Health Indicators of Pregnant Women in Tonkolili District, Rural Sierra Leone

Despite having reported one of the highest maternal mortality ratios and neonatal mortality rates in the world, surprisingly little is known about the general health status of pregnant women in rural parts of Sierra Leone. Malaria, anaemia and malnutrition are known contributors to adverse pregnancy outcomes. Although their prevalence is known to be high, the burden of these conditions in the rural pregnant population remains unknown. Our study aimed to gain more insight into the health status of pregnant women. An observational retrospective descriptive study was conducted at the Lion Heart Medical Centre using antenatal care (ANC) registers. The study revealed high prevalence of malaria (35.2%), maternal undernutrition (10.4%) and anaemia (65.9%). The proportion of teenage pregnancies in the ANC population was 16.4%. Both malaria and anaemia were more prevalent in this group, with odds ratios of 2.1 and 1.7, respectively. The findings reveal alarming high rates of anaemia, acute undernutrition and malaria among pregnant women and high numbers of pregnancy among adolescents, with increased health risks. These results will be used to advocate for a malnutrition program, specifically for pregnant women. Our study further emphasises the importance of preventing malaria and anaemia in pregnant women

Evolution of Mammalian Chitinase(-Like) Members of Family 18 Glycosyl Hydrolases

Family 18 of glycosyl hydrolases encompasses chitinases and so-called chi-lectins lacking enzymatic activity due to amino acid substitutions in their active site. Both types of proteins widely occur in mammals although these organisms lack endogenous chitin. Their physiological function(s) as well as evolutionary relationships are still largely enigmatic. An overview of all family members is presented and their relationships are described. Molecular phylogenetic analyses suggest that both active chitinases (chitotriosidase and AMCase) result from an early gene duplication event. Further duplication events, followed by mutations leading to loss of chitinase activity, allowed evolution of the chi-lectins. The homologous genes encoding chitinase(-like) proteins are clustered in two distinct loci that display a high degree of synteny among mammals. Despite the shared chromosomal location and high homology, individual genes have evolved independently. Orthologs are more closely related than paralogues, and calculated substitution rate ratios indicate that protein-coding sequences underwent purifying selection. Substantial gene specialization has occurred in time, allowing for tissue-specific expression of pH optimized chitinases and chi-lectins. Finally, several family 18 chitinase-like proteins are present only in certain lineages of mammals, exemplifying recent evolutionary events in the chitinase protein family

The biology of the Gaucher cell: the cradle of human chitinases

Gaucher disease (GD) is the most common lysosomal storage disorder and is caused by inherited deficiencies of glucocerebrosidase, the enzyme responsible for the lysosomal breakdown of the lipid glucosylceramide. GD is characterized by the accumulation of pathological, lipid laden macrophages, so-called Gaucher cells. Following the development of enzyme replacement therapy for GD, the search for suitable surrogate disease markers resulted in the identification of a thousand-fold increased chitinase activity in plasma from symptomatic Gaucher patients and that decreases upon successful therapeutic intervention. Biochemical investigations identified a single enzyme, named chitotriosidase, to be responsible for this activity. Chitotriosidase was found to be an excellent marker for lipid laden macrophages in Gaucher patients and is now widely used to assist clinical management of patients. In the wake of the identification of chitotriosidase, the presence of other members of the chitinase family in mammals was discovered. Amongst these is AMCase, an enzyme recently implicated in the pathogenesis of asthma. Chitinases are omnipresent throughout nature and are also produced by vertebrates in which they play important roles in defence against chitin-containing pathogens and in food processin

Detection of chitinase activity by 2-aminobenzoic acid labeling of chito-oligosaccharides

Chitinases are hydrolases capable of hydrolyzing the abundant natural polysaccharide chitin. Next to artificial fluorescent substrates, more physiological chito-oligomers are commonly used in chitinase assays. Analysis of chito-oligosaccharides products is generally accomplished by UV detection. However, the relatively poor sensitivity poses a serious limitation. Here we report on a novel, much more sensitive assay for the detection of chito-oligosaccharide reaction products released by chitinases, based on fluorescent detection, following chemical labeling by 2-aminobenzoic acid. Comparison with existing UV-based assays, shows that the novel assay offers the same advantages yet allows detection of chito-oligosaccharides in the low picomolar range. (C) 2008 Elsevier Inc. All rights reserve

Marked differences in tissue-specific expression of chitinases in mouse and man

Two distinct chitinases have been identified in mammals: a phagocyte-specific enzyme named chitotriosidase and an acidic mammalian chitinase (AMCase) expressed in the lungs and gastrointestinal tract. Increased expression of both chitinases has been observed in different pathological conditions: chitotriosidase in lysosomal lipid storage disorders like Gaucher disease and AMCase in asthmatic lung disease. Recently, it was reported that AMCase activity is involved in the pathogenesis of asthma in an induced mouse model. Inhibition of chitinase activity was found to alleviate the inflammation-driven pathology. We studied the tissue-specific expression of both chitinases in mice and compared it to the situation in man. In both species AMCase is expressed in alveolar macrophages and in the gastrointestinal tract. In mice, chitotriosidase is expressed only in the gastrointestinal tract, the tongue, fore-stomach, and Paneth cells in the small intestine, whereas in man the enzyme is expressed exclusively by professional phagocytes. This species difference seems to be mediated by distinct promoter usage. In conclusion, the pattern of expression of chitinases in the lung differs between mouse and man. The implications for the development of anti-asthma drugs with chitinases as targets are discusse

Suboptimal Viral Suppression Rates Among HIV-Infected Children in Low- and Middle-Income Countries: A Meta-analysis

The 90-90-90 goal to achieve viral suppression in 90% of all human immunodeficiency virus (HIV)-infected people on antiretroviral treatment (ART) is especially challenging in children. Global estimates of viral suppression among children in low- and middle-income countries (LMICs) are lacking.  We searched for randomized controlled trials and observational studies and analyzed viral suppression rates among children started on ART during 3 time periods: early (2000-2005), intermediate (2006-2009), and current (2010 and later), using random effects meta-analysis.  Seventy-two studies, reporting on 51 347 children (aged <18 years), were included. After 12 months on first-line ART, viral suppression was achieved by 64.7% (95% confidence interval [CI], 57.5-71.8) in the early, 74.2% (95% CI, 70.2-78.2) in the intermediate, and 72.7% (95% 62.6-82.8) in the current time period. Rates were similar after 6 and 24 months of ART. Using an intention-to-treat analysis, 42.7% (95% CI, 33.7-51.7) in the early, 45.7% (95% CI, 33.2-58.3) in the intermediate, and 62.5% (95% CI, 53.3-72.6) in the current period were suppressed. Long-term follow-up data were scarce.  Viral suppression rates among children on ART in LMICs were low and considerably poorer than those previously found in adults in LMICs and children in high-income countries. Little progress has been made in improving viral suppression rates over the past years. Without increased efforts to improve pediatric HIV treatment, the 90-90-90 goal for children in LMIC will not be reache

Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity

Man has been found to produce highly conserved chitinases. The most prominent is the phagocyte-derived chitotriosidase, the plasma levels of which are markedly elevated in some pathological conditions. Here, we report that both polymorphonuclear neutrophils (PMNs) and macrophages (m phi) are a source of chitotriosidase. The enzyme is located in specific granules of human PMNs and secreted following stimulation with granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, GM-CSF induces expression of chitotriosidase in m phi that constitutively secrete the enzyme and partly accumulate it in their lysosomes. Studies with recombinant human chitotriosidase revealed that the enzyme targets chitin-containing fungi. These findings are consistent with earlier observations concerning anti-fungal activity of homologous plant chitinases and beneficial effects of GM-CSF administration in individuals suffering from invasive fungal infections. In conclusion, chitotriosidase should be viewed as a component of the innate immunity that may play a role in defence against chitin-containing pathogens and the expression and release of which by human phagocytes is highly regulate