EMHJ • Vol. 21 No. 4 • 2015 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale Effectiveness of meglumine antimoniate against L. tropica in a recently emerged focus of cutaneous leishmaniasis in Birjand, eastern Islamic Republic of Iran M. Karamian,1 M.S. Faroghi Bojd,2 A. Salehabadi,3 M. Hemmati 4 and D.A. Barati 2 فعالية ميجلومني أنتيمونيات ضد الليشامنية املدارية يف بؤرة لداء الليشامنيات اجللدي ظهرت ّمؤخ ًرايف بريجاند، برشق مجهورية إيران اﻹسﻻمية مهدي كرميان، حممد صديق فاروقي بجد، علريضا صالح آبادي، مينا مهتي، درويشعيل برايت اخلﻻصــة: مــع حمدوديــة خيــارات معاجلــة داء الليشــانيات اجللــدي ﻻ بــد مــن القيــام برصــد مســتمر ملعــدل مقاومــة اﻷدويــة التــي أساســها اﻷنتيمــون مخــايس التكافــؤ. وقــد قامــت هــذه الدراســة بالتعــرف عــى نــوع الليشــانية املســببة للعــدوى وتقييــم نتائــج املعاجلــة بامليجلومــن أنتيمونيــات )جلوكانتيم ®Glucantime(يف بــؤرة جديــدة لــداء الليشــانيات اجللــدي يف بريجانــد، بــرق مجهوريــة إيــران اﻹســامية. فأظهــرت مســحات مأخــوذة مــن 150 ًمريضــا أن 141 ًمريضــا كانــوا مصابــن بالعــدوى بالليشــانية املداريــة و9 بالليشــانية الكبــرية. وقــد لوحــظ فشــل املعاجلــة باجللوكانتيــم فقــط لــدى املــرىض املصابــن بالليشــانية املداريــة. ويف اﻹمجــال، فــإن الـــ 141 ًمريضــا املصابــن بالعــدوى بالليشــانية املداريــة اســتكملوا املعاجلــة باجللوكانتيــم وأهنــوا املتابعــة؛ وقــد عولــج 63.8 % منهــم باحلقــن داخــل اﻵفــة و36.2 % عــن طريــق احلقــن العضــيل. وكان معــدل النجــاح العــام بعــد دورة عاجيــة واحــدة باجللوكانتيــم 96.5 % )136/141(، وكل حــاﻻت َالفشــل )5/141( حدثــت مــع احلقــن العضــيل. فأظهــر التحليــل اﻹحصائــي ًفرقــا كبــري ًا بــن ّمعــدﻻت َــلفش احلقــن العضــيل واحلقــن داخــل اﻵفــة. وكان ّمعــدل َالفشــل لــدى اﻷطفــال الذيــن تقــل أعارهــم عــن 10 ســنوات أعــى بكثــري منــه لــدى البالغــن. ABSTRACT With limited options to treat cutaneous leishmaniasis, constant monitoring of the rate of resistance to pentavalent antimony-based drugs is needed. This study identified the infectingLeishmania species and evaluated the results of meglumine antimoniate (Glucantime®) therapy in a new focus of cutaneous leishmaniasis in Birjand, eastern Islamic Republic of Iran. Smears from 150 patients showed that 141 patients were infected by L. tropica and 9 by L. major. In total, 141 patients with L. tropica infection completed Glucantime® treatment and follow-up; 63.8% were treated intralesionally and 36.2% by intramuscular administration. The overall success rate after one course of therapy with Glucantime® was 96.5% (136/141), and all the failures (5/141) occurred with intramuscular injections. Statistical analysis showed a significant difference between the failure rates of intramuscular and intralesional injections. Children < 10 years old had a significantly higher failure rate than adults. Efficacité de l'antimoniate de méglumine contreLeishmania tropica dans un nouveau foyer émergent de leishmaniose cutanée à Birjand, dans l'est de la République islamique d'Iran RÉSUMÉ Les options thérapeutiques pour la leishmaniose cutanée étant limitées, une surveillance constante du taux de résistance aux médicaments à base d'antimoine pentavalent est nécessaire. La présente étude a identifié les espèces infectantes de Leishmania et a évalué les résultats d'un traitement par antimoniate de méglumine (Glucantime®) dans un nouveau foyer de leishmaniose cutanée à Birjand, dans l'est de la République islamique d'Iran. Les frottis de 150 patients ont révélé que 141 patients étaient infectés par L. tropica et 9 patients par L. major. Au total, 141 patients infectés par L. tropica ont achevé le traitement par Glucantime® et sont allés jusqu'au bout du suivi ; 63,8 % ont reçu un traitement intralésionnel et 36,2 % une injection intramusculaire. Le taux de succès global après un traitement par Glucantime® était de 96,5 % (136/141), et tous les échecs (5/141) ont été observés chez les patients ayant reçu des injections intramusculaires. L'analyse statistique a mis en évidence une différence significative des taux d'échec entre les injections intramusculaires et les injections intralésionnelles. Le taux d'échec chez les enfants de moins de dix ans était supérieur à celui observé chez les adultes. 1Hepatitis Research Centre, School of Medicine; 2City Health Centre of Birjand, 3Department of Microbiology, School of Medicine; 4Department of Biochemistry, School of Medicine, Birjand University of Medical Sciences, Birjand, Islamic Republic of Iran (Correspondence to M. Karamian: [email protected]). Received: 10/04/14; accepted: 23/02/15 280 املجلة الصحية لرشق املتوسط املجلد احلادي و العرشون العدد الرابع Introduction (Glucantime®) and sodium stibogluco- is 170 mm. This region is the largest nate (Pentostam®, GlaxoWellcome) or producer of saffron and barberries in Cutaneous leishmaniasis is a public generic sodium stibogluconate (Albert the country. health concern in more than 70 coun- David Ltd, India) are the first line of A total of 188 parasitologically new tries across the world. It can be caused treatment against both New World and confirmed cases of cutaneous leishma- by several Leishmania spp. and is trans- Old World types of cutaneous leish- niasis (i.e. Giemsa-stained smear-posi- mitted to human beings and animals maniasis (8–10). However, increasing tive cases) who were referred to the city via sandflies 1( ). More than 90% of resistance of Leishmania spp. to these health centre of Birjand were recruited the world’s cases of cutaneous leish- compounds has limited their useful- for this study. Of these, 154 completed maniasis occur in only a few countries: ness in this context (11). Glucantime® the antimonial treatment course and Afghanistan, Algeria, Islamic Republic is a commonly used pentavalent anti- follow-up. Out of these patients, 4 with of Iran, Iraq, Saudi Arabia and Syrian mony-based drug for the treatment of previous treatment of cutaneous leish- Arab Republic in the Old World; and visceral and cutaneous leishmaniasis in maniasis were excluded from the study. Bolivia, Brazil, Colombia, Nicaragua the Islamic Republic of Iran. However, The study was approved by the eth- and Peru in the New World (2). in recent years, cases of glucantime- ics review committee of Birjand Univer- In the Islamic Republic of Iran the resistant L. tropica have been reported in sity of Medical Sciences. disease is endemic to over 50% of prov- unresponsive cutaneous leishmaniasis patients ( ). Data collection inces (3), with Leishmania major and 12 L. tropica being the primary agents of Because of the limited options for Collection of samples zoonotic cutaneous leishmaniasis and alternatives to treat cutaneous leish- Microscopic examination of Giemsa- anthroponotic cutaneous leishmaniasis maniasis and given that this is an en- stained scrapings taken from the respectively (4). Anthroponotic cutane- demic disease in different locations margins of skin lesions of patients ous leishmaniasis caused by L. tropica, throughout the Islamic Republic of Iran, was used for diagnosis of cutaneous which tends to be more problematic constant monitoring of the incidence leishmaniasis. A questionnaire was for both diagnosis and treatment and of resistance to these compounds is completed for each case to record lasts longer than infections caused by L. necessary (13). The objective of this information about name, age, sex, major (5), is mainly reported in urban study was to assess the effectiveness of number of lesions, patient’s address, areas of central, north east and south- meglumine antimoniate on patients date and place of acquiring the disease, east of the Islamic Republic of Iran (6). infected by L. tropica in this new focus of lesion sites and duration, work place The main reservoir host ofL. tropica cutaneous leishmaniasis. and travel history. is humans, and Phlebotomus sergenti is PCR–RFLP considered as main vector of anthro- Methods The dermal scrapings of the patients ponotic cutaneous leishmaniasis in the were used to identify species of causa- country (7). Study area and population tive agents by polymerase chain reac- Birjand, the centre of South Kho- The study was conducted from April tion (PCR) assay. DNA was purified rasan province, is located in the east- 2008 to March 2012 in Bijand county for PCR using an AccuPrep® genomic ern part of the country. In past years of Southern Khorasan province in the DNA extraction kit (Bioneer) accord- sporadic cases of cutaneous leishma- eastern part of the Islamic Republic of ing to the manufacturer's instruction. niasis have been diagnosed in Birjand Iran. All patients selected for the study Species-specific primers, LITSR (for- county, but it was thought that they were living in Birjand and its subsidi- ward, 5′-CTG GAT CAT TTT CCG were imported cases from neighbour- ary villages, a region of approximately ATG-3′) and L5.8S (reverse, 5′-TGA ing endemic areas. Studies of increased 6700 km2 (Figure 1). This region has a TAC CAC TTA TCG CAC TT-3′) number of cases, however, have re- cold desert climate with hot summers were carried out as described by Scho- vealed that an endemic focus of cutane- and cool winters. This area altitude nian et al. to amplify the ITS1 region of ous leishmaniasis formed around 2008 ranges between 1250 and 2050 m the Leishmania ribosomal DNA (14). and since then an annual average of 50 above sea level. The city has a dry The PCR product of ITS1 was sub- cases have been reported in the region. climate with a significant difference jected to restriction fragment length The region has a population