RCTs in child health in developing countries 2014 2015 2
RANDOMISED TRIALS IN CHILD HEALTH IN
DEVELOPING COUNTRIES
13th Edition
July 2014-June 2015
www.ichrc.org
Please send suggestions about this booklet to:
Prof Trevor Duke
Centre for International Child Health
University of Melbourne, Department of Paediatrics
Royal Children’s Hospital
Parkville, 3052, Victoria, Australia
Telephone: (613) 9345 5968
Email: trevor.duke@rch.org.au
Randomised trials in child health in developing countries 2014-15
SEARCH STRATEGY
Pubmed Advanced strategy, search: ((Developing countries; Developing country; Countries,
developing; Developed countries; Country, developing; Countries, developed; Developed
country; Country, developed; Nations, developing; Developing nations OR India OR Africa OR
Asia OR South America OR Papua New Guinea OR Asia-Pacific) and (Child*)) AND
(randomized controlled trial[Publication Type] OR (randomized[Title/Abstract] AND
controlled[Title/Abstract] AND trial[Title/Abstract])) publication date between July 1st 2014 and
June 30th 2015.
Introduction .................................................................................................................................. 4
Acute respiratory infection ......................................................................................................... 11
Treatment of pneumonia........................................................................................................ 11
Otitis media ........................................................................................................................... 13
Bronchiolitis .......................................................................................................................... 13
Upper respiratory tract infections, tonsilitis .......................................................................... 14
Adolescent health ....................................................................................................................... 17
Allergy........................................................................................................................................ 19
Anaemia and iron deficiency ..................................................................................................... 19
Anaesthesia and intensive care ................................................................................................... 24
Intensive care ......................................................................................................................... 29
Asthma and chronic lung disease ............................................................................................... 31
Community paediatrics and social support ................................................................................ 34
Dengue ....................................................................................................................................... 36
Development, cerebral palsy and mental health ........................................................................ 39
Diarrhoea .................................................................................................................................... 47
Water purification .................................................................................................................. 49
Endocrine disorders and bone health ......................................................................................... 50
Enterovirus infections ................................................................................................................ 56
Epilepsy and acute seizures ........................................................................................................ 57
Hygiene and environmental health............................................................................................. 60
Haematological disorders ........................................................................................................... 63
HIV / AIDS ................................................................................................................................ 65
Ante-retroviral therapy (ART) .............................................................................................. 65
Early infant diagnosis ............................................................................................................ 66
Management of HIV-related conditions ................................................................................ 67
Nutrition, growth and development of children with HIV .................................................... 68
Prevention of parent to child transmission of HIV ................................................................ 69
HIV vaccine ........................................................................................................................... 75
Integrated approaches to HIV care and prevention ............................................................... 75
Helminth and other gastrointestinal disorders............................................................................ 83
Injury prevention ........................................................................................................................ 88
Integrated management of Childhood Illness (IMCI) ................................................................ 90
Intravenous fluids ....................................................................................................................... 93
Kidney disease ........................................................................................................................... 95
Leprosy ....................................................................................................................................... 97
Malaria ....................................................................................................................................... 98
Diagnosis ............................................................................................................................... 98
Insecticide-treated bed nets ................................................................................................. 100
Other preventative interventions ......................................................................................... 102
Treatment of uncomplicated malaria ................................................................................... 107
2
Randomised trials in child health in developing countries 2014-15
Treatment of severe or complicated malaria ....................................................................... 119
Treatment of vivax malaria ................................................................................................. 120
Malnutrition.............................................................................................................................. 121
Maternal care ............................................................................................................................ 124
Maternal nutrition and micronutrient supplementation ....................................................... 129
Meningitis and encephalitis...................................................................................................... 136
Newborn care ........................................................................................................................... 137
Low birth weight and prematurity ....................................................................................... 144
Neonatal infection ............................................................................................................... 147
Nutrition, micronutrients and breast feeding ........................................................................... 150
Micronutients, multivitamins and food fortification ........................................................... 150
Macronutrient nutrition and complementary feeding .......................................................... 155
Breastfeeding ....................................................................................................................... 161
Community nutrition and agriculture .................................................................................. 162
Obesity................................................................................................................................. 164
Oncology .................................................................................................................................. 166
Ophthalmology ......................................................................................................................... 166
Trachoma ............................................................................................................................. 170
Oral health / dentistry ............................................................................................................... 170
Poisoning and toxins ................................................................................................................ 171
Quality of care .......................................................................................................................... 173
Research methods..................................................................................................................... 174
Schistosomiasis ........................................................................................................................ 176
School health and education..................................................................................................... 181
Skin and hair disease ................................................................................................................ 186
Surgical problems..................................................................................................................... 189
Tuberculosis ............................................................................................................................. 191
Urinary tract infection .............................................................................................................. 200
Vaccines and immunization ..................................................................................................... 200
Cholera vaccine ................................................................................................................... 201
Dengue vaccine ................................................................................................................... 203
HIV vaccine ......................................................................................................................... 204
HPV vaccine ........................................................................................................................ 205
Influenza vaccine ................................................................................................................. 206
Japanese encephalitis virus vaccine..................................................................................... 209
Malaria vaccine ................................................................................................................... 212
Measles vaccine ................................................................................................................... 214
Meningococcal vaccine ....................................................................................................... 215
Pneumococcal vaccine......................................................................................................... 216
Polio vaccine ....................................................................................................................... 219
Rotavirus vaccine ................................................................................................................ 220
Tuberculosis vaccine ........................................................................................................... 225
Typhoid vaccine .................................................................................................................. 228
Varicella vaccine ................................................................................................................. 229
Vitamin A ................................................................................................................................. 230
Vitamin D ................................................................................................................................. 238
Zinc .......................................................................................................................................... 240
3
Randomised trials in child health in developing countries 2014-15
Introduction
This booklet is compiled annually to summarize the evidence on child health derived from
randomized or controlled trials in developing countries over the previous year. The aim is to
make this information widely available to paediatricians, nurses, other health workers and
administrators in resource poor settings where up-to-date information is hard to find. It is hoped
that such information will be helpful in reviewing treatment policies, clinical practice and public
health strategies.
The method of searching for studies to include uses PubMed, a search engine that is freely
available and widely used in most countries throughout the world. The search strategy has been
chosen to capture as many relevant studies as possible, although it is possible that I have missed
some. If you know of a relevant RCT or meta-analysis that has not been included in this year’s
review, please let me know. The search strategy is reproducible by anyone with access to the
Internet, through http://www.ncbi.nlm.nih.gov/sites/entrez
Randomized controlled trials (RCTs) are far from the only valuable scientific evidence, and
some RCTs, because of problems with design or implementation have limited value. However
the method of the Randomized Trial is the Gold Standard for determining attributable benefit or
harm from clinical and public health interventions. When done properly they eliminate bias and
confounding. However their results should not be accepted uncritically and they should be
evaluated for quality and validity. Before the result of an RCT can be generalized to another
setting there must be consideration of the wider applicability, feasibility and potential for
sustainability.
This year 245 studies were identified. These came from all regions of the world, mostly from
developing country researchers. Several trials from 2014-15 will lead to significant changes in
child health approaches or clinical recommendations.
We have included the web-link for papers that are available in full-text on the Internet free of
charge. Through HINARI (http://www.who.int/hinari/en/) a program set up by WHO in
collaboration with publishers, the full-text versions of over 14,000 journal titles and 30,000 ebooks are available to health institutions in over 100 countries. If your health institution
(medical school, teaching hospital, nursing school, government office) has not registered with
HINARI, you can check your eligibility and register online.
Please feel free to distribute this booklet to any colleagues. The previous editions (2002-2014)
are available at: www.ichrc.org
Two years ago we published a summary of the first 11 years of the controlled trials. The
reference for this is: Duke T, Fuller D. Arch Dis Child 2014, 99:615–620, and you may
download it at: http://adc.bmj.com/content/99/7/615.full.pdf+html
A brief summary of some of the important results in 2014-15
In a high-mortality setting in Kenya where co-morbidities are common, among children with
non-severe pneumonia, oral amoxicillin was non-inferior to intravenous benzylpenicillin,
and failure rates at day 14 were 13.5 and 16.8% respectively. In Brazil oral amocycillin
given 2 times per day was as effective as 3 times per day in treating non-severe pneumonia
4
Randomised trials in child health in developing countries 2014-15
with treatment failure rates of 23% and 22% respectively.
Children in African hospitals with severe anaemia were more likely to die in the first 24
hours (case fatality rate 13%) than those with mild or moderate anaemia (7-8%). Children
with severe anaemia who were not transfused at 2.5 hours had a much higher risk of dying
than those who received blood early.
For Indian children with central nervous system infections cared for in an intensive care unit,
the targeting of a cerebral perfusion pressure >60mmHg using fluid boluses, and dopamine /
noradrenaline, resulted in lower mortality and less neuro-disability than a strategy aiming to
keep intracranial pressure 250, viral load
DEVELOPING COUNTRIES
13th Edition
July 2014-June 2015
www.ichrc.org
Please send suggestions about this booklet to:
Prof Trevor Duke
Centre for International Child Health
University of Melbourne, Department of Paediatrics
Royal Children’s Hospital
Parkville, 3052, Victoria, Australia
Telephone: (613) 9345 5968
Email: trevor.duke@rch.org.au
Randomised trials in child health in developing countries 2014-15
SEARCH STRATEGY
Pubmed Advanced strategy, search: ((Developing countries; Developing country; Countries,
developing; Developed countries; Country, developing; Countries, developed; Developed
country; Country, developed; Nations, developing; Developing nations OR India OR Africa OR
Asia OR South America OR Papua New Guinea OR Asia-Pacific) and (Child*)) AND
(randomized controlled trial[Publication Type] OR (randomized[Title/Abstract] AND
controlled[Title/Abstract] AND trial[Title/Abstract])) publication date between July 1st 2014 and
June 30th 2015.
Introduction .................................................................................................................................. 4
Acute respiratory infection ......................................................................................................... 11
Treatment of pneumonia........................................................................................................ 11
Otitis media ........................................................................................................................... 13
Bronchiolitis .......................................................................................................................... 13
Upper respiratory tract infections, tonsilitis .......................................................................... 14
Adolescent health ....................................................................................................................... 17
Allergy........................................................................................................................................ 19
Anaemia and iron deficiency ..................................................................................................... 19
Anaesthesia and intensive care ................................................................................................... 24
Intensive care ......................................................................................................................... 29
Asthma and chronic lung disease ............................................................................................... 31
Community paediatrics and social support ................................................................................ 34
Dengue ....................................................................................................................................... 36
Development, cerebral palsy and mental health ........................................................................ 39
Diarrhoea .................................................................................................................................... 47
Water purification .................................................................................................................. 49
Endocrine disorders and bone health ......................................................................................... 50
Enterovirus infections ................................................................................................................ 56
Epilepsy and acute seizures ........................................................................................................ 57
Hygiene and environmental health............................................................................................. 60
Haematological disorders ........................................................................................................... 63
HIV / AIDS ................................................................................................................................ 65
Ante-retroviral therapy (ART) .............................................................................................. 65
Early infant diagnosis ............................................................................................................ 66
Management of HIV-related conditions ................................................................................ 67
Nutrition, growth and development of children with HIV .................................................... 68
Prevention of parent to child transmission of HIV ................................................................ 69
HIV vaccine ........................................................................................................................... 75
Integrated approaches to HIV care and prevention ............................................................... 75
Helminth and other gastrointestinal disorders............................................................................ 83
Injury prevention ........................................................................................................................ 88
Integrated management of Childhood Illness (IMCI) ................................................................ 90
Intravenous fluids ....................................................................................................................... 93
Kidney disease ........................................................................................................................... 95
Leprosy ....................................................................................................................................... 97
Malaria ....................................................................................................................................... 98
Diagnosis ............................................................................................................................... 98
Insecticide-treated bed nets ................................................................................................. 100
Other preventative interventions ......................................................................................... 102
Treatment of uncomplicated malaria ................................................................................... 107
2
Randomised trials in child health in developing countries 2014-15
Treatment of severe or complicated malaria ....................................................................... 119
Treatment of vivax malaria ................................................................................................. 120
Malnutrition.............................................................................................................................. 121
Maternal care ............................................................................................................................ 124
Maternal nutrition and micronutrient supplementation ....................................................... 129
Meningitis and encephalitis...................................................................................................... 136
Newborn care ........................................................................................................................... 137
Low birth weight and prematurity ....................................................................................... 144
Neonatal infection ............................................................................................................... 147
Nutrition, micronutrients and breast feeding ........................................................................... 150
Micronutients, multivitamins and food fortification ........................................................... 150
Macronutrient nutrition and complementary feeding .......................................................... 155
Breastfeeding ....................................................................................................................... 161
Community nutrition and agriculture .................................................................................. 162
Obesity................................................................................................................................. 164
Oncology .................................................................................................................................. 166
Ophthalmology ......................................................................................................................... 166
Trachoma ............................................................................................................................. 170
Oral health / dentistry ............................................................................................................... 170
Poisoning and toxins ................................................................................................................ 171
Quality of care .......................................................................................................................... 173
Research methods..................................................................................................................... 174
Schistosomiasis ........................................................................................................................ 176
School health and education..................................................................................................... 181
Skin and hair disease ................................................................................................................ 186
Surgical problems..................................................................................................................... 189
Tuberculosis ............................................................................................................................. 191
Urinary tract infection .............................................................................................................. 200
Vaccines and immunization ..................................................................................................... 200
Cholera vaccine ................................................................................................................... 201
Dengue vaccine ................................................................................................................... 203
HIV vaccine ......................................................................................................................... 204
HPV vaccine ........................................................................................................................ 205
Influenza vaccine ................................................................................................................. 206
Japanese encephalitis virus vaccine..................................................................................... 209
Malaria vaccine ................................................................................................................... 212
Measles vaccine ................................................................................................................... 214
Meningococcal vaccine ....................................................................................................... 215
Pneumococcal vaccine......................................................................................................... 216
Polio vaccine ....................................................................................................................... 219
Rotavirus vaccine ................................................................................................................ 220
Tuberculosis vaccine ........................................................................................................... 225
Typhoid vaccine .................................................................................................................. 228
Varicella vaccine ................................................................................................................. 229
Vitamin A ................................................................................................................................. 230
Vitamin D ................................................................................................................................. 238
Zinc .......................................................................................................................................... 240
3
Randomised trials in child health in developing countries 2014-15
Introduction
This booklet is compiled annually to summarize the evidence on child health derived from
randomized or controlled trials in developing countries over the previous year. The aim is to
make this information widely available to paediatricians, nurses, other health workers and
administrators in resource poor settings where up-to-date information is hard to find. It is hoped
that such information will be helpful in reviewing treatment policies, clinical practice and public
health strategies.
The method of searching for studies to include uses PubMed, a search engine that is freely
available and widely used in most countries throughout the world. The search strategy has been
chosen to capture as many relevant studies as possible, although it is possible that I have missed
some. If you know of a relevant RCT or meta-analysis that has not been included in this year’s
review, please let me know. The search strategy is reproducible by anyone with access to the
Internet, through http://www.ncbi.nlm.nih.gov/sites/entrez
Randomized controlled trials (RCTs) are far from the only valuable scientific evidence, and
some RCTs, because of problems with design or implementation have limited value. However
the method of the Randomized Trial is the Gold Standard for determining attributable benefit or
harm from clinical and public health interventions. When done properly they eliminate bias and
confounding. However their results should not be accepted uncritically and they should be
evaluated for quality and validity. Before the result of an RCT can be generalized to another
setting there must be consideration of the wider applicability, feasibility and potential for
sustainability.
This year 245 studies were identified. These came from all regions of the world, mostly from
developing country researchers. Several trials from 2014-15 will lead to significant changes in
child health approaches or clinical recommendations.
We have included the web-link for papers that are available in full-text on the Internet free of
charge. Through HINARI (http://www.who.int/hinari/en/) a program set up by WHO in
collaboration with publishers, the full-text versions of over 14,000 journal titles and 30,000 ebooks are available to health institutions in over 100 countries. If your health institution
(medical school, teaching hospital, nursing school, government office) has not registered with
HINARI, you can check your eligibility and register online.
Please feel free to distribute this booklet to any colleagues. The previous editions (2002-2014)
are available at: www.ichrc.org
Two years ago we published a summary of the first 11 years of the controlled trials. The
reference for this is: Duke T, Fuller D. Arch Dis Child 2014, 99:615–620, and you may
download it at: http://adc.bmj.com/content/99/7/615.full.pdf+html
A brief summary of some of the important results in 2014-15
In a high-mortality setting in Kenya where co-morbidities are common, among children with
non-severe pneumonia, oral amoxicillin was non-inferior to intravenous benzylpenicillin,
and failure rates at day 14 were 13.5 and 16.8% respectively. In Brazil oral amocycillin
given 2 times per day was as effective as 3 times per day in treating non-severe pneumonia
4
Randomised trials in child health in developing countries 2014-15
with treatment failure rates of 23% and 22% respectively.
Children in African hospitals with severe anaemia were more likely to die in the first 24
hours (case fatality rate 13%) than those with mild or moderate anaemia (7-8%). Children
with severe anaemia who were not transfused at 2.5 hours had a much higher risk of dying
than those who received blood early.
For Indian children with central nervous system infections cared for in an intensive care unit,
the targeting of a cerebral perfusion pressure >60mmHg using fluid boluses, and dopamine /
noradrenaline, resulted in lower mortality and less neuro-disability than a strategy aiming to
keep intracranial pressure 250, viral load