Treatment of Infections in Young Infants in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis of Frontline Health Worker Diagnosis and Antibiotic Access
Background:
Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription?
Methods and Findings:
We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%–91%) and lower specificity (62%, 95% CI 48%–75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%–88%) and specificity of 69% (95% CI 54%–83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%–34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data.
Conclusions:
Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs.
Review Registration:
PROSPERO International prospective register of systematic reviews (CRD42013004586).
Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Treatment of Infections in Young Infants in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis of Frontline Health Worker Diagnosis and Antibiotic Access. PLoS Med 11(10): e32767. doi:10.1371/journal.pmed.1001741
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1001741
Souhrn
Background:
Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription?
Methods and Findings:
We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%–91%) and lower specificity (62%, 95% CI 48%–75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%–88%) and specificity of 69% (95% CI 54%–83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%–34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data.
Conclusions:
Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs.
Review Registration:
PROSPERO International prospective register of systematic reviews (CRD42013004586).
Please see later in the article for the Editors' Summary
Zdroje
1. SealeAC, BlencoeH, ZaidiA, GanatraH, SyedS, et al. (2013) Neonatal severe bacterial infection impairment estimates in South Asia, sub-Saharan Africa, and Latin America for 2010. Pediatr Res 74 Suppl 1: 73–85.
2. ThaverD, ZaidiAK (2009) Burden of neonatal infections in developing countries: a review of evidence from community-based studies. Pediatr Infect Dis J 28: S3–9.
3. LiuL, JohnsonHL, CousensS, PerinJ, ScottS, et al. (2012) Child Health Epidemiology Reference Group of WHO and UNICEF (2012) Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 379: 2151–2161.
4. LawnJE, CousensS, DarmstadtGL, PaulV, MartinesJ (2004) Why are 4 million newborn babies dying every year? Lancet 364: 2020.
5. GanatraHA, StollBJ, ZaidiAK (2010) International perspective on early-onset neonatal sepsis. Clin Perinatol 37: 501–523.
6. StollBJ (1997) The global impact of neonatal infection. Clin Perinatol 24: 1–21.
7. OsrinD, VergnanoS, CostelloA (2004) Serious bacterial infections in newborn infants in developing countries. Curr Opin Infect Dis 17: 217–224.
8. ZaidiAK, HuskinsWC, ThaverD, BhuttaZA, AbbasZ, et al. (2005) Hospital-acquired neonatal infections in developing countries. Lancet 365: 1175–1188.
9. DarmstadtGL, BhuttaZA, CousensS, AdamT, WalkerN, et al. (2005) Evidence-based, cost-effective interventions: how many newborn babies can we save? Lancet 365: 977–988.
10. TheodoratouE, Al-JilaihawiS, WoodwardF, FergusonJ, JhassA, et al. (2010) The effect of case management on childhood pneumonia mortality in developing countries. Int J Epidemiol 39: i155–171.
11. DarmstadtGL, SahaSK, ChoiY, El ArifeenS, BariS, et al. (2009) Population-based incidence and etiology of community-acquired neonatal sepsis in Mirzapur, Bangladesh. J Infect Disease 200: 906–915.
12. CutlandCL, MadhiSA, ZellER, KuwandaL, LaqueM, et al. (2009) PoPS Trial Team (2009) Chlorhexidine maternal-vaginal and neonate body wipes in sepsis and vertical transmission of pathogenic bacteria in South Africa: a randomised, controlled trial. Lancet 374: 1909–1916.
13. WeberMW, MulhollandEK, JaffarS, TroedssonH, GoveS, et al. (1997) Evaluation of an algorithm for the integrated management of childhood illness in an area with seasonal malaria in the Gambia. Bull World Health Organ 75 Suppl 1: 25–32.
14. Young Infants Clinical Signs Study Group (2008) Clinical signs that predict severe illness in children under age 2 months: a multicentre study. Lancet 371: 135–142.
15. BaquiAH, ArifeenSE, WilliamsEK, AhmedS, MannanI, et al. (2009) Effectiveness of home-based management of newborn infections by community health workers in rural bangladesh. Pediatr Infect Dis J 28: 304–310.
16. BangAT, BangRA, BaituleSB, ReddyMH, DeshmukhMD (1999) Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India. Lancet 354: 1955–1961.
17. ZaidiAK, TikmaniSS, WarraichHJ, DarmstadtGL, BhuttaZA, et al. (2012) Community-based treatment of serious bacterial infections in newborns and young infants: a randomized controlled trial assessing three antibiotic regimens. Pediatr Infect Dis J 31: 667–672.
18. DownieL, ArmientoR, SubhiR, KellyJ, CliffordV, et al. (2013) Community-acquired neonatal and infant sepsis in developing countries: efficacy of WHO's currently recommended antibiotics–systematic review and meta-analysis. Arch Dis Child 98: 146–154.
19. ZaidiAK, ThaverD, AliSA, KhanTA (2009) Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J 28: S10–18.
20. WHO (2003) Managing newborn problems: a guide for doctors, nurses, and midwives. Geneva: WHO.
21. Coffey P, Kelly K, Baqui A, Bartlett A, Bhutta Z, et al. (2012) Case study: injectable antibiotics for treatment of newborn sepsis. 1–24 p. Available: http://pdf.usaid.gov/pdf_docs/pnady703.pdf
22. DarmstadtGL, BatraM, ZaidiAK (2009) Parenteral antibiotics for the treatment of serious neonatal bacterial infections in developing country settings. Pediatr Infect Dis J 28: S37–42.
23. WHO (2002) Explore simplified antimicrobial regimens for the treatment of neonatal sepsis. Geneva: WHO, Department of Child and Adolescent Health and Development.
24. HerbertH, LeeA, ChandranA, RudanI, BaquiA (2011) Care Seeking for neonatal illness in low- and middle-income countries: a systematic review. PLoS Med 9: e1001183.
25. ChandranA, HerbertHK, LeeAC, RudanI, BaquiAH (2011) Assessment of the proportion of neonates and children in low and middle income countries with access to a healthcare facility: a systematic review. BMC Res Notes 4: 536.
26. CameronA, EwenM, Ross-DegnanD, BallD, LaingR (2009) Medicine prices, availability, and affordability in 36 developing and middle-income countries: a secondary analysis. Lancet 373: 240–249.
27. DarmstadtGL, BatraM, ZaidiAK (2009) Oral antibiotics in the management of serious neonatal bacterial infections in developing country communities. Pediatr Infect Dis J 28: S31–36.
28. Rational Pharmaceutical Management Plus Program (2001) How to investigate antimicrobial drug use in hospitals: selected indicators. Arlington (Virginia): Draft published for the US Agency for International Development by the Rational Pharmaceutical Management Plus Program.
29. WalkerN, Fischer-WalkerC, BryceJ, BahlR, CousensS (2010) CHERG Review Groups on Intervention Effects (2010) Standards for CHERG reviews of intervention effects on child survival. Int J Epidemiol 39: i21–31.
30. Deeks J, Bossuyt P, Gatsonis C (2010) Cochrane handbook for systematic reviews of diagnostic test accuracy. The Cochrane Collaboration.
31. WhitingPF, RutjesAW, WestwoodME, MallettS, DeeksJJ (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155: 529–536.
32. SchunemannHJ, OxmanAD, BrozekJ, GlasziouP, BossuytP, et al. (2008) GRADE: assessing the quality of evidence for diagnostic recommendations. ACP J Club 149: 2.
33. WalkerN, Fischer-WalkerC, BryceJ, BahlR, CousensS (2010) Standards for CHERG reviews of intervention effects on child survival. Int J Epidemiol 39 Suppl 1: i21–i31.
34. Hospital JH, Arcara K, Tschudy M (2011) The Harriet Lane Handbook, 19th edition. Baltimore: Elsevier.
35. BiswasAB, MukhopadhyayDK, MandalNK, PanjaTK, SinhaN, et al. (2011) Skill of frontline workers implementing integrated management of neonatal and childhood illness: experience from a district of West Bengal, India. J Trop Pediatr 57: 352–356.
36. KhanalS, SharmaJ, GCVS, DawsonP, HoustonR, et al. (2011) Community health workers can identify and manage possible infections in neonates and young infants: MINI–a model from Nepal. J Health Popul Nutr 29: 255–264.
37. BangAT, BangRA, StollBJ, BaituleSB, ReddyHM, et al. (2005) Is home-based diagnosis and treatment of neonatal sepsis feasible and effective? Seven years of intervention in the Gadchiroli field trial (1996 to 2003). J Perinatol 25 supp 1: S62–S71.
38. WeberMW, CarlinJB, GatchalianS, LehmannD, MuheL, et al. (2003) Predictors of neonatal sepsis in developing countries. Pediatr Infect Dis J 22: 711–717.
39. Clinical signs that predict severe illness in children under age 2 months: a multicentre study. Lancet 371: 135–142.
40. DarmstadtGL, BaquiAH, ChoiY, BariS, RahmanSM, et al. (2009) Bangladesh Projahnmo-2 (Mirzapur) Study Group (2009) Validation of community health workers' assessment of neonatal illness in rural Bangladesh. Bull World Health Organ 87: 12–19.
41. BaquiAH, ArifeenSE, RosenHE, MannanI, RahmanSM, et al. (2009) Projahnmo Study Group (2009) Community-based validation of assessment of newborn illnesses by trained community health workers in Sylhet district of Bangladesh. Trop Med Int Health 14: 1448–1456.
42. BangAT, BangRA, BaituleS, DeshmukhM, ReddyMH (2001) Burden of morbidities and the unmet need for health care in rural neonates - a prospective observational study in Gadchiroli, India. Indian Pediatrics 38: 952–965.
43. CarassoBS, LagardeM, TesfayeA, PalmerN (2009) Availability of essential medicines in Ethiopia: an efficiency-equity trade-off? Trop Med Int Health 14: 1394–1400.
44. EckerL, OchoaTJ, VargasM, Del ValleLJ, RuizJ (2013) Factors affecting caregivers' use of antibiotics available without a prescription in Peru. Pediatrics 131: e1771–1779.
45. MohannaM (2010) Self-medication with antibiotic in children in Sana'a City, Yemen. Oman Med J 25: 41–43.
46. MatsuiD (2007) Current Issues in pediatric medication adherence. Pediatric Drugs 9: 283–288.
47. EllerbeckE, KhallafN, el AnsaryKS, MoursiS, BlackR (1995) Caretaker compliance with different antibiotic formulations for treatment of childhood pneumonia. J Trop Pediatr 41: 103–108.
48. United Nations Commission on Life-Saving Commodities for Women and Children, Injectable Antibiotics for Newborn Sepsis – Product Profile.
49. BaquiAH, SahaSK, AhmedAS, ShahidullahM, QuasemI, et al. (2013) Safety and efficacy of simplified antibiotic regimens for outpatient treatment of serious infection in neonates and young infants 0–59 days of age in Bangladesh: design of a randomized controlled trial. Pediatr Infect Dis J 32: S12–18.
50. ZaidiAK, TikmaniSS, SultanaS, BalochB, KaziM, et al. (2013) Simplified antibiotic regimens for the management of clinically diagnosed severe infections in newborns and young infants in first-level facilities in Karachi, Pakistan: study design for an outpatient randomized controlled equivalence trial. Pediatr Infect Dis J 32: S19–25.
51. AFRINEST (AFRIcan NEonatal Sepsis Trial) Group (2013) Simplified regimens for management of neonates and young infants with severe infection when hospital admission is not possible: study protocol for a randomized, open-label equivalence trial. Pediatr Infect Dis J 32: S26–32.
52. AlmuzainiT, ChoonaraI, SammonsH (2013) Substandard and counterfeit medicines: a systematic review of the literature. BMJ Open 3: e002923.
53. WHO (2014) Antimicrobial resistance: global report on surveillance. Geneva: World Health Organization. Available: http://www.who.int/drugresistance/documents/surveillancereport/en/. Accessed 22 Sept 2014.
54. Le DoareKBJ, HeathPT, SharlandM (2014) Systematic review of antibiotic resistance rates among gram-negative bacteria in children with sepsis in resource-limited countries. J Ped Infect Dis In press. doi:10.1093/jpids/piu014
55. de ManP, VerhoevenBA, VerbrughHA, VosMC, van den AnkerJN (2000) An antibiotic policy to prevent emergence of resistant bacilli. Lancet 355: 973–978.
56. KotwaniA, HollowayK (2013) Access to antibiotics in New Delhi, India: implications for antibiotic policy. J Pharm Policy Pract 6: 6.
57. India National Neonatal-Perinatal Database (2003) India National Neonatal-Perinatal Database Report 2002–2003. New Delhi: Department of Pediatrics, WHO Collaborating Centre Newborn Training & Research, All India Insitute of Medical Sciences.
58. AiredeAI (1992) Neonatal septicemia in an African city of high altitude. J Trop Pediatr 38: 189–191.
59. KalterHD, SchillingerJA, HossainM, BurnhamG, SahaS, et al. (1997) Identifying sick children requiring referral to hospital in Bangladesh. Bull World Health Organ 75 Suppl 1: 65–75.
60. GuptaM, AggarwalAK (2008) Feasibility study of IMNCI guidelines on effective breastfeeding in a rural area of North India. Indian J Community Med 33: 201–203.
61. EnglishM, NgamaM, MwalekwaL, PeshuN (2004) Signs of illness in Kenyan infants aged less than 60 days. Bull World Health Organ 82: 323–329.
62. GoswamiV, DuttaAK, SinghV, ChandraJ (2006) Evaluation of simple clinical signs of illness in young infants (0–2 months) and its correlation with WHO IMCI algorithm (7 days to 2 months). Indian Pediatr 43: 1042–1049.
63. BaquiAH, El-ArifeenS, DarmstadtGL, AhmedS, WilliamsEK, et al. (2008) Effect of community-based newborn-care intervention package implemented through two service-delivery strategies in Sylhet district, Bangladesh: a cluster-randomised controlled trial. Lancet 371: 1936–1944.
64. BhattacharyyaA, SahaSK, GhoshP, ChatterjeeC, DasguptaS (2011) Study comparing the management decisions by IMNCI algorithm and pediatricians in a teaching hospital for the young infants between 0 to 2 months. Indian J Public Health 55: 324–328.
65. DarmstadtGL, BaquiAH, ChoiY, BariS, RahmanSM, et al. (2009) Validation of community health workers' assessment of neonatal illness in rural Bangladesh. Bull World Health Organ 87: 12–19.
66. KaurS, SinghV, DuttaAK, ChandraJ (2011) Validation of IMNCI algorithm for young infants (0–2 months) in India. Indian Pediatr 48: 955–960.
67. ShewadeHD, AggarwalAK, BhartiB (2013) Integrated Management of Neonatal and Childhood Illness (IMNCI): skill assessment of health and Integrated Child Development Scheme (ICDS) workers to classify sick under-five children. Indian J Pediatr 80: 448–454.
68. EnglishM, NgamaM, MusumbaC, WamolaB, BwikaJ, et al. (2003) Causes and outcome of young infant admissions to a Kenyan district hospital. Arch Dis Child 88: 438–443.
69. Gabra M, Kisalu A, Hazemba O (2000) Uganda assessment: drug management for childhood illness. Arlington (Virginia): Management Sciences for Health.
70. SimoesEA, PetersonS, GamatieY, KisangaFS, MukasaG, et al. (2003) Management of severely ill children at first-level health facilities in sub-Saharan Africa when referral is difficult. Bull World Health Organ 81: 522–531.
71. BartoloniA, CuttsF, LeoniS, AustinCC, MantellaA, et al. (1998) Patterns of antimicrobial use and antimicrobial resistance among healthy children in Bolivia. Trop Med Int Health 3: 116–123.
72. CheraghaliAM, NikfarS, BehmaneshY, RahimiV, HabibipourF, et al. (2004) Evaluation of availability, accessibility and prescribing pattern of medicines in the Islamic Republic of Iran. East Mediterr Health J 10: 406–415.
73. Hafner G, Nurghozin T, Gulyaev A, Laing R (2002) Summary of results: prices and availability of pharmaceuticals in Kazakhstan's pharmacies. Almaty: ABT.
74. KotwaniA, EwenM, DeyD, IyerS, LakshmiPK, et al. (2007) Prices and availability of common medicines at six sites in India using a standard metholodogy. Indian J Med Res 125: 645–654.
75. ZhangY, DaiY, ZhangS (2007) Impact of implementation of Integrated Management of Childhood Illness on improvement of health system in China. J Paediatr Child Health 43: 681–685.
76. YangH, DibHH, ZhuM, QiG, ZhangX (2010) Prices, availability and affordability of essential medicines in rural areas of Hubei Province, China. Health Policy Plan 25: 219–229.
77. KallanderK, Nsungwa-SabiitiJ, PetersonS (2004) Symptom overlap for malaria and pneumonia–policy implications for home management strategies. Acta Trop 90: 211–214.
78. NsimbaSE (2007) Assessing the performance, practices and roles of drug sellers/dispensers and mothers'/guardians' behaviour for common childhood conditions in Kibaha district, Tanzania. Trop Doct 37: 197–201.
79. KristianssonC, ReillyM, GotuzzoE, RodriguezH, BartoloniA, et al. (2008) Antibiotic use and health-seeking behaviour in an underprivileged area of Peru. Trop Med Int Health 13: 434–441.
80. PereiraFS, BucaretchiF, StephanC, CordeiroR (2007) Self-medication in children and adolescents. J Pediatr (Rio J) 83: 453–458.
81. SchorlingJB, De SouzaMA, GuerrantRL (1991) Patterns of antibiotic use among children in an urban Brazilian slum. Int J Epidemiol 20: 293–299.
82. Aboul FotouhAM, el-DamatySE, Abdel MegeidFY (1998) Mother's knowledge about antibiotic and role of self prescription. J Egypt Public Health Assoc 73: 57–69.
83. RayK, MukhopadhyayS, DuttD, ChatterjeePK, RoychowdhuryPK, et al. (2003) Cross-sectional study of consumption, compliance and awareness about antibiotic utilisation amongst the urban community in Kolkata. J Indian Med Assoc 101: 7, 9–10.
84. BiP, TongS, PartonKA (2000) Family self-medication and antibiotics abuse for children and juveniles in a Chinese city. Soc Sci Med 50: 1445–1450.
85. O'ConnorS, RifkinD, YangYH, WangJF, LevineOS, et al. (2001) Physician control of pediatric antimicrobial use in Beijing, China, and its rural environs. Pediatr Infect Dis J 20: 679–684.
86. TogoobaatarG, IkedaN, AliM, SonomjamtsM, DashdemberelS, et al. (2010) Survey of non-prescribed use of antibiotics for children in an urban community in Mongolia. Bull World Health Organ 88: 930–936.
Štítky
Interné lekárstvoČlánok vyšiel v časopise
PLOS Medicine
2014 Číslo 10
- Statinová intolerance
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Co dělat při intoleranci statinů?
- Pleiotropní účinky statinů na kardiovaskulární systém
- DESATORO PRE PRAX: Aktuálne odporúčanie ESPEN pre nutričný manažment u pacientov s COVID-19
Najčítanejšie v tomto čísle
- Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies: The CHARMS Checklist
- Developmental Profiles of Eczema, Wheeze, and Rhinitis: Two Population-Based Birth Cohort Studies
- Maternal Clinical Diagnoses and Hospital Variation in the Risk of Cesarean Delivery: Analyses of a National US Hospital Discharge Database
- Association of Medical Students' Reports of Interactions with the Pharmaceutical and Medical Device Industries and Medical School Policies and Characteristics: A Cross-Sectional Study