Epidemiology of malaria in Khorasan Razavi Province, northeast of , within 7 years (April 2001 - March 2008)

Reza Shafiei, Abbas Mahmoodzadeh, Massoud Hajia1, Aliakbar Sanati2, Fatemeh Shafiei2 Baqyatallah Medical Sciences Univ. Microbiology Department and Research Center of Molecular Biology, 1Research Center of Health Reference Laboratory, 2Health Center of Khorasan Razavi Province, Iran

SUMMARY Background: Malaria has become a critical world health problem in recent years. Several factors have been ORIGINAL ARTICLE Aim: responsible for increasing its incidence, such as wide usage of insecticides and drug resistance. It still remains studyas a matter of the ofmalaria concern is innecessary Iran. It isin under non-endemic control inprovinces. all parts, Materials except in andthree Methods: southeastern provinces. descriptiveKhorasan Razavi study isto one evaluate of the epidemiological Iranian provinces status with of a the lot malariaof immigrants in April each 2001–March year. Therefore, 2008 using epidemiological all patients’ data from whole of the province. Results: This research was a was observed in 2001 and the lowest in 2006. Plasmodium vivax was observed in 911 cases and 30 cases were positive for P. falciparum. Mixed species were Total seen recorded in four cases cases. were Malaria 945 withinincidence 7 years. had decreasedThe highest since incidence 2001. 34.6% of transmitted cases were local, 61% were transmitted from (other provinces) inside and outside the

incidence was observed in people of age 15 years and higher and mostly in men. and Sarakhs cities hadcountry, the highest relapse incidencecases formed rate. 5.4% Conclusion: and transmitted Preventive routes efforts of themust rest be of continually the cases weretaken unknown. in spite of The decreasing highest rate of the malaria.

Key words: Epidemiology, Khorasan Razavi Province, malaria, P. falciparum, P. vivax

Introduction the consolidation phase of MEP. In the southern parts of Zagross Mountains, the incidence of malaria cases Malaria is a preventable and curable and the most considerably reduced, and the total annual malaria important parasitic disease in the world[1,2] About cases in Iran came down to 12,000 in 1973. However, 40% of world population lives in malarious areas in these temporary relative successful results of MEP in underdeveloped countries. The control of this disease Iran encouraged the health authorities to integrate is one of the important socioeconomic factors for MEO into Communicable Diseases Control (CDC).[3] development of each country, as a lot of investment needs to be made for it. Malaria has been widely prevalent This integration caused reduction of MEP activities for a long time in Iran. The results of antimalaria and resulted in elevation of malaria incidence. The campaign and malaria eradication program (MEP) up objectives of antimalaria campaign were to decrease to 1973 caused almost elimination of malaria in the malaria transmission and infection rates in the northern parts of Zagross Mountains, which were in residual foci in southern part of Iran and sustaining the northern parts free of malaria as far as possible. In 1980, the Ministry of Health, according to suggestions Access this article online of Malaria National Scientific Committee and WHO Quick Response Code: Website: malaria advisors, changed MEP to MCP (malaria www.atmph.org control program).[4] Now, the most important malaria transmission areas, i.e. the problem areas, are in the southeast part of the country including Sistan and DOI: 10.4103/1755-6783.80515 Baluchestan, Hormozghan Provinces, and southern part of Kerman Province with a combined population of approximately 3 million and are considered to be

Correspondence: [email protected]

Dr. Massoud Hajia, Research Center of Reference Laboratories, Iran. E-mail: 1212 Annals of Tropical Medicine and Public Health | Jan-Jun 2011 | Vol 4 | Issue 1 Shafiei, et al.: Epidemiology of malaria "refractory malaria regions". Annual Parasite Incidence in the north and north-east, in the east, (API) was reported to be 8.74 per 1000 population.[5] Yazd, Semnan and North Khorasan Provinces in the west and South in the south. Its The present problems of MEP in the southern parts vicinity to Afghanistan and Pakistan has previously of Iran include plurality of malaria vectors and their caused an increased rate of the disease. various behaviors, resistance of the main vector “A. Stephensi” to some insecticides, long distances between Samples and staining method some villages and lack of suitable transportation roads, Peripheral blood smears were taken from all the persons structure of living houses, socioeconomic conditions, who had fever. Slides were prepared in both thin film immigration from malarious neighboring countries at one end and thick film at the other; only the thin and some other operational problems.[6] portion was fixed; both parts of the film were stained with Giemsa’s stain simultaneously[8] and examined Recently, a new threat of imported malaria has emerged under microscope by 100× magnification. from the northwestern part of the country, Parsabad area, which was affected by a serious epidemic of Plasmodium species, epidemiology, date of the Plasmodium vivax.[5] Thus, it can transfer from the infection, transmitted route to the patients and relapse endemic parts to other parts because of the ecological cases were determined. Positive results were entered in and regional conditions and its reservoirs. According to the study, after their confirmation in health center of the Deputy of Health, 24,241 microscopic slides (out of the province. 1,358,262) were positive for malaria in 2003, containing 19% Plasmodium falciparum, 80% P. vivax and 1% mixed Transmitted routes were categorized as local species. 90% of the positive cases were reported from transmission based on the following criteria: those south of Zagros and southeastern part of Iran.[7] individuals who had not traveled recently, not received blood, and with no history of any previous infection, Malaria has lost its previously importance in other transmission from outside the country, transmission provinces, and its incidence has come down since from the high-risk provinces. All data were analyzed by 1991. It seems the major problems encountering the SPSS (version 14) and square test. steps taken have been due to immigrants from Pakistan and Afghanistan.[5] Our objective was to design an Results epidemiological study of malaria in Khorasan Razavi Province, which sees rise in immigrants every year, to A total of 126,084 data were collected from 20 cities; of have appropriate health and treatment efforts. these, 945 cases were positive for malaria. P. vivax was detected in 911 cases and 30 cases were positive for P. Materials and Methods falciparum. Mixed species was observed in four cases. Annual Parasite Incidence (API) had decreased from 10 Study design: This research was a descriptive case series in 2001–2002 to 0.48 in 2007–2008, and the highest study based on collecting data from rural and urban positive rate was 494 in 2001–2002 and had reduced to populations referred to health centers for malaria, from 26 cases in 2007–2008 [Table 1]. 665 were males, while April 2001 to March 2008.[1] Active case finding was 4 cases of the remaining 280 were pregnant women. performed by checking suspected people at their house collecting blood smears, and inactive case finding was Highest positive rate of malaria was observed among based on collecting smears from the patients having students (26.1%), followed by workers (18.4%) and fever and chills, referred to health centers. housekeepers and self-employment groups (17.4%). Male patients were at higher risk than female patients Blood samples were collected from all the individuals by nearly three times (70.4%) [Figure 1]. All patients feeling feverish and belonging to immigrant population were studied in four age groups and those of age above from endemic areas, especially those from Sistan and 15 years had the highest infection rate (72.4%). The Baluchestan, Hormozghan and Kerman Provinces and youngest patient was a 28 day-old neonatal and the the groups from Pakistan and Afghanistan. eldest one was a patient of 81 years of age [Table 2].

Study area: Khorasan Province has recently been The highest positive rate was observed in Mashhad and divided into three provinces: South, North and Razavi Sarakhs cities [Table 3]. 315 positive cases (34.6%) were Provinces. Khorasan Razavi Province is vast with an locally transmitted and they were mostly reported in area of 127,432 km2 and with 20 cities and 3767 2001–2002 from Sarakhs city. 576 cases (61%) had their villages. It is bounded by the country of Turkmenistan route of infection from outside the province, including

Annals of Tropical Medicine and Public Health | Jan-Jun 2011 | Vol 4 | Issue 1 13 Shafiei, et al.: Epidemiology of malaria

Table 1: Distribution frequency of parasite and epidemiological criteria in Khorasan Razavi Province (2001–2008). Studied year4 Province Prepared Positive P. viovax P. falciparum Mix ABER1 API3 SPR2 population slides cases 2001-2002 4812241 19233 494 483 8 3 0.39 10.26 2.56 2002-2003 4818541 20388 208 204 4 0 0.42 4.31 1.02 2003-2004 5072541 22365 100 93 7 0 0.44 1.97 0.44 2004-2005 5127409 17854 54 52 2 0 0.34 1.05 0.31 2005-2006 5197674 15666 46 43 2 1 0.31 0.88 0.29 2006-2007 5267939 14788 17 13 4 0 0.28 0.32 0.11 2007-2008 5409873 15790 26 23 3 0 0.29 0.48 0.16 1ABER: annual blood exam rate, 2API: annual parasite incidence, 3SPR: slide positive rate; 4Data were analyzed based on Iranian year starting April ending March the following year

Table 2: Age distribution frequency of malaria in Khorasan Razavi Province (2001–2008) Age (Years) P. vivax P. falciparum Mixed Total No. Percent No. Percent No. Percent No. Percent 0-4 51 5.6 0 0 0 0 51 5.4 5-9 99 10.9 2 6.7 0 0 101 10.7 10-14 108 11.9 1 3.3 0 0 109 11.5 Over 15 653 71.7 27 90 4 100 684 72.4 Total 911 100 30 100 4 100 945 100

Table 3: Distribution frequency of malaria based on parasite species in Khorasan Razavi P. viovax P. falciparum Mix Total No. % No. % No. % No. % Mashhad 481 52.8 21 70 3 75 505 53.4 Sarakhs 351 38.5 2 10 1 25 354 37.6 Torbat-e-Jam 49 5.4 1 3.3 0 0 50 5.3 Nishabour 10 11 1 3.3 0 0 11 1.2 Taybad 8 9.0 1 3.3 0 0 9 1 Ghoochan 5 5.5 1 3.3 0 0 6 0.6 Kashmar 4 4.4 0 0 0 0 4 0.4 Fariman 2 2.2 1 3.3 0 0 3 0.3 Bardskan 0 0 1 3.3 0 0 1 0.1 Khauf 1 1.1 0 0 0 0 1 0.1 Figure 1: Prevalnce rate of malaria in Khorasan Razavi Province Total 910 100 30 100 5 100 945 100 based on the patient’s job Province (2001-2008) abroad, high-risk provinces and other provinces. Of these, 418 were from abroad: 381 patients (40%) were Chloroquine. Those cases infected with P. falciparum immigrants from Afghanistan and Pakistan, 37 of the were also treated with Chloroquine and Primaquine. positive cases were those who returned to the country Relapse was observed in 12 of these cases on treatment after acquiring infection from outside the country. with Fansidar and Quinine. High incidence rate was The rest 158 positive cases were from other provinces observed in summer with 506 cases (53.5%), especially including high-risk places. Relapse cases numbered in the month of August during the study period (20.6%) 49 (5.4%) which were mostly observed in 2002–2003 [Table 5]. in Sarakhs city. It was due to improper treatment of infected cases of Sarakhs city in 2001. We were not Discussion able to determine the transmission route in five cases [Table 4]. The most influential parameters on malaria are immunological and genetic characteristics of All cases infected with P. vivax suitably responded to population at risk of infection, parasitic species, type

1414 Annals of Tropical Medicine and Public Health | Jan-Jun 2011 | Vol 4 | Issue 1 Shafiei, et al.: Epidemiology of malaria

[11] Table 4: Distribution frequency of malaria based on a risk of malaria transmission. Malaria is the most living area in Khorasan Razavi Province (2001- 2008). important parasitic disease in Iran. Living Area Total Malaria has been controlled in most parts of the country Rural Urban in previous decade but reappeared again because of Local transmission 315z 0 315 drug-resistant parasites, immigrant population and Transmitted from outside the country(A) 40 378 418 people traveling especially to endemic areas. Thus, lot Transmitted from high risk provinces(B) 13 111 124 of steps need to taken.[12] One of the main problems in Transmitted from other provinces(C) 16 18 34 Relapse 45 4 49 the control of malaria is resistance of P. falciparum to Unknown 1 4 5 Chloroquine and some other antimalarial drugs, which Total 430 515 945 is now more or less common in the malaria endemic areas in the world.[9] of mosquito, rate of rainfall and humidity, distribution Khorasan Razavi has religious visitors, sometimes of mosquito feed areas, use of antimalarial drugs and about four times of its population. This caused an other controlling equipments for reducing the risk increase in the incidence of malaria cases. Malaria rate of transmission.[9,10] The geographic and climatic is 2.75 per 100,000 of population; 61% of these cases conditions, irrigation facilities, environmental are Afghan immigrants and visitors. Local transmission conditions, tribal and population movement, structure of the disease is about 33%. Many observed cases are of living houses, lack of road transportation and greater from infected family members of Afghan immigrant distance among villages, illiteracy, economic and social who were not properly treated in their own country. problems, etc. are favorable for malaria transmission Another high-risk group the family members of those in Iran.[5] called into military services in Sistan and Baluchestan Province, especially in Chahbahar city; these people Control and prevention of malaria faces serious problem transferred type B variant of the disease to their family because of parasitic resistance to some antimalarial members after they came back from service. drugs and mosquito resistance to some insecticides, as well as mosquito and parasite species. This study showed P. vivax as having the highest rate, which is comparable to studies conducted in other Distribution of malaria depend upon socioeconomic parts of Iran. P. vivax was observed in 97.5% cases in parameters and availability of primarily welfare a study performed in Baboulsar during 1996–1997.[13] facilities such as house, road, electricity, health In another study performed in Kermanshah, 8.5 per service and enough awareness on personal prevention. 100,000 reported during 1985–1996, with similar rates Therefore, these parameters play an important role in in males and females, with a mean age of 20 years. controlling malaria. At the present time, controlling Ninety-eight percent of cases were positive for P. vivax malaria is facing a major problem because of the at the Kermanshah study.[14] political situation of neighboring countries, especially Afghanistan, due to which several job-seeking people Decreasing and increasing rates of this study were are immigrating to Iran.[7] Iran is among the countries similar to that observed in a study performed in located in the Eastern Mediterranean Region with low Esfahan Province.[15] A study reported from Altamim malaria endemicity, and in some of its areas, there is Province of Iraq indicated that the highest cases were

Table 5: Distribution frequency of malaria during the 12 month of year in study period Studied Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Total Years 1 2001-2 18 44 63 84 140 10 12 11 7 2 6 0 494 2002-3 10 37 57 35 26 20 4 3 8 0 2 6 208 2003-4 9 11 11 13 8 18 15 4 3 4 2 2 100 2004-5 5 6 12 11 8 5 4 3 0 0 0 0 54 2005-6 2 3 6 8 6 3 8 3 4 1 2 0 46 2006-7 1 0 2 4 2 2 4 0 2 0 1 0 17 2007-8 0 2 0 2 3 1 2 3 2 4 5 1 26 Total 45 103 151 157 193 156 49 27 26 11 18 9 945 1Data were analyzed based on Iranian calendar, starting from April ending at March of the next Christian year.

Annals of Tropical Medicine and Public Health | Jan-Jun 2011 | Vol 4 | Issue 1 15 Shafiei, et al.: Epidemiology of malaria infected locally and not due to immigration, in contrast has been classified into four strata:[7] to our results that had direct correlation to economic i) Areas where local transmission of malaria situation and performance of control program in occurs, such as areas in Sistan and Baluchestan, the region.[11] Hormozghan and southern parts of Kerman Provinces and occasionally some areas in Ardebil, Decreasing and increasing rates of malaria have been Boushehr, Fars and Khorasan Provinces. observed in Nicaragua, which is one of the most ii) Areas where the imported cases are found and the infected countries in the Central America. High potential risk of malaria transmission exists, such prevalence of malaria in this country was due to the as areas in Gilan, Mazandaran, and Golestan war that distributed to non-war area.[16] Analyzed Provinces. data revealed malaria had increasing and decreasing iii) Areas where the imported cases are found, but rates in Khorasan Razavi Province. Increasing rate there is no risk of malaria transmission, such as in 2001–2002 and 2002–2003 was due to local Yazd, Kurdistan, and Hamadan Provinces. transmission of the disease as well as immigration iv) Areas where no malaria case was reported during of Afghan people, but it decreased from 52.3% in the last 3 years. It seems there was no such area 2001–2002 to 2.8% in 2007–2008 of all positive in Iran. cases at the end of study. This is in agreement with a The main technical elements of the strategy of malaria previously reported study. Total reported malaria cases control which should be applied in MCP all over the in Iran reduced from 96,340 (with 45% P. falciparum) country, particularly in areas where there are local in 1991 to 18,966 (with 12% P. falciparum) in 2005. malaria transmissions or there is potential risk of About 30–50% of malaria patients were among foreign malaria transmission, are usually the following: immigrants.[4] Besides, local transmission was not i) Early case detection and prompt treatment; observed from 2002-2003 because of ecological status ii) Plan and implement suitable preventive measures of the region and presence of Anopheles superpictus. It including vector control’ underlines the importance of efforts to prevent the risk iii) Improving information and reporting system; of malaria epidemic. iv) Providence and prevention of local malaria outbreak or epidemy; The most affected group of people was of age 15 years v) Carry on training and refreshing courses for senior and above and many of them were male patients. staff and technical personnel; Therefore, our concern should be on young males, that vi) Establish continuous quality control system for is the potentially working group. In accordance with malaria microscopic diagnosis and cross-checking other studies, the most prevalent time of the disease of examined slides; has been observed to be the warmer months due to an vii) Monitoring the response of P. falciparum and increase in the number of mosquitoes. P. vivax to antimalarial drugs; viii) Planning and performing basic and applied In the last study perfomed during 19821991 in east researches on the local existing malaria problems Azarbaijan Province, 184 out of total 444 locally and observed malaria cases were reported from Moghan ix) Sustaining supervision and evaluation malaria plateau.[17] In the meantime, Ataiyan reported just control activities. 44 of total 636 malaria cases to be Iranians from Zanjan Province and the rest of the infected people All of the above activities need financial and scientific had Afghan nationality.[18] This finding was observed support and supervision of the national health and confirmed in studies performed in Hamadan authorities and collaboration of academic and research Provinces.[19] The main transmission route in these centers as well as the international organizations such provinces is local transmitted form. Malaria is as Roll Back Malaria/WHO.[1,22] critical at Systan and Baluchestan Province because of immigration from Pakistan and Afghanistan. Conclusion Analyzed data determined 418 out of 945 cases of malaria were immigrants from other countries.[20] It Awareness of the people for transmission route of the also reported that 3532 out of 4991 observed malaria malaria, controlling visitors and immigrants of Iranian cases in Khorasan Province in 1986-1990 were and non-Iranian nationality and treatment of them, transmitted from abroad.[21] continuously identifying the Anopheles mosquitoes and finally exchanging epidemiological data and drug According to the National Strategy Plan for Malaria resistance rate of the disease are the most influencing Control, in respect to malaria status, the total country parameters to control malaria.

1616 Annals of Tropical Medicine and Public Health | Jan-Jun 2011 | Vol 4 | Issue 1 Shafiei, et al.: Epidemiology of malaria References 14. Rezai M, Khodaei MA, Khazaeir M. Epidemilogy of Malaria in Kermanshah Province of Iran 1987-1996. Symposium, Parasitology international 47(Suppl); 1998. p. 160. 1. Sadrizadeh B. Malaria in the world, in the eastern Mediterranean 15. Motevali EM, Khademi MR, Sadri GH. Epidemiological study of region and in Iran. Arch Iran Med 1999;2:31-7. Malaria and country’s indexes in Isfahan province during 1998-2002. 2. http://www.who.int/mediacentre Iran J Infect Dis Trop Med 2003;23:29-32. 3. Motabar M, Tabibzadeh I, Manouchehri AV. Malaria and its control in 16. Garfield R. Malaria control in Nicaragua: Social and political Iran. Trop Geogr Med. 1975; 27:71-8. influences on disease transmission and control activities. Lancet 4. Edrissian GH. Malaria in Iran: Past and Present Situation. Ir J 1999;354:414-8. Parasitol. 2006; 1:1-14. 17. Naghili B, Moghaddas PS, Majid PA, Bozorg ZI. Clinical and 5. Sadrizadeh B. Malaria in the world, in the eastern Mediterranean epidemiologic study of Malaria in east Azerbaijan. Med J Tabriz Univ region and in Iran: Review article. WHO/EMRO Report. 2001. p. Med sci Heal Serv 1983;20:73-84. 1-13. 18. Ataian A, Paykari H, Noorian AA, Nazarnia ME, Hosseini SH, Shahidi 6. Manouchehri AV, Emadian ZM. A review of malaria in Iran. J Am J, et al. Imported Malaria in Zanjan province, northwest part of Iran. Mosq Con Ass. 1992; 4381:385. J Zanjan Univ Med Sci Heal Serv 1993;2:6-11. 7. Raeisi A, Shahbazi A, Ranjbar M, Shoghli A, Vatandoost H, Faraji 19. Fallah M, Mirarab SA, Jamalian SF, Ghaderi A, Zolfaghari A. L. National strategy plan for malaria control in I.R.Iran, 2004-2008. Epidemiology of Malaria in Hamadan province during a 20-year Diseases Management Center, Undersecretary for Health, Ministry period, 1980-2001. Bebood. 2003;17:36-44. of Health and Medical Education. Seda: Seda Publicaton Co. 2004. 20. Sadjadi SM, Saba MS, Sharifian J, Razani GH, Smavati SH, p. 23 Dezfoolian H. A survey of Malaria in Hamadan province from 1980- 8. John DT, Petri WA. Markell and Vog`s Medical Parasitology. 92. Sci J Ham Univ Med sci Heal Serv. 1993;3:24-30. Sunders: Oklahoma; 2006. p. 4. 21. Karimi ZA, Mahmood ZA, Vatani H, Shirbazoo SH. An epidemiologic 9. Chwatt BL. History of malaria from prehistory to eradication. In: study of Malaria in borders of Sarakhs in Khorasan province. Iran J Wernsdorfer WH, Mac Gregor IA, editors. Malaria Principles and Infec Dis Trop Med. 2003;20:47-50. Practice of Malariology. London: Churchill Livingstone; 1989. p. 1-59. 22. World Health Organization. A global strategy for malaria control. 10. Nicholas J, Breman WJ. Malaria and babesiosis. In: Fauci A, Publ. No. ISBN924 1561610, Switzerland. 1993. Braunwald e, Martin JB, editors. Harrison's Principles of Internal Medicine. 14th ed. New York: Amazon Co.; 1998. p. 1180-9. 11. Martens P, Hall L. Malaria on the move: Human population movement Cite this article as: Shafiei R, Mahmoodzadeh A, Hajia M, Sanati A, and malaria transmission. Emerging Infect Dis 2000;6:103-9. Shafiei F. Epidemiology of malaria in khorasan razavi province, Northeast 12. Kadir MA, Ismail AK, Tahir SS. Epidemiology of malaria in AlTameem of Iran, within 7 years (April 2001 - March 2008). Ann Trop Med Public province, Irag, 1991- 2000. East Mediter heal J. 2003;5:1042-7. Health 2011;4:12-7. 13. Ghafari S, Kariminia H. Malaria in Mazandaran Province 1986-1996. Source of Support: Nil, Conflict of Interest: None declared. Journal of Mazandaran Medical Sciences University. 1999;32:42-8.

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