Clinical evaluation for morbidity associated with soil-transmitted helminth infection in school-age children on Pemba Island, Tanzania.

BACKGROUND: More than 1.5 billion people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, and Trichuris trichiura), causing an estimated global burden in excess of 3 million disability-adjusted life years. However, the relationship between soil-transmitted helminth infection, adverse health consequences, and beneficial effects of deworming are not well understood. METHODOLOGY: We pursued a detailed longitudinal clinical evaluation of school-age children to evaluate morbidity associated with soil-transmitted helminth infection and responses to treatment. This exploratory study was embedded into a randomized controlled trial. Overall, 434 children, aged 7-14 years, underwent a detailed medical history, physical examination, stool microscopy for soil-transmitted helminths, and hemoglobin (Hb) measurement at baseline. Medical history and stool examination were repeated at 3 and 18 weeks posttreatment. Additionally, Hb measurement was performed at the 18-week treatment follow-up. Logistic regression was employed to assess clinical factors associated with soil-transmitted helminth infection at baseline, and longitudinal data analysis to examine change in health outcomes following treatment over time. PRINCIPAL FINDINGS: All enrolled children were infected with T. trichiura, and randomized into four different treatment interventions. None of the medical history, physical examination, and laboratory (i.e., Hb) findings were associated with A. lumbricoides, hookworm, or S. stercoralis infection at baseline. A composite of physical exam findings for anemia, including pallor of the conjunctiva, nail beds, and palmar creases predicted lower Hb values (-3.8 g/dl, 95% confidence interval (CI): -6.9, -0.6 g/dl). When examining longitudinal trends, we did not find improvements to Hb or face Wong-Baker Likert scale among children with soil-transmitted helminth infection compared to those without infection, although there was a slight trend toward improving Hb values after treating hookworm infection. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates the challenges of measuring morbidity in the context of soil-transmitted helminth infection and treatment, thus confirming the mainly subtle morbidity effects of infection.

Effect of sanitation and water treatment on intestinal protozoa infection: a systematic review and meta-analysis.

BACKGROUND: Pathogenic intestinal protozoa infections are responsible for substantial mortality and morbidity, particularly in settings where people lack improved sanitation and safe drinking water. We assessed the relation between access to, and use of, sanitation facilities and water treatment and infection with intestinal protozoa. METHODS: We did a systematic review and searched PubMed, ISI Web of Science, and Embase from inception to June 30, 2014, without restrictions on language. All publications were examined by two independent reviewers and were included if they presented data at the individual level about access or use of sanitation facilities or water treatment, in combination with individual-level data on human intestinal protozoa infections. Meta-analyses using random effects models were used to calculate overall estimates. FINDINGS: 54 studies were included and odds ratios (ORs) extracted or calculated from 2 × 2 contingency tables. The availability or use of sanitation facilities was associated with significantly lower odds of infection with Entamoeba histolytica or Entamoeba dispar (OR 0·56, 95% CI 0·42-0·74) and Giardia intestinalis (0·64, 0·51-0·81), but not for Blastocystis hominis (1·03, 0·87-1·23), and Cryptosporidium spp (0·68, 0·17-2·68). Water treatment was associated with significantly lower odds of B hominis (0·52, 0·34-0·78), E histolytica or E dispar (0·61, 0·38-0·99), G intestinalis (0·63, 0·50-0·80), and Cryptosporidium spp infections (0·83, 0·70-0·98). INTERPRETATION: Availability and use of sanitation facilities and water treatment is associated with lower odds of intestinal protozoa infections. Interventions that focus on water and sanitation, coupled with hygiene behaviour, should be emphasised to sustain the control of intestinal protozoa infections. FUNDING: Swiss National Science Foundation (project numbers PBBSP3-146869 and P300P3-154634), Medicor Foundation, European Research Council (614739-A_HERO).

The roles of water, sanitation and hygiene in reducing schistosomiasis: a review.

Schistosomiasis is a disease caused by infection with blood flukes of the genus Schistosoma. Transmission of, and exposure to, the parasite result from faecal or urinary contamination of freshwater containing intermediate host snails, and dermal contact with the same water. The World Health Assembly resolution 65.21 from May 2012 urges member states to eliminate schistosomiasis through preventive chemotherapy (i.e. periodic large-scale administration of the antischistosomal drug praziquantel to school-aged children and other high-risk groups), provision of water, sanitation and hygiene (WASH) and snail control. However, control measures focus almost exclusively on preventive chemotherapy, while only few studies made an attempt to determine the impact of upgraded access to safe water, adequate sanitation and good hygiene on schistosome transmission. We recently completed a systematic review and meta-analysis pertaining to WASH and schistosomiasis and found that people with safe water and adequate sanitation have significantly lower odds of a Schistosoma infection. Importantly though, the transmission of schistosomiasis is deeply entrenched in social-ecological systems, and hence is governed by setting-specific cultural and environmental factors that determine human behaviour and snail populations. Here, we provide a comprehensive review of the literature, which explores the transmission routes of schistosomes, particularly focussing on how these might be disrupted with WASH-related technologies and human behaviour. Additionally, future research directions in this area are highlighted.

The relationship between water, sanitation and schistosomiasis: a systematic review and meta-analysis.

BACKGROUND: Access to "safe" water and "adequate" sanitation are emphasized as important measures for schistosomiasis control. Indeed, the schistosomes' lifecycles suggest that their transmission may be reduced through safe water and adequate sanitation. However, the evidence has not previously been compiled in a systematic review. METHODOLOGY: We carried out a systematic review and meta-analysis of studies reporting schistosome infection rates in people who do or do not have access to safe water and adequate sanitation. PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 31 December 2013, without restrictions on year of publication or language. Studies' titles and abstracts were screened by two independent assessors. Papers deemed of interest were read in full and appropriate studies included in the meta-analysis. Publication bias was assessed through the visual inspection of funnel plots and through Egger's test. Heterogeneity of datasets within the meta-analysis was quantified using Higgins' I2. PRINCIPAL FINDINGS: Safe water supplies were associated with significantly lower odds of schistosomiasis (odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.47-0.61). Adequate sanitation was associated with lower odds of Schistosoma mansoni, (OR = 0.59, 95% CI: 0.47-0.73) and Schistosoma haematobium (OR = 0.69, 95% CI: 0.57-0.84). Included studies were mainly cross-sectional and quality was largely poor. CONCLUSIONS/SIGNIFICANCE: Our systematic review and meta-analysis suggests that increasing access to safe water and adequate sanitation are important measures to reduce the odds of schistosome infection. However, most of the studies were observational and quality was poor. Hence, there is a pressing need for adequately powered cluster randomized trials comparing schistosome infection risk with access to safe water and adequate sanitation, more studies which rigorously define water and sanitation, and new research on the relationships between water, sanitation, hygiene, human behavior, and schistosome transmission.

A fundamental trade-off in covalent switching and its circumvention by enzyme bifunctionality in glucose homeostasis.

Covalent modification provides a mechanism for modulating molecular state and regulating physiology. A cycle of competing enzymes that add and remove a single modification can act as a molecular switch between "on" and "off" and has been widely studied as a core motif in systems biology. Here, we exploit the recently developed "linear framework" for time scale separation to determine the general principles of such switches. These methods are not limited to Michaelis-Menten assumptions, and our conclusions hold for enzymes whose mechanisms may be arbitrarily complicated. We show that switching efficiency improves with increasing irreversibility of the enzymes and that the on/off transition occurs when the ratio of enzyme levels reaches a value that depends only on the rate constants. Fluctuations in enzyme levels, which habitually occur due to cellular heterogeneity, can cause flipping back and forth between on and off, leading to incoherent mosaic behavior in tissues, that worsens as switching becomes sharper. This trade-off can be circumvented if enzyme levels are correlated. In particular, if the competing catalytic domains are on the same protein but do not influence each other, the resulting bifunctional enzyme can switch sharply while remaining coherent. In the mammalian liver, the switch between glycolysis and gluconeogenesis is regulated by the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2). We suggest that bifunctionality of PFK-2/FBPase-2 complements the metabolic zonation of the liver by ensuring coherent switching in response to insulin and glucagon.