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Dengue fever: a decade of burden in Iran


Introduction

Since the primary traveler case of dengue was reported in Tehran in 2008, Dengue virus (DENV) has regularly unfold all through Iran, with a steady improve in reported instances (1). As a mosquito-borne flavivirus transmitted by Aedes (Stegomyia) aegypti and Ae. (Stegomyia) albopictus mosquitoes, DENV shares its vectors with different notable viruses corresponding to chikungunya (CHIKV), Zika (ZIKV), and yellow fever (2). DENV has 4 serotypes (DENV-1 to DENV-4), every with distinct genotypes. DENV-2, ceaselessly related to extreme infections and epidemics, consists of six genotypes: Asian/American, Asian I, Asian II, Cosmopolitan, American, and sylvatic (3).

Dengue fever presents a variety of medical manifestations, from asymptomatic infections to gentle flu-like syndromes, dengue fever (DF), and extreme dengue illness (SDD), encompassing dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (4). Neurological issues might embody encephalopathy, encephalitis, seizures, intracranial hemorrhage, and Guillain-Barré syndrome (GBS) (5). With a 2.5% mortality price, dengue poses a major international well being concern, with the World Health Organization reporting an 8-fold improve in instances between 2000 and 2019 (from 505,430 to five.2 million) (6). In 2023, a worldwide resurgence was noticed, characterised by a marked rise in outbreaks in beforehand unaffected areas. Climate change-induced mosquito inhabitants progress is predicted to additional increase dengue-endemic areas and improve the at-risk inhabitants (7). One dengue vaccine, Dengvaxia®, is authorised within the United States for people aged 9–16 with a historical past of dengue an infection residing in high-risk areas (8, 9).

Epidemiological trajectories of Dengue virus in Iran

Dengue fever has change into a major public well being concern in Iran since 2008, following the affirmation of the primary case in a 58-year-old girl from Tehran with a journey historical past to Malaysia (1). Subsequent investigations revealed a gradual unfold of the Dengue virus (DENV) throughout the nation, elevating questions in regards to the epidemiological trajectories of this mosquito-borne flavivirus. A retrospective examine performed on 300 beforehand collected samples (2000–2012), primarily from the Sistan and Baluchistan province, detected 15 (5%) optimistic instances via serology and three (1%) optimistic instances via serology plus polymerase chain response (PCR) for DF. Notably, 7 (46.7%) of the 15 seropositive instances had no journey historical past outdoors Iran, with six originating from Sistan and Baluchestan, a area adjoining to Pakistan with a hot-dry local weather conducive to Aedes mosquito emergence (10). Further proof of DENV circulation emerged from Chabahar (2013), the place 30 out of 540 samples examined optimistic, and 11 had been equivocal for DENV IgG antibodies utilizing the ELISA methodology (11). Additionally, a 32-year-old girl with a current journey historical past to India was recognized with DENV in October 2015, highlighting the position of worldwide journey in illness transmission (12). In Zahedan (2013–2015), a examine involving 60 sufferers revealed proof of previous or current DENV publicity in 13 people, with IgM antibodies detected in 6.5% of sufferers (13). Notably, none of those sufferers had a journey historical past outdoors Iran, emphasizing the potential for native DENV transmission (13). A case report from 2016 documented a 39-year-old girl with a journey historical past to Malaysia being recognized with DENV in Sabzevar metropolis (14). Further proof of DENV circulation was present in a examine performed between December 2016 and November 2017 on the National Measles Laboratory in Tehran, the place 82 out of 1,306 examined sera had been dengue seropositive (15) (Table 1).

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Table 1. Summary of printed articles reporting DENV in Iran.

Recently, the Ministry of Health and Medical Education in Iran reported 137 dengue fever instances from 15 May to 10 July 2024. Only one affected person succumbed to the an infection, with most contaminated sufferers having a journey historical past to endemic international locations corresponding to Pakistan, the United Arab Emirates, Oman, and West Africa (Benin). Notably, twelve sufferers from Bandar Lengeh, Hormozgan Province, had no journey historical past to overseas international locations, indicating the presence of mosquito vectors in Iran (16).

The rise of Dengue virus endemic in Iran: Sistan and Baluchistan province on the forefront

Located within the southeastern area of Iran, Sistan and Baluchistan province has witnessed a surge in Dengue virus (DENV) endemic instances, positioning itself as a focus within the nation (13) (Figure 1). This improvement is a results of numerous elements working collectively, such because the province’s geographical place, the presence of Aedes mosquito vectors, the area’s local weather, and its worldwide commerce connections.

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Figure 1. Epidemiology of dengue in Iran. (A) The map exhibits cumulative dengue instances (ELISA-confirmed) in Iran from 2008 to 2024. (B) Annual reported seropositive dengue instances (ELISA-confirmed) in Iran from 2008 to 2024.

One main contributing issue to the unfold of DENV in Sistan and Baluchistan is its geographical proximity to Pakistan, a rustic additionally coping with DF endemics. The shared border between Iran and Pakistan permits for the attainable motion of contaminated people throughout the border, heightening the chance of DENV transmission within the province. A examine showcased this connection, with 46.7% of 15 seropositive instances having no journey historical past outdoors Iran, and 6 instances originating from Sistan and Baluchestan province (10).

Another contributor to the potential for DENV transmission in Iran is the presence of Aedes mosquito vectors, significantly Aedes albopictus and Aedes aegypti. Ae. albopictus was first reported in Chabahar, Sistan and Baluchestan Province, whereas Ae. aegypti was noticed in Bandar Lengeh, Hormozgan Province (17, 18). Although the institution of those Aedes mosquito species in Iran stays unconfirmed, continued monitoring and surveillance are needed because of the predicted chance of their presence in studied space based mostly on modeling. It seems that these species haven’t but tailored to the weather conditions of those areas (19, 20).

Additionally, local weather change projections point out that northern and southern areas of Iran, together with Sistan and Baluchistan, are extra vulnerable to DENV transmission attributable to favorable weather conditions for mosquito vectors (21). Studies performed in Iran have proven the next prevalence of Ae. albopictus within the southern areas of Sistan and Baluchestan Province (17, 22). This highlights the significance of incorporating local weather information into public well being methods to counteract the impression of local weather change on illness dynamics.

International commerce, significantly maritime transportation, additionally considerably influences the potential unfold of DENV and its vectors. Shipping containers and vessels might function excellent habitats for Aedes mosquitoes, permitting them to disperse to new areas (23). With Sistan and Baluchistan strategically situated alongside worldwide commerce routes, common and correct monitoring of entomological exercise at these entry factors is essential to attenuate the danger of DENV and its vectors being launched and unfold (24).

Preliminary genomic surveillance of Dengue virus in Iran

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Figure 2. A neighbor-net community evaluation was performed to look at the phylogenetic relationships amongst DENV-1 genotypes, utilizing partial nucleotide sequences of the capsid and premembrane genes (511 nucleotides) from numerous DENV strains. The standardized DENV pressure nomenclature and corresponding GenBank accession numbers are offered for every sequence included within the evaluation. DENV strains from Iran are highlighted in daring inside the community (31).

Seroprevalence, extreme manifestations, and deaths brought on by Dengue virus

While a complete systematic overview assessing the seroprevalence of DENV throughout Iran has but to be performed, a number of current research present helpful insights into the prevalence of DENV antibodies in particular areas and populations. One large-scale examine performed from September 2017 to June 2018 collected 1,257 serum samples from six provinces: Bushehr, Hormozgan, Sistan and Baluchestan, Khuzestan (southern areas), and Gilan and Mazandaran (northern areas). The examine included sufferers aged 15 years or older with a earlier historical past of fever, headache, physique ache, arthralgia, or rash sickness. Using Euroimmune ELISA kits, 74 (5.9%) serum samples had been discovered reactive for DENV IgG antibodies, with optimistic instances recognized primarily within the southern areas of Khuzestan and Bushehr (32). In one other examine, investigators examined the seroprevalence of DENV in 60 suspected sufferers from southeastern Iran. The outcomes confirmed that IgG antibodies had been detected in 5% (3 sufferers) of the cohort (13). Although a nationwide systematic overview of DENV seroprevalence continues to be wanted to achieve an entire understanding of the illness burden in Iran, these research spotlight the presence of DENV publicity in numerous areas and emphasize the significance of continued surveillance and focused interventions. Further analysis is warranted to observe the altering epidemiology of DENV in Iran and inform public well being insurance policies to mitigate the unfold of the virus.

Dengue fever, as outlined by the World Health Organization (WHO), is an acute febrile sickness lasting 2–7 days, usually presenting with a minimum of two of the next manifestations: headache, retro-orbital ache, myalgia, arthralgia, rash, hemorrhagic manifestation, and leukopenia (33). Iranian sufferers exhibit a variety of extreme manifestations that require cautious monitoring and administration. Leukopenia and thrombocytopenia have been recognized as the most typical laboratory abnormalities in Iranian sufferers with dengue fever (1, 14, 34). While these sufferers usually obtain supportive care, together with fluid resuscitation, electrolyte substitute, and transfusions when needed, you will need to observe that antiviral remedy is just not routinely administered in these instances. Fortunately, regardless of the severity of signs, intensive care has not been required for a lot of the sufferers in query (13). The medical course of dengue fever in Iranian sufferers is usually characterised by excessive fever, with temperatures as much as 38°C. Additional signs embody headache, gentle rash, bodily ache, nausea, lethargy, vomiting blood, and bone ache. Myalgia, particularly, has been reported with a severity rating of 6–7 out of 10 in some instances (13, 14). The vary of signs related to DENV infections highlights the significance of immediate analysis and acceptable supportive care to stop issues and guarantee optimum affected person outcomes.

DSS, a extreme type of dengue characterised by hemorrhagic fever and circulatory failure, is related to considerably excessive mortality charges. According to international estimates, roughly 390 million dengue infections and 96 million symptomatic instances happen yearly, together with over 2 million instances of DHF and round 15,000 deaths (35). The case-fatality price of DHF is round 5%, with the World Health Organization estimating greater than 20,000 deaths every year (36, 37). In Southeast Asia, the estimated lifetime variety of dengue infections per individual is round 3.3, with an general annual an infection price of 5%. This price is increased amongst youngsters underneath 15 (12.5%) in comparison with adults (2.8%) (38). Although there’s restricted rigorous proof on the mortality price of DENV in Iran, sporadic deaths have been reported through the years, emphasizing the necessity for continued surveillance and analysis to higher perceive the illness’s burden and enhance prevention methods within the nation.

Dengue virus in Iran: a name for motion

Conclusion

Addressing the danger of dengue epidemics in Iran is essential, given the institution of Ae. aegypti in southern Iran and dengue outbreaks in neighboring international locations. Since no efficient vaccine or particular remedy exists, well being training and vector management are probably the most very important instruments for prevention and management. Educating healthcare staff is especially essential, as they’re answerable for illness prevention, management, and administration. Investing of their capability can enhance dengue case administration and the general healthcare system.

Data availability assertion

Author contributions

ZH: Writing – unique draft, Writing – overview & enhancing. FH: Visualization, Writing – unique draft. FM: Investigation, Writing – overview & enhancing. MZ: Conceptualization, Supervision, Writing – overview & enhancing.

Funding

Conflict of curiosity

Publisher’s observe

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