Febrile illnesses are very common in the monsoon and post monsoon season in tropical countries. The term acute undifferentiated febrile illness (AUFI) is defined as fever of <14 days duration without any localised source of infection [1]. The common causes of AUFI’s are dengue fever, chikungunya, scrub typhus, malaria, Enteric fever, Leptospirosis etc. in the tropical countries [2].

Majority of the AUFI’s are arthropod vector borne and disease transmission is influenced by the increased vector density, temperature, humidity, increased growth of vegetation, biting patterns of vectors. Malaria is caused by mosquito-borne Plasmodium parasites; P. vivax and P. falciparum, being responsible for the majority of morbidity and mortality. Dengue and chikungunya are arboviral infections transmitted by the bite of infected Aedes mosquitoes. The dengue virus has an incubation of 4–10 days and the disease presentation varies from asymptomatic to severe life threatening complications. Incubation period of Chikungunya ranges from 1 to 12 days following the bite of an infected Aedes mosquito. The onset of the disease is characterized by an acute febrile illness, accompanied by rash and severe joint pain that can persist for months [3]. Similar clinical presentation with diverse aetiologies often confounds the diagnosis of febrile illnesses and delays initiation of appropriate treatment.

Infections with multiple organisms further complicate the situation. Malaria is a common co infection in dengue and is an emerging problem across Asian countries [4]. Coinfections of Dengue with Chikun-gunya are predictable as they are transmitted by the same Aedes mosquitoes and targeted control measures can potentially reduce the combined disease burden. Scrub typhus is an acute febrile illness caused by the obligate intracellular bacterium Orientia tsutsugamushi.

It is transmitted to humans through the bite of the trombiculid mite, which is both the vector and reservoir. Scrub typhus is often under-diagnosed due to nonspecific clinical features and relatively lesser prevalence of the characteristic eschar, making it difficult to differentiate from other febrile illnesses. Dual infections with Dengue and scrub typhus have been reported in the recent past though initially considered to be rare due to the different vectors involved [5].

Scrub typhus IgM ELISA was performed with Scrub typhus Detect IgM ELISA (InBios Inc, USA).

Advantage Chikungunya IgM card (J Mitra & Co) was used for diagnosis of Chikungunya. Mycoplasma IgG and IgM ELISA was performed by Calbiotech (USA) kits. Tydal antigen kit (Tulip Diagnostics) was used for performing Widal test.

Latex agglutination (Omega Diagnostics, UK) was used to detect antibodies to Brucella abortus and Brucella melitensis.

Data analysis: Statistical analysis was performed using the Graph Pad prism statistical software; categorical variables were compared using Fisher’ Test. MS Excel 2010 was used to analyse the data.

Ethical consideration: Ethical committee clearance was obtained from Institutional ethics committee and informed written and verbal consent was taken from all the patients.

Sixteen hundred and thirty-five serum samples were received from 932 patients during the study period. 58.4% (545/932) of them were males and 41.5% (387/932) were females with a mean age of 41 years (range 6 to 88 years). Microbiological diagnosis was available in 33.5% (313/932) patients.

Dengue was the most common infection seen in 21.6% (202/932) of patients followed by scrub typhus in 9.5% (89/932) of patients (Table 1).

Table-1: Prevalence of febrile illnesses

Most of the cases of dengue and scrub typhus cases were observed in August; there was a gradual decline of scrub typhus thereafter whereas dengue cases continued to rise till September and slightly tapered off in October (Figure 1).

Figure-1: Seasonal prevalence of undifferentiated fevers

Figure-3: Temporal distribution of dual infections

Acute febrile illnesses pose a diagnostic challenge due to their varied aetiology and limited diagnostic capabilities even in tertiary care hospitals. Most of them are caused by arthropod borne viral pathogens followed by bacteria and parasites. Serological tests are useful tools to diagnose these aetiological agents rapidly as they are relatively easy to perform and results can be delivered within a few hours of sample receipt in the laboratory.

The most common cause of AUFI in the present study was Dengue followed by scrub typhus with prevalence rates of 21.6% and 9.5% respectively. Dengue, malaria, scrub typhus, enteric fever and leptospirosis have been identified as major causes of AUFI in Thailand, Malaysia and Nepal [10-14] and a few studies from South India [2, 15, 16].

Dengue was reported to be the major cause of febrile illness from two studies in Dehradun [17] and Rourkela [18]. Scrub typhus is emerging as a major cause of AUFI in South India with one study reporting nearly half of inpatient admissions due to scrub typhus among the AUFI’s [3]. Two studies from a south Indian tertiary care hospital in 2007 and 2012-2013 have reported scrub typhus as predominant cause of AUFI-47.5% and 35.9% respectively [2,19]. Another study from Maharashtra in 2015-16 also found scrub typhus to be the predominant cause of AUFI [20].

The prevalence of Enteric fever in the present study was 1.8% compared to 16.5% and 3.7% from two similar studies [17, 19]. Enteric fever cases are expected to rise during the monsoon due to consumption of contaminated water but the apparently lesser prevalence in the present study could be attributed to the fact that the majority of patients access outpatient services for the diagnosis and treatment of enteric fever who were not included in the present study.

A meta analysis and literature review of 43 studies published from 1998 to 2019 to evaluate aetiologies of undifferentiated febrile illness in south and Southeast Asia revealed Dengue as the most common cause of AUFI in 16.6% of patients followed by Scrub typhus (10.7%), malaria (9.8%), Leptospirosis (6.3%) and typhoid (6%) [21].

Non infectious aetiologies of AUFI could account for a proportion of undiagnosed cases. Rates of determining the aetiologies of AUFI varied from 40% to 73.3% in various studies [13, 33, 34]. A large meta-analysis of 43 studies from 1998 -2019 found that the underlying diagnosis could not be ascertained in 64.6% of patients [21].

Limitations of the study: All the infectious causes of febrile illnesses could not be ascertained due to financial constraints and limited diagnostic capabilities in our hospital.

Awareness of the local and seasonal profile of acute undifferentiated fever is useful to draft logical clinical, diagnostic and treatment algorithms which help the physicians in the correct choice of empirical antibiotics.

This is useful especially for multiple infections coexisting with scrub typhus which respond rapidly to Doxycycline treatment, preventing further compli-cations. Knowledge of the local aetiology of the arthropod borne illnesses aids policy makers to implement appropriate and timely disease and vector control measures.

The present study establishes that Dengue and scrub typhus are the major causes of febrile illnesses during the monsoon in our geographical region.

Empirical treatment of febrile illnesses need to incorporate specific scrub typhus treatment as it coexists in the majority of coinfections and the nonspecific clinical picture precludes the diagnosis. Rising incidence of infections with multiple organisms emphasizes the need for a comprehensive diagnostic workup.

Dr. M. V. N. L. Ram Mohan: Conceptualised the study and prepared the manuscript.

Dr. VD. Teja: Reviewing and editing of the manuscript.

Mrs. K. Subhada: Performed the diagnostic tests and assisted in data analysis and editing of the manuscript.