Global burden of childhood pneumonia and diarrhoea

In the paper

“Children younger than 5 years can be a high-risk group for pneumonia after an influenza infection—either due to primary viral pneumonia or secondary bacterial pneumonia (mainly associated with pneumococci).86, 87”

What the sources say

• Partly supported

  The Main section (page not provided) reports pneumococcal superinfection in virus-associated pneumonia among hospitalized infants, including cases associated with influenza A. It does not establish that all children younger than five are a high-risk group after influenza infection, or specifically document primary viral pneumonia as the alternative cause. (LLM, conf=0.84)

  cites [86] Madhi, 2004, A role for Streptococcus pneumoniae in virus-associated pneumonia, Nat Med sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section reports that influenza-preinfected mice developed secondary pneumococcal pneumonia, supporting the bacterial-pneumonia part of the claim. The paper does not establish that children younger than five are a high-risk group, address primary viral pneumonia in those children, or show that pneumococci cause most secondary bacterial pneumonia after influenza. (LLM, conf=0.88)

  cites [87] McCullers, 2010, Influenza enhances susceptibility to natural acquisition of and disease due to Streptococcus pneumoniae in ferrets, J Infect Dis sourceExperimental — accuracy not yet measured

In the paper

“In 2011, 74% of the total burden of diarrhoea and pneumonia mortality in children younger than 5 years was in these 15 countries.”

In the paper

“Few data are available for sex differences in incidence and mortality.”

In the paper

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

In the paper

“Our results suggest a worldwide case-fatality ratio from severe diarrhoea of 2·0% (uncertainty range 1·4–4·4) and from severe pneumonia of 8·9% (3·1–12·5).”

In the paper

“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”

In the paper

“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.”

In the paper

“We identified 23 studies with information about sex with respect to the incidence of diarrhoea,20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42 seven24, 29, 30, 31, 36, 37, 39 of which showed significantly more cases in boys than in girls.”

What the sources say

• Not checked yetcites [20] Baqui, 1993, Malnutrition, cell-mediated immune deficiency, and diarrhea: a community-based longitudinal study in rural Bangladeshi children, Am J Epidemiol source
• Not checked yetcites [21] Bhan, 1989, Descriptive epidemiology of persistent diarrhoea among young children in rural northern India, Bull World Health Organ
• Not checked yetcites [22] Genser, 2006, Risk factors for childhood diarrhea incidence: dynamic analysis of a longitudinal study, Epidemiology source

In the paper

“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.”

In the paper

“The greatest proportions of severe episodes of diarrhoea and pneumonia were in the southeast Asian (26% and 39%, respectively) and African regions (26% and 30%, respectively).”

In the paper

“Our results suggest a worldwide case-fatality ratio from severe diarrhoea of 2·0% (uncertainty range 1·4–4·4) and from severe pneumonia of 8·9% (3·1–12·5).”

In the paper

“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.”

What the sources say

• Not checked yetcites [8] Fischer Walker, 2012, Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review, BMC Public Health source

In the paper

“Pneumonia incidence falls less rapidly with age than does mortality from the disease.”

In the paper

“A high proportion of deaths occurs in the first 2 years of life in both diseases—72% for diarrhoea and 81% for pneumonia.”

In the paper

“A high proportion of deaths occurs in the first 2 years of life in both diseases—72% for diarrhoea and 81% for pneumonia.”

In the paper

“The highest numbers of childhood deaths were in sub-Saharan Africa, where 50% of deaths from diarrhoea and 43% of deaths from pneumonia occurred in 2011.”

In the paper

“Undernutrition is a key shared risk factor for morbidity and mortality associated with diarrhoea and pneumonia, and interventions to improve nutrition should be prioritised”

In the paper

“The greatest proportions of severe episodes of diarrhoea and pneumonia were in the southeast Asian (26% and 39%, respectively) and African regions (26% and 30%, respectively).”

In the paper

“The global burden of incidence and severe disease for both diarrhoea and pneumonia is highest in southeast Asia and Africa”

In the paper

“Bronchiectasis was reported after 0·9% (0·7–8·7) of cases of severe pneumonia.”

In the paper

“More than ten countries have rates of decline for diarrhoea that are needed to achieve the target of the fourth Millennium Development Goal, but are unable to achieve the same rates for pneumonia (figure 2 [lower left quadrant]).”

In the paper

“The highest rates of severe disease occur at age 6–24 months.”

In the paper

“The risk of major sequelae was higher in children younger than 2 years (13·4% [4·5–22·3]) than in those aged 2–4 years.”

In the paper

“11 community-based studies had sex-specific data for pneumonia incidence, which was higher in boys than in girls (median odds ratio 1·3 [IQR 1·2–1·4]; unpublished); the largest differences were noted in south Asia.12”

What the sources say

• Not checked yetcites [12] Nair, 2013, Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis, Lancet source

In the paper

“The most common sequela was reduction in lung volume.”

In the paper

“The causes of life-threatening invasive bacterial infections in the neonatal period, when clinical syndromes of pneumonia, meningitis, and sepsis are practically indistinguishable, are uncertain.”

In the paper

“The other studies did not show significant differences between the sexes.”

In the paper

“The proportion of stunting that could be attributed to five or more episodes of diarrhoea before 2 years of age was 25% (8–38).”

In the paper

“11 community-based studies had sex-specific data for pneumonia incidence, which was higher in boys than in girls (median odds ratio 1·3 [IQR 1·2–1·4]; unpublished); the largest differences were noted in south Asia.12”

What the sources say

• Not checked yetcites [12] Nair, 2013, Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis, Lancet source

In the paper

“A pooled analysis of nine studies that assessed morbidity and anthropometry showed that the odds of growth stunting by age 2 years increased by 1·13 (95% CI 1·07–1·19) for every five episodes of diarrhoea.13”

What the sources say

• Not checked yetcites [13] Checkley, 2008, Multi-country analysis of the effects of diarrhoea on childhood stunting, Int J Epidemiol source

In the paper

“Conversely, no countries achieved the target rates for pneumonia but not for diarrhoea.”

In the paper

“Diarrhoea and pneumonia share many risk factors, such as not exclusively breastfeeding infants younger than 6 months, undernutrition, and zinc deficiency.”

In the paper

“Most of the deaths from both illnesses occur in children younger than 2 years.”

In the paper

“In Ghanaian children, a time-to-event analysis showed that, as the daily prevalence of diarrhoea increased, the risk of a subsequent acute lower-respiratory-tract infection increased by 1·08 (95% CI 1·0–1·15) per day of diarrhoea.”

In the paper

“In a similar analysis of two cohorts, one of Indian and the other of Nepali children, Fischer Walker and coworkers77 reported that, as the number of days with diarrhoea increased, the incidence of acute lower-respiratory-tract infections increased.”

What the sources say

• Not checked yetcites [77] Fischer Walker CL, Perin J, Katz J, Tielsch JM, Black RE. Diarrhea as a risk factor for acute lower respiratory tract infections among young children in low income settings. J Glob Health (in press).

In the paper

“Yet, a similar finding was not noted in the Brazilian cohort.”

In the paper

“Exposure to indoor air pollution from solid fuel combustion increases the incidence of pneumonia by 80% (95% CI 43–125).”

In the paper

“Various definitions and outcomes were used in studies of crowding,70, 71, 72, 73 but effects on pneumonia were consistently moderate.”

What the sources say

• Not checked yetcites [70] Fonseca, 1996, Risk factors for childhood pneumonia among the urban poor in Fortaleza, Brazil: a case-control study, Bull World Health Organ
• Not checked yetcites [71] Broor, 2001, Risk factors for severe acute lower respiratory tract infection in under-five children, Indian Pediatr
• Not checked yetcites [72] Cerqueiro, 1990, Epidemiologic risk factors for children with acute lower respiratory tract infection in Buenos Aires, Argentina: a matched case-control study, Rev Infect Dis source

In the paper

“Acute lower-respiratory-tract infections were only a risk factor for diarrhoea in a stratified subgroup of infants younger than 6 months.”

In the paper

“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.”

In the paper

“The rate of reduction correlates strongly across countries.”

In the paper

“Almost three-quarters of this mortality was in 15 high-burden countries.”

In the paper

“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.”

In the paper

“Within regions, disparities exist between countries that have achieved rapid reductions in mortality for both diarrhoea and pneumonia and those that have not.”

In the paper

“In a subgroup of countries in which rates of mortality from diarrhoea and pneumonia are falling slowly, child deaths continue to rise because of high birth rates.”

In the paper

“Diarrhoea deaths have decreased quicker than have those caused by pneumonia.”

In the paper

“Rapid reductions in mortality have not occurred in all low-income and middle-income countries.”

In the paper

“Thus, achievement of the fourth Millennium Development Goal and the longer-term target3 of reduction of child mortality to 20 deaths or fewer per 1000 livebirths in all countries by 2035 will necessitate substantial decreases in mortality from the two illnesses.4”

What the sources say

• Not checked yetcites [3] Glass, 2012, Ending preventable child death in a generation, JAMA source
• Not checked yetcites [4] Rudan, 2007, Childhood pneumonia and diarrhoea: setting our priorities right, Lancet Infect Dis source

In the paper

“Thus, as outcomes become more severe, more of the global burden is concentrated in the highest burden countries.”

In the paper

“In the late neonatal and postneonatal periods, Gram-positive cocci (primarily Streptococcus spp) cause about two of every three infections.”

In the paper

“Klebsiella spp and Staphylococcus aureus, but also Escherichia coli and group B streptococci are thought to be the leading causes in the early neonatal period, when most deaths occur.”

In the paper

“Bordetella pertussis, which causes pertussis, an acute respiratory infection, can cause severe pneumonia, particularly in the first 6 months of life.”

In the paper

“The causes of diarrhoea and pneumonia vary by age, and differ particularly in neonates (panel 1 ) and with disease severity.65”

What the sources say

• Not checked yetcites [65] Waters, 2011, Aetiology of community-acquired neonatal sepsis in low and middle income countries, J Glob Health

In the paper

“These findings are consistent with large population-based studies of children in the early 1990s,46, 47, 48 which showed a 6–7% increased risk of reduced lung capacity after childhood pneumonia.”

What the sources say

• Not checked yetcites [46] Johnston, 1998, Effect of pneumonia and whooping cough in childhood on adult lung function, N Engl J Med source
• Not checked yetcites [47] Barker, 1991, Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease, BMJ source
• Not checked yetcites [48] Shaheen, 1998, Birth weight, childhood lower respiratory tract infection, and adult lung function, Thorax source

In the paper

“However, for children in low-income and middle-income countries, several episodes per year can lead to nutritional deficits and long-term consequences.”

In the paper

“Some data from community-based studies in developing countries suggest that Gram-negative rods are the major cause in early neonates (0–6 days), in whom such rods might cause as many as three of every four infections.”

In the paper

“For example, symptomatic rotavirus disease is less common in the first than in the second 6 months of life.55”

What the sources say

• Not checked yetcites [55] Black, 1989, Incidence and etiology of infantile diarrhea and major routes of transmission in Huascar, Peru, Am J Epidemiol source

In the paper

“Rates of illness then fall as children age because the first infection induces at least partial active immunity, which protects against subsequent illnesses.”

In the paper

“However, even hospital-born babies in developing countries have a three times greater to 20 times greater risk of neonatal infections because of poor infection-control practices.56, 57, 58, 59”

What the sources say

• Not checked yetcites [56] Zaidi, 2005, Hospital-acquired neonatal infections in developing countries, Lancet source
• Not checked yetcites [57] Zaidi, 2009, Pathogens associated with sepsis in newborns and young infants in developing countries, Pediatr Infect Dis J source
• Not checked yetcites [58] Jawad, 2012, Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality, J Global Health source

In the paper

“The contribution of H influenzae type b is falling quite rapidly because of widespread vaccination in many low-income and middle-income countries.”

In the paper

“Infection with the influenza A (H1N1) pdm09 strain resulted in much higher rates of hospital admission in young children than are reported during a normal influenza season.84, 85”

What the sources say

• Not checked yetcites [84] Clara, 2012, Estimated incidence of influenza-virus-associated severe pneumonia in children in El Salvador, 2008–2010, Bull World Health Organ source
• Not checked yetcites [85] Udompornwattana, 2012, The clinical features, risk of prolonged hospitalization and household infections of hospitalized children for pandemic 2009 influenza A (H1N1) virus infection in Thailand, J Med Assoc Thai

In the paper

“The case fatality of severe pneumonia associated with measles is more than twice that of severe pneumonia without measles.80”

What the sources say

• Not checked yetcites [80] Duke, 2002, Chloramphenicol versus benzylpenicillin and gentamicin for the treatment of severe pneumonia in children in Papua New Guinea: a randomised trial, Lancet source

In the paper

“Measles is an established risk factor for diarrhoea.”

What the sources say

• Not checked yetcites [78] Feachem, 1983, Interventions for the control of diarrhoeal diseases among young children: measles immunization, Bull World Health Organ

In the paper

“In addition to the causes of pneumonia listed in table 2 , Pneumocystis jirovecii, M tuberculosis, cytomegalovirus, and Gram-negative infections are important causes of severe pneumonia in HIV-positive children in the postneonatal period.”

In the paper

“Diarrhoea and pneumonia are important causes of child morbidity and mortality in emergency or refugee settings.”

What the sources say

• Not checked yetcites [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 source

In the paper

“This increased mortality is largely due to the immunosuppressive and systemic effects of measles with bacterial superinfection.”

In the paper

“Diarrhoea and pneumonia share many risk factors, and reduction of risk factors, immunisation, and case management comprise the main approaches to disease control.”

In the paper

“Diarrhoea and pneumonia have each been investigated as independent risk factors for increasing the risk of simultaneous or sequential infection with each other.”

In the paper

“Child mortality can be particularly high during the initial emergency phase of a complex humanitarian emergency, and pneumonia and diarrhoea are major avoidable causes of these deaths.82”

What the sources say

• Not checked yetcites [82] Spiegel, 2002, Health programmes and policies associated with decreased mortality in displaced people in postemergency phase camps: a retrospective study, Lancet source

In the paper

“Child mortality can be particularly high during the initial emergency phase of a complex humanitarian emergency, and pneumonia and diarrhoea are major avoidable causes of these deaths.82”

What the sources say

• Not checked yetcites [82] Spiegel, 2002, Health programmes and policies associated with decreased mortality in displaced people in postemergency phase camps: a retrospective study, Lancet source

In the paper

“Mean incidences of pneumonia and diarrhoea in children younger than 5 years were substantially higher than those noted in these countries in non-emergency settings.83”

What the sources say

• Not checked yetcites [83] Rudan, 2008, Epidemiology and etiology of childhood pneumonia, Bull World Health Organ source

In the paper

“Diarrhoea and pneumonia share many risk factors, and reduction of risk factors, immunisation, and case management comprise the main approaches to disease control.”

In the paper

“Children infected with HIV have a greatly increased risk of pneumonia, particularly bacterial pneumonia (S pneumoniae and H influenzae).61”

What the sources say

• Not checked yetcites [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 source

In the paper

“Reductions in underweight and measles (because of immunisation programmes) might have contributed to falls in deaths from diarrhoea and pneumonia.101”

What the sources say

• Not checked yetcites [101] Stevens, 2012, Trends in mild, moderate, and severe stunting and underweight, and progress towards MDG 1 in 141 developing countries: a systematic analysis of population representative data, Lancet source

In the paper

“The Integrated Mmanagement of Childhood Illnesses102 approach in health facilities has improved the quality of clinical care.”

What the sources say

• Not checked yetcites [102]

In the paper

“Pneumonia in neonates and in early infancy will become increasingly important.”

In the paper

“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.”

In the paper

“Diarrhoea and pneumonia are the most important causes of child mortality, and thus the continuing absence of reliable population-based morbidity or mortality data from countries with high disease burdens is remarkable.”

In the paper

“Most deaths from diarrhoea and pneumonia are preventable95 with high coverage of existing interventions (as shown in the second paper in this Series96).”

What the sources say

• Not checked yetcites [95] Jones, 2003, How many child deaths can we prevent this year?, Lancet source
• Not checked yetcites [96] Bhutta, 2013, Interventions to address deaths from childhood pneumonia and diarrhoea equitably: what works and at what cost?, Lancet source

In the paper

“High coverage with highly effective vaccines against these pathogens has the potential to reduce mortality and severe morbidity substantially.”

In the paper

“Replacement of the first-line antibiotics nalidixic acid with ciprofloxacin for dysentery, and co-trimoxazole with amoxicillin for pneumonia,104 shows the effect of resistance on public health policies and costs.”

What the sources say

• Not checked yetcites [104] Laxminarayan, 2006, Drug resistance

In the paper

“We present new estimates of the incidence of severe pneumonia and diarrhoea, which imply potential burdens on hospital services in low-income and middle-income countries.”

In the paper

“Because no notable improvements in diarrhoea treatment practices have been implemented in the past decade,97 we speculate that improvements in nutrition and general environmental and socioeconomic development have more prominent roles in diarrhoea than in pneumonia.98”

What the sources say

• Not checked yetcites [97] 2009