Challenges in the Etiology and Diagnosis of Acute Febrile Illness in Children in Low- and Middle-Income Countries

Pui-Ying Iroh Tam, Stephen K Obaro, Gregory Storch, Pui-Ying Iroh Tam, Stephen K Obaro, Gregory Storch

Abstract

Acute febrile illness is a common cause of hospital admission, and its associated infectious causes contribute to substantial morbidity and death among children worldwide, especially in low- and middle-income countries. Declining transmission of malaria in many regions, combined with the increasing use of rapid diagnostic tests for malaria, has led to the increasing recognition of leptospirosis, rickettsioses, respiratory viruses, and arboviruses as etiologic agents of fevers. However, clinical discrimination between these etiologies can be difficult. Overtreatment with antimalarial drugs is common, even in the setting of a negative test result, as is overtreatment with empiric antibacterial drugs. Viral etiologies remain underrecognized and poorly investigated. More-sensitive diagnostics have led to additional dilemmas in discriminating whether a positive test result reflects a causative pathogen. Here, we review and summarize the current epidemiology and focus particularly on children and the challenges for future research.

Keywords: antimicrobial stewardship; clinical algorithm; diagnostics; epidemiology; etiology; management; molecular; resource-limited settings; serology; undifferentiated fever.

© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

References

    1. Liu L , Johnson HL , Cousens S et al. . Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000 . Lancet 2012. ; 379 : 2151 – 61 .
    1. Archibald LK , den Dulk MO , Pallangyo KJ , Reller LB . Fatal Mycobacterium tuberculosis bloodstream infections in febrile hospitalized adults in Dar es Salaam, Tanzania . Clin Infect Dis 1998. ; 26 : 290 – 6 .
    1. Bell M , Archibald LK , Nwanyanwu O et al. . Seasonal variation in the etiology of bloodstream infections in a febrile inpatient population in a developing country . Int J Infect Dis 2001. ; 5 : 63 – 9 .
    1. Aregawi MW , Ali AS , Al-mafazy AW et al. . Reductions in malaria and anaemia case and death burden at hospitals following scale-up of malaria control in Zanzibar, 1999–2008 . Malaria J 2011. ; 10 : 46 .
    1. Bouyou-Akotet MK , Mawili-Mboumba DP , Kendjo E et al. . Evidence of decline of malaria in the general hospital of Libreville, Gabon from 2000 to 2008 . Malaria J 2009. ; 8 : 300 .
    1. D'Acremont V , Lengeler C , Genton B . Reduction in the proportion of fevers associated with Plasmodium falciparum parasitaemia in Africa: a systematic review . Malaria J 2010. ; 9 : 240 .
    1. Karema C , Aregawi MW , Rukundo A et al. . Trends in malaria cases, hospital admissions and deaths following scale-up of anti-malarial interventions, 2000–2010, Rwanda . Malaria J 2012. ; 11 : 236 .
    1. Mharakurwa S , Mutambu SL , Mberikunashe J , Thuma PE , Moss WJ , Mason PR . Changes in the burden of malaria following scale up of malaria control interventions in Mutasa District, Zimbabwe . Malaria J 2013. ; 12 : 223 .
    1. Otten M , Aregawi M , Were W et al. . Initial evidence of reduction of malaria cases and deaths in Rwanda and Ethiopia due to rapid scale-up of malaria prevention and treatment . Malaria J 2009. ; 8 : 14 .
    1. Chipwaza B , Mugasa JP , Mayumana I , Amuri M , Makungu C , Gwakisa PS . Community knowledge and attitudes and health workers’ practices regarding non-malaria febrile illnesses in eastern Tanzania . PLoS Negl Trop Dis 2014. ; 8 : e2896 .
    1. Crump JA , Morrissey AB , Nicholson WL et al. . Etiology of severe non-malaria febrile illness in northern Tanzania: a prospective cohort study . PLoS Negl Trop Dis 2013. ; 7 : e2324 .
    1. Nadjm B , Mtove G , Amos B et al. . Severe febrile illness in adult hospital admissions in Tanzania: a prospective study in an area of high malaria transmission . Trans R Soc Trop Med Hyg 2012. ; 106 : 688 – 95 .
    1. O'Meara WP , Mott JA , Laktabai J et al. . Etiology of pediatric fever in western Kenya: a case-control study of falciparum malaria, respiratory viruses, and streptococcal pharyngitis . Am J Trop Med Hyg 2015. ; 92 : 1030 – 7 .
    1. Naing C , Kassim AI . Scaling-up attention to nonmalaria acute undifferentiated fever . Trans R Soc Trop Med Hyg 2012. ; 106 : 331 – 2 .
    1. Adams WG , Deaver KA , Cochi SL et al. . Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era . JAMA 1993. ; 269 : 221 – 6 .
    1. Whitney CG , Farley MM , Hadler J et al. . Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine . N Engl J Med 2003. ; 348 : 1737 – 46 .
    1. Hsiao AL , Chen L , Baker MD . Incidence and predictors of serious bacterial infections among 57- to 180-day-old infants . Pediatrics 2006. ; 117 : 1695 – 1701 .
    1. Rudinsky SL , Carstairs KL , Reardon JM , Simon LV , Riffenburgh RH , Tanen DA . Serious bacterial infections in febrile infants in the post-pneumococcal conjugate vaccine era . Acad Emerg Med 2009. ; 16 : 585 – 90 .
    1. Watt K , Waddle E , Jhaveri R . Changing epidemiology of serious bacterial infections in febrile infants without localizing signs . PloS One 2010. ; 5 : e12448 .
    1. Colvin JM , Muenzer JT , Jaffe DM et al. . Detection of viruses in young children with fever without an apparent source . Pediatrics 2012. ; 130 : e1455 – 62 .
    1. Levine OS , O'Brien KL , Deloria-Knoll M et al. . The Pneumonia Etiology Research for Child Health Project: a 21st century childhood pneumonia etiology study . Clin Infect Dis 2012. ; 54 ( Suppl 2 ): S93 – 101 .
    1. Mtove G , Amos B , Nadjm B et al. . Decreasing incidence of severe malaria and community-acquired bacteraemia among hospitalized children in Muheza, north-eastern Tanzania, 2006–2010 . Malaria J 2011. ; 10 : 320 .
    1. Worldwide Antimalarial Resistance Network (WWARN) . Nonmalarial febrile illness map . Available at: . Accessed December 22, 2015.
    1. Misallati A , el-Bargathy S , Shembesh N . East Mediterr Health J 2000. ; 6 : 483 – 6 .
    1. Walsh AL , Phiri AJ , Graham SM , Molyneux EM , Molyneux ME . Bacteremia in febrile Malawian children: clinical and microbiologic features . Pediatr Infect Dis J 2000. ; 19 : 312 – 8 .
    1. Kayange N , Kamugisha E , Mwizamholya DL , Jeremiah S , Mshana SE . BMC Pediatr 2010. ; 10 : 39 .
    1. World Health Organization . Guidelines for the Diagnosis and Treatment of Malaria in Africa . AFRO Technical Papers . Vol. 22 . Geneva: : World Health Organization; ; 1992. : pp 1 – 46 .
    1. Lundgren IS , Heltshe SL , Smith AL , Chibwana J , Fried MW , Duffy PE . Bacteremia and malaria in Tanzanian children hospitalized for acute febrile illness . J Trop Pediatr 2015. ; 61 : 81 – 5 .
    1. D'Acremont V , Kilowoko M , Kyungu E et al. . Beyond malaria—causes of fever in outpatient Tanzanian children . N Engl J Med 2014. ; 370 : 809 – 17 .
    1. Archibald LK , Nwanyanwu O , Kazembe PN et al. . Detection of bloodstream pathogens in a bacille Calmette-Guerin (BCG)-vaccinated pediatric population in Malawi: a pilot study . Clin Microbiol Infect 2003. ; 9 : 234 – 8 .
    1. O'Dempsey TJ , McArdle TF , Lloyd-Evans N et al. . Importance of enteric bacteria as a cause of pneumonia, meningitis and septicemia among children in a rural community in the Gambia, West Africa . Pediatr Infect Dis J 1994. ; 13 : 122 – 8 .
    1. Nathoo KJ , Chigonde S , Nhembe M , Ali MH , Mason PR . Community-acquired bacteremia in human immunodeficiency virus-infected children in Harare, Zimbabwe . Pediatr Infect Dis J 1996. ; 15 : 1092 – 7 .
    1. Okwara FN , Obimbo EM , Wafula EM , Murila FV . Bacteraemia, urinary tract infection and malaria in hospitalised febrile children in Nairobi: is there an association ? East Afr Med J 2004. ; 81 : 47 – 51 .
    1. Sigauque B , Roca A , Mandomando I et al. . Community-acquired bacteremia among children admitted to a rural hospital in Mozambique . Pediatr Infect Dis J 2009. ; 28 : 108 – 13 .
    1. Meremikwu MM , Nwachukwu CE , Asuquo AE , Okebe JU , Utsalo SJ . Bacterial isolates from blood cultures of children with suspected septicaemia in Calabar, Nigeria . BMC Infect Dis 2005. ; 5 : 110 .
    1. Thriemer K , Ley B , Ame SS et al. . Clinical and epidemiological features of typhoid fever in Pemba, Zanzibar: assessment of the performance of the WHO case definitions . PloS One 2012. ; 7 : e51823 .
    1. Gordon MA , Walsh AL , Chaponda M et al. . Bacteraemia and mortality among adult medical admissions in Malawi—predominance of non-Typhi salmonellae and Streptococcus pneumoniae . J Infect 2001. ; 42 : 44 – 9 .
    1. Crump JA , Ramadhani HO , Morrissey AB et al. . Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania . Clin Infect Dis 2011. ; 52 : 341 – 8 .
    1. Brooks WA , Hossain A , Goswami D et al. . Bacteremic typhoid fever in children in an urban slum, Bangladesh . Emerg Infect Dis 2005. ; 11 : 326 – 9 .
    1. Naheed A , Ram PK , Brooks WA et al. . Burden of typhoid and paratyphoid fever in a densely populated urban community, Dhaka, Bangladesh . Int. J Infect Dis 2010. ; 14 ( Suppl 3 ): e93 – 9 .
    1. Owais A , Sultana S , Zaman U , Rizvi A , Zaidi AK . Incidence of typhoid bacteremia in infants and young children in southern coastal Pakistan . Pediatr Infect Dis J 2010. ; 29 : 1035 – 9 .
    1. Akram DS , Igarashi A , Takasu T . Dengue virus infection among children with undifferentiated fever in Karachi . Indian J Pediatr 1998. ; 65 : 735 – 40 .
    1. Thompson CN , Blacksell SD , Paris DH et al. . Undifferentiated febrile illness in Kathmandu, Nepal . Am J Trop Med Hyg 2015. ; 92 : 875 – 8 .
    1. Brown GW , Shirai A , Jegathesan M et al. . Febrile illness in Malaysia—an analysis of 1,629 hospitalized patients . Am J Trop Med Hyg 1984. ; 33 : 311 – 5 .
    1. Pradutkanchana J , Pradutkanchana S , Kemapanmanus M , Wuthipum N , Silpapojakul K . The etiology of acute pyrexia of unknown origin in children after a flood . Southeast Asian J Trop Med Public Health 2003. ; 34 : 175 – 8 .
    1. Chheng K , Carter MJ , Emary K et al. . A prospective study of the causes of febrile illness requiring hospitalization in children in Cambodia . PloS One 2013. ; 8 : e60634 .
    1. Shwe TN , Nyein MM , Yi W , Mon A . Blood culture isolates from children admitted to Medical Unit III, Yangon Children's Hospital, 1998 . Southeast Asian J Trop Med Public Health 2002. ; 33 : 764 – 71 .
    1. Libraty DH , Myint KS , Murray CK et al. . A comparative study of leptospirosis and dengue in Thai children . PLoS Negl Trop Dis 2007. ; 1 : e111 .
    1. Mayxay M , Castonguay-Vanier J , Chansamouth V et al. . Causes of non-malarial fever in Laos: a prospective study . Lancet Glob Health 2013. ; 1 : e46 – 54 .
    1. Capeding MR , Chua MN , Hadinegoro SR et al. . Dengue and other common causes of acute febrile illness in Asia: an active surveillance study in children . PLoS Negl Trop Dis 2013. ; 7 : e2331 .
    1. Silpapojakul K , Chupuppakarn S , Yuthasompob S et al. . Scrub and murine typhus in children with obscure fever in the tropics . Pediatr Infect Dis J 1991. ; 10 : 200 – 3 .
    1. Gatchalian SR , Quiambao BP , Morelos AM et al. . Bacterial and viral etiology of serious infections in very young Filipino infants . Pediatr Infect Dis J 1999. ; 18 ( 10 Suppl ): S50 – 5 .
    1. Bruce MG , Sanders EJ , Leake JA et al. . Leptospirosis among patients presenting with dengue-like illness in Puerto Rico . Acta Trop 2005. ; 96 : 36 – 46 .
    1. Valero N , Anez F , Larreal Y , Arias J , Rodriguez Z , Espina LM . Evaluation of immunity against Venezuelan equine encephalitis virus and dengue in the human population of San Carlos, the Almirante Padilla Island Municipality, Zulia State, Venezuela . 1996 [in Spanish]. Invest Clin 2001. ; 42 : 161 – 9 .
    1. Manock SR , Jacobsen KH , de Bravo NB et al. . Etiology of acute undifferentiated febrile illness in the Amazon basin of Ecuador . Am J Trop Med Hyg 2009. ; 81 : 146 – 51 .
    1. Forshey BM , Guevara C , Laguna-Torres VA et al. . Arboviral etiologies of acute febrile illnesses in western South America, 2000–2007 . PLoS Negl Trop Dis 2010. ; 4 : e787 .
    1. Prasad N , Murdoch DR , Reyburn H , Crump JA . Etiology of severe febrile illness in low- and middle-income countries: a systematic review . PloS One 2015. ; 10 : e0127962 .
    1. Leelarasamee A , Chupaprawan C , Chenchittikul M , Udompanthurat S . Etiologies of acute undifferentiated febrile illness in Thailand . J Med Assoc Thai 2004. ; 87 : 464 – 72 .
    1. Redd SC , Kazembe PN , Luby SP et al. . Clinical algorithm for treatment of Plasmodium falciparum malaria in children . Lancet 1996. ; 347 : 223 – 7 .
    1. Anderson KE , Joseph SW , Nasution R et al. . Febrile illnesses resulting in hospital admission: a bacteriological and serological study in Jakarta, Indonesia . Am J Trop Med Hyg 1976. ; 25 : 116 – 21 .
    1. Richens J , Smith T , Mylius T , Spooner V . An algorithm for the clinical differentiation of malaria and typhoid: a preliminary communication . P N G Med J 1992. ; 35 : 298 – 302 .
    1. Ross IN , Abraham T . Predicting enteric fever without bacteriological culture results . Trans R Soc Trop Med Hyg 1987. ; 81 : 374 – 7 .
    1. Vollaard AM , Ali S , Widjaja S et al. . Identification of typhoid fever and paratyphoid fever cases at presentation in outpatient clinics in Jakarta, Indonesia . Trans R Soc Trop Med Hyg 2005. ; 99 : 440 – 50 .
    1. Isaacman DJ , Karasic RB , Reynolds EA , Kost SI . Effect of number of blood cultures and volume of blood on detection of bacteremia in children . J Pediatr 1996. ; 128 : 190 – 5 .
    1. Kiragu AW , Zier J , Cornfield DN . Utility of blood cultures in postoperative pediatric intensive care unit patients . Pediatr Crit Care Med 2009. ; 10 : 364 – 8 .
    1. Zadroga R , Williams DN , Gottschall R et al. . Comparison of 2 blood culture media shows significant differences in bacterial recovery for patients on antimicrobial therapy . Clin Infect Dis 2013. ; 56 : 790 – 7 .
    1. Rosenblum J , Lin J , Kim M , Levy AS . Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative . Pediatr Blood Cancer 2013. ; 60 : 923 – 7 .
    1. Gilman RH , Terminel M , Levine MM , Hernandez-Mendoza P , Hornick RB . Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella Typhi in typhoid fever . Lancet 1975. ; 1 : 1211 – 13 .
    1. Wain J , Diep TS , Ho VA et al. . Quantitation of bacteria in blood of typhoid fever patients and relationship between counts and clinical features, transmissibility, and antibiotic resistance . J Clin Microbiol 1998. ; 36 : 1683 – 7 .
    1. Iroh Tam PY , Bernstein E , Ma X , Ferrieri P . Blood culture in evaluation of pediatric community-acquired pneumonia: a systematic review and meta-analysis . Hosp Pediatr 2015. ; 5 : 324 – 36 .
    1. Sehgal SC , Vijayachari P , Sharma S , Sugunan AP . LEPTO Dipstick: a rapid and simple method for serodiagnosis of acute leptospirosis . Trans R Soc Trop Med Hyg 1999. ; 93 : 161 – 4 .
    1. Dutta S , Sur D , Manna B et al. . Evaluation of new-generation serologic tests for the diagnosis of typhoid fever: data from a community-based surveillance in Calcutta, India . Diagn Microbiol Infect Dis 2006. ; 56 : 359 – 65 .
    1. Parry CM , Hoa NT , Diep TS et al. . Value of a single-tube Widal test in diagnosis of typhoid fever in Vietnam . J Clin Microbiol 1999. ; 37 : 2882 – 6 .
    1. Strid MA , Dalby T , Molbak K , Krogfelt KA . Kinetics of the human antibody response against Salmonella enterica serovars Enteritidis and Typhimurium determined by lipopolysaccharide enzyme-linked immunosorbent assay . Clin Vaccine Immunol 2007. ; 14 : 741 – 7 .
    1. Cleton NB , Godeke GJ , Reimerink J et al. . Spot the difference-development of a syndrome based protein microarray for specific serological detection of multiple flavivirus infections in travelers . PLoS Negl Trop Dis 2015. ; 9 : e0003580 .
    1. Mayxay M , Sengvilaipaseuth O , Chanthongthip A et al. . Causes of fever in rural southern Laos . Am J Trop Med Hyg 2015. ; 93 : 517 – 20 .
    1. Punjabi NH , Taylor WR , Murphy GS et al. . Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia . Am J Trop Med Hyg 2012. ; 86 : 46 – 51 .
    1. Kurokawa I , Kondo M , Akachi S . Early diagnosis of Japan spotted fever by PCR using skin samples . J Infect Chemother 2013. ; 19 : 628 – 32 .
    1. Andrews JR , Ryan ET . Diagnostics for invasive Salmonella infections: current challenges and future directions . Vaccine 2015. ; 33 ( Suppl 3 ): C8 – 15 .
    1. Holtz LR , Wylie KM , Sodergren E et al. . Astrovirus MLB2 viremia in febrile child . Emerg Infect Dis 2011. ; 17 : 2050 – 2 .
    1. McElvaniaTeKippe E , Wylie KM , Deych E , Sodergren E , Weinstock G , Storch GA . Increased prevalence of anellovirus in pediatric patients with fever . PloS One 2012. ; 7 : e50937 .
    1. Wilson MR , Naccache SN , Samayoa E et al. . Actionable diagnosis of neuroleptospirosis by next-generation sequencing . N Engl J Med 2014. ; 370 : 2408 – 17 .
    1. Byington CL , Ampofo K , Stockmann C et al. . Community surveillance of respiratory viruses among families in the Utah Better Identification of Germs-Longitudinal Viral Epidemiology (BIG-LoVE) study . Clin Infect Dis 2015. ; 61 : 1217 – 24 .
    1. Sumino KC , Walter MJ , Mikols CL et al. . Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illness . Thorax 2010. ; 65 : 639 – 44 .
    1. Wylie TN , Wylie KM , Buller RS , Cannella M , Storch GA . Development and evaluation of an enterovirus D68 real-time reverse transcriptase PCR assay . J Clin Microbiol 2015. ; 53 : 2641 – 7 .
    1. Wylie KM , Weinstock GM , Storch GA . Emerging view of the human virome . Transl Res 2012. ; 160 : 283 – 90 .
    1. Mueller TC , Siv S , Khim N et al. . Acute undifferentiated febrile illness in rural Cambodia: a 3-year prospective observational study . PloS One 2014. ; 9 : e95868 .
    1. O'Shea MK , Clay KA , Craig DG et al. . Diagnosis of febrile illnesses other than ebola virus disease at an ebola treatment unit in Sierra Leone . Clin Infect Dis 2015. ; 61 : 795 – 8 .
    1. Thriemer K , Ley B , Menten J , Jacobs J , van den Ende J . A systematic review and meta-analysis of the performance of two point of care typhoid fever tests, Tubex TF and Typhidot, in endemic countries . PloS One 2013. ; 8 : e81263 .
    1. Abba K , Kirkham AJ , Olliaro PL et al. . Rapid diagnostic tests for diagnosing uncomplicated non- falciparum or Plasmodium vivax malaria in endemic countries . Cochrane Database Syst Rev 2014. ; ( 12 ): CD011431 .
    1. Leslie T , Mikhail A , Mayan I et al. . Rapid diagnostic tests to improve treatment of malaria and other febrile illnesses: patient randomised effectiveness trial in primary care clinics in Afghanistan . BMJ 2014. ; 348 : g3730 .
    1. Masanja IM , Selemani M , Amuri B et al. . Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests . Malaria J 2012. ; 11 : 221 .
    1. Odaga J , Sinclair D , Lokong JA , Donegan S , Hopkins H , Garner P . Rapid diagnostic tests versus clinical diagnosis for managing people with fever in malaria endemic settings . Cochrane Database Syst Rev 2014. ; ( 4 ): CD008998 .
    1. Akachi Y , Atun R . Effect of investment in malaria control on child mortality in sub-Saharan Africa in 2002–2008 . PloS One 2011. ; 6 : e21309 .
    1. Sievers AC , Lewey J , Musafiri P et al. . Reduced paediatric hospitalizations for malaria and febrile illness patterns following implementation of community-based malaria control programme in rural Rwanda . Malaria J 2008. ; 7 : 167 .
    1. Mwanziva C , Shekalaghe S , Ndaro A et al. . Overuse of artemisinin-combination therapy in Mto wa Mbu (river of mosquitoes), an area misinterpreted as high endemic for malaria . Malaria J 2008. ; 7 : 232 .
    1. Bouyou-Akotet MK , Mawili-Mboumba DP , Kendjo E et al. . Complicated malaria and other severe febrile illness in a pediatric ward in Libreville, Gabon . BMC Infect Dis 2012. ; 12 : 216 .
    1. Joshi R , Colford JM Jr , Reingold AL , Kalantri S . Nonmalarial acute undifferentiated fever in a rural hospital in central India: diagnostic uncertainty and overtreatment with antimalarial agents . Am J Trop Med Hyg 2008. ; 78 : 393 – 9 .
    1. Kibuuka A , Byakika-Kibwika P , Achan J et al. . Bacteremia among febrile Ugandan children treated with antimalarials despite a negative malaria test . Am J Trop Med Hyg 2015. ; 93 : 276 – 80 .
    1. Amexo M , Tolhurst R , Barnish G , Bates I . Malaria misdiagnosis: effects on the poor and vulnerable . Lancet 2004. ; 364 : 1896 – 8 .
    1. Wain J , Hien TT , Connerton P et al. . Molecular typing of multiple-antibiotic-resistant Salmonella enterica serovar Typhi from Vietnam: application to acute and relapse cases of typhoid fever . J Clin Microbiol 1999. ; 37 : 2466 – 72 .
    1. Mengo DM , Kariuki S , Muigai A , Revathi G . Trends in Salmonella enteric serovar Typhi in Nairobi, Kenya from 2004 to 2006 . J Infect Dev Ctries 2010. ; 4 : 393 – 6 .
    1. Folster JP , Pecic G , Rickert R et al. . Characterization of multidrug-resistant Salmonella enterica serovar Heidelberg from a ground turkey-associated outbreak in the United States in 2011 . Antimicrob Agents Chemother 2012. ; 56 : 3465 – 6 .
    1. Miriagou V , Tassios PT , Legakis NJ , Tzouvelekis LS . Expanded-spectrum cephalosporin resistance in non-typhoid Salmonella . Int J Antimicrob Agents 2004. ; 23 : 547 – 55 .
    1. Bate R , Coticelli P , Tren R , Attaran A . Antimalarial drug quality in the most severely malarious parts of Africa—a six country study . PloS One 2008. ; 3 : e2132 .
    1. Bate R , Tren R , Mooney L et al. . Pilot study of essential drug quality in two major cities in India . PloS One 2009. ; 4 : e6003 .
    1. Caudron JM , Ford N , Henkens M , Mace C , Kiddle-Monroe R , Pinel J . Substandard medicines in resource-poor settings: a problem that can no longer be ignored . Trop Med Int Health 2008. ; 13 : 1062 – 72 .
    1. Flannery B , Pereira MM , Velloso LdF et al. . Referral pattern of leptospirosis cases during a large urban epidemic of dengue . Am J Trop Med Hyg 2001. ; 65 : 657 – 63 .
    1. Watt G , Jongsakul K . Acute undifferentiated fever caused by infection with Japanese encephalitis virus . Am J Trop Med Hyg 2003. ; 68 : 704 – 6 .
    1. Sogoba N , Feldmann H , Safronetz D . Lassa fever in West Africa: evidence for an expanded region of endemicity . Zoonoses Public Health 2012. ; 59 ( Suppl 2 ): 43 – 7 .
    1. Hoeboer SH , Alberts E , van den Hul I , Tacx AN , Debets-Ossenkopp YJ , Groeneveld AB . J Infect 2012. ; 64 : 484 – 93 .
    1. Hoeboer SH , Groeneveld AB . PloS One 2013. ; 8 : e65564 .
    1. Engelmann I , Dubos F , Lobert PE et al. . Pediatrics 2015. ; 135 : e985 – 93 .
    1. Mejias A , Suarez NM , Ramilo O . Detecting specific infections in children through host responses: a paradigm shift . Curr Opin Infect Dis 2014. ; 27 : 228 – 35 .
    1. Mahajan P , Kuppermann N , Suarez N et al. . RNA transcriptional biosignature analysis for identifying febrile infants with serious bacterial infections in the emergency department: a feasibility study . Pediatr Emerg Care 2015. ; 31 : 1 – 5 .
    1. Kaforou M , Wright VJ , Levin M . Host RNA signatures for diagnostics: an example from paediatric tuberculosis in Africa . J Infect 2014. ; 69 ( Suppl 1 ): S28 – 31 .
    1. Kotloff KL , Nataro JP , Blackwelder WC et al. . Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study . Lancet 2013. ; 382 : 209 – 22 .
    1. Vaughn DW , Green S , Kalayanarooj S et al. . Dengue in the early febrile phase: viremia and antibody responses . J Infect Dis 1997. ; 176 : 322 – 30 .
    1. Wijedoru LP , Kumar V , Chanpheaktra N et al. . Typhoid fever among hospitalized febrile children in Siem Reap, Cambodia . J Trop Pediatr 2012. ; 58 : 68 – 70 .
    1. Lehmann D , Michael A , Omena M et al. . Bacterial and viral etiology of severe infection in children less than three months old in the highlands of Papua New Guinea . Pediatr Infect Dis J 1999. ; 18 ( 10 Suppl ): S42 – 9 .
    1. Lepage P , Bogaerts J , Van Goethem C et al. . Community-acquired bacteraemia in African children . Lancet 1987. ; 1 : 1458 – 61 .
    1. Petit PL , Haarlem JV , Poelman M , Haverkamp MC , Wamola IA . Bacteraemia in patients presenting with fever . East Afr Med J 1995. ; 72 : 116 – 20 .
    1. Muhe L , Tilahun M , Lulseged S et al. . Etiology of pneumonia, sepsis and meningitis in infants younger than three months of age in Ethiopia . Pediatr Infect Dis J 1999. ; 18 ( 10 Suppl ): S56 – 61 .
    1. Dougle ML , Hendriks ER , Sanders EJ , Dorigo-Zetsma JW . Laboratory investigations in the diagnosis of septicaemia and malaria . East Afr Med J 1997. ; 74 : 353 – 6 .
    1. Fry AM , Lu X , Olsen SJ et al. . Human rhinovirus infections in rural Thailand: epidemiological evidence for rhinovirus as both pathogen and bystander . PloS One 2011. ; 6 : e17780 .
    1. Morris CM , Tefuarani N , Ripa P , Laki R , Vince JD . Urinary tract infection in infants and young children presenting with fever without a focus in Port Moresby . P N G Med J 2007. ; 50 : 145 – 51 .
    1. Vong S , Khieu V , Glass O et al. . Dengue incidence in urban and rural Cambodia: results from population-based active fever surveillance, 2006–2008 . PLoS Negl Trop Dis 2010. ; 4 : e903 .
    1. Ayoola OO , Adeyemo AA , Osinusi K . Predictors of bacteraemia among febrile infants in Ibadan, Nigeria . J Health Popul Nutr 2002. ; 20 : 223 – 9 .
    1. Sirivichayakul C , Limkittikul K , Chanthavanich P et al. . Dengue infection in children in Ratchaburi, Thailand: a cohort study. II. Clinical manifestations . PLoS Negl Trop Dis 2012. ; 6 : e1520 .
    1. Ba O , Fleming JA , Dieye Y et al. . Hospital surveillance of childhood bacterial meningitis in Senegal and the introduction of Haemophilus influenzae type b conjugate vaccine . Am J Trop Med Hyg 2010. ; 83 : 1330 – 5 .
    1. Obaro S , Lawson L , Essen U et al. . Community acquired bacteremia in young children from central Nigeria—a pilot study . BMC Infect Dis 2011. ; 11 : 137 .
    1. Mtove G , Amos B , von Seidlein L et al. . Invasive salmonellosis among children admitted to a rural Tanzanian hospital and a comparison with previous studies . PloS One 2010. ; 5 : e9244 .
    1. Aarsland SJ , Castellanos-Gonzalez A , Lockamy KP et al. . Treatable bacterial infections are underrecognized causes of fever in Ethiopian children . Am J Trop Med Hyg 2012. ; 87 : 128 – 33 .
    1. Thriemer K , Ley B , Ame S et al. . The burden of invasive bacterial infections in Pemba, Zanzibar . PLoS One 2012. ; 7 : e30350 .
    1. Graham RR , Juffrie M , Tan R et al. . A prospective seroepidemiologic study on dengue in children four to nine years of age in Yogyakarta, Indonesia I. studies in 1995–1996 . Am J Trop Med Hyg 1999. ; 61 : 412 – 9 .
    1. Boonsilp S , Thaipadungpanit J , Amornchai P et al. . Molecular detection and speciation of pathogenic Leptospira spp. in blood from patients with culture-negative leptospirosis . BMC Infect Dis 2011. ; 11 : 338 .
    1. Tien NT , Luxemburger C , Toan NT et al. . A prospective cohort study of dengue infection in schoolchildren in Long Xuyen, Viet Nam . Trans R Soc Trop Med Hyg 2010. ; 104 : 592 – 600 .
    1. Samransamruajkit R , Jitchaiwat S , Wachirapaes W , Deerojanawong J , Sritippayawan S , Prapphal N . Prevalence of Mycoplasma and Chlamydia pneumonia in severe community-acquired pneumonia among hospitalized children in Thailand . Jpn J Infect Dis 2008. ; 61 : 36 – 9 .
    1. Bhengsri S , Baggett HC , Peruski LF et al. . Bartonella seroprevalence in rural Thailand . Southeast Asian J Trop Med Public Health 2011. ; 42 : 687 – 92 .
    1. Chen X , Stanton B , Pach A et al. . Adults’ perceived prevalence of enteric fever predicts laboratory-validated incidence of typhoid fever in children . J Health Popul Nutr 2007. ; 25 : 469 – 78 .
    1. Siddiqui FJ , Rabbani F , Hasan R , Nizami SQ , Bhutta ZA . Typhoid fever in children: some epidemiological considerations from Karachi, Pakistan . Int J Infect Dis 2006. ; 10 : 215 – 22 .
    1. Anderson KB , Chunsuttiwat S , Nisalak A et al. . Burden of symptomatic dengue infection in children at primary school in Thailand: a prospective study . Lancet 2007. ; 369 : 1452 – 9 .
    1. Chong CY , Lim WH , Heng JT , Chay OM . The changing trend in the pattern of infective etiologies in childhood acute lower respiratory tract infection . Acta Paediatr Jpn 1997. ; 39 : 317 – 21 .
    1. Senn N , Luang-Suarkia D , Manong D , Siba PM , McBride WJ . Contribution of dengue fever to the burden of acute febrile illnesses in Papua New Guinea: an age-specific prospective study . Am J Trop Med Hyg 2011. ; 85 : 132 – 7 .

Source: PubMed

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