Global burden of childhood pneumonia and diarrhoea

Probably not a substantial claim: may not pass S3 (load-bearing).

Of the 2010 pneumonia episodes in children younger than 5 years, 14 million progressed to severe episodes.

“We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years.”

May combine two claims.

15 countries account for 53% of total diarrhoea episodes and 56% of severe diarrhoea episodes.

“15 countries—namely, Afghanistan, Angola, Burkina Faso, China, Democratic Republic of the Congo, Ethiopia, India, Indonesia, Kenya, Mali, Niger, Nigeria, Pakistan, Tanzania, and Uganda—account for 53% of total episodes of diarrhoea and 56% of severe episodes, and 65% of total episodes of pneumonia and 64% of severe episodes (appendix).”

May combine two claims.

Morbidity and mortality from childhood pneumonia and diarrhoea are falling.

“Morbidity and mortality from childhood pneumonia and diarrhoea are falling, but action is needed globally and at country level to accelerate the reduction.”

May combine two claims.

15 countries account for 65% of total pneumonia episodes and 64% of severe pneumonia episodes.

“15 countries—namely, Afghanistan, Angola, Burkina Faso, China, Democratic Republic of the Congo, Ethiopia, India, Indonesia, Kenya, Mali, Niger, Nigeria, Pakistan, Tanzania, and Uganda—account for 53% of total episodes of diarrhoea and 56% of severe episodes, and 65% of total episodes of pneumonia and 64% of severe episodes (appendix).”

May combine two claims.

Adjusted for immunisation against H influenzae type b and S pneumoniae, pneumonia incidence was lowest in the European region and highest in the African and southeast Asian regions.

“Pneumonia incidence is more variable between regions than is diarrhoea incidence; adjusted for immunisation against H influenzae type b and S pneumoniae, it was lowest in the European region and highest in the African and southeast Asian regions.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In 2011, diarrhoea caused about 700,000 deaths in children younger than 5 years.

“We estimated that, in 2011, 700 000 episodes of diarrhoea and 1·3 million of pneumonia led to death.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In 2011, the combined number of deaths from diarrhoea and pneumonia in children younger than 5 years was 1.97 million.

“In 2011, the number of deaths from the two diseases fell to 1·97 million (0·71 million associated with diarrhoea and 1·26 million with pneumonia).”

May combine two claims.

Rotavirus is the most common cause of vaccine-preventable severe diarrhoea and is associated with 28% of severe diarrhoea cases.

“Rotavirus is the most common cause of vaccine-preventable severe diarrhoea (associated with 28% of cases), and Streptococcus pneumoniae (18·3%) of vaccine-preventable severe pneumonia.”

May combine two claims.

Streptococcus pneumoniae is the most common cause of vaccine-preventable severe pneumonia and is associated with 18.3% of cases.

“Rotavirus is the most common cause of vaccine-preventable severe diarrhoea (associated with 28% of cases), and Streptococcus pneumoniae (18·3%) of vaccine-preventable severe pneumonia.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Of the 2010 diarrhoea episodes in children younger than 5 years, 36 million progressed to severe episodes.

“We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In 2011, pneumonia caused about 1.3 million deaths in children younger than 5 years.

“We estimated that, in 2011, 700 000 episodes of diarrhoea and 1·3 million of pneumonia led to death.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In 2010, there were 120 million episodes of pneumonia in children younger than 5 years worldwide.

“We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Data sources from the 15 highest-burden countries are scant.

“Nearly three-quarters of diarrhoea mortality and pneumonia mortality are concentrated in 15 high-burden countries, yet data sources from these countries are scant”

May combine two claims.

Vaccine-preventable pneumonias account for at least one third of severe pneumonia episodes and two thirds of pneumonia deaths.

“Nearly a third of episodes of severe diarrhoea are preventable by vaccination (ie, against rotavirus and cholera), whereas vaccine-preventable pneumonias (ie, those caused by Streptococcus pneumoniae, Haemophilus influenzae type b, and the influenza virus) account for at least a third of severe episodes and two-thirds of deaths”

May combine two claims.

Diarrhoea incidence peaks at age 6-11 months and then decreases with age.

“Diarrhoea incidence peaks at age 6–11 months and then decreases with age;8 proportionate mortality is highest from age 0–11 months, the ages at which the risk of disease and severe disease also peak.”

• cites [8] Fischer Walker, 2012, Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review, BMC Public Health sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Diarrhoea incidence and case-fatality ratios are much higher in low-income than in middle-income and high-income countries.

“The incidence of diarrhoea does not differ substantially between regions, but incidence and case-fatality ratios are much higher in low-income than in middle-income and high-income countries.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In 2010, there were 1.731 billion episodes of diarrhoea in children younger than 5 years worldwide.

“We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years.”

May combine two claims.

2% of diarrhoea episodes and 12% of pneumonia episodes progress to severe disease.

“We estimate that 2% of diarrhoea episodes and 12% of pneumonia episodes progress to severe disease.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Vibrio cholerae causes roughly 1% of severe diarrhoea worldwide and is endemic in south Asia and some countries in sub-Saharan Africa.

“V cholerae causes roughly 1% of severe diarrhoea worldwide, but is endemic in south Asia and some countries in sub-Saharan Africa.”

May combine two claims.

The risk of at least one long-term major sequela after pneumonia is 5.5% (95% CI 2.8-8.3) in non-severe pneumonia and 13.6% (6.2-21.1) in severe pneumonia treated in hospital.

“A systematic review14 of pneumonia sequelae showed that the risk of at least one long-term major sequela was 5·5% (95% CI 2·8–8·3) in non-severe pneumonia and 13·6% (6·2–21·1) in severe pneumonia treated in hospital.”

• cites [14] Edmond, 2012, Long term sequelae from childhood pneumonia; systematic review and meta-analysis, PLoS One sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Most data from developing countries on neonatal infections are from unrepresentative hospital-based studies with little relevance in home-birth settings.

“Most data from developing countries are reported from unrepresentative hospital-based studies, which have little relevance in home-birth settings (where most children are born in many countries).56, 57, 58, 59”

• cites [56] Zaidi, 2005, Hospital-acquired neonatal infections in developing countries, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [57] Zaidi, 2009, Pathogens associated with sepsis in newborns and young infants in developing countries, Pediatr Infect Dis J sourceNot checked yet

  Not checked in the free run.

• cites [58] Jawad, 2012, Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality, J Global Health sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The link between childhood pneumonia and obstructive lung disease is not yet clear.

“The link between childhood pneumonia and obstructive lung disease is not yet clear.14”

• cites [14] Edmond, 2012, Long term sequelae from childhood pneumonia; systematic review and meta-analysis, PLoS One sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Rates of mortality from diarrhoea and pneumonia are highly correlated, and changes over time are similar for both diseases within the same country.

“Rates of mortality from diarrhoea and pneumonia are highly correlated, and changes in mortality with time are similar for both diseases within the same country (figure 2 ).”

May combine two claims.

Pathogen-specific incidences of diarrhoea vary by age, but few data are available for generation of age-specific estimates by enteropathogen.

“Pathogen-specific incidences of diarrhoea vary by age, yet few data are available for generation of age-specific estimates by enteropathogen.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The global estimate of severe diarrhoea associated with V cholerae differs slightly from the estimate based on regional data.

“The global estimate of cases of severe diarrhoea associated with V cholerae, which is based on available data from a global model, differs slightly from that based on regional estimates derived from a subset of regional data (table 2).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Haemophilus influenzae type b causes 4% of severe pneumonia episodes and 16% of pneumonia deaths.

“Important vaccine-preventable causes of severe pneumonia are S pneumoniae (which causes at least 18% of severe episodes and 33% of deaths worldwide), the influenza virus (7% of severe episodes and 11% of deaths), and H influenzae type b (4% of severe episodes and 16% of deaths).”

May combine two claims.

The yearly rate of change in diarrhoea and pneumonia mortality varies substantially between countries, with China reaching 12% for both diseases.

“The yearly rate of change varies substantially between countries, with China reaching 12% for both diseases, whereas other countries have rates that are much less than the fourth Millennium Development Goal target rate of 4·4%.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Streptococcus pneumoniae causes at least 18% of severe pneumonia episodes and 33% of pneumonia deaths worldwide.

“Important vaccine-preventable causes of severe pneumonia are S pneumoniae (which causes at least 18% of severe episodes and 33% of deaths worldwide), the influenza virus (7% of severe episodes and 11% of deaths), and H influenzae type b (4% of severe episodes and 16% of deaths).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Influenza virus causes 7% of severe pneumonia episodes and 11% of pneumonia deaths.

“Important vaccine-preventable causes of severe pneumonia are S pneumoniae (which causes at least 18% of severe episodes and 33% of deaths worldwide), the influenza virus (7% of severe episodes and 11% of deaths), and H influenzae type b (4% of severe episodes and 16% of deaths).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Guillain-Barré syndrome, haemolytic uraemic syndrome, and reactive arthritis are rarely noted and are attributable only to selected pathogens.

“Guillain-Barré syndrome, haemolytic uraemic syndrome, and reactive arthritis are rarely noted and are attributable only to selected pathogens (unpublished).15, 45”

• cites [15] Poropatich, 2010, Quantifying the association between Campylobacter infection and Guillain-Barré syndrome: a systematic review, J Health Popul Nutr sourceNot checked yet

  Not checked in the free run.

• cites [45] Fischer Walker, 2012, Haemolytic-ureaemic syndrom as a sequela of diarrhoeal disease, J Health Popul NutrNot checked yet

  Not checked in the free run.

May combine two claims.

Rotavirus is associated with 28% of severe diarrhoea cases and 28% of fatal diarrhoea cases worldwide.

“The most common cause of severe and fatal diarrhoea worldwide is rotavirus (associated with 28% of severe cases and 28% of fatal cases); the data analysed here are from before the rotavirus vaccine was available, and thus this proportion might be slightly lower in 2011 in the Americas and a few other countries where the vaccine is used (unpublished).”

May combine two claims.

In a randomised controlled trial in rural Guatemala, wood stoves with chimneys had non-significant reductions in pneumonia incidence compared with open fires (RR 0.84, 95% CI 0.63-1.13); in an exposure-response analysis the reduction was significant (0.82, 0.70-0.98).

“In a randomised controlled trial75 in rural Guatemala, participants who were given wood stoves with chimneys had non-significant reductions in the incidence of pneumonia compared with those who continued to use open fires (RR 0·84, 95% CI 0·63–1·13); however, in an exposure–response analysis the reduction was significant (0·82, 0·70–0·98).”

• cites [75] Smith, 2011, Effect of reduction in household air pollution on childhood pneumonia in Guatemala (RESPIRE): a randomised controlled trial, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Risk relations between specific water and sanitation risk factors and diarrhoea morbidity and mortality have been shown, but for some outcomes poor evidence permits only rough estimates.

“Risk relations between specific water and sanitation risk factors (ie, unwashed hands and poor water quality) and diarrhoea morbidity and mortality have been shown, but for some outcomes, such as inappropriate excreta disposal, poor availability of evidence permits only rough estimates of risk.68, 69”

• cites [68] Esrey, 1991, Effects of improved water supply and sanitation on ascariasis, diarrhoea, dracunculiasis, hookworm infection, schistosomiasis, and trachoma, Bull World Health OrganNot checked yet

  Not checked in the free run.

• cites [69] Cairncross, 2010, Water, sanitation and hygiene for the prevention of diarrhoea, Int J Epidemiol sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Vitamin A deficiency increases the risk of severe diarrhoea and diarrhoea mortality (RR 1.5, 95% CI 1.3-1.8), but is not an important risk factor for diarrhoea or pneumonia incidence or pneumonia mortality.

“Vitamin A deficiency increases the risk of severe diarrhoea and thus diarrhoea mortality (relative risk [RR] 1·5, 95% CI 1·3–1·8),66 but is not an important risk factor for the incidence of diarrhoea or pneumonia, or for pneumonia-related mortality.66”

• cites [66] Black, 2008, Maternal and child undernutrition: global and regional exposures and health consequences, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Both diarrhoea and pneumonia are associated with poverty.

“Both diseases are associated with poverty, and child mortality from them is higher in low-income than in high-income countries and in populations in crisis situations (panel 2 ).”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Severe morbidity and mortality and yearly changes in mortality with time are strongly correlated for childhood diarrhoea and pneumonia.

“Severe morbidity and mortality and yearly changes in mortality with time are strongly correlated for childhood diarrhoea and pneumonia.”

May combine two claims.

In neither Ghana nor Brazil was pneumonia a risk factor for diarrhoea.

“In neither country was the reverse relation—ie, pneumonia as a risk for diarrhoea—noted.”

May combine two claims.

In a small group of studies, exposure to indoor air pollution was associated with increased risk of severe pneumonia and pneumonia mortality; additional studies are needed before a combined analysis can be done.

“In a small group of studies,74 exposure to indoor air pollution (various definitions of risk were used) was associated with increased risk of severe pneumonia and pneumonia mortality; additional studies are needed before a combined analysis can be done to produce a risk estimate.”

• cites [74] Dherani, 2008, Indoor air pollution from unprocessed solid fuel use and pneumonia risk in children aged under five years: a systematic review and meta-analysis, Bull World Health Organ sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Intrauterine growth restriction and prematurity are risk factors for all-cause neonatal mortality, but cause-specific data are not available so risk relations cannot be quantified.

“Other factors, such as intrauterine growth restriction and prematurity, are risk factors for all-cause neonatal mortality, but cause-specific data are not available and thus risk relations cannot be quantified.67”

• cites [67] Fishman, 2004, Childhood and maternal underweightNot checked yet

  Not checked in the free run.

May combine two claims.

Child mortality from diarrhoea and pneumonia is higher in low-income than in high-income countries and in populations in crisis situations.

“Both diseases are associated with poverty, and child mortality from them is higher in low-income than in high-income countries and in populations in crisis situations (panel 2 ).”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Little information is available about the effect of HIV infection on neonatal pneumonia.

“Little information is available about the effect of HIV infection on neonatal pneumonia.”

May combine two claims.

Crowding and exposure to indoor air pollution increase pneumonia incidence, but are not associated with increased risk for diarrhoea morbidity or mortality.

“Crowding and exposure to indoor air pollution increase pneumonia incidence, but are not associated with increased risk for diarrhoea morbidity or mortality.”

May combine two claims.

72% of deaths from diarrhoea and 81% of deaths from pneumonia occur within the first 2 years of life.

“72% of deaths from diarrhoea and 81% of deaths from pneumonia occur within the first 2 years of life, which has clear implications for health policy.”

May combine two claims.

Rotavirus is the most important cause of diarrhoea mortality in children, whereas S pneumoniae, H influenzae, and influenza virus are three of the four main causes of pneumonia mortality.

“Rotavirus is the most important cause of diarrhoea mortality in children, whereas S pneumoniae, H influenzae, and influenza virus are three of the four main causes of pneumonia mortality.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

For some risk factors, such as inadequate water and sanitation, poor handwashing, indoor air pollution, and crowding, risk relations have been difficult to define.

“For some risk factors, such as inadequate water and sanitation, poor handwashing, indoor air pollution, and crowding, risk relations have been difficult to define, but addressing them will probably have benefits for disease reduction.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Childhood pneumonia and diarrhoea were estimated to account for about 2 million child deaths in 2011 (28·5% of total mortality in children younger than 5 years).

“Childhood pneumonia and diarrhoea were estimated to account for about 2 million child deaths in 2011 (28·5% of total mortality in children younger than 5 years), and are a high priority for child health programmes.”

May combine two claims.

In Burkina Faso, estimated diarrhoea and pneumonia mortality rates fell from 2000 to 2010, but estimated numbers of deaths in children younger than 5 years increased (diarrhoea 13 447 to 14 648; pneumonia 17 389 to 21 763).

“For example, in Burkina Faso, the estimated rates of diarrhoea and pneumonia specific mortality fell from 2000 to 2010, yet the estimated number of deaths in children younger than 5 years increased (from 13 447 to 14 648 for diarrhoea and 17 389 to 21 763 for pneumonia); we note similar trends in Afghanistan, Cameroon, Chad, Democratic Republic of the Congo, and Mali.”

May combine two claims.

Mortality from both diarrhoea and pneumonia fell substantially between 2000 and 2011.

“Mortality from both diarrhoea and pneumonia fell substantially between 2000 and 2011.”

May combine two claims.

In Cambodia, diarrhoea mortality rates fell by 12% and pneumonia mortality rates by 8% each year from 2000 to 2010, contrasting with yearly decreases of 2·4% and 1·6% in Papua New Guinea.

“In Cambodia, for example, diarrhoea mortality rates have been falling by 12% and pneumonia mortality rates by 8% each year from 2000 to 2010—findings which contrast with yearly decreases of 2·4% and 1·6% in Papua New Guinea.”

May combine two claims.

No adjustments were made for the effects of the HIV/AIDS pandemic because the relation between HIV/AIDS and severe pneumonia morbidity and mortality is not sufficiently understood.

“We made no adjustments for the effects of the HIV/AIDS pandemic, because the relation between HIV/AIDS and severe morbidity and mortality from pneumonia is not sufficiently understood.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The epidemiology of childhood diarrhoea and pneumonia overlaps, partly because of shared risk factors such as undernutrition, suboptimum breastfeeding, and zinc deficiency.

“The epidemiology of childhood diarrhoea and that of pneumonia overlap, which might be partly because of shared risk factors, such as undernutrition, suboptimum breastfeeding, and zinc deficiency.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Diarrhoea and pneumonia account for about 30% of all child deaths worldwide.

“Despite large reductions in child mortality between 2000 and 2010 (both all-cause mortality, and that specifically associated with diarrhoea and pneumonia), these diseases remain major causes of avoidable deaths and account for about 30% of all child deaths worldwide.1, 2”

• cites [1] Liu, 2012, Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [2] 2012Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Risk factors were retained only if they met GRADE criteria level 1 or 2 in favour of a definite effect.

“We did a systematic review of published reviews of risk factors for childhood pneumonia and diarrhoea and retained risk factors that met the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria level 1 or 2 in favour of a definite effect.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

As children grow older, the causes of clinical pneumonia are mainly respiratory syncytial virus, influenza virus, Streptococcus pneumoniae, and Haemophilus influenzae.

“As children grow older, the causes of clinical pneumonia are mainly respiratory syncytial virus, influenza virus, Streptococcus pneumoniae, and Haemophilus influenzae.”

May combine two claims.

Stunting is an important sequela because it indicates long-term nutritional deficit and is associated with decreased cognitive function.

“Stunting is an important sequela because it is indicative of long-term nutritional deficit and is associated with decreased cognitive function.43”

• cites [43] Walker, 2011, Inequality in early childhood: risk and protective factors for early child development, Lancet sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The HIV/AIDS pandemic has changed the risk for both diseases and the range of causes in countries with high prevalences of HIV infection.

“The HIV/AIDS pandemic has also changed the risk for both diseases and the range of causes in countries with high prevalences of HIV infection.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Giardia lamblia and Entamoeba histolytica do not typically cause severe dehydrating diarrhoea, but Cryptosporidium can in some circumstances.

“G lamblia and E histolytica do not typically cause severe dehydrating diarrhoea, but Cryptosporidium spp can in some circumstances.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Chronic diarrhoea is part of the clinical syndrome of AIDS; it occurs in roughly 50% of children younger than 5 years with AIDS in high-income countries and nearly all in low-income and middle-income countries.

“Chronic diarrhoea is part of the clinical syndrome of AIDS; it occurs in roughly 50% of children younger than 5 years who have AIDS in high-income countries and nearly all of those in low-income and middle-income countries.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In pathogen-endemic areas, infants receive passive protection from transplacental and breastmilk antibodies for the first 6 months of life.

“In pathogen-endemic areas, infants receive passive protection from transplacental and breastmilk antibodies for the first 6 months of life.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The rotavirus proportion might be slightly lower in 2011 in the Americas and a few other countries where rotavirus vaccine is used.

“The most common cause of severe and fatal diarrhoea worldwide is rotavirus (associated with 28% of severe cases and 28% of fatal cases); the data analysed here are from before the rotavirus vaccine was available, and thus this proportion might be slightly lower in 2011 in the Americas and a few other countries where the vaccine is used (unpublished).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Many other viruses, bacteria, and parasites cause severe diarrhoea but cannot be prevented by vaccines.

“Many other viruses (including norovirus, astrovirus, and adenovirus), bacteria (the most common of which are pathogenic Escherichia coli, Shigella, Campylobacter, and Salmonella) and parasites (including Giardia lamblia, Entamoeba histolytica, and Cryptosporidium) cause severe diarrhoea but cannot be prevented by vaccines.”

May combine two claims.

For an otherwise healthy child, a single episode of diarrhoea is typically self-limiting and has no long-term sequelae.

“For an otherwise healthy child, a single episode of diarrhoea is typically self-limiting and has no long-term sequelae.”

May combine two claims.

Klebsiella pneumoniae, other Gram-negative rods, and S aureus are major pathogens isolated from the bloodstream in hospital settings in the neonatal period, and about 70% of these blood isolates might be untreatable in low-income settings.

“Klebsiella pneumoniae, other Gram-negative rods (E coli, Pseudomonas spp, Acinetobacter spp), and S aureus are the major pathogens isolated from the bloodstream in hospital settings in the neonatal period, and about 70% of these blood isolates might be untreatable in low-income settings.56, 57, 58, 59”

• cites [56] Zaidi, 2005, Hospital-acquired neonatal infections in developing countries, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [57] Zaidi, 2009, Pathogens associated with sepsis in newborns and young infants in developing countries, Pediatr Infect Dis J sourceNot checked yet

  Not checked in the free run.

• cites [58] Jawad, 2012, Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality, J Global Health sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Repeated episodes of diarrhoea can lead to cognitive deficits via stunting, but not independently.

“Repeated episodes of diarrhoea can thus lead to cognitive deficits via stunting, but not independently as some researchers have postulated.44”

• cites [44] Fischer Walker, 2012, Does childhood diarrhea influence cognition beyond the diarrhea-stunting pathway, PLoS One sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The Haiti cholera outbreak beginning in October 2010 is not included in the estimates, which cover endemic disease only.

“The outbreak of cholera that began in October, 2010, in Haiti is not included in these estimates, which are for endemic disease only.51”

• cites [51] CraviotoNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

As the immune system fails, generally when CD4 count is below 200 cells per μL, HIV-infected individuals become susceptible to opportunistic pathogens.

“Additionally, as the immune system fails, generally when patients have fewer than 200 CD4 cells per μL, such individuals are also susceptible to many opportunistic pathogens, such as Mycobacterium tuberculosis, the Mycobacterium avium complex, cryptosporidium, microsporidia, and cytomegalovirus.”

Probably not a substantial claim: may not pass S3 (load-bearing).

HIV-infected individuals who are not yet immunodeficient are susceptible to the same microbial causes of diarrhoea as HIV-negative individuals.

“Individuals who are infected with HIV and not yet immunodeficient are susceptible to the same microbial causes of diarrhoea as are HIV-negative individuals.”

May combine two claims.

After passive immunity wanes, the first exposure to a pathogen often results in severe disease, while subsequent illnesses tend to be milder.

“After passive immunity wanes, the child's first exposure to a pathogen often results in severe disease; subsequent illnesses tend to be milder and less likely to result in severe dehydration, admission to hospital, and death.”

May combine two claims.

In the early neonatal period, infections might be environmentally acquired because of unhygienic delivery practices rather than perinatally acquired, which might explain the predominance of Gram-negative infections in home-born infants.

“In the early neonatal period, any of these infections might be environmentally acquired because of unhygienic delivery practices in low-income settings rather than perinatally acquired, which might explain the predominance of Gram-negative infections in home-born infants.56, 57, 58, 59”

• cites [56] Zaidi, 2005, Hospital-acquired neonatal infections in developing countries, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [57] Zaidi, 2009, Pathogens associated with sepsis in newborns and young infants in developing countries, Pediatr Infect Dis J sourceNot checked yet

  Not checked in the free run.

• cites [58] Jawad, 2012, Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality, J Global Health sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Exclusively breastfed infants are exposed less to many pathogens than are infants who are not breastfed or receive mixed feedings.

“Additionally, exclusively breastfed infants are exposed less to many pathogens than are infants who are not breastfed or receive mixed feedings.”

May combine two claims.

The risk of reduced lung capacity after pneumonia is highest in the first year of life, presumably because damage to lung parenchyma and bronchioles impairs lung growth.

“These studies suggested that risk was highest in the first year of life, presumably because of damage to lung parenchyma and bronchioles in an early stage of lung development, which is postulated to impair lung growth and reduce vital capacity and forced expiratory volume.14”

• cites [14] Edmond, 2012, Long term sequelae from childhood pneumonia; systematic review and meta-analysis, PLoS One sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

A vaccine against respiratory syncytial virus is in development.

“A vaccine against respiratory syncytial virus is in development.50”

• cites [50] Rudan I, O'Brien KL, Nair H, et al. Epidemiology and etiology of childhood pneumonia in 2010: estimates of incidence, severe morbidity, mortality, underlying risk factors and causing pathogens for 192 countries. J Glob Health (in press).Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Clostridium difficile infection is common in patients exposed to antimicrobials and hospital settings.

“Infection with Clostridium difficile is common in patients exposed to antimicrobials and hospital settings.”

Probably not a substantial claim: may not pass S3 (load-bearing).

As antiretroviral therapy and co-trimoxazole prophylaxis become more widely used and improve survival of HIV-positive children, severe pneumonia and chronic lung disease can be expected to become more common in older children.

“As antiretroviral therapy and co-trimoxazole prophylaxis become more widely used and lead to improved survival of HIV-positive children, severe pneumonia and chronic lung disease can be expected to become more common in older children.”

May combine two claims.

In areas where tuberculosis is endemic, M tuberculosis is an important cause of pneumonia in HIV-positive children and can present as acute severe pneumonia.

“In areas where tuberculosis is endemic, M tuberculosis is an important cause of pneumonia in HIV-positive children and can present as acute severe pneumonia.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

With moderate measles vaccine coverage (45-90%) in infants, diarrhoea incidence could be reduced by 0·6-3·8% and diarrhoea mortality by 6-26% in children under 5 years.

“In 1983, Feachem and Koblinsky78 estimated that, with moderate coverage of the measles vaccine (45–90%) in infants, the incidence of diarrhoea could be reduced by 0·6–3·8%, and, more importantly, diarrhoea mortality could be reduced by 6–26% in children younger than 5 years.”

• cites [78] Feachem, 1983, Interventions for the control of diarrhoeal diseases among young children: measles immunization, Bull World Health OrganNot checked yet

  Not checked in the free run.

May combine two claims.

Infections with more than one pathogen or antibiotic-resistant bacteria are more common in HIV-positive than HIV-negative children and lead to higher case-fatality ratios.

“Infections with more than one pathogen or antibiotic-resistant bacteria are more common in HIV-positive than in HIV-negative children, and lead to higher case-fatality ratios.62, 63”

• cites [62] Enarson, 2010, Impact of HIV on standard case management for severe pneumonia in children, Expert Rev Respir Med sourceNot checked yet

  Not checked in the free run.

• cites [63] Graham, 2007, HIV-related pulmonary disorders: practice issues, Ann Trop Paediatr sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Cholera infection typically causes acute secretory diarrhoea with rice-water stools and can result in hypotensive shock and high case-fatality rates in susceptible individuals.

“Infection typically causes acute secretory diarrhoea with so-called rice-water stools (as much as 1 L/h), and can result in hypotensive shock and high case-fatality rates in susceptible individuals.90”

• cites [90] Harris, 2012, Cholera, Lancet sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Cholera epidemics occur in areas with poor water and sanitation facilities, little basic infrastructure, and high population densities.

“Epidemics occur in areas with poor water and sanitation facilities, little basic infrastructure, and high population densities.93”

• cites [93] Hartley, 2006, Hyperinfectivity: a critical element in the ability of V. cholerae to cause epidemics?, PLoS Med sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

HIV can directly affect the intestinal mucosa, resulting in enteropathy with diarrhoea due to changed intestinal functions.

“HIV can directly affect the intestinal mucosa, resulting in enteropathy with diarrhoea due to changed intestinal functions.60”

• cites [60] Wilcox, 2000, Etiology and evaluation of diarrhea in AIDS: a global perspective at the millennium, World J GastroenterolNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

In epidemics when V cholerae infects a naive population, morbidity and mortality occur at all ages.

“In epidemics when V cholerae infects a naive population, morbidity and mortality occur at all ages.92”

• cites [92] Feachem, 1982, Environmental aspects of cholera epidemiology. III. Transmission and control, Trop Dis BullNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In emergency or refugee populations, pneumonia accounted for 20% of all child deaths and 17% of illness episodes, whereas diarrhoea accounted for 7% of deaths and 10% of illness episodes.

“Data from health information systems81 in these populations show that pneumonia (defined by WHO thresholds for fast breathing) accounted for 20% of all child deaths and 17% of illness episodes, whereas diarrhoea accounted for 7% of deaths and 10% of illness episodes.”

• cites [81] Hershey, 2011, Incidence and risk factors for malaria, pneumonia and diarrhea in children under 5 in UNHCR refugee camps: a retrospective study, Confl Health sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Pneumonia is the most common mode of death from measles and is associated with 56-86% of measles deaths.

“Pneumonia is the most common mode of death from measles, and is associated with 56–86% of measles deaths.79”

• cites [79] Duke, 2003, Measles: not just another viral exanthem, Lancet sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In endemic areas, cholera incidence peaks in children younger than 5 years because at least partial immunity develops after illness.

“In endemic areas, incidence peaks in children younger than 5 years because at least partial immunity develops after illness.88, 91”

• cites [88] Glass, 1992, The epidemiology of choleraNot checked yet

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• cites [91] Glass, 1982, Endemic cholera in rural Bangladesh, 1966–1980, Am J Epidemiol sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Cholera is one of the most devastating diarrhoeal diseases and causes high rates of mortality and widespread social upheaval during epidemics.

“Cholera is one of the most devastating diarrhoeal diseases, and causes high rates of mortality and widespread social upheaval during epidemics.88”

• cites [88] Glass, 1992, The epidemiology of choleraNot checked yet

  Not checked in the free run.

May combine two claims.

Chronic lung disease is common in HIV-positive children and is due to bacterial pneumonias responding poorly to treatment, tuberculosis, bronchiectasis, lymphoid interstitial pneumonia, or opportunistic fungal infections.

“Chronic lung disease is common (although no accurate estimates are available) in HIV-positive children and is due to bacterial pneumonias responding poorly to treatment, tuberculosis, bronchiectasis, lymphoid interstitial pneumonia, or opportunistic fungal infections.61, 63, 64”

• cites [61] Madhi, 2000, Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children, Clin Infect Dis sourceNot checked yet

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• cites [63] Graham, 2007, HIV-related pulmonary disorders: practice issues, Ann Trop Paediatr sourceNot checked yet

  Not checked in the free run.

• cites [64] Graham, 2005, Non-tuberculosis opportunistic infections and other lung diseases in HIV-infected infants and children, Int J Tuberc Lung DisNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based).

Pneumonia is a major cause of death from pandemic influenza in young children.

“because pneumonia is a major cause of death from pandemic influenza in young children.”

Probably not a substantial claim: may not pass S3 (load-bearing).

P jirovecii and cytomegalovirus pneumonia occur mainly in infants aged 2-6 months.

“Of these pathogens, P jirovecii and cytomegalovirus pneumonia occur mainly in infants aged 2–6 months.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Cholera is caused by infection of the small intestine with the Gram-negative Vibrio cholerae.

“It is caused by infection of the small intestine with the Gram-negative Vibrio cholerae.89”

• cites [89] Morris, 2003, Cholera and other types of vibriosis: a story of human pandemics and oysters on the half shell, Clin Infect Dis sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Pneumonia has been postulated to be a climate-sensitive disease that is likely to be affected substantially by pronounced climate change.

“Pneumonia has also been postulated to be a climate-sensitive disease that is likely to be affected substantially by pronounced climate change.107”

• cites [107] Paynter, 2010, Childhood pneumonia: a neglected, climate-sensitive disease?, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Referrals of severe disease to hospitals would be substantially reduced for both diarrhoea and pneumonia, but management of remaining cases would be more complicated and expensive, with increased health-service costs per case.

“Referrals of severe disease to hospitals would be substantially reduced for both disorders, but management of the remaining cases would be more complicated and expensive, with increased health-service costs per case.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Addressing inadequate water and sanitation, poor handwashing, indoor air pollution, and crowding will probably have benefits for disease reduction.

“For some risk factors, such as inadequate water and sanitation, poor handwashing, indoor air pollution, and crowding, risk relations have been difficult to define, but addressing them will probably have benefits for disease reduction.”

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

An effective health-service response to the burden of severe pneumonia and diarrhoea will necessitate development of hospital services, improved access to inpatient care, and community approaches to management before hospital care becomes necessary.

“An effective health-service response to this burden of severe disease will necessitate not only development of hospital services and improved access to inpatient care, but also community approaches to management of illness before hospital care becomes necessary.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Differences in immunisation rates, breastfeeding practices, and community case management of diarrhoea and pneumonia might be important factors in these discrepancies.

“Differences in immunisation rates, breastfeeding practices, and community case management of diarrhoea and pneumonia might be important factors in these discrepancies.”

May combine two claims.

Estimates of deaths from pneumonia and diarrhoea in children younger than 5 years from the 2010 Global Burden of Disease group are lower than WHO and UNICEF estimates used by the paper, probably because of differences in inclusion data, cause-of-death classification, and modelling approaches.

“Estimates of deaths from pneumonia and diarrhoea in children younger than 5 years are lower than are the WHO and UNICEF estimates we used, which is probably because of differences in the inclusion data, cause-of-death classification, and modelling approaches.”

May combine two claims.

Many available data on diarrhoea and pneumonia are not nationally representative and do not come from the highest mortality stratum.

“Many of the available data are not nationally representative and do not come from the highest mortality stratum, and so they might underestimate the true national burden of disease,4, 5 and consequently our estimates have wide CIs.”

• cites [4] Rudan, 2007, Childhood pneumonia and diarrhoea: setting our priorities right, Lancet Infect Dis sourceNot checked yet

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• cites [5] Rudan, 2005, Gaps in policy-relevant information on burden of disease in children: a systematic review, Lancet sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Checkley and colleagues reported increases in hospital admissions for diarrhoea in Peru associated with El Niño in 1997-98, suggesting that if ambient temperatures increase because of climate change, admissions associated with diarrhoea could be expected to rise.

“Checkley and colleagues106 reported increases in hospital admissions for diarrhoea in Peru associated with El Niño in 1997–98, suggesting that if ambient temperatures increase because of climate change, admissions associated with diarrhoea could be expected to rise.”

• cites [106] Checkley, 2000, Effect of El Niño and ambient temperature on hospital admissions for diarrhoeal diseases in Peruvian children, LancetNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Reports from WHO and the Intergovernmental Panel on Climate Change have identified changes in the incidence of diarrhoea as one of the most important future health effects of climate change.

“Reports from WHO105 and the Intergovernmental Panel on Climate Change have identified changes in the incidence of diarrhoea as one of the most important future health effects of climate change.105”

• cites [105] 2009Not checked yet

  Not checked in the free run.

May combine two claims.

Monitoring disease trends over time or assessing the effect of new interventions is difficult.

“Therefore, monitoring of disease trends with time or assessment of the effect of new interventions is difficult.”

May combine two claims.

A substantial change in the causative range for pneumonia would be expected with high coverage of available and new vaccines, which could necessitate fundamental change to case management guidelines.

“A substantial change in the causative range for pneumonia would be expected with high coverage of these vaccines (both available vaccines and effective new vaccines), which could necessitate fundamental change to case management guidelines.”

May combine two claims.

Improved access and expanded treatment can lead to increased antibiotic use, which can lead to increased antimicrobial resistance and more multidrug resistant pathogens.

“Although improved access and expanded treatment is an important public health goal, the associated rise in antibiotic use can lead to increased antimicrobial resistance and more multidrug resistant pathogens.”

May combine two claims.

Prevention of some severe episodes of pneumonia and diarrhoea is possible through routine and timely immunisation, especially of high-risk children, and timely community-based case management.

“Prevention of some of these severe episodes is possible through routine and timely immunisation, especially of high-risk children, and timely community-based case management.99, 100”

• cites [99] Chowdhury, 2008, Care at first-level facilities for children with severe pneumonia in Bangladesh: a cohort study, Lancet sourceNot checked yet

  Not checked in the free run.

• cites [100] Soofi, 2012, Effectiveness of community case management of severe pneumonia with oral amoxicillin in children aged 2–59 months in Matiari district, rural Pakistan: a cluster-randomised controlled trial, Lancet sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Incidence of pneumonia in many settings is strongly associated with rainfall, and predicted increased intensity of rainy seasons in Asia, Africa, the western Pacific region, and parts of South America will probably be associated with a raised burden of childhood pneumonia.

“Incidence in many settings is strongly associated with rainfall, and thus the predicted increased intensity rainy seasons in Asia, Africa, the western Pacific region, and parts of South America in the future will probably be associated with a raised burden of childhood pneumonia.108”

• cites [108] Torti, 2012, Floods in southeast Asia: a health priority, J Glob Health sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Integrated Community Case Management of pneumonia, diarrhoea, and malaria improves access to care, and community health workers can safely and effectively treat such disorders.

“Integrated Community Case Management103 of pneumonia, diarrhoea, and malaria improves access to care, and community health workers can safely and effectively treat such disorders.”

• cites [103] Young, 2012, World Health Organization/United Nations Children's Fund joint statement on integrated community case management: an equity-focused strategy to improve access to essential treatment services for children, Am J Trop Med Hyg sourceNot checked yet

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