Development and/or evaluation of scoring systems, rapid diagnostic tests and treatment thresholds to guide management of neglected bacterial febrile illnesses endemic to the Indian subcontinent

Project Details


Tropical Febrile Illnesses are significant causes of mortality and morbidity in low-resource countries (1). One of the most known tropical febrile
illnesses around the world is malaria. While it is still a significant problem in many countries, its incidence in South Asia is decreasing (2). Viral
febrile illnesses like dengue and chikungunya have been included in the WHO’s neglected tropical diseases list (3). Still, several bacterial febrile
illnesses endemic in South Asia are particularly important as targeted antibiotic interventions early in illness directly impact the clinical outcomes.
Bacterial febrile illnesses such as scrub typhus (Orientia tsutsugamushi) and leptospirosis (Leptospira spp.) present with acute undifferentiated fever
(fever for less than 14 days and without localisation to a single organ or system) (1). The microbiological diagnosis of scrub typhus and
leptospirosis requires molecular and serological tests, without which it is often difficult to differentiate from other febrile illnesses such as malaria,
dengue, and chikungunya (4). Many of these bacterial febrile illnesses, such as leptospirosis, melioidosis and scrub typhus, see an upsurge in postmonsoon season and excessive numbers of patients present to all levels of healthcare with different manifestations (5–7). Etiological diagnosis is
challenging for most patients with febrile illnesses in resource-limited settings, as laboratory support is very limited in such settings. In a recent
study in rural hospitals in India, more than half of the patients with acute febrile illnesses were undiagnosed (1). Also, nearly 50% of the deaths
were within 48 hours of admission (1). Early diagnosis and treatment, therefore, is the key to preventing this adverse outcome.
Similar to scrub typhus and leptospirosis, Burkholderia pseudomallei and Brucella spp. require laboratory support (culture-based methods with
extended incubation) and are often confused with other differentials (8,9). The most common presenting feature of melioidosis is communityacquired pneumonia. It is important to understand the prevalence of melioidosis in these patients as these patients are often acutely ill, and empiric
antimicrobials used to treat community-acquired pneumonia (ceftriaxone/ amoxicillin-clavulanate and azithromycin) are not enough to treat
pulmonary melioidosis (10) Similarly, the most common manifestation of Brucella in South India is Brucella spondylodiscitis. Brucella
spondylodiscitis is commonly misdiagnosed as tubercular spondylodiscitis and treated with empiric anti-mycobacterial, and delay in appropriate
management results in significant morbidity (11).
The poor availability of diagnostics in resource-limited settings leads to excessive reliance on subjective decision-making. Without evidenceinformed recommendations, physicians in resource-limited settings face significant difficulty when they are confronted with febrile illness and its
large differential diagnosis. This leads to either missed diagnosis or rampant misuse of multiple empiric antibiotics promoting antimicrobial
resistance. There is a need for educational intervention to help reach an evidence-informed conclusion. Clinical scoring systems have been helpful
in diagnosing classic infectious syndromes such as acute appendicitis (12). However, region-specific scoring systems have not been developed
adequately for bacterial febrile illnesses due to a lack of systematic generation and analysis of local literature. Bedside point-of-care tests can
supplement the scoring systems in case of scrub typhus and leptospirosis. These rapid diagnostic tests can help circumvent the significant turnaround time issue. There is a need to assess these tests' diagnostic accuracy and study their real-world impact on clinically relevant outcomes.
Additionally, delay or unavailability of microbiological diagnosis forces physicians to make the difficult decision to start empirical treatment for
patients with bacterial febrile illness. To avoid a subjective decision for initiating or withholding treatment, the determination of treatment
thresholds might prove to be helpful in these settings.
1. Mørch K, Manoharan A, Chandy S, Singh A, Kuriakose C, Patil S, et al. Clinical features and risk factors for death in acute
undifferentiated fever: A prospective observational study in rural community hospitals in six states of India. Trans R Soc Trop Med Hyg. 2023 Feb
2. The Lancet Regional Health-Southeast Asia null. 2030 - Countdown to malaria elimination in India and southeast Asia. Lancet Reg
Health Southeast Asia. 2022 Jul;2:100033.
3. Neglected tropical diseases -- GLOBAL [Internet]. [cited 2023 Oct 23]. Available from:
4. Gupta N, Nischal N. Management of acute febrile diseases in limited resource settings: a case-based approach. Infez Med. 2020 Mar
5. Devasagayam E, Dayanand D, Kundu D, Kamath MS, Kirubakaran R, Varghese GM. The burden of scrub typhus in India: A systematic
review. PLoS Negl Trop Dis. 2021 Jul 27;15(7):e0009619.
6. Gupta N, Wilson W, Ravindra P. Leptospirosis in India: a systematic review and meta-analysis of clinical profile, treatment and
outcomes. Infez Med. 31(3):290–305.
7. Mohapatra PR, Mishra B. Burden of melioidosis in India and South Asia: Challenges and ways forward. Lancet Reg Health Southeast
Asia. 2022 Jul;2:100004.
8. Currie BJ. Melioidosis and Burkholderia pseudomallei : progress in epidemiology, diagnosis, treatment and vaccination. Curr Opin Infect
Dis. 2022 Dec 1;35(6):517–23.
9. Yagupsky P, Morata P, Colmenero JD. Laboratory Diagnosis of Human Brucellosis. Clin Microbiol Rev. 2019 Dec 18;33(1):e00073-19.
10. Dance D. Treatment and prophylaxis of melioidosis. Int J Antimicrob Agents. 2014 Apr;43(4):310–8.
11. Guo H, Lan S, He Y, Tiheiran M, Liu W. Differentiating brucella spondylitis from tuberculous spondylitis by the conventional MRI and
MR T2 mapping: a prospective study. Eur J Med Res. 2021 Oct 28;26(1):125.
12. Andersson REB. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg. 2004 Jan;91(1):28–37.
Effective start/end date29/05/24 → …


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