Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load

Background and Aims

Despite the high prevalence of chronic hepatitis B (CHB) in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM) and two biochemical scores (FibroTest®, Fibrometer®) to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log₁₀ IU/mL and normal alanine aminotransferase (ALT) values.

Methods

LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB). Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring.

Results

225 patients were evaluated (84% male) and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7–13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT), and Fibrometer® (FM) using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis) and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively.

Conclusion

In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis.     

A systematic map of genetic variation in Plasmodium falciparum

Discovering novel genes involved in immune evasion and drug resistance in the human malaria parasite, Plasmodium falciparum, is of critical importance to global health. Such knowledge may assist in the development of new effective vaccines and in the appropriate use of antimalarial drugs. By performing a full-genome scan of allelic variability in 14 field and laboratory strains of P. falciparum, we comprehensively identified approximately 500 genes evolving at higher than neutral rates. The majority of the most variable genes have paralogs within the P. falciparum genome and may be subject to a different evolutionary clock than those without. The group of 211 variable genes without paralogs contains most known immunogens and a few drug targets, consistent with the idea that the human immune system and drug use is driving parasite evolution. We also reveal gene-amplification events including one surrounding pfmdr1, the P. falciparum multidrug-resistance gene, and a previously uncharacterized amplification centered around the P. falciparum GTP cyclohydrolase gene, the first enzyme in the folate biosynthesis pathway. Although GTP cyclohydrolase is not the known target of any current drugs, downstream members of the pathway are targeted by several widely used antimalarials. We speculate that an amplification of the GTP cyclohydrolase enzyme in the folate biosynthesis pathway may increase flux through this pathway and facilitate parasite resistance to antifolate drugs.     

Comparative analysis of QTLs affecting domestication traits between two domesticated x wild pearl millet ( Pennisetum glaucum L., Poaceae) crosses

Comparative mapping of Quantitative trait loci (QTLs) involved in domestication of adaptative syndrome traits of pearl millet was realized at the intra-specific level using two F(2) populations derived from domesticated ( Pennisetum glaucum ssp. glaucum) x wild ( Pennisetum glaucum ssp. monodii) crosses. The two domesticated parents analyzed differ in their geographical origins, agronomic characteristics and life cycles. In both populations, two regions of the genome were identified on linkage groups 6 and 7, that controlled most of the key morphological differences. The importance of these two linkage groups reveals their central role both in the developmental control of spikelet structure and in the domestication process of this crop. In contrast, QTLs involved in traits that are components of yield and measure differences in resource allocation (such as the shape of the spike, the number of spikes per plant and plant height) show a low level of correspondence among our two crosses. The results of the comparative mapping between cereals, although preliminary, reveal that genes involved in seed-shattering could correspond in maize, rice and sorghum. The evolutionary significance of our results, and especially the relationships between genome organization and cereal domestication, are discussed. The potential use of these results in pearl millet genetic-resources enhancement are presented.     

Genetic control of domestication traits in pearl millet (Pennisetum glaucum L., Poaceae)

Quantitative trait loci (QTLs) controlling the morphological differences between pearl millet (Pennisetum glaucum ssp. glaucum) and its wild ancestor (Pennisetum glaucum ssp. monodii, form mollissimum) were investigated in a cultivated/wild F₂ population by means of RFLP markers. The most critical adaptive changes resulting from the domestication process involved the spikelet structure: non-shedding seeds with reduced bracts and bristles and long involucral pedicel. Major differences also concerned characters describing the plant architecture, phenology and spike sizes. Many morphological differences could be attributed to the effect of a small number of loci with relatively large effects. These loci are mainly concentrated on four linkage groups (2, 5, 6 and 7). The loss of shedding ability, due to the absence of a functional abscission layer, is controlled by a single locus on linkage group 6 (al6). Genetic control of the other spikelet traits involved factors with large effects which are located in the region of linkage group 6 close to al6 and to an esterase gene, Esterase-E. Moreover, QTLs with large effects on plant and spike morphology traits such as plant height, number of spikes and weight of the spike were also mapped on linkage groups 6 and 7. This strong linkage of factors in the domestication syndrome may be involved in the maintenance of the phenotypic identity of wild and cultivated populations in sympatry. This result also brings new arguments in the understanding of the domestication process of this allogamous crop. Received: 8 March 1999 / Accepted: 29 April 1999     

Allozyme variation within and among populations of onion (Allium cepa L.) from West Africa

Local germplasm of onion (Allium cepa L.) in West Africa is threatened by extinction. Sixteen populations of onion collected in five countries in West Africa were investigated for isozyme polymorphism using four polymorphic enzyme systems (ADH, MDH, 6-PGDH and PGI) among nine enzyme systems assayed. This is the first report on the genetic diversity of local landraces of onion. The inheritance of two dimeric enzyme systems PGI and MDH was demonstrated using F₂ progeny arrays. The PGI system revealed a single locus with three alleles, and the MDH system revealed three loci with four alleles. Four polymorphic systems revealed nine alleles (adh-a1 and a2, mdh-c1 and c2, 6-pgdh-a1 and a2, and pgi-a1, a2 and a3) in the 16 local populations observed. The mean number of alleles per polymorphic locus was 2.25, and 67% of the alleles were present in all populations. Allele 6-pgdh-a2 was present in only two landraces (from Niger and Nigeria); it is considered to be a rare allele (frequency approximately 2%). Among the 16 populations, within-population diversity was greater (90%) than between-population diversity (10%). Genetic distance analyses showed an aggregate of all populations except for two, which originated from Nigeria, an English-speaking country. Received: 24 August 1995 / Accepted: 26 February 2001     

Phylogenetic diversity of indigenous cowpea bradyrhizobia from soils in Japan based on sequence analysis of the 16S-23S rRNA internal transcribed spacer (ITS) region

Cowpea [Vigna unguiculata (L.) Walp.] is an important legume crop and yet its rhizobia have not been well characterized in many areas. In the present study, sequence analysis of the bacterial 16S-23S rRNA internal transcribed spacer (ITS) region was performed to characterize genetically 76 indigenous cowpea rhizobia from five different geographic regions (Okinawa, Miyazaki, Kyoto, Fukushima and Hokkaido) of Japan. The sequence analysis clustered all isolates in the genus Bradyrhizobium. They were conspecific with B. japonicum, B. yuanmingense, B. elkanii and Bradyrhizobium sp., although none of them grouped with B. liaoningense, B. canariense, B. betae or B. iriomotense. B. yuanmingense was only isolated from the southern region (Okinawa) where it achieved the highest frequency of 69%. B. japonicum was predominant at Miyazaki, Fukushima and Hokkaido with more than 60% of the isolates. B. elkanii was mainly recorded in the southern (Okinawa: 31%, Miyazaki: 33%) and middle (Kyoto: 33%) regions. This species was present at a very low frequency in Fukushima and absent in Hokkaido in the northern area. Bradyrhizobium sp. like-strains were absent in the southern part (Okinawa, Miyazaki) but were concentrated either in the middle regions with 67% of Kyoto isolates and 28% of Fukushima isolates, and in the northern region with 40% of the Hokkaido isolates. This study revealed a geographical distribution of cowpea bradyrhizobia which seemed to be related to the differences in the environmental characteristics (soil type and soil pH, temperature, climate, moisture) of the different regions in Japan.