Identification of the cryptosporidium pig genotype in a human patient.
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Adult↗
Biomedical subjects
Altaf A Lal
Publications and source records attributed to Altaf A Lal.
Protective effects of the sickle cell gene against malaria morbidity and mortality.
The high frequency of the sickle-cell haemoglobin (HbS) gene in malaria endemic regions is believed to be due to a heterozygote (HbAS) advantage against fatal malaria. Data to prospectively confirm the protection associated with HbAS against mortality are lacking. We show that HbAS provides significant protection against all-cause mortality, severe malarial anaemia, and high-density parasitaemia. This significant reduction in mortality was detected between the ages of 2 and 16 months, the highest risk period for severe malarial anaemia in this area. These data are important in understanding the role of malaria in the selection and maintenance of the sickle cell gene.
Cohort Studies↗
Polymorphism in the gene encoding the Pfs48/45 antigen of Plasmodium falciparum. XI. Asembo Bay Cohort Project.
We have investigated the genetic diversity of the gene encoding the transmission-blocking vaccine antigen Pfs48/45 of Plasmodium falciparum parasites from western Kenya and compared it with parasite populations from Thailand, India, and Venezuela. We report 44 complete new sequences. Overall, the antigen is less polymorphic as compared with other pre-erythrocytic and blood stage antigens. Contrary to other P. falciparum antigens, the number of synonymous substitutions per synonymous site exceeds the number of non-synonymous substitutions per non-synonymous site. We have found that the Pfs48/45 gene of Kenyan parasites is more polymorphic than parasites from other geographic origins. Our analysis reveals that positive natural selection is involved in the maintenance of the observed polymorphism. No evidence of intragenic recombination was found. F(st) values reveal high levels of gene flow between India and Thailand, however, there are strong constraints in gene flow among Kenyan, Southeast Asian, and Venezuelan parasites. No alleles could be linked to a specific geographic region. The results of this study suggest that this gametocyte antigen, like other asexual blood stage antigens, is under selection pressure.
Alleles↗
Detection and differentiation of Cryptosporidium parasites that are pathogenic for humans by real-time PCR.
Cryptosporidiosis is a significant cause of food-borne and waterborne outbreaks of diarrheal diseases. To better understand the route of transmission of Cryptosporidium parasites, a number of genotyping techniques have been developed, based on PCR-restriction fragment length polymorphism or sequencing analysis of antigen, structural, and housekeeping genes. In this study, a real-time assay for the detection of Cryptosporidium oocysts is described. This technique had a detection limit of five oocysts. By melting curve analysis of PCR products with fluorescence-labeled hybridization probes, this technique was able to differentiate five common Cryptosporidium parasites that are pathogenic for humans in a single PCR. We evaluated and validated the test using samples from presently known Cryptosporidium parasites that are pathogenic for humans. This technique provides an alternative molecular tool in epidemiologic studies of human cryptosporidiosis.
Animals↗
Adjuvants and malaria vaccine development.
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Adjuvants, Immunologic↗
Molecular phylogeny and evolutionary relationships of Cryptosporidium parasites at the actin locus.
To further validate previous observations in the taxonomy of Cryptosporidium parasites, the phylogenetic relationship was analyzed among various Cryptosporidium parasites at the actin locus. Nucleotide sequences of the actin gene were obtained from 9 putative Cryptosporidium species (C. parvum, C. andersoni, C. baileyi, C. felis, C. meleagridis, C. muris, C. saurophilum, C. serpentis, and C. wrairi) and various C. parvum genotypes. After multiple alignment of the obtained actin sequences, genetic distances were measured, and phylogenetic trees were constructed. Results of the analysis confirmed the presence of genetically distinct species within Cryptosporidium and various distinct genotypes within C. parvum. The phylogenetic tree constructed on the basis of the actin sequences was largely in agreement with previous results based on small subunit rRNA, 70-kDa heat shock protein, and Cryptosporidium oocyst wall protein genes. The Cryptosporidium species formed 2 major clades; isolates of C. andersoni, C. muris, and C. serpentis formed the first major group, whereas isolates of all other species, as well as various C. parvum genotypes, formed the second major group. Intragenotype variations were low or absent at this locus.
Actins↗
Three drinking-water-associated cryptosporidiosis outbreaks, Northern Ireland.
Three recent drinking-water-associated cryptosporidiosis outbreaks in Northern Ireland were investigated by using genotyping and subgenotyping tools. One Cryptosporidium parvum outbreak was caused by the bovine genotype, and two were caused by the human genotype. Subgenotyping analyses indicate that two predominant subgenotypes were associated with these outbreaks and had been circulating in the community.
Animals↗
A biologic basis for integrated malaria control.
In a series of models of Plasmodium falciparum dynamics, spontaneous local extinctions of the parasite sometimes occurred under steady, perennial-transmission conditions. These extinctions occurred only with extremely low mosquito densities or when the parameter describing the duration of human infection-blocking immunity was at its maximum value, and, simultaneously, those describing vector survivorship and the duration of human infectivity were at their minimum values. The range and frequency of extinctions increased with seasonal transmission, and decreased with the emergence of recombinant genotypes. Here we extend the immunity parameter up to levels that would describe a successful vaccine, and examine the combined influences of seasonality, genotype cross-reactivity, meiotic recombination, and human population turnover on parasite persistence. As Ross did 90 years ago, we conclude that malaria control programs that encompass several methods and targets of intervention are the most likely to succeed. Success is more likely if programs are cognizant of local circumstances of transmission, and, within that context, aim to reduce vector survivorship and human infectivity as well as augment human immunity.
Animals↗
Immunity to placental malaria. III. Impairment of interleukin(IL)-12, not IL-18, and interferon-inducible protein-10 responses in the placental intervillous blood of human immunodeficiency virus/malaria-coinfected women.
Pregnant women are highly susceptible to malaria, and human immunodeficiency virus (HIV) infection increases this susceptibility. In our previous studies, placental malaria (PM), HIV infection, and HIV/PM coinfection were all associated with decreased interferon (IFN)-gamma production by maternal placental (intervillous) blood mononuclear cells (IVBMC). This study investigated whether in vitro production of the IFN-gamma regulatory cytokines interleukin (IL)-12 and IL-18 and the chemokine IFN-inducible protein (IP)-10 by IVBMC is altered in women who have been exposed to malaria and are infected with HIV. IL-12 production from IVBMC was significantly lower in HIV-positive women, regardless of PM status, in contrast to HIV-negative, PM-negative women. IL-18 and IP-10 production by IVBMC was reduced in HIV-positive, PM-negative women but elevated in HIV-positive, PM-positive women. These results reveal a substantial impairment of IL-12 production by IVBMC in HIV-positive women, implicating this cytokine as a potentially critical regulator of malaria antigen-specific IFN-gamma responses in HIV-infected and HIV/PM-coinfected women.
Chemokine CXCL10↗
A study of genetic diversity in the gene encoding the circumsporozoite protein (CSP) of Plasmodium falciparum from different transmission areas--XVI. Asembo Bay Cohort Project.
We have investigated the genetic diversity of the gene encoding the CS protein. A total of 75 complete and 96 partial sequences are studied. We find high levels of genetic polymorphisms as evidenced by 50 and 24 alleles at the Th2R and Th3R epitopes, respectively. Overall, we find that African isolates are more polymorphic as compared with parasites from other geographic regions. We conclude that the uneven geographic polymorphism may have an adverse impact on the effectiveness of vaccines based on this antigen alone. We find extensive polymorphism in the repeat allotypes, or RATs. In order to explore how the protein structure may impose restrictions in the number of repeats, we have simulated the stability of the structure of the tandem repeat region. Our analysis suggests that the protein structure may play an important role in the observed polymorphism in the number of CS repeats in Plasmodium falciparum. We explored the linkage and recombination events among the polymorphic sites. We found that putative recombination events overlap with linked sites. We discuss how this pattern is explained by the action of positive natural selection, where the recombination events detected are convergent mutations. We conclude that it is inappropriate to use linkage-recombination patterns on genes under positive selection for assessing the structure of parasite populations.
Alleles↗
Evidence for intragenic recombination in Plasmodium falciparum: identification of a novel allele family in block 2 of merozoite surface protein-1: Asembo Bay Area Cohort Project XIV.
We have investigated intragenic recombination in Block 2 of the merozoite surface protein-1 (MSP-1), where three allele-specific families: K1, Mad20, and RO33 were previously known. Using parasites from western Kenya, we have found a fourth Block 2 allele type, which is a recombinant between Mad20 and RO33 alleles. These recombinant alleles, which we have termed MR, contain sequence from the 5' region of Mad20 and the 3' region of RO33. The results of this study provide new data on the complexity of the MSP-1 antigen gene, which is a candidate vaccine antigen, and further support the importance of intragenic recombination in generating genetic variability in Plasmodium falciparum parasites in nature.
Alleles↗