Ultrasound evidence of early fetal growth restriction after maternal malaria infection

Background

Intermittent preventive treatment (IPT), the main strategy to prevent malaria and reduce anaemia and low birthweight, focuses on the second half of pregnancy. However, intrauterine growth restriction may occur earlier in pregnancy. The aim of this study was to measure the effects of malaria in the first half of pregnancy by comparing the fetal biparietal diameter (BPD) of infected and uninfected women whose pregnancies had been accurately dated by crown rump length (CRL) before 14 weeks of gestation.

Methodology/Principal Findings

In 3,779 women living on the Thai-Myanmar border who delivered a normal singleton live born baby between 2001–10 and who had gestational age estimated by CRL measurement <14 weeks, the observed and expected BPD z-scores (<24 weeks) in pregnancies that were (n = 336) and were not (n = 3,443) complicated by malaria between the two scans were compared. The mean (standard deviation) fetal BPD z-scores in women with Plasmodium (P) falciparum and/or P.vivax malaria infections were significantly lower than in non-infected pregnancies; −0.57 (1.13) versus −0.10 (1.17), p<0.001. Even a single or an asymptomatic malaria episode resulted in a significantly lower z-score. Fetal female sex (p<0.001) and low body mass index (p = 0.01) were also independently associated with a smaller BPD in multivariate analysis.

Conclusions/Significance

Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy.     

Effect of malaria in pregnancy on foetal cortical brain development: a longitudinal observational study

ABSTRACT: BACKGROUND: Malaria in pregnancy has a negative impact on foetal growth, but it is not known whether this also affects the foetal nervous system. The aim of this study was to examine the effects of malaria on foetal cortex development by three-dimensional ultrasound. METHODS: Brain images were acquired using a portable ultrasound machine and a 3D ultrasound transducer. All recordings were analysed, blinded to clinical data, using the 4D view software package. The foetal supra-tentorial brain volume was determined and cortical development was qualitatively followed by scoring the appearance and development of six sulci. Multilevel analysis was used to study brain volume and cortical development in individual foetuses, RESULTS: Cortical grading was possible in 161 out of 223 (72%) serial foetal brain images in pregnant women living in a malaria endemic area. There was no difference between foetal cortical development or brain volumes at any time in pregnancy between women with immediately treated malaria infections and non-infected pregnancies. CONCLUSION: The percentage of images that could be graded was similar to other neuro-sonographic studies. Maternal malaria does not have a gross effect on foetal brain development, at least in this population, which had access to early detection and effective treatment of malaria.     

HLA-DRB1 and HLA-DQB1 Are Associated with Adult-Onset Immunodeficiency with Acquired Anti-Interferon-Gamma Autoantibodies

Recently a newly identified clinical syndrome of disseminated non-tuberculous mycobacterial diseases (with or without other opportunistic infections in adult patients who were previously healthy, has been recognized in association with an acquired autoantibody to interferon-gamma. This syndrome is emerging as an important cause of morbidity and mortality, especially among people of Asian descent. Trigger for the production of this autoantibody remains unknown, but genetic factors are strongly suspected to be involved. We compared HLA genotyping between 32 patients with this clinical syndrome, and 38 controls. We found that this clinical syndrome was associated with very limited allele polymorphism, with HLA-DRB1 and DQB1 alleles, especially HLA-DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02. Odds ratio of DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02 were 7.03 (95% CI, 2.18–22.69, P<0.0001, 9.06 (95% CI, 2.79–29.46, P<0.0001), 6.68 (95% CI, 2.29–19.52, P = 0.0004), and 6.64 (95% CI, 2.30–19.20, P = 0.0004), respectively. Further investigation is warranted to provide better understanding on pathogenesis of this association.     

Digital PCR to Detect and Quantify Heteroresistance in Drug Resistant Mycobacterium tuberculosis

Drug resistance in Mycobacterium tuberculosis presents an enormous public health threat. It is typically defined as >1% of drug resistant colonies using the agar proportion method. Detecting small numbers of drug resistant Tb in a population, also known as heteroresistance, is challenging with current methodologies. Here we have utilized digital PCR to detect heteroresistance within M. tuberculosis populations with excellent accuracy versus the agar proportion method. We designed dual TaqMan-MGB probes to detect wild-type and mutant sequences of katG (315), rpoB (531), gyrA (94,95) and rrs (1401), genes that associate with resistance to isoniazid, rifampin, fluoroquinolone, and aminoglycoside respectively. We generated heteroresistant mixtures of susceptible and extensively drug resistant Tb, followed by DNA extraction and digital PCR. Digital PCR yielded a close approximation to agar proportion''s percentages of resistant colonies, and yielded 100% concordance with agar proportion''s susceptible/resistant results. Indeed, the digital PCR method was able to identify mutant sequence in mixtures containing as little as 1000∶1 susceptible:resistant Tb. By contrast, real-time PCR or PCR followed by Sanger sequencing were less sensitive and had little resolution to detect heteroresistance, requiring fully 1∶1 or 10∶1 susceptible:resistant ratios in order to detect resistance. Our assay can also work in sputum so long as sufficient quantities of Tb are present (>1000 cfu/ml). This work demonstrates the utility of digital PCR to detect and quantify heteroresistance in drug resistant Tb, which may be useful to inform treatment decisions faster than agar proportion.     

Thermostable mannose-binding lectin from Dendrobium findleyanum with activities dependent on sulfhydryl content

A mannose-binding lectin was purified from Dendrobium (D.) findleyanum pseudobulb using mannan-agarose column chromatography. After heating in the presence of SDS with or without 2-mercaptoethanol on SDS-PAGE with a continuous gradient of 8%-20% acrylamide, the purified lectin showed only one protein band with a molecular mass of 14.5 kDa. Without heating, two bands were seen on the gel at the positions of 14.5 kDa and 53.7 kDa, but a higher amount of the 53.7 kDa protein was observed in the presence of 2-mercaptoethanol. Protein identification of both protein bands by liquid chromatography-tandem mass spectrometry showed three peptide fragments identical to parts of a lectin precursor from D. officinale; the lectin was named D. findleyanum agglutinin (DFA). Using various concentrations of native-PAGE and Ferguson plot, only one protein band revealed a molecular mass of 56.2 kDa, indicating four 14.5 kDa polypeptide subunits in the DFA. Isoelectric focusing revealed that the DFA had three conformational forms with an isoelectric point of 5.18, 4.87 and 4.72, whereas 2-mercaptoethanol-treated DFA showed only one band with an isoelectric point of 5.18. DFA exhibited specificity towards mannose using the solid-phase method. The binding activity, anti-fungal activity and hemagglutination activity of DFA were not affected by heat, but were increased by free sulfhydryl groups.     

Multi-probe Real-Time PCR Identification of Four Common Candida Species in Blood Culture Broth

We developed a single-tube real-time polymerase chain reaction (PCR) assay with multiple hybridization probes for detecting Candida albicans, C. tropicalis, C. glabrata, and C. parapsilosis. Primers were designed to amplify 18S rRNA gene of the genus Candida, and DNA probes were designed to hybridize two areas of the amplicons. The amplification curves and specific melting peaks of the probes hybridized with PCR product were used for definite species identifications. The reaction specificity was 100 % when evaluating the assay using DNA samples from 21 isolates of fungal and bacterial species. The assay was further evaluated in 129 fungal blood culture broth samples which were culture positive for fungus. Of the 129 samples, 119 were positively identified as: C. albicans (39), C. tropicalis (30), C. parapsilosis (23), C. glabrata (20), Candida spp. (5), and two samples containing mixed C. glabrata/C. albicans and C. glabrata/C. tropicalis. The five Candida spp. were identified by sequencing analysis as C. krusei, C. dubliniensis, C. aquaetextoris, and two isolates of C. athensensis. Of the ten samples which showed negative PCR results, six were Cryptococcus neoformans, and the others were Trichosporon sp., Rhodotorula sp., Fusarium sp., and Penicillium marneffei. Our findings show that the assay was highly effective in identifying the four medically important Candida species. The results can be available within 3 h after positivity of a blood culture broth sample.     

Differences of skin morphology in Bos indicus,Bos taurus,and their crossbreds

Cutaneous evaporation is the main avenue by which cattle dissipate heat via the involvement of sweat glands and other skin components. The difference in skin morphology between B. indicus and B. taurus has been recognized, as well as differences in their ability to tolerate heat. The objective of this study was to compare skin morphology between B. indicus, B. taurus, and their crossbreds. Skin samples of Sahiwal (B. indicus) (n?=?10, reddish brown skin) and Holstein Friesian (HF) (B. taurus) (n?=?10, black and white skin) and crossbred of HF75% (n?=?10, black and white skin) and HF87.5 % (n?=?10, black and white skin) were biopsied for histological study, followed by measurement of skin components. The results indicated that breed significantly affected sweat gland morphology. The shape of the sweat gland, as indicated by the ratio of length/diameter, in Sahiwal was baggier in shape compared to HF (5.99 and 9.52) while values for crossbreds were intermediate (7.82, 8.45). The density and volume of sweat glands in Sahiwal (1,058 glands/cm²; 1.60 μ³?×?10^?6) were higher than in HF (920 glands/cm²; 0.51 μ³x10^?6) and crossbreds, both HF 75 % (709 glands/cm²; 0.68 μ³?×?10^?6) and HF 87.5 % (691 glands/cm²; 0.61 μ³?×?10^?6) respectively. However, capillary surface area was greater for HF (2.07 cm²) compared to Sahiwal (1.79 cm²); accordingly, the lower genetic fraction of HF in crossbred cattle showed less capillary surface area (1.83 and 1.9 cm² for HF75% and HF87.5 %) (P?<?0.01). Nerve density was not significantly different between Sahiwal and HF but was higher in the crossbred (P?<?0.01) cattle. Moreover, the effect of skin color (black and white) was evaluated and it was found that there was an interaction (P?<?0.01) between breed and skin color on the skin components. This study reveals that there are differences in skin morphology among B. indicus, B. taurus and their crossbreds, with these differences being more or less related to the genetic fraction of HF. This may imply that capability for cutaneous evaporative heat loss and tolerance to heat in crossbred cattle could be related to skin morphology.     

Dynamics of dissolved O2, CO2, CH4, and N2O in a tropical coastal swamp in southern Thailand

We studied the distribution of dissolved O₂, CO₂, CH₄, and N₂O in a coastal swamp system in Thailand with the goal to characterize the dynamics of these gases within the system. The gas concentrations varied spatially and seasonally in both surface and ground waters. The entire system was a strong sourcefor CO₂ and CH₄, and a possible sink for atmospheric N₂O. Seasonal variation in precipitation primarily regulated the redox conditions in the system. However, distributions of CO₂, CH₄, and N₂O in the river that received swamp waters were not always in agreement with redox conditions indicated by dissolvedO₂ concentrations. Sulfate production through pyriteoxidation occurred in the swamp with thin peat layerunder aerobic conditions and was reflected by elevatedSO ₄ ^2– /Cl^– in the river water. When SO ₄ ^2– /Cl^– was high, CO₂ and CH₄ concentrations decreased, whereas the N₂O concentration increased. The excess SO ₄ ^2– in the river water was thus identified as a potential indicator for gas dynamics in this coastal swamp system.