Publications by authors named "Geoffrey A Preidis"

39 Publications

Reply to Letters to the Editor on Probiotic Guidelines.

Gastroenterology 2021 Feb 24. Epub 2021 Feb 24.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1053/j.gastro.2021.02.046DOI Listing
February 2021

Coagulopathy in Malnourished Mice Is Sexually Dimorphic and Regulated by Nutrient-Sensing Nuclear Receptors.

Hepatol Commun 2020 Dec 22;4(12):1835-1850. Epub 2020 Oct 22.

Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX USA.

Liver dysfunction, including coagulopathy, is a prominent feature of protein-energy malnutrition. To identify mechanisms underlying malnutrition-associated coagulopathy, we administered a low-protein low-fat diet to lactating dams and examined hepatic transcription and plasma coagulation parameters in young adult weanlings. Malnutrition impacted body composition to a greater extent in male versus female mice. Transcriptional profiles suggested opposing effects of nutrient-sensing nuclear receptors, namely induction of peroxisome proliferator-activated receptor α (PPARα) targets and repression of farnesoid-X-receptor (FXR) targets. Coagulopathy with decreased synthesis of fibrinogen-α (FGA) and factor 11 (F11) was observed in malnourished male animals but not female animals. In primary mouse hepatocytes, FXR agonist increased and PPARα agonist decreased and messenger RNA expression. Nuclear receptor DNA response elements were identified in the and gene regulatory regions, and opposing effects of FXR and PPARα were confirmed with luciferase assays. Unexpectedly, hepatic PPARα protein was markedly depleted in malnourished male liver and was not enriched on or response elements. Rather, there was loss of FXR binding at these response elements. Reduced PPARα protein was associated with loss of hepatocyte peroxisomes, which are necessary for bile acid biosynthesis, and with decreased concentrations of bile acids that function as FXR ligands, most notably the FXR agonist chenodeoxycholic acid. : Malnutrition impairs growth and liver synthetic function more severely in male mice than in female mice. Malnourished male mice are coagulopathic and exhibit decreased hepatocyte peroxisomes, FXR agonist bile acids, FXR binding on and gene regulatory elements, and coagulation factor synthesis. These effects are absent in female mice, which have low baseline levels of PPARα, suggesting that nutrient-sensing nuclear receptors regulate coagulation factor synthesis in response to host nutritional status in a sex-specific manner.
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http://dx.doi.org/10.1002/hep4.1622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706303PMC
December 2020

Early-life malnutrition causes gastrointestinal dysmotility that is sexually dimorphic.

Neurogastroenterol Motil 2020 12 6;32(12):e13936. Epub 2020 Jul 6.

Section of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.

Background: Slow gastrointestinal (GI) transit occurs in moderate-to-severe malnutrition. Mechanisms underlying malnutrition-associated dysmotility remain unknown, partially due to lack of animal models. This study sought to characterize GI dysmotility in mouse models of malnutrition.

Methods: Neonatal mice were malnourished by timed maternal separation. Alternatively, low-protein, low-fat diet was administered to dams, with malnourished neonates tested at two weeks or weaned to the same chow and tested as young adults. We determined total GI transit time by carmine red gavage, colonic motility by rectal bead latency, and both gastric emptying and small bowel motility with fluorescein isothiocyanate-conjugated dextran. We assessed histology with light microscopy, ex vivo contractility and permeability with force-transduction and Ussing chamber studies, and gut microbiota composition by 16S rDNA sequencing.

Key Results: Both models of neonatal malnutrition and young adult malnourished males but not females exhibited moderate growth faltering, stunting, and grossly abnormal stomachs. Progression of fluorescent dye was impaired in both neonatal models of malnutrition, whereas gastric emptying was delayed only in maternally separated pups and malnourished young adult females. Malnourished young adult males but not females had atrophic GI mucosa, exaggerated intestinal contractile responses, and increased gut barrier permeability. These sex-specific abnormalities were associated with altered gut microbial communities.

Conclusions & Inferences: Multiple models of early-life malnutrition exhibit delayed upper GI transit. Malnutrition affects young adult males more profoundly than females. These models will facilitate future studies to identify mechanisms underlying malnutrition-induced pathophysiology and sex-specific regulatory effects.
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http://dx.doi.org/10.1111/nmo.13936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688589PMC
December 2020

Microbiota on biotics: probiotics, prebiotics, and synbiotics to optimize growth and metabolism.

Am J Physiol Gastrointest Liver Physiol 2020 09 5;319(3):G382-G390. Epub 2020 Aug 5.

Section of Gastroenterology, Hepatology, & Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

The early stages of the metagenomics era produced countless observational studies linking various human diseases to alterations in the gut microbiota. Only recently have we begun to decipher the causal roles that gut microbes play in many of these conditions. Despite an incomplete understanding of how gut microbes influence pathophysiology, clinical trials have tested empirically numerous microbiota-targeting therapies to prevent or treat disease. Unsurprisingly, these trials have yielded mixed results. Nonetheless, the consumer market for probiotics, prebiotics, and synbiotics continues to grow. This theme paper highlights recent discoveries of mechanisms underlying diet-microbial-host interactions as they pertain to growth and metabolism and discusses current and future applications of microbiota-targeting therapies in the context of child malnutrition as well as obesity and its metabolic comorbidities, including nonalcoholic fatty liver disease and cardiovascular disease. We also highlight current challenges and identify future directions to facilitate a more efficient and direct path to clinical impact.
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http://dx.doi.org/10.1152/ajpgi.00028.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509258PMC
September 2020

Spotlight: Probiotics Guidelines.

Gastroenterology 2020 08 22;159(2):707. Epub 2020 Jul 22.

Section of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Baylor College of, Medicine and Texas Children's Hospital, Houston, TX.

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http://dx.doi.org/10.1053/j.gastro.2020.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046260PMC
August 2020

Evidence from systematic reviews of randomized trials on enteral lactoferrin supplementation in preterm neonates.

Biochem Cell Biol 2021 Feb 28;99(1):20-24. Epub 2020 Jul 28.

WINNER Centre for Newborn Research, NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW 2050, Australia.

In this commentary, we summarize the current evidence from randomized controlled trials on enteral lactoferrin supplementation in preterm neonates. Our recently completed systematic review includes 12 randomized controlled trials performed all over the world. Our meta-analysis suggests clinical benefit in decreasing late-onset sepsis, late-onset fungal sepsis, length of stay in the hospital and urinary tract infections. There were no adverse effects. There was no statistically significant decrease in necrotizing enterocolitis, mortality or neurodevelopmental impairment in lactoferrin supplemented preterm infants. There was significant statistical heterogeneity in the effects of lactoferrin on late-onset sepsis between larger and smaller studies, which may reflect either small study biases, differences in the effectiveness, dose or duration of supplemental lactoferrin products, or differences in underlying population risk, or any or all of these.
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http://dx.doi.org/10.1139/bcb-2020-0136DOI Listing
February 2021

Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials.

Gastroenterology 2020 08 24;159(2):467-480. Epub 2020 Jun 24.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Anesthesia, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada; The Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada. Electronic address:

Background & Aims: We aimed to compare the effectiveness of single- vs multiple-strain probiotics in a network meta-analysis of randomized trials.

Methods: We searched MEDLINE, Embase, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through January 1, 2019, for studies of single-strain and multistrain probiotic formulations on the outcomes of preterm, low-birth-weight neonates. We used a frequentist approach for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Primary outcomes included all-cause mortality, severe necrotizing enterocolitis (NEC) (Bell stage II or more), and culture-proven sepsis.

Results: We analyzed data from 63 trials involving 15,712 preterm infants. Compared with placebo, a combination of 1 or more Lactobacillus species (spp) and 1 or more Bifidobacterium spp was the only intervention with moderate- or high-quality evidence of reduced all-cause mortality (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.39-0.80). Among interventions with moderate- or high-quality evidence for efficacy compared with placebo, combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp, Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced severe NEC (OR, 0.35 [95% CI, 0.20-0.59]; OR, 0.31 [95% CI, 0.13-0.74]; OR, 0.55 [95% CI, 0.34-0.91]; and OR, 0.44 [95% CI, 0.21-0.90], respectively). There was moderate- or high-quality evidence that combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp and Saccharomyces boulardii reduced the number of days to reach full feeding (mean reduction of 3.30 days [95% CI, reduction of 5.91-0.69 days]). There was moderate- or high-quality evidence that, compared with placebo, the single-species product B animalis subsp lactis or L reuteri significantly reduced duration of hospitalization (mean reduction of 13.00 days [95% CI, reduction of 22.71-3.29 days] and mean reduction of 7.89 days [95% CI, reduction of 11.60-4.17 days], respectively).

Conclusions: In a systematic review and network meta-analysis of studies to determine the effects of single-strain and multistrain probiotic formulations on outcomes of preterm, low-birth-weight neonates, we found moderate to high evidence for the superiority of combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp vs single- and other multiple-strain probiotic treatments. The combinations of Bacillus spp and Enterococcus spp, and 1 or more Bifidobacterium spp and Streptococcus salivarius subsp thermophilus, might produce the largest reduction in NEC development. Further trials are needed.
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http://dx.doi.org/10.1053/j.gastro.2020.05.096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014956PMC
August 2020

AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders.

Gastroenterology 2020 08 9;159(2):708-738.e4. Epub 2020 Jun 9.

Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1053/j.gastro.2020.05.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018518PMC
August 2020

Sexual dimorphism in upper gastrointestinal motility is dependent on duration of fast, time of day, age, and strain of mice.

Neurogastroenterol Motil 2019 09 3;31(9):e13654. Epub 2019 Jun 3.

Section of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

Background: An important limitation of gastrointestinal motility testing is high variability. Conditions that could contribute to variability, including the duration of pretest fasting and time of day, are rarely reported and have not been examined systematically. This study aimed to explore whether these conditions, as well as age, sex, and strain of mice, affect the results of a standard laboratory test of upper gastrointestinal motility.

Methods: Male and female 8-week-old C57BL/6J mice received a gastric gavage of fluorescein isothiocyanate (FITC)-conjugated dextran. FITC-dextran distribution was measured 30 minutes later. Mean geometric centers (MGCs) were calculated to determine the effects of short versus prolonged fasting and morning versus afternoon testing. The influence of age was assessed in 2- to 10-week-old animals, and the influence of strain was determined in C57BL/6J, BALB/c, and CD-1 mice.

Key Results: Motility was sexually dimorphic. MGC progressed 19% further in 8-week-old C57BL/6J males versus females when tested in the morning after a short fast. Similar patterns were observed in morning or afternoon testing after overnight fasting. In males, motility was unaffected by time of day; however, MGC progressed 31% further in females tested in the afternoon versus morning after a short fast. Sex differences also were present in CD-1 but not BALB/c mice. Testing in neonates revealed strikingly low variability and no sex differences.

Conclusions & Inferences: Fasting duration, time of day, age, sex, and strain of mice all influence upper gastrointestinal motility testing. Sex differences are not present in neonatal pups, but develop soon after weaning.
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http://dx.doi.org/10.1111/nmo.13654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693981PMC
September 2019

Improved feeding tolerance and growth are linked to increased gut microbial community diversity in very-low-birth-weight infants fed mother's own milk compared with donor breast milk.

Am J Clin Nutr 2019 04;109(4):1088-1097

Section of Neonatology, Department of Pediatrics.

Background: Mother's own milk (MOM) is protective against gut microbiota alterations associated with necrotizing enterocolitis (NEC) and feeding intolerance among preterm infants. It is unclear whether this benefit is preserved with donor milk (DM) feeding.

Objective: We aimed to compare microbiota development, growth, and feeding tolerance in very-low-birth-weight (VLBW) infants fed an exclusively human milk diet of primarily MOM or DM.

Methods: One hundred and twenty-five VLBW infants born at Texas Children's Hospital were enrolled and grouped into cohorts based on percentage of MOM and DM in enteral feeds. Feeds were fortified with DM-derived fortifier per unit protocol. Weekly stool samples were collected for 6 wk for microbiota analysis [16S ribosomal RNA (rRNA) sequencing]. A research nurse obtained weekly anthropometrics. Clinical outcomes were compared via Wilcoxon's rank-sum test and Fisher's exact test, as well as multivariate analysis.

Results: The DM cohort (n = 43) received on average 14% mothers' milk compared with 91% for the MOM cohort (n = 74). Diversity of gut microbiota across all time points (n = 546) combined was increased in MOM infants (P < 0.001). By 4 and 6 wk of life, microbiota in MOM infants contained increased abundance of Bifidobacterium (P = 0.02) and Bacteroides (P = 0.04), whereas DM-fed infants had increased abundance of Staphylococcus (P = 0.02). MOM-fed infants experienced a 60% reduction in feeding intolerance (P = 0.03 by multivariate analysis) compared with DM-fed infants. MOM-fed infants had greater weight gain than DM-fed infants.

Conclusions: Compared with DM-fed infants, MOM-fed infants have increased gut microbial community diversity at the phylum and genus levels by 4 and 6 wk of life, as well as better feeding tolerance. MOM-fed infants had superior growth. The incidence of NEC and other gastrointestinal morbidity is low among VLBW infants fed an exclusively human milk diet including DM-derived fortifier. This trial was registered at clinicaltrials.gov as NCT02573779.
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http://dx.doi.org/10.1093/ajcn/nqz006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462428PMC
April 2019

New Insights into the Pathogenesis and Treatment of Malnutrition.

Gastroenterol Clin North Am 2018 12 28;47(4):813-827. Epub 2018 Sep 28.

Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Feigin Tower, 1102 Bates Avenue, Suite 860, Houston, TX 77030, USA. Electronic address:

The volume of research into the pathogenesis and treatment of malnutrition has increased markedly over the past ten years, providing mechanistic insights that can be leveraged into more effective treatment options. These discoveries have been driven by several landmark studies employing metabolomics, metagenomics, and new preclinical models. This review highlights some of the most important recent findings, focusing in particular on the emerging roles of prenatal and perinatal factors, protein deficiency, impaired gut barrier function, immune deficiency, and the intestinal microbiome.
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http://dx.doi.org/10.1016/j.gtc.2018.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484436PMC
December 2018

The Gut Microbiome in Adult and Pediatric Functional Gastrointestinal Disorders.

Clin Gastroenterol Hepatol 2019 01 25;17(2):256-274. Epub 2018 Aug 25.

Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address:

The importance of gut microbiota in gastrointestinal (GI) physiology was well described, but our ability to study gut microbial ecosystems in their entirety was limited by culture-based methods prior to the sequencing revolution. The advent of high-throughput sequencing opened new avenues, allowing us to study gut microbial communities as an aggregate, independent of our ability to culture individual microbes. Early studies focused on association of changes in gut microbiota with different disease states, which was necessary to identify a potential role for microbes and generate novel hypotheses. Over the past few years the field has moved beyond associations to better understand the mechanistic implications of the microbiome in the pathophysiology of complex diseases. This movement also has resulted in a shift in our focus toward therapeutic strategies, which rely on better understanding the mediators of gut microbiota-host cross-talk. It is not surprising the gut microbiome has been implicated in the pathogenesis of functional gastrointestinal disorders given its role in modulating physiological processes such as immune development, GI motility and secretion, epithelial barrier integrity, and brain-gut communication. In this review, we focus on the current state of knowledge and future directions in microbiome research as it pertains to functional gastrointestinal disorders. We summarize the factors that help shape the gut microbiome in human beings. We discuss data from animal models and human studies to highlight existing paradigms regarding the mechanisms underlying microbiota-mediated alterations in physiological processes and their relevance in human interventions. While translation of microbiome science is still in its infancy, the outlook is optimistic and we are advancing in the right direction toward precise mechanism-based microbiota therapies.
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http://dx.doi.org/10.1016/j.cgh.2018.08.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314902PMC
January 2019

Nutrient-sensing nuclear receptors PPARα and FXR control liver energy balance.

J Clin Invest 2017 Apr 13;127(4):1193-1201. Epub 2017 Mar 13.

The nuclear receptors PPARα (encoded by NR1C1) and farnesoid X receptor (FXR, encoded by NR1H4) are activated in the liver in the fasted and fed state, respectively. PPARα activation induces fatty acid oxidation, while FXR controls bile acid homeostasis, but both nuclear receptors also regulate numerous other metabolic pathways relevant to liver energy balance. Here we review evidence that they function coordinately to control key nutrient pathways, including fatty acid oxidation and gluconeogenesis in the fasted state and lipogenesis and glycolysis in the fed state. We have also recently reported that these receptors have mutually antagonistic impacts on autophagy, which is induced by PPARα but suppressed by FXR. Secretion of multiple blood proteins is a major drain on liver energy and nutrient resources, and we present preliminary evidence that the liver secretome may be directly suppressed by PPARα, but induced by FXR. Finally, previous studies demonstrated a striking deficiency in bile acid levels in malnourished mice that is consistent with results in malnourished children. We present evidence that hepatic targets of PPARα and FXR are dysregulated in chronic undernutrition. We conclude that PPARα and FXR function coordinately to integrate liver energy balance.
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http://dx.doi.org/10.1172/JCI88893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373864PMC
April 2017

Mechanisms of cross-talk between the diet, the intestinal microbiome, and the undernourished host.

Gut Microbes 2017 03 5;8(2):98-112. Epub 2016 Dec 5.

b Section of Gastroenterology, Hepatology, and Nutrition , Department of Pediatrics , Baylor College of Medicine and Texas Children's Hospital , Houston , TX , USA.

Undernutrition remains one of the most pressing global health challenges today, contributing to nearly half of all deaths in children under five years of age. Although insufficient dietary intake and environmental enteric dysfunction are often inciting factors, evidence now suggests that unhealthy gut microbial populations perpetuate the vicious cycle of pathophysiology that results in persistent growth impairment in children. The metagenomics era has facilitated new research identifying an altered microbiome in undernourished hosts and has provided insight into a number of mechanisms by which these alterations may affect growth. This article summarizes a range of observational studies that highlight differences in the composition and function of gut microbiota between undernourished and healthy children; discusses dietary, environmental and host factors that shape this altered microbiome; examines the consequences of these changes on host physiology; and considers opportunities for microbiome-targeting therapies to combat the global challenge of child undernutrition.
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http://dx.doi.org/10.1080/19490976.2016.1267888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390823PMC
March 2017

Microbial-Derived Metabolites Reflect an Altered Intestinal Microbiota during Catch-Up Growth in Undernourished Neonatal Mice.

J Nutr 2016 05 6;146(5):940-8. Epub 2016 Apr 6.

Department of Molecular Virology and Microbiology and Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX.

Background: Protein-energy undernutrition during early development confers a lifelong increased risk of obesity-related metabolic disease. Mechanisms by which metabolic abnormalities persist despite catch-up growth are poorly understood.

Objective: We sought to determine whether abnormal metabolomic and intestinal microbiota profiles from undernourished neonatal mice remain altered during catch-up growth.

Methods: Male and female CD1 mouse pups were undernourished by timed separation from lactating dams for 4 h at 5 d of age, 8 h at 6 d of age, and 12 h/d from 7 to 15 d of age, then resumed ad libitum nursing, whereas controls fed uninterrupted. Both groups were weaned simultaneously to a standard unpurified diet. At 3 time points (0, 1, and 3 wk after ending feed deprivation), metabolites in urine, plasma, and stool were identified with the use of mass spectrometry, and fecal microbes were identified with the use of 16S metagenomic sequencing.

Results: Undernourished mice completely recovered deficits of 36% weight and 9% length by 3 wk of refeeding, at which time they had 1.4-fold higher plasma phenyllactate and 2.0-fold higher urinary p-cresol sulfate concentrations than did controls. Plasma serotonin concentrations in undernourished mice were 25% lower at 0 wk but 1.5-fold higher than in controls at 3 wk. Whereas most urine and plasma metabolites normalized with refeeding, 117 fecal metabolites remained altered at 3 wk, including multiple N-linked glycans. Microbiota profiles from undernourished mice also remained distinct, with lower mean proportions of Bacteroidetes (67% compared with 83%) and higher proportions of Firmicutes (26% compared with 16%). Abundances of the mucolytic organisms Akkermansia muciniphila and Mucispirillum schaedleri were altered at 0 and 1 wk. Whereas microbiota from undernourished mice at 0 wk contained 11% less community diversity (P = 0.015), refed mice at 3 wk harbored 1.2-fold greater diversity (P = 0.0006) than did controls.

Conclusion: Microbial-derived metabolites and intestinal microbiota remain altered during catch-up growth in undernourished neonatal mice.
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http://dx.doi.org/10.3945/jn.115.229179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841929PMC
May 2016

Composition and function of the undernourished neonatal mouse intestinal microbiome.

J Nutr Biochem 2015 Oct 15;26(10):1050-7. Epub 2015 May 15.

Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030, USA.

Undernutrition remains one of the key global health challenges facing children today. Distinct microbial profiles have been associated with obesity and undernutrition, although mechanisms behind these associations are unknown. We sought to understand how protein-energy undernutrition alters the microbiome and to propose mechanisms by which these alterations influence the malnourished phenotype. Outbred CD1 neonatal mice were undernourished by timed separation from lactating dams, while control animals nursed ad libitum. 16S rRNA gene sequencing and compositional analysis identified microbes from luminal contents of ileum, cecum and colon, while whole metagenome shotgun sequencing identified microbial gene content. Our results suggest that the most important determinant of microbiome composition is body compartment; communities derived from ileum are distinct from those from cecum and colon as observed by phylogenetic clustering analysis. However, within each compartment, microbiota from undernourished and control mice cluster separately. At the phylum level, undernourished mice harbor more Verrucomicrobia and less Bacteroidetes in the distal intestine; these changes are driven by an increase in Akkermansia muciniphila and decreases in Bacteroides and Alistipes. Undernourished mice have an overall loss of microbial community richness and diversity and are deficient in multiple microbial genetic pathways including N-glycan, inositol phosphate and one-carbon metabolism. Losses in these microbial genes may confer less efficient extraction of energy from nondigestible dietary components including glycans and phytates, whereas epigenetic alterations provide a means of persistently altering metabolism even after adequate nutrition is restored. Thus, the microbiome of an undernourished host may perpetuate states of poor nutrition via multiple mechanisms.
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http://dx.doi.org/10.1016/j.jnutbio.2015.04.010DOI Listing
October 2015

The newest "omics"--metagenomics and metabolomics--enter the battle against the neglected tropical diseases.

PLoS Negl Trop Dis 2015 Feb 12;9(2):e0003382. Epub 2015 Feb 12.

National School of Tropical Medicine, Department of Pediatrics and Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas, United States of America; Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Houston, Texas, United States of America; James A. Baker III Institute for Public Policy, Rice University, Houston, Texas, United States of America; Department of Biology, Baylor University, Waco, Texas, United States of America.

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http://dx.doi.org/10.1371/journal.pntd.0003382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326130PMC
February 2015

Improved identification and enrolment into care of HIV-exposed and -infected infants and children following a community health worker intervention in Lilongwe, Malawi.

J Int AIDS Soc 2015 7;18:19305. Epub 2015 Jan 7.

ICAP, Mailman School of Public Health and College of Physicians & Surgeons, Columbia University, New York, NY, USA.

Background: Early identification and entry into care is critical to reducing morbidity and mortality in children with HIV. The objective of this report is to describe the impact of the Tingathe programme, which utilizes community health workers (CHWs) to improve identification and enrolment into care of HIV-exposed and -infected infants and children.

Methods: Three programme phases are described. During the first phase, Mentorship Only (MO) (March 2007-February 2008) on-site clinical mentorship on paediatric HIV care was provided. In the second phase, Tingathe-Basic (March 2008-February 2009), CHWs provided HIV testing and counselling to improve case finding of HIV-exposed and -infected children. In the final phase, Tingathe-PMTCT (prevention of mother-to-child transmission) (March 2009-February 2011), CHWs were also assigned to HIV-positive pregnant women to improve mother-infant retention in care. We reviewed routinely collected programme data from HIV testing registers, patient mastercards and clinic attendance registers from March 2005 to March 2011.

Results: During MO, 42 children (38 HIV-infected and 4 HIV-exposed) were active in care. During Tingathe-Basic, 238 HIV-infected children (HIC) were newly enrolled, a six-fold increase in rate of enrolment from 3.2 to 19.8 per month. The number of HIV-exposed infants (HEI) increased from 4 to 118. During Tingathe-PMTCT, 526 HIC were newly enrolled over 24 months, at a rate of 21.9 patients per month. There was also a seven-fold increase in the average number of exposed infants enrolled per month (9.5-70 patients per month), resulting in 1667 enrolled with a younger median age at enrolment (5.2 vs. 2.5 months; p < 0.001). During the Tingathe-Basic and Tingathe-PMTCT periods, CHWs conducted 44,388 rapid HIV tests, 7658 (17.3%) in children aged 18 months to 15 years; 351 (4.6%) tested HIV-positive. Over this time, 1781 HEI were enrolled, with 102 (5.7%) found HIV-infected by positive PCR. Additional HIC entered care through various mechanisms (including positive linkage by CHWs and transfer-ins) such that by February 2011, a total of 866 HIC were receiving care, a 23-fold increase from 2008.

Conclusions: A multipronged approach utilizing CHWs to conduct HIV testing, link HIC into care and provide support to PMTCT mothers can dramatically improve the identification and enrolment into care of HIV-exposed and -infected children.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287633PMC
http://dx.doi.org/10.7448/IAS.18.1.19305DOI Listing
May 2016

If you text them, they will come: using the HIV infant tracking system to improve early infant diagnosis quality and retention in Kenya.

AIDS 2014 Jul;28 Suppl 3:S313-21

aUniversity of Kansas Medical Center, Department of Family Medicine, Kansas City, Kansas bGlobal Health Innovations, Kansas City, Missouri, USA cKenya Medical Research Institute, Nairobi, Kenya dHealth Services and Outcomes Research, Children's Mercy Hospital, Kansas City, Missouri eTexas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital fDepartment of Pathology & Immunology, Baylor College of Medicine gHealth Empowering Humanity, Houston, Texas, USA hKenya Ministries of Health, National AIDS and STI Control Programme, Nairobi, Kenya iUniversity of Kansas, Department of Global Studies, Lawrence, Kansas jDepartment of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, USA.

Objective: The objective of this study is to evaluate the impact of the HIV Infant Tracking System (HITSystem) for quality improvement of early infant diagnosis (EID) of HIV services.

Design And Setting: This observational pilot study compared 12 months of historical preintervention EID outcomes at one urban and one peri-urban government hospital in Kenya to 12 months of intervention data to assess retention and time throughout the EID cascade of care.

Participants: Mother-infant pairs enrolled in EID at participating hospitals before (n = 320) and during (n = 523) the HITSystem pilot were eligible to participate.

Intervention: The HITSystem utilizes Internet-based coordination of the multistep PCR cycle, automated alerts to trigger prompt action from providers and laboratory technicians, and text messaging to notify mothers when results are ready or additional action is needed.

Main Outcome Measures: The main outcome measures were retention throughout EID services, meeting time-sensitive targets and improving results turn-around time, and increasing early antiretroviral therapy (ART) initiation among HIV-infected infants.

Results: The HITSystem was associated with an increase in the proportion of HIV-exposed infants retained in EID care at 9 months postnatal (45.1-93.0% urban; 43.2-94.1% peri-urban), a decrease in turn-around times between sample collection, PCR results and notification of mothers in both settings, and a significant increase in the proportion of HIV-infected infants started on antiretroviral therapy at each hospital(14 vs. 100% urban; 64 vs. 100% peri-urban).

Conclusion: The HITSystem maximizes the use of easily accessible technology to improve the quality and efficiency of EID services in resource-limited settings.
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http://dx.doi.org/10.1097/QAD.0000000000000332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226133PMC
July 2014

Implementing the Jadelle implant for women living with HIV in a resource-limited setting: concerns for drug interactions leading to unintended pregnancies.

AIDS 2014 Mar;28(5):791-3

aBaylor College of Medicine, Baylor International Pediatric AIDS Initiative, Children's Foundation bDepartment of Pediatrics, Baylor College of Medicine/Texas Children's Hospital cBaylor Bristol-Myers Squibb Children's Clinical Center of Excellence-Swaziland dKingdom of Swaziland Ministry of Health, Sexual and Reproductive Health Unit, Mbabane, Swaziland.

An analysis of 570 HIV-infected women in Swaziland using the Jadelle implant showed that age, condom use, the provider who placed the implant, and CD4 cell count had no effect on unintentional pregnancy rates. Antiretroviral regimen at the time of pregnancy, however, correlated with pregnancy outcomes (P < 0.001). None of the women on nevirapine or lopinavir/ritonavir-based regimens (n = 208 and 13, respectively) became pregnant, whereas 15 women on efavirenz (n = 121; 12.4%) became pregnant.
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http://dx.doi.org/10.1097/QAD.0000000000000177DOI Listing
March 2014

The undernourished neonatal mouse metabolome reveals evidence of liver and biliary dysfunction, inflammation, and oxidative stress.

J Nutr 2014 Mar 31;144(3):273-81. Epub 2013 Dec 31.

Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX.

Undernutrition contributes to half of all childhood deaths under the age of 5 y, and confers upon survivors a life-long predisposition to obesity, type 2 diabetes, and cardiovascular disease. Mechanisms underlying the link between early nutrient deprivation and noncommunicable diseases are unknown. Using outbred CD1 neonatal mice, we measured metabolic profile differences between conventionally reared mice given unrestricted access to nursing, the control group, and undernourished mice subjected to protein-calorie deprivation through timed separation from lactating mothers. After 11 d of undernutrition, urine, plasma, liver, ileal fluid, cecal fluid, and stool were harvested from 8 pools of 4 neonatal mice per group. The metabolome was identified using a multiplatform mass spectrometry-based approach, and random forest metrics were used to identify the most important metabolites that distinguished the undernourished from the control group. Our data reveal striking metabolic changes in undernourished mice consistent with the known mammalian response to starvation, including evidence of muscle and fat catabolism and increased reliance on the tricarboxylic acid cycle for energy. However, we also revealed evidence of liver and biliary injury, anomalies in bile acid metabolism, oxidative stress and inflammation, accelerated heme breakdown, and altered regulation of DNA methylation. Among the metabolites that most strongly distinguished the 2 groups were 2-hydroxyisobutyrate, increased 3-fold in plasma of undernourished mice (P = 2.19 × 10(-11)); urobilinogen, increased 11-fold in urine of undernourished mice (P = 4.22 × 10(-7)); deoxycholate, decreased 94% in stool of undernourished mice (P = 3.0 × 10(-4)); and 12 different products of the enzyme γ-glutamyltransferase, increased in all 6 compartments of undernourished mice. This model of the undernourished neonatal metabolome illustrates the wide range of pathways disrupted by undernutrition in early development, and suggests mechanistic links between early starvation and persistent metabolic diseases.
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http://dx.doi.org/10.3945/jn.113.183731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927544PMC
March 2014

Clinical versus rapid molecular HIV diagnosis in hospitalized African infants: a randomized controlled trial simulating point-of-care infant testing.

J Acquir Immune Defic Syndr 2014 May;66(1):e23-30

*University of North Carolina Project, Lilongwe, Malawi; †Department of Pediatrics, Division of Pulmonology, Johns Hopkins School of Medicine, Baltimore, MD; ‡Department of Pediatrics, Baylor College of Medicine, Houston, TX; §Department of Pediatrics, Division of Infectious Diseases, University of Colorado, Aurora, CO; ‖Baylor College of Medicine Children's Foundation Malawi, Lilongwe, Malawi; and ¶Department of Medicine, Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC.

Objective: Many African infants fail to receive their diagnostic HIV molecular test results and subsequently, antiretroviral therapy (ART). To determine whether a point-of-care molecular HIV test increases ART access for hospitalized Malawian infants, we simulated a point-of-care test using rapid HIV RNA polymerase chain reaction (Rapid PCR) and compared patient outcomes with an optimized standard care that included assessment with the World Health Organization clinical algorithm for HIV infection plus a DNA PCR with a turnaround time of several weeks (standard care).

Design: Randomized controlled trial.

Methods: Hospitalized HIV-exposed Malawian infants aged <12 months were randomized into Rapid PCR or standard care. Rapid PCR infants obtained molecular test results within 48 hours to facilitate immediate ART, similar to a point-of-care test. Standard care infants meeting clinical criteria were also offered inpatient ART. The primary outcome was appropriate in-hospital ART for DNA or RNA PCR-confirmed HIV-infected infants.

Results: Three hundred infants were enrolled. A greater proportion of HIV-infected infants receiving Rapid PCR, versus standard care, started inpatient ART (72.3% vs 47.8%, P = 0.016). Among molecular test-negative infants, 26.9% receiving standard care unnecessarily initiated inpatient ART, versus 0.0% receiving Rapid PCR (P < 0.001). Rapid PCR modestly reduced the median days to ART (3.0 vs 6.5, P = 0.001) but did not influence outpatient follow-up for HIV-infected infants (78.1% vs 82.4%, P = 0.418).

Conclusions: Rapid PCR, versus an optimized standard care, increased the proportion of hospitalized HIV-infected infants initiating ART and reduced ART exposure in molecular test-negative infants, without meaningfully impacting time to ART initiation or follow-up rates.
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http://dx.doi.org/10.1097/QAI.0000000000000080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345126PMC
May 2014

Determining the quality of IMCI pneumonia care in Malawian children.

Paediatr Int Child Health 2014 Feb 6;34(1):29-36. Epub 2013 Dec 6.

Background: Although pneumonia is the leading cause of child mortality worldwide, little is known about the quality of routine pneumonia care in high burden settings like Malawi that utilize World Health Organization's Integrated Management of Childhood Illnesses (IMCI) guidelines. Due to severe human resource constraints, the majority of clinical care in Malawi is delivered by non-physician clinicians called Clinical Officers (COs).

Aim: To assess the quality of child pneumonia care delivered by Malawian COs in routine care conditions.

Methods: At an outpatient district-level clinic in Lilongwe, Malawi, 10 COs caring for 695 children who presented with fever, cough, or difficulty breathing were compared to IMCI pneumonia diagnostic and treatment guidelines.

Results: Fewer than 1% of patients received an evaluation by COs that included all 16 elements of the history and physical examination. The respiratory rate was only determined in 16.1% of patients presenting with cough or difficulty breathing. Of the 274 children with IMCI-defined pneumonia, COs correctly diagnosed 30%, and administered correct pneumonia care in less than 25%. COs failed to hospitalize 40.8% of children with severe or very severe pneumonia.

Conclusions: IMCI pneumonia care quality at this Malawian government clinic is alarmingly low. Along with reassessing current pneumonia training and supervision approaches, novel quality improvement interventions are necessary to improve care.
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http://dx.doi.org/10.1179/2046905513Y.0000000070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424282PMC
February 2014

Development of a severity of illness scoring system (inpatient triage, assessment and treatment) for resource-constrained hospitals in developing countries.

Trop Med Int Health 2013 Jul;18(7):871-8

Department of Pediatrics, University of Colorado, Denver, CO, USA.

Objective: To develop a new paediatric illness severity score, called inpatient triage, assessment and treatment (ITAT), for resource-limited settings to identify hospitalised patients at highest risk of death and facilitate urgent clinical re-evaluation.

Methods: We performed a nested case-control study at a Malawian referral hospital. The ITAT score was derived from four equally weighted variables, yielding a cumulative score between 0 and 8. Variables included oxygen saturation, temperature, and age-adjusted heart and respiratory rates. We compared the ITAT score between cases (deaths) and controls (discharges) in predicting death within 2 days. Our analysis includes predictive statistics, bivariable and multivariable logistic regression, and calculation of data-driven scores.

Results: A total of 54 cases and 161 controls were included in the analysis. The area under the receiver operating characteristic curve was 0.76. At an ITAT cut-off of 4, the sensitivity, specificity and likelihood ratio were 0.44, 0.86 and 1.70, respectively. A cumulative ITAT score of 4 or higher was associated with increased odds of death (OR 4.80; 95% CI 2.39-9.64). A score of 2 for all individual vital signs was a statistically significant independent predictor of death.

Conclusions: We developed an inpatient triage tool (ITAT) appropriate for resource-constrained hospitals that identifies high-risk children after hospital admission. Further research is needed to study how best to operationalise ITAT in developing countries.
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http://dx.doi.org/10.1111/tmi.12137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713504PMC
July 2013

Low rates of mother-to-child HIV transmission in a routine programmatic setting in Lilongwe, Malawi.

PLoS One 2013 31;8(5):e64979. Epub 2013 May 31.

Baylor College of Medicine International Pediatric AIDS Initiative at Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, United States of America.

Background: The Tingathe program utilizes community health workers to improve prevention of mother-to-child transmission (PMTCT) service delivery. We evaluated the impact of antiretroviral (ARV) regimen and maternal CD4+ count on HIV transmission within the Tingathe program in Lilongwe, Malawi.

Methods: We reviewed clinical records of 1088 mother-infant pairs enrolled from March 2009 to March 2011 who completed follow-up to first DNA PCR. Eligibility for antiretroviral treatment (ART) was determined by CD4+ cell count (CD4+) for women not yet on ART. ART-eligible women initiated stavudine-lamivudine-nevirapine. Early ART was defined as ART for ≥14 weeks prior to delivery. For women ineligible for ART, optimal ARV prophylaxis was maternal AZT ≥6 weeks+sdNVP, and infant sdNVP+AZT for 1 week. HIV transmission rates were determined for ARV regimens, and factors associated with vertical transmission were identified using bivariate logistic regression.

Results: Transmission rate at first PCR was 4.1%. Pairs receiving suboptimal ARV prophylaxis were more likely to transmit HIV (10.3%, 95% CI, 5.5-18.1%). ART was associated with reduced transmission (1.4%, 95% CI, 0.6-3.0%), with early ART associated with decreased transmission (no transmission), compared to all other treatment groups (p = 0.001). No association was detected between transmission and CD4+ categories (p = 0.337), trimester of pregnancy at enrollment (p = 0.100), or maternal age (p = 0.164).

Conclusion: Low rates of MTCT of HIV are possible in resource-constrained settings under routine programmatic conditions. No transmissions were observed among women on ART for more than 14 weeks prior to delivery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064979PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669205PMC
January 2014

Task shifting an inpatient triage, assessment and treatment programme improves the quality of care for hospitalised Malawian children.

Trop Med Int Health 2013 Jul 22;18(7):879-86. Epub 2013 Apr 22.

Department of Pediatrics, University of Colorado, Denver, CO, USA.

Objective: We aimed to improve paediatric inpatient surveillance at a busy referral hospital in Malawi with two new programmes: (i) the provision of vital sign equipment and implementation of an inpatient triage programme (ITAT) that includes a simplified paediatric severity-of-illness score, and (ii) task shifting ITAT to a new cadre of healthcare workers called 'vital sign assistants' (VSAs).

Methods: This study, conducted on the paediatric inpatient ward of a large referral hospital in Malawi, was divided into three phases, each lasting 4 weeks. In Phase A, we collected baseline data. In Phase B, we provided three new automated vital sign poles and implemented ITAT with current hospital staff. In Phase C, VSAs were introduced and performed ITAT. Our primary outcome measures were the number of vital sign assessments performed and clinician notifications to reassess patients with high ITAT scores.

Results: We enrolled 3994 patients who received 5155 vital sign assessments. Assessment frequency was equal between Phases A (0.67 assessments/patient) and B (0.61 assessments/patient), but increased 3.6-fold in Phase C (2.44 assessments/patient, P < 0.001). Clinician notifications increased from Phases A (84) and B (113) to Phase C (161, P = 0.002). Inpatient mortality fell from Phase A (9.3%) to Phases B (5.7) and C (6.9%).

Conclusion: ITAT with VSAs improved vital sign assessments and nearly doubled clinician notifications of patients needing further assessment due to high ITAT scores, while equipment alone made no difference. Task shifting ITAT to VSAs may improve outcomes in paediatric hospitals in the developing world.
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http://dx.doi.org/10.1111/tmi.12114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683117PMC
July 2013

Multicenter study of hypoxemia prevalence and quality of oxygen treatment for hospitalized Malawian children.

Trans R Soc Trop Med Hyg 2013 May;107(5):285-92

Department of Pediatrics, Division of Pulmonology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Background: Although hypoxemic children have high mortality, little is known about hypoxemia prevalence and oxygen administration in African hospitals. We aimed to determine the hypoxemia prevalence and quality of oxygen treatment by local clinicians for hospitalized Malawian children.

Methods: The study was conducted in five Malawian hospitals during January-April 2011. We prospectively measured the peripheral oxygen saturation (SpO(2)) using pulse oximetry for all children <15 years old and also determined clinical eligibility for oxygen treatment using WHO criteria for children <5 years old. We determined oxygen treatment quality by Malawian clinicians by comparing their use of WHO criteria for patients <5 years old using two standards: hypoxemia (SpO(2) <90%) and the use of WHO criteria by study staff.

Results: Forty of 761 (5.3%) hospitalized children <15 years old had SpO(2) <90%. No hospital used pulse oximetry routinely, and only 9 of 40 (22.5%) patients <15 years old with SpO(2) <90% were treated with oxygen by hospital staff. Study personnel using WHO criteria for children <5 years old achieved a higher sensitivity (40.0%) and lower specificity (82.7%) than Malawian clinicians (sensitivity 25.7%, specificity 94.1%).

Conclusion: Although hypoxemia is common, the absence of routine pulse oximetry results in most hospitalized, hypoxemic Malawian children not receiving available oxygen treatment.
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http://dx.doi.org/10.1093/trstmh/trt017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030433PMC
May 2013

Routine inpatient provider-initiated HIV testing in Malawi, compared with client-initiated community-based testing, identifies younger children at higher risk of early mortality.

J Acquir Immune Defic Syndr 2013 May;63(1):e16-22

Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA.

Objective: To determine how routine inpatient provider-initiated HIV testing differs from traditional community-based client-initiated testing with respect to clinical characteristics of children identified and outcomes of outpatient HIV care.

Design: Prospective observational cohort.

Methods: Routine clinical data were collected from children identified as HIV-infected by either testing modality in Lilongwe, Malawi, in 2008. After 1 year of outpatient HIV care at the Baylor College of Medicine Clinical Center of Excellence, outcomes were assessed.

Results: Of 742 newly identified HIV-infected children enrolling into outpatient HIV care, 20.9% were identified by routine inpatient HIV testing. Compared with community-identified children, hospital-identified patients were younger (median 25.0 vs 53.5 months), with more severe disease (22.2% vs 7.8% WHO stage IV). Of 466 children with known outcomes, 15.0% died within the first year of HIV care; median time to death was 15.0 weeks for community-identified children vs 6.0 weeks for hospital-identified children. The strongest predictors of early mortality were severe malnutrition (hazard ratio, 4.3; 95% confidence interval, 2.2-8.3), moderate malnutrition (hazard ratio, 3.2; confidence interval, 1.6-6.6), age < 12 months (hazard ratio, 3.2; 95% confidence interval, 1.4-7.2), age 12 to 24 months (hazard ratio, 2.5; 95% confidence interval, 1.1-5.7), and WHO stage IV (hazard ratio, 2.2; 95% confidence interval, 1.1-4.6). After controlling for other variables, hospital identification did not independently predict mortality.

Conclusions: Routine inpatient HIV testing identifies a subset of younger HIV-infected children with more severe, rapidly progressing disease that traditional community-based testing modalities are currently missing.
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http://dx.doi.org/10.1097/QAI.0b013e318288aad6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364280PMC
May 2013

The Tingathe programme: a pilot intervention using community health workers to create a continuum of care in the prevention of mother to child transmission of HIV (PMTCT) cascade of services in Malawi.

J Int AIDS Soc 2012 Jul 11;15 Suppl 2:17389. Epub 2012 Jul 11.

Baylor College of Medicine International Pediatric AIDS Initiative at Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.

Introduction: Loss to follow-up is a major challenge in the prevention of mother to child transmission of HIV (PMTCT) programme in Malawi with reported loss to follow-up of greater than 70%. Tingathe-PMTCT is a pilot intervention that utilizes dedicated community health workers (CHWs) to create a complete continuum of care within the PMTCT cascade, improving service utilization and retention of mothers and infants. We describe the impact of the intervention on longitudinal care starting with diagnosis of the mother at antenatal care (ANC) through final diagnosis of the infant.

Methods: PMTCT service utilization, programme retention and outcomes were evaluated for pregnant women living with HIV and their exposed infants enrolled in the Tingathe-PMTCT programme between March 2009 and March 2011. Multivariate logistic regression was done to evaluate maternal factors associated with failure to complete the cascade.

Results: Over 24 months, 1688 pregnant women living with HIV were enrolled. Median maternal age was 27 years (IQR, 23.8 to 30.8); 333 (19.7%) were already on ART. Among the remaining women, 1328/1355 (98%) received a CD4 test, with 1243/1328 (93.6%) receiving results. Of the 499 eligible for ART, 363 (72.8%) were successfully initiated. Prior to, delivery there were 93 (5.7%) maternal/foetal deaths, 137 (8.1%) women transferred/moved, 51 (3.0%) were lost and 58 (3.4%) refused ongoing PMTCT services. Of the 1318 live births to date, 1264 (95.9%) of the mothers and 1285 (97.5%) of the infants received ARV prophylaxis; 1064 (80.7%) infants were tested for HIV by PCR and started on cotrimoxazole. Median age at PCR was 1.7 months (IQR, 1.5 to 2.5). Overall transmission at first PCR was 43/1047 (4.1%). Of the 43 infants with positive PCR results, 36 (83.7%) were enrolled in ART clinic and 33 (76.7%) were initiated on ART.

Conclusions: Case management and support by dedicated CHWs can create a continuum of longitudinal care in the PMTCT cascade and result in improved outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499848PMC
http://dx.doi.org/10.7448/IAS.15.4.17389DOI Listing
July 2012