Two Middle East Respiratory Syndrome Coronavirus related deaths in Saudi Arabia in the last year.

From 13 September 2022 to 12 August 2023, three laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus, including two deaths, were reported to the World Health Organization by the Ministry of Health of the Kingdom of Saudi Arabia, according to a press release issued by the World Health Organization on 29 August 2023.  Close contacts for the three cases were followed up by the Ministry of Health, and no secondary cases were identified. The notification of these cases reiterates the need for global awareness of Middle East Respiratory Syndrome Coronavirus as the disease continues to pose a threat in countries where Middle East Respiratory Syndrome Coronavirus is circulating in Dromedary Camels, including those in the Middle East.  

Between 13 September 2022 to 12 August 2023, the Ministry of Health of the Kingdon of Saudi Arabia reported three additional cases of Middle East Respiratory Syndrome Coronavirus, with two associated deaths. The cases were reported from Riyadh, Aseer, and Makkah provinces. Laboratory confirmation of the cases was performed by real-time polymerase chain reaction.

Middle East Respiratory Syndrome Coronavirus cases reported by Kingdon of Saudi Arabia between 13 September 2022 and 12 August 2023. World Health Organization.

All three cases were non-health-care workers, who presented with fever, cough, and shortness of breath, and had comorbidities. Of the three cases, two had a history of contact with Dromedary Camels and all three cases had a history of consumption of raw Camel milk in the 14 days prior to the onset of symptoms. All three cases were male, and aged 42, 83, and 85 years respectively.

Since the first report of Middle East Respiratory Syndrome Coronavirus in the Kingdom of Saudi Arabia in 2012, human infections have been reported from 27 countries, in all six World Health Organization regions. Of the reported 2605 cases of Middle East Respiratory Syndrome Coronavirus, the majority cases (2196 cases or 84% the total) have been reported from the Kingdom of Saudi Arabia, including these newly reported cases. Of the 937 deaths reported from 27 countries, a total of 856 (91%) deaths have been reported from the Kingdom of Saudi Arabia, including the newly reported deaths.

Epidemic curve of Middle East Respiratory Syndrome Coronavirus cases and deaths reported in the Kingdom of Saudi Arabia between 2012 and 12 August 2023. World Health Organization.

Middle East Respiratory Syndrome is a viral respiratory infection caused by the Middle East Respiratory Syndrome Coronavirus, a form of positive sense single-strand RNA Virus. Approximately 36% of patients with Middle East Respiratory Syndrome have died, though this may be an overestimate of the true mortality rate, as mild cases of Middle East Respiratory Syndrome Coronavirus may be missed by existing surveillance systems, and the case fatality ratio is calculated based only on laboratory-confirmed cases.

Structure and genomic organization of a Middle East Respiratory Syndrome Coronavirus Viron. Bleibtreu et al. (2020). 

Humans are infected with Middle East Respiratory Syndrome Coronavirus from direct or indirect contact with Dromedary Camels, which are the natural host and zoonotic source of the Virus. Middle East Respiratory Syndrome Coronavirus has demonstrated the ability to transmit between Humans. So far, non-sustained Human-to-Human transmission has occurred among close contacts and in healthcare settings and outside of the healthcare setting, there has been limited Human-to-Human transmission.

Middle East Respiratory Syndrome Coronavirus infections range from showing no symptoms (asymptomatic) or mild respiratory symptoms, to severe acute respiratory disease and death. A typical presentation of Middle East Respiratory Syndrome disease is fever, cough, and shortness of breath. Pneumonia is a common finding, but not always present. Gastrointestinal symptoms, including diarrhoea, have also been reported. Severe illness can cause respiratory failure that requires mechanical ventilation and support in an intensive care unit. The virus appears to cause more severe disease in older people, persons with weakened immune systems, and those with comorbidities or chronic diseases such as renal disease, cancer, chronic lung disease, and diabetes.

No vaccine or specific treatment is currently available, although several Middle East Respiratory Syndrome Coronavirus-specific vaccines and therapeutics are in development. Treatment is supportive and based on the patient’s clinical condition and symptoms.

Follow-up of the close contacts was conducted for all three cases, and no secondary cases were identified. For the two cases reporting contact with camels, the Ministry of Agriculture was informed, and an investigation of camels was conducted. There are no treatments available for Middle East Respiratory Syndrome Coronavirus in animals. The identified positive camels were isolated until real-time polymerase chain reaction testing was negative.

From 13 September 2012 to 12 August 2023, the total number of laboratory-confirmed Middle East Respiratory Syndrome Coronavirus infection cases reported globally to the World Health Organization was 2605, with 937 associated deaths (a case fatality ratio of 36%). The majority of cases occurred in countries in the Arabian Peninsula, including 2196 cases with 856 related deaths (a case fatality ratio of 39%) in the Kingdom of Saudi Arabia. There has been one large outbreak outside of the Middle East, in the Republic of Korea, in May 2015, during which 186 laboratory-confirmed cases (185 in the Republic of Korea and 1 in China) and 38 deaths were reported. The index case in that outbreak had a travel history to the Middle East. The global number reflects the total number of laboratory-confirmed cases reported to the World Health Organization under the International Health Regulations (2005) or directly by Ministries of Health. The total number of deaths includes the deaths that the World Health Organization is aware of to date through follow-up with affected Member States. 

The World Health Organization expects that additional cases of Middle East Respiratory Syndrome Coronavirus infection will be reported from the Middle East and/or other countries where Middle East Respiratory Syndrome Coronavirus is circulating in Dromedaries, and that cases will continue to be exported to other countries by individuals who were exposed to the virus through contact with dromedaries or their products (for example, consumption of raw camel milk), or in a healthcare setting. the World Health Organization continues to monitor the epidemiological situation and conducts risk assessment based on the latest available information.  

The number of Middle East Respiratory Syndrome cases reported to the World Health Organization has substantially declined since the beginning of the COVID-19 pandemic. This is likely the result of epidemiological surveillance activities for COVID-19 being prioritized and the similar clinical picture of both diseases, resulting in reduced testing and detection of Middle East Respiratory Syndrome Coronavirus cases. The Ministry of Health of the Kingdom of Saudi Arabia is working to improve testing capacities for better detection of Middle East Respiratory Syndrome Coronavirus during the COVID-19 pandemic. In addition, measures taken during the COVID-19 pandemic to reduce the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (the causative agent of COVID-19, such as mask wearing, hand hygiene, physical distancing, improving ventilation of indoor spaces, respiratory etiquette, stay-at-home orders, reduced mobility, also likely reduced opportunities for onward human-to-human transmission of Middle East Respiratory Syndrome Coronavirus.

Based on the current situation and available information, the World Health Organization re-emphasizes the importance of strong surveillance by all Member States for acute respiratory infections, including Middle East Respiratory Syndrome Coronavirus, and to carefully review and investigate any unusual patterns. 

Human-to-human transmission of Middle East Respiratory Syndrome Coronavirus in healthcare settings has been associated with delays in recognizing the early symptoms of Middle East Respiratory Syndrome Coronavirus infection, slow triage of suspected cases, and delays in implementing infection, prevention, and control measures. Infection, prevention, and control measures are critical to prevent the possible spread of Middle East Respiratory Syndrome Coronavirus between people in healthcare facilities. Healthcare workers should always apply standard precautions consistently with all patients, at every interaction in healthcare settings. Droplet precautions should be added to the standard precautions when providing care to patients with symptoms of acute respiratory infection; contact precautions and eye protection should be added when caring for probable or confirmed cases of Middle East Respiratory Syndrome Coronavirus infection; airborne precautions should be applied when performing aerosol generating procedures or in settings where aerosol generating procedures are conducted. Early identification, case management and isolation of cases, quarantine of contacts, together with appropriate infection prevention and control measures in health care setting and public health awareness can prevent human-to-human transmission of Middle East Respiratory Syndrome Coronavirus. 

Middle East Respiratory Syndrome Coronavirus appears to cause more severe disease in people with underlying chronic medical conditions such as diabetes, renal failure, chronic lung disease, and immunocompromised persons. Therefore, people with these underlying medical conditions should avoid close contact with Animals, particularly Dromedaries, when visiting farms, markets, or barn areas where the Virus may be circulating. General hygiene measures, such as regular hand washing before and after touching Animals and avoiding contact with sick Animals, should be adhered to. 

Food hygiene practices should be observed. People should avoid drinking raw camel milk, camel urine or eating meat that has not been thoroughly cooked.  The consumption of raw or undercooked Animal products, including milk and meat, carries a high risk of infection from pathogens that may cause disease in Humans. Animal products that are processed appropriately through cooking or pasteurization are safe for consumption. Foods that have gone through these processes should be handled with care to avoid cross contamination with uncooked/unsafe foods. Camel meat and Camel milk are nutritious products that can continue to be consumed after cooking, pasteurization, or other thermal treatments.

The World Health Organization does not advise special screening at points of entry regarding this event, nor does it currently recommend the application of any travel or trade restrictions. 

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Sharp rise in the number of Dengue Fever cases in Bangladesh.

From 1 January to 7 August 2023, the Ministry of Health and Family Welfare of Bangladesh reported a total of 69 483 laboratory-confirmed Dengue Fever cases and 327 related deaths, with a case fatality rate of 0.47%, according to a press release issued by the World Health Organization on 11 August 2023. Of these, 63% of cases and 62% of the deaths were reported in the month of July 2023. Although dengue is endemic in Bangladesh, the current Dengue Fever surge is unusual in terms of seasonality and the early sharp increase in comparison to previous years, where the surge started around -late June. The case fatality rate so far this year is relatively high compared to previous years for the full-year period. The pre-monsoon Aedes survey shows that the density of Mosquitoes, and the number of potential hotspots is at the highest level in the past five years. 

The higher incidence of Dengue Fever is taking place in the context of an unusual episodic amount of rainfall, combined with high temperatures and high humidity, which have resulted in an increased Mosquito population throughout Bangladesh. 

Between 1 January and 7 August 2023, a total of 69 483 Dengue Fever cases including 327 related deaths (a case fatality rate of 0.47%) were reported by the Ministry of Health and Family Welfare. As of 30 June 2023, a total of 7978 cases and 47 deaths were reported, however, the cases started surging rapidly from late June and in the month of July alone 63% of cases (43 854) and 62% of deaths (204) were reported.

The number of cases and deaths are higher compared to similar periods in the past five years. Dengue Fever cases started to rise in May 2023 and have been continuing since then, and the peak is unlikely to have been reached. The reported number of Dengue Fever cases this year is the highest compared to the same periods recorded since 2000.

Number of Dengue Fever cases in Bangladesh (A) and deaths (B) reported by epidemic week from 2018 to 2023, as of 5 August (epidemiological week 31) 2023. World Health Organization.

Cases have been reported from all 64 districts of Bangladesh. Cases in Dhaka Division started to increase in epidemic week 17 (23-29 April 2023) and in all eight divisions since epidemic week 26 (25 June to 1 July 2023).  The most affected area in the Dhaka Division is Dhaka City, accounting for 52.8% of cases and 78.9% of deaths. Other affected divisions include Chattogram Division (13.2% of cases and 9.2% of deaths), Dhaka Division excluding Dhaka City (11.6% of cases and 2.8% of deaths), and Barisal Division (10.5% of cases and 4.3% of deaths). The Sylhet Division has the lowest number of cases (560) and no deaths reported so far.

As of 7 August 2023, the reported case fatality rate is 0.47%, which is higher compared to previous years. The overall case fatality rate is higher in females than in males (0.72% compared to 0.32%) with females having four times higher case fatality rate than males among those aged 21-40 years (0.71% compared to 0.18%). The older age group recorded a higher case fatality rate compared to the younger age group (1.87% in the age group over 60 years compared to 0.74% in the age group between 41 to 60 years and 0.34% in those aged 40 years and below).

Dengue cases, deaths, and case fatality rate in Bangladesh for 2018, 2019, 2021, 2022 and 2023. World Health Organization. 

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.

Dengue Fever Virus-2 was the predominant circulating serotype in Bangladesh until 2018, when it was replaced by Dengue Fever Virus-3, which has remained the predominant serotype since 2019.  However, Dengue Fever Virus-2 has been identified as the primary circulating serotype in the 2023 outbreak, and this may result in more severe Dengue Fever infections and hospitalizations as a result of a second infection with a heterologous (similar but not identical) serotype. Of the 66 serotyped samples in the month of June 2023, Dengue Fever Virus-2 comprised 51.5% of cases and Dengue Fever Virus-2 comprised 43.9%.

There is no specific treatment for Dengue Fever; however, the timely detection of cases, identifying any warning signs of severe dengue infection, and appropriate case management are key elements of care to lower case fatality rates to less than 1%.

Dengue Fever was first recorded in the 1960s in Bangladesh (then known as East Pakistan) and was known as 'Dacca Fever'. Since 2010 cases of Dengue Fever have appeared to coincide with the rainy season from May to September and higher temperatures. Bangladesh’s climate conditions are becoming more favourable for the transmission of Dengue Fever and other vector-borne diseases including Malaria and Chikungunya Virus due to excessive rainfall, waterlogging, flooding, rise in temperature and the unusual shifts in the country’s traditional seasons. 

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Neonatal Enterovirus infection leads to seven deaths in France.

France has reported an increase in cases of severe neonatal sepsis associated with the Echovirus-11 Enterovirus, according to a press release issued by the World Health Organization on 31 May 2023. A total of nine cases of neonatal sepsis with hepatic impairment and multi-organ failure were reported between July 2022 and April 2023 from four hospitals in three regions of France. As of 5 May 2023, seven cases have died and two were still hospitalized in neonatal unit.

The current increase in incidence and severity in neonates, associated with a recombinant lineage of Echovirus-11 that previously was not detected in France, and is considered unusual due to the extremely rapid deterioration and associated case fatality rate amongst the affected babies. 

Based on the limited information available, the World Health Organization assesses the public health risk for the general population to be low, despite the concerning nature of the increase.

Of the nine cases of severe neonatal sepsis reported, eight were preterm (born before 38 weeks of gestation). Four pairs of twins were affected and presented with late-onset neonatal sepsis (occurring after one week of birth to three months).

The cases were reported from four hospitals in three regions between July 2022 and April 2023. Of the nine reported cases, six were reported in 2022 (two cases each in July, October, and December) and three were reported in 2023 (one case in January and two cases in April).

All cases presented with one or more clinical signs less than seven days after birth, suggesting a mother-to-child transmission route. The clinical presentation of these cases was considered to be atypical due to their extremely rapid deterioration and the associated case fatality rate. As of 5 May 2023, seven cases have died and two were still hospitalized in the neonatal unit; their short-term prognosis is no longer threatened.

Enterovirus reverse transcription polymerase chain reaction testing of all nine cases (including blood samples, throat swabs, nasopharyngeal swabs, cerebrospinal fluid samples, and/or post-mortem biopsies) confirmed the presence of Enterovirus, typed as Echovirus-11. Echovirus-11 maternal infection was confirmed by reverse transcription polymerase chain reaction testing and enterovirus genotyping by analyzing blood samples from four out of five mothers. All tested mothers presented with gastrointestinal signs or fever within the three days before or at delivery.

Sequence analyses of all typed Enterovirus infections in 2022 showed the circulation of at least two lineages of recombinant origin, of which the predominant one included all the sequences associated with the nine cases together with sequences associated with non-neonatal or non-severe neonatal infections. Further genetic analyses are ongoing.

According to historical data from 2016 to 2021, Echovirus-11 represented 6.2% (3 of 48) of reported severe neonatal infections with known Enterovirus type while this proportion increased to 55% (11 of 20) in 2022.

Enteroviruses are a group of Viruses that can cause various infectious illnesses and are responsible for annual epidemics. Illness is usually mild but has been found to affect neonates differently and sometimes more severely than older children and adults. There are multiple transmission routes, particularly in the neonatal period, including intrapartum by exposure to maternal blood, secretions, and/or stool, or postnatally from close contacts with infected caregivers. Echovirus 11 is a positive-strand RNA Virus belonging to the Genus Enterovirus of the Family Picornaviridae.

Structure of an Echovirus. Wang et al. (2020).

Echovirus 11 infections can cause severe inflammatory illnesses in neonates, including severe acute hepatitis with coagulopathy. 

On 28 April 2023, the French National Reference Centre for Enteroviruses and Parechoviruses informed clinicians and virologists involved in the care of newborns, to reinforce the diagnosis and surveillance of Enterovirus infection in neonates with severe sepsis through a professional network. In particular, the message focused on what to do in newborns with a picture of severe sepsis of indeterminate aetiology to sensitize about the risk of transmission. Clinicians were invited to systematically consider Enterovirus infection in neonates with severe liver failure, enterocolitis, meningoencephalitis, or myocarditis. Close monitoring of liver function, cardiac function, neurological function, and risk of enterocolitis were recommended in neonates with severe neonatal sepsis of undetermined cause.  Clinicians were also invited to undertake an early notification of referral hospitals in order to discuss potential therapeutic options. The risk of maternal transmission of Echovirus 11 was raised and recommendations made to monitor the infant closely for at least 7 days if the mother was known to have had an infection before or during childbirth. Emphasis was placed on importance of collecting additional samples (blood, stool, and nasopharyngeal samples) in newborns and mothers for Enterovirus, as was the importance of genotyping Enterovirus-positive samples: Clinical virologists were invited to send Enterovirus-positive samples in a prospective manner, especially from patients presenting with severe clinical signs. Samples are sent to the National Reference Laboratories for genotyping and genome studies.

Continuous information sharing regarding this event among France and other Member States (through the European Non-Polio Enterovirus Network), the European Centre for Disease Prevention and Control and World Health Organization is ongoing. To date, no comparable increase of Echovirus 11 cases associated with neonatal sepsis has been observed in countries that have reported to the European Centre for Disease Prevention and Control (Belgium, Denmark, Netherlands, Norway, and Spain) in 2022 and 2023.

A review of the epidemiological data collected from 2016 to 2022 in France through routine surveillance of Enterovirus infections among hospitalized patients showed a significant increase in incidence and mortality for all severe neonatal infections associated with Echovirus 11, defined as infections with at least one organ failure and/or requiring admission to intensive care.

A total of 443 Enterovirus neonatal infections (severe and non-severe types) including seven deaths (a case fatality rate of 1.6%) were reported in France in 2022. Of these, 72% (317 cases) had a known Enterovirus type. Echovirus 11 was the predominant circulating Enterovirus type (all ages included) and was identified in 30.3% (96 of 317) of neonatal infections (severe and non-severe) with known Enterovirus type. It has been continuously detected since June 2022.

Of the reported neonatal infections in 2022, 4.5% (22 of 443) were classified as severe. Of these 20 had known Enterovirus types. Echovirus 11 represented 55% (11 of 20) of these cases as compared to 6.2% (3 of 48) of cases with known Enterovirus type out of the total reported severe neonatal infections (62 cases) between 2016 to 2021. 

In 2022, there were seven deaths (case fatality rate, a case fatality ratio of 1.6%) out of the cumulative 443 Enterovirus neonatal infections recorded in 2022 (six associated with Echovirus 11), compared to seven deaths (a case fatality ratio of 0.4%), out of 1774 neonatal infections from 2016 to 2021 (none associated with Echovirus 11). There have also been seven deaths so far in 2023.

Sequence analyses showed the circulation of at least two lineages of recombinant origin, of which the predominant one included all the sequences associated with the nine severe cases together with sequences associated with non-neonatal or non-severe neonatal infections. This new variant of Echovirus 11 had not been observed in France before July 2022, nor elsewhere based on available sequences on the GenBank database, as of 28 April 2023. As of 5 May 2023, Echovirus 11 sequences retrieved from samples collected in 2023 all belong to this predominant lineage. Although higher pathogenicity of this new lineage cannot be excluded, the severity of infections may also be explained by the young age, prematurity, and the absence of maternal immunity. Further analyses are warranted to delineate the characteristics of this recombinant Virus.

Based on the limited information available, the World Health Organization assesses the public health risk for the general population to be low. However, asymptomatic carriage and shedding of infectious Viruses are a feature of Enterovirus infection. Echovirus infection was confirmed in four out of five mothers by analyzing blood samples three days before or at delivery. There have been previous reports of severe Echovirus 11 infection in twin neonates, however, the observation of four sets of twins amongst nine cases is more than expected. As non-Polio Enterovirus infection is often not a notifiable disease in Member States, additional cases of severe neonatal Enterovirus infection may have gone undiagnosed and/or unreported.

Non-Polio Enteroviruses are common and distributed worldwide. Although infections often are asymptomatic, some may present with respiratory tract infections. Symptoms include fever, runny nose, and body weakness. These Viruses are also associated with occasional outbreaks in which an unusually high proportion of patients develop clinical disease, sometimes with serious and fatal consequences. The World Health Organization recommends that clinicians managing neonates and young infants presenting with circulatory shock should consider an underlying diagnosis of sepsis and perform appropriate diagnostic investigations, including testing for Enteroviruses.

The World Health organization further recommends that health and care workers working with samples suspicious of non-Polio Enteroviruses should be properly trained to collect, store, and transport various samples. If samples are referred domestically and/or internationally for confirmation, typing, or sequencing purposes, appropriate national and international regulations on the transport of infectious substances should be strictly followed. Laboratories that perform sequencing should consider sharing genetic sequence data through publicly accessible databases.

No specific antiviral therapy for Echovirus infection is available, and treatment focuses on preventing complications. Health facilities caring for neonate populations in France should familiarize themselves with the signs and symptoms of Enterovirus and maintain vigilance for potential healthcare-associated infection cases and outbreaks in wards providing neonatal care. 

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