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1.
Vet World ; 15(10): 2414-2424, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36425132

ABSTRACT

A parasite-host relationship is complicated and largely remained poorly understood, especially when mixed infections involving pathogenic bacteria and viruses are present in the same host. It has been found that most parasites are able to manipulate the host's immune responses to evade or overcome its defense systems. Several mechanisms have been postulated that may explain this phenomenon in different animal species. Recent evidence suggests that coinfections involving many parasitic species alter the host's vulnerability to other microorganisms, hinder diagnostic accuracy, and may negatively impact vaccination by altering the host's immune responsiveness. The objective of this review was to provide a comprehensive summary of the current understanding of how parasites interact with other pathogens in different animal species. A better understanding of this complex relationship will aid in the improvement efforts of disease diagnosis, treatment, and control measures such as novel and effective vaccines and therapeutics for infectious diseases.

2.
PLoS Negl Trop Dis ; 15(6): e0009378, 2021 06.
Article in English | MEDLINE | ID: mdl-34081700

ABSTRACT

BACKGROUND: Sand fly saliva exposure plays an important role in immunity against leishmaniasis where it has mostly been associated with protection. Phlebotomus (Ph.) alexandri transmits Leishmania (L.) infantum, the causative agent of visceral leishmaniasis (VL), in Iraq. Our group recently demonstrated that 20% of Operation Iraqi Freedom (OIF) deployers had asymptomatic VL (AVL) indicative of prior infection by the parasite L. infantum. Little is known about Ph. alexandri saliva, and the human immune response to it has never been investigated. Here, we characterize the humoral and cellular immune response to vector saliva in OIF deployers naturally exposed to bites of Ph. alexandri and characterize their immunological profiles in association to AVL. METHODOLOGY/PRINCIPAL FINDINGS: The humoral response to Ph. alexandri salivary gland homogenate (SGH) showed that 64% of 200 OIF deployers developed an antibody response. To assess the cellular immune response to saliva, we selected a subcohort of subjects based on their post-travel (median 4 months; range 1-22 months) antibody response (SGH Antibody [Ab] positive or negative) as well as their AVL status; ten never-traveled controls were also included. Banked peripheral blood mononuclear cells (PBMC), collected ~10 years after end of deployment, were stimulated with SGH for 96 hours. The levels of IFN- γ, IL-6, IL-10, IL-13 and IL-17 were determined by ELISA. Our findings indicate that OIF deployers mounted a cellular response to SGH where the anti-SGH+ asymptomatic subjects developed the highest cytokine levels. Further, stimulation with SGH produced a mixture of pro-inflammatory and anti-inflammatory cytokines. Contrary to our hypothesis, we observed no correlation between the cellular immune response to Ph. alexandri SGH and prevention from asymptomatic infection with L. infantum. CONCLUSIONS/SIGNIFICANCE: As we found, although all infected deployers demonstrated persistent disease control years after deployment, this did not correlate with anti-saliva systemic cellular response. More exposure to this vector may facilitate transmission of the L. infantum parasite. Since exposure to saliva of Ph. alexandri may alter the human immune response to bites of this vector, this parameter should be taken into consideration when considering the VL risk.


Subject(s)
Insect Vectors/immunology , Leishmaniasis, Visceral/transmission , Phlebotomus/immunology , Saliva/immunology , Adult , Animals , Antibodies/blood , Female , Humans , Immunity, Cellular , Immunity, Humoral , Iraq/epidemiology , Leishmania infantum/immunology , Leishmaniasis, Visceral/epidemiology , Leukocytes, Mononuclear , Male , Risk , Th2 Cells
3.
PLoS Negl Trop Dis ; 14(11): e0008852, 2020 11.
Article in English | MEDLINE | ID: mdl-33226979

ABSTRACT

Cutaneous leishmaniasis (CL) is a zoonotic vector-borne neglected tropical disease transmitted by female Phlebotomine sand flies. It is distributed globally but a large proportion of cases (70-75%) are found in just ten countries. CL is endemic in Jordan yet there is a lack of robust entomological data and true reporting status is unknown. This study aimed to map habitat suitability of the main CL vector, Phlebotomus papatasi, in Jordan as a proxy for CL risk distribution to (i) identify areas potentially at risk of CL and (ii) estimate the human population at risk of CL. A literature review identified potential environmental determinants for P. papatasi occurrence including temperature, humidity, precipitation, vegetation, wind speed, presence of human households and presence of the fat sand rat. Each predictor variable was (a) mapped; (b) standardized to a common size, resolution and scale using fuzzy membership functions; (c) assigned a weight using the analytical hierarchy process (AHP); and (d) included within a multicriteria decision analysis (MCDA) model to produce monthly maps illustrating the predicted habitat suitability (between 0 and 1) for P. papatasi in Jordan. Suitability increased over the summer months and was generally highest in the north-western regions of the country and along the Jordan Valley, areas which largely coincided with highly populated parts of the country, including areas where Syrian refugee camps are located. Habitat suitability in Jordan for the main CL vector-P. papatasi-was heterogeneous over both space and time. Suitable areas for P. papatasi coincided with highly populated areas of Jordan which suggests that the targeted implementation of control and surveillance strategies in defined areas such as those with very high CL vector suitability (>0.9 suitability) would focus only on 3.42% of the country's total geographic area, whilst still including a substantial proportion of the population at risk: estimates range from 72% (European Commission's Global Human Settlement population grid) to 89% (Gridded Population of the World) depending on the human population density data used. Therefore, high impact public health interventions could be achieved within a reduced spatial target, thus maximizing the efficient use of resources.


Subject(s)
Ecosystem , Leishmaniasis, Cutaneous/epidemiology , Leishmaniasis, Cutaneous/transmission , Phlebotomus/parasitology , Animals , Disease Reservoirs/parasitology , Environment , Female , Humans , Insect Vectors/parasitology , Jordan/epidemiology , Leishmania/growth & development , Rats , Refugees , Risk
4.
PLoS Negl Trop Dis ; 14(7): e0007489, 2020 07.
Article in English | MEDLINE | ID: mdl-32658913

ABSTRACT

Phlebotomus papatasi sand flies inject their hosts with a myriad of pharmacologically active salivary proteins to assist with blood feeding and to modulate host defenses. In addition, salivary proteins can influence cutaneous leishmaniasis disease outcome, highlighting the potential of the salivary components to be used as a vaccine. Variability of vaccine targets in natural populations influences antigen choice for vaccine development. Therefore, the objective of this study was to investigate the variability in the predicted protein sequences of nine of the most abundantly expressed salivary proteins from field populations, testing the hypothesis that salivary proteins appropriate to target for vaccination strategies will be possible. PpSP12, PpSP14, PpSP28, PpSP29, PpSP30, PpSP32, PpSP36, PpSP42, and PpSP44 mature cDNAs from field collected P. papatasi from three distinct ecotopes in the Middle East and North Africa were amplified, sequenced, and in silico translated to assess the predicted amino acid variability. Two of the predicted sequences, PpSP12 and PpSP14, demonstrated low genetic variability across the three geographic isolated sand fly populations, with conserved multiple predicted MHCII epitope binding sites suggestive of their potential application in vaccination approaches. The other seven predicted salivary proteins revealed greater allelic variation across the same sand fly populations, possibly precluding their use as vaccine targets.


Subject(s)
Insect Proteins/genetics , Insect Vectors/genetics , Phlebotomus/genetics , Salivary Proteins and Peptides/genetics , Amino Acid Sequence , Animals , Base Sequence , Egypt , Humans , Insect Proteins/immunology , Insect Vectors/immunology , Jordan , Phlebotomus/immunology , Salivary Proteins and Peptides/immunology , Sequence Alignment
5.
Clin Infect Dis ; 68(12): 2036-2044, 2019 05 30.
Article in English | MEDLINE | ID: mdl-30239631

ABSTRACT

BACKGROUND: Visceral leishmaniasis (VL), due to Leishmania infantum, is a persistent intracellular parasitic infection transmitted by the bite of infected sand flies. Symptomatic VL has been reported in U.S. soldiers with Iraq deployment. Untreated symptomatic VL can be fatal; asymptomatic VL (AVL) may establish a lifelong risk of reactivation. We report prevalence and AVL risk factors in Operation Iraqi Freedom (OIF) deployers during 2002-11. METHODS: Healthy soldiers exposed to VL endemic areas in Iraq and 50 controls who never traveled to endemic regions were recruited through military healthcare facilities (2015-17). Responses to a risk factor survey and blood samples were obtained. Leishmania research diagnostics utilized included enzyme-linked immunosorbent assay (ELISA), rk39 test strips, quantitative polymerase chain reaction (PCR), and interferon gamma release (IGRA) assays. Statistical analyses included Fisher exact test, Pearson χ2 test, Mann-Whitney U test, and logistic regression. RESULTS: 200 deployed subjects were enrolled, mostly males (84.0%), of white ethnicity (79.0%), and median age 41 (range 24-61) years. 64% were seropositive for Phlebotomus alexandri saliva antibodies. Prevalence of AVL (any positive test result) was 39/200 (19.5%, 95% confidence interval 14.4%-25.8%). Two (1.0%) PCR, 10 (5%) ELISA, and 28 (14%) IGRA samples were positive. Travel to Ninewa governorate increased risk for AVL (P = .01). CONCLUSION: AVL was identified in 19.5% of OIF deployers; travel to northwest Iraq correlated with infection. Further studies are needed to inform risk for reactivation VL in US veterans and to target additional blood safety and surveillance measures.


Subject(s)
Asymptomatic Infections , Leishmania infantum , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/parasitology , Military Personnel , Adult , Female , Geography , Humans , Iraq/epidemiology , Leishmaniasis, Visceral/diagnosis , Male , Middle Aged , Public Health Surveillance , United States/epidemiology , Young Adult
6.
Parasit Vectors ; 11(1): 214, 2018 03 27.
Article in English | MEDLINE | ID: mdl-29587873

ABSTRACT

BACKGROUND: Phlebotomus papatasi sand flies are major vectors of Leishmania major and phlebovirus infection in North Africa and across the Middle East to the Indian subcontinent. Population genetics is a valuable tool in understanding the level of genetic variability present in vector populations, vector competence, and the development of novel control strategies. This study investigated the genetic differentiation between P. papatasi populations in Egypt and Jordan that inhabit distinct ecotopes and compared this structure to P. papatasi populations from a broader geographical range. METHODS: A 461 base pair (bp) fragment from the mtDNA cytochrome b (cyt b) gene was PCR amplified and sequenced from 116 individual female sand flies from Aswan and North Sinai, Egypt, as well as Swaimeh and Malka, Jordan. Haplotypes were identified and used to generate a median-joining network, F ST values and isolation-by-distance were also evaluated. Additional sand fly individuals from Afghanistan, Iran, Israel, Jordan, Libya, Tunisia and Turkey were included as well as previously published haplotypes to provide a geographically broad genetic variation analysis. RESULTS: Thirteen haplotypes displaying nine variant sites were identified from P. papatasi collected in Egypt and Jordan. No private haplotypes were identified from samples in North Sinai, Egypt, two were observed in Aswan, Egypt, four from Swaimeh, Jordan and two in Malka, Jordan. The Jordan populations clustered separately from the Egypt populations and produced more private haplotypes than those from Egypt. Pairwise F ST values fall in the range 0.024-0.648. CONCLUSION: The clustering patterns and pairwise F ST values indicate a strong differentiation between Egyptian and Jordanian populations, although this population structure is not due to isolation-by-distance. Other factors, such as environmental influences and the genetic variability in the circulating Le. major parasites, could possibly contribute to this heterogeneity. The present study aligns with previous reports in that pockets of genetic differentiation exists between populations of this widely dispersed species but, overall, the species remains relatively homogeneous.


Subject(s)
Cytochromes b/genetics , Genetic Variation , Genetics, Population , Haplotypes , Phlebotomus/classification , Phlebotomus/growth & development , Phylogeography , Animals , Egypt , Insect Vectors/classification , Insect Vectors/genetics , Insect Vectors/growth & development , Jordan , Phlebotomus/genetics
7.
Exp Parasitol ; 185: 23-28, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29309786

ABSTRACT

Little is known about the prevalence of Giardia duodenalis in human patients in Jordan and all previous studies have used direct microscopy, which lacks sensitivity. The present study developed a novel quantitative PCR (qPCR) assay at the ß-giardin (bg) locus and evaluated its use as a frontline test for the diagnosis of giardiasis in comparison with a commercially available ELISA using nested PCR and sequencing of the glutamate dehydrogenase (gdh) locus (gdh nPCR) as the gold standard. A total of 96 human faecal samples were collected from 96 patients suffering from diarrhoea from 5 regions of Jordan and were screened using the ELISA and qPCR. The analytical specificity of the bg qPCR assay revealed no cross-reactions with other genera and detected all the Giardia isolates tested. Analytical sensitivity was 1 Giardia cyst per µl of DNA extract. The overall prevalence of Giardia was 64.6%. The clinical sensitivity and specificity of the bg qPCR was 89.9% and 82.9% respectively compared to 76.5 and 68.0% for the ELISA. This study is the first to compare three different methods (ELISA, bg qPCR, nested PCR and sequencing at the gdh locus) to diagnose Jordanian patients suffering from giardiasis and to analyze their demographic data.


Subject(s)
Diarrhea/parasitology , Giardia lamblia/isolation & purification , Giardiasis/parasitology , Adolescent , Adult , Antigens, Protozoan/analysis , Child , Child, Preschool , Colic/parasitology , Cytoskeletal Proteins/genetics , DNA, Protozoan/chemistry , DNA, Protozoan/isolation & purification , Enzyme-Linked Immunosorbent Assay , Feces/parasitology , Female , Giardia lamblia/genetics , Giardia lamblia/immunology , Giardiasis/epidemiology , Glutamate Dehydrogenase , Humans , Infant , Jordan/epidemiology , Male , Middle Aged , Polymerase Chain Reaction , Prevalence , Protozoan Proteins/genetics , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Vomiting/parasitology , Young Adult
8.
Vet Q ; 37(1): 200-205, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28537782

ABSTRACT

BACKGROUND: In the last decade, Parascaris spp. resistance to anthelmintics has been recorded in many countries. In Saudi Arabia, there are limited data available on Parascaris spp. resistance to anthelmintics. OBJECTIVE: To determine the current status of ivermectin, abamectin and praziquantel combined, and fenbendazole resistance to Parascaris spp. in horses in Saudi Arabia. METHODS: Three hundred and forty-one foals from eleven different farms were examined by faecal egg count (FEC). The foals were all Arab horses aged 17.2 ± 4.5 (SD) months. Ivermectin (n = 46 foals), abamectin and praziquantel combined (n = 46), and fenbendazole (n = 46) were administered on day 0 and faeces were collected on day 14. The study comprised 41 untreated foals as controls. Animals that have FEC of ≥100 eggs per gram (EPG) were used to measure anthelmintic efficacy. Parascaris spp. populations were considered susceptible when faecal egg count reduction (FECR) was ≥95% associated with a lower 95% confidence limit (LCL) >90%, suspected resistant when FECR ≤90% or LCL <90% and resistant when FECR <90% and LCL <90%. RESULTS: Prevalence of Parascaris spp. infection was 53% (179/341 horses). Anthelmintic resistance to Parascaris spp. were highest following fenbendazole (55% of farms and 65% of foals) and to a lower extent following ivermectin or the combination of abamectin and praziquantel which comprised 27% of farms (and 46% of foals) and 18% of farms (and 10% of foals), respectively. CONCLUSION: These data indicate that anthelmintics-resistant Parascaris spp. populations are present on horse farms in Saudi Arabia.


Subject(s)
Anthelmintics/pharmacology , Ascaridida Infections/veterinary , Ascaridoidea/drug effects , Horse Diseases/drug therapy , Horse Diseases/epidemiology , Animals , Antinematodal Agents/pharmacology , Ascaridida Infections/drug therapy , Ascaridida Infections/epidemiology , Case-Control Studies , Drug Combinations , Drug Resistance , Feces/parasitology , Fenbendazole/pharmacology , Horses , Ivermectin/analogs & derivatives , Ivermectin/pharmacology , Parasite Egg Count , Praziquantel/pharmacology , Saudi Arabia/epidemiology
9.
Vet Parasitol ; 228: 116-120, 2016 Sep 15.
Article in English | MEDLINE | ID: mdl-27692311

ABSTRACT

Little is known about the epidemiology of Cryptosporidium in Jordan and to date, only one genotyping study has been conducted on Cryptosporidium isolates from Jordanian children. In the present study, a total of 284 faecal samples from Jordanian cattle, sheep, goats and chicken and 48 human faecal samples were screened for the presence of Cryptosporidium using an 18S quantitative PCR (qPCR) and a C. parvum/C. hominis specific qPCR at a lectin locus. Of these, 37 of 284 animal faecal samples were positive by qPCR at the 18S locus giving an overall prevalence of 11.6%. The point prevalence of Cryptosporidium in chickens, sheep, horses, cattle and goats ranged from 4.8% (chickens) to 18.7% (cattle). A total of six species were detected; C. xiaoi (n=9),C. andersoni (n=7),C. ryanae (n=5),C. parvum (n=4),C. baileyi (n=1) and a genetically distinct and potentially novel species in two isolates from horses. Sub-genotype analysis of the 4 C. parvum isolates at the 60-kDa glycoprotein (gp60) locus identified subtype IIaA19G2R1 (n=2) and IIaA16GR1 (n=2). For the human samples, 4 positives (8.3% prevalence) were detected. Of these, two were C. parvum (subtypes IIdA20G1 and IIaA15G2R1) and two were C. hominis (subtypes 1bA9G3 and 1bA10G2R2). Further studies are required to better understand the epidemiology and transmission of Cryptosporidium in Jordan.


Subject(s)
Cattle Diseases/parasitology , Cryptosporidiosis/parasitology , Cryptosporidium/genetics , Goat Diseases/parasitology , Horse Diseases/parasitology , Poultry Diseases/parasitology , Animals , Cattle , Cattle Diseases/epidemiology , Chickens , Cryptosporidiosis/epidemiology , Cryptosporidium/isolation & purification , Feces/parasitology , Genotype , Goat Diseases/epidemiology , Goats , Horse Diseases/epidemiology , Horses , Humans , Jordan/epidemiology , Molecular Typing , Poultry Diseases/epidemiology , Prevalence , Sheep , Zoonoses
10.
Parasitol Res ; 115(9): 3345-55, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27160331

ABSTRACT

Phlebotomine sand flies are the known vectors of Leishmania parasites. New approaches in vaccination against Leishmania have investigated the possibility of integrating Phlebotomus papatasi salivary proteins to enhance the immune response and protect against the transmission of the infection. The aim of the present study was to screen human immune responses to wild sand fly saliva and evaluate immunogenic salivary proteins. Blood samples were collected from donors in control and sand fly infested areas. Antibodies specific for sand fly antigens in donor plasma were probed using immunoblotting. In addition, recall proliferation capability of peripheral blood mononuclear cells (PBMC) was tested after sand fly salivary homogenates stimulation. The significant immunogenic salivary proteins (SPs) identified by immunoblotting were SP28, SP32, and SP36. A specific proliferative response of PBMC after stimulation with sand fly salivary homogenates was evident in donors that have antibody responses against sand fly salivary proteins. Individuals with antibody recognition to a higher number of salivary proteins (i.e., 3 or more SP bands) showed lower PBMC proliferative responses after in vitro stimulation with salivary gland homogenates (SGH) only in the sand fly infested, leishmaniasis free area. Interestingly, the presence of a humoral immune response to many SP antigens inversely correlates with a strong cell-mediated immune response (CMI). It was also noticed that some other heavily expressed antigens, in sand fly salivary homogenate, lack or have weak humoral immune reactivity in exposed individuals. Therefore, considering these antigens alone as CMI activators, without including the immunodominant humoral immune response proteins, needs future investigation.


Subject(s)
Antibody Formation , Insect Proteins/immunology , Leishmaniasis/immunology , Phlebotomus/immunology , Salivary Proteins and Peptides/immunology , Adult , Animals , Female , Humans , Insect Proteins/genetics , Leishmania/immunology , Leishmaniasis/parasitology , Leishmaniasis/prevention & control , Leishmaniasis/transmission , Leukocytes, Mononuclear/immunology , Male , Phlebotomus/genetics , Phlebotomus/parasitology , Salivary Proteins and Peptides/genetics , Vaccines/genetics , Vaccines/immunology , Young Adult
11.
Parasitol Res ; 115(10): 3723-9, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27206655

ABSTRACT

Little is known about the epidemiology of Giardia in Jordan and to date, no genotyping studies have been conducted on Giardia isolates from Jordanians. In the present study, a total of 49 microscopy-positive faecal samples from Jordanian patients suffering from giardiasis were analysed at two loci: the triose phosphate isomerase (tpi) gene and the glutamate dehydrogenase (gdh) gene. At the tpi locus, a total of 28 samples amplified and assemblage A was identified in 46.4 % (13/28) samples, while assemblage B was identified in 50 % (14/28) samples and a mixed assemblage A and B was identified in one sample (3.6 %) (Table 1). At the gdh locus 48 isolates amplified and of these assemblages A was identified in 43.7 % (21/48) of isolates and assemblage B in 56.3 % (27/48) of isolates. No mixed infections were detected at the gdh locus. Subtyping at the gdh locus identified sub-assemblage AII in 43.7 % (21/48) of isolates and sub-assemblages BIII and BIV in 25 % (12/48) and 31.2 % (15/48) of isolates, respectively, with more genetic diversity in AII isolates than BIII or BIV isolates. Novel sub-types within each sub-assemblage were identified suggesting unique endemicity and anthroponotic transmission of Giardia in Jordanian patients suffering from giardiasis. Further studies are required to better understand the epidemiology and transmission of Giardia in Jordan.


Subject(s)
Genetic Variation , Giardia/genetics , Giardiasis/parasitology , Adolescent , Adult , Child , Child, Preschool , Feces , Female , Genotype , Giardia/isolation & purification , Giardiasis/epidemiology , Glutamate Dehydrogenase/genetics , Humans , Infant , Jordan/epidemiology , Male , Middle Aged , Protozoan Proteins/genetics , Triose-Phosphate Isomerase/genetics , Young Adult
12.
Parasit Vectors ; 8: 298, 2015 May 29.
Article in English | MEDLINE | ID: mdl-26022221

ABSTRACT

BACKGROUND: The Phlebotomus papatasi salivary protein PpSP15 was shown to protect mice against Leishmania major, suggesting that incorporation of salivary molecules in multi-component vaccines may be a viable strategy for anti-Leishmania vaccines. METHODS: Here, we investigated PpSP15 predicted amino acid sequence variability and mRNA profile of P. papatasi field populations from the Middle East. In addition, predicted MHC class II T-cell epitopes were obtained and compared to areas of amino acid sequence variability within the secreted protein. RESULTS: The analysis of PpSP15 expression from field populations revealed significant intra- and interpopulation variation.. In spite of the variability detected for P. papatasi populations, common epitopes for MHC class II binding are still present and may potentially be used to boost the response against Le. major infections. CONCLUSIONS: Conserved epitopes of PpSP15 could potentially be used in the development of a salivary gland antigen-based vaccine.


Subject(s)
Insect Proteins/genetics , Phlebotomus/genetics , Amino Acid Sequence , Animals , Genetic Variation , Insect Proteins/chemistry , Insect Proteins/metabolism , Molecular Sequence Data , Phlebotomus/chemistry , Phlebotomus/metabolism , Polymorphism, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment
13.
Am J Trop Med Hyg ; 90(5): 923-938, 2014 May.
Article in English | MEDLINE | ID: mdl-24615125

ABSTRACT

Phlebotomus papatasi sand flies are among the primary vectors of Leishmania major parasites from Morocco to the Indian subcontinent and from southern Europe to central and eastern Africa. Antibody-based immunity to sand fly salivary gland proteins in human populations remains a complex contextual problem that is not yet fully understood. We profiled the immunoreactivities of plasma antibodies to sand fly salivary gland sonicates (SGSs) from 229 human blood donors residing in different regions of sand fly endemicity throughout Jordan and Egypt as well as 69 US military personnel, who were differentially exposed to P. papatasi bites and L. major infections in Iraq. Compared with plasma from control region donors, antibodies were significantly immunoreactive to five salivary proteins (12, 26, 30, 38, and 44 kDa) among Jordanian and Egyptian donors, with immunoglobulin G4 being the dominant anti-SGS isotype. US personnel were significantly immunoreactive to only two salivary proteins (38 and 14 kDa). Using k-means clustering, donors were segregated into four clusters distinguished by unique immunoreactivity profiles to varying combinations of the significantly immunogenic salivary proteins. SGS-induced cellular proliferation was diminished among donors residing in sand fly-endemic regions. These data provide a clearer picture of human immune responses to sand fly vector salivary constituents.


Subject(s)
Adaptive Immunity , Immunoglobulin G/immunology , Insect Proteins/immunology , Phlebotomus/metabolism , Salivary Proteins and Peptides/immunology , Animals , Cell Proliferation , Cluster Analysis , Egypt , Female , Host-Parasite Interactions , Humans , Immunoglobulin G/blood , Iraq , Jordan , Male , Phlebotomus/parasitology
14.
BMC Ecol ; 11: 24, 2011 Oct 10.
Article in English | MEDLINE | ID: mdl-21985688

ABSTRACT

BACKGROUND: Sand fly saliva can drive the outcome of Leishmania infection in animal models, and salivary components have been postulated as vaccine candidates against leishmaniasis. In the sand fly Phlebotomus papatasi, natural sugar-sources modulate the activity of proteins involved in meal digestion, and possibly influence vectorial capacity. However, only a handful of studies have assessed the variability of salivary components in sand flies, focusing on the effects of environmental factors in natural habitats. In order to better understand such interactions, we compared the expression profiles of nine P. papatasi salivary gland genes of specimens inhabiting different ecological habitats in Egypt and Jordan and throughout the sand fly season in each habitat. RESULTS: The majority of investigated genes were up-regulated in specimens from Swaymeh late in the season, when the availability of sugar sources is reduced due to water deprivation. On the other hand, these genes were not up-regulated in specimens collected from Aswan, an irrigated area less susceptible to drought effects. CONCLUSION: Expression plasticity of genes involved with vectorial capacity in disease vectors may play an important epidemiological role in the establishment of diseases in natural habitats.


Subject(s)
Genes, Insect , Phlebotomus/genetics , Seasons , Animals , Carbohydrate Metabolism , Droughts , Egypt , Jordan , Leishmania/physiology , Phlebotomus/parasitology , Salivary Glands , Up-Regulation
15.
Int J Parasitol ; 40(2): 157-61, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20004204

ABSTRACT

Infection of C3HeB/FeJ and C57BL/6 mice with Leishmania major stimulates a healing cell-mediated immune response, while Leishmania amazonensis infection leads to chronic disease. Here we show C3HeB/FeJ mice co-infected with both species of Leishmania heal, while co-infected C57BL/6 mice do not. Using an in vitro killing assay we determined B cells from infected C57BL/6 mice are ineffective in promoting parasite killing compared with B cells from infected C3HeB/FeJ mice. Furthermore, infected C57BL/6 mice produce less antigen-specific antibodies compared with infected C3HeB/FeJ mice. These findings suggest B cells play a required role in the cell-mediated immune response against L. amazonensis.


Subject(s)
B-Lymphocytes/immunology , Leishmania mexicana/immunology , Leishmaniasis, Cutaneous/immunology , Macrophages/immunology , Mice/immunology , Phagocytosis , Animals , B-Lymphocytes/parasitology , Cells, Cultured , Leishmaniasis, Cutaneous/parasitology , Macrophages/parasitology , Mice, Inbred C3H , Mice, Inbred C57BL
16.
Infect Immun ; 77(12): 5668-75, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19797068

ABSTRACT

Leishmania major is an obligately intracellular protozoan parasite that causes cutaneous leishmaniasis. Like numerous intracellular pathogens, Leishmania exploits cell surface receptors as a means of entry into host cells. Complement receptor 3 (CR3; also called CD11b/CD18), a beta(2) integrin on phagocytic cells, is one such receptor. Ligation of CR3 has been shown to inhibit the production of interleukin-12, the cytokine that is pivotal in establishing the cell-mediated response necessary to combat intracellular infection. Here we investigate the role that CR3 plays in the establishment and progression of cutaneous leishmaniaisis in vivo. Dermal lesions of wild-type BALB/c mice are characteristically progressive and lead to extensive tissue necrosis coupled with elevated parasite burdens; CD11b-deficient BALB/c mice, however, demonstrate an intermediate phenotype characterized by chronic lesions and a reduced incidence of tissue damage. Infection followed by a reinfection challenge indicates that both susceptible (BALB/c) and resistant (C57BL/6) mice, regardless of CD11b status, develop resistance to L. major. In addition, CD11b does not bias the T helper cytokine response to L. major infection. Our results further indicate that CD11b is not necessary for disease resolution in resistant mice; rather, this protein appears to play a minor role in susceptibility.


Subject(s)
Leishmania major/pathogenicity , Leishmaniasis, Cutaneous/pathology , Leishmaniasis, Cutaneous/parasitology , Macrophage-1 Antigen/genetics , Animals , Antibodies, Protozoan/blood , CD11b Antigen/genetics , Cytokines/metabolism , Dendritic Cells/immunology , Disease Susceptibility , Female , Leukocytes/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Severity of Illness Index , Skin/parasitology , Skin/pathology
17.
Am J Trop Med Hyg ; 76(4): 669-75, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17426168

ABSTRACT

The requirements for effective and efficient intracellular killing of Leishmania amazonensis by activated macrophages are unknown. Despite resistance to the arginase inhibitor LOHA by intracellular L. amazonensis amastigotes, enhanced replication did not account for the relative resistance of this parasite to macrophage activation. Herein we report that the presence of both superoxide and nitric oxide is necessary for efficient killing of L. amazonensis amastigotes within LPS/IFN-gamma-activated bone marrow-derived macrophages generated from C3H mice. Addition of an extracellular signal-regulated kinase (ERK) inhibitor to L. amazonensis-infected macrophages increased the ability of these activated macrophages to kill L. amazonensis amastigotes. This enhanced macrophage killing through addition of ERK inhibitor was abrogated by inhibition of superoxide or iNOS, whereas inhibiting superoxide had no effect on the killing of L. major. These results suggest that ERK activation may modulate effective macrophage killing, leading to the ability of L. amazonensis to resist elimination within activated macrophages.


Subject(s)
Leishmania/growth & development , Leishmania/immunology , Macrophages/immunology , Macrophages/metabolism , Nitric Oxide/metabolism , Superoxides/metabolism , Animals , Cells, Cultured , Extracellular Signal-Regulated MAP Kinases/metabolism , Flavonoids/pharmacology , Mice , Mice, Inbred C3H , Nitric Oxide Synthase Type II/metabolism
18.
Microbes Infect ; 8(9-10): 2547-55, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16934514

ABSTRACT

In contrast to L. major, the factors required for clearance of Leishmania amazonensis parasites from infected macrophages have been difficult to define. Multiple studies have made progress towards identifying the phenotypic differences in various cell types secondary to L. amazonensis infection as compared to L. major infection, but few have shown the cell types or factors required for parasite clearance. Based on studies which identified that mice previously infected with L. major and healed can mount a protective immune response against L. amazonensis, this study identifies cell types and factors from draining lymph node cells of L. major-infected mice that are necessary and sufficient to control infection in L. amazonensis-infected bone-marrow derived macrophages. Using a transwell system we show that soluble factors from CD4+T cells and B cells were required to kill intracellular parasites. One of these factors, L. major-specific immunoglobulin, may serve to trigger macrophage activation and promote parasite killing via superoxide production. Identification of these factors will provide more precise knowledge of host-cell signaling required to promote an effective immune response against L. amazonensis.


Subject(s)
B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Leishmania major/immunology , Leishmania/immunology , Leishmaniasis/immunology , Macrophages/parasitology , Animals , Bone Marrow Cells/immunology , Immunoglobulin G/immunology , Leishmania/growth & development , Leishmaniasis/parasitology , Lymph Nodes/immunology , Macrophages/immunology , Mice , Mice, Inbred C3H
19.
Prev Vet Med ; 55(3): 201-7, 2002 Oct 15.
Article in English | MEDLINE | ID: mdl-12383656

ABSTRACT

From March 1996 to February 1997, slaughtered-sheeps' heads were examined for the metacestode of Taenia multiceps. Out of 451 sheep heads, only 12 (3%) were infested. All cysts but one were in the age group 0.5-2.5 years old, with prevalence of 10% (11 of 108). Eleven of 12 infested heads were found during the spring and autumn seasons. Out of 95 flocks involved in questionnaire survey unrelated to the abattoir survey, all the farmers reported the existence of the clinical signs known for coenurosis and described it in locally known names and diseases. Twenty-five of them had recent cases that were diagnosed by the veterinarian as coenurosis cases. Each flock reported one or two cases at the time of survey. A variety of clinical signs were reported from these cases (n = 42). These included circling (86%), head pressing (52%), blindness (29%) and paresis (40%). Coenurosis is a sheep-health problem and an important cause of sheep culling in Jordan.


Subject(s)
Sheep Diseases/parasitology , Sheep/parasitology , Taenia/isolation & purification , Taeniasis/epidemiology , Taeniasis/veterinary , Abattoirs , Aging , Animals , Goats/parasitology , Jordan/epidemiology , Prevalence , Seasons , Sheep Diseases/diagnosis , Sheep Diseases/epidemiology , Sheep Diseases/physiopathology , Taeniasis/diagnosis , Taeniasis/physiopathology
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