Integration and evaluation of cutaneous leishmaniasis laboratory diagnosis in the primary health care laboratory network.

Background: The lack of an integrated national system prevents the Islamic Republic of Iran from registering and reporting all cases of cutaneous leishmaniasis. Aim: To establish a laboratory network for the improvement of diagnosis and surveillance of cutaneous leishmaniasis in endemic areas of the Islamic Republic of Iran using parasitological and molecular methods. Methods: This descriptive, cross-sectional, pilot study examined 49 laboratories in the 2 endemic areas for cutaneous leishmaniasis in the Islamic Republic of Iran. Samples were taken for identification of the dominant Leishmania species from individuals with cutaneous leishmaniasis referred to the laboratories and had not travelled to other endemic regions. Statistical analysis was conducted using SPSS version 25.0. Using the primary healthcare laboratory network, we established a 3-level surveillance system. We compared misdiagnosis, new cases, clinical relapses, treatment resistance, and treatment failure before and after establishment of the network. Results: Network implementation reduced relapse of cutaneous leishmaniasis. After the laboratory training, the average misdiagnosis rate decreased from 49.3% to 4.2% for positive microscopic slides and from 31.6% to 12% for negative slides. Correct diagnosis was significantly higher in the study areas after the intervention. Conclusion: Implementation of a cutaneous leishmaniasis laboratory network can enhance diagnosis, unify diagnostic methods and improve patient care.

Visceral Leishmaniasis in Iran: An Update on Epidemiological Features from 2013 to 2022.

Background: Visceral leishmaniasis (VL) is one of the most important neglected tropical diseases. The zoonotic form of VL is endemic in some areas of Iran. We aimed to determine the status of VL identified in humans and canines in different parts of Iran from 2013 to 2022. Method: A national representative cross-sectional study was conducted in 10 provinces of Iran, including the national leishmaniasis reference lab. We employed the direct agglutination test (DAT) as a reliable serological method to detect anti-Leishmania infantum antibodies in humans and animal reservoir hosts. Additionally, a narrative literature review was conducted to identify relevant studies on VL seroprevalence in Iran from 2013 to 2023. Results: The results of 21281 human and 5610 canine serum samples from 2013 to 2022 are reported. Altogether, 448 (2.1%, 95%CI: 2.0-2.3) human serum samples showed anti-L. infantum antibody levels of ≥1:3200. Of these samples, 13716 (64.5%) were collected actively, which showed a seroprevalence of 0.6% (95% CI: 0.5-0.8) and 7565 (35.5%) were collected passively, which showed a seroprevalence of 4.8% (95%CI: 4.3-5.3). Overall, 1035 (20.1%, 95%CI: 19.0-21.2) of 5160 domestic dogs (Canis familiaris) samples showed anti-L. infantum antibody levels of ≥1:320. Northwest (2.8%) and northeast (0.96%) regions had the highest human VL seroprevalence, while northwest (21.5%) and south (14.4%) regions had the highest canine VL seroprevalence. Conclusion: Zoonotic VL, an endemic parasitic disease, is still present in several different distinct areas across Iran. While human VL cases have shown a declining trend over the last decade, the prevalence of canine VL remains significant.

Mapping current and future risk of scorpion sting from a species with low medical concern, Mesobuthus phillipsii (Scorpiones: Buthidae) in Iran.

Scorpion stings are one of the most important health challenges and high priority research topic in public health. In this study, we aimed to model habitat suitability of the Mesobuthus phillipsii (Pocock 1889), a species with low medical concern, under current and future climatic conditions in Iran. We also identified vulnerable populations to scorpion stings in the country. Scorpion sting risk modeling was done using an ensemble approach by considering two species distribution modeling methods: MaxEnt and Random Forest methods. Distribution modeling was performed using the sdm R package. The results showed that due to climate change in 2070, the high-risk areas will increase from 20,839 to 79,212 km2. Habitats with a moderate risk of scorpion stings will also increase from 139,347 to 222,833 km2. Consequently, the number of villages in high-risk areas of scorpion stings will increase from 2,870 to 7,017, while this number will increase from 12,759 to 20,104 in the case of medium-risk villages. The results of this study can be used for scorpion stings management in Iran. This study can be used as an example for similar studies on scorpions with high medical emergency.

SARS-CoV-2 in domestic cats (Felis catus) in the northwest of Iran: Evidence for SARS-CoV-2 circulating between human and cats.

This study aimed to investigate the prevalence of COVID-19 in domestic cats, focusing on the disease in the northwest of Iran and then showing the natural transmission of SARS-COV-2 circulating between domestic cats and humans. After receiving ethic codes from Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1399.303) and confirmed by the Center of Communicable Diseases Control (CDC) of Iran, 124 domestic cats were collected from the homes and only one hospital of Meshkin -Shahr district from northwestern Iran where SARS-CoV-2 patients were hospitalized and quarantined during 2020. Samples were prepared from fluid materials of oropharynx and nasopharynx. All samples were tested by real-time PCR (RT-PCR) using specific genes N and ORF1ab in Pasteur Institute of Iran, and then partial sequence analyses of S gene were performed. All collected cats were kept in separated cages until SARS-COV-2 infection was confirmed with the RT-PCR. RT- PCR Ct values of 123 collected cats were ≥40; thus, all of them showed negative results, but one of the collected cats with close contact with its owner, whom confirmed SARS-CoV-2 showed positive results with gene N(Ct=30) and gene ORF1ab (Ct=32). Furthermore, the positive pet cat showed respiratory and gastro-intestinal clinical manifestations, and its owner was infected with SARS-CoV-2 two weeks ago. Cats are susceptible animals to SARS-CoV-2 infection. Epidemiological evidence showed that SARS-COV-2 is able to transmit to healthy cats due to having close contact with its owner as a reverse zoonosis.

Leishmania spp. infection in Rhombomys opimus and Meriones libycus as main reservoirs of zoonotic cutaneous leishmaniasis in central parts of Iran: Progress and implications in health policy.

Rodents from the subfamily Gerbillinae are the principal reservoir of cutaneous leishmaniasis (CL) caused by Leishmania major in the center and northeast of Iran. This study was conducted to determine both naturally occurring Leishmania infection rates and the distribution of Leishmania species in the central parts of Iran during 2019-2020. In this regard, presence of Leishmania parasites were confirmed by microscopic examination and the species were identified by nested-PCR using the Internal Transcribed Spacer2- Ribosomal DNA (ITS2-rDNA). Finally, some samples were sequenced and, the blast analysis of L. major samples, showed a 92.45-100% homology to the L. major sequence. Of the 181 wild gerbils collected (Rhombomys opimus=157 and Meriones lybicus=24), 88 (48.6%) tested positive for Leishmania sp. by microscopic examination whereas 162 (89.5%) were positive by nested-PCR. Of the 162 infected gerbils, 103 showed single strain infections (30 L. major, 28 L. gerbilli and 45 L. turanica), 43 showed dual infections with only the non-human species (L. gerbilli and L. turanica), and 16 were mixed infections of L. major and L. turanica (n = 14) or L. gerbilli (n = 2). All single or mixed L. major infections were detected in gerbils from areas with reports of human CL during the last decade. These findings suggest that Rhombomys opimus and Meriones libycus have a potential role in the maintenance of human and non-human transmission of Leishmania species in the CL foci.

Spatial Distribution of Common Pathogenic Human Intestinal Protozoa in Iran: A Systematic Review.

BACKGROUND: Pathogenic intestinal protozoa are considered as a serious public health problem in developing countries. This study aimed to elucidate the overall prevalence and spatial distribution of three common human pathogenic intestinal protozoan infections in Iran. METHODS: Six English and Persian databases were explored for published papers on the prevalence of Entamoeba histolytica/dispar, Giardia lamblia, and Cryptosporidium spp. in the general population of Iran from 2000 to 2015. All eligible data were collected using a pre-designed data extraction form, and the overall prevalence was estimated using a random-effects meta-analysis model. We used ArcMap for mapping the prevalence of the studied protozoa and clustering analysis. RESULTS: Altogether, 118 eligible papers from 24 provinces of Iran were included and analyzed. The weighted prevalence of E. histolytica/dispar, G. lamblia, and Cryptosporidium spp. infection among Iranian general population were calculated 1.3% (95% CI 1.1-1.5%), 10.6% (95% CI 9.6-11.5%) and 2% (95% CI 1.5-2.5%), respectively. CONCLUSION: Our findings indicated human intestinal protozoan infections caused by E. histolytica/dispar, G. lamblia, and Cryptosporidium spp. have still public health importance in some parts of Iran.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Evaluation of Radiation Sensitivity in Patients with Hyper IgM Syndrome.

BACKGROUND: HIGM syndrome is a rare form of primary immunodeficiencies characterized by normal/increased amounts of serum IgM and decreased serum levels of other switched immunoglobulin classes. Since the affected patients are continuously infected with various types of pathogens and are susceptible for cancers, diagnostic and therapeutic tests including imaging techniques are recommended for the diagnosis and treatment of these patients, which predispose them to higher accumulated doses of radiation. Given the evidence of class switching recombination machinery defect and its association with an increased rate of DNA repair, we aimed to evaluate radiation sensitivity among a group of patients diagnosed with HIGM syndrome. METHODS: 19 HIGM patients (14 CD40 L and 3 AID deficiencies and 2 unsolved cases without known genetic defects) and 17 control subjects (10 healthy subjects as negative control group, 7 ataxia-telangiectasia patients as positive control group) were enrolled. G2 assay was carried out for the determination of radiosensitivity. RESULTS: Based on radiation-induced chromosomal changes among the studied HIGM patients and their comparison with the controls, almost all (95%) the patients had degrees of radiosensitivity: 6 patients with low to moderate, 1 patient with moderate, 11 patients with severe and 1 patient without radiation sensitivity. CONCLUSION: Today, X-ray radiation plays a very important role in diagnostic and therapeutic procedures; while increased exposure has devastating effects especially in radiosensitive patients. Considering higher sensitivity in HIGM patients, utilizing radiation-free techniques could partly avoid unnecessary and high-level exposure to radiation, thus preventing or reducing its harmful effects on the affected patients.

Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients.

Objectives: Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement caused by homozygous or compound heterozygous mutations in the ataxia telangiectasia mutated (ATM) gene which encodes a serine/threonine protein kinase. The aims of this study were to investigate class switch recombination (CSR) and to review the clinical and immunologic phenotypes of 3 groups of A-T patients, including A-T patients with CSR defects (CSR-D), A-T patients with selective immunoglobulin A deficiency (IgA-D) and A-T patients with normal Ig level. Methods: In this study, 41 patients with confirmed diagnosis of A-T (16 A-T patients with HIgM, 15 A-T patients with IgA-D, and 10 A-T patients with normal Ig levels) from Iranian immunodeficiency registry center were enrolled. B-cell proliferation, in vitro CSR toward IgE and IgA were compared between three groups as well as G2 radiosensitivity assay. Results: Earliest presentation of telangiectasia was a significant hallmark in A-T patients with CSR-D (p = .036). In this investigation, we found that the frequency of respiratory infection (p = .002), pneumonia (p = .02), otitis media (p = .008), chronic fever (p < .001), autoimmunity (p = .02) and hepatosplenomegaly (p = .03) in A-T patients with HIgM phenotype were significantly higher than the other groups. As expected IgE production stimulation and IgA CSR were perturbed in HIgM patients that were aligned with the higher readiosenstivity scores in this group. Conclusion: A-T patients with HIgM compared to other A-T patients presenting more infections and noninfectious complications, therefore, early detection and careful management of these patients is necessary.

The diagnostic accuracy of direct agglutination test for serodiagnosis of human visceral leishmaniasis: a systematic review with meta-analysis.

BACKGROUND: Direct agglutination test (DAT) as a simple, accurate and reliable method, has been widely used for serodiagnosis of visceral leishmaniasis (VL) during the last three decades. The present study is a systematic review and meta-analysis to evaluate the diagnostic accuracy of DAT for serodiagnosis of human VL. METHODS: Electronic databases, including MEDLINE (via PubMed), SCOPUS, Web of Science, SID and Mag Iran (two Persian scientific search engines) were searched from December 2004 to April 2019. We determined the pooled sensitivity and specificity rates of DAT for the diagnosis of human VL, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic (ROC) curves parameters across the eligible studies. RESULTS: Of the 2928 records identified in the mentioned electronic databases and after examining reference lists of articles, 24 articles met inclusion criteria and were enrolled in the systematic review and out of them 20 records qualified for meta-analysis. The pooled sensitivity and specificity rates of DAT was 96% [95% CI, 92-98] and 95% [CI95% 86-99], respectively. The likelihood ratio of a positive test (LR+) was found to be 21 [CI95%, 6.6-66.5] and the likelihood ratio of a negative test (LR-) was found to be 0.04 [(CI95%, 0.02-0.08]. The combined estimate of the diagnostic odds ratio for DAT was high [467 (CI95%, 114-1912]). We found that the summary receiver operating characteristic curve (SROC) is positioned near the upper left corner of the curve and the area under curve (AUC) was 0.98 (95% CI, 0.97 to 0.99). CONCLUSION: Referring to our analysis, we determined that DAT can be considered as a valuable tool for the serodiagnosis of human VL with high sensitivity and specificity. As DAT is a simple, accurate and efficient serological test, it can be recommended for serodiagnosis of human VL particularly in endemic areas.

Tehran environmental and neurodevelopmental disorders (TEND) cohort study: Phase I, feasibility assessment.

PURPOSE: To advance knowledge about childhood neurodevelopmental disorders and study their environmental determinants, we conducted a study in Tehran, Iran to assess the feasibility of prospective birth cohort study. METHODS: We evaluated participation of pregnant women, feasibility of sampling biological material, and health care services availability in Tehran in four steps: (1) first trimester of pregnancy; (2) third trimester of pregnancy; (3) at delivery; and (4) two to three months after delivery. We collected related data through questionnaires, also various biological samples were obtained from mothers (blood, urine, milk and nails-hands and feet) and newborns (umbilical cord blood, meconium, and urine samples) from February 2016 to October 2017. RESULTS: overall 838 eligible pregnant women were approached. The participation rate was 206(25%) in our study and about 185(90%) of subjects were recruited in hospitals. Out of 206 participants in the first trimester, blood, urine, hand nail, and foot nail samples were collected from 206(100%),193(93%), 205(99%), and 205(99%), respectively. These values dropped to 65(54%), 83(69%), 84(70%), and 84(70%) for the remaining participants 120(58%) in the third trimester, respectively. Also, we gathered milk samples from 125(60%) of mothers at two to three months after delivery. CONCLUSION: Our findings suggest that hospitals were better places for recruitment of subjects in a birth cohort in Tehran. We further concluded that birth cohort study recruitment can be improved by choosing appropriate gestational ages. Obtaining the newborn's urine, meconium, and umbilical cord blood were challenging procedures and require good collaboration between hospital staff and researchers.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Evaluation of respiratory complications in patients with X-linked and autosomal recessive agammaglobulinemia.

BACKGROUND: Congenital agammaglobulinemia is the first primary immunodeficiency disorder characterized by a defect in B lymphocyte development and subsequently decreased immunoglobulin levels. These patients are prone to suffer from recurrent infections mostly involving the respiratory tract. In this study, we aimed to describe in detail respiratory tract complications as the most prominent clinical feature among agammaglobulinemic patients. METHODS: A total number of 115 patients were included. Demographic, clinical, and genetic data were collected from the patients' medical records. Among the available patients, pulmonary function tests (PFTs) and/or high-resolution computed tomography (HRCT) were performed. RESULTS: Respiratory tract complications (85.2%) especially pneumonia (62.6%) were the most prominent clinical features in our cohort. Among patients with abnormal PFT results (N = 19), a mixed respiratory pattern was observed in 36.8%. HRCT was carried out in 29 patients; Bhalla scoring-based evaluation of these patients indicated excellent (44.8%), followed by good (34.5%) and mild (20.7%) results. Bronchiectasis was found in 13 patients undergoing HRCT (44.8%). We found significant inverse correlations between the Bhalla score and incidence rate of pneumonia, as well as the presence of bronchiectasis. Patients with abnormal PFT results had statistically significant higher bronchiectasis frequency and lower Bhalla scores compared to those with normal results. Forty-one patients were deceased, and here, respiratory failure was the most common cause of death (45.5%). CONCLUSION: High prevalence of respiratory tract infections among agammaglobulinemic patients and subsequent progression to permanent lung damage highlights the importance of implementing respiratory evaluation as part of routine follow-up program of agammaglobulinemic patients. Physicians should be aware of this and regularly monitor the respiratory function of these patients to allow for timely diagnosis and treatment initiation aiming to improve patients' prognosis and quality of life.

Primary Immunodeficiency Diseases and Bacillus Calmette-Guérin (BCG)-Vaccine-Derived Complications: A Systematic Review.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccine is a live attenuated bacterial vaccine derived from Mycobacterium bovis, which is mostly administered to neonates in regions where tuberculosis is endemic. Adverse reactions after BCG vaccination are rare; however, immunocompromised individuals and in particular patients with primary immunodeficiencies (PIDs) are prone to develop vaccine-derived complications. OBJECTIVE: To systematically review demographic, clinical, immunologic, and genetic data of PIDs that present with BCG vaccine complications. Moreover, we performed a meta-analysis aiming to determine the BCG-vaccine complications rate for patients with PID. METHODS: We conducted electronic searches on Embase, Web of Science, PubMed, and Scopus (1966 to September 2018) introducing terms related to PIDs, BCG vaccination, and BCG vaccine complications. Studies with human subjects with confirmed PID, BCG vaccination history, and vaccine-associated complications (VACs) were included. RESULTS: A total of 46 PIDs associated with BCG-VAC were identified. Severe combined immunodeficiency was the most common (466 cases) and also showed the highest BCG-related mortality. Most BCG infection cases in patients with PID were reported from Iran (n = 219 [18.8%]). The overall frequency of BCG-VAC in the included 1691 PID cases was 41.5% (95% CI, 29.9-53.2; I2 = 98.3%), based on the results of the random-effect method used in this meta-analysis. Patients with Mendelian susceptibility to mycobacterial diseases had the highest frequency of BCG-VACs with a pooled frequency of 90.6% (95% CI, 79.7-1.0; I2 = 81.1%). CONCLUSIONS: Several PID entities are susceptible to BCG-VACs. Systemic neonatal PID screening programs may help to prevent a substantial amount of BCG vaccination complications.

The evaluation of neutropenia in common variable immune deficiency patients.

Objectives: Common variable immunodeficiency is a primary immunodeficiency disease characterized by hypogammaglobulinemia and heterogeneous clinical features. Neutropenia is a rare complication among CVID patients leading to a higher rate of infections and morbidity. Multiple factors (e.g. autoimmunity, infections, drugs and etc.) are found to underlie this complication.Methods: In the present study, demographic, clinical and laboratory data were compared between two groups of CVID patients with and without neutropenia.Results: Frequency of neutropenia was 8.1%. Infectious complications were the most prevalent clinical manifestations regardless of presence of neutropenia. However, candida infection and septicemia were significantly higher in neutropenic patients (p = 0.001 and p = 0.01, respectively). The most prominent clinical phenotypes of CVID patients with neutropenia were polyclonal lymphocytic infiltration and autoimmunity, both being considerably higher compared to the non-neutropenic group (p = 0.04 and p = 0.009, respectively). The mortality rate in neutropenic patients was higher than in patients without neutropenia (61.1 vs. 25.2%, p = 0.004).Conclusion: Although neutropenia is a rare complication among CVID patients, it is associated with frequent and severe clinical complications, including autoimmunity and lymphoproliferative conditions. Also, its accompaniment with higher mortality frequency in CVID patients indicates a need for more precise attention and consideration regarding specific treatment in neutropenic patients.

Comparison of clinical and immunological features and mortality in common variable immunodeficiency and agammaglobulinemia patients.

Common Variable Immunodeficiency (CVID) and agammaglobulinemia are two of the main types of symptomatic primary antibody deficiencies. The pathogenic origins of these two diseases are different; agammaglobulinemia is a group of inherited disorders that usually are caused by mutations in the gene encoding Bruton Tyrosine Kinase (BTK) protein while CVID is a heterogeneous disorder mainly without monogenic cause. However, both diseases share a characteristic of frequent bacterial infections, a decline in serum immunoglobulin levels, and abnormality in antibody responses. The demographics and immunologic parameters, clinical manifestation, and mortality statistics from 297 patients with CVID and agammaglobulinemia followed up over 2 decades in the Children's Medical Center of Iran. Age at onset of symptom in agammaglobulinemia was earlier than CVID but the course of disease in CVID patients was longer than agammaglobulinemia patients. Pulmonary infections were the most prevalent clinical manifestations in both groups of patients. Lymphadenopathy, hepatomegaly, and splenomegaly were significantly higher in CVID patients than agammaglobulinemia patients and there was a significant association between these complications and mortality in CVID patients. Among 297 patients, 128 patients (88 CVID and 40 agammaglobulinemia) deceased. The predominant causes of death in CVID patients were infections, chronic lung disease, and malignancy while in agammaglobulinemia patients were infections and respiratory failure. Infections, especially respiratory infections were the most common complication and cause of death in both CVID and agammaglobulinemia groups and recent treatment advances even Immunoglobulin replacement cannot completely control these complications. Thus prompt recognition and specific management of these complications are worthwhile.

Retrieving ascarid and taeniid eggs from the biological remains of a Neolithic dog from the late 9th millennium BC in Western Iran.

BACKGROUND: Paleoparasitology reveals the status of parasitic infections in humans and animals in ancient times based on parasitic particles found in biological remains from archaeological excavations. This line of research emerged in Iran in 2013. OBJECTIVE: The identification of parasites from Neolithic times is an attractive subject that shows the oldest origins of parasitic infections in a given geographical region. From an archaeological point of view, this archaeological site is well-known for animal domestication and agriculture in ancient Iran. METHODS: In this study, soil deposited on the surface and in the pores of a dog pelvic bone was carefully collected and rehydrated using trisodium phosphate solution. FINDINGS: The results showed ascarid and taeniid eggs retrieved from the biological remains of a dog excavated at the East Chia Sabz archaeological site, which dates back to the Neolithic period (8100 BC). MAIN CONCLUSION: The current findings clearly illustrate the natural circulation of nematode and cestode parasites among dogs at that time. These ancient helminth eggs can also be used to track the oldest parasitic infections in the Iranian plateau and contribute to the paleoparasitological documentation of the Fertile Crescent.

Retrieving ascarid and taeniid eggs from the biological remains of a Neolithic dog from the late 9th millennium BC in Western Iran

BACKGROUND Paleoparasitology reveals the status of parasitic infections in humans and animals in ancient times based on parasitic particles found in biological remains from archaeological excavations. This line of research emerged in Iran in 2013. OBJECTIVE The identification of parasites from Neolithic times is an attractive subject that shows the oldest origins of parasitic infections in a given geographical region. From an archaeological point of view, this archaeological site is well-known for animal domestication and agriculture in ancient Iran. METHODS In this study, soil deposited on the surface and in the pores of a dog pelvic bone was carefully collected and rehydrated using trisodium phosphate solution. FINDINGS The results showed ascarid and taeniid eggs retrieved from the biological remains of a dog excavated at the East Chia Sabz archaeological site, which dates back to the Neolithic period (8100 BC). MAIN CONCLUSION The current findings clearly illustrate the natural circulation of nematode and cestode parasites among dogs at that time. These ancient helminth eggs can also be used to track the oldest parasitic infections in the Iranian plateau and contribute to the paleoparasitological documentation of the Fertile Crescent.

Simplified Pan-species Real-time PCR-based Detection of Plasmodium Spp. in Blood Smear.

BACKGROUND: We aimed to quicken and simplify the detection of Plasmodium in blood samples by developing and testing a pan-Plasmodium real-time PCR for accurate screening of individuals suspected of malaria. METHODS: A single primer/probe set for pan-species Plasmodium-specific real time PCR targeting a conserved region of the small subunit 18S ribosomal DNA was designed and evaluated for rapid diagnosis and screening of malaria infections using dried blood smears. FTA cards were used for rapid and simple DNA extraction. RESULTS: The primers and probes showed a positive response with the DNA extracted from bloods infected with P. falciparum and P. vivax but not with DNA extracted from various smears from uninfected blood samples. Seven positive cases positive by both microscopy and nested PCR were found among 280 blood samples taken from in South and Southeast Iran. Five samples were identified as positive for P. vivax and two as positive for P. falciparum. All positive samples were positive by real-time PCR. Furthermore, all 38-blood samples positive by microscopy were positive by real-time PCR. No microscopy-negative samples were positive by real-time PCR. CONCLUSION: By using a simple FTA card for DNA extraction and by application of the real-time PCR developed in this study, sensitivity similar to nested-PCR and microscopy was achieved. This format simplifies the detection of Plasmodium in large numbers of samples.