THE RISE OF LEPTOSPIROSIS IN KELANTAN 204: CHARACTERISTICS, GEOGRAPHICAL PATTERN AND ASSOCIATED FACTORS Azimullah AZ, Aziah BD, Fauziah MN 2 Department of Community Health, School of Medical Sciences, Universiti Sains Malaysia, 650 Kubang Kerian, Kelantan, Malaysia. 2 Communicable Disease Centre Unit, Kelantan State Health of Department, 550 Kota Bharu, Kelantan, Malaysia. *Corresponding author: Dr Aziah Daud, MD(UKM), Master ComMed(USM) Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, 650 Kubang Kerian, Kelantan, Malaysia. E-mail: aziahkb@usm.my ABSTRACT Introduction: Leptospirosis is a zoonotic disease largely attributed to climatic and environmental condition. The occurrence signifies the complex interaction between man, animal host and the environment whereby socioeconomic status, occupation, association with animals, recreational activity and climate are all connected with occurrence of leptospirosis. The aim of this study was to determine the sociodemographic characteristics, geographical pattern and associated factors of leptospirosis cases in Kelantan 204. Methods: This was a cross-sectional study done among leptospirosis cases in Kelantan 204 based on E-notifikasi database from January 204 to December 204. Climate data were taken from National Meteorology Department. The data were analyzed using IBM SPSS 22 and Map Source Version 6 Software. Results: There were 620 confirmed Leptospirosis cases in Kelantan. Majority was Malay (88.7%) and male (63.7%). The mean (SD) age was 33.2 (8.23) years with age range from 2 to 89 years old. Most were in low risk occupational group (6.3%). Multiple logistic regression analysis showed high risk occupation (adjusted OR:.67, 95% CI:.228, 2.273, p=0.00) and age (adjusted OR:.00, CI:.003,.08, p= 0.008) were the significant associated factors. In relation to rainfall, majority of the cases occur from August to December 204 with rainfall range from 60.3 mm to 092.6 mm. Most resided in settlement area (22.9%), followed by plantation (6.%), rural area (4.4%) and paddy field (3.8%). Conclusions: High risk occupation mostly agricultural workers and food handlers were associated with leptospirosis. Rainfall distribution and type of land were observed to influence number of leptospirosis cases in Kelantan. Combination of these multifactorial factors contributed to leptospirosis in Kelantan 204. Keywords: Leptospirosis, high risk occupation, rainfall distribution, Kelantan Azimullah AZ, Aziah BD, Fauziah MN 52
.0 Introduction The incidence of leptospirosis is ranging from 0. to per 00 000 per year in temperate climates to 0 or more per 00 000 per year in the humid tropics and may reach up 00 per 00 000 during outbreaks. The wet and warm climate is favourable conditions for survival of leptospires in environment contributes to the magnitude of the problem in Malaysia. The incidence in Malaysia is estimated between 2 to 5 per 00 000 per year (El Jalii and Bahaman, 2004). The data from Disease Control Division of Ministry of Health generally showed the increasing trend of Leptospirosis in Malaysia from 2009 to 203 where 48 cases in 2009 and 4457 cases in 203 reported. The same goes for Kelantan state in 204, in which the data from Kelantan State Health Department indicated the case of leptospirosis has increased tremendously up to almost 200 % in year 204 as compared to 203 (Kelantan State Health Department,KSHD,204). Yet, the factors associated to rise of these cases have not yet being described. Therefore this study was conducted to identify the sociodemographic characteristics, geographical pattern related to leptospirosis and the associated factors contributed to the increment of leptospirosis cases in 204. It is known, leptospirosis closely related with environmental factors and climate changes especially rainfall distribution and temperature however to this date after extensive searching of research in Malaysia there is limited published study about the association of environmental factor with occurrence of leptospirosis diseases. This study is very important to formulate effective strategy for control and prevention of the disease. 2.0 Materials and Methods This was a cross sectional study done among leptospirosis cases in Kelantan in year 204. All confirmed leptospirosis cases were taken from E-notifikasi database from first January 204 to 3 st December 205. Leptospirosis cases with coinfection with other diagnosis such as Dengue fever and incomplete data were excluded in the study. No sampling method applied as all eligible cases were included. The information obtained from E- notifikasi database includes sociodemographic data, geographical location based on latitude and longitude and occupational history. The geographical location of leptospirosis cases from E- notifikasi database were transferred to Map Source software version 6 for mapping, geographical distribution and to determine type of land resided by the cases. Data for rainfall distribution and temperature were obtained from National Meteorology Department from first January 204 to 3 st December 204 for Kelantan state. The data was analyzed using the IBM SPSS 22. All continuous variables were described using mean (SD) and/ or median (IQR) whereas for categorical data as frequency (%). The Azimullah AZ, Aziah BD, Fauziah MN 53
continuous variables were age while categorical variables were sex, race, citizenship, and occupational classification. At univariate analysis, simple logistic regression was used to compare the sociodemographic characteristics, occupational classification and confirmed leptospirosis. The results of simple logistic regression, crude odd ratio (OR), p- value, and 95% confidence interval (CI) were recorded for each variable. p Value of <0.05 (two sided) was taken as significant at 95% confidence interval. Multiple logistic regression model was performed to predict factors associated with the leptospirosis cases in Kelantan 204. All the variables were tested whether there is an association between factors and confirmed leptospirosis case in Kelantan 204. The final model was presented with adjusted odds ratio and 95% confidence interval (CI), Wald statistics and p- value. The level of significance was set at p- value less than 0.05. 3.0 Result 3. Socio demographic characteristics of confirmed leptospirosis cases in Kelantan 204 There were 620 confirmed Leptospirosis cases in Kelantan in year 204. Majority of leptospirosis cases were Malay (88.7%) and male cases contributed about 63.7% outnumbered female cases (36.3%), non-malaysian contributed 7.9 % of the leptospirosis cases in Kelantan. The mean (SD) age was 33.2 (8.23) years with range from 2 years old to 89 years old. Majority of the leptospirosis cases were in low risk occupational group (6.3%). Table shows the sociodemographic characteristics of confirmed leptospirosis cases in Kelantan in year 204. Table : Sociodemographic characteristics of confirmed leptospirosis cases Variable Mean(sd) n (%) Age (year) [range:2-89] 33.2(8.23) Gender Female Male 225 (36.3) 395 (63.7) Race Malay Non Malay 550 (88.7) 70 (.3) Citizenship Malaysian Non-Malaysian Occupation High risk Low risk 57(92.) 49 (7.9) 240 (38.7) 380 (6.3) Azimullah AZ, Aziah BD, Fauziah MN 54
3.2 Type of occupation for confirmed leptospirosis in Kelantan 204 The highest percentage of confirmed leptospirosis case was students which contributed 26.9% followed by agriculture worker 22.%, housewife.8% and unemployed 9.8%. High risk occupation such as outdoor worker, food handler medical personnel, and military contributed 7.%, 5.5 %, 2.4% and.8% respectively. Figure shows the proportion of confirmed leptospirosis according to type of occupation Figure : The proportion of confirmed leptospirosis according to type of occupation 3.3 Distribution of leptospirosis cases based on district in Kelantan 204 Leptospirosis cases were distributed in all districts throughout the state with the highest number was in Pasir Mas (53), followed by Kota Bharu ( 94), Kuala Krai (88), Gua Musang ( 88), Machang ( 63 ), Tumpat ( 48 ), Jeli ( 29 ), Bachok (25), and the lowest number were Tanah Merah (6) and Pasir Puteh ( 6 ). Table 2 shows the proportion of confirmed leptospirosis cases and the outcome in Kelantan 204. Table 2: Proportion of confirmed leptospirosis cases based on districts in Kelantan 204 (n = 620) District Cases, n (%) Pasir Mas Kota Bharu 53(24.7) 94 (5.2) Gua Musang 88 (4.2) Kuala Krai Machang Tumpat Bachok 88 (4.2) 63 (0.2) 48 (7.7) 25 (4.0) Jeli 29 (4.7) Pasir Puteh 6 (2.6) Tanah Merah 6 (2.6) Total 620 Azimullah AZ, Aziah BD, Fauziah MN 55
3.4 Type of land resided by leptospirosis in Kelantan 204 In relation to type of land resided by leptospirosis cases in Kelantan state, Most of the confirmed leptospirosis in Kelantan 204 resided in settlement area (22.9%), followed by plantation (6.%), rural area (4.4%) and paddy field (3.8%). Table 3: Type of land in relation to number of leptospirosis cases in Kelantan 204 Type of land use Leptospirosis case Frequency % Settlement area 4 22.9 Plantation 99 6. Rural area 89 4.4 Paddy field 85 3.8 Forest 73.9 Urban area 65 0.6 Others 62 0.4 3.5 Climatological Data in Kelantan 204 The rainfall pattern from January to December 204 indicates variation of distribution over the Kelantan. November and December are the months with maximum rainfalls documented 690.6 mm and 092.6 mm respectively. The lowest rainfall was in February with number of rain days only one day with total rainfall less than mm. Mean temperature of Kelantan range from 24.9 o C to 28.2 o C. Majority of the cases occur from August to December 204 between 44 cases to 78 cases with most of the rainfall documented along this month range from 60.3 mm to 092.6 mm. The lowest number of cases was in February with documented 2 leptospirosis cases. Temperature changes have not much different in Kelantan. Table 4: Climatological data of Kelantan 204 in relation to number of leptospirosis Month Mean temperature o C (Daily minimum,daily Maximum) total rainfall (mm) Number of Leptospirosis cases (%) January 24.9 (23.6,26.2) 33.3 28(4.5%) February 25.4(23.4,26.5) 0.3 2(3.4%) March 26.5(25.2,28.05) 83.9 67(0.8%) April 28.2(27.5,29.) 2.8 37(6.0%) Azimullah AZ, Aziah BD, Fauziah MN 56
May 28.0(26.,29.3) 52.9 7(.4%) June 28.0(26.3,29.7) 95.3 34(5.5%) July 27.3(25.7,28.6) 55.6 4(6.6%) August 26.4(25.8,27.4) 24.4 78(2.6%) September 26.4(25.9,27.3) 60.3 44(7.%) October 26.2(25.0,27.4) 245.6 60(9.7%) November 24.5(23.9,27.3) 690.6 78(2.6%) December 25.8(23.2,27.5) 092.6 6(9.8%) 3.6 Factors associated with leptospirosis case in Kelantan 204 Simple logistic regression was used for the analysis of sociodemographic risk factors for confirmed leptospirosis and non-leptospirosis as the dependent variable. The significant unadjusted variables were age, citizenship, race, and occupational classification. Non- Malaysian or basically foreign worker have 2.3 times higher odds to have leptospirosis compared to Malaysian and those who are working in high risk occupation have.8 times higher odds to contracted with leptospirosis compared to those who are working in low risk occupation. Table 5: shows the univariate analysis of risk factors for leptospirosis. Variable β Wald df Crude OR 95% CI p-value Age (years) 0.04 4.670.04.007,.02 <0.00 Gender Female Male -0.95 2.28 0.823 0.633,.069 0.45 Race Malay Non-Malay -0.67 6.826 0.540 0.340,0.857 0.009 Citizenship Non-Malaysian Malaysian 0.840 7.734 2.37.282,4.89 0.005 Azimullah AZ, Aziah BD, Fauziah MN 57
Occupational classification High risk Low risk 0.626 20.209.87.424,2.458 <0.00 a Simple logistic regression OR = Odds Ratio CI = Confidence Interval df = Degree of freedom In multivariable analysis, multiple logistic regression (MLR) analysis was used to identify the independent associated factors for confirmed leptospirosis. All such variable from the simple logistic regression with p value of < 0.25 were included in multiple logistic regression (MLR). Forward and Backward stepwise variable selection methods were done to obtain preliminary main effect model and the highest numbers of variables were included in the further analysis. The independent variables that were statistically significant as predictors towards the leptospirosis were citizenship, age, race, and occupational classification. Final model of multiple logistic regression showed that high risk occupation group (adjusted OR:.67, 95% CI:.228, 2.273, p=0.00) and age (adjusted OR:.00, CI:.003,.08, p= 0.0080) were the significant associated factors. 95% CI p- Variable Β Wald Df Adjusted OR a value Age 0.00 7.092.00.003,.08 0.008 Occupational Classification Low risk High risk 0.53 0.69.67.228,2.273 0.00 Table 6: Factor associated with confirmed leptospirosis by multiple logistic regressions a Multiple logistic regression OR = Odds Ratio CI = Confidence Interval Df = Degree of freedom 4.0 Discussion The mean age of this study was almost similar with the findings by Rafizah et al (203), which is a hospital based study done in Kelantan in 202 with mean age of 39.4 ( 7.6). Most of the study done also found to have the higher percentage of male due to occupational exposure or recreational exposure (Narita et al., 2005). This study indicates that leptospirosis is primarily a disease of productive age group which mostly due to occupational exposure. Azimullah AZ, Aziah BD, Fauziah MN 58
This study found that students (26.9%) were one of the predominant occupational types to be contracted with leptospirosis apart from agriculture worker (22.%), and housewife (.8%). This finding contradicted study by Rafizah et al (203) who found the highest percentage was agriculture worker (34.5%) followed by housewives (20.2%) and students only contributed to 8.3% of the leptospirosis cases. Higher proportion of students contracted leptospirosis even though considered as low risk indicated other important risk factor contributed to the diseases such as recreational activities and hobby related to water activity (Sugunan et al., 2009). Housewife despite classified as low risk occupational classification have been shown to be significant risk factors in many of the studies due to handling raw animal meat and guts without protective gloves as well as agricultural work (Joel et al., 20). This study showed Pasir Mas has the highest numbers of cases as its land is mostly agricultural land together with occupational exposure predispose its population to leptospirosis infection. Kuala Krai and Gua Musang which one of the rural area in Kelantan also among the highest numbers of cases whereby the transmission and infection may associated with agricultural and outdoor occupation. Gua Musang is known associated with leptospirosis since 970 in which a study in one of the rubber estates Gua Musang indicated high seroprevalence ratio which reported 42.6% compared to other rubber estates in other states (Tan, 970). This study also found those work in high risk occupational group was significantly associated with leptospirosis infection such as agricultural worker, outdoor worker, military and medical personnel. This finding was strengthened by another study by Angnani et al (2003) revealed similar association of high risk occupation such as agricultural worker and those who involved with animal production has highest seropositivity with up to 35% compared to others workers. The maximum rainfalls distribution occurred in November and December 204 documented total rainfall distribution of 690.6 mm and 092.6 mm respectively in which most of the cases occur at this 2 month. This findings was also similar to rainfall pattern in Sri Lanka with rainfall ranging from 400 to 200 mm during northeast monsoon where majority of leptospirosis cases occur (Robertson et al., 202). Heavy rainfall was associated with increased risk of leptospirosis and responsible for numerous outbreak occur worldwide such as in India, Laos, Indonesia, and Brazil (Lau et al., 200, Trevejo et al., 998; Maskey et al., 2006). Temperature in Kelantan did not show any obvious variation and from our study observed mean temperature range from 24.9 o C to 28.2 o C throughout the year 204. In relation to number of leptospirosis cases, temperature changes in Kelantan observed did not show any obvious findings. However in Guadeloupe, leptospirosis incidences has been reported to increased fourfold during 2002-2004 following very hot and wet seasons which is associated with two El Nino events (Storck et al., 2008). Evaluation the proportion of the leptospirosis cases that resided by type of lands in Kelantan provided the common type of land encountered in leptospirosis. Our findings were majority of leptospirosis cases resided in agricultural area which included plantation, paddy field, rural area, and tree cultivation followed by resided in settlement area or residential area and urban. This findings were similar with others study whereby agriculture land was associated with most of leptospirosis cases worldwide (Robertson et al,.20). Same goes a study in Azimullah AZ, Aziah BD, Fauziah MN 59
American Semoa found people living in agricultural land were statistically significant associated with leptospirosis whereby it is related to exposures to animal and farming activities (Lau et al, 200). 5.0 Conclusions The rise of leptospirosis in Kelantan in 204 was unevenly distributed in all districts without no districts spared from the disease in which most of the cases mainly occur in four districts which were Pasir Mas, Kota Bharu, Kuala Krai and Gua Musang districts. High risk occupation mostly agricultural workers and food handlers, were associated with leptospirosis. However most of the leptospirosis cases in Kelantan occur among low risk group such as students and housewife requiring further study to explore risk factors among student and housewife to be contracted with leptospirosis infections such as recreational history and hobby associated with leptospirosis infections. In this study, temperature changes were observed not to be associated with the number of cases of leptospirosis but rainfall distribution was observed to be one of the climate factor that influence number of leptospirosis cases in Kelantan whereby most of the cases happen in the end of the years 204. Type of lands especially agricultural land favored the spread of leptospirosis infection which is correlated as well with nature of occupation in agricultural workers. Combination of these multifactorial factors contributed to the rise of leptospirosis in Kelantan 204 required multi sectoral control and prevention strategies to combat the diseases. 6.0 Recommendations The result of this study which contributed from secondary data in E-notifikasi database only indicated occupation as one of the significant risk factors of leptospirosis in Kelantan whereby other significant risk factors such as recreational history, hobby and other environmental risk factor such as waste deposits need to be further explored. Therefore these factors are suggested need to be included in the E-notifikasi database so that these significant factors can be studied and analyzed. The association between climate and leptospirosis basically require long duration to identify the pattern of climate changes and leptospirosis infection. As in this study, one year duration is inadequate to establish the pattern and association. Therefore further study should be conducted with longer duration to look pattern and the association of climate and the disease itself. Azimullah AZ, Aziah BD, Fauziah MN 60
Acknowledgements The authors would like to thank the Director General of Health Malaysia for data collection from E-Notifikasi database for leptospirosis in which ethics approval was obtained from Ministry of Health (NMRR-4-765-23505). My gratitude and thanks also goes to the Kelantan CDC unit for their assistance during data collection. Declaration Author(s) declare that all works are original and that the research and publication has not been published in a different journal. Authors contribution Author : Prepare research proposal, data collection, data analysis, and drafting final manuscript. Author 2: Contributing in methodological aspects, planning of research activities and reviewed final draft of manuscript Author 3: Contributing in methodology and data collection of the research References Angnani, R., Pathak, A. A. & Mishra, M. (2003). Prevalence of leptospirosis in various risk groups. Indian J Med Microbiol, 2(4), 27-3. Bharti, A. R., Nally, J. E., Ricaldi, J. N., Matthias, M. A., Diaz, M. M., Lovett, M. A., Levett, P. N., Gilman, R. H., Willig, M. R., Gotuzzo, E., Vinetz, J. M. & Peru-United States Leptospirosis, C. (2003). Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis, 3(2), 757-7. El Jalii, I. M. & Bahaman, A. R. (2004). A review of human leptospirosis in Malaysia. Trop Biomed, 2(2), 3-9. Joel, N. E., Maribel, M. M., Beatriz, R. S. & Oscar, V. C. (20). Leptospirosis prevalence in a population of Yucatan, Mexico. J Pathog, 20, 408604. Lau, C. L., Smythe, L. D., Craig, S. B. & Weinstein, P. (200). Climate change, flooding, urbanisation and leptospirosis: fuelling the fire? Trans R Soc Trop Med Hyg, 04(0), 63-8. Azimullah AZ, Aziah BD, Fauziah MN 6
Lim, V. K. (20). Leptospirosis: a re-emerging infection. Malays J Pathol, 33(), -5. Maskey, M., Shastri, J. S., Saraswathi, K., Surpam, R. & Vaidya, N. (2006). Leptospirosis in Mumbai: post-deluge outbreak 2005. Indian J Med Microbiol, 24(4), 337-8. Narita, M., Fujitani, S., Haake, D. A. & Paterson, D. L. (2005). Leptospirosis after recreational exposure to water in the Yaeyama islands, Japan. Am J Trop Med Hyg, 73(4), 652-6. Rafizah, A. A., Aziah, B. D., Azwany, Y. N., Imran, M. K., Rusli, A. M., Nazri, S. M., Nikman, A. M., Nabilah, I., Asma, H. S., Zahiruddin, W. M. & Zaliha, I. (203a). A hospital-based study on seroprevalence of leptospirosis among febrile cases in northeastern Malaysia. Int J Infect Dis, 7(6), e394-7. Robertson, C., Nelson, T. A. & Stephen, C. (202). Spatial epidemiology of suspected clinical leptospirosis in Sri Lanka. Epidemiol Infect, 40(4), 73-43. Sejvar, J., Bancroft, E., Winthrop, K., Bettinger, J., Bajani, M., Bragg, S., Shutt, K., Kaiser, R., Marano, N., Popovic, T., Tappero, J., Ashford, D., Mascola, L., Vugia, D., Storck, C. H., Postic, D., Lamaury, I. & Perez, J. M. (2008). Changes in epidemiology of leptospirosis in 2003--2004, a two El Nino Southern Oscillation period, Guadeloupe archipelago, French West Indies. Epidemiol Infect, 36(0), 407-5. Sugunan, A. P., Vijayachari, P., Sharma, S., Roy, S., Manickam, P., Natarajaseenivasan, K., Gupte, M. D. & Sehgal, S. C. (2009). Risk factors associated with leptospirosis during an outbreak in Middle Andaman, India. Indian J Med Res, 30(), 67-73. Tan, D. S. (970). Leptospirosis in rural West Malaysia. Med J Malaya, 24(4), 26-6. Trevejo, R. T., Rigau-Perez, J. G., Ashford, D. A., McClure, E. M., Jarquin-Gonzalez, C., Amador, J. J., de los Reyes, J. O., Gonzalez, A., Zaki, S. R., Shieh, W. J., McLean, R. G., Nasci, R. S., Weyant, R. S., Bolin, C. A., Bragg, S. L., Perkins, B. A. & Spiegel, R. A. (998). Epidemic leptospirosis associated with pulmonary hemorrhage- Nicaragua, 995. J Infect Dis, 78(5), 457-63. Vanasco, N. B., Schmeling, M. F., Lottersberger, J., Costa, F., Ko, A. I. & Tarabla, H. D. (2008). Clinical characteristics and risk factors of human leptospirosis in Argentina (999-2005). Acta Trop, 07(3), 255-8. Vijayachari, P., Sugunan, A. P. & Shriram, A. N. (2008). Leptospirosis: an emerging global public health problem. J Biosci, 33(4), 557-69. Azimullah AZ, Aziah BD, Fauziah MN 62