Pasteur Institute of Iran

---

  Introduction : Rabies is a disease that has been known since antiquity. It is a highly fatal acute disease of the central nervous system caused by a lyssavirus. Prior to the discovery of the rabies vaccine, rabies-infected individuals fell victim to the delusions and superstitions associated with this disease. Though it has been neglected in many regions of the world, rabies remains one of the most feared diseases in many developing countries, where it takes the majority of its victims. The virus circulates mainly in domestic and wild carnivores, taking 60,000 human lives worldwide every year and inflicting significant financial damage. It can, however, be well controlled due to the availability of effective Post-Exposure Prophylaxis (PEP) protocols. Pasteur Institute of Iran has had a significant role in the establishment of current PEP protocols in the world. In spite of the availability of effective PEP protocols, preventive vaccination would be preferable in endemic regions. Annually, a considerable number of exposures to animal bites occur in Iran. The current situation in the country is well-controlled by virtue of a robust surveillance system and efficient PEP treatments, resulting in considerably low death incidences from rabies. High quality vaccines recommended by the World Health Organization (WHO) are expensive and unaffordable in developing countries, where the need for rabies vaccination is greatest. Therefore, there is an increasing need to develop new cost-effective and efficient vaccines requiring fewer injections and providing longer-lasting immunity. J Med Microbiol Infec Dis, 2014, 1 (2): 10 pages.

---

Introduction: Essential oils are used as flavoring agents in various foods. Layer-by-Layer (LBL) technique is a method in which the material is dipped into a series of different solutions containing oppositely charged polyelectrolytes. The aim of this study is to investigate the effectiveness of a multilayered edible coating with an antimicrobial compound (Lemon and Peppermint) in enhancing the quality and shelf-life of rainbow trout (Oncorhynchus mykiss) during refrigerated storage (4 ± 1˚C) over a period of 16 days. Methods: In this study, multilayered coating was used with two concentrations of Lemon (LEO) and Peppermint (PEO) essential oils (0.5 and 1%). Antibacterial effect of these treatments was evaluated by enumeration of bacteria in special culture media. The control and the coated fish samples were analyzed periodically for pH and microbiological (total viable count, psychrotrophic count, lactic acid bacteria, Enterobacteriaceae, and coliform) characteristics. Results: The results obtained in this study demonstrate that multilayered coating in combination with Lemon and Peppermint essential oils can significantly decrease the number of bacteria and delay the spoilage of the samples (p<0.05). Conclusion: Multilayered edible coating with an antimicrobial compound can properly delay the growth of spoilage microorganisms and prolong the shelf life of meat products.

---

Neutrophils are part of the first line of immune response and are essential for resistance against a variety of pathogens. They professionally mediate direct killing of pathogens, recruit other phagocytes by specific chemokines, produce cytokines and interact with different immune cells to shape the adaptive response. Leishmania as an obligatory intracellular parasite has evolved to benefit this early innate response to find its way into macrophages, the final host cells. Therefore it is important to reconsider the role of neutrophils for further improvement of the current vaccine status.

---

Leishmaniasis is now accounted as a health problem and categorized as a class I disease (emerging and uncontrolled) by World Health Organization (WHO), causing highly significant morbidity and mortality with different clinical presentations. The incidence of human leishmaniasis is increasing and its geographic distribution in humans and animals is shown to be wider than estimated before. Indeed, more than 350 million people are at risk of Leishmania infection, and about 1.6 million new cases occur causing more than 50 thousand death annually. Control of leishmaniasis is highly dependent to the early diagnosis and treatment of the disease. In recent years, there have been advances in diagnosis of Leishmania infection. However, the main challenge in Leishmania diagnosis is the lack of a gold standard test in order to establish an effective strategic program to control and eradicate the disease. This review provides the latest information regarding the diagnosis of the disease, which is based on a combination of clinical features (supported by epidemiologic data) and laboratory tests including direct parasitological (microscopy, histopathology, and parasite culture), serological and molecular tests.

---

Rabies is a zoonotic viral disease. The causative agent is a negative-sense RNA genome virus of the genus Lyssavirus (Family: Rhabdoviridae). The disease, commonly transmitted by rabid dogs, is the cause of mortality of over 59000 humans worldwide annually. This disease can be prevented before the development of symptoms through proper vaccination even after exposure. Hence, improvement of the vaccination schedule in the countries where rabies is endemic is essential. In addition to the type of vaccine, injection routes also contribute to enhanced immune responses and increased potency of the vaccines. The vaccines approved by the World Health Organization (WHO) include cell culture and embryonated egg-based rabies vaccines (CCEEVs). In order to develop a vaccine against rabies, it is necessary to use an appropriate delivery system to promote a proper antigen-specific immune response. Different routes of injection such as intradermal (ID), intramuscular (IM) or subcutaneous (SC) are practiced, with controversies over their suitability. In this article, we discuss the immunological aspects of rabies vaccination by comparing ID and IM delivery systems.

---

Brucellosis and Crimean Congo Hemorrhagic Fever (CCHF) are both common zoonoses that may co-occur in similar epidemiological conditions, e.g., among young livestock breeders, veterinarians, and farmers in rural areas. Transmission of Brucella bacteria is through ingestion of contaminated dairy products, while CCHF virus infection occurs via infective tick bite or exposure of damaged skin and mucosa to the tissues and blood of viremic animals. Brucellosis occurs almost in all seasons, while CCHF is of lower incidence in the cold seasons due to decreased activity of tick vectors. CCHF mimics brucellosis and vice versa, mainly when the latter manifests severe thrombocytopenia and hemorrhage. Occasionally, the two illnesses present similar clinical features and laboratory results, e.g., fever, muscle aches, increased liver enzymes, and thrombocytopenia. This article discusses the similar clinical, epidemiological and laboratory aspects of the two diseases and warns physicians to avoid the inappropriate use of drugs such as ribavirin, which is dangerous in patients with kidney failure and pregnancy.

---

Cutaneous leishmaniasis (CL) in Iran could be considered as an emerging disease that is rapidly increasing and expanding its traditional geographical range to new foci. Sixteen registered emerging epidemics have occurred since 1998 in different provinces. Various risk factors, including agricultural development, earthquake, movement to endemic areas, construction of buildings near colonies of rodents, sleeping outside, cross-border movements, and poor sanitation, play crucial roles in the expansion of the disease. The mentioned risk factors can lead to the gradual or sudden emergence of new CL epidemics, and long-lasting endemic foci can also erupt into epidemics. This paper reviews the emerging epidemics published between 1998 and 2019 in Iran with particular emphasis on the operational aspects of control and related risk factors caused by anthroponotic CL (ACL) and zoonotic CL (ZCL). The competent surveillance system should be extended to all high-risk areas to facilitate controlling the emerging epidemics of ACL and ZCL in the affected areas.

---

The acute inflammatory response is the body’s natural reaction to inciting stimuli including trauma and pathogens. Well-known pro-inflammatory metabolites take control of this reaction to recruit the leukocytes into the inflamed tissue. These cells professionally ingest and kill the invading pathogens and clear the debris of dead or injured cells. This further signals the tissue regeneration and gain of function, another active process mediated by newly uncovered metabolites. These newly identified metabolites are anti-inflammatory in nature and downregulate the active inflammation. These molecules and their cognate receptors are novel targets for the treatment of chronic inflammatory diseases. Although not very well understood, these mediators are suspected to support intracellular parasite survival (as Leishmania parasite) and are worth further investigation for innovative therapeutic interventions.

---

Introduction: Despite considerable efforts to control AIDS pandemic, it is still one of the significant infectious concerns worldwide. The advance in medical research has led to the development of highly active antiretroviral therapy with a considerable effect to suppress the disease. However, an effective vaccine capable of eradication the HIV pandemic is not available yet. Failure to develop a prophylactic vaccine diverted the efforts to clinical trials of therapeutic vaccines. Methods: Here, we review different approaches to dendritic cell-based HIV therapeutic vaccines. We have summarized the dendritic cell-based trials as HIV therapeutic vaccination, registered in the United States clinical trial database. Results and Conclusion: The strategies applied in the clinical trials were mostly of low success rates; however, by using dendritic cell therapy, they could trigger the host immune response against HIV-1 infections.

---

Rasoul Pournaki (1921-2008), a prominent researcher, worked with the Pasture Institute of Iran from 1948 to 1978. He served meritoriously to control infectious diseases in Iran. His main research fields were the plague, relapsing fever, and poliomyelitis. He was the Director of Epidemiology and Virology Departments in the Pasteur Institute of Iran. This paper aims to appreciate his scientific contributions in control of infectious diseases by reviewing his notable services and studies.

---

Leishmaniases are tropical diseases caused by various types of intracellular protozoan species of the genus Leishmania. The infection is transmitted to vertebrate hosts by the infective bite of female sandflies. Depending on the location of the parasite in mammalian tissues and Leishmania species, leishmaniasis presents at least three primary clinical forms: visceral (VL), cutaneous (CL), and mucocutaneous (MCL). Iran is one of the significant endemic areas for CL in Asia. Here, we comprehensively reviewed the literature published from 2009 to 2019 and focused on the distribution, clinical aspects, causatives agents, reservoirs, and vectors of CL and VL in different parts of North Khorasan Province, northeast of Iran. North Khorasan Province in northeastern Iran is one of the principal foci of CL, but VL is just known as an endemic parasitic disease in some areas of this province. Based on a comprehensive literature search on studies published from 2009 to 2019, distribution, causatives agents, reservoirs, and vectors of CL and VL in different parts of North Khorasan Province were determined. Zoonotic cutaneous leishmaniasis )ZCL( due to Leishmania major is the main form of CL in this province. The principal animal reservoir hosts of the infection are rodents and Ph. sergenti is the most predominant species. VL, caused by Leishmania infantum, occurs in some parts of the province, and wild canines were confirmed as reservoirs.

---

The production of recombinant vaccines in green plants is an attractive and promising topic in genetic engineering. However, the stable transformation of green plants is a time-consuming, costly, and labor-intensive practice. Moreover, public concerns about genetically modified plants put another limitation on the development and release of transgenic plant-based recombinant vaccines. These shortcomings were addressed by developing transient gene expression systems that allow researchers to investigate candidate recombinant vaccines quickly without tedious work and high costs. A comprehensive literature review was used to gather relevant information. This approach has received much attention in various recombinant vaccine production platforms, including mammalian cell culture, insect cell culture, yeast expression systems, and, more importantly, in plant hosts. Due to their simplicity and efficiency, transient gene expression systems are now widely used to validate gene constructs and transgene expression within plant tissues. This paper describes the concept of transient gene expression and discusses the significant advantages of this approach for producing recombinant vaccines. Notably, the major types of transient gene expression viz. agroinfiltration, viral-based systems, and application of naked plasmid in plant cell culture are introduced, and some examples illustrate the pros and cons of each system. Our literature review also discusses some practical notes on the successful application of this system to provide a more comprehensive image of transient gene expression applicability in green plants. As a whole, this review contributes to the existing literature by shedding more light on various aspects of transient gene expression that have not been addressed thoroughly yet.

---

For several generations, people from some parts of Ghana have suffered in the hands of a yard-long "spaghetti-thin" worm, known as Dracunculus medinensis, which infects humans and leads to a disease known as Dracunculiasis, literally meaning "afflictions with little dragons." The disease, also commonly known as Guinea Worm Disease, Dracuntiasis, or Dracunculosis, is a 3000-year-old known parasitic infection that rarely made headlines before the mid-1980s. Guinea Worm Disease, a plague so ancient that it is believed to be the "fiery serpent torturing the Israelites in the desert," as described in the Old Testament. This paper reviews local and global efforts and strategies at eradicating the disease in Ghana and further diagnoses the problems that hindered the early realization of the desired results of these strategies. This article did not evaluate Ghana's performance in the program. It is equally arduous to unearth all the reasons contributing to the somewhat uneasy road to eradication over three decades of efforts. This review analyzes time-trends, program documents, technical and non-technical reports, and research documents that reveal that Ghana's program ended a decade of disappointing stagnation following the disruptive ethnic conflicts in the early 1990s in its most disease-endemic areas. Despite substantial reductions in the number of guinea worm cases during the mid-1980s, efforts to break the transmission chain in Ghana remained a daunting task. The efforts required continued international and political commitment, active surveillance, strengthening of interventions, and honesty of documenters at all levels.

---

The coronavirus infectious disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a severe global health challenge. The primary target for this virus is the lung. However, SARS-CoV-2 can also attack other organs, including the kidney and liver.  Some COVID-19 case reports demonstrated elevated liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin. Indeed, higher levels of liver enzymes occur in severe cases compared with mild to moderate cases. The relationship between liver injury and COVID-19 might be due to various possible reasons such as reactivation of pre-existing liver disease, viral replication in hepatic cells causing direct cytotoxicity, liver ischemia and hypoxia, cytokine storm, and drug-induced liver injury (DILI). Thus, hepatitis prevention and care services are necessary during the COVID-19 pandemic. For instance, drugs that might reactivate hepatitis B should not be prescribed for treating COVID-19. Generally, the long-term effects of SARS-CoV-2 on human health and various organs are not well understood. This review briefly discusses the relationship between SARS-CoV-2 and liver injury (hepatitis), coinfection of hepatitis and COVID-19, and SARS-CoV-2 infection in autoimmune hepatitis.

---

The term "Nosocomial" is attributed to the diseases acquired by the patient under medical care. Various microorganisms, including bacteria, viruses, and fungi, may contribute to developing nosocomial infections (NIs). Urinary tract infections (UTI), surgical-site infections (SSI), bloodstream infections (BSI), and pneumonia are the most well-known instances. We investigated various aspects of NIs and the main causative agents of NIs, particularly bacteria, antibiotic resistance, crucial viral infections in hospitals, and a brief survey of fungal infections. It was concluded that specific human body tissues such as those in the lungs and urinary tract are more likely to be a target for nosocomial pathogens. The fatalities associated with these infections, particularly in the intensive care unit (ICU), are serious concerns, and transmission by health facilities has become a primary medical issue because of its spread into the community. Another medical point is antibiotic resistance which is a leading cause of prolonged periods of hospitalization and makes the treatment procedure harder and costlier. Additionally, measures to prevent the spread of NIs and minimize the economic loss are discussed. All physicians and medical students must be updated about different kinds of these infections, their causative agents, challenges, and how to deal with them to reduce the consequences and improve public health.

---

Introduction: COVID-19 ocular manifestations commonly occur in adults; however, there is limited data on this manifestation in children. This systematic review and meta-analysis investigated the prevalence of ocular manifestations in children. Methods: We searched PubMed, Scopus, EMBASE, Web of Science, and MedRxiv from December 1, 2019, to February 3, 2021. Two independent reviewers screened the articles, extracted the data, and assessed the quality of the articles. Results: After screening 1,510 articles, 19 were approved and included in the systematic review and meta-analysis. The literature review showed that 89 out of 749 children with COVID-19 had at least one ocular manifestation. The estimated pooled prevalence of ocular manifestations was 8.0% (95% confidence intervals 4.0 – 12.0). The most common symptoms were conjunctival discharge (n = 31, 23.1%), conjunctival congestion (n = 21, 16.0%), eye rubbing (n = 19, 14.2%). Conclusion:  Ocular manifestations are common in children with COVID-19; one out of 14 infected children shows at least one ocular manifestation. Physicians should pay attention to the ocular manifestations associated with COVID-19 in children.

---

Enteric viruses are the most common cause of gastroenteritis or infectious diarrhea worldwide. The genera Rotavirus (RoV), astrovirus (AstV), and Norovirus (NoV) are predominant viruses causing acute diarrhea in children and inflammation in the gastrointestinal tract. Apart from the enteric viruses, human papillomavirus (HPV), John Cunningham human polyomavirus (JCV), and human immunodeficiency viruses (HIV) are also significantly linked with gastrointestinal inflammation and gastric neoplasia. Moreover, recent studies demonstrated the direct induction of acute gut inflammation by Norovirus infection. Though mild inflammation occurs with astroviral infection, pro-inflammatory signaling pathways are also activated. Epstein-Barr virus (EBV), a significant tumor-causing pathogenic gammaherpesvirus, is also associated with diarrheal disease due to increased local and systemic inflammation. The association of EBV infection with ulcer colitis (UD), Crohn's disease (CD), inflammatory bowel syndrome (IBD), peptic ulcers, and chronic fatigue syndrome (CFS) indicates its potentiality for enhancing gut inflammation and gastric cancers. In the current scenario, extensive research is a prerequisite to understanding and achieving in-depth knowledge of the molecular mechanisms involved with enteric and tumor viral antigen-induced gut inflammation and cancer progression. This review represents new insights into the current research linking enteric and other pathogenic viruses as a trigger for gut inflammation and gastrointestinal malignancies. 

---

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant health and financial issue in the current century. Despite significant attempts to manage the illness, the transmission routes of the virus and its widespread genomic mutations have led to an increasing number of new infections and mortality rates. In the absence of specific treatment for this new virus, identifying and managing factors affecting the prognosis of the disease is one of the critical strategies to reduce disease mortality. Patients with iron deficiency anemia (IDA), who account for an estimated half a billion people globally, are more prone to infections due to immune system disorders. Since they visit hospitals more frequently for follow-up care and diagnosis, they are more susceptible to becoming infected with SARS-CoV-2. Once infected with SARS-CoV-2, low hemoglobin (Hb) levels and compromised immune systems disrupt the restriction of infection in these individuals, ultimately leading to severe complications of COVID-19.
 

---

The SARS-COV-2 virus is the cause of the 2020 pandemic that has infected and killed millions worldwide. While the upper respiratory tract cells are the primary targets of COVID-19, the virus can infiltrate other tissues and organs, leading to potentially serious complications. The new coronavirus primarily affects angiotensin II receptor and cytokine pathways, which can result in acute pulmonary inflammation, pulmonary edema, acute respiratory distress syndrome, vascular endothelial dysfunction, pulmonary embolism in the lungs, and cardiomyopathy, arrhythmia, heart failure, and intravenous thrombosis in the heart. COVID-19 infection can be associated with gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Also, reports of mild and transient liver damage, polyneuropathy, encephalitis, stroke, acute renal failure, hypocortisolism, and damage to the hypothalamus and pituitary system are available. COVID-19 can also be associated with skin symptoms such as rash, urticaria, maculopapular lesions, and vascular lesions such as chill blain, petechiae purpura, and scalpopathy. This narrative review evaluates the pathogenesis of novel coronavirus on body organs based on relevant published papers and reference books.

 

---