Dengue Epidemics: Understanding its Outbreak in Nepal

Historically, the term "dengue" originates from the Swahili word "ka-dinga pepo," which refers to a "cramp-like seizure" caused by an evil spirit. The Spanish term "dengue," which describes the stride of a person experiencing severe bone pain, may have been the source of the Swahili word [1]. We now understand dengue is a viral illness caused by the dengue virus, which is a member of the Flaviviridae family. In the Jin Dynasty (265–420), dengue was first mentioned in a Chinese medical encyclopedia and it was described as a water toxin connected to flying insects. Dengue was first reported in Philadelphia in 1780. Benjamin Rush coined the name breakbone fever because of the severe muscle, bone, and muscle pain it can cause.

Dengue is a neglected mosquito-borne viral disease. It is transmitted from one person to another by the bite of infected female mosquitoes, particularly the Aedes species (Aedes aegypti or Aedes albopictus) (Figure 1). Aedes mosquitoes are primarily active during the daytime. Dengue viruses (DENV) belong to the family Flaviviridae and genus Flavivirus. Infection is caused by any one of four closely related dengue viruses (called serotypes). Dengue has four main serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. A person obtains lifelong immunity to the serotype that infect to them but a second infection with a different serotype might cause severe dengue. Most of the dengue infections are self-recovering [2]. On the other hand, a small percentage of patients may experience potentially fatal outcomes like acute dengue hemorrhagic fever, dengue shock syndrome, and multiple organ failure [3].

Figure 1. Adult Aedes aegypti and Aedes albopictus mosquitoes [4]

DENV is a positive single-stranded encapsulated RNA virus of about 11 kb. The genome is encoded a single open reading frame flanked by highly structured 5′ and 3′ untranslated regions (UTRs). Large stem loop structures are formed by the genome's 5′ and 3′ terminal RNA sequences. It is made up of seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), three structural protein genes that encode the nucleocapsid or core (C) protein, a membrane-associated (M) protein, and an enveloped (E) glycoprotein (Figure 2). Structural proteins are organized into virions together with the viral genome. The nonstructural proteins play important roles in viral RNA replication, virion assembly, and evasion of host immune response through their enzymatic activities or protein–protein interactions [5,6].

Figure 2. Structure of dengue virus genome [7].

Epidemiology of Dengue

Tropical and subtropical regions are home to a higher prevalence of DENV. Over the past 20 years, DENV has become worldwide, which presents a serious public health risk. Between 2000 and 2019, there was a ten-fold increase (500,000 to 5.2 million) in reported cases globally, according to data from the World Health Organization. 2019 saw an all-time high, with cases reported in 129 different nations. Following the COVID-19 pandemic, there was reduction in dengue cases between 2020 and 2021. More than five million cases and more than 5000 dengue-related deaths have been reported since the beginning of 2023 in over 80 nations [8].

The dengue virus is known to be prevalent in 10 of the 11 Member States of the WHO Southeast Asia region. Compared to past years, a number of nations, notably Thailand and Bangladesh, have reported a notable increase in dengue incidence in 2023 [8]. Specifically, the world's 30 most heavily endemic countries include India, Indonesia, Myanmar, Sri Lanka, and Thailand.

Dengue Outbreak in Nepal

Dengue is the most recently discovered infectious diseases in Nepal. In 2004, Chitwan district of Nepal reported its first dengue case in a Japanese travelers [9]. In 2006, nine districts of Terai regions had the first dengue outbreak with 32 dengue cases. In that year, all four DENV serotypes were reported [10]. During years 2007, 2008, and 2009, there were isolated DENV cases in four districts of the Terai region of Nepal, indicating that the disease remained dormant. In 2010, there was a major, nationwide dengue outbreak that resulted in 917 DENV cases and 5 fatalities [11]. The DENV-1 was responsible for the majority of the 2010 DENV outbreak (Table 1), which were recorded from six districts of Nepal. The disease was also first time reported from the capital city of Nepal (Kathmandu valley). Another significant dengue outbreak occurred in 2013, resulting in 686 cases in 25 districts in the nation. DENV-2 was responsible for the 2013 outbreak [12]. Dengue cases in Nepal expanded in 2014 from the country's highlands to its hill regions and DENV-2 is responsible for the outbreak.

 

Table 1. Year wise dengue serotypes and the death due to dengue in Nepal

 

The 2016 outbreak saw a substantial rise in incidence to 1527 as well as a wider distribution of the disease, even in mountain regions. Dengue serotype 1 and 2 is responsible for the dengue outbreak. When compared to 2016, the number of dengue cases increased by 38% in 2017 and were recorded from 28 districts [13]. Nepal saw the biggest dengue outbreak in its history in 2019, with 17,992 confirmed cases, six fatalities, and a geographic spread to 68 districts nationwide. In the year 2017 and 2019, DENV-2 was responsible for the outbreak [14]. During the COVID-19 pandemic period (2020–2021), dengue cases were substantial decline (530 and 540). The key factors that likely contributed to the decline in the number of dengue cases during the COVID-19 pandemic were the implementation of strict rules and restrictions on human movement [15]. Nepal experienced the biggest dengue outbreak on record in 2022. Reports of dengue cases have been received from all 77 districts across the nation. In all, 54,784 cases of dengue were reported. The nation's capital, Kathmandu, was found to be the most severely affected, with 14,376 cases of dengue and DENV1 and 3 was responsible for it [16]. In the year 2023, a total of 51,243 dengue cases were reported slightly lower than previous years. Every three years, dengue cases reached peaks and in the year 2010, 2013, 2016, 2019, and 2022, there was an increase in the dengue epidemics in different geographical areas (Figure 4).

Figure 4. Trend of dengue cases in Nepal from 2006 to 2023 (Data source: Epidemiology Disease Control Division, Ministry of Health and Population, Government of Nepal).

Over the past 20 years, there has been a noticeable rise in the number of dengue patients from lowlands to high altitudes and valleys. Furthermore, as time goes on, there are an increasing number of dengue infections and deaths associated to the disease. The possible reasons behind Nepal's dengue outbreaks are climate change, unplanned urbanization, water scarcity, increased human mobility, expansion of mosquitoes to higher altitudes, open border between India and Nepal, inefficient efforts of the government, gaps in the surveillance system.

Symptoms of Dengue Fever

Most dengue patients have mild or no symptoms and are self-limiting. It will improve in one to two weeks. Rarely, dengue can be severe and lead to death. In most cases, symptoms appear 4–10 days after infection and persist for 2–7 days. Those who have had dengue may have fatigue for a few weeks following their recovery. Dengue shows the any of the following symptoms:

Figure 5. Patient showing dengue symptoms [17]

 

People who contract dengue virus for the second time are at greater risk of severe dengue. Symptoms appear after the fever has gone away. Individuals who exhibit the severe symptoms need to seek medical attention immediately. Following symptoms may appear to the patients.

  • Severe abdominal pain
  • Persistent vomiting
  • Rapid breathing
  • Bleeding gums or nose
  • Restlessness
  • Blood in vomit or stool
  • Being very thirsty
  • Pale and cold skin
  • Fatigue and feeling weak.

Treatment for Dengue Fever

The primary focus of dengue treatment is to relieve symptoms and manage complications. Dengue doesn't have a particular medication. Symptomatic treatment is commonly done. Here are some commonly recommended measures: Adequate rest and drinking plenty of fluids (water, oral rehydration solutions, and electrolyte-rich drinks) can help prevent dehydration.

Painkillers can be used at home to treat the majority of dengue fever cases. Paracetamol is often used to control pain and fever. Aspirin and ibuprofen should not be used as they cause the risk of bleeding. Regular monitoring of vital signs, such as temperature, blood pressure, and platelet count, is crucial for early detection of complications. It's important to seek medical attention if symptoms are worsened. Doctors can provide personalized advice based on specific condition of the patients.

Prevention and Control of Dengue Virus

  1. Eliminating mosquito breeding sites: Mosquitoes that carry the dengue virus flourish in stagnant water. Ensuring that the bins (flower vases, buckets, pet water bowls, unused tires etc.) are regularly empty.
  2. Using mosquito repellent: Applying mosquito repellent on exposed skin.
  3. Wearing protective clothing: When spending time outdoors, especially during peak mosquito activity times (early morning and late afternoon), it's a good idea to wear long-sleeved shirts, long pants, socks, and shoes to reduce exposed skin.
  4. Installing window and door nets: Keeping living spaces mosquito-free by installing nets on windows and doors.
  5. Enhancing public awareness: Increasing public knowledge about dengue prevention measures, symptoms, and available treatment options is essential. This can be achieved through educational campaigns, social media, and community engagement programs.
  6. Efficient surveillance and reporting systems: Developing a robust surveillance system to track dengue cases and identify high-risk areas can aid in targeted interventions. Prompt reporting and data sharing among healthcare facilities and local authorities can facilitate early detection and response.
  7. Improving healthcare infrastructure: Enhancing the capacity of healthcare facilities, especially in high-risk areas, by providing necessary resources and training healthcare professionals on dengue diagnosis and treatment can contribute to better patient management and outcomes.
  8. Collaboration and partnership: Encouraging collaboration among government agencies, healthcare organizations, non-governmental organizations, and communities can lead to a more coordinated and comprehensive approach in tackling dengue. Sharing resources, expertise, and best practices can help optimize efforts and achieve greater impact.
  9. Research and innovation: Investing in research to understand the local epidemiology and transmission patterns of dengue in Nepal can support evidence-based decision-making.

Conclusion

Considering the two-decade pattern of dengue epidemiology in Nepal, outbreaks are happening more regularly (almost every three years) and the number of dengue cases are rising. The keys to stopping future dengue epidemics are appropriate case management, sufficient research on dengue virus, mosquito control, development of vaccines, improved surveillance techniques, and community-based awareness campaigns.

References

  1. Hotta, S (1952). Experimental Studies on Dengue: I. Isolation, Identification and Modification of the Virus. J. Infect. Dis., 90, doi:10.1093/infdis/90.1.1.
  2. Bhatt, S, Gething, PW, Brady, OJ, Messina, JP, Farlow, AW, Moyes, CL, Drake, JM, Brownstein, JS, Hoen, AG, Sankoh, O, et al. (2013). The global distribution and burden of dengue. Nature, doi:10.1038/nature12060.
  3. Guidelines (1996). Dengue and dengue hemorrhagic fever in the Americas: guidelines for prevention and control.
  4. Okafor, II (2016). Zika Virus: The Emerging Global Health Challenge. Divers. Equal. Heal. Care, 13, doi:10.21767/2049-5471.100083.
  5. Nasar, S, Rashid, N, & Iftikhar, S (2020). Dengue proteins with their role in pathogenesis, and strategies for developing an effective anti-dengue treatment: A review. J. Med. Virol., 92.
  6. Li, Q, & Kang, C (2022). Structures and Dynamics of Dengue Virus Nonstructural Membrane Proteins. Membranes (Basel), 12.
  7. Nanaware, N, Banerjee, A, Bagchi, SM, Bagchi, P, & Mukherjee, A (2021). Dengue virus infection: A tale of viral exploitations and host responses. Viruses, 13.
  8. World Health Organization (2023). Disease Outbreak News; Dengue – Global situation Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON498;
  9. Pandey, BD, Rai, SK, Morita, K, & Kurane, I (2004). First case of Dengue virus infection in Nepal. Nepal Med. Coll. J.
  10. Malla, S, Thakur, GD, Shrestha, SK, Banjeree, MK, Thapa, LB. Gongal, G, Ghimire, P, Upadhyay, BP, Gautam, P, Khanal, S, et al. (2008). Identification of all dengue serotypes in Nepal. Emerg. Infect. Dis.
  11. Pandey, BD, Nabeshima, T, Pandey, K, Rajendra, SP, Shah, Y, Adhikari, BR, Gupta, G, Gautam, I, Tun, MMN, Uchida, R, et al. (2012-17). First isolation of dengue virus from the 2010 epidemic in Nepal. Trop. Med. Health 2013, doi:10.2149/tmh.
  12. Rijal, KR, Adhikari, B, Ghimire, B, Dhungel, B, Pyakurel, UR, Shah, P, Bastola, A, Lekhak, B, Banjara, MR, Pandey, BD, et al. (2021), Epidemiology of dengue virus infections in Nepal, 2006–2019. Infect. Dis. Poverty, 10, doi:10.1186/s40249-021-00837-0.
  13. Ngwe Tun, MM, Pandey, K, Nabeshima, T, Kyaw, AK, Adhikari, M, Raini, SK, Inoue, S, Dumre, SP, Pandey, BD, Morita, K (2021) An Outbreak of Dengue Virus Serotype 2 Cosmopolitan Genotype in Nepal, 2017. Viruses, 13, doi:10.3390/v13081444.
  14. Poudyal, P, Sharma, K, Dumre, SP, Bastola, A, Chalise, BS, Shrestha, B, Poudel, A, Giri, A, Bhandari, P, Shah, Y, et al. (2021). Molecular study of 2019 dengue fever outbreaks in Nepal. Trans. R. Soc. Trop. Med. Hyg.
  15. Pandey, BD, Ngwe Tun, MM, Pandey, K, Dumre, SP, Bhandari, P, Pyakurel, UR, Pokhrel, N, Dhimal, M, Gyanwali, P, Culleton, R, et al. (2022) Has COVID-19 suppressed dengue transmission in Nepal? Epidemiol. Infect. 150, e196, doi:10.1017/S0950268822001790.
  16. Rimal, S, Shrestha, S, Pandey, K, Nguyen, TV, Bhandari, P, Shah, Y, Acharya, D, Adhikari, N, Rijal, KR, Ghimire, P, et al. (2023). Co-Circulation of Dengue Virus Serotypes 1, 2, and 3 during the 2022 Dengue Outbreak in Nepal: A Cross-Sectional Study. Viruses, 15, doi:10.3390/v15020507.
  17. CDC Symptoms and Treatment | Dengue | CDC.

 

The Author: Dr Kishor Pandey is the Associate Professor at Central Department of Zoology, Tribhuvan University. He is also a visiting faculty of BSc & MSc Microbiology at KIST.

 

 

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