Reducing the burden of HIV/AIDS in infants: the contribution of improved diagnostics.
Explore the source record for details and available documents.
AIDS Serodiagnosis↗
Biomedical subjects
Richard L Guerrant
Publications and source records attributed to Richard L Guerrant.
Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development.
Our group and others have reported a series of studies showing that heavy burdens of diarrheal diseases in the formative first two years of life in children in urban shantytowns have profound consequences of impaired physical and cognitive development lasting into later childhood and schooling. Based on these previous studies showing that apolipoprotein E4 (APOE4) is relatively common in favela children, we review recent data suggesting a protective role for the APOE4 allele in the cognitive and physical development of children with heavy burdens of diarrhea in early childhood. Despite being a marker for cognitive decline with Alzheimer's and cardiovascular diseases later in life, APOE4 appears to be important for cognitive development under the stress of heavy diarrhea. The reviewed findings provide a potential explanation for the survival advantage in evolution of the thrifty APOE4 allele and raise questions about its implications for human development under life-style changes and environmental challenges.
Alleles↗
Heavy cryptosporidial infections in children in northeast Brazil: comparison of Cryptosporidium hominis and Cryptosporidium parvum.
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 x 10(6) vs. 1.7 x 10(6)perml; 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.
Animals↗
Infectious diarrhea: new pathogens and new challenges in developed and developing areas.
Explore the source record for details and available documents.
Developed Countries↗
Cholera--still teaching hard lessons.
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
Early childhood diarrhea predicts impaired school performance.
OBJECTIVE: Diarrhea is a leading cause of mortality worldwide; however, its long-term morbidity is poorly understood. Recently, early childhood diarrhea (ECD) has been associated with impaired physical fitness, growth and cognitive function 6 to 9 years later. We studied the effects of ECD on school functioning in a shantytown in northeastern Brazil. DESIGN: We administered 77 educational surveys. Complete diarrhea surveillance (ie, >90%) in the first 2 years of life and demographic and anthropometric information were available for 73 children. Age at starting school was calculated for 62 children, whereas age appropriateness for the current grade (AFG) was calculated for all 73 children who were >6 years old. Stepwise regression was used to examine the independent effect of ECD on school functioning after controlling for socioeconomic factors, maternal education, breast feeding, growth and cognitive functioning. RESULTS: ECD correlated with age at starting school (r = 0.55, P = 0.0005) and remained a significant predictor even after controlling for family demographics, days of breast feeding, early growth and TONI-3 test of nonverbal intelligence. This was true despite significant correlations of ECD with growth shortfalls and impaired cognitive functioning. ECD also correlated with AFG (r = 0.38, P = 0.001). Only TONI-3 test scores explained this association, suggesting that ECD may hinder school performance, but only in part school readiness, by impairing cognitive function as measured by performance on the TONI-3 nonverbal intelligence test. CONCLUSIONS: These findings document effects of early childhood diarrhea on later school readiness and performance and hence potential long-term human and economic costs of ECD, which warrant further attention and far greater investment for the control of ECD and its consequences.
Age Factors↗
Real-time PCR detection and speciation of Cryptosporidium infection using Scorpion probes.
At least eight species of Cryptosporidium can cause human infection and disease. A real-time PCR (qPCR) assay based on the 18S rRNA gene and utilizing a Scorpion probe was developed to detect all human-pathogenic Cryptosporidium without the usual need for nested amplification. Sensitivity of detection in stool samples was highest using a glass bead-based DNA extraction method (under 10(3) oocysts per stool sample). The assay was validated against 123 human stool specimens from Bangladesh and Tanzania, exhibited a sensitivity and specificity of >91% versus microscopy, and detected an additional eight microscopy-negative infections. Cryptosporidium parvum-specific and Cryptosporidium meleagridis-specific Scorpion qPCR assays that provided 100% accurate speciation compared with VspI RFLP analysis and sequencing were developed subsequently. These Scorpion probe qPCR assays are simpler to perform than existing nested PCR and RFLP methods for diagnosis and epidemiological investigation of cryptosporidiosis.
Animals↗
Caspase and bid involvement in Clostridium difficile toxin A-induced apoptosis and modulation of toxin A effects by glutamine and alanyl-glutamine in vivo and in vitro.
Clostridium difficile is the leading cause of nosocomial bacterial diarrhea. Glutamine and its stable and highly soluble derivative alanyl-glutamine, have been beneficial in models of intestinal injury. In this study, we extend our work on the mechanisms of Clostridium difficile toxin A (TxA)-induced apoptosis in human intestinal epithelial T84 cells and evaluate the effects of glutamine and alanyl-glutamine on TxA-induced apoptosis in vitro and disruption of ileal mucosa in vivo. T84 cells were incubated with TxA (100 ng/ml) in medium with or without glutamine or alanyl-glutamine (3 to 100 mM). Apoptosis was evaluated by DNA fragmentation in vitro and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling method in vivo. Caspase and Bid involvement were investigated by Western blotting. Ligated rabbit ileal loops were used for the evaluation of intestinal secretion, mucosal disruption, and apoptosis. TxA induced caspases 6, 8, and 9 prior to caspase 3 activation in T84 cells and induced Bid cleavage by a caspase-independent mechanism. Glutamine or alanyl-glutamine significantly reduced TxA-induced apoptosis of T84 cells by 47% and inhibited activation of caspase 8. Both glutamine and alanyl-glutamine reduced TxA-induced ileal mucosal disruption and secretion. Altogether, we further delineated the apoptosis-signaling cascade induced by TxA in T84 cells and demonstrated the protective effects of glutamine and alanyl-glutamine. Glutamine and alanyl-glutamine inhibited the apoptosis of T84 cells by preventing caspase 8 activation and reduced TxA-induced intestinal secretion and disruption.
Animals↗
Prevalence and species distribution of E. Histolytica and E. Dispar in the Venda region, Limpopo, South Africa.
The prevalence and species distribution of Entamoeba histolytica and E. dispar in the Venda region were determined in stool samples collected from public hospitals and primary schools by ELISA and a nested polymerase chain reaction (PCR). E. histolytica was detected in 37/197 (18.8%) and 1/47 (2.1%) samples, whereas 50/197 (25.3%) and 4/47 (8.5%) had E. dispar in the hospitals and schools, respectively. The age groups most infected were 0-2 (33%) years followed by 20-29 years (27%). E. histolytica was significantly associated with diarrhea (77.4% versus 22.6%; chi 2 = 39.48, P < 0.05), and with the presence of lactoferrin (85.7% versus 14.2%) in the stools, indicating intestinal inflammation (chi 2 = 29.605, P < 0.05). E. histolytica was found in 5 (16.12%) of the 31 HIV-positive individuals and in 33 (15.5%) of the 213 HIV-negative individuals. E. histolytica infections are common in the Venda region and are associated with diarrhea and intestinal inflammation.
Adolescent↗
Global impact of diarrheal diseases that are sampled by travelers: the rest of the hippopotamus.
Travelers who experience diarrhea (i.e., "turista") are exposed to the same pathogens and illnesses that pose some of the greatest threats to life and development among malnourished children in developing areas around the world, where inadequate water and poor sanitation remain. This article focuses on new findings about the impact, diagnosis, and control of these illnesses and the genetic predispositions of persons who acquire them. Despite the reductions in mortality due to dehydrating diarrhea, the morbidity associated with diarrheal illnesses continues unabated. Furthermore, we increasingly recognize the lasting detrimental effects of enteric infections that occur during early childhood on later physical and cognitive development and, in patients with acquired immunodeficiency syndrome, on the absorption of antiretroviral drugs. Genetic predispositions to inflammation and potential protection associated with such alleles as ApoE4, which are not suspected of being involved in diarrhea, remind us of how much we have to learn about the effect and interactions of enteric tropical infectious diseases with regard to our host genome. New diagnostic methods hold promise for improved recognition and, hopefully, control of enteric infections worldwide.
Diarrhea↗
Angiotensin II subtype 1 receptor blockade inhibits Clostridium difficile toxin A-induced intestinal secretion in a rabbit model.
Angiotensin II (ANG II) has been described in the regulation of intestinal secretion and absorption via angiotensin subtype 1 (AT(1)) and AT(2) receptors, respectively, in rats. We investigated the role that ANG II plays in the rabbit ileal-loop model of Clostridium difficile infection. Expression of AT(1), the more abundant ANG II receptor, was demonstrated in ileal loops, and an AT(1) receptor blocker, losartan, inhibited hypersecretion induced by C. difficile toxin A (mean volume : length ratio, 0.27+/-0.06 vs. 0.60+/-0.06 mL/cm in controls). Losartan also decreased production of ANG II in the ileum (0.48+/-0.06 vs. 0.87+/-0.12 pg/mg in controls), raising the possibility that ANG II may participate in a positive feedback loop involving the hypersecretory response. Our findings suggest that ANG II plays a significant role in the pathogenesis of C. difficile toxin-induced diarrhea.
Angiotensin II↗
Clostridium difficile toxin A induces intestinal epithelial cell apoptosis and damage: role of Gln and Ala-Gln in toxin A effects.
The aim of this study was to investigate the effect of Clostridium difficile toxin A (TxA) on intestinal epithelial cell migration, apoptosis, and transepithelial resistance and to evaluate the effect of glutamine (Gln) and its stable derivative, alanyl-glutamine (Ala-Gln), on TxA-induced damage. Migration was measured in rat intestinal epithelial cells (IEC-6) 6 and 24 hr after a razor scrape of the cell monolayer. Cell proliferation was indirectly measured utilizing the tetrazolium salt WST-1. The cells were incubated with TxA (1-100 ng/ml) in medium without Gln or medium containing Gln or Ala-Gln (1-30 mM). Apoptosis was quantified in IEC-6 cells using annexin V assay. Transepithelial resistance was measured using an epithelial voltohmmeter across T84 cells seeded on a transwell filter. TxA-induced a dose-dependent reduction of migration and also caused dose and time-dependent apoptosis in IEC-6 cells. Gln and Aln-Gln significantly enhanced IEC-6 cell migration and proliferation. Gln and Ala-Gln also prevented the inhibition of migration, apoptosis, and the initial drop in transepithelial resistance induced by TxA. In conclusion, both peptides reduced toxin-induced epithelial damage and thus might play an adjunctive role in C. difficile-induced colitis therapy.
Animals↗
Limitations in verbal fluency following heavy burdens of early childhood diarrhea in Brazilian shantytown children.
The effects of heavy burdens of diarrhea in the first 2 years of life on specific executive control function like verbal fluency are not well understood. In previous studies, we have shown associations of early childhood diarrhea (ECD) with nonverbal intelligence and school functioning. Therefore, we postulated that ECD might affect early neuropsychological development leading to long-term deficits in normal cognitive development. Based on our extensive 14-year prospective cohort studies of early childhood diarrheal illnesses in a Brazilian shantytown community, we examined ECD correlations between specific impairments of higher mental function and executive skills in shantytown children 5-10 years later (now at 6-12) years of age. Specifically we examined whether heavy diarrheal illnesses correlate with reduced performance on selected tests of executive function. Our study, for the first time, suggests a disproportional impairment in semantic but not phonetic fluency in a subset of children with heavy burdens of diarrhea in their first 2 years of life even when controlling for maternal education, breastfeeding, and child schooling. Similar semantic decrements have been associated with impaired recovery from brain injury. These exploratory studies suggest the importance of verbal fluency tests to assess executive functioning in children challenged by poor nutrition and diarrhea in early life. In addition, our unique findings show the potential influences of early childhood diarrhea on language development that is so critical to productive adulthood and potentially set a foundation for new neuropsychological approaches, which assess early burdens of enteric illnesses on childhood development.
Age Factors↗
Intestinal barrier function and weight gain in malnourished children taking glutamine supplemented enteral formula.
OBJECTIVE: We examined the effect of standard formula and glutamine or glycine supplemented enteral formula on intestinal permeability and weight gain in children with malnutrition. METHODS: 80 children aged 2 to 60 months with a weight-for-age z-score less than -- 2 were studied. From December 1996 to April 1999, 27 study patients received nonsupplemented formula. From June 2001 to June 2002 an additional 53 patients were randomly assigned to receive formula supplemented with glutamine or glycine (isosmolar concentrations) for 10 days. Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed before and after 10 days of nutritional rehabilitation. Weight was measured before and after treatment. RESULTS: Patients were similar on admission with regard to age, sex, nutritional status and lactulose/mannitol ratio. The lactulose/mannitol ratio significantly improved (decreased) in children receiving formula supplemented with glutamine for 10 days but not in those receiving glycine or nonsupplemented formula. Weight gain occurred during therapy in all groups and was not statistically different among groups. CONCLUSION: Formula supplemented with glutamine improves intestinal barrier function compared with nonsupplemented formula but does not augment weight gain.
Child Nutrition Disorders↗
Glutamine for childhood malnutrition: is it needed?
Explore the source record for details and available documents.
Child↗
Glutamine depletion potentiates leucocyte-dependent inflammatory events induced by carrageenan or Clostridium difficile toxin A in rats.
This research investigated the effect of glutamine (Gln) depletion on leucocyte-dependent inflammatory events. Rats were treated intraperitoneally, 16 hr prior to the peak of every parameter evaluated, with either 0.9% NaCl, methionine-sulphoximine (MSO, an inhibitor of endogenous Gln synthesis, 25 mg/kg) or with MSO + Gln (MSO as above plus Gln 3 g/kg in three doses). MSO-induced Gln depletion increased paw oedema induced both by carrageenan (Cg) and by Clostridium difficile toxin A (TxA) (66.2% and 45.5%, respectively; P < 0.05). In dextran-injected animals, oedema and myeloperoxidase (MPO) activity were not modified by Gln depletion. In Cg-treated paws, Gln depletion increased MPO activity by 44% (P < 0.05), interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) concentrations by 47% and 52%, respectively (P < 0.05), and immunostaining for TNF-alpha in paw tissue. In TxA-injected paws, Gln depletion increased MPO activity (46%; P < 0.05). Gln depletion increased Cg- and TxA-induced neutrophil migration to subcutaneous air pouches by 56% and 77% (P < 0.05), respectively, but did not affect migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). Gln infusions reversed all the effects of MSO. Leucocyte counts did not differ between groups. Gln depletion potentiates acute inflammation, possibly by increasing neutrophil migration through resident cell activation and production of IL-1beta and TNF-alpha. Gln supplementation reverses these effects and may be useful during inflammatory catabolic stress.
Animals↗
Pathophysiology and impact of enteric bacterial and protozoal infections: new approaches to therapy.
Despite numerous scientific advances in the past few years regarding the pathogenesis, diagnostic tools and treatment of infectious enteritis, enteric infections remain a serious threat to health worldwide. With globalization of the food supply, the increase in travel, mass food processing and antibiotic resistance, infectious diarrhea has become a critical concern for both developing and developed countries. Oral rehydration therapy has been cited as the most important medical discovery of the century due to the millions of lives that have been saved. However, statistics concerning diarrhea-induced mortality and the highly underestimated morbidity continue to demonstrate the severity of the problem. A more complete understanding of the pathogenesis of infectious diarrhea and potential new vaccines and effective treatments are badly needed. In addition, public health preventive actions, such as early detection of outbreaks, care with food, water and sanitation and, where relevant, immunization, should be considered a priority. This article provides an overview of the epidemiological impact, pathogenesis and new approaches to the management of enteric infections.
Anti-Infective Agents↗
Short report: asymptomatic Cryptosporidium hominis infection among human immunodeficiency virus-infected patients in Tanzania.
Few data exist on the relative importance of individual Cryptosporidium species in acquired immunodeficiency syndrome cryptosporidiosis. We characterized 127 inpatients infected with human immunodeficiency virus (HIV) in Tanzania for their CD4 cell count and by stool analysis, including Cryptosporidium immunofluorescence and polymerase chain reaction-restriction fragment length polymorphism. Cryptosporidium was detected in patients both with and without diarrheal symptoms (defined as > or = 3 liquid stools/day, 11 of 61 versus 11 of 66; P = not significant) and was a marker for low CD4 cell count (median = 124/microL versus 212/microL in Cryptosporidium-negative patients; P < 0.04). Cryptosporidium hominis was the predominant species in this region and was associated with a longer duration of symptoms, a higher rate of asymptomatic infection, and a lower CD4 cell count versus C. parvum-infected patients (P < 0.05). This study suggests there may be important differences in the natural history of Cryptosporidium infection in HIV-infected persons depending on parasite species.
AIDS-Related Opportunistic Infections↗