Epidemiology of tularemia in the countries of the WHO Eastern Mediterranean Region (EMRO): A systematic review and meta-analysis.

BACKGROUND: Francisella tularensis, the bacterium that causes tularemia, has been a persistent and widespread pathogen in various regions of the world for centuries. Francisella tularensis can affect humans and various domestic and wild animals. The current study aimed to determine the epidemiological status of tularemia in countries of the WHO Eastern Mediterranean Region (EMRO) through a systematic review and meta-analysis. METHODS: All included studies were identified through a systematic search of online databases, including Scopus, PubMed, Web of Science, and EMBASE, through July 26, 2022, using keywords and suitable combinations. We focused on cross-sectional studies investigating the prevalence of F. tularensis. The weighted pooled prevalence was calculated using a random-effects model. RESULTS: A total of 206 studies were identified, of which 20 were finally included in the analysis. The human seroprevalence of tularemia in WHO-EMRO countries was 6.2% (95% CI, 4.2 9.2). In the subgroup analysis, anti-F. tularensis antibodies were found in 6.92% and 5.5% of the high-risk individuals and Iran, respectively. The pooled prevalence of F. tularensis in environmental samples (water and soil) from the WHO-EMRO countries was 5.8% (9.4% by PCR and 0.5% by culture). In addition, 2.5% (95% CI, 0.2 0.22.7) of ticks in WHO-EMRO countries were positive for F. tularensis. The pooled prevalence of F. tularensis in rodents is 2.0% (1.1% by PCR and 3.7% by serology). In addition, 0.6% of domestic ruminants (0.4% by PCR and 2.4% by serology) were positive for F. tularensis in WHO-EMRO countries. CONCLUSION: According to the results of the present study, tularemia is an endemic but neglected disease in the WHO-EMRO region. However, most studies on tularemia are limited to a few countries in this region. Studies on tularemia in human populations, reservoirs, and vectors have been conducted in all countries in the WHO-EMRO region to obtain more detailed information about the epidemiology of tularemia in these regions.

The Epidemiological Investigation of Yersinia pestis, Francisella tularensis, and Arenavirus Infections in Small Mammals in Northwestern Iran.

Background: The control and prevention of rodent-borne diseases are mainly based on our knowledge of ecology and the infectious status of their reservoir hosts. This study aimed to evaluate the prevalence of Francisella tularensis, Yersinia pestis, and arenavirus infections in small mammals and to assess the potential of disease occurrence in East Azerbaijan, northwest of Iran, in 2017 and 2018. Methods: Spleen and lung samples were obtained from all trapped small mammals. The real-time quantitative PCR (qPCR) method was used to detect nucleic acid sequences of F. tularensis, Y. pestis, and arenaviruses. Serum samples were tested for antibodies indicating the host response to F. tularensis and Y. pestis infections using the standard tube agglutination test and enzyme-linked immunosorbent assay (ELISA), respectively. Results: A total of 205 rodents, four Eulipotyphla, and one carnivore were captured. The most common rodent species captured (123 of 205 rodents, 60%) belonged to the genus Meriones (mainly Persian jird, Meriones persicus). In total, 317 fleas were removed from trapped animals. Flea species belonged to Xenopsylla buxtoni, Xenopsylla nuttalli, Stenoponia tripectinata, Paraceras melis, Ctenophthalmus rettigi smiti, Rhadinopsylla bivirgis, Paradoxopsyllus grenieri, and Nosopsyllus iranus. Using the qPCR tests, five spleen samples from M. persicus were positive for F. tularensis. The qPCR tests were negative for the detection of Y. pestis and arenaviruses. Finally, all serum samples tested were negative for antibodies against Y. pestis and F. tularensis. Conclusions: F. tularensis was the only zoonotic agent detected in rodents captured in East Azerbaijan. However, the diversity of trapped rodents and fleas provides the potential for the spread of various rodent-borne viral and bacterial diseases in the studied areas.

Development, Strategies, and Challenges for Tularemia Vaccine.

Francisella tularensis is a facultative intracellular bacterial pathogen that affects both humans and animals. It was developed into a biological warfare weapon as a result. In this article, the current status of tularemia vaccine development is presented. A live-attenuated vaccine that was designed over 50 years ago using the less virulent F. tularensis subspecies holarctica is the only prophylactic currently available, but it has not been approved for use in humans or animals. Other promising live, killed, and subunit vaccine candidates have recently been developed and tested in animal models. This study will investigate some possible vaccines and the challenges they face during development.

Geographical distribution of Bartonella spp in the countries of the WHO Eastern Mediterranean Region (WHO-EMRO).

Bartonellosis is a vector-borne and zoonotic diseases in humans, especially in immunocompromised individuals. However, there is no complete data about the geographical distribution of different species of Bartonella, as well as the status of its reservoirs, vectors, and human cases in most parts of the world. In this study, published reports related to Bartonella species from WHO-EMRO region countries were searched in different databases until October 2023. The eighteens different species of Bartonella were reported in WHO-EMRO countries including Bartonella henselae, Bartonella quintana, Bartonella elizabethae, Bartonella bovis, Bartonella clarridgeiae, Bartonella vinsonii, Bartonella doshiae, Bartonella taylorii, Bartonella rochalimae, Bartonella tribocorum, Bartonella rattimassiliensis, candidatus Bartonella merieuxii, candidatus Bartonella dromedarii, Bartonella acomydis, Bartonella jaculi, Bartonella coopersplainsensis and Bartonella koehlerae. Also, only human cases of B. henselae and B. quintana infections were reported from WHO-EMRO countries. The infections of Bartonella are important in the WHO-EMRO region, but they have been neglected by clinicians and healthcare systems.

Distribution of different Rickettsia species in countries of the WHO Eastern Mediterranean (WHO-EMRO) region: An overview.

SUBJECT: Rickettsia is a zoonotic bacterial pathogen transmitted by vectors and has extensive reservoirs in animal and human populations. Rickettsiosis is a public health problem all over the world. However, comprehensive information on the geographical distribution of different Rickettsia species, infection status of reservoirs, vectors, and human cases is lacking in most parts of the world. Therefore, this study aimed to investigate the geographical distribution of different Rickettsia species and their vectors in countries of the WHO-EMRO region. METHODS: In this review study, a search was conducted for reports and published studies on Rickettsia species from WHO-EMRO region countries in various databases from 1995 to 2022. Finally, the reported status of human cases, reservoirs, and vectors associated with each species in different countries was documented. RESULTS: Reports of infections related to the detection of Rickettsia species were only available for 15 out of 22 WHO-EMRO member countries. A total of twenty-four Rickettsia species, including R. sibrica, R. lusitaniae, R. africae, R. prowazekii, R. felis, R. typhi, R. rickettsii, R. aeschlimannii, R. conorii, R. massiliae, R. helvetica, R. monacensis, R. rhipicephali, R. bellii, R. asembonensis, R. hoogstraalii, R. andeanae, R. raoultii, R. asiatica, R. slovaca, R. australis, R. barbariae, Candidatus R. amblyommii, and Candidatus R. goldwasserii, were reported from WHO-EMRO member countries. Furthermore, human cases infected with six different Rickettsia species, including R. sibrica, R. prowazekii, R. felis, R. typhi, R. rickettsii, R. aeschlimannii, R. conorii, R. massiliae, and R. helvetica, were reported from these countries. CONCLUSION: The vast diversity of Rickettsia vectors has contributed to the ongoing discovery of new Rickettsia species. Therefore, further research on the reservoir hosts of Rickettsia infections in the understudied WHO-EMRO region is crucial. This research sheds light on Rickettsia disease's epidemiology and transmission dynamics in this region.

Molecular examination for Coxiella burnetii and Brucella spp. infections in Iranian women experiencing spontaneous miscarriage.

BACKGROUND: Spontaneous miscarriage, a leading health concern globally, often occurs due to various factors, including infections. Among these, Coxiella burnetii and Brucella spp. may have adverse effects on pregnancy outcomes. While previous research has established a link between infections and spontaneous miscarriage, our study aimed specifically to investigate the presence of these two pathogens in abortion samples from women who experienced spontaneous miscarriages in Iran. Our study can add to the existing knowledge by focusing on Iran, a region with a high prevalence of C. burnetii and Brucella spp. As a result, it could provide a better understanding and unique insights into the relationship of these pathogens with spontaneous miscarriages in endemic regions. METHODS: From March 2021 to March 2022, a total of 728 abortion samples (including placenta and cotyledon) were collected from 409 women who had experienced spontaneous miscarriages in the provinces of Tehran, Fars, and West Azerbaijan in Iran. The specimens included 467 Formalin-Fixed Paraffin-Embedded (FFPE) and 261 fresh frozen samples. After DNA extraction from abortion samples, the quantitative real-time PCR (qPCR) assay targeted a specific fragment of the IS1111 and IS711 elements for molecular identification of C. burnetii and Brucella spp., respectively. Furthermore, the qPCR assay employing specific primers for different species was used to determine the species of Brucella. RESULTS: Among the studied women, 1 out of 409 (0.24%) samples tested positive for Brucella spp., specifically Brucella melitensis. There were no positive specimens for C. burnetii. CONCLUSIONS: Our study contributes to understanding the potential involvement of Brucella species in spontaneous infectious abortion within endemic regions. The identification of B. melitensis in this study highlights the need for further research in this area. However, while our results suggest a relatively low or zero identification of these pathogens in our sample population, this does not rule out the possibility of undetected infections. Therefore, it is critical to acknowledge the limitations of the molecular techniques used (qPCR), which may have potential limitations such as sensitivity and specificity. Moreover, because 64.15% of our samples were FFPE, the sensitivity of the qPCR test may be reduced. These raise concerns about the accuracy of the reported prevalence rates and the potential for false positives or negatives.

Rickettsia conorii subsp. israelensis infection in a pediatric patient presenting skin rash and abdominal pain: a case report from Southeast Iran.

BACKGROUND: The healthcare system in Iran appears to overlook Mediterranean spotted fever (MSF) as an endemic disease, particularly in pediatric cases, indicating the need for greater attention and awareness. CASE PRESENTATION: A six-year-old patient with fever, abdominal pain, headache, skin rashes, diarrhea, vomiting, and black eschar (tache noire) from southeast Iran was identified as a rickettsiosis caused by Rickettsia conorii subsp. israelensis through clinical and laboratory assessments, including IFA and real-time PCR. The patient was successfully treated with doxycycline. CONCLUSIONS: Symptoms like rash, edema, eschar, and abdominal pain may indicate the possibility of MSF during the assessment of acute febrile illness, IFA and real-time PCR are the primary diagnostic methods for this disease.

Molecular investigation of Coxiella burnetii in aborted fetus of small ruminants in southeast Iran.

The domestic animal, known as a main reservoir of Coxiella burnetii, is susceptible to the occurrence of coxiellosis, which can lead to abortions in domestic animals, causing significant economic damage and posing risks to human health. Therefore, the purpose of this study is to investigate C. burnetii as the causative agent of Q fever in abortion samples of small ruminants in southeastern Iran. This study was conducted between 2020 and 2021 in Zarand city, located in Kerman province (southeast Iran). In this study, 50 abomasum swab samples of aborted sheep and goat fetuses were collected and analyzed using molecular methods to identify C. burnetii. The results revealed that 26% (n: 13) of the collected abortion samples were infected with C. burnetii. Among the positive samples, two (50%) belonged to goat abortion samples while 11 (23.9%) belonged to sheep abortion samples. This study demonstrates that C. burnetii is one of the causes of abortion in small ruminants in southeastern Iran. It is recommended to pay more attention to C. burnetii in domestic animals due to its significant economic impact on livestock and its potential implication for human health in Iran.

Molecular detection of Brucella species among aborted small ruminants in southeast Iran.

Brucellosis, caused by Brucella bacteria, is a common zoonotic infectious disease with various clinical manifestations in humans and animals. The disease is endemic in human and ruminant populations in Iran, with a particular prevalence in areas where humans have close interactions with livestock. Since domestic animals serve as the primary reservoir for brucellosis, this study aimed to identify the presence of Brucella spp. among aborted small ruminants in southeast Iran. Between 2021 and 2022, aborted fetuses of small ruminants (46 sheep and 4 goats) were collected from Zarand County in the Kerman province. Swab samples from the abomasum contents of these fetuses were obtained and subjected to DNA extraction. The samples were then tested for Brucella spp. detection using the polymerase chain reaction (PCR) method. Out of the 50 aborted fetuses examined, Brucella spp. was detected in 15 (30%) specimens, comprising 13 (28%) sheep and 2 (50%) goats. Species typing revealed the presence of Brucella ovis (6 sheep and 1 goat), Brucella melitensis (6 sheep), and Brucella abortus (1 sheep) among the positive specimens. This cross-sectional study highlights the high prevalence of various Brucella species in samples from small ruminant abortions in southeast Iran. Additionally, the identified Brucella species were not limited to their primary host livestock. These indicated potential cross-species transmission among small ruminants.

The surveillance of plague among rodents and dogs in Western Iran.

BACKGROUND: The causative agent of plague, Yersinia pestis, is maintained in nature via a flea-rodent cycle. Western Iran is an old focus for plague, and recent data indicate that rodents and dogs in this region have serological evidence of Y. pestis infection. The purpose of this study was to conduct a large-scale investigation of Y. pestis infection in shepherd dogs, rodents, and their fleas in old foci for plague in Western Iran. MATERIALS AND METHODS: This study was conducted in Hamadan province from 2014 to 2020. Rodents and fleas were collected from various locations throughout this region. Y. pestis was investigated in rodent spleen samples and fleas using culture, serology, and real-time PCR methods. Additionally, sera samples were collected from carnivores and hares in this region, and the IgG antibody against the Y. pestis F1 antigen was assessed using an ELISA. RESULTS: In this study, 927 rodents were captured, with Meriones spp. (91.8%) and Microtus qazvinensis (2.6%) being the most prevalent. A total of 6051 fleas were collected from rodents and carnivores, most of which were isolated from Meriones persicus. None of the rodents or fleas examined tested positive for Y. pestis using real-time PCR and culture methods. Meanwhile, IgG antibodies were detected in 0.32% of rodents. All serologically positive rodents belonged to M. persicus. Furthermore, none of the sera from the 138 carnivores (129 sheepdogs, five Vulpes vulpes, four Canis aureus), and nine hares tested positive in the ELISA test. CONCLUSION: This primary survey of rodent reservoirs shows serological evidence of Y. pestis infection. Western Iran is an endemic plague focus, and as such, it requires ongoing surveillance.

Genotyping and phylogenetic analysis of Coxiella burnetii in domestic ruminant and clinical samples in Iran: insights into Q fever epidemiology.

Coxiella burnetii, a zoonotic pathogen, is the causative agent of Q fever, an endemic disease in Iran. However, there is currently a lack of available data on the genotypes of C. burnetii in the country. Here, we typed 26 C. burnetii isolates detected in milk, abortion, cotylodon, and cardiac valve samples from various geographical areas and hosts (7 cattle, 8 goats, 10 sheep, and 1 human) using Multilocus Variable Number Tandem Repeat Analysis (MLVA/VNTR) with five loci:ms24, ms27, ms28, ms33, and ms34. As IS1111 was observed to be spontaneously inserted in locus ms23 across all of our examined C. burnetii samples, five loci were employed for MLVA/VNTR genotyping. Among the 26 C. burnetii strains, 22 distinct genotypes (A-V) were identified in the discriminative loci. In silico analysis categorized Iranian C. burnetii strains into five genomic groups along with seven singletons, representing 11 exiting clonal complexes worldwide. Clusters 10 and 11 exclusively consisted of Iranian samples. These findings revealed high genotyping diversity among C. burnetii isolates in Iran. The genotypes circulating in Iran differed significantly from those found in other regions worldwide. To gain a comprehensive understanding of Q fever epidemiology in Iran, it is crucial to conduct large-scale studies that assess the distribution of C. burnetii genotypes across different geographical areas, hosts, and sources.

Molecular investigation of Coxiella burnetii and Francisella tularensis infection in ticks in northern, western, and northwestern Iran.

Tularemia and Q fever are endemic diseases in Iran; however, little information is available on the prevalence of the causative agents, Coxiella burnetii and Francisella tularensis, in Iranian ticks. This study investigated C. burnetii and F. tularensis among hard ticks in this country. We collected ticks from livestock and other mammals in Guilan, Mazandaran, Golestan (northern Iran), Kurdistan (western Iran), and West Azerbaijan (northwestern Iran) provinces. Genomic DNA from collected ticks was extracted and screened for C. burnetii and F. tularensis using Real-time PCR. A total of 4,197 ticks (belonging to 12 different species) were collected, and Ixodes ricinus (46.4%), Rhipicephalus turanicus (25%), and Rhipicephalus sanguineus sensu lato (19.1%) were the most collected species. Of 708 pooled tick samples, 11.3% and 7.20% were positive for C. burnetii and F. tularensis, respectively. The genus of Rhipicephalus had the highest (18.3%) C. burnetii infection among the collected tick pools (P<0.001). Furthermore, the most positive pools for F. tularensis belonged to Haemaphysalis spp. (44.4%). Kurdistan had the most significant percentage of C. burnetii-infected ticks (92.5%), and there was a meaningful relationship between the provinces and the infection (P< 0.001). The ticks from Golestan exhibited the highest F. tularensis infection rate (10. 9%), and the infection showed no significant relationship with the provinces (P = 0.19). Ticks collected from grasslands had a higher Coxiella burnetii infection rate than those collected from animals (39.4% vs. 7.9%; p<0.01). However, ticks collected from animal surfaces had a slightly higher rate of Francisella tularensis infection than those collected from grasslands (7.6% vs. 3.9%; p = 0.24). Here, we demonstrated the presence of both pathogens in the north (Guilan, Mazandaran, and Golestan provinces), the west (Kurdistan province), and the northwest (West Azerbaijan province) of Iran. The public health system should pay particular attention to tick bites in veterinary medicine and humans.

Clinical, hematological and molecular evaluation of piroplasma and Anaplasma infections in small ruminants and tick vectors from Kurdistan province, western Iran.

Tick-borne haemoparasite infections are a major challenge in small ruminant (SR) production across tropical areas. The present study evaluated the prevalence of Theileria, Babesia and Anaplasma in SRs and their tick vectors and estimated the association between pathogen prevalence with clinical hematological findings among SR populations in Kurdistan province, western Iran. In total, 250 blood samples and 250 tick species (one per animal) were collected from SR populations, along with clinical and hematological examinations. Microscopy of blood smears and molecular analysis were performed to detect potential infection with Theileria, Babesia and Anaplasma. Moreover, haemoparasites were explored in the isolated ticks using semi-nested PCR. Based on microscopy, the prevalence of Theileria, Anaplasma and Babesia infections was 91.2%, 23.2% and 2.4%, respectively. Semi-nested PCR analysis of blood samples demonstrated 86.8%, 78.8% and 14% prevalence for T. ovis, A. ovis and B. ovis, respectively. Dermacentor marginatus and Rhipicephalus turanicus were predominant isolated tick vectors from SR, while D. marginatus was the most contaminated tick in all investigated counties. There were, also, a statistically significant association between the estimated molecular prevalence rates with semi-yellow conjunctiva (A. ovis), body temperature (T. ovis and A. ovis), heart rate (T. ovis and B. ovis), mean white blood cell count (T. ovis and A. ovis), mean red blood cell count (T. ovis and B. ovis), as well as mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in all haemoparasite infections. Future studies are recommended to reveal the epidemiology of such infections in SRs in Iran.

Serological evidence of Yersinia pestis infection in rodents and carnivores in Northwestern Iran.

BACKGROUND: Plague may recur after several decades in its endemic regions; therefore, the continuous monitoring of wildlife is essential, even when no human cases are reported in the old foci. The present study was conducted to monitor rodents and their ectoparasites as well as carnivores to learn about the epidemiology of plague infection in an old focus of Iran. METHODOLOGY: The present study was conducted from 2019 to 2020 in Takestan county of Qazvin Province in northwestern Iran. Rodents were caught using live traps, and their fleas were separated. Blood and spleen specimens were taken from the captured rodents. Serum samples were also collected from sheepdogs and wild carnivores. The collected samples were tested by culture, serology (ELISA), and molecular methods to detect Yersinia pestis infection. FINDINGS: A total of 399 small mammals were caught, of which 68.6% were Meriones persicus. A total of 2438 fleas were collected from the rodents, 95.3% of which were Xenopsylla buxtoni. Overall, 23 out of 377 tested rodents (5.7%, CI 95%, 3.9-9.0) had IgG antibodies against the F1 antigen of Y. pestis, and all the positive samples belonged to M. persicus. Nine (4.8%) out of 186 collected sera from the sheepdogs' serum and one serum from the Canis aureus had specific IgG antibodies against the F1 antigen of Y. pestis. There were no positive cases of Y. pestis in the rodents and fleas based on the culture and real-time PCR. CONCLUSION: Serological evidence of Y. pestis circulation was observed in rodents and carnivores (sheepdogs and C. aureus). The presence of potential plague vectors and serological evidence of Y. pestis infection in the surveyed animals could probably raise the risk of infection and clinical cases of plague in the studied region. Training health personnel is therefore essential to encourage their detection of possible human cases of the disease.

Molecular surveillance for Rickettsia spp. and Bartonella spp. in ticks from Northern Iran.

Tick-borne zoonotic diseases pose a threat to public health; hence, identifying the pathogenic agents associated with them is critical. The prevalence of Bartonella and Rickettsia in Iran is unknown. This study aimed to detect Rickettsia spp. and Bartonella species in ticks in northeast Iran and conduct phylogenetic analysis on these bacteria. Ticks from the sample bank in the Research Center for Emerging and Re-emerging Diseases were included in this study. The ticks were collected in 2017 and 2018 from domestic animals (sheep, goats, cows, camels, horses, dogs, and donkeys) and rodents in Golestan, Mazandaran, and Guilan provinces. Molecular methods were used to examine the DNA extracted from these samples to detect Rickettsia spp. and Bartonella species. The study examined a total of 3999 ticks. Ixodes ricinus (46.4%), Rhipicephalus turanicus (26.3%), and Rhipicephalus sanguineus (17.1%) were the most prevalent species. Among 638 DNA pools, real-time-PCR detected Rickettsia spp. in 161 (25.2%), mostly belonging to Rh. sanguineus (48.9%) and Rh. turanicus (41.9%). Golestan Province had the highest number of positive pools (29.7%). No positive samples for Bartonella were detected in a 638 pooled samples. Eight distinct Rickettsia species were detected in 65 sequenced samples, the majority of which were R. massiliae (n = 32, 49.2%) and R. sibirica (n = 20, 30.8%). Other species included R. rhipicephali (n = 3), R. aeschlimannii (n = 5), R. helvetica (n = 5), R. asiatica (n = 4), R. monacensis (n = 6), and R. raoultii (n = 1). The research findings may provide helpful information about tick-borne Rickettsiae in Iran and help to clarify the role of these arthropods in maintaining these agents. Rickettsia species were found to be circulating in three Northern provinces; thus, it is recommended that this disease be considered in the differential diagnosis of febrile diseases caused by tick bites and febrile diseases with skin rashes such as Crimean-Congo hemorrhagic fever (CCHF).

Targeted gene inactivation in Salmonella Typhi by CRISPR/Cas9-assisted homologous recombination.

BACKGROUND: Targeted gene inactivation (TGI) is a widely used technique for the study of genes' functions. There are many different methods for TGI, however, most of them are so complicated and time-consuming. New promising genetic engineering tools are developing for this purpose. In the present study, for the first time we disrupted a virulence gene from Salmonella enterica serovar Typhi (S. Typhi), located in the bacterial chromosome using CRISPR/Cas9 system and homology directed repair (HDR). METHODS: For this aim, pCas9 plasmid containing Cas9 enzyme and required proteins for homology directed recombination was transferred to S. Typhi by electroporation. On the other hand, a specific guide RNA (gRNA) was designed using CRISPOR online tool. Synthetic gRNA was cloned into pTargetF plasmid. Also, a DNA fragment (HDR fragment) was designed to incorporate into the bacterial chromosome following the cleavage of the bacterial genome by Cas9 enzyme. pTargetF containing gRNA and HDR fragment were co-transferred to S. Typhi containing pcas9 plasmid. The transformed bacteria were screened for recombination using PCR, restriction digestion and sequencing. RESULTS: The results of PCR, restriction digestion and sequencing showed the successful recombination of S. Typhi, in which the gidA gene is disrupted. CONCLUSION: In the present study we aimed to develop a rapid and robust method for targeted gene inactivation in a bacterial species, S. Typhi. This procedure can be exploited for disruption of other Salmonella as well as other bacteria's genes.

Assessment of Helicobacter pylori positive infected patients according to Clarithromycin resistant 23S rRNA, rpl22 associated mutations and cyp2c19*1, *2, *3 genes pattern in the Early stage of Gastritis.

OBJECTIVE: Clarithromycin resistant Helicobacter pylori (CAM-R) is the main cause of standard triple therapy eradicating failure. Proton pump inhibitors (PPIs) directly pose bacteriocidic activity and prepare the optimum condition for Clarithromycin's best function. In counter with Poor metabolizer subjects, Homozygote Extensive Metabolizers have well characterized by treatment failure. Eventually, determination of CAM-R profile and estimation of PPIs metabolization rate support clinicians in better prescription. So, we explored Helicobacter pylori'mutations in 23S rRNA and rpl22 resistant genes, and cyp2c19 *1, *2, *3 allele variations, and PPIs metabolization patterns in patients, consequently the results reported to the physician. RESULTS: Sixteen out of 96 patients considered to be CAM-R Helicobacter pylori. A2143C (1/16), rpl22 insertion (16/16), and GTG deletion (2/16) recorded in CAM-R strains. P450 2C19 human genotyping demonstrated that the highest proportion of the H. pylori- positive strains infected patients 43/61(70.49%) categorized in Homozygote extensive metabolizer class. The rest (12/61)19.67% classified as Poor metabolizers, and 6/61(9.83%) distinct from Heterozygote extensive metabolizer group. Proportion of poor metabolizers and Heterozygote extensive metabolizer phenotypes between CAM-R strains mentioned to be 10/16(62.5%), and 6/16(37.5%). Cross points between the most frequently distributed allele in CAM-R strains indicated 81.25% for *2, and w2 for 18.75%.

Genetic Diversity of Coxiella burnetii in Iran by Multi-Spacer Sequence Typing.

Coxiella burnetii, the zoonotic agent of Q fever, has a worldwide distribution including Iran. However, no information regarding the circulating genotype of this infection has been reported in Iran. This study aimed to evaluate the genetic diversity of C. burnetii in Iran using the multi-spacer sequence typing (MST) method. First, 14 positive C. burnetii samples (collected from four sheep, three goats, and seven cattle) were confirmed using quantitative polymerase chain reaction (qPCR) targeting the IS1111 gene. Then, ten spacers (Cox 2, 5, 18, 20, 22, 37, 51, 56, 57, and 61) were amplified using PCR for future MST analysis. The in-silico MST genotyping analysis of domestic ruminant samples revealed two new alleles (Cox5.11 and Cox56.15) in Cox5 and Cox56 loci that led to the emergence of four novel MST genotypes (MST62, 63, 64, and 65) and one MST genotype that has been previously described (MST61). This study showed the circulation of five MST C. burnetii genotypes among Iranian domestic ruminants. Understanding the C. burnetii genotypic profiles is critical in determining and preventing Q fever outbreaks.