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Biomedical subjects

M Coluzzi

Publications and source records attributed to M Coluzzi.

At least 19 recordsLinked to original sources
PubMed2006

Genetic complexity and gametocyte production of Plasmodium falciparum in Fulani and Mossi communities in Burkina Faso.

We have examined Plasmodium falciparum gametocyte prevalence, density and their genetic complexity among children of 2 sympatric ethnic groups (Mossi and Fulani) in villages in Burkina Faso. The 2 groups are known to have distinct differences in their susceptibility and immune responses to malaria. We used RT-PCR and sequence-specific probes to detect and type RNA of the gametocyte-specific protein Pfs48/45. There were no differences in detection rates of asexual forms and gametocytes among the 2 groups, using PCR and RT-PCR, respectively. However, there were significant differences in densities of asexual forms and gametocytes, which were both higher among Mossi than Fulani. Both asexual forms and gametocyte densities were influenced by age and ethnicity. Multiple-clone infections with more than 1 gametocyte genotype were equally prevalent among Fulani and Mossi. These differences can most probably be attributed to genetic differences in malaria susceptibility in the 2 ethnic groups.

Age Factors↗
PubMed2006

Distribution of mosquito species in areas with high and low incidence of classic Kaposi's sarcoma and seroprevalence for HHV-8.

The 'promoter-arthropod' hypothesis, which postulates that exposure to the bites of certain species of haematophagous arthropods is an environmental risk cofactor linked to human herpes virus 8 (HHV-8) and Kaposi's sarcoma, was investigated in the Po River valley, northern Italy. The presence and density of adult female mosquitoes (Diptera: Culicidae) was determined by CDC light trap catches in two adjacent districts, at variance with respect to Kaposi's sarcoma incidence and HHV-8 seroprevalence. A total of 3910 specimens belonging to 11 species was collected in 34 rural sites (six municipalities) representative of the two districts. Five of these species are considered to be possible 'promoters' because of the irritation their bites cause humans: Aedes vexans (Meigen) and Ae. caspius (Pallas) (87% of sampled promoters), Culex modestus Ficalbi, Culiseta annulata (Schrank) and Coquillettidia richiardii (Ficalbi). Six are probable 'non-promoters': Cx. pipiens s.l., Cx. martinii Medschid, Anopheles claviger (Meigen), An. maculipennis s.l., An. plumbeus Stephens and Uranotaenia unguiculata Edwards. The density of promoters by site was correlated with the incidence rates of Kaposi's sarcoma at the district level (Pearson's r = 0.33, P = 0.06) and at the municipal level (r = 0.50, P< 0.01). Similar correlations emerged for non-promoters (r = 0.48, P< 0.01 and r = 0.42, P = 0.01, respectively). The density of promoters was higher than that of non-promoters in sites with livestock (odds ratio, OR = 2.8, 95% CI 2.2-3.6) and in municipalities with Kaposi's sarcoma cases (OR = 2.5, 95% CI 1.7-3.5). The study provides additional evidence of the association between the density of some mosquito species and Kaposi's sarcoma.

Animals↗
PubMed2005

An Anopheles gambiae salivary gland promoter analysis in Drosophila melanogaster and Anopheles stephensi.

Regulatory regions driving gene expression in specific target organs of the African malaria vector Anopheles gambiae are of critical relevance for studies on Plasmodium-Anopheles interactions as well as to devise strategies for blocking malaria parasite development in the mosquito. In order to identify an appropriate salivary gland promoter we analysed the transactivation properties of genomic fragments located just upstream of the An. gambiae female salivary gland-specific genes AgApy and D7r4. An 800 bp fragment from the AgApy gene directed specific expression of the LacZ reporter gene in the salivary glands of transgenic Anopheles stephensi. However, expression levels were lower than expected and the transgene was expressed in the proximal-rather than in the distal-lateral lobes of female glands. Surprisingly, a promoter fragment from the D7r4 gene conferred strong tissue-specific expression in Drosophila melanogaster but only low transcription levels in transgenic An. stephensi. These results imply a certain conservation of gland-specific control elements between the fruit fly and the mosquito suggesting that an increased degree of complexity, probably connected to the evolution of haematophagy, underlies the regulation of tissue-specific expression in mosquito female salivary glands.

Animals↗
PubMed2003

The pyrethroid knock-down resistance gene in the Anopheles gambiae complex in Mali and further indication of incipient speciation within An. gambiae s.s.

In Mali the Anopheles gambiae complex consists of An. arabiensis and Mopti, Savanna and Bamako chromosomal forms of An. gambiae s.s. Previous chromosomal data suggests a complete reproductive isolation among these forms. Sequence analysis of rDNA regions led to the characterization of two molecular forms of An. gambiae, named M-form and S-form, which in Mali correspond to Mopti and to Savanna/Bamako, respectively, while it has failed so far to show any molecular difference between Savanna and Bamako. The population structure of An. gambiae s.l. was analysed in three villages in the Bamako and Sikasso areas of Mali and the frequency of pyrethroid resistance of the knock-down resistance (kdr) type was calculated. The results show that the kdr allele is associated only with the Savanna form populations and absent in sympatric and synchronous populations of Bamako, Mopti and An. arabiensis. This is the first molecular indication of barriers to gene flow between the Bamako and Savanna chromosomal forms. Moreover, analyses of specimens collected in the Bamako area in 1987 show that the kdr allele was already present in the Savanna population at that time, and that the frequency of this allele has gradually increased since then.

Animals↗
PubMed2003

Reduced seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV), human herpesvirus 8 (HHV8), related to suppression of Anopheles density in Italy.

In two formerly malarious parts of Italy, age-related seroprevalence rates of Kaposi's sarcoma-associated herpesvirus [human herpesvirus 8 (KSHV/HHV8)] were determined from local blood donors and correlated with periods of vector control during anti-malaria campaigns. In Veneto, decreased KSHV/HHV8 seroprevalence in the 1951-1955 birth cohort coincides with the peak of DDT house-spraying. In Sardinia, where larviciding augmented indoor DDT-spraying, a significant drop of KSHV/HHV8 seroprevalence between 1945 and 1950 and 1951-1955 birth cohorts (P = 0.0046) coincides with suppression of the malaria vector Anopheles labranchiae Falleroni (Diptera: Culicidae). These results are consistent with age-related association between KSHV/HHV8 seroprevalence rates in native/resident populations and the density of malaria vectors in Veneto and Sardinia. This example supports our 'promoter arthropod' hypothesis on the role of haematophagous insects [putatively blackflies (Simuliidae), sandflies (Phlebotominae) and biting midges (Ceratopogonidae), as well as mosquitoes] when their bites induce hypersensitivity and immunosuppression, potentiate KSHV/HHV8 transmission via human saliva (when insect bite lesions are licked by another person whose saliva carries the virus) and may facilitate Kaposi's sarcoma.

Animals↗
PubMed2002

A cluster of four D7-related genes is expressed in the salivary glands of the African malaria vector Anopheles gambiae.

Four genes expressed in the Anopheles gambiae adult female salivary glands and similar in sequence to the Aedes aegypti D7 gene were identified. The genes, called D7-related (D7r), are included in a single cluster encompassing approximately six kilobases on chromosome arm 3R. The deduced proteins contain secretory signals and they are probably injected by the mosquito into the host with the saliva during blood feeding. The region of similarity to D7 encompasses the carboxy-terminal part of the Ae. aegypti protein and the different An. gambiae D7r show a degree of similarity to each other, varying from 53% to 73%. The weak but significant similarity to members of a wide family of insect proteins, including odourant- and pheromone-binding proteins, raises the possibility that the D7r-encoded proteins may bind and/or carry small hydrophobic ligands.

Aedes↗
PubMed2002

The bloodsucking arthropod bite as possible cofactor in the transmission of human herpesvirus-8 infection and in the expression of Kaposi's sarcoma disease.

Based on a review of the literature on human herpesvirus-8 (HHV8) and Kaposi's sarcoma (KS) and on the distribution of KS in Italy (Veneto region particularly), we hypothesize that the bite of bloodsucking arthropods is a cofactor in the seroconversion to HHV8 positivity and probably in the pathogenesis of KS. The bloodsucking arthropod releases with saliva powerful antihaemostatics and immunomodulators which may favour the replication and the establishment of the pathogen. Transmission would depend on the close contact of the child with a seropositive mother (or relatives) whose infective saliva is used to relieve itching and scratching at the arthropod bite's sites. During any deregulation of the immune system (e.g. ageing), local immune responses to new insect bites may induce virus activation which could prelude KS insurgence. The pathogen is not directly transmitted by the arthropod which merely prepares the cutaneous microenvironment for the virus. We have therefore introduced a new category of medically important arthropods, "promoter arthropods", besides those already defined as biological or mechanical vectors. Promoter arthropods are species able to induce in the host long-lasting, immediate or delayed-type hypersensitivity responses as well as local immunosuppression due to substances injected with their saliva. The striking variability of ORF-K1 gene of HHV8 could be due to the adaptation of the virus to the specific microenvironments resulting from the immune response to the salivary antigens characteristic of the bloodsucking arthropod species prevalent in each geographical area. It is worth noting that other viruses (especially Hepatitis B Virus) may exploit the same non-sexual transmission route.

Animals↗
PubMed2002

An alternative focus in strategic research on disease vectors: the potential of genetically modified non-biting mosquitoes.

We examine the constraints and the feasibility of field experiments involving the release of genetically modified (GM) pathogen-resistant mosquitoes, and whether there are alternatives to the research line based on the production of refractory strains. The production of a GM mosquito strain characterized instead by obligate primiparous and parous autogeny and by disrupted host seeking and biting behaviour could make the release more acceptable by the general public. Genetic transformation should act in this case to reverse some of the essential steps of the evolutionary process that gave rise to hematophagy. The replacement strategy could be based on the mass release of both sexes in a well defined ecological niche made temporarily empty of the natural population, thus avoiding the problems related to the need of sexual competitiveness of the released material. This option is encouraged by the growing evidence that competitive exclusion mechanisms influence the pattern of distribution of different taxa within Anopheles gambiae s.s. and by the fact that the plesiomorphic characteristics of vitellogenesis without a blood meal (autogeny), which exploits fat body reserve accumulated during larval life and food other than blood in adult life, persist as genetic variants in various hematophagous insect groups, and it has been found secondarily fixed in others showing stable reversions to primiparous and parous autogeny. If this has been the result of natural selection, then the artificial production of non-biting mosquito strains, by selection and/or transgenesis, should be feasible.

Animals↗
PubMed2001

Haemoglobin C protects against clinical Plasmodium falciparum malaria.

Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.

Adolescent↗
PubMed2001

HLA class I in three West African ethnic groups: genetic distances from sub-Saharan and Caucasoid populations.

Fulani of Burkina Faso (West Africa) are a particularly interesting ethnic group because of their lower susceptibility to Plasmodium falciparum malaria as compared to sympatric populations, Mossi and Rimaibé. Moreover, the occurrence of a Caucasoid component in their genetic make-up has been suggested on the basis of their physical traits and cultural traditions even though this view was not supported by genetic studies. A total of 149 unrelated subjects (53 Mossi, 47 Rimaibé and 49 Fulani) have been typed for 97 HLA class I alleles with the amplification refractory mutation system/polymerase chain reaction (ARMS/PCR) technique. Mossi and Rimaibé data were pooled since none of the 42 statistically testable alleles exhibited a significant heterogeneity. These pooled gene frequencies were found to be very different from those of Fulani: a certain (P<0.001) or a likely (0.001 <P<0.01) difference was found for 5 and 12 alleles, respectively. Four alleles (A*24, A*29, B*27, B*3701) appeared to be essentially "private" Fulani alleles with respect to the other two populations but their presence was not associated with higher resistance to P. falciparum. Our data have then been compared using chord distances (CD) with those from the literature on Africans (including Gambian Fulani) and Caucasoids. The Burkina Faso and Gambian Fulani turned out to be very different (CD=2.191). Moreover, Burkina Faso Fulani were very distant from sympatric Mossi and Rimaibé (CDs=1.912 and 1.884), whereas Gambian Fulani were similar to sympatric Mandinka and Wolof (CDs=0.412 and 0.388) to an extent comparable to that found between Mossi and Rimaibé (CD=0.555). Our study does not suggest the involvement of HLA I in the higher resistance to malaria of Fulani, and confirms a low, if any, Caucasoid component in their gene pool.

Adolescent↗
PubMed2001

Antimalarial antibody levels and IL4 polymorphism in the Fulani of West Africa.

The Fulani are less clinically susceptible and more immunologically responsive to malaria than neighbouring ethnic groups. Here we report that anti-malarial antibody levels show a wide distribution amongst the Fulani themselves, raising the possibility that quantitative analysis within the Fulani may be an efficient way of screening for important genetic factors. The Th2 cytokine interleukin-4 is an obvious candidate: in Fulani, the IL4-524 T allele is at high frequency and is associated with elevated antibody levels against malaria antigens. These data highlight the possibility of combining inter- and intra-ethnic comparisons to characterize critical determinants of malarial immunity in a natural setting.

Africa, Western↗
PubMed2001

Electroantennogram and behavioural responses of the malaria vector Anopheles gambiae to human-specific sweat components.

Afrotropical malaria vectors of the Anopheles gambiae complex (Diptera: Culicidae), particularly An. gambiae sensu stricto, are attracted mainly to human hosts. A major source of human volatile emissions is sweat, from which key human-specific components are the carboxylic acids (E)- and (Z)-3-methyl-2-hexenoic acid and 7-octenoic acid. Electrophysiological studies on the antennae of An. gambiae s.s. showed selective sensitivity to these compounds, with a threshold at 10(-6) g comparable to that of known olfactory stimulants 1-octen-3-ol, p-cresol, isovaleric acid, and lower than threshold sensitivity to L-lactic acid and the synthetic mosquito repellent N,N-diethyltoluamide (DEET). A combination of the acids released at concentrations > 10(-5) g in wind tunnel bioassays significantly reduced the response to CO2, the major attractant released by human hosts, for strains of An. gambiae s.s. originating from East and West Africa. Field trials with odour-baited entry traps (OBETs) in Burkina Faso showed that 7-octenoic acid significantly increased (by 1.7-fold) the catch of females of An. gambiae sensu lato (comprising two sibling species: An. arabiensis Patton and An. gambiae s.s.) in OBETs baited with CO2, whereas combinations of the acids significantly reduced the catch in CO2-baited traps (by 2.1-fold) and in whole human odour-baited traps (by 1.5-fold). The pure (E) and (Z) geometric isomers of 3-methyl-2-hexenoic acid gave comparable results to the (EIZ) isomer mixture. These results provide the first experimental evidence that human-specific compounds affect the behaviour of highly anthropophilic An. gambiae s.l. mosquitoes. The compounds appear to inhibit the upwind flight' response to known long-range attractants, and may serve either to mask' the attractants present or, more probably, to 'arrest' upwind flight when mosquitoes arrive at a host under natural conditions. In the final approach to hosts, vectors are known to reduce their flight speed and increase their turning rate, to avoid overshooting the source. In our experimental apparatus, these changes in flight behaviour would reduce the number of mosquitoes entering the ports of the collection devices.

Animals↗
PubMed2001

Molecular evidence of incipient speciation within Anopheles gambiae s.s. in West Africa.

We karyotyped and identified by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis Anopheles gambiae s.s. samples collected in several African countries. The data show the existence of two non-panmictic molecular forms, named S and M, whose distribution extended from forest to savannahs. Mosquitoes of the S and M forms are homosequential standard for chromosome-2 inversions in forest areas. In dry savannahs, S is characterized mainly by inversion polymorphisms typical of Savanna and Bamako chromosomal forms, while M shows chromosome-2 arrangements typical of Mopti and/or Savanna and/or Bissau, depending on its geographical origin. Chromosome-2 inversions therefore seem to be involved in ecotypic adaptation rather than in mate-recognition systems. Strong support for the reproductive isolation of S and M in Ivory Coast comes from the observation that the kdr allele is found at high frequencies in S specimens and not at all in chromosomal identical M specimens. However, the kdr allele does not segregate with molecular forms in Benin.

Africa, Western↗
PubMed2001

Patterns of DNA sequence variation in chromosomally recognized taxa of Anopheles gambiae: evidence from rDNA and single-copy loci.

Patterns of DNA sequence variation in the ribosomal DNA (rDNA) second internal transcribed spacer (ITS2) and five unlinked single-copy nuclear loci were examined for evidence of reproductive isolation among four chromosomally recognized taxa of Anopheles gambiae from West Africa: Savanna, Bamako, Mopti and Forest, as well as sibling species An. arabiensis and An. merus. Included among the single-copy loci were three sequence-tagged random amplified polymorphic DNA (RAPD) loci, two of which (R15 and R37) had been reported as discriminating between Mopti and other chromosomal forms. Each of the five single-copy sequences were highly polymorphic in most samples. However, the R15 and R37 loci had no diagnostic value, and therefore are not recommended as tools in recognition of field-collected An. gambiae chromosomal forms. Although pairwise comparisons between species generally revealed significant levels of differentiation at all five loci, variation was not partitioned by chromosomal form within An. gambiae at any single-copy locus examined. The few exceptions to these trends appear related to a location either inside or nearby chromosomal inversions. At the tryptophan oxygenase locus inside inversion 2Rb, variation was structured only by inversion orientation and not by taxonomic designation even between An. gambiae and An. arabiensis, providing the first molecular evidence that the 2Rb inversion was transferred between species by introgressive hybridization. By contrast, the rDNA showed fixed differences between species and a difference diagnostic for Mopti, consistent with effective, if not complete, reproductive isolation. The apparent disagreement between the data from this locus and multiple single-copy loci within An. gambiae may be explained by the much lower effective population size of rDNA, owing to concerted evolution, which confers increased sensitivity at much shorter divergence times. Taken together with the accompanying reports by della Torre et al. (2001), Favia et al. (2001) and Gentile et al. (2001), our data suggest that neutral molecular markers may not have the sensitivity required to detect isolation between these recently established taxa.

Animals↗