From fever to action: diagnosis, treatment, and prevention of acute undifferentiated febrile illnesses

Abstract Acute Undifferentiated Febrile Illness (AUFI) presents a clinical challenge, often characterized by sudden fever, non-specific symptoms, and potential life-threatening implications. This review highlights the global prevalence, types, challenges, and implications of AUFI, especially in tropical and subtropical regions where infectious diseases thrive. It delves into the difficulties in diagnosis, prevalence rates, regional variations, and potential causes, ranging from bacterial and viral infections to zoonotic diseases. Furthermore, it explores treatment strategies, preventive measures, and the critical role of the One Health approach in addressing AUFI. The paper also addresses the emerging zoonotic risks and ongoing outbreaks, including COVID-19, Rickettsia spp., and other novel pathogens, emphasizing their impact on AUFI diagnosis and management. Challenges in resource-limited settings are analyzed, highlighting the need for bolstered healthcare infrastructure, enhanced diagnostics, and collaborative One Health strategies. Amidst the complexity of emerging zoonotic threats, this review underscores the urgency for a multifaceted approach to mitigate the growing burden of AUFI, ensuring early diagnosis, appropriate treatment, and effective prevention strategies.


Acute undifferentiated febrile illness (AUFI)
Undifferentiated febrile illness (UFI) is a common clinical presentation in healthcare settings worldwide.Patients with acute undifferentiated febrile illness (AUFI) often seek medical attention due to fe v er and other nonspecific symptoms (Wangdi et al. 2019 ).It is essential for healthcare professionals to accurately diagnose and manage AUFI to provide appropriate care.AUFI is a medical condition c har acterized by a sudden onset of fe v er ( ≥38 • C or ≥ 100.4 • F) that lasts for less than 2 weeks and cannot be attributed to a specific cause after a thorough clinical evaluation and appropriate laboratory testing (Shrestha et al. 2020 ).Acute febrile illness (AFI) is marked by the abrupt and r a pid de v elopment of fe v er with other symptoms such as chills , headache , muscle aches , fatigue , and malaise .T he fe v er may a ppear suddenl y without warning and may not be preceded by any noticeable symptoms .T he fe v er is associated with a range of non-specific symptoms, such as headac he, body ac hes, c hills, sweating, fatigue, cough, sore thr oat, gastr ointestinal disturbances, and others .It ma y r esolv e on its own within a few days or may persist for up to two weeks (Shrestha et al. 2018 ).AFI is a common clinical presentation and can be caused by a wide range of infectious and non-infectious conditions.AFI can be a sign of serious illness and can lead to further complications if left untreated (Khirikoekkong et al. 2023 ).AFI is often the first indication that a person may have a more serious condition, earl y dia gnosis is essential for isolating and treating the patient, which helps prevent the spread of the disease to others and can be crucial in the context of outbreaks (Elven et al. 2020 ).AFI can r esult fr om a wide range of underlying causes, including infections, inflammatory disorders, autoimmune diseases, and malignancies.Some of these conditions can be life-threatening if not pr operl y mana ged.Man y serious infections, suc h as sepsis, bacterial endocarditis, and certain viral infections, can present with a sudden high fe v er as a primary symptom.Without prompt intervention, these infections can lead to kidne y, li ver, and heart failur e e v entuall y lead to br ain dama ge and death (Wainaina et al. 2022 ).For instance, untreated bacterial infections can result in abscess formation, which is a localized collection of pus that forms as a result of the body's immune response to infection.Abscesses can de v elop in v arious parts of the body, suc h as the skin, internal organs, or within tissues.They ar e typicall y c har acterized by symptoms such as localized pain, redness, swelling, warmth, and sometimes fe v er (Br ook 2004 ).

AUFI and types
AUFI can be br oadl y categorised into thr ee sub-types, based on the signs and se v erity of the illness, the dia gnosed acute febrile illness (Diagnosed AFI), non-malarial acute febrile illness (Non-Malarial AFI) and undiagnosed acute febrile illness (Undiagnosed AFI) (Aufi et al. 2021 ).Dia gnosed AFI subtype r efers to cases of AUFI wher e the underlying cause of fever has been identified and diagnosed wher eby healthcar e pr ofessionals would hav e successfull y determined the specific pathogen or non-infectious condition (autoimmune disease, malignancy responsible for the fever.This will lead to application of appropriate treatment and management strategies to the patients .Meanwhile , non-malarial AFI subtype of AUFI excludes cases of fe v er caused by malaria.It encompasses a wide range of infectious and non-infectious causes of fe v er, including viral, bacterial, parasitic, autoimmune, and inflammatory condi-tions.Non-Malarial AFI often r equir es thor ough dia gnostic e v aluation to identify the specific cause, and it can be challenging to differentiate between these various conditions based on clinical pr esentation alone.Undia gnosed AFI r efers to cases wher e the cause of fe v er r emains unclear or unknown e v en after a compr ehensiv e dia gnostic e v aluation (Wangdi et al. 2019 ).Despite medical assessments and testing, the specific underlying condition responsible for the fe v er cannot be identified.These cases pose a dia gnostic c hallenge and may r equir e ongoing monitoring and further investigations as new information becomes available (Brown et al. 1984 ).The se v erity of acute AFI in the tropics and sub-tropics countries are now being recognized widely since there is a delay among medical community worldwide to reach the exact underlying causes of AUFI (Lokida et al. 2020 ).Hence it is essential to diagnosis febrile illness at early or at least intermediate stage since ther e ar e v arious r eported infectious and noninfectious bacteria, viruses, fungus, and parasites that potentially trigger high fe v er among the patients.In addition, emer ging ne w pathogen at the community level could also lead to poor point-of-care diagnosis of febrile illness.

AUFI and pre v alence
Globall y, the pr e v alence of AUFI is often higher in tropical and subtr opical r egions, this possibl y due to a conv er gence of factors that create fertile ground for a diverse range of infectious diseases .T hese r egions typicall y experience warm and humid climates, whic h pr ovide an ideal environment for disease vectors like mosquitoes and ticks to thrive (Alexander et al. 2013 ).As a r esult, v ector-borne diseases such as malaria, dengue fe v er, Zika virus, and various forms of encephalitis are endemic in these areas .T he pr olifer ation of v ectors and their inter actions with humans and animals contribute significantly to the transmission of febrile illnesses .Furthermore , tropical and subtropical regions often exhibit ric h biodiv ersity and a close interface between humans , wildlife , and domestic animals .T his ecological diversity increases the risk of zoonotic diseases, where infectious agents can jump from animals to humans.Wildlife species often serve as natur al r eservoirs for v arious pathogens, facilitating spillov er e v ents (Keesing and Ostfeld 2021 ).Limited access to healthcare, inadequate infr astructur e, and socio-economic c hallenges in some of these regions can lead to delays in diagnosis and treatment, allowing infectious diseases to pr ogr ess and become more severe.Climate c hange, whic h alters temper atur e and pr ecipitation patterns, can shift the geogr a phic distribution of disease vectors and pathogens, potentially expanding the prevalence of febrile illnesses.Hence AUFIs such as bacterial zoonotic diseases (scrub typhus and leptospir osis), r espir atory tr act infections , arbo viral disease , mononucleosis , malaria, and typhoid fe v er hav e been commonl y r eported wher eby mor e than 1 million leptospir osis, 5.2 million dengue, 5 million typhoid fe v er, 10 million malaria, 150.7 million of r espir atory tr act and 4 million mononucleosis cases hav e been dia gnosed eac h year (Alexander et al. 2013, K eesing and Ostfeld 2021, Leal Filho et al. 2022 ).Another systematic revie ws has demonstr ated that the top infectious causes of AUFI were dengue fever (11.8% of cases), leptospirosis (4.4% of cases), typhoid (4.0% of cases), scrub typhus (4.0% of cases) and influenza other than H1N1 (3.1% of cases) in most countries in the South and Southeast Asia regions (Leal Filho et al. 2022 ).Among admitted patients, dengue fe v er was the primary cause of AUFI, while leptospirosis was the main cause for outpatients .T he study also highlighted regional variations in the causes of AUFI.In South Asia, dengue fe v er was the main cause, while in Southeast Asia, leptospirosis was the primary diagnosis.Another paper also indicated that Burkina Faso and Sudan, both countries located in Sub-Sahar an Africa, ar e mentioned as places wher e malaria is a particularl y pr e v alent cause of AUFI in c hildr en.These r egions hav e a high incidence of malaria cases due to the presence of malariatransmitting mosquitoes.In addition to malaria, acute respiratory infections (ARIs) are noted as a primary cause of AUFI in Sub-Saharan Africa.ARIs encompass a range of respiratory illnesses, including pneumonia and br onc hitis .T hese infections can lead to fe v er, cough, and difficulty breathing, making them a common cause of febrile illness (Ouédraogo et al. 2020 ).Another prospectiv e observ ational study conducted among se v en hospitals in India has demonstrated a mortality rate of 2.4% (37 deaths and 46.9% died within 2 days of admission, suggesting delayed hospitalization due to lack of clinical presentation as a contributing factor.Malaria, leptospirosis, scrub typhus, dengue fe v er and bacterial blood stream infections (including enteric fe v er) wer e to be most common causes in those fatal cases (Mørch et al. 2023 ).A case-contr ol anal ysis fr om Vietnam has mentioned that out of 378 AUFI patients nearly 42.9% were undiagnosed AFI cases and bacterial infections and parasitic diseases bacterial infections and parasitic diseases, might be underrepresented (Le-Viet et al. 2019 ).Inter estingl y, an inv estigation has analysed that among 765 travelers r eturning fr om tr opical and subtr opical r egions to Eur ope, 310 (40.5%) had a clear source of infection (mainly traveler's diarrhea or r espir atory infections), while 455 (59.5%) were categorized as having AUFI.Over 40% of returning travelers with AUFI were diagnosed with malaria or dengue, infections that can be easily diagnosed by rapid diagnostic tests .T his calls for development of ne w dia gnostic tests and tr eatments for AUFI (Mørc h et al. 2017 ).A study has reported that 340 patients with acute undifferentiated fe v er (AUF), 193 (56.8%) r emained undia gnosed after extensiv e inv estigations, r epr esenting a significantly high prevalence of undia gnosed undiffer entiated fe v er (UUDF) in Far North Queensland, Australia.After the prolonged diagnosis, dengue fever was the most frequent diagnosis (78 cases), follo w ed b y other infectious diseases like influenza, leptospirosis, and melioidosis.The study also r e v ealed a higher incidence of UUDF during the r ain y season (December to March), suggesting a potential link with increased mosquito activity and transmission of vector-borne diseases (Susilawati and McBride 2014 ).
Ho w e v er, clinicians belie v e that most of these cases are underdia gnosed and underr eported as febrile illness hence the actual number is most likely much higher.A study has reviewed that the most common causativ e a gent for AUFI cases in Peninsular Malaysia are dengue virus and Leptospira meanwhile malaria is mor e pr e v alent in Borneo.Ho w e v er, a r ecent study conducted in Teluk Intan, Perak at Peninsular Malaysia demonstrates that rickettsial infections are a significant cause of AFI whereby out of 309 hospitalized adults with AFI, 42 (19%) individuals were diagnosed with rickettsial infections and 4 (11%) patients with rickettsial infections died, highlighting the potential se v erity of this condition (Yuhana et al. 2022 ).
In addition, a 10 month period (2012 to 2013) cross-sectional study was conducted in University of Malaya Medical Centre (UMMC) with a collaboration of United States Naval Medical Research Unit 2 (NAMR U2), in volving 119 adult inpatients from the infectious diseases w ar d.It w as found that 67 (52.3%) cases of probable dengue and 25 (19.5%)cases of confirmed dengue, follo w ed b y typhus 8 (6.2%) cases, influenza 8 (6.2%) cases and leptospirosis 7(5.5%) cases have been reported using only serology testing which limits the diversity and relative importance of com-

AUFI and treatment
The treatment of AUFI depends on several factors, including the underlying cause of the fever, the severity of symptoms, and the patient's ov er all health.Since AUFI r epr esents a br oad category of illnesses, the treatment approach may vary widely .Firstly , the first step in treating AUFI is to identify the specific cause of the fe v er.This often r equir es a thor ough medical history, physical ex- ).If a bacterial infection is suspected or confirmed, antibiotics may be prescribed to treat the specific bacteria responsible for the illness .T he choice of antibiotics depends on the type of bacteria and its susceptibility to specific antibiotics.If a viral infection is diagnosed (e.g.influenza), antiviral medications may be used in some cases to reduce the severity and duration of symptoms (Gupta and Nischal 2020 ).Ho w ever, not all viral infections have specific antivir al tr eatments.In r egions wher e malaria is endemic, and if malaria is suspected or diagnosed, antimalarial medications are pr escribed to tr eat the infection.In the case of dengue fe v er, whic h is a mosquito-borne viral illness, it's important to manage the patient's condition car efull y.Hospitalization and supportive care are often necessary, as se v er e cases of dengue can be life-threatening (Rao et al. 2019 ).Patients with AUFI should be closely monitored for any worsening of symptoms, especially if they de v elop warning signs such as severe headache, difficulty breathing, chest pain, confusion, or persistent vomiting (Holgersson et al. 2022 ).Timely medical intervention may be needed.In regions where mosquito-borne illnesses like dengue fe v er and malaria are prevalent, preventing mosquito bites is par amount.Furthermor e, addr essing food and water safety is vital, involving safe food handling pr actices, thor ough cooking, and the consumption of purified water in areas where waterborne diseases are a concern (Wiemer et al. 2017 ).In situations where contagion risk is high, such as during outbreaks or in healthcare settings, using a ppr opriate personal pr otectiv e equipment (PPE) like masks , glo ves , and gowns is essential.It's equally important to avoid close contact with sick individuals, especially those displaying fe v er or symptoms of conta gious illnesses.Pr acticing r espir atory hygiene by covering the mouth and nose when coughing or sneezing helps pr e v ent disease transmission.Maintaining a clean environment by r egularl y disinfecting fr equentl y touc hed surfaces contributes to reducing the risk of infection.Table 3 shows potential intervention to control AUFI

T he rela tionship betw een One Health and AUFI
The One Health a ppr oac h is highly relevant when dealing with acute febrile illnesses, as it recognizes the interconnectedness of human health, animal health, and environmental health.Many AUFI are indeed zoonotic, which means they can be transmitted between animals and humans .T hese zoonotic diseases are caused by infectious a gents, suc h as bacteria, viruses, par asites, and fungi that can jump from animals to humans and vice versa (Mackenzie and Jeggo 2019 ).These are examples to illustrate the diversity of zoonotic diseases that can lead to AUFI.First, influenza, commonly known as the flu, which known to infect various animal species, including birds and pigs.It fr equentl y pr esents as an acute febrile illness.Influenza viruses are highly contagious and can lead to sudden fe v er, c hills, body ac hes, and r espiratory symptoms.Influenza shares many clinical symptoms with other acute febrile illnesses .T his includes fe v er, cough, and After being exposed to the rabies virus, a person may experience symptoms that are not specific to rabies, including fever, malaise , headache , and discomfort.T hese symptoms can resemble those of an acute febrile illness (Shepherd et al. 2023 ).Hantavirus Pulmonary Syndrome (HPS) is a se v er e r espir atory illness caused by the Hanta virus .HPS typically begins with non-specific symptoms, including fe v er, m uscle ac hes , fatigue , and sometimes gastrointestinal symptoms like nausea, vomiting, and abdominal pain.These symptoms can mimic those of an acute febrile illness caused by various pathogens.Howe v er, HPS is a potentiall y lifethreatening disease, and its severity sets it apart from most cases of acute febrile illness .T he r a pid pr ogr ession to r espir atory failur e and the risk of se v er e complications makes HPS a critical medical condition (Ramos 2008 ).On the other hand, brucellosis and acute febrile illness are related in the sense that brucellosis is a type of acute febrile illness c har acterized by fe v er, among other symptoms .Brucellosis , also known as undulant fe v er or Malta fe v er, is a bacterial infection caused by various species of the genus Brucella.Brucellosis is always considered one of the classic causes of acute febrile illness, especially in regions where the disease is endemic.Acute febrile illnesses are characterized by a sudden onset of fe v er and often involv e non-specific symptoms such as fatigue , malaise , headache , and m uscle ac hes, all of which can be present in brucellosis (Saddique et al. 2019 ).Leptospirosis is caused by the Leptospira bacteria and can vary in severity from mild to se v er e. Leptospir osis is classified as an acute febrile illness, which means it presents as a sudden and short-term fe v erish condition.Patients with leptospirosis often experience a rapid onset of symptoms, including fe v er, headac he, and m uscle pain (Haake and Le v ett 2015 ).Dia gnosing this zoonotic disease can be c hallenging because its symptoms ov erla p with those of other febrile illnesses, such as dengue fever or influenza.Laboratory tests, including blood cultures and serological tests, are often needed for confirmation.F ebrile illnesses ma y be tr eated with antimicr obial a gents, and the misuse of antibiotics refers to situations where antibiotics are used inappropriately or unnecessarily.This can include taking antibiotics for viral infections (common cold or flu), using antibiotics without a prescription, not completing the full course of prescribed antibiotics, or using antibiotics in animal a gricultur e for gr owth pr omotion r ather than disease tr eatment (Haake and Le v ett 2015 ).By promoting responsible antimicrobial use in both healthcare sectors and by addressing AMR through a One Health a ppr oac h, it is possible to mitigate the de v elopment and spread of antimicrobial resistance, ensuring that antibiotics remain effective for treating bacterial infections in the future.One Health can help improve disease surveillance inv olves the coor dinated collection, analysis, and interpretation of health data fr om m ultiple sources, including human health, animal health, and environmental data, prevention, and control strategies for AUFI, ultimately benefiting both human and animal populations and the environment (Nadjm et al. 2012, Ajuwon et al. 2021, Blair et al. 2022, Grundy and Houpt 2022, Raab et al. 2022 ).

Emerging Zoonotic Risks and Ongoing Outbreaks
The threat of novel zoonotic diseases and ongoing outbreaks COVID-19 and its potential ev olution to w ar ds endemicity, due to ov erla pping symptoms and difficulty in r a pid dia gnosis, this adds a complex layer to the already challenging landscape of AUFI.The emerging zoonotic risks are due to increased human encroachment on wildlife habitats and deforestation heighten the risk of zoonotic pathogens jumping from animals to humans (Meurens et al. 2021 ).Ne w vir al str ains , bacterial zoonoses , and e v en fungal infections could present as AUFI, posing diagnostic challenges (Bardhan et al. 2023 ).In addition, Climate change is one of the gr eatest thr eats to human health in the 21st century.Shifting temper atur e and pr ecipitation patterns can alter the geogr a phic distribution of vector-borne diseases like arbo viruses , expanding their r eac h and contributing to AUFI cases in pr e viousl y unaffected regions (Caminade et al. 2019 ).Lastly, the intensification of animal a gricultur e and close contact with domesticated animals create additional pathways for zoonotic transmission.Emerging pathogens originating in liv estoc k may manifest as AUFI in human populations (Jones et al. 2013 ).On top of that, the emergence of antimicrobial resistance in pathogens causing common AUFI-associated diseases like leptospirosis and enteric fever can complicate treatment and lead to prolonged illness, contributing to undiagnosed or misdiagnosed cases.In addition, incomplete or insufficient vaccine coverage for established zoonotic diseases like influenza and rabies can leave populations vulnerable to outbreaks, leading to an upsurge in AUFI cases with similar presentations (Trott et al. 2018 ).
Emer ging cor onaviruses is one the example of zoonotic disease including SARS-CoV-2, can jump from animals to humans thr ough v arious contacts and ada pt to human tr ansmission.SARS-CoV-2 is a nov el cor onavirus that was identified as the cause of the COVID-19 pandemic, which began in late 2019 (Haider et al. 2020 ).SARS-CoV-2 has demonstrated the ability to mutate and de v elop ne w v ariants, some of whic h may impact tr ansmissibility, se v erity, or imm une e v asion.Continuous monitoring of v ariants is crucial for understanding their potential impact on public health.Another example, enter ohemorrha gic Esc heric hia coli (E.coli) O157:H7 is a strain of E. coli bacteria that can cause se v er e illness, particularl y thr ough foodborne tr ansmission.It stands out due to its association with se v er e complications suc h as hemolytic ur emic syndr ome, r enal failur e, and a significant contribution to foodborne outbreaks worldwide.Outbreaks associated with this str ain hav e been r e ported world wide, often link ed to consumption of contaminated food, including leafy greens like spinach or lettuce .T he bacteria can contaminate these foods during production, processing, or handling (Lim et al. 2010 ).Rickettsia is a genus of bacteria that includes se v er al species r esponsible for causing diseases in humans, such as Rocky Mountain spotted fever, typhus, and rick ettsial po x.Changes in climate patterns, including temper atur e, humidity, and precipitation, can influence the distribution and behavior of vectors like ticks , fleas , and mites that tr ansmit Ric kettsia bacteria.These alter ations in envir onmental conditions might expand the geogr a phical r ange of these vectors, potentiall y incr easing the incidence of Ric kettsia-r elated diseases in new areas or elevations where they were previously uncommon (Blanton 2019 ).Meanwhile , Henipa virus: belongs to the Henipa virus genus , also r esponsible for Nipah and Hendr a viruses known for their high mortality rates.Recent cases in China suggest animal-to-human transmission, with shrews identified as potential reservoirs .T he virus is ne wl y discov er ed, and m uc h r emains unknown about its transmission dynamics, pathogenic-ity, and long-term consequences (Quarleri et al. 2022 ).The outbreak of monk e ypo x outside its usual endemic regions in Africa during 2022-2023 indeed raised significant concerns in the public health sphere.Monk e ypo x is a r ar e vir al zoonotic disease that is primarily found in Central and West African countries .T he outbreak outside of these regions alerted health authorities globally about the potential for the disease to spread beyond its endemic ar ea.The outbr eak highlighted the possibility of zoonotic spillover e v ents, wher e the virus can jump from animals to humans, potentiall y thr ough contact with infected animals or contaminated animal products (Antunes and Virgolino 2022 ).During the COVID-19 pandemic , mucormycosis , a r ar e but se v er e fungal infection primaril y affecting imm unocompr omised individuals, witnessed a concerning sur ge, notabl y among COVID-19 patients .T he infection's escalation was attributed to compromised immune sys-Figur e 2. T his flowc hart pr ovides a structur ed a ppr oac h to diagnosing AUFI by considering various potential causes and guiding clinicians through the dia gnostic pr ocess based on clinical pr esentation, epidemiological factors, and laboratory findings.tems due to COVID-19 se v erity, corticoster oid tr eatments, and v arious medical interventions, emphasizing the susceptibility to opportunistic infections.Heightened awareness among healthcare providers became crucial for early identification of mucormycosis symptoms-facial swelling, nasal congestion, and black lesionsand prompt initiation of appropriate antifungal therapies and, if necessary, sur gical interv entions (Dam et al. 2023 ).Meanwhile, melioidosis is a soil-and water-borne bacterium is causing increasing infections in Southeast Asia and Northern Australia, causing pneumonia, abscesses, and e v en death.Brucellosis bacterial disease transmitted through contact with livestock (mainly cattle) can cause c hr onic fatigue, fe v er, and joint pain.Str onger public health measures and liv estoc k v accination pr ogr ams ar e necessary for control (Boone et al. 2017 ). Figure 1 displays AUFI complex clinical presentation.

Challenges in resource-limited settings handling AUFI
Resource-limited settings gr a pple with m ultifaceted c hallenges in dealing with emerging zoonotic diseases, significantly impeding effectiv e healthcar e access, dia gnosis, tr eatment, public health interventions , and o verall disease management.The dearth of healthcar e infr astructur e , scarcity of medical facilities , and a critical shortage of healthcare personnel hinder timely diagnosis and pr ovision of car e, exacerbating the c hallenges faced by patients seeking essential healthcare services (Shiferaw et al. 2017 ).Di- agnostic difficulties arise from the absence of advanced laboratory facilities and r a pid tests, compounded by limited awareness among healthcare workers about emerging zoonotic diseases and ov erla pping symptoms with more common ailments, leading to misdiagnoses and delayed treatments.Compounding this issue, limited access to specific antiviral, antibacterial, or antiparasitic medications and inadequate supportive care due to financial constr aints significantl y hamper effectiv e tr eatment, leaving man y patients untreated or facing suboptimal therapeutic options (John et al. 2008 ).Weak disease surveillance systems, coupled with insufficient public awareness and education about zoonotic diseases, impede earl y detection, outbr eak contr ol, and pr e v entiv e measures, allowing these diseases to spread undetected (Villarroel et al. 2023 ).Moreover, fragmented communication and collaboration between human and animal health sectors hinder the implementation of effective One Health strategies, limiting pre-v entiv e measur es and exacerbating disease tr ansmission.These c hallenges r esult in undia gnosed cases , dela yed treatments , incr eased disease tr ansmission, and ov erwhelming str ain on alr eady ov erburdened healthcar e systems, ultimatel y impacting patient outcomes and escalating mortality rates (Ghai et al. 2022 ).Addressing these complex challenges demands a concerted effort to w ar d bolstering healthcare infrastructure, enhancing diagnostic ca pabilities, expanding healthcar e w orkfor ce, ensuring access to affordable medications and supportive care, strengthening disease surveillance, conducting robust public awareness campaigns, and fostering effective collaboration between human and animal health sectors through a comprehensive One Health appr oac h, crucial for mitigating the de v astating impact of emerging zoonotic diseases in resource-limited settings and curbing their widespr ead tr ansmission.Figur e 2 pr o vides the o v er all flowc hart on a structured approach to diagnosing AUFI by considering vari-ous potential causes and guiding clinicians through the diagnostic process based on clinical presentation, epidemiological factors, and laboratory findings.

Conclusion
The challenge of Acute Undifferentiated Febrile Illness (AUFI) encompasses a complex landscape of diverse causes, diagnostic hurdles, and tr eatment intricacies, particularl y accentuated in resource-limited settings .T his condition, c har acterized by fe v er and nonspecific symptoms, presents a diagnostic puzzle often compounded by limited healthcare access, inadequate diagnostic tools , and o v erla pping disease manifestations .T he multifaceted subtypes within AUFI demand tailored approaches for Diagnosed AFI, Non-Malarial AFI, and Undiagnosed AFI, emphasizing the critical need for impr ov ed dia gnostics and ongoing r esearc h.Mitigating AUFI's impact r equir es a m ultifaceted str ategy incor por ating pr e v entiv e measur es, enhanced healthcar e infr astructur e, heightened disease surveillance, interdisciplinary collaboration under the One Health fr ame work, and a concerted effort to addr ess emer ging zoonotic risks and ongoing outbr eaks.A compr ehensiv e a ppr oac h is vital for effectiv el y mana ging AUFI, ensuring timel y dia gnosis, a ppr opriate tr eatment, and pr e v entiv e measur es, especiall y crucial in resource-limited regions where healthcar e c hallenges ar e most pr onounced.
Table 1 displays the various subtype of AUFI.

Table 1 .
Various subtype of acute febrile illness.
mon infectious causes of AUFI (unpublished data).Table2shows the pr e v alence of AUFI worldwide.

Table 2 .
Acute febrile illness and pr e v alence.

Table 3 .
(Nayak 2014 )ervention to control AUFI.uscle pain, whic h ar e common featur es of both influenza and other febrile illnesses.Influenza is known for causing seasonal outbr eaks, commonl y r eferr ed to as the flu season.During these periods, healthcar e pr ofessionals should particularl y vigilant for cases of acute febrile illnesses that might be attributed to influenza(Nayak 2014 ).Secondly, zoonotic coronaviruses such as COVID-19, caused by the novel coronavirus SARS-CoV-2.It is belie v ed to hav e originated in bats and possibl y passed to humans through an intermediate host.Both acute febrile illnesses and COVID-19 often present with fever as a prominent symptom.Fever is the body's response to infections and can be caused by a wide range of pathogens, including viruses, bacteria, and parasites.COVID-19 is primarily a respiratory illness and typically presents with symptoms such as cough, shortness of br eath, and c hest discomfort.While acute febrile illnesses can have respiratory symptoms , they ma y not always be as prominent as in COVID-19.The pr e v alence of COVID-19 in a community and a patient's exposure history are important considerations in diagnosing and managing febrile illnesses.Healthcare providers need to consider the possibility of COVID-19, especially during the ongoing pandemic (Alana gr eh et al. 2020 ).Another one is rabies is a viral infection caused by the rabies virus, which is primarily transmitted through the saliva of infected animals, usually through bites or scratches. m