleventh reported outbreak of an Ebola-type disease in the Democratic Republic of the Congo, and was close to the location of a previous outbreak in the Bikoro health zone of Équateur Province, which occurred in 2018. The Democratic Republic of the Congo suffered fifteen outbreaks of Ebola-type diseases between 1 September 1976 and 22 August 2022, with the 2020 Équateur Province outbreak being the eleventh of these. The majority of these were caused by the Ebolavirus, and occurred in the north of the country, although one, in Haut-Uélé Province in 2012, was caused by the Bundibugyo Virus.

Ebolavirus has not been found in Bats in the Democratic Republic of the Congo, but the closely related Marburg Virus has, and Bats with antibodies to Ebolavirus have been found in Nord Kivu Province and Équateur provinces, as well as in the neighbouring Republic of Congo. Outbreaks of Ebola have been associated with the handling of Chimpanzees and Gorillas in the Republic of Congo and Gabon, and Ape populations have been known suffer dramatic declines at the same time as local Human populations have suffered outbreaks of Ebola-type diseases. Furthermore, as with other Filoviruses, Ebolavirus can persist in the system of survivors after they have apparently recovered, and cause new infections via sexual transmission or other exchange of bodily fluids. Before it became possible to identify Ebolaviruses by rapid genetic sequencing, it was impossible to tell whether outbreaks of the disease were caused by new infections from zoonotic sources (i.e. Animals) or transmission from apparently heathy survivors.

In a paper published in the journal The Lancet Microbe on 23 January 2024, a team of scientists led by Eddy Kinganda-Lusamaki of the Pathogen Genomics Laboratory at the Institut National de Recherche Biomédicale in Kinshasa, the Faculté de Médecine at the Université de Kinshasa, and the Institut de Recherche pour le Développement at the University of Montpellier, present the results of an assessment of the epidemiological and genetic properties of the 2020 Équateur Province Ebola outbreak.

The 2020 Équateur Province outbreak was the Democratic Republic of the Congo's eleventh Ebola outbreak, and started while the tenth outbreak, in North Kivu Province, was still ongoing. This led to suspicions that the two events were related, with the Équateur Province potentially being caused by an infected person travelling from North Kivu. Kinganda-Lusamaki et al. were able to demonstrate that this was not the case, with the two outbreaks being caused by different strains of Ebolavirus, and the Équateur Province outbreak having a zoonotic origin.

Ebolavirus outbreaks in the Democratic Republic of the Congo, 1976–2022. (A) The distribution of Ebolavirus disease outbreaks in the Democratic Republic of the Congo. Coloured circles identify locations of previous outbreaks and the size of circles represents the number of positive Human cases. The map shows the affected 2020 health zones (orange and purple shading) and sites of the 2018 Équateur outbreak (orange shading). The red star indicates the location of the Kinshasa diagnostic laboratory during the Équateur Province 2020 outbreak. (B) The locations and prevalence of Ebolavirus disease cases during the 2020 Ebola virus disease outbreak in the Équateur Province. The red stars indicate the location of the diagnostic and field laboratories during the Équateur Province 2020 outbreak (Mbandaka, Ingende, Itipo, Bikoro, and Bolomba). Kinganda-Lusamaki et al. (2024).

Blood samples from live patients with suspected Ebola and oral swabs from deceased patients thought to have died of Ebola were tested for signs of the Virus. Unlike in previous outbreaks, the presence of a fever was not required for patients to be included in the suspected group, since it has been demonstrated that not all people infected with Ebolavirus develop a fever.

Between 19 May and 16 September 2020, 130 probable cases of Ebola were reported in., 119 of which were confirmed by laboratory analysis. Of the 130 suspected cases, 55 died, a case fatality rate of 42%. Cases were reported in thirteen health zones, Bikoro, Bolenge, Bolomba, Bomongo, Iboko, Ingende, Lilanga Bobangi, Lolanga Mampoko, Lotumbe, Mkanza, Mbandaka, Monieka, and Wangata. The epidemic declined rapidly after August, with the last case being reported on 12 September. Thhe highest number of infections was among men in the 45 or older age bracket, while the least affected group were children aged 5-14. This is surprising, as Équateur Province has a young population, with many more children than older men. This was particularly true in the early stages of the epidemic, with no individuals of 15 or younger affected in May or June, while several children were infected between July and September. The date of the first onset of symptoms was identified for all cases. Forty seven infected persons visited more one health clinic after the onset of symptoms, with three individuals visiting four separate health clinics. The earliest identified case was a 37-year-old woman identified as a housewife, residing in the Mbandaka health zone, who had no contact with any known earlier case, but who was known to have consumed wild Bat meat, strongly suggesting a zoonitic origin for the epidemic.

Demographics of Ebolavirus Disease cases during the 2020 Équateur Province outbreak (A) Epidemiological curve of confirmed and probable Ebolavirus Disease cases over time. (B) Age distribution of confirmed and probable Ebolavirus Disease cases by gender (the black horizontal bars represent the 2020 Democratic Republic of the Congo known age and gender population distribution from the World Health Organization). (C) Temporal age distribution of individuals with Ebolavirus Disease. (D) Distribution of patients with Ebolavirus Disease who visited multiple health-care facilities after symptoms onset. Kinganda-Lusamaki et al. (2024).

Three of the people infected during the epidemic were healthcare workers, and one a traditional healer. Two of these died. Thirty seven of the infected were described as farmers, fishers, or hunters, 25 as housewives, and seven as businesspeople. Ninety four of the infected people are known to have had contact with another known case before becoming infected. Nine reported having contact with an unidentified person who they thought might be infected, 23 had no known link to another case, and four reported contact with Animals which may have passed on the infection.

Nineteen of the infected are believed to have contracted the Virus from a member of their household, twenty from another member of their community, twelve people are thought to have contracted the Virus at a funeral. Twenty seven patients reported multiple potential contact sources, in 44 cases the route of exposure was unknown.

While it was not possible to obtain specimens from all patients, Kinganda-Lusamaki et al. were able to obtain 188 specimens from 122 of the patients, from which they were able to sequence 87 viral genomes. This led to the discovery that there were in fact two separate variants of the Virus circulating during the epidemic, with 83 of the genomes belonging to the Mbandaka variant of the Virus and three belonging to the Tumba variant; a partial sequence (defined as a sequence where less than 70% of the Viruses DNA was recovered) obtained from another patient was also identified as belonging to the Tumba variant. All of the Mbandaka variant cases were calculated to have descended from a last common ancestor which probably existed in a non-Human host in January 2020, with two separate instances of the Virus jumping to Human hosts and then spreading within the community. The first known example of the Tumba variant in the 2020 outbreak was a nineteen-year-old man who visited two separate healthcare clinics before being diagnosed. This patient had no-known contact with any earlier patient, nor had he consumed bushmeat or had contact with any wild or domestic Animals. All three subsequent cases had had contact with this initial case. The previous outbreak of Ebola in Équateur Province in 2018 was also the Tumba variant of the Virus, although it was impossible to determine whether the new outbreak was due to a persistent infection from the earlier epidemic.

By using patient-generated data, Kinganda-Lusamaki et al. were able to generate a history of the 2020 Ebolavirus outbreak in Équateur Province, Democratic Republic of the Congo, which included genetic data, records of health centre visits, dates of infection, identification of the Virus, isolation of patients, and deaths. This enabled them to plot chains of infection, with nineteen chains of infection being determined before generic data was incorporated into the study, and eighteen of these subsequently being stitched together with genetic data to form the Mbandaka variant tree. Twenty of the patients had no determined route of infection, with eleven of these also subsequently added to the Mbandaka variant tree from genetic data; genetic data was not available from the remaining nine patients. Three individuals reported that believing they had contracted the Virus from contact with Animals, but were demonstrated to be part  of the Human-to-Human chain of Mbandaka variant infection. Two individuals were identified from samples taken when they visited healthcare clinics for reasons unrelated to Ebolavirus; both went on to develop symptoms of the disease.

Kinganda-Lusamaki et al. were able to develop an extensive overview of the 2020 Ebolavirus outbreak in Équateur Province, but caution that this data is still probably incomplete, with cases for which the infection routes were unknown or only probable, making it likely that there were other, unidentified cases within the community. A similar pattern was observed in the concurrent epidemic in North Kivu Province. The outbreak appeared to start with an individual who consumed Bat meat, and was of a newly identified strain of the Ebolavirus, identified as the Mbandaka variant. A minority of the cases belonged to a second strain, the Tumba variant, which caused an epidemic of the disease in 2018, and appeared to re-emerge from a survivor in 2020. The Équateur Province outbreak was found to be unrelated to the concurrent North Kivu Province epidemic, contrary to expectations. Their hope is that by utilising both social and genetic data to understand the transmission of the Virus their study will enable healthcare workers to be able to better manage future outbreaks of Ebolavirus.

Kinganda-Lusamaki et al. identified several different routes of Ebolavirus infection during the 2020 outbreak, including zoonotic transmission from Animals, person-to-person infection due to close contact with infected individuals, and the re-emergence of the Virus from a persistent infection. The ability of the Virus to re-emerge as a persistent infection from apparently healthy individuals after quite long intervals has proven to be a problem in other Ebolavirus outbreaks elsewhere in the Democratic Republic of the Congo, as well as in Guinea. This can be differentiated from fresh zoonotic infections by genetic testing (the persistent infection will be genetically close to the previous outbreak, whereas a fresh zoonotic infection is likely to have a novel genome, forming their own distinct clade of infections.

Research around the 2014 Ebolavirus outbreak in Guinea, Sierra Leone, and Liberia demonstrated the importance of educating survivors of the disease of the potential dangers of transmitting the disease after all symptoms have passed, something which Kinganda-Lusamaki et al.'s emphasise.

In the 2020 Équateur Province it took an average of six days between the onset of symptoms and patients being isolated within medical facilities (which was quite often longer than the patient lived), as a consequence, many patients visited multiple healthcare facilities, increasing the number of other people they came into contact with. Based upon this, Kinganda-Lusamaki et al. strongly recommend that in future outbreaks a system of rapid testing is introduced as quickly as possible. They note that an enhanced viral haemorrhagic fever surveillance programme has helped the country to respond rapidly to several outbreaks of different haemorrhagic diseases (including Marburg Virus Disease, Crimean-Congo haemorrhagic fever, and Rift Valley fever), resulting in the severity and duration of the outbreaks being reduced. A similar system would enable the Democratic Republic of the Congo to respond in the same way.

During the last three weeks of the 2020 Équateur Province outbreak, cases were limted to six healthcare districts, falling to two in the last two weeks. Eight of the thirteen new cases reported in the last three weeks were children under fourteen years of age, possibly suggesting that the majority of older people in the area by this time were producing antibodies to the disease, either as a result of prior exposure or vaccination. During the outbreak the rVSVΔG-ZEBOV-GP vaccine was administered to all known contacts of patients who were more than six months old, as part of a  ring vaccination strategy. Unfortunately, record keeping was imperfect, and it is unclear if the reported cases in the last few weeks had been vaccinated, or whether they had been in contact with unvaccinated people. During the North Kivu outbreak the same vaccine was found not to offer absolute protection from infection, but infected people were found to suffer fewer symptoms, recovered more quickly, and were less likely to die. Vaccinated people were found to be producing antibodies to the Virus six months after they were vaccinated. It is unclear whether natural immunity, or the immunity offered by vaccination, wanes over time for Ebolavirus. 

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Outbreak of Dengue Fever in Chad.

On 15 August 2023, a Dengue Fever outbreak was declared by the Ministry of Public Health and Prevention in Chad, according to a press release issued by the World Health Organization on 16 October 2023. As of 1 October, there have been 1342 suspected cases, including 41 confirmed cases reported across eight health districts in four provinces. Among the confirmed cases, one death was reported. Abéché Health District in Ouaddaï Province, in the east of the country, is the current epicentre of the outbreak. The Ministry of Public Health and Prevention has initiated a number of key response activities by implementing, in collaboration with the World Health Organization and other partners, the national contingency plan for Dengue preparedness and response. Dengue is a viral infection transmitted to Humans through the bite of infected Mosquitoes. Many dengue infections produce only mild flu-like illness and over 80% of cases are asymptomatic. There is no specific treatment for Dengue; however, timely detection of cases and appropriate case management are key elements of care to prevent severity and fatality of Dengue. This is the first Dengue outbreak ever reported in Chad, and the country has limited surveillance, clinical and laboratory capabilities. Given the favorable environmental conditions for Mosquito spread, an ongoing humanitarian crisis due to a massive influx of refugees and returnees from Sudan and limited response capacities, the World Health Organization assesses the risk posed by this outbreak as high at the national level.

The outbreak of Dengue declared in Abéché Health District, Ouaddaï Province, represents the first Dengue outbreak ever reported in Chad. The declaration was made after the confirmation of Dengue infection in eight out of 12 blood samples tested using real-time polymerase chain reaction at the national Biosafety and Epidemics Laboratory in N'Djamena. Subsequently, the samples were sent to the Institut Pasteur in Cameroon for confirmation, which was completed on 22 August by polymerase chain reaction and enzyme-linked immunosorbent assay, confirming the presence of Dengue. The Dengue serotype responsible for this outbreak remains unknown.

As of 1 October, there have been 1342 suspected cases, including 41 confirmed cases reported across eight health districts in four provinces. Among the confirmed cases, one death was reported (a Case Fatality Ratio among confirmed cases 2.4%). Eight districts in four provinces (NDjamena, Ouaddaï, Sila, and Wadi Fira) have reported confirmed Dengue cases. Notably, Ouaddaï, the epicentre of the outbreak, has reported the highest number of confirmed cases, accounting for 31 out of the total 41 confirmed cases (76% of confirmed cases). The age group most affected by this outbreak are those between 15 to 34 years old, representing 27% of the reported confirmed cases. 

Dengue is a Viral infection transmitted to humans through the bite of infected Mosquitoes and is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas. The primary vectors that transmit the disease are Aedes aegypti Mosquitoes and, to a lesser extent, Aedes albopictus.

Dengue Fever is caused by a Positive Single-strand RNA Virus of the Flaviviridae family and there are four distinct, but closely related, serotypes of the Virus that cause Dengue Fever (Dengue Fever Virus-1, Dengue Fever Virus-2, Dengue Fever Virus-3 and Dengue Fever Virus-4). Recovery from infection is believed to provide lifelong immunity against that serotype. However, cross-immunity to the other serotypes after recovery is only partial, and temporary. Subsequent infections (secondary infection) by other serotypes increase the risk of developing Severe Dengue Fever.

A transmission electron micrograph showing Dengue Virus virions (the cluster of dark dots near the centre). Centers for Disease Control and Prevention/Wikimedia Commons.

Although Chad has previously experienced outbreaks of Arboviruses (Arthropod-born Viruses) such as Chikungunya and Yellow Fever, this is the first Dengue outbreak ever reported in the country. Chad, including the Ouaddaï Province, experienced a Chikungunya outbreak in 2020, with a total of 34 052 cases recorded and one associated death.

The Ministry of Public Health and Prevention has initiated a number of key response activities, with the support of the World Health Organization and other partners, including mobilizing resources for the implementation of the national contingency plan for Dengue preparedness and response, strengthening surveillance and coordinating the response, including active case finding in healthcare facilities and the community and in-depth epidemiological investigations including regularly updating the case line list, increasing early case detection capacity by disseminating community alert definition of cases and procuring rapid diagnostic tests for health facilities, ensuring effective logistics and operational support, including the transportation of samples for confirmation, developing standard operating procedures for clinical management of suspected and confirmed Dengue cases, including severe Dengue and ensuring inventory of existing case management kits and address gaps, strengthening cross-border collaboration and implementing prevention and vector control measures in border areas, srengthening entomological surveillance, including aquatic and adult stages of the vectors, and characterizing vector bionomics, implementing effective vector control measures as part of integrated vector management, and strengthening community mobilization and commitment to disseminate key information on transmission and control to the population.

This is the first dengue outbreak reported in Chad, and the country lacks the necessary public health preparedness and response capacities. Community cases are likely underreported because Dengue is unknown to the general public and clinicians are not yet sensitised to its presentation, which is sometimes confused with those of other common febrile infections, making early diagnosis challenging, particularly in settings with lack of laboratory facilities for testing. There is a high risk of spread due to the presence of Mosquitoes in large, densely populated cities in eastern Chad near the Sudan border, with a tropical climate, and poor sanitation conditions suitable for Mosquito development.

The province of Ouaddaï, which borders Sudan, is the epicentre of the outbreak and is also the province most affected by the ongoing humanitarian crisis due to a massive influx of refugees and returnees from Sudan. According to the United Nations High Commissioner for Refugees, the number of refugees in the Ouaddaï Province is currently more than 400 000. The movement of returning Sudanese refugees and Chadian nationals has the potential to spread the outbreak to new provinces and across the border. Based on the information available for this event, the World Health Organization assesses the risk posed by this outbreak as high at the national level, moderate at regional level, and low at global level.

The proximity of Mosquito breeding sites to human habitation is a significant risk factor for Dengue Virus infection. The prevention and control of Dengue depend on effective vector control. Vector control activities should focus on all areas where there is a risk of human-vector contact (place of residence, workplaces, schools, and hospitals). The World Health Organization promotes a strategic approach known as Integrated Vector Management to control Aedes spp., the vector of Dengue. Integrated Vector Management should be enhanced to remove potential breeding sites, reduce vector populations, and minimize individual exposure. This should involve vector control strategies for larvae and adults (i.e. environmental management and source reduction), especially of water storage practices, and include covering, draining and cleaning household water storage containers on a weekly basis, applying larvicide in non-potable waters using World Health Organization-prequalified larvicides at correct dosages, distribution of insecticide-treated nets for fever/Dengue inpatients to contain spread of virus from health facilities, as well as strategies for protecting people and households. Indoor space spraying (fogging) is another approach for rapid containment of Dengue-infected Mosquitoes but may be challenging to deliver in densely populated areas of camps.

A health agent at work fumigating an area to prevent Mosquitoes. Sia Kambou/AFP.

Personal protective measures during outdoor activities include topical application of repellents to exposed skin or treatment of clothing, and wearing long-sleeved shirts and pants. Indoor protection can include household insecticide aerosol products, or Mosquito coils. Window and door screens can reduce the probability of Mosquitoes entering the house. Insecticide-treated nets offer good protection against mosquito bites while sleeping during the day. Since Aedes Mosquitoes (the primary vector for transmission) are active at dawn and dusk, personal protective measures are recommended, particularly at these times of day, both in residential areas and also at places of work and schools for children.

Entomological surveillance should be undertaken to assess the breeding potential of Aedes Mosquitoes in containers and monitor insecticide resistance to help select the most effective insecticide-based interventions. There is no specific treatment for Dengue infection, but early detection and access to appropriate healthcare for case management can reduce mortality. Case surveillance should continue to be enhanced in all affected areas and nationwide. Where feasible, resources should be allocated to strengthen a sample referral mechanism for the confirmation and sub-typing of the Dengue Virus.

Communities play a major role in the success and sustainability of vector control activities. While coordination among many stakeholders is required, vector control is critically dependent on ensuring that communities are aware of the risk of infection and know which measures to take to protect themselves. Community engagement and mobilization involve working with local residents to improve vector control and build resilience against future disease outbreaks. Where appropriate participatory community-based approaches are in place, communities are supported to take responsibility for and implement vector control. Participatory community-based approaches aim to ensure that healthy behaviours become part of the social fabric and that communities take ownership of vector control at both inside and outside households.

Based on the information available for this event, the World Health Organization does not recommend travel or trade restrictions be applied to Chad.

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Tanzania and Equatorial Guinea declare end to Marburg Virus outbreaks.

On 2 June 2023, the Ministry of Health of the United Republic of Tanzania declared the end of its first documented outbreak of Marburg Virus Disease, according to a press release issued by the World Health Organization on 2 June 2023. Between 21 March and 31 May, a total of nine cases (eight laboratory-confirmed and one probable) were reported in Tanzania. All cases were reported from Bukoba district, Kagera region. A total of six deaths (a case fatality ratio of 67%) were reported during the outbreak. The declaration was made 42 days (twice the maximum incubation period for Marburg virus infection) after the last possible exposure to an Marburg Virus Disease probable or confirmed case, in accordance with World Health Organization recommendations.

On 8 June 2023, after two consecutive incubation periods (42 days) without a new confirmed case reported, the Ministry of Health of Equatorial Guinea declared the end of the Marburg Virus Disease outbreak, again as per the World Health Organization recommendations, according to a second press release, issued by the World Health Organization on 9 June 2023. A total of 17 confirmed and 23 probable cases were reported from five districts in four provinces; 12 of the 17 confirmed cases died and all the probable cases were reported deaths.  

The World Health Organization encourages countries to maintain most response activities for three months after the outbreak ends. This is to make sure that if the disease re-emerges, health authorities would be able to detect it immediately, prevent the disease from spreading again, and ultimately save lives.

On 21 March 2023, the Ministry of Health of the United Republic of Tanzania officially declared the first Marburg Virus Disease outbreak in the country. Between 21 March and 31 May, a total of nine cases, including eight laboratory-confirmed cases and one probable (the index case), were reported. The last confirmed case was reported on 11 April 2023 and the date of sample collection of the second negative polymerase chain reaction test was on 19 April 2023. All cases were reported from Bukoba District in Kagera Region, in the north of the country.

Map of district reporting Marburg Virus Disease confirmed and probable cases in the United Republic of Tanzania, as of 31 May 2023. World Health Organization.

In Tanzania cases ranged in age from 1 to 59 years old (median 35 years old), with males being the most affected (six cases, or 67% of the total). Six cases were close relatives of the index case, and two were healthcare workers who provided medical care to the patients.

Distribution of Marburg Virus Disease cases (confirmed and probable) by date of symptom onset in the United Republic of Tanzania, as of 31 May 2023. World Health Organization.

From the outbreak declaration until 7 June 2023, 17 confirmed and 23 probable cases of Marburg Virus Disease were reported in the continental region of Equatorial Guinea. Twelve of the confirmed cases died and all the probable cases were reported deaths (the case fatality ratio among confirmed cases is 75%, excluding one confirmed case with an unknown outcome).

The last confirmed case admitted to a Marburg treatment centre in Bata District in Litoral Province was discharged on 26 April, after two consecutive negative polymerase chain reaction tests for Marburg Virus Disease. On 8 June 2023, after two consecutive incubation periods (42 days) without a new confirmed case reported, the Ministry of Health of Equatorial Guinea declared the end of the outbreak.

Confirmed or probable cases were reported in five districts (Bata, Ebebiyin, Evinayong, Nsok Nsomo and Nsork) in four of the country’s eight provinces (Centro Sur, Kié-Ntem, Litoral and Wele-Nzas). 

Map of districts reporting Marburg Virus Disease confirmed and probable cases during the outbreak, Equatorial Guinea. World Health Organization.

Five cases (31%) were identified among healthcare workers, of whom two died (a case fatality ratio of 40% among health care workers). Four patients recovered and were enrolled in a survivor care programme to receive psychosocial and other post-recovery support.

Marburg Virus Disease cases by week of symptoms onset* and case classification, Equatorial Guinea, as of 7 June 2023. World Health Organization.

Marburg Virus is a negative-strand RNA Virus belonging to the Family Filoviridae, which also includes the Ebola Virus. The Virus spreads between people via direct contact through broken skin or mucous membranes with the blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials such as bedding, and clothing contaminated with these fluids, although the natural reservoir of the Virus is thought to be Egyptian Fruit Bats, Rousettus aegyptiacus, with outbreaks often starting when people come into contact with colonies of these Bats in caves or mines. Healthcare workers have previously been infected while treating suspected or confirmed Marburg Virus Disease patients. Burial ceremonies that involve direct contact with the body of the deceased can also contribute to the transmission of Marburg Virus.

Negative stained transmission electron micrograph of a number of filamentous Marburg Virions, which had been cultured on Vero cell cultures, and purified on sucrose, rate-zonal gradients. Erskine Palmer/Russell Regnery/Centers for Disease Control and Prevention/Wikimedia Commons.

The incubation period varies from two to 21 days. Illness caused by Marburg Virus begins abruptly, with high fever, severe headache, and severe malaise. Severe haemorrhagic manifestations may appear between five and seven days from symptom onset, although not all cases have haemorrhagic signs, and fatal cases usually have some form of bleeding, often from multiple areas.

Early supportive care – rehydration with oral or intravenous fluids – and treatment of specific symptoms and co-infections can improve survival. A range of potential treatments are being evaluated, including blood products, immune therapies, and drug therapies.  

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Outbreak of Marburg Virus in Equatorial Guinea claims nine lives.

On 7 February 2023, the Ministry of Health and Social Welfare of Equatorial Guinea reported the deaths of a number of individuals with suspected hemorrhagic fever, according to a press release issued by the World Health Organization on 25 February 2023. On 12 February 2023, one sample was confirmed positive for Marburg Virus by real-time polymerase chain reaction, at the Institut Pasteur in Dakar, Senegal. Investigations are ongoing to find additional cases. The World Health Organization is supporting the response by strengthening contact tracing, case management, infection prevention and control, laboratory, risk communication and community engagement, and assesses the risk posed by the outbreak as high at the national level, moderate at the regional level and low at the global level. This is the first Marburg Virus Disease outbreak reported in Equatorial Guinea.

On 7 February 2023, the Ministry of Health and Social Welfare of Equatorial Guinea reported at least eight deaths that occurred between 7 January and 7 February 2023, in two villages located in the district of Nsock Nsomo, in eastern the province of Kie-Ntem, in the Río Muni Region. According to the ongoing epidemiological investigation, the cases presented with fever, followed by weakness, vomiting, and blood-stained diarrhoea; two cases also presented with skin lesions and otorrhagia (bleeding from the ear).

On 9 February 2023, eight blood samples were collected from contacts and sent to the Centre Interdisciplinaire de Recherches Médicales de Franceville in Gabon, where they tested negative for both Ebola and Marburg viruses by real-time polymerase chain reaction.

An additional eight blood samples were collected from other contacts and sent to the Institute Pasteur in Dakar, Senegal, on 12 February 2023. One of these samples was taken from a suspected case that was confirmed positive for Marburg virus by real-time polymerase chain reaction. This case presented with fever, non-bloody vomiting, bloody diarrhoea, and convulsions and died on 10 February 2023 at Ebebiyin District Hospital. The case also had epidemiological links to four deceased cases from one of the villages in Nsoc-Nsomo district.

As of 21 February 2023, the cumulative number of cases is nine, including one confirmed case, four probable cases and four suspected cases. All the cases have died, one in a health facility and the other eight in the community. There are no cases among healthcare workers. Thirty-four contacts are currently under follow-up.

Marburg Virus is the causative agent of Marburg Virus Disease, which has a case-fatality ratio of up to 88%. Marburg Virus Disease was initially detected in 1967 after simultaneous outbreaks in Marburg and Frankfurt in Germany, and in Belgrade, Serbia.

Negative stained transmission electron micrograph of a number of filamentous Marburg Virions, which had been cultured on Vero cell cultures, and purified on sucrose, rate-zonal gradients. Erskine Palmer/Russell Regnery/Centers for Disease Control and Prevention/Wikimedia Commons.

The Egyptian Fruit Bat, Rousettus aegyptiacus is considered to be the natural host for Marburg Virus, from which the Virus is then transmitted to Humans. Marburg spreads through Human-to-Human transmission via direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials (e.g. bedding, clothing) contaminated with these fluids. Healthcare workers have previously been infected while treating patients with suspected or confirmed Marburg Virus Disease. Burial ceremonies that involve direct contact with the body of the deceased can also contribute to the transmission of Marburg.

The incubation period varies from two to 21 days. Illness caused by Marburg Virus begins abruptly, with high fever, severe headache and severe malaise. Severe watery diarrhoea, abdominal pain and cramping, nausea and vomiting can begin on the third day. Severe haemorrhagic manifestations appear between five and seven days from symptoms onset, and fatal cases usually have some form of bleeding, often from multiple areas. In fatal cases, death occurs most often between eight and nine days after symptom onset, usually preceded by severe blood loss and shock.

In the early course of the disease, the clinical diagnosis of Marburg Virus Disease is difficult to distinguish from many other tropical febrile illnesses due to the similarities in the clinical symptoms. Other viral haemorrhagic fevers need to be excluded, including Ebola Virus Disease, as well as Malaria, Typhoid Fever, Leptospirosis, Rickettsial infections, and Plague. Laboratory confirmation can be made by different tests, such as antibody-capture enzyme-linked immunosorbent assay, antigen-capture detection tests, serum neutralization test, reverse transcriptase polymerase chain reaction assay, electron microscopy, and Virus isolation by cell culture. 

Although no vaccines or antiviral treatments are approved to treat the Virus, supportive care, rehydration with oral or intravenous fluids, and treatment of specific symptoms improve survival. A range of potential treatments are being evaluated, including blood products, immune therapies, and drug therapies.

This is the first time that Equatorial Guinea has reported an outbreak of Marburg Virus Disease, and the World Health Organization assesses that the country's capacity to manage the outbreak is insufficient. The most recently reported outbreak of Marburg Virus Disease was in Ghana in 2022 (three confirmed cases). Other Marburg Virus Disease outbreaks have been previously reported in Guinea (2021), Uganda (2017, 2014, 2012, 2007), Angola (2004-2005), the Democratic Republic of the Congo (1998 and 2000), Kenya (1990, 1987, 1980) and South Africa (1975).

Based on available information, all nine deceased cases were in contact with a relative with the same symptoms or participated in a burial of a person with symptoms compatible with Marburg Virus Disease. At this stage it cannot be ruled out that all Marburg Virus Disease cases have been identified, therefore there could be transmission chains that have not been tracked. To date, most of the contacts of the nine deceased cases have not been identified.

It should also be noted that with the exception of one case who died in a health facility, the other eight died in the community and their burial conditions are unknown.

Cross-border population movements are frequent, and the borders are very porous, between Ebebiyin and Nsock Nsomo districts (Equatorial Guinea), Cameroon and Gabon. This constitutes a risk of cross-border spread. Considering the above described scenario, the risk is considered high at the national level, moderate at the regional level and low at the global level.

Marburg Virus Disease outbreak control relies on using a range of interventions, namely case management, surveillance including contact tracing, a good laboratory service, infection prevention and control including safe and dignified burials, and social mobilization. Community engagement is key to successfully controlling Marburg Virus Disease outbreaks. Raising awareness of risk factors for Marburg infection and protective measures that individuals can take is an effective way to reduce Human transmission.

Communities affected by Marburg should make efforts to ensure that the population is well informed, both about the nature of the disease itself and about necessary outbreak containment measures.

Outbreak containment measures include prompt, safe and dignified burial of the deceased cases, identifying people who may have been in contact with someone infected with Marburg and monitoring their health for 21 days, isolating and providing care to confirmed patients and maintaining good hygiene and a clean environment.

Healthcare workers caring for patients with or suspected of Marburg Virus Disease should apply additional infection control measures in addition to standard precautions to avoid contact with patients’ blood and body fluids and with surfaces and objects contaminated.

The World Health Organization recommends that male survivors of Marburg Virus Disease practice safer sex and hygiene for 12 months from onset of symptoms or until their semen twice tests negative for Marburg Virus. Contact with body fluids should be avoided and washing with soap and water is recommended. The World Health Organization does not recommend isolation of male or female convalescent patients whose blood has tested negative for Marburg Virus, nor the implementation of any restrictions on travel and/or trade to Equatorial Guinea based on available information for the current outbreak.

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Sharp rise in the number of Dengue Fever cases reported in Rohingya Refugee Camps in the Cox's Bazar District of Bangladesh.

Rohingya Refugee Camps in the Cox's Bazaar District of Bangladesh are experiencing an acute surge in dengue cases as compared to the previous four years (2018 to 2021), according to a press release issued by the World Health Organization on 3 August 2022. As of 24 July, a total of 7687 confirmed cases and 6 deaths have been reported in 2022, with 93% (7178) of the cumulative number of cases being reported since the start of the surge at the end of May. Dengue is endemic in Bangladesh, but a similar surge has not been observed in the larger Cox’s Bazar district outside of the Rohingya Refugee Camps nor at the national level with case numbers and trends within expected levels of incidence for the same period. As dengue is recurrent in this part of the country, the population may be at risk of secondary infection, which puts them at higher risk for severe disease.

Rapid diagnostic test-confirmed cases of Dengue Fever in Rohingya Refugee Camps in Cox’s Bazar District, Bangladesh by notification date, 1 January 2018 to 24 July 2022. World Health Organization.

From 1 January to 24 July 2022, a total of 7687 cases of Dengue, confirmed by rapid diagnostic test (RDT), and six deaths (case fatality rate, 0.08%) have been reported from the  Rohingya Refugee Camps in the Ukhia Upazila and Teknaf Upazila (sub-districts) of Cox’s Bazar, with the former sub-district being the most affected of the two. An acute surge of cases began during the week commencing 23 May, and peaked the week ending 26 June, with 93% (7178) of the cumulative number of cases being reported between 23 May and 24 July. A decreasing trend in reported Dengue cases was observed following the peak.

Cases of reported Dengue in  Rohingya Refugee Camps are significantly higher as compared to similar periods over the past four years; 2018 (4 cases), 2019 (7 cases), 2020 (3 cases), and 2021 (1530 cases and 3 deaths with a surge from October to December).  However, at a national level and in the larger Cox’s Bazar district, case numbers have been within expected endemic levels of incidence; by comparison to the Dengue case from the camps, the larger Cox’s Bazar district reported approximately 121 cases from 1 January to the end of June.

Camps located in Ukhia Upazila are predominantly affected by the outbreak. Camp 3 accounted for over 50% of all reported cases and Camps 4 and 1W each account for less than 10% of cases as of 24 July 2022. More than two-thirds of cases (67%) were among persons 15 years and older with males accounting for 60% of cases. The majority of cases (81%) were hemodynamically stable, i.e. not showing any warning signs for Severe Dengue Syndrome (such as Dengue Hemorrhagic Fever or Dengue Shock Syndrome) nor having any coexisting conditions, while approximately 15% of cases were mild and required observation and admission to primary health facilities. Severe Dengue with signs of Dengue Hemorrhagic Fever and Dengue Shock Syndrome was observed in 0.3% of cases and required admission to Cox’s Bazar District Hospital located within the camp. Among patients admitted to the hospital, 1% required blood transfusion. Previous Dengue infection was reported in 1% of current cases.

Serotyping results from 10 samples processed at the Institute of Epidemiology, Disease Control and Research reference laboratory in the capital Dhaka identified Dengue Fever Virus-3 (5 samples) and Dengue Fever Virus-2 (3 samples). Two samples had inconclusive results.

Dengue is endemic in Bangladesh with recurrent outbreaks. The Rohingya Refugee Camps in Cox’s Bazar district previously experienced an acute Dengue outbreak from October to December 2021 during which 1530 cases, including 3 deaths, were reported. Case numbers began to decline at the beginning of 2022, and by the end of February, the event was under control until the resurgence of cases in May 2022.

Dengue is a viral infection transmitted to humans through the bite of infected Mosquitoes and is found in tropical and sub-tropical climates worldwide, mostly in urban and semi-urban areas. The primary vectors that transmit the disease are Aedes aegypti mosquitoes and, to a lesser extent, Aedes albopictus.  These mosquitoes are also vectors of Chikungunya, Yellow Fever and Zika viruses. Dengue is widespread throughout the tropics, with local variations in risk influenced by climate parameters as well as social and environmental factors.

Dengue causes a wide spectrum of disease. This can range from subclinical disease (people may not know they are even infected) to severe flu-like symptoms in those infected. Although less common, some people develop Severe Dengue, which can be any number of complications associated with severe bleeding, organ impairment and/or plasma leakage. Severe Dengue has a higher risk of death when not managed appropriately. Severe Dengue was first recognised in the 1950s during Dengue epidemics in the Philippines and Thailand. Today, Severe Dengue affects most Asian and Latin American countries and has become a leading cause of hospitalisation and death among children and adults in these regions.

Dengue is caused by a Virus of the Flaviviridae family and there are four distinct, but closely related, serotypes of the Virus that cause Dengue (Dengue Fever Virus-1, Dengue Fever Virus-2, Dengue Fever Virus-3 and Dengue Fever Virus-4). Recovery from infection is believed to provide lifelong immunity against that serotype. However, cross-immunity to the other serotypes after recovery is only partial, and temporary. Subsequent infections (secondary infection) by other serotypes increase the risk of developing Severe Dengue.

A transmission electron micrograph showing Dengue Virus virions (the cluster of dark dots near the centre). Centers for Disease Control and Prevention/Wikimedia Commons.

Dengue has distinct epidemiological patterns, associated with the four serotypes of the Virus. These can co-circulate within a region, and indeed many countries are hyper-endemic for all four serotypes. Dengue has an alarming impact on both human health and the global and national economies. Dengue Fever Virus is frequently transported from one place to another by infected travellers; when susceptible vectors are present in these new areas, there is the potential for local transmission to be established.

The incidence of Dengue has grown dramatically around the world in recent decades. A vast majority of cases are asymptomatic or mild and self-managed, and hence the actual numbers of dengue cases are under-reported. Many cases are also misdiagnosed as other febrile illnesses

One modelling estimate indicates 390 million Dengue Virus infections per year, of which 96 million manifest clinically (with any severity of disease). Another study on the prevalence of dengue estimates that 3.9 billion people are at risk of infection with dengue viruses. Despite a risk of infection existing in 129 countries, 70% of the actual burden is in Asia.

The number of dengue cases reported to the World Health Organization increased over 8 fold over the last two decades, from 505 430 cases in 2000, to over 2.4 million in 2010, and 5.2 million in 2019. Reported deaths between the year 2000 and 2015 increased from 960 to 4032, affecting mostly younger age group. The total number of cases seemingly decreased during years 2020 and 2021, as well as for reported deaths. However, the data is not yet complete and COVID-19 pandemic might have also hampered case reporting in several countries.

The overall alarming increase in case numbers over the last two decades is partly explained by a change in national practices to record and report Dengue to the Ministries of Health, and to the World Health Organization. But it also represents government recognition of the burden, and therefore the pertinence to report Dengue disease burden.

Before 1970, only 9 countries had experienced Severe Dengue epidemics. The disease is now endemic in more than 100 countries in the World Health Organization regions of Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific. The Americas, South-East Asia and Western Pacific regions are the most seriously affected, with Asia representing about 70% of the global burden of disease.

Not only is the number of cases increasing as the disease spreads to new areas including Europe, but explosive outbreaks are occurring. The threat of a possible outbreak of Dengue now exists in Europe; local transmission was reported for the first time in France and Croatia in 2010 and imported cases were detected in 3 other European countries. In 2012, an outbreak of Dengue on the Madeira islands of Portugal resulted in over 2000 cases and imported cases were detected in mainland Portugal and 10 other countries in Europe. Autochthonous cases are now observed on an annual basis in few European countries.

The largest number of dengue cases ever reported globally was in 2019. All regions were affected, and Dengue transmission was recorded in Afghanistan for the first time. The American region alone reported 3.1 million cases, with more than 25 000 classified as severe. Despite this alarming number of cases, deaths associated with Dengue were fewer than in the previous year. High number of cases were reported in Bangladesh (101 000), Malaysia (131 000) Philippines (420 000), Vietnam (320 000) in Asia.

In 2020, Dengue affected several countries, with reports of increases in the numbers of cases in Bangladesh, Brazil, Cook Islands, Ecuador, India, Indonesia, Maldives, Mauritania, Mayotte (France), Nepal, Singapore, Sri Lanka, Sudan, Thailand, Timor-Leste and Yemen. Dengue continues to affect Brazil, India, Vietnam, the Philippines, Cook Islands, Colombia, Fiji, Kenya, Paraguay, Peru and, Reunion islands, in 2021. 

The COVID-19 pandemic is placing immense pressure on health care and management systems worldwide. The World Health Organization has emphasised the importance of sustaining efforts to prevent, detect and treat vector-borne diseases during this pandemic such as Dengue and other Arboviral diseases, as case numbers increase in several countries and place urban populations at highest risk for both diseases. The combined impact of the COVID-19 and dengue epidemics could have devastating consequences on the populations at risk.

The virus is transmitted to humans through the bites of infected female Mosquitoes, primarily the Aedes aegypti Mosquito. Other species within the Aedes genus can also act as vectors, but their contribution is secondary to Aedes aegypti.

After feeding on an Dengue Fever Virus-infected person, the virus replicates in the Mosquito midgut, before it disseminates to secondary tissues, including the salivary glands. The time it takes from ingesting the Virus to actual transmission to a new host is termed the extrinsic incubation period. The extrinsic incubation period takes about 8-12 days when the ambient temperature is between 25-28°C. Variations in the extrinsic incubation period are not only influenced by ambient temperature; a number of factors such as the magnitude of daily temperature fluctuations, Virus genotype, and initial viral concentration, can also alter the time it takes for a Mosquito to transmit Virus. Once infectious, the Mosquito is capable of transmitting Virus for the rest of its life.

Mosquitoes can become infected from people who are viremic with Dengue Fever Virus. This can be someone who has a symptomatic Dengue infection, someone who is yet to have a symptomatic infection (they are pre-symptomatic), but also people who show no signs of illness as well (they are asymptomatic).

Human-to-Mosquito transmission can occur up to 2 days before someone shows symptoms of the illness, up to 2 days after the fever has resolved. Risk of Mosquito infection is positively associated with high viremia and high fever in the patient; conversely, high levels of Dengue Fever Virus-specific antibodies are associated with a decreased risk of Mosquito infection. Most people are viremic for about 4-5 days, but viremia can last as long as 12 days.

The primary mode of transmission of Dengue Fever Virus between Humans involves Mosquito vectors. There is evidence however, of the possibility of maternal transmission (from a pregnant mother to her baby). While vertical transmission rates appear low, with the risk of vertical transmission seemingly linked to the timing of the Dengue infection during the pregnancy. When a mother does have a Dengue Fever Virus infection when she is pregnant, babies may suffer from pre-term birth, low birthweight, and fetal distress.

Rare cases of transmission via blood products, organ donation and transfusions have been recorded. Similarly, transovarial transmission (i.e. the transmission of the Virus from a female Mosquito to her young) of the Virus within Mosquitoes have also been recorded. 

The Aedes aegypti mosquito is considered the primary vector of Dengue Fever Virus. It could breed in natural containers such as tree holes and Bromeliads, but nowadays it has well adapted to urban habitats and breeds mostly in man-made containers including buckets, mud pots, discarded containers and used tyres, storm water drains etc., thus making Dengue an insidious disease in densely populated urban centres. Aedes aegypti is a day-time feeder; its peak biting periods are early in the morning and in the evening before sunset. Female Aedes aegypti frequently feed multiple times between each egg-laying period leading to clusters of infected individuals. Once a female has laid her eggs, these eggs can remain viable for several months in dry condition, and will hatch when they are in contact with water.

Colour print of the Dengue Mosquito Aedes aegypti (then called Stegomyia fasciata, today also Stegomyia aegypti). To the left, the male, in the middle and on the right, the female. Above left, a flying pair in copula. Emil August Goeldi (1905)/Wikimedia Commons.

Aedes albopictus, a secondary Dengue vector and, has spread to more than 32 states in the USA, and more than 25 countries in the European Region, largely due to the international trade in used tyres (a breeding habitat) and other goods (e.g. lucky Bamboo). It favours breeding sites close to dense vegetation including plantations which is linked to increased risk of exposure for rural workers such as those in Rubber and Palm Oil plantation, but it is also found to be established abundantly in urban areas. Aedes albopictus is highly adaptive. Its geographical spread is largely due to its tolerance of colder conditions, as an egg and adult. Similar to Aedes aegypti, Aedes albopictus is also a day biter and it has been implicated as the primary vector of Dengue Fever Virus in a limited number of outbreak, where Aedes aegypti is either not present, or present in low numbers.

While majority of Dengue cases are asymptomatic or show mild symptoms, it can manifest as a severe, flu-like illness that affects infants, young children and adults, but seldom causes death. Symptoms usually last for 2–7 days, after an incubation period of 4–10 days after the bite from an infected Mosquito. The World Health Organization classifies Dengue into 2 major categories: Dengue (with or without warning signs) and Severe Dengue. The sub-classification of Dengue with or without warning signs is designed to help health practitioners triage patients for hospital admission, ensuring close observation, and to minimise the risk of developing Severe Dengue.

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