Global knowledge gaps in acute febrile illness etiologic investigations: A scoping review

Rhee, Chulwoo; Kharod, Grishma A.; Schaad, Nicolas; Furukawa, Nathan W.; Vora, Neil M.; Blaney, David D.; Crump, John A.; Clarke, Kevin R.

doi:10.1371/journal.pntd.0007792

Cited by 20 publications

(28 citation statements)

References 29 publications

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“…This study provides an important epidemiologic characterization of AFI in 3 sub-Saharan African countries to complement previous work [ 13 , 28 , 29 ]. The study involved predominantly outpatient children and adolescents from sites in Burkina Faso, Madagascar, and Sudan.…”

Section: Discussionmentioning

confidence: 52%

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Pathogens That Cause Acute Febrile Illness Among Children and Adolescents in Burkina Faso, Madagascar, and Sudan

Marks

Liu

Soura

et al. 2021

Clinical Infectious Diseases

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Background The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood. Methods Blood samples taken from study participants with acute fever (≥37.5°C) or a history of fever and recruited into the previous Typhoid-Fever-Surveillance-in-Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral and parasitic pathogens. Clinical metadata were also assessed. Results A total of 615 blood samples available for analysis originated from Burkina Faso (n=53), Madagascar (n=364) and Sudan (n=198) and were taken from participants ranging from 0-19 years of age. Most individuals [86.4% (531/615)] presenting at healthcare facilities were outpatient adolescents (11-19 years-old). Leading clinical diagnoses were respiratory tract infections [45.9% (282/615)], malaria [27.3% (168/615)], and gastrointestinal tract infections [10.7% (66/615)]. Through the TaqMan-Array Card, at least one pathogen was detected in 62% (33/53), 24% (86/364), and 60% (118/198) of specimens, from Burkina Faso, Madagascar and Sudan, respectively. The leading identified pathogen overall was Plasmodium spp., accounting for 47% (25/53), 2.2% (8/364) and 45% (90/198) of AFI at respective sites. In Madagascar, dengue virus was the most prevalent pathogen (10.2%). Overall, 69% (357/516) of patients with clinical diagnoses of malaria, respiratory, or gastrointestinal infections were prescribed a WHO-guideline-recommended empiric antibiotic,whereas only 45% (106/237) of patients with pathogens detected were treated with an antibiotic exerting likely activity. Conclusions A PCR-approach for identifying multiple bacterial, viral and parasitic pathogens in whole blood unveiled a diversity of previously undetected pathogens in AFI cases and carries implications for the appropriate management of this common syndrome.

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Section: Discussionmentioning

confidence: 52%

“…Therefore, for an accurate diagnosis, a wide range of tests must be applied. Due to practical and economic constraints, most studies focus on a narrow range of suspect pathogens [ 13 ].…”

mentioning

confidence: 99%

Pathogens That Cause Acute Febrile Illness Among Children and Adolescents in Burkina Faso, Madagascar, and Sudan

Marks

Liu

Soura

et al. 2021

Clinical Infectious Diseases

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“…Most antipyretic takers consumed one class (85.9%), and the median number of doses taken was 2 [IQR 1 -3]. Of these 249 subjects, 167/249 (67%) reported the last dose administered at a mean of 2 [2][3][4][5] hours before hospital presentation. Subjects who were treated with an antipyretic drug before arrival did not differ from untreated ones regarding the temperature at arrival at the ED visit (37 ± 0.99 vs. 36.8 ± 0.86, p = 0.20) or the documented Tmax before the ED arrival (38.8 ± 0.79 vs. 38.4 ± 0.60, p = 0.29).…”

Section: 6%)mentioning

confidence: 99%

“…AFI investigations aim to provide national and subregional epidemiology and infectious diseases surveillance and to inform treatment guidelines about empirical and pathogen-specific management algorithms to prioritize interventions and funding. Several AFI investigations have been conducted primarily in Southeast Asia, with few global initiatives in resource-constrained countries [2]. However, there is no standardized approach to conducting such studies, limiting the interpretation and comparability of study findings.…”

Section: Introductionmentioning

confidence: 99%

The time is ripe to harmonize global acute febrile illness etiologic investigations

Moreira

Fernando-Carballo

Escadafal

et al. 2022

Preprint

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Acute febrile illness (AFI) is common for people seeking care globally and represents a spectrum of infectious and non-infectious etiologies with significant geographical variations. However, AFI research follows a heterogeneous methodology and reporting, making it challenging for individual fever studies interpretation and comparison and thus generating evidence-based decisions. Herein, we aim to conduct a pilot study investigating the impact of considering different case definitions of fever as inclusion criteria among febrile patients attending two Emergency Departments (ED) in Rio de Janeiro, Brazil, from October 28, 2018, to March 29, 2019. Secondarily, we explored the impact of the recent use of antipyretics in measured temperature at the arrival of the EDs. A prospective study was conducted, and we screened all consecutive non-severe patients who presented to the EDs. The inclusion criterion was the self-report of fever regardless of the temperature measured. A logistic regression model was built to investigate the factors associated with a febrile presentation at the arrival of EDs. We triaged 1551 subjects, and 374 [24.1% (95% CI 22-26)] had a history of fever, of whom 248 (66.3%), 115 (30.7%), and 11 (2.9%) had a temperature < 37.5 °C, ≥ 37.5 °C, and no temperature measurement registered at arrival, respectively. 198/374 (53%) had a suspicion of infection, and the site of infection varied according to the height of temperate at presentation. The antibiotic prescription was more likely in those who had a temperature ≥37.5 °C compared to those with a temperature <37.5 °C [crude OR: 2 (95% 1.1-3.5)]. 249/374 (66.6%) subjects reported self-administering an antipyretic within 2h [IQR 2-6] before EDs. Recent antipyretic uptake did not influence the measured temperature at presentation. In conclusion, we suggest harmonizing the case definition of fever in AFI research for a history of fever regardless of temperature cut-off would enable a complete picture of the different clinical fever phenotypes, thus improving our understanding of the global burden of febrile illness.

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“…Many patients with UFI in Nepal and other parts of South Asia are treated empirically [ 11 ] for enteric fever. In Nepal and the wider region, the selected antimicrobials depend upon availability and cost, but trimethoprim-sulfamethoxazole (SXT) and azithromycin are very commonly prescribed antibiotics [ 12 , 13 ].…”

mentioning

confidence: 99%

Trimethoprim-sulfamethoxazole Versus Azithromycin for the Treatment of Undifferentiated Febrile Illness in Nepal: A Double-blind, Randomized, Placebo-controlled Trial

Giri

Karkey

Dangol

et al. 2020

Clinical Infectious Diseases

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Background Azithromycin and trimethoprim-sulfamethoxazole (SXT) are widely used to treat undifferentiated febrile illness (UFI). We hypothesized that azithromycin is superior to SXT for UFI treatment, but the drugs are non-inferior to each other for culture-confirmed enteric fever treatment. Methods We conducted a double blind, randomized, placebo-controlled trial of azithromycin (20 mg/kg/day) or SXT (trimethoprim 10 mg/kg/day + sulfamethoxazole 50 mg/kg/day) orally for 7 days for UFI treatment in Nepal. We enrolled patients (aged 3-64 years) presenting to two Kathmandu hospitals with temperature ≥ 38.0°C for ≥4 days without localising signs. The primary endpoint was fever clearance time (FCT); secondary endpoints were treatment failure and adverse events. ClinicalTrials.gov number: NCT02773407. Results From June 2016 to May 2019, we randomized 326 participants (163 in each arm); 87 (26.7%) had blood culture-confirmed enteric fever. In all participants, the median FCT was 2.7 days (95% CI 2.6-3.3) in the SXT arm and 2.1 days (95% CI 1.6-3.2) in the azithromycin arm 1.25 (95% CI 0.99-1.58, P=0.059). The hazard ratio of treatment failures by 28 days between azithromycin and SXT was 0.62 (95% CI 0.37-1.05, p=0.073). Planned sub-group analysis showed azithromycin resulted in faster FCT in those with sterile blood cultures and less relapses in culture-confirmed enteric fever. Nausea, vomiting, constipation, and headache were more common in the SXT arm. Conclusions Despite similar FCT and treatment failure in the two arms, significantly fewer complications and relapses make azithromycin a better choice for empirical treatment of UFI in Nepal.

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Global knowledge gaps in acute febrile illness etiologic investigations: A scoping review

Cited by 20 publications

References 29 publications

Pathogens That Cause Acute Febrile Illness Among Children and Adolescents in Burkina Faso, Madagascar, and Sudan

Pathogens That Cause Acute Febrile Illness Among Children and Adolescents in Burkina Faso, Madagascar, and Sudan

The time is ripe to harmonize global acute febrile illness etiologic investigations

Trimethoprim-sulfamethoxazole Versus Azithromycin for the Treatment of Undifferentiated Febrile Illness in Nepal: A Double-blind, Randomized, Placebo-controlled Trial

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