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  Table of Contents  
Year : 2017  |  Volume : 35  |  Issue : 4  |  Page : 480-484

Spectrum of infections in acute febrile illness in central India

Department of Microbiology, Mahatma Gandhi Institute of Medical Sciences, Wardha, Maharashtra, India

Date of Web Publication1-Feb-2018

Correspondence Address:
Dr. Vijayshri Suresh Deotale
Department of Microbiology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha - 442 102, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmm.IJMM_17_33

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 ~ Abstract 

Introduction: Infectious agent when enters in the host results in febrile illness. This may lead to increase in morbidity or even mortality in undiagnosed/untreated cases. There are many aetiological agents which lead to acute febrile illness. Among these aetiological agents, important is bacterial or viral aetiology. Objective: The objective of this study is: (i) To know the aetiological agents responsible for acute undifferentiated febrile illness (AUFI) by serological test or by bacterial culture and (ii) To know the clinical profile of AUFI. Methodology: A total of 270 patients were enroled in the study with a history of AUFI admitted in medicine and paediatric department from January 2015 to November 2016 of tertiary care hospital of central India. Blood sample was collected for blood culture, clot culture and serological tests for immunochromatographic tests (ICTs) and ICT-positive results were confirmed by respective enzyme-linked immunosorbent assay (ELISA). All negative serum samples by immunochromatography were retested for disease-specific ELISA as scrub typhus, dengue and leptospirosis. Results: Out of 270 patients, 127 (47%) were of scrub typhus, 33 (12%) were malaria cases, 47 (17.40%) were dengue, 12 (4%) were enteric fever, 5 (2%) were leptospirosis, undiagnosed were 18 (6.66%) and other infections (viz viral, urinary tract infection, upper and lower respiratory tract infection and acute gastroenteritis) accounts for 28 (10.37%) cases. We have also noticed that there was co-infection of scrub typhus and dengue, leptospirosis and scrub typhus. Conclusion: It is important to know the cause and clinical profile of AUFIs for their proper management also it will help to prevent morbidity and mortality in AUFI cases.

Keywords: Acute undifferentiated febrile illness, enzyme-linked immunosorbent assay, rapid diagnostic test

How to cite this article:
Shelke YP, Deotale VS, Maraskolhe DL. Spectrum of infections in acute febrile illness in central India. Indian J Med Microbiol 2017;35:480-4

How to cite this URL:
Shelke YP, Deotale VS, Maraskolhe DL. Spectrum of infections in acute febrile illness in central India. Indian J Med Microbiol [serial online] 2017 [cited 2021 Jan 26];35:480-4. Available from:

 ~ Introduction Top

Fever is a common symptom of any infectious systemic illness which may act as an important cause of morbidity. Most of the febrile illness which is not specified, their cause for which treatment is rather generic, typically with antipyretics and antibiotics.[1] Because of this, clinical decision-making compromised since evidence-based epidemiologic data on fever is insufficient in a tropical area.[2]

Depending on the duration of fever, febrile illness is termed as an acute febrile illness (AFI) or chronic febrile illness. AFI is routinely defined as any illness associated with fever of 2 weeks or shorter in duration, rapid in onset, caused by diverse pathogens without any evidence of organ or system-specific aetiology.[3],[4] It is common in the tropics and subtropics regions. AFI with no localising sign and symptoms is termed as acute undifferentiated febrile illness (AUFI). Due to unavailability of facilities to diagnose, there is delay or lack of correct diagnosis of the patient which may lead to deaths in patients suffering from AUFI. Hence, it has become important that depending on the cause of AUFI, guidelines for investigation and antimicrobial therapy can be developed for general physicians to deal with AUFI. Laboratory facilities and serological tests which are required to diagnose the infections can also be developed or made available. The aim behind this development of testing and treatment guideline is to manage the causes of AUFI and also to eliminate the primary bacteraemia with antimicrobial therapy, and since it can pose a serious threat to each patient.[5]

AUFI accounts for the majority of outpatient visits and inpatient admissions in India. The causes for the same are variable and need a systematic approach to identify the cause of appropriate therapy.[6] AUFI can be potentially fatal if the aetiology is not recognised and if not appropriately treated early. AUFI have been widely studied in South India as well as Northern India, but there is only limited number of studies from central India, reported on the aetiology of fever and there is lack of surveillance data. Hence, this study was carried out to describe the distribution of aetiological agents of AUFI in patient who gets admitted in our hospital due to AUFI and to describe disease-specific clinical profiles based on their haematological and microbiological investigations.

 ~ Methodology Top

This cross-sectional prospective 18-month study was conducted in a rural hospital of central India from January 2015 to November 2016. The study includes adult and paediatric age group patients who were admitted with febrile illness for <2 weeks duration, and the enroled patients were not on any antibiotic therapy. The study protocol was followed as mentioned in [Figure 1].
Figure 1: Study protocol for workup of acute undifferentiated febrile illness

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This study was conducted in 270 patients among the 449 patients admitted to the hospital as per the inclusion criteria. In total, 10 and 5 ml blood was collected from each adult and paediatric patients, respectively. 5ml (adult) or 2 ml (paediatric) of blood sample was inoculated in blood culture bottles and transported to the laboratory within 2 h. The remaining 5 ml (adult) or 3 ml (paediatric) of blood was collected in plain and ethylenediaminetetraacetic acid (EDTA) bulb. Blood collected in the plain bulb was centrifuged at 3000 g for 10 min, and serum was stored at 20°C for serological testing. The remaining clot was used for clot culture. Serum was used for Widal test as well as for other serological tests for the diagnosis of leptospirosis, dengue, Japanese encephalitis and scrub typhus by rapid diagnostic tests (RDTs). The tests which were positive by RDT were confirmed by respective enzyme-linked immunosorbent assay (ELISA). Tests which were negative by RDT were retested for dengue ELISA, leptospirosis ELISA and scrub typhus ELISA. Japanese encephalitis ELISA was not done due to unavailability. EDTA sample was tested by RDT and peripheral blood smear for malaria.

 ~ Results Top

A total of 449 patients were admitted with AFI. Out of which, 270 (60.13%) were included in the study as per the inclusion criteria of AUFI. Out of 270 patients, 138 (51.11%) were male and 132 (48.88%) were female. Nearly 25.95% were belonging to 15–25 years of age group and 16.29% were from 36 to 45 years of age group. In our study, we found that the maximum enrolment of patients were 62.22% in the month of September and August [Figure 2]. It was also revealed that 18.88% patients visited hospital on the 5th day of fever and 25.18% visited on 8th day of fever [Figure 3]. [Table 1] summarises the common clinical symptoms and length of patients hospital stay. In all AUFI patients, mean affected age was 34.35 ± 19.57 years (STDEV) and average duration of fever at the time of presentation was 6.66 ± 2.97 days, and mean duration of hospitalisation was 5.34 ± 3.42 days.
Figure 2: Month wise enrolment of acute undifferentiated febrile illness cases in study

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Figure 3: Days of fever at the time of presentation

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Table 1: Clinical profile of acute febrile illness cases (n=270)

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Haematological investigations were carried out in AUFI. It was observed that 16.91% patients present with severe thrombocytopenia i.e., platelet count <50,000. Leucocytosis was seen in 36.66% patients.

Out of total 270 samples, 195 (72.22%) were positive by RDTs [Table 2], and 75 (27.78%) were negative by RDT. Out of these 75, 12 (16%) were diagnosed as enteric fever (10 by Widal test, one by blood culture and one by clot culture). The remaining 63 samples among these 75 were subjected to ELISA for scrub typhus, leptospirosis and dengue [Table 3].
Table 2: Number of acute febrile illness positive cases by specific rapid diagnostic test

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Table 3: Correlation of ELISA positives in RDT Negative cases

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This study revealed the causes of AUFI included scrub typhus were 127 (47%), dengue were 47 (17.40%), malaria were 33 (12%), enteric fever were 12 (4%), leptospirosis were 5 (2%), other diagnosis 28 (10.37%) and undiagnosed AUFI 18 (6.6%) [Table 4].
Table 4: Spectrum of infections in acute febrile illness cases

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 ~ Discussion Top

AUFI is the clinical illness in which, it is difficult to find out aetiological agents and once detected can be treated on the line of aetiological agents aetiological agent and once detected can be treated on the line of aetiological agents. The predominance of this infection is usually observed during post-monsoon period. A total of 449 patients were admitted with AUFI symptoms, but out of these 270 (60.13%) were enrolled as per the inclusion criteria. Many studies has shown increased in number of AUFI cases from September to November. Male predominance was noticed in all infections except malaria. This may be due to male gets more exposed to the outer environment and post-monsoon environment gets favourable breeding places for the mosquitoes.

Our study revealed that scrub typhus was the predominant (47%) infection among the AUFI cases, followed by dengue 17.40% and malaria in 12% cases. In our study, 11.82% patients withscrub typhus were presented with eschar on the body [Figure 4]. It has well circumscribed with well delineated margin and predominantly present in lower extremities and lower abdominal parts of body. A study conducted by Jung et al. in 2015[7] showed 56.6%, a study conducted by Sinha et al. in 2014[8] did not show scrub typhus patients with eschar among 42 positive cases of scrub typhus which was included in their study.
Figure 4: Typical eschar in diagnosed scrub typhus patient

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Scrub typhus has become one of the most predominant infection in all the regions of India. This may be due to earlier infection used to be unnoticed and now due to the availability of serological tests and polymerase chain reaction (PCR) kits in markets microbiologists started testing AUFI cases for the infection.

In our study, among the AUFI cases, the second predominant cause was dengue fever. In 17.40% cases, dengue cases were positive by IgM ELISA and EARLY NS1 antigen ELISA. Among these 17.40% cases, IgM positivity was 27.65% and NS1 ELISA (72.34%). Our study results were similar to study conducted by Solanke et al. in 2015,[9] in which positivity was 28.4%. They had also detected dengue by PCR. In India, dengue positivity ranged between 8% and 71% among AUFI cases.[10],[11] The studies conducted in Tamil Nadu, Deharadun, showed dengue is a prime cause of AUFI cases.

Malaria was the third common cause of infection among the AUFI cases. About 11% cases were positive by peripheral smear (3.33%) and RDT (11%) detecting HRP2 and PLDH antigen. A study conducted by Singh et al.[12] reported malaria 12.8% and reported as second cause in AUFI cases. A previously conducted study from our hospital has depicted non-malarial AUFI cases account for 88% aetiological agent.[4]

In 270 AUFI cases, only 9 (3.33%) cases were positive by smear microscopy, and 33 (11%) cases were positive by RDT kit. The sensitivity, specificity of RDT in comparison with microscopy was 88.9% and 90.4%, respectively. The sensitivity of RDT in our study was contrary to study done by Garba et al.,[13] who showed very low sensitivity (9.09%) of RDT in acute febrile patients.

In AUFI cases, enteric fever accounts for 4% cases, which was similar finding in studies carried out in South India by Rani et al.[3] in 2016. Various studies carried out in India noted enteric fever was contributed as an aetiological agent in 8%–20% cases among AUFI.[14]

Leptospirosis was diagnosed in 2% of AUFI cases in our study which was similar to the study carried out by Joshi et al.[4] in 3 cases were positive among 11 clinically suspected cases.

In our study, 6.6% patients remained undiagnosed as we did not look for all the infections which are less prevalent in our area such as chikungunya and viral infections.

Nearly 10.37% cases were diagnosed due to other infection such as urinary tract infection, upper and lower respiratory tract infection, viral encephalitis and suspected TB.

In our study, due to funds constraint, we could not carry out PCR. By using PCR, we could have detected more causative agent for AUFI cases. Although we have reported 11% of eschar patients, to correlate the scrub typhus seropositivity in eschar positives cases we could have done PCR in these patients.

The second flaws in our study were we could not collect the second serum samples to know the rise in titre in patients as patients used to get discharged as soon as febrile state was over.

 ~ Conclusion Top

It was proven in our study that majority of the AUFI could be reliably predicted using proper history, good physical examination and laboratory tests. Despite of all limitations, our study clearly revealed that predominant cause of AUFI in our area was scrub typhus, dengue, malaria, followed by typhoid and leptospirosis on the basis of serological tests both RDT and ELISA.

It is also revealed from our study that if proper protocol was used for AUFI cases, it helps in the proper use of antibiotics as well as investigations. This reduces cost and resistance to antibiotics.

Financial support and sponsorship

This study was financially supported by Kasturba Health Society, Sevagram, Wardha, Maharashtra, India.

Conflicts of interest

There are no conflicts of interest.

 ~ References Top

Phuong HL, de Vries PJ, Nga TT, Giao PT, Hung le Q, Binh TQ, et al. Dengue as a cause of acute undifferentiated fever in Vietnam. BMC Infect Dis 2006;6:123.  Back to cited text no. 1
Zaidi AK, Awasthi S, deSilva HJ. Burden of infectious diseases in South Asia. BMJ 2004;328:811-5.  Back to cited text no. 2
Rani RV, Sundararajan T, Rajesh S, Jeyamurugan T. A study on common etiologies of acute febrile illness detectable by microbiological tests in a tertiary care hospital. Int J Curr Microbiol Appl Sci 2016;5:670-4.  Back to cited text no. 3
Joshi R, Colford JM Jr., Reingold AL, Kalantri S. Nonmalarial acute undifferentiated fever in a rural hospital in central India: Diagnostic uncertainty and overtreatment with antimalarial agents. Am J Trop Med Hyg 2008;78:393-9.  Back to cited text no. 4
Leelarasamee A, Chupaprawan C, Chenchittikul M, Udompanthurat S. Etiologies of acute undifferentiated febrile illness in Thailand. J Med Assoc Thai 2004;87:464-72.  Back to cited text no. 5
Prakash GM, Anikethana GV. Clinical, biochemical and hematological pointers toward dengue infection in patients with acute undifferentiated fever. Int J Sci Stud 2016;4:111-3.  Back to cited text no. 6
Jung HC, Chon SB, Oh WS, Lee DH, Lee HJ. Etiologies of acute undifferentiated fever and clinical prediction of scrub typhus in a non-tropical endemic area. Am J Trop Med Hyg 2015;92:256-61.  Back to cited text no. 7
Sinha P, Gupta S, Dawra R, Rijhawan P. Recent outbreak of scrub typhus in North Western part of India. Indian J Med Microbiol 2014;32:247-50.  Back to cited text no. 8
[PUBMED]  [Full text]  
Solanke VN, Karmarkar MG, Mehta PR. Early dengue diagnosis: Role of rapid NS1 antigen, NS1 Early ELISA and PCR assay. Trop J Med Res 2015;18:95.  Back to cited text no. 9
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Robertson C, Pant DK, Joshi DD, Sharma M, Dahal M, Stephen C, et al. Comparative spatial dynamics of Japanese encephalitis and acute encephalitis syndrome in Nepal. PLoS One 2013;8:e66168.  Back to cited text no. 10
Gopalakrishnan S, Arumugam B, Kandasamy S, Rajendran S, Krishnan B, Balaji A. Acute undifferentiated febrile illness among adults – A hospital based observational study. J Evol Med Dent Sci 2013;2:2305-19.  Back to cited text no. 11
Singh R, Singh SP, Ahmad N. A study of etiological pattern in an epidemic of acute febrile illness during monsoon in a tertiary health care institute of Uttarakhand, India. J Clin Diagn Res 2014;8:MC01-3.  Back to cited text no. 12
Garba BI, Muhammad AS, Musa A, Edem B, Yusuf I, Bello NK, et al. Diagnosis of malaria: A comparison between microscopy and rapid diagnostic test among under-five children at Gusau, Nigeria. Sub Saharan Afr J Med 2016;3:96.  Back to cited text no. 13
Sushi KM, Sivasangeetha K, Kumar AS, Shastri P, Ganesan A, Anitha D, et al. Seroprevalence of leptospirosis, enteric fever and dengue in patients with acute febrile illness in Tamil Nadu, India. Indian J Basic Applied Med Res 2014;3:615-23.  Back to cited text no. 14


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4]


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