Infectious Diseases, Viruses

Alkhurma Hemorrhagic Fever (AHFV): The Lethal Disease No One’s Talking About

Author Chandana Balasubramanian , 11-Jan-2023

Alkhurma Hemorrhagic Fever Virus (AHFV) is spread by ticks  and causes life-threatening hemorrhagic fevers in humans. It belongs to the genus Flavivirus of the family Flaviviridae [1,2].     

 

AHFV is not contagious, and there is no evidence that it spreads from person to person. Currently, no treatment or vaccine is available to protect against AHFV [1].

 

Alkhurma HFV can lead to severe symptoms and fatal bleeding. It is similar to other viral hemorrhagic fevers like Dengue Hemorrhagic Fever (DHF), Crimean-Congo Hemorrhagic Fever (CCHFV), Ebola Hemorrhagic Fever (EHF), and Marburg Hemorrhagic Fever (MHF). Alkhurma HFV is characterized by severe clinical manifestations and can lead to a fatal hemorrhage. The case-fatality rate of the disease can be as high as 30% [3].

 

The World Health Organization (WHO) considers Alkhurma an emerging infectious disease, and more research is needed to understand this highly-fatal illness [4]. Since the disease is relatively rare and endemic to one region, Alkhurma is not a high priority for research in other parts of the world. This is understandable, considering that, so far, we have not seen it spread from person to person. It is also transmitted mainly by ticks local to the area. However, AHFV has a high fatality rate, has been identified in mosquitoes, and can mutate and become highly transmissible, like all viruses. 

 

While it may be impractical to label Alkhurma a top priority, public health officials across the globe must not dismiss it entirely. In this highly-connected world, an outbreak in one region can become a pandemic in a blink of an eye, causing widespread devastation (COVID-19 pandemic, anyone?). So, awareness and continued surveillance are necessary. 

 

It is essential to educate primary care practitioners to include patients’ travel histories during differential diagnoses. This vigilance can help curb outbreaks before they become full-fledged epidemics and pandemics.

History

 

AHFV was first isolated in 1995 in Jeddah, Saudi Arabia, from the blood samples of local butchers with hemorrhagic fever [1]. The butchers developed a high fever after slaughtering sheep. A broadly reactive flavivirus monoclonal antibody that reacts with dengue and other flaviviruses was used to confirm that the newly identified virus is a flavivirus [5].  

A flavivirus belongs to the family Flaviviridae. They are a group of single-strand, enveloped RNA viruses. They are mainly found in ticks, mosquitoes, and similar vectors, and occasionally, they infect humans. The AHFV virus has been isolated from Ornithodoros savignyi ticks found on camels in Saudi Arabia [6].  

Alkhurma Hemorrhagic fever was initially suspected to be CCHV but was later found to be a distinct variant of Kyasanur Forest Disease Virus (KFDV), a tick-borne virus s first reported in India [3]. Analysts indicate that AHFV must have diverged from KFDV some 700 years ago [1]. 

In 2001, the pathogen was referred to as the Alkhurma virus for the first time by Professor Tariq Ahmed Madani of King Abdulaziz University in Saudi Arabia. The name ‘Alkhurma’ comes from the town ‘Alkhurma’ in the Mecca region in Saudi, where the infected sheep were first sourced [3].

Epidemiology

 

The primary vector responsible for the spread of AHFV is Ornithodoros Savignyi ticks (also called Sand Tampan) [1]. Sand Tampans are prevalent in Africa, the Middle East, and India [3]. They are more active during the spring and summer seasons. This explains the reason behind the occurrence of AHFV outbreaks during these seasons [1]. O.savignyi attacks humans, camels, and other animals found resting under trees [6]. 

Alkhurma does not seem to prefer a certain age or gender. Risk factors seem directly related to the level of direct contact with animals. There is still much left to learn about this disease. 

AHFV is endemic to Saudi Arabia, Egypt, and the east coast of Africa, including Djibouti. Farmers, butchers, and people in close contact with livestock or domestic animals in these regions are at a higher risk of being exposed to ticks carrying the virus. 

Around eight cases were reported in Saudi Arabia between 2003 and 2007. During a major outbreak in the country’s Najran region between 2008 and 2009, about 70 cases of AHFV were reported.

Between 1995 and 2020, a total of around 604 cases were reported in Saudi Arabia alone. Najran remains one of the most affected regions in the country, accounting for about 74.3% of cases. It is followed by Jeddah and Makkah, which accounted for about 11.8% and 11.6% of cases, respectively.

Saudi Arabia remains one of the most affected countries in the world, accounting for about 58.1% of all confirmed cases. Other cases were reported from countries such as Djibouti, Egypt, and Yemen, where cattle rearing is more common.

In 2011, around 93 cases were reported across the globe – the highest number of cases to be reported in a year since it was discovered in 1995. The number of cases gradually came down after 2011. 

In Spring 2018, the country of Saudi Arabia was on high alert for an “Alkurma outbreak.’ However, it turned out that the media had misread communication from the country’s public health agency to healthcare workers, asking them to stay vigilant. In the end, only eight confirmed cases were reported, and there have been no more instances of the disease since then [3].

How is it spread?

 

AHFV is a zoonotic virus. There is no tangible evidence to say whether human-to-human transmission of AHFV is possible [1]. There is also no proof that the virus can be transmitted by consuming animal milk. 

What we do know is that AHFV can be transmitted by: 

  • Tick bites: When an infected tick bites a person. So far, AHFV has been shown to be spread by Ornithodoros Savignyi and hard-bodied ticks like Hyalomma dromedari [1]
  • Crushing infected ticks: When a person crushes an infected tick [2].   

 

Camels and sheep infected by AHFV do not show symptoms, but infected humans do.

Biology of the disease

 

The medical field is still learning about the pathogenesis of AHFV [3]. But, the virus’s replication cycle is quite similar to viral infections by other flaviviruses [1]. The virus attaches itself to a host cell using an envelope of proteins on its surface. Once it has attached, the virus injects its RNA into the host’s cells. Here, the virus’s genetic material hijacks the host cell machinery and begins to replicate. In the process, the host cell gets destroyed, and the virus continues to infect other cells. 

Viral infections like Alkhurma damage the body’s organs and tissues, including blood vessels, which leads to bleeding.

Symptoms

 

Alkhurma symptoms appear two to four days after viral exposure. They begin with:

  • High fever
  • Headache
  • Body and muscle aches
  • Diarrhea
  • Vomiting
  • Loss of appetite [1,6]
  • Trouble falling asleep
  • Cough
  • Bleeding – usually in the gums, nose, or gastrointestinal tract [7].

 

Within the first week of illness, patients exhibit the following clinical manifestations:

  • Decreased heart rate and blood pressure.
  • Abnormal blood chemistry with elevated liver enzymes, creatinine, phosphokinase, and blood urea nitrogen levels.
  • Reduction in eosinophils, neutrophils, and lymphocytes.

 

Neurological signs such as seizures, encephalitis (inflammation of the brain), and severe muscular weakness are seen in about 10% of patients [1].

Diagnosis

 

RT-PCR (Reverse transcription polymerase chain reaction) tests are one of the most effective diagnostic methods to detect the presence of AHFV in blood samples. They are quick, accurate, and capable of detecting viruses, even in samples with very low viral loads.

ELISA (enzyme-linked immunosorbent assay) is effective in detecting AHFV-specific antibodies in serum plasma or serum of humans. It is particularly effective in determining the serostatus (presence or absence of a serological marker in the blood) of a population in tick-infested areas [1].

Treatment

 

Treatment for Alkurma involves providing supportive care to ease the symptoms. This is because there are no antiviral drugs to cure the disease. The supportive care involves:

  • Keeping the patient hydrated through intravenous fluids, colloids, and electrolytes.
  • Ensuring that proper oxygen levels and blood pressure is maintained.
  • Treating any other complications that may arise depending on the severity of the disease [1,3]. 

Prevention

 

There is no vaccine to protect against AHFV. People living in (or visiting) tick-infested endemic areas should consider:

  • Applying tick repellents on their bodies
  • Avoiding close contact with livestock or domestic animals
  • Wearing long-sleeved clothing, full pants, and closed-toe shoes
  • Regularly checking themselves to see if there are any ticks attached to their clothes or bodies
  • Using tick collars and dipping livestock and pets in acaricides
  • Wearing protective gear when working with livestock or animals in slaughterhouses
  • Getting screened regularly for AHFV infection – especially those who work in farms and slaughterhouses
  • Having livestock and domestic animals regularly inspected [1,3].

 

Alkhurma is one of the lesser-known tick-borne diseases. Lyme disease is one of the most common diseases spread by ticks in the United States, the UK, and other European countries. Other diseases caused by ticks include tick-borne encephalitis, Colorado tick fever, Crimean-Congo hemorrhagic fever, Powassan fever, ehrlichiosis, babesiosis, and more. 

One of the challenges in preventing tick bites is that tick repellents were originally designed against mosquitoes. Mosquitoes move quickly, bite their victims, and fly away. This behavior is quite different from ticks that crawl around on their host, feed on them, and can stay for days. Recent advancements in this field in 2022 may help. 

Researchers from the University of Massachusetts developed ‘spatial repellants.’ This technology is meant to repel ticks from arriving at their preferred destination on the host. The repellants even altered the ticks’ behavior. Many of the ticks in the experiment moved more slowly and less efficiently [8]. While the research is still at an early stage, it offers promise for humans to minimize the spread of tick-borne diseases.

The GIDEON Difference

 

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References

[1] B. Bhatia, H. Feldmann, and A. Marzi, “Kyasanur Forest disease and Alkhurma hemorrhagic fever virus-two neglected zoonotic pathogens,” Microorganisms, vol. 8, no. 9, p. 1406, 2020. 

[2] CDC, “Transmission,” Centers for Disease Control and Prevention, 27-Feb-2019. [Online]. Available: https://www.cdc.gov/vhf/alkhurma/transmission/index.html 

[3] A. A. Abdulhaq, A. A. Hershan, K. Karunamoorthi, and H. M. Al-Mekhlafi, “Human Alkhumra hemorrhagic Fever: Emergence, history and epidemiological and clinical profiles,” Saudi J. Biol. Sci., vol. 29, no. 3, pp. 1900–1910, 2022.

[4] Communicable Diseases, “Crimean-Congo haemorrhagic fever, hantavirus and Alkhurma haemorrhagic fever, as emerging infectious diseases: report by the Secretariat,” Who.int, 04-Dec-2011. [Online]. Available: https://www.who.int/publications/i/item/10665-3127. [Accessed: 06-Dec-2022].

[5] Z. A. Memish et al., “Alkhurma viral hemorrhagic fever virus: proposed guidelines for detection, prevention, and control in Saudi Arabia,” PLoS Negl. Trop. Dis., vol. 6, no. 7, p. e1604, 2012.

[6] R. N. Charrel, S. Fagbo, G. Moureau, M. H. Alqahtani, S. Temmam, and X. de Lamballerie, “Alkhurma hemorrhagic fever virus in Ornithodoros savignyi ticks,” Emerg. Infect. Dis., vol. 13, no. 1, pp. 153–155, 2007.

[7] CDC, “Signs and symptoms,” Centers for Disease Control and Prevention, 27-Feb-2019. [Online]. Available: https://www.cdc.gov/vhf/alkhurma/symptoms/index.html 

[8] E. L. Siegel et al., “Spatial repellents transfluthrin and metofluthrin affect the behavior of Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis in an in vitro vertical climb assay,” PLoS One, vol. 17, no. 11, p. e0269150, 2022.

 

Author
Chandana Balasubramanian

Chandana Balasubramanian is an experienced healthcare executive who writes on the intersection of healthcare and technology. She is the President of Global Insight Advisory Network, and has a Masters degree in Biomedical Engineering from the University of Wisconsin-Madison, USA.

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