A few days ago, a friend called to inform me that one of his relatives was suffering from symptoms similar to the dengue virus. Since Nepal is witnessing the biggest ongoing dengue outbreak, laboratory testing was thus advised to confirm the virus. The patient tested negative for dengue, contrary to what was expected and tested negative again the second time. In fact, since the beginning of the 2022 dengue outbreak, dozens of patients with symptoms similar to dengue have tested negative for the virus, here dubbed as ‘Kathmandu Syndrome’. The emergence of such unidentified dengue-like illness or ‘Kathmandu Syndrome’ in Nepal is a matter of grave concern.

Dengue virus is transmitted by the bite of infected Aedes mosquitoes, namely Aedes aegypti and Aedes albopictus. Both Aedes mosquitoes are widespread in Kathmandu. The dengue virus symptoms appear four to 10 days after the infected mosquito bites. Fever, headache, pain behind the eyes, nausea/vomiting, joint/muscle pain, and rash are the common symptoms of dengue fever. Severe lower back pain, loose motion, chills/sweating, severe pain in the calf muscle, and difficulty falling asleep are some other remarkable symptoms found in patients with fever during the current dengue outbreak. Despite having these symptoms, many patients don’t test positive (NS1 antigen or IgM test) for the dengue virus. Nevertheless, a decrease in platelets and white blood cell count was found in those dengue-negative patients, usually found in patients with dengue fever. It raises questions about the cause of illness that is co-circulating with dengue-like symptoms in Kathmandu.

For the first time, in 2017, dengue-like illness among patients admitted for fever drew the attention of physicians working at Sukraraj Tropical and Infectious Disease Hospital. The patients were from Lalbandi, Sarlahi district. This means that dengue-like illness is not a new phenomenon in Nepal. Most recently, Pakistan reported several patients having symptoms similar to dengue virus or dengue-like illness, but showed negative results following dengue virus antigen (NS1) detection and polymerase chain reaction (PCR) tests. Likewise, India has also frequently reported dengue-like illness in the past. It shows that this mysterious illness is increasingly seen in South Asia and needs to be identified as early as possible.

A possible explanation for the emerging dengue-like illness might be due to mutations in the dengue virus and lack of testing of other mosquito-borne viruses such as chikungunya and zika which are also transmitted by Aedes Aegypti and Aedes Albopictus. The other contributing factors could be the introduction of new viruses similar to the dengue virus and the likelihood of false-negative results from testing kits. Genome sequencing can be a useful tool to address this issue. It was established during the Covid-19 pandemic in Nepal to identify or search for new variants/mutations of SARS-CoV-2. Chikungunya was first reported in 2013 in Nepal and has been reported annually during the monsoon or post-monsoon season. However, testing for the chikungunya virus has been discontinued for a couple of years; and hence, its presence or impact in Nepal is now unknown.

Chikungunya virus has very similar signs and symptoms to the acute phases of the dengue virus, such as fever, rash and particularly severe joint pain or body pain. Zika, another Aedes mosquito-borne virus, is not included or considered in routine testing or during dengue outbreaks. Zika virus is known to cause brain problems and a birth defect called microcephaly. Microcephaly is a condition where the size of a baby’s head is smaller when compared to babies of the same sex and age. In 2015, Brazil reported a large outbreak of zika virus infection, where between late 2015 and the end of 2017 a total of 18,282 suspected cases of microcephaly were recorded. India reported its first confirmed case of the zika virus in 2016. In 2021, an outbreak of the zika virus was reported in Uttar Pradesh, India.

Zika and dengue have similar symptoms like fever, rash, joint pain, headache, red eyes and malaise. In short, all these viruses are transmitted by the same mosquito and display similar signs and symptoms, but their disease outcomes or complications are different; hence, we need better surveillance to identify the viruses to mitigate and manage cases before they get out of hand.

There are four serotypes of dengue viruses, known as DEN-1, DEN-2, DEN-3 and DEN-4; all serotypes have already been reported in Nepal. In 2019, serotype DEN-2 was found to be responsible for the large dengue outbreak across the country. However, at the time of writing this article, the serotype responsible for the current 2022 dengue outbreak was not known and had not been announced officially. It is known that people who contract dengue infection for the second time with a different serotype suffer from severe dengue symptoms. Currently, doctors working at Sukraraj Tropical & Infectious Disease Hospital are observing patients with more severe dengue symptoms compared to previous outbreaks. An average of five to seven patients had experienced a sudden loss of consciousness during a hospital visit or at home.

Moreover, many patients visited Sukraraj Tropical & Infectious Disease Hospital's dengue clinic with complaints of bleeding gums, nosebleeds (epistaxis) and heavy periods. The current 2022 dengue outbreak reminds the situation that we faced during the Covid-19 second wave (delta wave), known for the worst Covid-19 wave in Nepal. As of October 10, 2022, a total of 33,975 dengue cases and 44 deaths have been reported. However, the actual number of dengue cases could be much higher (approximately four to six times) than that. Currently, most patients with dengue fever or dengue-like symptoms prefer to stay at home and are under self-medication. They have not been added to official data.

So far, there is no specific treatment for dengue fever, except the management of symptoms. Paracetamol is recommended to control fever and relieve muscle aches and pain. Oral fluid and electrolyte therapy is essential for dengue patients. Patients with dengue-like symptoms are being treated symptomatically and are recovering uneventfully.

Currently, Nepal is facing its worst dengue outbreak crisis in terms of the number of cases concerning hospitalisations, deaths and geographical coverage reported from 76 out of 77 districts. Although the majority of patients showing dengue fever symptoms tested positive for dengue virus, dozens of others who displayed such symptoms tested negative, which makes ‘Kathmandu Syndrome’ a cause for concern.