Besides this possibility of false-negative results, there is also an issue of false-positive results. Nepal, and Cambodia), consecutive patients aged 5?years or older with persistent fever were prospectively recruited from January 2013 to October 2014. Participants underwent a reference diagnostic workup targeting a pre-established list of 12 epidemiologically relevant priority infections (i.e., malaria, tuberculosis, HIV, enteric fever, leptospirosis, rickettsiosis, brucellosis, melioidosis, relapsing fever, visceral leishmaniasis, human African trypanosomiasis, amebic liver abscess). The likelihood ratios (LRs) of clinical and basic laboratory features were determined by pooling all cases of each identified ubiquitous infection (i.e., found in all countries). In addition, we assessed the diagnostic accuracy of five antibody-based rapid diagnostic tests (RDTs): Typhidot Rapid IgM, Test-itTM Typhoid IgM Lateral Flow Assay, and SD Bioline Salmonella typhi IgG/IgM for Typhi infection, and Test-itTM Leptospira IgM Lateral Flow Assay and SD Bioline Leptospira IgG/IgM for leptospirosis. Results A total of 1922 patients (median age: 35?years; female: 51%) were enrolled (Sudan, Typhi and were 9% and 16% for the two RDTs targeting leptospirosis. Specificities ranged from 86 to 99% for Typhi detecting RDTs and were 96% and 97% for leptospirosis RDTs. Conclusions Leptospirosis, rickettsiosis, and enteric fever accounted each for a substantial proportion of the persistent fever caseload across all tropical areas, in addition to malaria, tuberculosis, and HIV. Very few discriminative features were however identified, and RDTs for leptospirosis and Typhi infection performed poorly. Improved field diagnostics are urgently needed for these challenging infections. Trial registration “type”:”clinical-trial”,”attrs”:”text”:”NCT01766830″,”term_id”:”NCT01766830″NCT01766830 at ClinicalTrials.gov. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-022-02347-8. Typhi or Paratyphi), leptospirosis, and rickettsiosis (spotted fever, typhus or groups), were expected to be found in most of the study sites, as AFI studies have shown all three to be endemic throughout the tropics . While the FH1 (BRD-K4477) field diagnosis of the former three infections has improved a lot in the past decade, the latter three bacterial infections remain notoriously difficult to diagnose in low-resource settings. The aims of this study were to determine the frequency of the conditions causing persistent fever in the tropics, FH1 (BRD-K4477) with a focus on the priority infections, and to identify by pooled analysis the clinical and laboratory predictors of the subset of ubiquitous infections. A secondary objective was to report on the diagnostic accuracy of five rapid diagnostic tests (RDTs) evaluated for some of these infections (three targeting Typhi infection and two leptospirosis). Methods Study design and setting This was a prospective multicentric FH1 (BRD-K4477) clinical and diagnostic study embedded in the NIDIAG project, which was launched in 2010 2010 by a consortium Grem1 gathering three African, four Asian, and six European institutions. The overall aim of the NIDIAG project was the diagnosis of (neglected) infectious diseases in resource-poor settings by making the best possible use of existing assays. More specifically, the project focused on the timely detection of priority severe and treatable infectious diseases and on the development and evaluation of pathogen-specific RDTs. Three challenging clinical syndromes were investigated: persistent fever, neurological disorders, and persistent digestive syndrome (the latter two syndromes are reported elsewhere) [11, 12]. The persistent fever study took place in six study sites located in two African (Sudan and Democratic Republic of Congo, DRC) and two Asian (Nepal and Cambodia) countries: a rural hospital in Gedaref State, Sudan; a rural district hospital and an outpatient health center in Mosango, province of Kwilu, DRC; a rural district hospital in Dhankuta and a university hospital in Dharan, Nepal; and the referral-level Sihanouk hospital center of Hope FH1 (BRD-K4477) in Phnom Penh, Cambodia: a rural hospital in Gedaref State, Sudan; a rural district hospital and an outpatient health center in Mosango, province of Kwilu, DRC; a rural district hospital in Dhankuta and a university hospital in Dharan, Nepal; and the referral-level Sihanouk hospital center of Hope in Phnom Penh, Cambodia. The NIDIAG sites were purposively chosen using the following criteria: presence of diverse etiologies of persistent fever (and in some cases FH1 (BRD-K4477) also neurological and digestive disorders) including local as well as ubiquitous and neglected as well as common infectious diseases, a sufficiently large number of patients seeking care for the targeted syndromes, capacity to carry out a range of laboratory tests, experience with good clinical and good clinical laboratory practice.