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ORIGINAL ARTICLE
Year : 2019  |  Volume : 17  |  Issue : 4  |  Page : 103-107

Acute undifferentiated febrile illness in the elderly: A clinical profile


Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission13-Sep-2019
Date of Decision03-Oct-2019
Date of Acceptance17-Oct-2019
Date of Web Publication12-Dec-2019

Correspondence Address:
Dr. Darpanarayan Hazra
Department of Emergency Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmi.cmi_39_19

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  Abstract 

Introduction: Geriatric patients are more prone to have serious viral or bacterial infections that may present with acute febrile illness (acute undifferentiated febrile illness [AUFI]) and have significantly increased the risk for morbidity and mortality. It is important for the community to know the clinical presentation and local etiology of AUFI. Methodology: This is a subgroup analysis of a large prospective study on determining the etiology of AUFI. We included geriatric population (>60 years) for our analysis. Results: This cohort study included 126 elderly patients who presented with AUFI, in which 56.3% were men. Scrub typhus (57.4%) was the most common cause of AUFI followed by dengue (19.1%), malaria (3.2%), enteric fever (1%), and leptospirosis (0.8%). Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The requirement of supplemental oxygen, invasive ventilation, and inotropes was highest among the scrub typhus patients followed by leptospirosis and malaria. Bleeding manifestations were seen in scrub typhus (6.8%), dengue (14.2%), and malaria (25%). The overall mortality rate was 6.3% and was highest with scrub typhus 5.4%. Conclusion: The similarity in clinical presentation and diversity of etiological agents demonstrate the complexity of diagnosis and treatment of AUFI in South India. Even though respiratory tract, urinary tract, and skin infections present with acute febrile illness in the elderly, other undifferentiated causes such as scrub typhus, dengue, malaria, enteric fever, and leptospirosis should also be considered while treating the elderly, especially in developing nations. Once a clinical profile is formed, the local population can be educated to identify the possible life-threatening complications based on endemicity and seasonal trends.

Keywords: Febrile illness, dengue, elderly, malaria, scrub typhus


How to cite this article:
Fernandes JP, Hazra D, David SN, Abhilash KP. Acute undifferentiated febrile illness in the elderly: A clinical profile. Curr Med Issues 2019;17:103-7

How to cite this URL:
Fernandes JP, Hazra D, David SN, Abhilash KP. Acute undifferentiated febrile illness in the elderly: A clinical profile. Curr Med Issues [serial online] 2019 [cited 2020 Jul 15];17:103-7. Available from: http://www.cmijournal.org/text.asp?2019/17/4/103/272802




  Introduction Top


Acute undifferentiated febrile illness (AUFI) in the elderly is similar to any other acute illness in the geriatric age group and may present in a varied atypical, non classical pattern. Fever is the cardinal symptom of an infection which may be obvious (seen) or blunt as in 20-30% of cases. The absence of fever may cause a diagnostic dilemma that may contribute to the delayed treatment. On the other hand, the presence of fever in the elderly is most likely associated with a serious viral or bacterial infection, with an increased rate of mortality and morbidity due to other comorbid conditions. In many developing countries, where diagnostic facilities are limited, the etiology of AUFI remains largely unknown. Physicians often diagnose disorders based on clinical features augmented by microbiological and serological tests. The AUFI spectrum which includes scrub typhus, dengue fever, malaria, enteric fever, and leptospirosis among others causes significant mortality and morbidity. These infections may be indistinguishable clinically, and the choice of empiric antibiotics depends on the etiological profile, which is variable and region-specific. Dengue fever and malaria are arthropod-borne diseases and are endemic in many parts of India during the monsoon season. Leptospirosis and scrub typhus are zoonotic infections and are widely prevalent in areas with heavy monsoon and agrarian way of life. As early presentation can make a difference in the final outcome of the patient, it is crucial for the community, especially the family members to be able to recognize warning signs so that prompt medical care can be sought. By profiling geriatric undifferentiated febrile illness, it is possible to identify symptoms and signs accompanied by life-threatening complications of febrile illnesses which can help increase the awareness among the community. It is therefore crucial to determine the prevalence and epidemiology of the causative pathogens to develop protocols for empiric antibiotics. In this context, we have conducted a cross-sectional prospective observational study to investigate the causes of AUFI, clinical predictors, and the seasonal trend throughout the year.


  Methodology Top


Design

This is a subgroup analysis of a large prospective study, involving only elderly (60 years and above) from the Abhilash et al. study on AUFI, conducted in Christian Medical College and Hospital.[1]

Setting

We conducted this study in the Adult Emergency Department and Medicine Outpatient Department (OPD) of Christian Medical College and Hospital, Vellore, a 2700-bed tertiary care hospital in Tamil Nadu, South India, between October 2012 and September 2013.

Participants

All patients who were more than 60 years of age presenting with an AUFI lasting between 3 and 14 days with no evident focus of infection following initial clinical evaluation were included in the study. Patients with hematological malignancies, autoimmune disorders, and those on immunosuppressant were excluded from the study.

Variables

Patient data were obtained through the hospital's electronic database. Details of history and physical examination findings and demographic details were recorded on a standard data collection sheet. The variables included were age, sex, comorbidities, clinical features, examination findings, and laboratory results.

Outcome variable

Etiology of AUFI in elderlies and in-hospital mortality.

Bias

This study recruited all consecutive patients presented to our hospital during the study period.

Study size

As one of the objectives is to determine the seasonal variation, we recruited patients over 1-year duration.

Laboratory test

Blood investigations included serum electrolytes, liver and renal function tests, and complete blood count analysis. Single blood culture was obtained from all the enrolled patients in an aerobic BacT/Alert 3D (bioMérieux, Hazelwood, MO, USA) bottle and was incubated for up to 7 days. Thin smear was performed to detect malarial parasites in all patients. If tests for malarial parasites and blood cultures were negative after the 7th day of fever, serological tests were done that included dengue IgM enzyme-linked immunosorbent assay (ELISA) (Panbio ®; Dengue Duo Cassette), scrub typhus IgM ELISA (InBios International, Inc., Seattle, WA, USA), Leptospira IgM ELISA (Panbio ®), and a Widal test. ELISA test was performed in patients from endemic regions. This was interpreted according to the manufacturer's instruction as positive, equivocal, or negative. In case the serological diagnosis was not clear, convalescent serological testing was done after 2–4 weeks. All inpatients were followed up until discharge from the hospital.

Statistical analysis

Details of history and results of a thorough physical examination were entered on a standard data collection sheet after obtaining written informed consent. Statistical analysis was performed using SPSS software (SPSS Inc., Released 2007, SPSS for Windows, and version 16.0, Chicago, IL, USA). Mean (standard deviation [SD]) was calculated for the continuous variables, and t-test or Mann–Whitney U-test was used to test the significance. Categorical variables were expressed in proportion.

Ethical considerations

The study was approved by the Institutional Review Board (IRB Min. No. 8007 dated 19/09/2012), and the patient's confidentiality was maintained using unique identifiers and password-protected data entry software with restricted uses.


  Results Top


During the study period, a total of 1372 patients presented to the emergency department and general medicine OPDs with AUFI. Among these 1372 patients, 114 patients were excluded as they either did not give consent or blood samples for the confirmation of diagnosis. Among the remaining 1258 patients, etiological evaluation was done for 126 patients who belonged to the geriatric age group [Figure 1]. Within the study group, the mean age was 65 (SD) years. Around 49.1% of the patients were male, thus suggesting that there was no gender preponderance. Common comorbidities included diabetes mellitus (23%) and systemic hypertension (24%) [Table 1]. The most common etiology was found to be scrub typhus (57.4%), followed by dengue (19.1%). Majority of the patients with scrub and dengue presented with central nervous system symptoms such as headache, vomiting, and altered sensorium, followed by respiratory symptoms, and finally, gastrointestinal symptoms. Respiratory involvement was seen 49% in scrub typhus and 25% in malaria. Malaria was diagnosed in 3.2% of the patients, and 1.6% had Gram-negative bacteria (GNB) sepsis [Table 2]. Incidences of leptospirosis or aseptic meningitis were minimal (0.8%). The mean duration of fever of 8.2 (SD: 3.08) days was maximum among patients with scrub typhus when compared to the rest. Hematological involvement was seen mostly in scrub typhus (79%) and malaria (75%) and minimal in dengue fever (57.1%) [Figure 2]. The overall severity of the disease as measured by the sequential organ failure assessment scores was highest in scrub typhus (6.1%), followed by malaria (5.2%). The total number of patients requiring oxygen, ventilator, and inotropic supports was also highest among those with scrub typhus [Figure 3]. The overall mortality rate was 6.4% and was highest with scrub typhus (4.6%), followed by dengue fever (2.3%). On plotting the incidence against the time of the year, a marked increase in all cases of AUFI, especially in scrub typhus, was noticed from July to February, the highest being in September, marking a seasonal trend during the monsoon and winter seasons [Figure 4].
Figure 1: Flowchart of patients presenting with acute undifferentiated febrile illness.

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Table 1: Baseline characteristics and clinical features of the population

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Table 2: Examination findings and laboratory parameters

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Figure 2: Organ involvement.

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Figure 3: Requirements of supports.

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Figure 4: Seasonal distribution of acute undifferentiated febrile illness.

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  Discussion Top


Our study showed the etiological profile of AUFI among the elderly population in South India. In developing countries like ours where laboratory facilities are limited, etiologies of AUFI remain largely unknown.[1],[2],[3]

Physiological reserves are diminished in the geriatric population. There is an increased susceptibility to infection in the geriatric populations because of low cellular immunity. Continuous antigenic stimulation causes an increase in circulating memory T-cells, while naive T-cells decrease due to the involution of the thymus. The response to foreign antigens also decreases because of increasing lack of regulatory control of T-cells on B-cells. On the other hand, neutrophils, macrophages, and neutral killer cells continue to function reasonably well.[4]

Scrub typhus, dengue, malaria, and leptospirosis are endemic in many parts of South India. Physicians often diagnose patients based on clinical features and assumptions regarding circulating pathogens. Local public health authorities have limited data to access disease burden to estimate priorities for health resources or to make protocols for empiric antibiotics for patients presenting with AUFI that causes significant mortality and morbidity. These infections may be clinically indistinguishable, and the choice of empiric antibiotics depends on the etiologic profile which is variable as well as region-specific.[2]

Dengue fever and malaria are arthropod-borne diseases and are endemic in many parts of India, which shows a seasonal trend during the monsoon and winter seasons.[2] However, studies done by Sharma and Malakar in India and by Owais et al. in Pakistan [3],[5] demonstrated an increased incidence of typhoid fever during the monsoon season.

Leptospirosis and scrub typhus are zoonotic infections, which are widely prevalent in areas with heavy monsoon and agrarian way of life. Unlike Kerala, our study population did not demonstrate too many that fulfilled the diagnostic criteria for leprospirosis.[1],[2],[6] In patients with scrub typhus infection, an eschar is the most useful clinical diagnostic tool, and therefore, a thorough physical search for an eschar is mandatory to initiate antibiotics promptly.[7],[8] Male gender comprised the larger proportion of the cases, except in scrub typhus, probably explained by the fact that exposure to mosquitoes and transmission of vector-borne diseases are more associated with the predominantly outdoor occupational exposure of males.[7] The overall mortality rate in our study was 6.3%, with more than one-third of the deaths resulting from scrub typhus. However, the case fatality rate among inpatients diagnosed with scrub typhus in our hospital has decreased from 12.2% to 6.9%.[8] This is probably due to a greater awareness and early recognition of this re-emerging infection. However, in our study, GNB sepsis showed higher mortality, while scrub typhus had a lower mortality rate.

Based on this profile, it is possible to educate the community regarding warning symptoms and signs of undifferentiated febrile illnesses, based on which family members of the elderly can obtain timely medical help, which can improve the outcome of the patients. It is also possible to educate the community regarding seasonal variations of endemic diseases such as scrub typhus and malaria so that they are aware of the same and can have a high suspicion, which will improve the overall outcome of AUFI in the elderly.

Our study has certain limitations. Malaria may have been underdiagnosed, as only a single thin smear was done to rule out malaria due to logistical constraints in most patients. Routine tests for potential pathogens such as spotted fever, Hantaan virus, and chikungunya virus were not done due to financial constraints. Some patients were lost to follow-up, and hence, convalescent sera could not be obtained for the confirmation of diagnosis.


  Conclusion Top


Malnutrition and poor natural mechanical barriers are commonly seen in the elderly that contribute to infections. The diversity in clinical presentation and etiological agents with limited laboratory facilities demonstrates the complexity of diagnosis and treatment of AUFI in South India. This etiological profile will be of use in the development of rational guidelines for infectious disease control and treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interes



 
  References Top

1.
Abhilash KP, Jeevan JA, Mitra S, Paul N, Murugan TP, Rangaraj A, et al. Acute undifferentiated febrile illness in patients presenting to a tertiary care hospital in South India: Clinical spectrum and outcome. J Glob Infect Dis 2016;8:147-54.  Back to cited text no. 1
    
2.
Chrispal A, Boorugu H, Gopinath KG, Chandy S, Prakash JA, Thomas EM, et al. Acute undifferentiated febrile illness in adult hospitalized patients: The disease spectrum and diagnostic predictors - An experience from a tertiary care hospital in south India. Trop Doct 2010;40:230-4.  Back to cited text no. 2
    
3.
Owais A, Sultana S, Zaman U, Rizvi A, Zaidi AK. Incidence of typhoid bacteremia in infants and young children in southern coastal Pakistan. Pediatr Infect Dis J 2010;29:1035-9.  Back to cited text no. 3
    
4.
Yoshikawa TT. Epidemiology and unique aspects of aging and infectious diseases. Clin Infect Dis 2000;30:931-3.  Back to cited text no. 4
    
5.
Sharma J, Malakar M. Distribution of typhoid fever in different rural and urban areas of Lakhimpur district of Assam. Int J Res Dev Health 2013;1:109-14.  Back to cited text no. 5
    
6.
Blacksell SD, Smythe L, Phetsouvanh R, Dohnt M, Hartskeerl R, Symonds M, et al. Limited diagnostic capacities of two commercial assays for the detection of leptospira immunoglobulin M antibodies in Laos. Clin Vaccine Immunol 2006;13:1166-9.  Back to cited text no. 6
    
7.
Kundavaram AP, Jonathan AJ, Nathaniel SD, Varghese GM. Eschar in scrub typhus: A valuable clue to the diagnosis. J Postgrad Med 2013;59:177-8.  Back to cited text no. 7
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8.
Chrispal A, Boorugu H, Gopinath KG, Prakash JA, Chandy S, Abraham OC, et al. Scrub typhus: An unrecognized threat in South India-clinical profile and predictors of mortality. Trop Doct 2010;40:129-33.  Back to cited text no. 8
    


    Figures

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

  [Table 1], [Table 2]



 

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