RCTs in child health in developing countries 2010-2011
RANDOMISED TRIALS IN CHILD HEALTH IN
DEVELOPING COUNTRIES
9th Edition
July 2010-June 2011
www.ichrc.org
Please send suggestions about this booklet to:
Prof Trevor Duke
Centre for International Child Health
University Department of Paediatrics
Royal Children’s Hospital
Parkville, 3052, Victoria, Australia
Telephone: (613) 9345 5968
Fax: (613) 9345 6667
Email: trevor.duke@rch.org.au
Randomised trials in child health in developing countries 2010-11
SEARCH STRATEGY
Pubmed Hayne’s 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])).
Introduction .................................................................................................................................. 4
Acute respiratory infection........................................................................................................... 7
Treatment of severe pneumonia .............................................................................................. 7
Treatment of non-severe pneumonia ....................................................................................... 9
Micronutrients and pneumonia.............................................................................................. 10
Adolescent health ....................................................................................................................... 13
Anaemia and iron deficiency ..................................................................................................... 17
Anaesthesia and intensive care................................................................................................... 18
Community health services ........................................................................................................ 22
Development and mental health................................................................................................. 24
Diabetes...................................................................................................................................... 26
Diarrhoea.................................................................................................................................... 26
Zinc in diarrhoea ................................................................................................................... 27
Probiotics............................................................................................................................... 29
Water purification.................................................................................................................. 34
Emergency care.......................................................................................................................... 36
Intravenous fluids .................................................................................................................. 36
Envenomation........................................................................................................................ 39
Epilepsy and acute seizures........................................................................................................ 41
Hepatitis and liver disease.......................................................................................................... 42
HIV / AIDS ................................................................................................................................ 43
Anti-retroviral treatment........................................................................................................ 43
Management of HIV-related conditions................................................................................ 45
Prevention of parent to child transmission ............................................................................ 48
Helminth and other gastrointestinal infections .......................................................................... 53
Hygiene ...................................................................................................................................... 55
Integrated management of childhood illness.............................................................................. 56
Leishmaniasis............................................................................................................................. 57
Visceral leishmaniasis ........................................................................................................... 57
Cutaneous leismaniasis.......................................................................................................... 60
Malaria ....................................................................................................................................... 61
Malaria vaccines.................................................................................................................... 62
Intermittent preventative treatment ....................................................................................... 65
Other preventative strategies ................................................................................................. 73
Treatment of uncomplicated malaria..................................................................................... 74
Treatment of severe or complicated malaria ......................................................................... 87
Treatment of vivax malaria ................................................................................................... 89
Malnutrition................................................................................................................................ 90
Maternal health........................................................................................................................... 92
Maternal micronutrients ........................................................................................................ 93
Maternal mental health .......................................................................................................... 97
2
Randomised trials in child health in developing countries 2010-11
Womens groups ..................................................................................................................... 98
Neonatal care.............................................................................................................................. 99
Neurocysticercosis ................................................................................................................... 102
Nutrition, micronutrients and breast feeding ........................................................................... 103
Micronutients and food fortification ................................................................................... 106
Breastfeeding and Complementary feeding ........................................................................ 111
Oncology .................................................................................................................................. 112
Ophthalmology......................................................................................................................... 113
Trachoma............................................................................................................................. 113
Oral health / dentistry............................................................................................................... 117
Parasites – other ....................................................................................................................... 118
Tungiasis – sand flea disease............................................................................................... 118
Renal disease............................................................................................................................ 119
School health............................................................................................................................ 120
Skin disease.............................................................................................................................. 122
Surgical problems..................................................................................................................... 123
Tuberculosis ............................................................................................................................. 126
Typhoid .................................................................................................................................... 127
Vaccines and immunization ..................................................................................................... 128
Immunization coverage ....................................................................................................... 128
Non-specific effects............................................................................................................. 129
BCG vaccine........................................................................................................................ 130
Diptheria – Tetanus – Pertussus - Haemophilus influenzae vaccine................................... 131
Hepatitis B vaccine.............................................................................................................. 133
HPV vaccine........................................................................................................................ 133
Japanese Encephalitis Virus vaccine ................................................................................... 135
Polio vaccine ....................................................................................................................... 136
Shigella vaccine................................................................................................................... 136
Typhoid vaccine .................................................................................................................. 137
Rotavirus vaccine ................................................................................................................ 138
Cholera vaccine ................................................................................................................... 138
Rabies vaccine ..................................................................................................................... 139
Influenza vaccine................................................................................................................. 140
Meningococcal vaccine ....................................................................................................... 140
Vitamin A................................................................................................................................. 141
Vitamin D and calcium ............................................................................................................ 142
Zinc .......................................................................................................................................... 145
3
Randomised trials in child health in developing countries 2010-11
Introduction
This booklet is compiled annually to summarize the evidence on child health derived from
randomized 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 try to capture as many relevant studies as possible, although it is possible that some
are missed. If you know of a relevant RCT 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 appropriately performed 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 200 studies were identified. These came from all regions of the world, mostly from
developing country researchers. Several trials from 2010-11 will lead to significant changes in
child health approaches or clinical recommendations.
We have included the web-link for papers that are freely available in full-text on the Internet.
More importantly, through HINARI (http://www.who.int/hinari/en/) a program set up by
WHO in collaboration with major publishers, the full-text version of over 7000 journal titles are
now available to health institutions in 109 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. Previous editions (2002-2010) are
available at: www.ichrc.org
Four trials reported significant reductions in mortality (marked with *** in the booklet),
among these:
In Kenya, South Africa and Burkina Faso giving a combination of three antiretroviral
(ARV) drugs to pregnant women who had HIV infection, from the last trimester through
to six months of breastfeeding, reduced the risk of transmitting HIV to the baby and
improves survival, compared to zidovudine in pregnancy and single dose nevirapine.
In 11 centres in 9 African countries among more than 5000 children with severe malaria
Artesunate substantially reduced mortality compared to quinine treatment.
In rural China, micronutrient supplementation to pregnant women from the poorest
households reduced neonatal mortality, and reduced low birth weight. Standard iron and
4
Randomised trials in child health in developing countries 2010-11
folic acid provided more protection against neonatal death than multiple micronutrient
supplements.
In Pakistan, in a trial involving over 46,000 households, a community-based program
involving lady health workers who delivered antenatal care and maternal health
education, clean delivery kits, promoted facility births, immediate newborn care,
identification of danger signs, and care seeking, significantly reduced still-births and
neonatal deaths.
Other important results in 2010-11
•
In Rwanda paying primary health facilities for performance resulted in a 23% increase in
the number of institutional deliveries and a significant increase in the number of
preventive care visits by children
•
In Bangladesh, day-case management of severe pneumonia in hospital was successful, as
long as those with hypoxia were identified and managed as in-patients.
•
A green banana-supplemented diet hastened recovery of acute and prolonged childhood
diarrhoea managed at home in rural Bangladesh.
•
There were several trials of zinc in India, Bangladesh and Pakistan this year. In a
community-based effectiveness trial in India, educating caregivers to provide zinc
supplementation to infants
DEVELOPING COUNTRIES
9th Edition
July 2010-June 2011
www.ichrc.org
Please send suggestions about this booklet to:
Prof Trevor Duke
Centre for International Child Health
University Department of Paediatrics
Royal Children’s Hospital
Parkville, 3052, Victoria, Australia
Telephone: (613) 9345 5968
Fax: (613) 9345 6667
Email: trevor.duke@rch.org.au
Randomised trials in child health in developing countries 2010-11
SEARCH STRATEGY
Pubmed Hayne’s 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])).
Introduction .................................................................................................................................. 4
Acute respiratory infection........................................................................................................... 7
Treatment of severe pneumonia .............................................................................................. 7
Treatment of non-severe pneumonia ....................................................................................... 9
Micronutrients and pneumonia.............................................................................................. 10
Adolescent health ....................................................................................................................... 13
Anaemia and iron deficiency ..................................................................................................... 17
Anaesthesia and intensive care................................................................................................... 18
Community health services ........................................................................................................ 22
Development and mental health................................................................................................. 24
Diabetes...................................................................................................................................... 26
Diarrhoea.................................................................................................................................... 26
Zinc in diarrhoea ................................................................................................................... 27
Probiotics............................................................................................................................... 29
Water purification.................................................................................................................. 34
Emergency care.......................................................................................................................... 36
Intravenous fluids .................................................................................................................. 36
Envenomation........................................................................................................................ 39
Epilepsy and acute seizures........................................................................................................ 41
Hepatitis and liver disease.......................................................................................................... 42
HIV / AIDS ................................................................................................................................ 43
Anti-retroviral treatment........................................................................................................ 43
Management of HIV-related conditions................................................................................ 45
Prevention of parent to child transmission ............................................................................ 48
Helminth and other gastrointestinal infections .......................................................................... 53
Hygiene ...................................................................................................................................... 55
Integrated management of childhood illness.............................................................................. 56
Leishmaniasis............................................................................................................................. 57
Visceral leishmaniasis ........................................................................................................... 57
Cutaneous leismaniasis.......................................................................................................... 60
Malaria ....................................................................................................................................... 61
Malaria vaccines.................................................................................................................... 62
Intermittent preventative treatment ....................................................................................... 65
Other preventative strategies ................................................................................................. 73
Treatment of uncomplicated malaria..................................................................................... 74
Treatment of severe or complicated malaria ......................................................................... 87
Treatment of vivax malaria ................................................................................................... 89
Malnutrition................................................................................................................................ 90
Maternal health........................................................................................................................... 92
Maternal micronutrients ........................................................................................................ 93
Maternal mental health .......................................................................................................... 97
2
Randomised trials in child health in developing countries 2010-11
Womens groups ..................................................................................................................... 98
Neonatal care.............................................................................................................................. 99
Neurocysticercosis ................................................................................................................... 102
Nutrition, micronutrients and breast feeding ........................................................................... 103
Micronutients and food fortification ................................................................................... 106
Breastfeeding and Complementary feeding ........................................................................ 111
Oncology .................................................................................................................................. 112
Ophthalmology......................................................................................................................... 113
Trachoma............................................................................................................................. 113
Oral health / dentistry............................................................................................................... 117
Parasites – other ....................................................................................................................... 118
Tungiasis – sand flea disease............................................................................................... 118
Renal disease............................................................................................................................ 119
School health............................................................................................................................ 120
Skin disease.............................................................................................................................. 122
Surgical problems..................................................................................................................... 123
Tuberculosis ............................................................................................................................. 126
Typhoid .................................................................................................................................... 127
Vaccines and immunization ..................................................................................................... 128
Immunization coverage ....................................................................................................... 128
Non-specific effects............................................................................................................. 129
BCG vaccine........................................................................................................................ 130
Diptheria – Tetanus – Pertussus - Haemophilus influenzae vaccine................................... 131
Hepatitis B vaccine.............................................................................................................. 133
HPV vaccine........................................................................................................................ 133
Japanese Encephalitis Virus vaccine ................................................................................... 135
Polio vaccine ....................................................................................................................... 136
Shigella vaccine................................................................................................................... 136
Typhoid vaccine .................................................................................................................. 137
Rotavirus vaccine ................................................................................................................ 138
Cholera vaccine ................................................................................................................... 138
Rabies vaccine ..................................................................................................................... 139
Influenza vaccine................................................................................................................. 140
Meningococcal vaccine ....................................................................................................... 140
Vitamin A................................................................................................................................. 141
Vitamin D and calcium ............................................................................................................ 142
Zinc .......................................................................................................................................... 145
3
Randomised trials in child health in developing countries 2010-11
Introduction
This booklet is compiled annually to summarize the evidence on child health derived from
randomized 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 try to capture as many relevant studies as possible, although it is possible that some
are missed. If you know of a relevant RCT 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 appropriately performed 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 200 studies were identified. These came from all regions of the world, mostly from
developing country researchers. Several trials from 2010-11 will lead to significant changes in
child health approaches or clinical recommendations.
We have included the web-link for papers that are freely available in full-text on the Internet.
More importantly, through HINARI (http://www.who.int/hinari/en/) a program set up by
WHO in collaboration with major publishers, the full-text version of over 7000 journal titles are
now available to health institutions in 109 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. Previous editions (2002-2010) are
available at: www.ichrc.org
Four trials reported significant reductions in mortality (marked with *** in the booklet),
among these:
In Kenya, South Africa and Burkina Faso giving a combination of three antiretroviral
(ARV) drugs to pregnant women who had HIV infection, from the last trimester through
to six months of breastfeeding, reduced the risk of transmitting HIV to the baby and
improves survival, compared to zidovudine in pregnancy and single dose nevirapine.
In 11 centres in 9 African countries among more than 5000 children with severe malaria
Artesunate substantially reduced mortality compared to quinine treatment.
In rural China, micronutrient supplementation to pregnant women from the poorest
households reduced neonatal mortality, and reduced low birth weight. Standard iron and
4
Randomised trials in child health in developing countries 2010-11
folic acid provided more protection against neonatal death than multiple micronutrient
supplements.
In Pakistan, in a trial involving over 46,000 households, a community-based program
involving lady health workers who delivered antenatal care and maternal health
education, clean delivery kits, promoted facility births, immediate newborn care,
identification of danger signs, and care seeking, significantly reduced still-births and
neonatal deaths.
Other important results in 2010-11
•
In Rwanda paying primary health facilities for performance resulted in a 23% increase in
the number of institutional deliveries and a significant increase in the number of
preventive care visits by children
•
In Bangladesh, day-case management of severe pneumonia in hospital was successful, as
long as those with hypoxia were identified and managed as in-patients.
•
A green banana-supplemented diet hastened recovery of acute and prolonged childhood
diarrhoea managed at home in rural Bangladesh.
•
There were several trials of zinc in India, Bangladesh and Pakistan this year. In a
community-based effectiveness trial in India, educating caregivers to provide zinc
supplementation to infants