Retention in Care of HIV-Infected Children from HIV Test to Start of Antiretroviral Therapy: Systematic Review

Background

In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined.

Methods

We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate.

Results

Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years.

Conclusion

Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.     

Mycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic host lysolipids

The pathogen Mycobacterium tuberculosis (M.tb) resides in human macrophages, wherein it exploits host lipids for survival. However, little is known about the interaction between M.tb and macrophage plasmalogens, a subclass of glycerophospholipids with a vinyl ether bond at the sn-1 position of the glycerol backbone. Lysoplasmalogens, produced from plasmalogens by hydrolysis at the sn-2 carbon by phospholipase A₂, are potentially toxic but can be broken down by host lysoplasmalogenase, an integral membrane protein of the YhhN family that hydrolyzes the vinyl ether bond to release a fatty aldehyde and glycerophospho-ethanolamine or glycerophospho-choline. Curiously, M.tb encodes its own YhhN protein (MtbYhhN), despite having no endogenous plasmalogens. To understand the purpose of this protein, the gene for MtbYhhN (Rv1401) was cloned and expressed in Mycobacterium smegmatis (M.smeg). We found the partially purified protein exhibited abundant lysoplasmalogenase activity specific for lysoplasmenylethanolamine or lysoplasmenylcholine (pLPC) (V_max∼15.5 μmol/min/mg; K_m∼83 μM). Based on cell density, we determined that lysoplasmenylethanolamine, pLPC, lysophosphatidylcholine, and lysophosphatidylethanolamine were not toxic to M.smeg cells, but pLPC and LPC were highly toxic to M.smeg spheroplasts, which are cell wall–deficient mycobacterial forms. Importantly, spheroplasts prepared from M.smeg cells overexpressing MtbYhhN were protected from membrane disruption/lysis by pLPC, which was rapidly depleted from the media. Finally, we found that overexpression of full-length MtbYhhN in M.smeg increased its survival within human macrophages by 2.6-fold compared to vector controls. These data support the hypothesis that MtbYhhN protein confers a growth advantage for mycobacteria in macrophages by cleaving toxic host pLPC into potentially energy-producing products.     

Malnutrition,anemia, micronutrient deficiency and parasitic infections among schoolchildren in rural Tanzania

BackgroundMalnutrition, anemia, micronutrient deficiency and parasitic infections continue to impact the nutritional status and health of children in lower-income countries. However, not enough data concerning this issue is available. The aim of this study was to assess the distribution of nutritional indicators, anemia and micronutrient deficiency and their underlying risk factors among schoolchildren in south-eastern Tanzania.Methodology/Principal findingsThis cross-sectional study enrolled primary schoolchildren aged 6–12 years from Kikwawila and Kiberege wards, Tanzania. In total, 471 schoolchildren underwent a physical examination and provided blood, stool and urine samples for an assessment of the levels of different micronutrients, nutritional and anemia status, and parasitic infection status. We employed bivariate and multivariate logistic regression to determine the association between nutritional statuses, anemia, micronutrient deficiency and parasitic infections. We found that 23.90%, 12.60% and 16.20% of schoolchildren were stunted, underweight and wasted, respectively. About 14.0% of schoolchildren were found to be anemic. Children diagnosed with Plasmodium falciparum infection were more likely to have low levels of ferritin (aOR: 10.40, 95% CI: 2.88-40.53) and elevated levels of serum soluble transferrin receptor (aOR: 3.59, 95% CI: 1.27-11.23), respectively. Vitamin A (34.71%) and vitamin B12 (8.79%) were the most prevalent micronutrients found to be deficient in diagnosed children. Finally, we found that schoolchildren attending the most rural schools were five times more likely to be diagnosed with at least one micronutrient deficiency (aOR: 5.04, 95% CI: 2.38–11.44).Conclusions/SignificanceMalnutrition, anemia and micronutrient deficiency still pose a significant health burden among schoolchildren living in rural Tanzania. To effectively tackle this burden, health interventions such as deworming, micronutrient supplementation, vector control, health education and access to clean water and improved sanitation should be strengthened and made sustainable.     

G-quadruplexes in helminth parasites

Parasitic helminths infecting humans are highly prevalent infecting ∼2 billion people worldwide, causing inflammatory responses, malnutrition and anemia that are the primary cause of morbidity. In addition, helminth infections of cattle have a significant economic impact on livestock production, milk yield and fertility. The etiological agents of helminth infections are mainly Nematodes (roundworms) and Platyhelminths (flatworms). G-quadruplexes (G4) are unusual nucleic acid structures formed by G-rich sequences that can be recognized by specific G4 ligands. Here we used the G4Hunter Web Tool to identify and compare potential G4 sequences (PQS) in the nuclear and mitochondrial genomes of various helminths to identify G4 ligand targets. PQS are nonrandomly distributed in these genomes and often located in the proximity of genes. Unexpectedly, a Nematode, Ascaris lumbricoides, was found to be highly enriched in stable PQS. This species can tolerate high-stability G4 structures, which are not counter selected at all, in stark contrast to most other species. We experimentally confirmed G4 formation for sequences found in four different parasitic helminths. Small molecules able to selectively recognize G4 were found to bind to Schistosoma mansoni G4 motifs. Two of these ligands demonstrated potent activity both against larval and adult stages of this parasite.     

A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma

BACKGROUND: Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. METHODS: We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. RESULTS: Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%-100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%-100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07). CONCLUSION: Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma.     

Prevalence and intensity of avian malaria in a quail hybrid zone

Hybrid zones have been described as natural laboratories by researchers who study speciation and the various mechanisms that may affect gene flow. The evolutionary consequences of hybridization depend not only on reproductive compatibility between sympatric species, but also on factors like vulnerability to each other''s predators and parasites. We examined infection patterns of the blood parasite Haemoproteus lophortyx, a causative agent of avian malaria, at a site in the contact zone between California quail (Callipepla californica) and Gambel''s quail (C. gambelii). Controlling for the potential influence of sex and year, we tested whether species identity predicted infection status and intensity. We found that infection prevalence was lower in California and hybrid quail compared with Gambel''s quail. However, infected California and hybrid quail had higher infection intensities than Gambel''s quail. California and hybrid quail exhibited no significant differences in prevalence or intensity of infection. These findings suggest that infection by H. lophortyx has the potential to influence species barrier dynamics in this system; however, more work is necessary to determine the exact evolutionary consequences of this blood parasite on hybridization.     

Food-borne trematodiasis: current chemotherapy and advances with artemisinins and synthetic trioxolanes

Over 40 million people are infected with food-borne trematodes and 750 million are at risk of food-borne trematodiasis, and yet this tropical disease is neglected. The current arsenal for the treatment and control of food-borne trematodiasis comprises praziquantel and triclabendazole, which were developed 20-30 years ago. The safety, therapeutic profiles and concern about resistance of these two drugs are summarized here. Recent advances with the artemisinins, which are best known for their antimalarial and antischistosomal properties, and the synthetic trioxolanes in different trematode-rodent models are reviewed. Lastly, prospects for the development of a safe, efficacious, inexpensive and broad-spectrum trematocidal drug are considered.