PMID- 29694816
OWN - NLM
STAT- MEDLINE
DCOM- 20180509
LR  - 20181114
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 378
IP  - 17
DP  - 2018 Apr 26
TI  - Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa.
PG  - 1583-1592
LID - 10.1056/NEJMoa1715474 [doi]
AB  - BACKGROUND: We hypothesized that mass distribution of a broad-spectrum antibiotic
      agent to preschool children would reduce mortality in areas of sub-Saharan Africa
      that are currently far from meeting the Sustainable Development Goals of the
      United Nations. METHODS: In this cluster-randomized trial, we assigned
      communities in Malawi, Niger, and Tanzania to four twice-yearly mass
      distributions of either oral azithromycin (approximately 20 mg per kilogram of
      body weight) or placebo. Children 1 to 59 months of age were identified in
      twice-yearly censuses and were offered participation in the trial. Vital status
      was determined at subsequent censuses. The primary outcome was aggregate
      all-cause mortality; country-specific rates were assessed in prespecified
      subgroup analyses. RESULTS: A total of 1533 communities underwent randomization, 
      190,238 children were identified in the census at baseline, and 323,302
      person-years were monitored. The mean (+/-SD) azithromycin and placebo coverage
      over the four twice-yearly distributions was 90.4+/-10.4%. The overall annual
      mortality rate was 14.6 deaths per 1000 person-years in communities that received
      azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths 
      per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5
      in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence
      interval [CI], 6.7 to 19.8) in communities that received azithromycin than in
      communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi
      (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4%
      lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5
      months had the greatest effect from azithromycin (24.9% lower mortality than that
      with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a
      week after administration of the trial drug or placebo were uncommon, and the
      rate did not differ significantly between the groups. Evaluation of selection for
      antibiotic resistance is ongoing. CONCLUSIONS: Among postneonatal, preschool
      children in sub-Saharan Africa, childhood mortality was lower in communities
      randomly assigned to mass distribution of azithromycin than in those assigned to 
      placebo, with the largest effect seen in Niger. Any implementation of a policy of
      mass distribution would need to strongly consider the potential effect of such a 
      strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates
      Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).
FAU - Keenan, Jeremy D
AU  - Keenan JD
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Bailey, Robin L
AU  - Bailey RL
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - West, Sheila K
AU  - West SK
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Arzika, Ahmed M
AU  - Arzika AM
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Hart, John
AU  - Hart J
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Weaver, Jerusha
AU  - Weaver J
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Kalua, Khumbo
AU  - Kalua K
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Mrango, Zakayo
AU  - Mrango Z
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Ray, Kathryn J
AU  - Ray KJ
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Cook, Catherine
AU  - Cook C
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Lebas, Elodie
AU  - Lebas E
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - O'Brien, Kieran S
AU  - O'Brien KS
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Emerson, Paul M
AU  - Emerson PM
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Porco, Travis C
AU  - Porco TC
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
FAU - Lietman, Thomas M
AU  - Lietman TM
AD  - From the Francis I. Proctor Foundation (J.D.K., K.J.R., C.C., E.L., K.S.O.,
      T.C.P., T.M.L.), the Departments of Ophthalmology (J.D.K., T.C.P., T.M.L.) and
      Epidemiology and Biostatistics (T.C.P., T.M.L.), and the Institute for Global
      Health Sciences (T.C.P., T.M.L.), University of California, San Francisco, San
      Francisco; London School of Hygiene and Tropical Medicine, London (R.L.B., J.H.);
      the Dana Center, Johns Hopkins University School of Medicine, Baltimore (S.K.W., 
      J.W.); the Carter Center, Niamey, Niger (A.M.A.); Blantyre Institute for
      Community Outreach and the College of Medicine, University of Malawi, Blantyre
      (K.K.); National Institute for Medical Research, Dar es Salaam, Tanzania (Z.M.); 
      and the International Trachoma Initiative, Decatur (P.M.E.), and Emory
      University, Atlanta (P.M.E.) - both in Georgia.
CN  - MORDOR Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT02047981
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Anti-Bacterial Agents)
RN  - 83905-01-5 (Azithromycin)
SB  - AIM
SB  - IM
CIN - N Engl J Med. 2018 Oct 04;379(14):1382. PMID: 30284802
CIN - N Engl J Med. 2018 Oct 04;379(14):1382. PMID: 30284803
CIN - N Engl J Med. 2018 Oct 04;379(14):1382-3. PMID: 30284804
CIN - J Pediatr. 2018 Sep;200:291-294. PMID: 30144922
MH  - Administration, Oral
MH  - Anti-Bacterial Agents/*therapeutic use
MH  - Azithromycin/*therapeutic use
MH  - *Child Mortality/trends
MH  - Child, Preschool
MH  - Communicable Disease Control
MH  - Communicable Diseases/*mortality
MH  - Drug Resistance, Bacterial
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant Mortality/trends
MH  - Malawi/epidemiology
MH  - Male
MH  - *Mass Drug Administration/mortality
MH  - Niger/epidemiology
MH  - Public Health
MH  - Tanzania/epidemiology
PMC - PMC5849140
IR  - Doan T
FIR - Doan, Thuy
IR  - Oldenburg CE
FIR - Oldenburg, Catherine E
IR  - Cotter SY
FIR - Cotter, Sun Y
IR  - Stoller NE
FIR - Stoller, Nicole E
IR  - Vanderschelden B
FIR - Vanderschelden, Benjamin
IR  - Fry DM
FIR - Fry, Dionna M
IR  - Rosenthal PJ
FIR - Rosenthal, Philip J
IR  - Rutherford GW
FIR - Rutherford, George W
IR  - Zhou Z
FIR - Zhou, Zhaoxia
IR  - Zhong L
FIR - Zhong, Lina
IR  - Gaynor BD
FIR - Gaynor, Bruce D
IR  - Whitcher JP
FIR - Whitcher, John P
IR  - Mabey DCW
FIR - Mabey, David C W
IR  - Burr SE
FIR - Burr, Sarah E
IR  - Solomon AW
FIR - Solomon, Anthony W
IR  - Dreger K
FIR - Dreger, Kurt
IR  - Munoz B
FIR - Munoz, Beatriz
IR  - Coles CL
FIR - Coles, Christian L
IR  - Labrique AB
FIR - Labrique, Alain B
IR  - Sommer A
FIR - Sommer, Alfred
IR  - Kaur H
FIR - Kaur, Hemjot
IR  - Bloch EM
FIR - Bloch, Evan M
IR  - Chisambi A
FIR - Chisambi, Alvin
IR  - Kamwendo Z
FIR - Kamwendo, Zachariah
IR  - Maleta K
FIR - Maleta, Ken
IR  - Callahan EK
FIR - Callahan, E Kelly
IR  - Stewart AE
FIR - Stewart, Aisha E
IR  - Kane S
FIR - Kane, Salissou
IR  - Abdou A
FIR - Abdou, Amza
IR  - Kadri B
FIR - Kadri, Boubacar
IR  - Beido N
FIR - Beido, Nassirou
IR  - Kasubi M
FIR - Kasubi, Mabula
IR  - Mboera L
FIR - Mboera, Leonard
EDAT- 2018/04/26 06:00
MHDA- 2018/05/10 06:00
CRDT- 2018/04/26 06:00
PHST- 2018/04/26 06:00 [entrez]
PHST- 2018/04/26 06:00 [pubmed]
PHST- 2018/05/10 06:00 [medline]
AID - 10.1056/NEJMoa1715474 [doi]
PST - ppublish
SO  - N Engl J Med. 2018 Apr 26;378(17):1583-1592. doi: 10.1056/NEJMoa1715474.