Tenofovir Use and Renal Insufficiency among Pregnant and General Adult Population of HIV-infected, ART-Naïve Individuals in Lilongwe, Malawi

Background

The Malawian government recently changed its prevention of mother-to-child transmission (PMTCT) regimen and plans to change its first-line antiretroviral therapy (ART) regimen to Tenofovir(TDF)/Lamivudine/Efavirenz as a fixed-dose combination tablet. Implementation could be challenging if baseline creatinine clearance (CrCl) screening were required to assess renal function prior to TDF therapy. Our goal is to determine predictors of CrCl<50 ml/min among HIV-infected, ART-naïve individuals.

Methodology

Data on HIV-infected, ART-naïve adults screened for enrollment into 5 HIV clinical trials in Lilongwe, Malawi were combined for a pooled analysis of predictors for CrCl<50 ml/min. CrCl was derived from the Cockroft-Gault equation. Multivariable logistic regression modeled the association of age, body mass index (BMI), hemoglobin, CD4 cell count <350 cells/mm³, gender, and pregnancy with CrCl<50 ml/min.

Results

The analysis included 3508 patients with values for creatinine clearance. Most subjects were female (90.6%) with a median age of 26 years (IQR 22–29). The median CD4 cell count was 444 (IQR 298.0–561.0), and 85.2% percent of women in our study were pregnant. Few patients had CrCl<50 ml/min (n = 38, 1.1%). A BMI less than 18.5 in non-pregnant females (OR = 8.87, 95% CI = 2.45–32.09)) was associated with CrCl<50 ml/min. Hemoglobin level higher than 10 g/dL in males (OR = 0.69, 95% CI = 0.56–0.86) and non-pregnant females (OR = 0.21, 95% CI = 0.04–0.97) was protective against CrCl<50 ml/min.

Discussion

Our findings indicate few patients would be excluded from a TDF-based antiretroviral regimen, suggesting baseline creatinine clearance assessment may not be necessary for implementation. However, in ART settings individuals with low BMI or anemia could potentially be at increased risk for lower CrCl.     

Rapid Emergence of Multidrug Resistant,H58-Lineage Salmonella Typhi in Blantyre,Malawi

Introduction

Between 1998 and 2010, S. Typhi was an uncommon cause of bloodstream infection (BSI) in Blantyre, Malawi and it was usually susceptible to first-line antimicrobial therapy. In 2011 an increase in a multidrug resistant (MDR) strain was detected through routine bacteriological surveillance conducted at Queen Elizabeth Central Hospital (QECH).

Methods

Longitudinal trends in culture-confirmed Typhoid admissions at QECH were described between 1998–2014. A retrospective review of patient cases notes was conducted, focusing on clinical presentation, prevalence of HIV and case-fatality. Isolates of S. Typhi were sequenced and the phylogeny of Typhoid in Blantyre was reconstructed and placed in a global context.

Results

Between 1998–2010, there were a mean of 14 microbiological diagnoses of Typhoid/year at QECH, of which 6.8% were MDR. This increased to 67 in 2011 and 782 in 2014 at which time 97% were MDR. The disease predominantly affected children and young adults (median age 11 [IQR 6-21] in 2014). The prevalence of HIV in adult patients was 16.7% [8/48], similar to that of the general population (17.8%). Overall, the case fatality rate was 2.5% (3/94). Complications included anaemia, myocarditis, pneumonia and intestinal perforation. 112 isolates were sequenced and the phylogeny demonstrated the introduction and clonal expansion of the H58 lineage of S. Typhi.

Conclusions

Since 2011, there has been a rapid increase in the incidence of multidrug resistant, H58-lineage Typhoid in Blantyre. This is one of a number of reports of the re-emergence of Typhoid in Southern and Eastern Africa. There is an urgent need to understand the reservoirs and transmission of disease and how to arrest this regional increase.     

Oxidation and Structural Modification of Full-Fat and Defatted Flour Based Soy Protein Isolates Induced by Natural and Synthetic Extraction Chemicals

Soy protein has been extracted and differently treated to yield products of diverse desirable characteristics. Generally, synthetic chemicals (NaOH and HCl) are used to extract the protein from n-hexane-defatted soy flour (DF). Some researchers have tried to extract it from full-fat flour (FF) using natural chemicals (NC) in response to the ever-increasing consumer preference for naturally processed foods. The effects of these chemicals on the structure of the resultant protein product are not known. This study examined oxidative and structural modification effects of NC and SC as they interact with proteins in the DF and FF systems. Significant differences (p?<?0.01) were observed in all samples in lipoxygenase activity, degree of oxidation, free and total sufhydryl content and intrinsic fluorescence, which indicated increased structural changes in the FF-based samples as compared to those prepared from DF. Circular dichroism spectroscopy showed existence of α-helices and β-sheets protein secondary structures. However, DF samples showed increase in unordered structural conformation changes than the FF sample. Surface hydrophobicity and size exclusion chromatography results were more related to the extraction chemicals than the type of flour used, with samples prepared with SC showing an increase. That’s, the use of natural and synthetic protein extraction chemicals from FF and DF have different effects on the structure and degree of oxidation of the resultant proteins.