High Parasitological Failure Rate of Visceral Leishmaniasis to Sodium Stibogluconate among HIV Co-infected Adults in Ethiopia

Background

Antimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern.

Objectives

This study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).

Methods

Retrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed.

Results

The study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues. High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7).

Conclusion

SSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region.     

Visceral Leishmaniasis and HIV Coinfection in East Africa

Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.     

An analysis of the complete strain field within Flexercell membranes

The purpose of the current investigation was to use finite element analysis to quantify the complete strain field for the membranes of the Flexercell^TM apparatus, a device extensively used to study the effects of mechanical loading on cultured cells. Four vacuum pressure simulations were run for the membrane for both the uniaxial and biaxial loading post, yielding the distribution of longitudinal (E_xx) and transverse (E_yy) strain for the uniaxial post, and the radial (E_rr) and the circumferential (E_θθ) strain for the biaxial post. The discrete values of each strain were evaluated at the center of the loading post as well as the region off of the post. Experimental measurements were made for both types of loading posts in order to validate our simulations. The biaxial post simulation was found to provide a central circular region of equal and constant E_rr and E_θθ in the membrane on the post. Likewise, the uniaxial post simulation provided a definitive region of constant E_xx for a central rectangular region on the post. For the uniaxial simulation, the region on the post resulted in small compressive E_yy, while the region off the post resulted in tensile E_yy. The biaxial simulation resulted in large tensile E_rr and E_θθ on the post, while the region off the post resulted in large E_rr and smaller E_θθ. Our simulations were reasonably consistent with the experimental measurements made for both types of loading posts. We believe that the results of this study will allow scientists to more accurately describe the response of cells to known strains on all portions of the membrane, thus increasing the range of known strain regions for investigation in the Flexercell^TM apparatus.     

Identification and functional characterization of nonmammalian Toll-like receptor 20

Like other vertebrate Toll-like receptors (TLRs), the TLRs of teleost fish can be subdivided into six major families, each of which recognize a general class of molecular patterns. However, there also are a number of Tlrs with unknown function, the presence of which seems unique to the bony fish, among which is Tlr20. We identified full-length complementary DNA (cDNA) sequences for tlr20 of zebrafish and common carp, two closely related fish species. Zebrafish have six copies of tlr20, whereas carp express only a single copy. Both zebrafish Tlr20 (at least Tlr20a–d) and carp Tlr20 have 26 leucine-rich repeats (LRRs). Three-dimensional modeling indicates a best fit to the crystal structure of TLR8. Phylogenetic analyses place Tlr20 in the TLR11 family closest to Tlr11 and Tlr12, which sense ligands from protozoan parasites in the mouse. Conservation of genes on zebrafish chromosome 9, which carries tlr20, with genes on mouse chromosome 14, which carries tlr11, indicates Tlr11 could be a possible ortholog of Tlr20. Confocal microscopy suggests a subcellular localization of Tlr20 at the endoplasmatic reticulum. Although in vitro reporter assays could not identify a ligand unique to Tlr20, in vivo infection experiments indicate a role for Tlr20 in the immune response of carp to protozoan parasites (Trypanoplasma borreli). Carp tlr20 is mainly expressed in peripheral blood leukocytes (PBL) with B lymphocytes, in particular, expressing relatively high levels of Tlr20. In vitro stimulation of PBL with T. borreli induces an upregulation of tlr20, supportive of a role for Tlr20 in the immune response to protozoan parasites.     

Weakened Resilience in Parenting Self-Efficacy in Pregnant Women Who Were Abused in Childhood: An Experimental Test

This study tested experimentally whether the combination of a history of childhood abuse and confrontation with difficult infant temperament is associated with negative changes in parenting self-efficacy. First-time pregnant women (N = 243) participated in the Adult Attachment Interview, which was used to assess the occurrence of abuse by parents in childhood and unresolved representations, and completed a task asking them to respond to infant cries. Sixty of the 243 participants (25%) experienced childhood abuse, mostly physical or sexual. The task simulated infant temperamental difficulty by manipulating soothing success in order to reflect an easy-to-soothe (80% soothing success) and a difficult-to-soothe infant (20% soothing success). Both after baseline and after each of the two stimulus series women assessed their parenting self-efficacy. Women who reported childhood abuse did not differ from women who reported no childhood abuse in parenting self-efficacy at baseline or in response to the easy-to-soothe infant (relative to baseline), but decreased more in parenting self-efficacy following the difficult-to-soothe infant. Effects did not vary according to resolution of trauma. These findings suggest that in response to infant temperamental difficulty, women who experienced childhood abuse may more easily lose confidence in their parenting abilities, which underlines the importance of preparing at-risk women for the possible challenges that come along with parenthood.     

Detoxification of Fusarium-contaminated maize with sodium sulphite – in vivo efficacy with special emphasis on mycotoxin residues and piglet health

A feeding experiment with piglets was performed to examine the efficacy of a wet preservation of Fusarium (FUS)-contaminated maize with sodium sulphite (SoS) based on deoxynivalenol (DON) and zearalenone (ZEN) residue levels in urine, bile and liquor and health traits of piglets. For this purpose, 80 castrated male piglets (7.57 ± 0.92 kg BW) were assigned to four treatment groups: CON? (control diet, with 0.09 mg DON and <0.01 mg ZEN/kg diet), CON+ (diet CON?, wet-preserved with 5 g SoS/kg maize; containing 0.05 mg DON and <0.01 mg ZEN/kg diet), FUS? (diet with mycotoxin-contaminated maize; containing 5.36 mg DON and 0.29 mg ZEN/kg diet), and FUS+ (diet FUS?, wet-preserved with 5 g SoS/kg maize; resulting in 0.83 mg DON and 0.27 mg ZEN/kg diet). After 42 d, 40 piglets (n = 10 per group) were sampled. A clear reduction of DON levels by approximately 75% was detected in all specimens of pigs fed diet FUS+. ZEN was detected in all urine, bile and liquor samples, while their metabolites were only detectable in urine and bile. Additionally, their concentrations were not influenced by SoS treatment. Among the health-related traits, feeding of FUS diets increased the total counts of leukocytes and segmented neutrophil granulocytes irrespective of SoS treatment. SoS treatment increased the total blood protein content slightly with a similar numerical trend in albumin concentration. These effects occurred at an obviously lower level in FUS-fed groups. Moreover, SoS treatment recovered the reduction of NO production induced by feeding diet FUS? indicating an effect on the redox level. As this effect only occurred in group FUS+, it is obviously related to the adverse effects of the Fusarium toxins. In conclusion, treatment of FUS-contaminated maize with SoS decreased the inner exposure with DON as indicated by the lower DON levels in various piglet specimens. However, health-related traits did not consistently reflect this decreased exposure.     

Benzyladenine effects on the development of the photosynthetic apparatus in Zea mays: Studies on photosynthetic activity, enzymes and (etio)chloroplast ultrastructure

Primary leaf segments from 8-day-old dark-grown, and from 4- and 8-day-old light-grown seedlings of Zea mays L. cv. Fronica, were treated with 10^-bM benzyladenine (BA) in the dark for 14 h. The segments were then studied after an exposure to light for 14 h. Photosynthetic activity (O₂ evolution and CO₂ fixation) and chlorophyll accumulation were stimulated by BA in dark-grown leaf segments with etioplastids in the earliest stage of development. In these segments BA stimulated the activities of ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39), phosphoenolpyruvate carboxylase (EC 4.1.1.31), NADP⁺-malic enzyme (EC 1.1.1.40) and pyruvate, orthophosphate dikinase (EC 2.7.9.1). In segments taken from 4- and 8-day light-grown seedlings, BA did not enhance the photosynthetic activity nor the chlorophyll accumulation. The activity of the enzymes mentioned above, was significantly enhanced by the BA-treatment. BA mainly affected grana stacking in mesophyll cell chloroplasts in primary leaf segments taken from 3- to 5-day light-grown seedlings. Stroma thylakoid development was stimulated only in leaf segments from 3-day-old plants. At the same time BA accelerated grana loss in chloroplasts of bundle sheath cells, a typical phenomenon of development in such chloroplasts. Stroma thylakoid length in these chloroplasts increased by a BA treatment in segments from 3- and 4-day light-grown plants. A significantly higher number of chloroplasts was only observed with segments taken from 8-day light-grown seedlings and treated with BA. The etiochloroplast number in segments taken from 8-day etiolated plants was significantly higher in BA-treated segments after 26 h illumination. In etiochloroplasts from both mesophyll and bundle sheath cells, BA enhanced grana stacking after illumination for 4 h or more, whereas stroma membrane length was significantly higher only after 26 h light. It is concluded that the effects of BA depend on the developmental stage. BA accelerates the development of mesophyll and bundle sheath cell (etio)chloroplasts, but does not affect the ultrastructure of mature chloroplasts.