Table 1.

Summary of selected studies investigating the aetiology of febrile illness in Africa, published 2013-2018

	Study population	Study size	Testing	Main diagnoses	Comment and limitations
D’Acremont, Tanzania, 2006 (7)	Paediatric Outpatient District Hospital HIV prevalence: not stated	1005	Blood culture, respiratory virus and arboviral nucleic acid amplification testing (NAAT); arboviral serology; Leptospira, Coxiella, and Toxoplasma serology	Viral aetiology in 78% of systemic infections, 100% of nasopharyngeal infections, and 51% of lower respiratory infections Overall: 9% malaria, 4.2% bacteraemia	Challenging to determine causation due to high prevalence (76.9%) of co-infection and lack of healthy controls.
Crump, Tanzania, 2007–08 (6)	Paediatric/ adult Referral hospitals Inpatient HIV prevalence <13 years 12.2% ≥13 years : 39.0%	870	Antigen detection for Cryptococcus, Histoplasma capsulatum, Legionella pneumophila, Streptococcus pneumoniae; blood culture (aerobic and mycobacterial); NAAT for arboviruses; serology for Brucella, Leptospira, Coxiella, and Rickettsia; thick and thin blood film for parasites	<13 years: chikungunya 10.2%, leptospirosis 7.7%, 7.4% spotted fever group rickettsiosis (SFGR), 3.4% bacteraemia, 2.6% Q fever, 2.0% brucellosis, 1.3% malaria, 0.9% fungaemia, ≥13 years: 17.1% bacteraemia, 10.1% leptospirosis, 8.7% SFGR, 7.9% Q fever, 5.3% brucellosis, 5.7% chikungunya, 5.2% fungaemia, 3.5% mycobacteraemia, 2% malaria	Large proportion of patients (64.0% aged <13 years, and 33.2% ≥ 13 years without a aetiologic diagnosis. Respiratory viruses not sought.
Baba, Nigeria, 2006 (9)	Adult Referral hospital Hospitalisation and HIV status not reported	310	Serology for chikungunya, dengue, typhoid, West Nile virus (WNV), yellow fever; thick and thin film for malaria	67% dengue, 50.2% chikungunya, 32.6% typhoid, 29.4% malaria, 24.9% WNV,	The high prevalence of co-infection of mlalaria, serologically diagnosed typhoid, and arboviral infections highlights challenges of making diagnoses through non-reference standard tests
Jacob, Uganda, 2008-09 (10)	Adult Referral hospital Inpatients with severe sepsis HIV prevalence 100%	368	Antigen detection of Cryptococcus, blood culture (aerobic and mycobacterial); serology for HIV; thick and thin blood film for malaria,	23.4% Mycobacterium tuberculosis, 11% bacteraemia, 4% non-tuberculous mycobacteria, 2% Cryptococcus neoformans	Highly selected population, with limmited breadth of pathogens investigated
Chipwaza, Tanzania 2013 (8, 11)	District hospital Outpatient/ Inpatient HIV prevalence not stated	370	NAAT for influenza and dengue; serology for brucellosis, chikungunya, dengue, leptospirosis, typhoid; thick and thin blood films for malaria; urine microscopy for bacteria	<5 years: 31.3% dengue, 22.9% malaria, leptospirosis 19.5%, brucellosis 13.2%, typhoid 6.8%, 5.4% chikungunya, 1% influenza ≥5 years: 81.1% dengue, 49.7% brucellosis, 31% leptospirosis, 22.6% malaria, typhoid 14.4%, 4.1 influenza	High prevalence of co-infection of serologically diagnosed typhoid and zoonotic infections highlights the challenges o determining causation when non-reference standard tests are used
O’Meara, Maine Kenya, 2011-12 (12, 13)	Paediatric District hospital Outpatient HIV prevalence 0.4%	370	Antigen detection for group A Streptococcus, NAAT for adenovirus, influenza A and B, human metapneumovirus, parainfluenza virus 1-3, malaria, respiratory syncitial virus (RSV); serology for Rickettsia, Coxiella; thick and think films for parasites	22.4% SFGR, ‘ 20.3% influenza A/B, 10.5% adenovirus, 10.1% parainfluenza virus 1-3, 8.9% Q fever, 5.3% RSV 5.2% malaria 5.2%, 3.6% scrub typhus, hMNV 3.2%, group A Streptococcus 2.3%, 1.0% typhus group Rickettsia	Study notable for inclusion of healthy controls, in whom ≥1 pathgen was detected in 49.1%. Limitations include a limited selection of pathogens sought.