Table 3. Summary of 45 eligible studies of etiology of severe febrile illness in low- and middle-income countries, 1980–2013.
| First Author (Reference) | Location; study dates | Total no. of patients in study | Hospital type | Age (population type) | Diagnostic tests conducted | N (%) of diseases searched in review investigated in study | Patients (%) with confirmed infection | Patients infected with HIV (proportion of patients tested) | Most common pathogens |
|---|---|---|---|---|---|---|---|---|---|
| Eastern Africa | |||||||||
| Aarsland, S. J. et al[44] | Ethiopia, December 2009—January 2010 | 102 | Urban referral hospital. | 1 month –18 years. Primarily children. | DNA extraction and NAAT from malaria blood smears for S. pneumoniae, Salmonella spp, Rickettsia spp, Borrelia spp, Leptospira spp. (NAAT for Salmonella and S.pneumoniae did not meet case definitions) | 3 (12.0%) | 12 (11.8%) with positive NAAT* | Plasmodium spp, Rickettsia spp, Borrelia spp* | |
| Archibald, L. K., et al[2] | Tanzania; February 1995-April 1995 | 517 | Urban referral hospital | >15 years. | Blood culture. Thick and thin blood smears | 2 (8.0%) | 145 (28.9%) positive blood culture. 49 (9.8%) malaria slide positive | 282 (56.2%) | Mycobacterium tuberculosis, Non-typhoidal Salmonella, S.aureus, |
| Archibald, L. K., et al[56] | Malawi; July 1998—August 1998 | 229 | Urban referral hospital. | 1 month–13 years | Blood culture. Thick and thin blood smears | 2 (8.0%) | 35 (15.3%) positive blood culture. 13 (5.7%) malaria slide positive | 63 (28%) | Non-typhoidal Salmonella, E.coli, Acinetobacter |
| Bell, M., et al[47] | Malawi; March 1998—May 1998 | 238 | Urban referral hospital. | >14 years. Primarily adults | Blood culture (mycobacteria), Thick and thin blood smears | 2 (8.0%) | 67 (28.2%) positive blood culture. 72 (31.2%) malaria slide positive | 173 (75.9%) | Non-typhoidal Salmonella, Mycobacterium tuberculosis, Cryptococcus neoformans |
| Christopher, A., et al[48] | Tanzania; September 2011—Feb 2012 | 317 | Urban referral hospital. | 2–60 months | Blood culture. Thick and thin blood smears | 2 (8.0%) | 21 (6.6%) positive blood culture. 82 (25.9%) malaria slide positive | Plasmodium falciparum, E.coli, Klebsiella spp. | |
| Dougle, M., et al[51] | Kenya; July 1994—October 1994 | 228 | Urban referral, teaching hospital. | > 5 years. Primarily adults | Blood culture. Thick and thin blood smears | 2 (8.0%) | 51 (22.4%) positive blood culture. 25 (11.0%) malaria slide positive | 51 (22.5%) | S enterica serotype Typhi, S.pneumoniae, Non-typhoidal Salmonella |
| Gordon, M. A., et al. [5] | Malawi; December 1997—November 1998 | 9,298 | Urban referral teaching hospital. | Unspecified. Primarily adults | Blood culture | 1 (4.0%) | 449 (16.1%) positive blood culture | Non-typhoidal Salmonella, S.pneumoniae, E.coli | |
| McDonald, L. C., et al[35] | Malawi; August—September 1997 | 128 | Urban referral hospital (Malawi) | > 18 years | Mycobacterial blood culture | 1 (4.0%) | 14 (10.9%) positive blood culture | 101 (78.9%) in Malawi. | Mycobacterium tuberculosis |
| Meremo, A., et al[52] | Tanzania; June 2011—December 2011 | 346 | Urban tertiary referral hospital. | Unspecified. Primarily adults | Blood culture | 1 (4.0%) | 33(9.5%) positive blood culture | 156 (45.0%) | Non-typhoidal Salmonella, S.pneumoniae, E.coli |
| Nadjm, B., et al[53] | Tanzania; July 2006—May 2007 | 3,639 | District, rural hospital | 2 months—13 years. | Blood culture, malaria rapid diagnostic test, thick and thin blood smears | 2 (8.0%) | 341 (9.4%) positive blood culture. 2195 (60.3%) malaria slide positive | 142 (3.9%) | Non-typhoidal Salmonella |
| Petit, P. L. C., et al[54] | Kenya, 1990 | 336 | Study 1 urban and referral | > 8 years. Primarily adults | Blood culture, thick and thin blood smears | 2 (8.0%) | Only study 1–104 (30.9%) positive BSI. 25 (7.4%) malaria slide positive | 12 (3.6%) | Plasmodium spp, Salmonella spp, E.coli |
| Sigaúque, B., et al[40] | Mozambique; May 2001- April 2006 | 18,944 | Rural district hospital | <15 years | Blood culture. Thick and thin blood smears (Blood smears included neonates) | 2 (8.0%) | 1395 (7.4%) true positive blood culture. 9939 (52.5%) with malaria slide positive | Non-typhoidal Salmonella, S.pneumoniae, E.coli, | |
| Ssali, F. N., et al[6] | Uganda; January 2007—April 2007 | 299 | Urban referral, hospital | >15 years. | Blood culture (mycobacterial) | 1 (4.0%) | 71 (23.7%) positive blood culture | 228 (76.3%) | Mycobacterium tuberculosis, S.pneumoniae |
| Strøm, G. E. A[41] | Tanzania; January 2009- June 2009 | 304 | Urban referral hospital. | 1 month- 7 years. | Thick and thin blood smears, malaria rapid diagnostic test, NAAT | 1 (4.0%) | 76 (25.0%) NAAT positive for malaria | Plasmodium falciparum | |
| Lofgren, S. M., et al[34] | Tanzania; August 2007—September 2008 | 628 | Urban referral medical center and Regional hospital. | >13 years. Primarily adults | Histoplasma urine antigen testing | 1 (4.0%) | 7 (1.1%) positive for histoplasmosis | Histoplasma spp | |
| Crump, J. A., et al[4] | Tanzania; September 2007—August 2008 | 870 | Urban referral hospital. | Children (>2 years <13 years) Adults >13 years | Blood culture, thick and thin blood smears. Cryptococcal, S.pneumoniae, H.capsulatum antigen testing. Leptospirosis/ Brucellosis standard microscopic reciprocal test (MAT). Acute and convalescent serological investigation for Q fever and Spotted and typhus fever group rickettsiosis. NAAT for DENG, CHIKV and flavivirus RNA | 11 (44.0%) | Q fever (n = 24; 5.0%) spotted fever rickettsiosis (n = 36; 8.0%) typhus group rickettsiosis (n = 2; 0.4%) chikungunya (n = 55; 7.9%) brucellosis (n = 16; 3.5%) leptospirosis (n = 40; 8.8%) | Chikungunya virus, Leptospira, Rickettsial spp, | |
| Crump, J. A., et al[49] | Tanzania; September 2007—August 2008 | 403 | Urban referral hospital. | >13 years. Primarily adults | Blood culture (mycobacteria), Thick and thin blood smears | 2 (8.0%) | 104 (25.8%) positive blood culture. 8 (2.0%) with malaria slide positive | 161(39%) | S enterica serotype Typhi, S.pneumoniae, E.coli, Mycobacterium tuberculosis |
| Crump, J. A., et al[49] | Tanzania; September 2007—August 2008 | 467 | Urban referral hospital. | >2 years <13 years | Blood culture. Thick and thin blood smears | 2 (8.0%) | 20 (4.3%) positive blood culture. 6 (1.3%) malaria slide positive | 57 (12.2%) | S enterica serotype Typhi, S.pneumoniae, E.coli, Plasmodium spp |
| Western Africa | |||||||||
| Akpede, G. O., et al[55] | Benin; October 1988—October 1989 | 642 | Urban referral hospital. Children's emergency room | 1 month-5 years | Blood culture. Thick and thin blood smears | 2 (8.0%) | 24 (3.7%) positive blood culture. 403 (62.8%) malaria slide positive | Plasmodium spp, S.aureus | |
| Akpede, G. O., et al[60] | Benin; October 1988—October 1989 | 156 | Urban referral hospital. Children's emergency room | 1 month-5 years | Blood culture. Thick and thin blood smears | 2 (8.0%) | 67 (42.9%) positive blood culture. 116 (74.4%) malaria slide positive | Plasmodium spp, S.aureus, Citrobacter spp | |
| Ayoola, O. O., et al[61] | Nigeria; June 1998—November 1998 | 102 | Urban referral hospital. Children's emergency room | 1–12months | Blood culture. Thick and thin blood smears | 2 (8.0%) | 39 (38.2%) positive blood culture. 31 (30.4%) with malaria slide positive | Plasmodium spp, S.aureus, E.coli | |
| Baba, M., et al[45] | Nigeria, July 2008- December 2008 | 310 | Urban, referral, tertiary, teaching hospital | All age groups. Primarily adults | Thick and thin blood smears, Widal test. Plaque reduction neutralization tests for CHIK, YF, DENG, WNV (Did not meet case definitions for Widal and viral tests) | 1 (4.0%) | 49 (15.8%) malaria slide positive | Plasmodium spp | |
| Ki-Zerbo, G. A., et al[57] | Burkina Faso; January 1995—March 1995 | 183 | Teaching hospital | >15 years | Acute and convalescent serological investigation for Spotted and typhus group rickettsiosis and Q fever | 2 (8.0%) | 17 (5.5%) | Rickettsial spp (SFG) Rickettsial spp (TG) Coxiella spp | |
| Lekweiry, K. M., et al[33] | Mauritania; 2009–2010 | 301 | National hospital | 1 month -14 years | Thick and thin blood smears, NAAT for malaria | 1 (4.0%) | 105 malaria positive by NAAT | Plasmodium spp | |
| Obaro, S., et al[38] | Nigeria; September 2008—November 2009 | 969 | 7 hospitals | 2 months -5 years | Blood culture | 1 (4.0%) | 111 (11.5%) with positive blood cultures | S enterica serotype Typhi, Non typhoidal Salmonella, S. aureus | |
| North Africa | |||||||||
| Afifi, S., et al[26] | Egypt; 1999–2003 | 10,130 | Public infectious disease hospital | > 4 years. Primarily adults | Blood culture | 1 (4.0%) | 1005 (10.2%) with positive blood culture | Salmonella enterica serotype Typhi, Brucella spp, S.aureus | |
| Hyams, K. C., et al[62] | Sudan; Jan 1984—Feb 1984 | 100 | Urban hospital | > 12 years. Primarily adults | Blood culture, virology test- isolation and acute and convalescent serological investigation for DENV, YF, WNV, CHIK, thick and thing blood smears | 5 (5.0%) | 25 (25%) positive blood culture, 21(21%) virus isolation, 13 (13%) malaria slide positive | Dengue virus, Salmonella enterica serotype Typhi, Plasmodium spp | |
| South Central Asia | |||||||||
| Abbasi et al[25] | Pakistan; September 2007—January 2008 | 112 | Urban teaching hospital | > 13 years. Primarily adults | Thick and thin blood smears. Dengue viral specific immunoglobulin detection (Did not meet dengue case definition) | 1 (4.0%) | 26 (23.2%) malaria slide positive | Plasmodium spp | |
| Akram, D. S[63] | Pakistan; June 1994—September 1994 | 25 | Urban, Pediatric hospital | 1 month- 12 years | Acute and convalescent serology for dengue virus, West Nile virus, JEV | 3 (12.0%) | 10 (4%) serologically confirmed cases | Dengue virus, West Nile virus | |
| Blacksell, S. D., et al[46] | Nepal, Kathmandu; July 2002—June 2004 | 103 | Urban, referral, community general hospital | > 17 years | Blood culture. Serology for scrub typhus, murine typhus, leptospirosis, dengue. Included only for blood culture and paired acute and convalescent sera | 3 (12.0%) | 29 (28.1%) positive blood culture, 14 (13.5%) confirmed serology | Salmonella enterica serotype Typhi, Salmonella enterica Paratyphi A, R.typhi | |
| Chrispal, A., et al[29] | South India; January 2007—January 2008 | 398 | Tertiary care referral hospital | >16 years | Blood culture, thick and thin blood smears, serological testing for scrub typhus, Dengue virus, Leptospira spp, SFG rickettsiosis (did not meet serological case definitions) | 1 (4.0%) | 32 (8.0%) positive blood cultures, 68 malaria slide positive | Salmonella enterica serotype Typhi, Salmonella enterica Paratyphi A, Plasmodium spp | |
| Faruque, L. I[30] | Bangladesh; December 2008—November 2009 | 462 | Six tertiary level, teaching, referral hospital | Unspecified. Primarily adults | Malaria rapid diagnostic test. Serological testing for dengue virus (Did not meet dengue case definition) | 1 (4.0%) | 3 (0.6%) positive for malaria rapid diagnostic test | Plasmodium spp | |
| Kaushik, J. S., et al[32] | India; June 2008—December2008 | 1,680 | Urban tertiary, hospital | 1 month- 12 years | Thick and think blood films for malaria parasites | 1 (4.0%) | 38 (2.3%) malaria slide positive | Plasmodium spp | |
| Murdoch, D. R., et al[36] | Nepal, Kathmandu; Jan 2001—March 2001 and July—August 2001 | 876 | Urban, general hospital | >14 years old. | Blood culture, Urinary antigen testing, serological testing for IgM antibodies dengue virus, Leptospira spp, Scrub typhus and R.typhi (did not meet serological case definition) | 1 (4.0%) | 137 (15.6%) positive blood culture | Salmonella enterica serotype Typhi, Salmonella enterica Paratyphi A | |
| Pattanaik, Sarit S[39] | India; 2008–2009 | 67 | Teaching hospital | >15 years. | Blood culture, NAAT | 1 (4.0%) | No positive results | ||
| Zimmerman, M. D., et al[43] | Nepal, Kathmandu; Jan 2001—March 2001 and July—August 2001 | 756 | Urban, tertiary care hospital | >14 years old | R.typhi NAAT | 1 (4.0%) | 50 (6.6%) positive NAAT | R.typhi | |
| South East Asia | |||||||||
| Archibald, L. K., et al[27] | Thailand, Bangkok; February 1997—April 1997 | 246 | Urban, referral, infectious disease hospital. | >15 years. | Blood culture (mycobacterial) | 1 (4.0%) | 119 (48.4%) positive blood culture | C. neoformans, Mycobacterium tuberculosis, Non-typhoidal Salmonella | |
| Blair, P. J., et al[28] | Cambodia; December 2006—December 2008 | 4,233 | Two referral hospitals | > 2 years | Blood, throat and nasal specimen. rRT- NAAT, virus isolation, HI assay | 1 (4.0%) | 1151 (27.2%) with confirmed influenza | ||
| Chheng, K., et al[3] | Cambodia; October 2009—October 2010 | 1,193 | Urban, referral, government hospital. | < 16 years, neonates excluded | Blood culture. Thick and thin blood smear. Nucleic amplification test, serological testing for JEV, DENV), Acute and convalescent serological testing for R.typhi and Orientia tsutsugamushi, NAAT for Leptospira spp, nasal and throat specimen, rRT-NAAT for influenza (Did not meet case definitions for DENV and JEV) | 6 (24.0%) | 149 (12.5%) positive blood culture, 96 (8.0%) Orientia tsutsugamushi, 27 (2.2%) R.typhi, Influenza 25 (2.1%) 24(2.0%) malaria slide positive, 17 (1.4%) Leptospira spp | Orienta tsutsugamushi, S.aureus R.typhi | |
| McDonald, L. C., et al[35] | Thailand; February 1997—March 1997 and August—September 1997 | 216 | Urban, referral hospital in Thailand. | > 18 years | Mycobacterial blood culture | 1 (4.0%) | 20 (9.3%) positive blood culture | 154 (71.3%) in Thailand | Mycobacterium tuberculosis |
| Cohen, Adam L[58] | Thailand; February 2002—February 2003 | 704 | Four district rural hospitals | > 6 years. Primarily adults | Acute and convalescent serological examination for dengue virus, and Leptospira spp | 2 (8.0%) | 199 (28.3%) with confirmed serology | Dengue virus, Leptospira spp | |
| Kalayanarooj, S., et al[31] | Thailand; April 1994—December 1994 | 172 | One urban children's hospital. One rural provincial hospital | 6 months—14 years | Dengue virus isolation and acute and convalescent serological examination | 1 (4.0%) | 60 (34.9%) with confirmed serology | Dengue virus | |
| Wijedoru, L.P., et al[42] | Cambodia; April 2009—June 2009 | 134 | Children's hospital | > 1 year <16 years | Blood culture | 1 (4.0%) | 5 (3.7%) positive blood culture | Salmonella enterica serotype Typhi | |
| Libraty, D. H., et al[59] | Thailand; 1994–1999 | 812 | One urban children's hospital. One rural provincial hospital | 6 months–14 years | Acute and convalescent serological examination for Leptospira spp and dengue. | 2 (8.0%) | 468 (44.8%) with confirmed serology | Dengue virus, Leptospira spp | |
| Western Asia | |||||||||
| Nimri, L. F., et al[37] | Jordan; 1998–1999 | 210 | Urban pediatric teaching hospital. | 1 month—10 years | Blood culture | 1 (4.0%) | 94 (44.8%) positive blood culture | S.pneumoniae, E.coli, Klebsiella spp | |
*NAAT–Nucleic acid amplification test
*spp.—species