Distribution of Leishmania Infection in Humans, Animal Reservoir Hosts and Sandflies in Golestan Province, Northeastern Iran: a Systematic Review and Meta-Analysis
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Iran J Public Health, Vol. 49, No.12, Dec 2020, pp.2308-2319 Review Article Distribution of Leishmania Infection in Humans, Animal Reservoir Hosts and Sandflies in Golestan Province, Northeastern Iran: A Systematic Review and Meta-Analysis Omid MOZAFARI 1, *Aioub SOFIZADEH 2, Hamid Reza SHORAKA 3 1. Health Management & Social Development Research Center, Golestan University of Medical Sciences, Gorgan, Iran 2. Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran 3. Vector-Borne Diseases Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran *Corresponding Author: Email: [email protected] (Received 12 Dec 2019; accepted 17 Feb 2020) Abstract Background: Leishmaniasis is one of the most important parasitic diseases in the Golestan Province, northeast- ern Iran. In this study, we summarize the results of studies on the disease and its causative agent Leishmania in humans, vectors and reservoirs in the Golestan Province, Iran. Methods: We retrieved all articles related to leishmaniasis in the Golestan Province, northern Iran from 1994 to 2018 in various databases including PubMed, Scopus and Web of Science. Articles in Persian were retrieved from the IranMedex, SID and Magiran. Reference lists of relevant articles were also hand-searched. Local active re- searchers in the field of leishmaniasis were contacted to avoid missing any relevant articles. Overall, 54 papers were extracted, later evaluated by two research team members based on inclusion criteria. All analyses were per- formed using the Stata 14 software. Pooled prevalence was calculated using the metaprop command and a ran- dom-effect model. The I² statistic was used for measuring heterogeneity of studies. Results: Ten articles in the province were related to detection of Leishmania species in patients with suspected cutaneous or visceral leishmaniasis. Fifteen articles were dedicated to identification of Leishmania species in dis- ease reservoirs and five articles were about detection of the parasite in sand flies. The pooled prevalence of L. major in patients with acute ulcer, wild rodents and sandflies was 83%, 29% and 11%, respectively. Conclusion: Our findings highlight the need for implementation of control measures among the reservoirs of both cutaneous and visceral leishmaniasis in the Golestan Province, Iran. Keywords: Leishmania; Reservoir host; Sand fly; Systematic review; Iran Introduction Leishmaniasis is one of the most important vec- form of the disease), cutaneous (the most com- tor-borne diseases transmitted to humans and mon), and mucocutaneous, it is estimated that other animals through bite of infected sandflies 700000 to one million new cases of leishmaniasis (1). It is also the third most important vector- and some 26000 to 65000 deaths occur annually. borne parasitic disease after malaria and lymphatic Moreover, about 600000 to one million people be- filariasis (2). come infected with cutaneous leishmaniasis and There are three main forms of leishmaniases – vis- 50000 to 90000 with visceral leishmaniasis (3). ceral (also known as kala-azar and the most serious 2308 Available at: http://ijph.tums.ac.ir Mozafari et al.: Distribution of Leishmania Infection in Humans, Animal Reservoir … Iran is facing both form of leishmaniasis: cutane- Currently, the health system of Iran’s approach to ous and visceral and cutaneous leishmaniasis is re- cope with leishmaniasis has been mainly estab- ported in two forms: zoonotic cutaneous leish- lished on timely recording and reporting of cases, maniasis (ZCL), anthroponotic cutaneous leish- education, providing free rapid diagnosis and maniasis (ACL) and Visceral leishmaniasi in zoon- treatment of patients as well as implementation of otic visceral leishmaniasis (ZVL) form. Iran is rodents- and sandflies-targeted control measures. amongst the six countries where 95% of global The Golestan Province is known as the most im- cases of cutaneous leishmaniasis occur (3), and portant foci of leishmaniasis in Iran. ZCL is en- each year, more than 22,000 new cases of cutane- demic and visceral leishmaniasis is sporadic in this ous leishmaniasis are reported in Iran, 80% of province, particularly in its northeastern areas. which are ZCL (4). However, the actual new cases Given the importance of leishmaniasis in this is estimated to be 4-5 fold higher than these re- province, numerous studies have been conducted ports (5). Golestan Province is amongst the 17 in this area on features of this disease. Therefore, provinces of Iran that are endemic for ZCL (5). we aimed to summarize results of these studies to In these areas, Leishmania major is the causative contribute to decision-making for prevention, di- agent, while Phlebotomus papatasi and wild rodents agnosis, control and treatment of this disease in (Rhombomys opimus and Meriones libycus) are known this area. as the vectors and reservoir hosts, respectively (5). In ACL foci, L. tropica is the agent, while Ph. sergenti Methods and dogs and humans are known as the vector and reservoir hosts, respectively (5). Study area Every year, 100-300 new cases of ZVL are re- The Golestan Province (53°57′- 56°23′ E, 36°30′- ported in Iran. The disease is sporadic in most 38°08′ N) is located northeast of Iran, bordering parts of the country but has become endemic in the Caspian Sea and Turkmenistan. The province the northwestern and southern areas. In these ar- has a dry and semi-arid climate in the north and eas, L. infantum is the agent, domestic dogs are northeastern parts, a temperate climate in the cen- known as the main and potential reservoir hosts tral parts and a mountainous and cold climate in and wild canines (jackal, fox and wolf) have poten- the southern parts. It comprises 14 counties and tial role in sylvatic transmission cycle of ZVL (6- has an area of 20437.74 Km² (Fig. 1). 8). Ph. neglectus, Ph. kandelakii, Ph. keshishiani, Ph. per- filiewi transcaucasicus and Ph. alexandri are considered as probable vectors for ZVL (9-13). Maraveh Tappeh ® Kalaleh Gonbad-e Kavus Galikesh Aqqala Minudasht Gomishan Azadshahr Ramiyan Bandar-e Torkaman Aliabad-e Katul Gorgan Kordkuy Counties of Golestan Province 0 15 30 60 90 120 Kilometers Fig. 1: Location of the Golestan Province and its counties Available at: http://ijph.tums.ac.ir 2309 Iran J Public Health, Vol. 49, No.12, Dec 2020, pp.2308-2319 This study has been designed and performed ac- consensus was reached after holding a group dis- cording to the MOOSE guidelines for meta-anal- cussion. yses and systematic reviews of observational stud- ies. Data extraction Data were extracted from the selected articles us- Search strategy ing a data extraction form. Quality of the studies First, the following search terms were determined was evaluated and scored on a scale of 0 to 10 us- for finding articles related to leishmaniasis in the ing the Joanna Briggs Institute's critical evaluation Golestan Province from 1994 to 2018: Golestan, checklist for studies reporting prevalence data. Gonbad-e Kavus, Maraveh Tappeh, Turkmen Studies with a quality score of ≥6 were included in Sahra, Leishmaniasis, Leishmania, Kala-azar and the meta-analysis. A table was also designed to sandfly. Since some of the words may have differ- present the type, location, date, results and quality ent spelling, the following search syntax was used: of each study. (Leishmanian* OR Kala*azar OR Sand*fl*) AND (Golestan OR Turkemen* OR Gonbad* or Mara- Subgroup combination veh*). The data were classified into subgroups of preva- The search was performed using the following da- lence, type of parasite in human, reservoirs and tabases: Medline, PubMed, Scopus and Web of vectors. Science. Related articles in Persian were retrieved from the SID, Magiran and IranMedex. In addi- Data analysis tion, the "Iranian Journal of Arthropod-Borne Meta-analysis was performed with the Stata soft- Disease" and the "Iranian Journal of Parasitology" ware (ver. 14). Pooled prevalence was calculated were investigated as key journals. Reference lists using the metaprop command and a random-ef- of relevant articles were also hand-searched. Fi- fect model. Moreover, the I² statistic was used to nally, we contacted local active researchers in the measure heterogeneity of studies. If heterogeneity field of leishmaniasis to avoid missing any articles (I2 ≥ 50%) was noted among studies, sensitivity on leishmaniasis in the Goletan Province. analysis was carried out by removing studies. We calculated the pooled prevalence of L. major in hu- Selection of articles mans, reservoirs (rodents) and sandflies using for- The following inclusion criteria were considered est plot (at 95% confidence interval). for the entry of articles to the study: 1. Articles on Leishmania and its prevalence in hu- Results mans, vectors and reservoirs. 2. Articles that solely report the results of research After searching keywords in Persian and English conducted in the Golestan Province. databases, 235 papers were found in English and Articles of studies conducted in other parts of Iran 198 in Persian. Overall, 390 papers remain for re- or several provinces were entered in the study only viewing their titles and abstracts after reviewing if they had reported data related to the Golestan and removing duplicates; and 324 records ex- Province separately and clearly. Subsequently, two cluded after title and abstract screening by inclu- research team members evaluated the selected ar- sion criteria, described in methods. The text of 66 ticles independently by reading titles, abstracts, papers was carefully investigated and their data en- and if necessary full texts. Articles that did not tered into the data extraction form. Finally, 34 meet the inclusion criteria were excluded from the studies included in qualitative and quantitative analysis. Articles repeated in two or more data- study (Fig. 2). bases were excluded. There was a disagreement re- garding inclusion/exclusion of an article, but a 2310 Available at: http://ijph.tums.ac.ir Mozafari et al.: Distribution of Leishmania Infection in Humans, Animal Reservoir … Fig.2: Flowchart describing the study design process Twelve articles investigated detection of different were positive in the PCR method (24).