Campylobacter is an important cause of foodborne gastroenteritis. We determined the occurrence of Campylobacter jejuni and Campylobacter coli, using culture-based methods and PCRs targeting ...virulence-associated genes (VAGs) among children aged ≤14 years who were treated for diarrhoea at emergency rooms in northeastern Brazil. Genomic DNA was extracted directly from stool samples collected from 366 children. A questionnaire was also applied to qualify the clinical conditions presented by each child at the time of admission. C. jejuni and C. coli were detected in 16.4 % (60/366) and 1.4 % (5/366) of the diarrhoeal samples, respectively, by PCR, a much higher proportion than that detected by conventional methods. C. jejuni VAGs were detected in the following proportions of hipO-positive samples: ciaB, 95 % (57/60); dnaJ, 86.7 % (52/60); racR, 98.3 % (59/60); flaA, 80 % (48/60); pldA, 45 % (27/60); cdtABC, 95 % (57/60); and pVir 0 % (0/60). Particular symptoms, such as blood in faeces, vomiting, fever, and/or abdominal pain, were not associated with detection of C. jejuni nor were they associated with any particular VAG or combination of VAGs (P>0.05). C. jejuni and its VAGs were detected in a substantial proportion of the children admitted. Further efforts shall be directed towards elucidating whether these genetic factors or their expressed proteins play a role in Campylobacter pathogenesis.
We examined the effect of a diet supplemented with alanyl-glutamine (AG) or placebo glycine (G) on intestinal barrier function and growth in children in northeastern Brazil.
One hundred seven ...children ages 7.9 to 82.2 months with a weight-for-age (WAZ), height-for-age (HAZ), or weight-for-height (WHZ) z-score less than -1 were studied. From July 2003 to November 2004, 51 study patients received AG (24 g/d) and 56 received G (25 g/d; isonitrogenic concentration) control for 10 days. Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed on days 1 and 10 of nutritional supplementation. Weight and height were measured on days 1, 10, 30, and 120 of the protocol.
The patients were similar on admission with regard to age, sex, birth weight, nutritional status, lactulose/mannitol ratio, and serum concentrations of glutamine and arginine. The percentage of lactulose urinary excretion significantly improved (decreased) in children receiving AG for 10 days but not in those receiving glycine controls. AG significantly increased cumulative change over 120 days in WHZ and WAZ scores but not HAZ scores after adjustment for age and season in comparison with the placebo glycine group.
Children tolerated AG-supplemented enteral formula well, and it significantly improved cumulative WHZ and WAZ over 120 days in comparison with children in the placebo glycine group. The data also suggested a beneficial effect of AG in the barrier function paracellular pathway, albeit with reduced mannitol excretion. Thus, although the effect of AG on reduced mannitol concentration requires clarification, AG appears to improve nutrition and barrier function.
Data on the relationship between the two genotypes of
Giardia duodenalis that infect humans, assemblages A and B, their clinical presentation and intestinal inflammation are limited. We analyzed 108 ...stool samples previously collected for a diarrhoeal study among Brazilian children, representing 71 infections in 47 children. Assemblage B was most prevalent, accounting for 43/58 (74.1%) infections, while assemblage A accounted for 9/58 (15.5%) infections and 6/58 (10.3%) infections were mixed (contained both assemblage A and B). There was no significant difference in diarrhoeal symptoms experienced during assemblage A, B or mixed infections. Children with assemblage B demonstrated greater variability in
G. duodenalis cyst shedding but at an overall greater level (
n
=
43, mean 3.6
×
10
5, range 5.3
×
10
2–2.5
×
10
6
cysts/ml) than children infected with assemblage A (
n
=
9, mean 1.4
×
10
5, range 1.5
×
10
4–4.6
×
10
5
cysts/ml;
P
=
0.009). Children with mixed infections shed more cysts (mean 8.3
×
10
5, range 3.1
×
10
4–2.8
×
10
6
cysts/ml) than children with assemblage A or B alone (
P
=
0.069 and
P
=
0.046 respectively). This higher rate of cyst shedding in children with assemblage B may promote its spread, accounting for its increased incidence. Additionally, second and third infections had decreasing faecal lactoferrin, suggesting some protection against severity, albeit not against infection, by prior infection.
Background & Aims Prolonged episodes of acute diarrhea (ProD; duration 7–13 days) or persistent diarrhea (PD; duration ≥14 days) are important causes of undernutrition, yet the epidemiology and ...nutritional impact of ProD are poorly understood. Methods We conducted a 10-year cohort study of 414 children from a Brazilian shantytown who were followed from birth; data were collected on diarrhea, enteric pathogens, and anthropometry. Results During 1276 child-years of observation, we recorded 3257 diarrheal episodes. ProD was twice as common as PD (12% and 5% of episodes, respectively); ProD and PD together accounted for 50% of all days with diarrhea. ProD was more common in infants whose mothers had not completed primary school (relative risk RR, 2.1; 95% confidence interval: 1.02–2.78). Early weaning was associated with earlier onset of ProD (Spearman ρ = 0.309; P = .005). Infants with ProD were twice as likely to develop PD in later childhood (log rank, P = .002) compared with infants with only acute diarrhea (AD; duration <7 days), even after controlling for confounders. Children's growth was more severely stunted before their first episode of ProD, compared with AD (mean height-for-age Z score (HAZ) −0.81 vs −0.51, respectively, P < .05, unpaired t test). Following ProD, HAZ (ΔHAZ = −0.232) and weight-for-age (ΔWAZ = −0.26) significantly decreased ( P < .005 in paired t tests). ProD was associated with Cryptosporidium and Shigella infections. Conclusions ProD accounts for significant morbidity and identifies children at risk of a vicious cycle of diarrhea and malnutrition. Further studies are needed to address the recognition and control of ProD and its consequences in resource-limited settings and assess its role in PD pathogenesis.
Vaccine studies for
and enterotoxigenic
have been impaired by the lack of optimal animal models. We used two murine models to show that a
2a bivalent vaccine (CVD 1208S-122) expressing ...enterotoxigenic
colonization factor antigen-I (CFA/I) and the binding subunits A2 and B of heat labile-enterotoxin (LTb) is immunogenic and protects against weight loss and diarrhea. These findings document the immunogenicity and pre-clinical efficacy effects of CVD 1208S-122 vaccine and suggest that further work can help elucidate relevant immune responses and ultimately its clinical efficacy in humans.
Cryptosporidium is an important cause of infectious diarrhoea worldwide, but little is known about the course of illness when infected with different species. Over a period of 5 years,
...Cryptosporidium was identified in the stools of 58 of 157 children prospectively followed from birth in an urban slum (favela) in northeast Brazil. Forty isolates were available for quantification and 42 for speciation (24
Cryptosporidium hominis and 18
C. parvum). Children with
C. hominis shed significantly more oocysts/ml of stool (3.5
×
10
6 vs. 1.7
×
10
6
per
ml;
P
=
0.001), and oocyst counts were higher among symptomatic children (
P
=
0.002). Heavier
C. parvum shedding was significantly associated with symptoms (
P
=
0.004), and symptomatic
C. parvum-infected children were significantly more likely than asymptomatic children to be lactoferrin-positive (
P
=
0.004). Height-for-age (HAZ)
Z-scores showed significant declines within 3 months of infection for children infected with either
C. hominis (
P
=
0.028) or
C. parvum (
P
=
0.001). However, in the 3–6 month period following infection, only
C. hominis-infected children continued to demonstrate declining HAZ score and asymptomatic children showed even greater decline (
P
=
0.01).
Cryptosporidium hominis is more common than
C. parvum in favela children and is associated with heavier infections and greater growth shortfalls, even in the absence of symptoms.
In Ceará, Brazil, seasonal influenza transmission begins before national annual vaccination campaigns commence. To assess the perinatal consequences of this misalignment, we tracked severe acute ...respiratory infection (SARI), influenza, and influenza immunizations during 2013–2018. Among 3,297 SARI cases, 145 (4.4%) occurred in pregnant women. Statewide vaccination coverage was >80%; however, national vaccination campaigns began during or after peak influenza season. Thirty to forty weeks after peak influenza season, birthweights decreased by 40 g, and rates of prematurity increased from 10.7% to 15.5%. We identified 61 children born to mothers with SARI during pregnancy; they weighed 10% less at birth and were more likely to be premature than 122 newborn controls. Mistiming of influenza vaccination campaigns adversely effects perinatal outcomes in Ceará. Because Ceará is the presumptive starting point for north-to-south seasonal influenza transmission in Brazil, earlier national immunization campaigns would provide greater protection for pregnant women and their fetuses in Ceará and beyond.
In this longitudinal multicenter study, 65% of children experienced Cryptosporidium infection during the first 2 years of life. Cryptosporidium was associated with severe diarrhea and dehydration ...and, in 2 South Asian sites, with stunted growth at age 2 years.
Abstract
Background
Cryptosporidium species are enteric protozoa that cause significant morbidity and mortality in children worldwide. We characterized the epidemiology of Cryptosporidium in children from 8 resource-limited sites in Africa, Asia, and South America.
Methods
Children were enrolled within 17 days of birth and followed twice weekly for 24 months. Diarrheal and monthly surveillance stool samples were tested for Cryptosporidium by enzyme-linked immunosorbent assay. Socioeconomic data were collected by survey, and anthropometry was measured monthly.
Results
Sixty-five percent (962/1486) of children had a Cryptosporidium infection and 54% (802/1486) had at least 1 Cryptosporidium-associated diarrheal episode. Cryptosporidium diarrhea was more likely to be associated with dehydration (16.5% vs 8.3%, P < .01). Rates of Cryptosporidium diarrhea were highest in the Peru (10.9%) and Pakistan (9.2%) sites. In multivariable regression analysis, overcrowding at home was a significant risk factor for infection in the Bangladesh site (odds ratio, 2.3 95% confidence interval {CI}, 1.2-4.6). Multiple linear regression demonstrated a decreased length-for-age z score at 24 months in Cryptosporidium-positive children in the India (β = -.26 95% CI, -.51 to -.01) and Bangladesh (β = -.20 95% CI, -.44 to .05) sites.
Conclusions
This multicountry cohort study confirmed the association of Cryptosporidium infection with stunting in 2 South Asian sites, highlighting the significance of cryptosporidiosis as a risk factor for poor growth. We observed that the rate, age of onset, and number of repeat infections varied per site; future interventions should be targeted per region to maximize success.
BackgroundWhile head circumference (HC) has been related to intracranial volume and brain size, its association with cognitive function remains unclear. We sought to understand the relationship among ...various biological and socioeconomic risk factors, HC and cognitive development.MethodsWe analysed data across resource-poor settings in Bangladesh, India, Nepal, Peru, South Africa and Tanzania from the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development longitudinal birth cohort study. Participating children were enrolled and followed up between 2009 and 2014. A final sample of 1210 children aged 0–24 months were included in the analyses. The main outcomes were HC for age Z-score and cognitive, gross motor and language scores from Bayley Scales of Infant Development-III tests. Length, weight and HC were measured monthly, and cognitive tests were administered at 6, 15 and 24 months of age. To disentangle the associations between risk factors and HC from linear growth and to distinguish the direct and indirect effects of these risk factors on cognitive function, we conducted mediation analysis using longitudinal models to account for all data measured during follow-up.ResultsAverage HC-for-age Z-score (HCAZ) was −0.54 (95% CI −0.47 to −0.62) near birth and −1.01 (95% CI −0.94 to −1.08) at 24 months. Children with higher enrolment weight (p<0.0001), higher socioeconomic score (p=0.00037) and taller mothers (p=0.00084) had higher HCAZ at all ages, while enteropathogen infection (p=0.013) and more febrile episodes (p=0.013) were associated with lower HCAZ. The associations between HCAZ and enrolment weight-for-age, maternal height, socioeconomic status or pathogen burden were partly mediated through their associations with length-for-age. HCAZ showed no association with cognitive, gross motor or language skills at 6, 15 and 24 months of age.ConclusionsThe main risk factors associated with HC are similar to those associated with body length, and HC is not related to cognitive function.
Enteric infections, enteropathy and undernutrition in early childhood are preventable risk factors for child deaths, impaired neurodevelopment, and later life metabolic diseases. However, the ...mechanisms linking these exposures and outcomes remain to be elucidated, as do biomarkers for identifying children at risk. By examining the urinary metabolic phenotypes of nourished and undernourished children participating in a case-control study in Semi-Arid Brazil, we identified key differences with potential relevance to mechanisms, biomarkers and outcomes. Undernutrition was found to perturb several biochemical pathways, including choline and tryptophan metabolism, while also increasing the proteolytic activity of the gut microbiome. Furthermore, a metabolic adaptation was observed in the undernourished children to reduce energy expenditure, reflected by increased N-methylnicotinamide and reduced β-aminoisobutyric acid excretion. Interestingly, accelerated catch-up growth was observed in those undernourished children displaying a more robust metabolic adaptation several months earlier. Hence, urinary N-methylnicotinamide and β-aminoisobutyric acid represent promising biomarkers for predicting short-term growth outcomes in undernourished children and for identifying children destined for further growth shortfalls. These findings have important implications for understanding contributors to long-term sequelae of early undernutrition, including cognitive, growth, and metabolic functions.
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