Case Analysis of Leptospirosis in Pituruh and Purwodadi, Purworejo District, Central Java Province, Indonesia 2019

 
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Case Analysis of Leptospirosis in Pituruh and Purwodadi, Purworejo District, Central Java Province, Indonesia 2019
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021   Vol. 24 Issue 01

        Case Analysis of Leptospirosis in Pituruh and Purwodadi,
        Purworejo District, Central Java Province, Indonesia 2019

      Tri Wijayanti1*, Zumrotus Sholichah1, Bina lkawati1, Bondan Fajar Wahyudi1,
                                   Dewi Marbawati1

                       1
                       Banjarnegara Health Research and Development Unit

*Corresponding author:
Tri Wijayanti
Banjarnegara Health Research and Development Unit
Handphone number +62 81325548594
Facsimile numbers +62 (0286) 594972
E-mail address tri.wijayanti.76@gmail.com

Abstract
Background: Leptospirosis has been an outbreak in Purworejo since 2005 with 4 cases and 100%
Case Fatality Rate (CFR). In the last years, 2 cases of this disease with 50% CFR was reported in
2018 and another 10 from January until April 2019. Aims: This paper described species of rats,
examined Leptospira bacteria on their kidneys and water, analyzed risk and supporting factors of high
leptospirosis fatality. Methods and Material: This was a descriptive study with cross sectional design,
and the activity was held in Pituruh and Purwodadi, Purworejo District, Central Java Province,
Indonesia on May 13-16th, 2019. Rats trapping used single live traps, while environmental survey and
interview was conducted for the dead leptospirosis patients’ family. Furthermore, the kidneys of these
animals and water samples from environment were examined by Polymerase Chain Reaction (PCR).
Statistical analysis used: descriptive analysis. Results: All of the trapped rats were Rattus
tanezumi and the shrew Suncus murinus at success rate of 7% and 9% respectively in Pituruh and
Purwodadi. One out of 21 R. tanezumi was Leptospira infected, and all of the tested water samples
were negative. Risk factors include flooding and occupation related to farming, while delay in the
diagnosis of leptospirosis had impact on higher CFR. Conclusions: Promoting early diagnosis and
medical test for leptospira are necessary in the Public Health Center, especially in flood areas to
anticipate fatality of the disease.

Keywords: leptospirosis, cases, case fatality rate, rats , Purworejo

Key Messages :
The high case fatality rate of leptospirosis in Purworejo District needs attention about the importance
of promoting leptospirosis to health workers and the community. There is need for early detection and
warning, together with availability of leptospirosis diagnostic tools at first-level health facilities to

  Annals of Tropical       Medicine & Public Health http://doi.org/10.36295/ASRO.2021.241105
Case Analysis of Leptospirosis in Pituruh and Purwodadi, Purworejo District, Central Java Province, Indonesia 2019
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021       Vol. 24 Issue 01

anticipate more severe symptoms, especially in flooding areas and communities with risk factors such
as farming.

How to cite this article: Wijayanti T, Sholichah Z, et al (2021): Case analysis of leptospirosis in Pituruh
and Purwodadi, Purworejo district, Central Java Province, Indonesia 2019, Ann Trop Med & Public
Health; 22(S01): SP241105. DOI: http://doi.org/10.36295/ASRO.2021.241105

Introduction
      Leptospirosis is an infectious disease that has death risk, caused by the Leptospira bacteria.
The main reservoir for leptospirosis is rodents, especially rats which are the maintenance hosts of
Leptospira.1 The bacteria are preserved in the liver and kidneys of rats throughout their life and are
excreted in large amounts of urine.1 Leptospira is not harmful to the reservoir but tend to be deadly
when present in humans.
      Leptospirosis in Indonesia for 2011 - 2018 showed a peak point in 2011, 2013, 2016 and 2018
with the highest Case Fatality Rate/CFR in 2012, 2015 and 2017. In 2018, there were 894 cases with
148 deaths (CFR 16.5 %)2 and the highest was reported from Central Java. Leptospirosis in Central
Java from 2015 - 2018 have increased starting from 149, 164, 316 to 427 cases respectively. The
highest cases and fatality due to leptospirosis in 2018 occurred in this region with 20.84% CFR. 3
      Leptospirosis became an outbreak in Purworejo District in 2005 with 4 cases and 100% CFR. In
2007, only 1 case was reported and it was zero in the following 3 years. In 2011, there were 25
cases,4 but after several years none was reported, then there were 12 leptospirosis cases with the
youngest patient aged 14 years old in 2016, and in 2017 there were 10, all without death record. In
2018, 2 cases were reported with 1 death (50% CFR), and in 2019 there were 10 with 6 deaths (60%
CFR) until April 2019.5
      To anticipate the increase of the cases with higher CFR and to confirm leptospirosis
transmission, it is necessary to conduct a rat and environmental survey, as well as interview to family
of the infected persons that died in Pituruh and Purwodadi, Purworejo District. The objectives of this
activity were to identify the species of rats and shrews that were trapped, measure the trap success
rate, detect the presence of Leptospira in the two animal categories and water found in the patient's
environment, analyze risk and supporting factors for leptospirosis fatality.

Methods and Material
      The activity was descriptive with a cross sectional survey design that was carried out on May
13-16th 2019. Rat trapping, environmental surveys and interviews to family of the dead leptospirosis
patients were held in Pituruh and Purwodadi, Purworejo District, Central Java Province, Indonesia.
The location selection was based on reports from the hospital, about presence of the dead
leptospirosis patients.
      Samples consist of all captured rats' kidneys and water in the environment where transmission
was possible from the interview results, and were collected by purposive sampling. Rat trapping with
single live traps using grilled coconut bait or salted fish, totaling around 150 pieces installed in the
patients’ house for one night. The rats trapped were anaesthetized with ketamine HCL 100 mg / kg

  Annals of Tropical      Medicine & Public Health http://doi.org/10.36295/ASRO.2021.241105
Case Analysis of Leptospirosis in Pituruh and Purwodadi, Purworejo District, Central Java Province, Indonesia 2019
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021   Vol. 24 Issue 01

body weight. These animals were also identified with rat identification key,6,7 while the samples were
examined    for the presence of Leptospira bacteria using PCR method. Interviews were used to
determine the disease, medical history and risk factor of leptospirosis in 1 and 2 persons in Purwodadi
and Pituruh Sub Districts respectively.

Results
1.   Rats trapping
     The number of rats trapped in Pituruh was as many as 10 which were all Rattus tanezumi species
     from 150 traps installed (7% success rate). The results of the rat survey in Purwodadi conducted
     overnight had 12 rats from 136 traps installed (9% success rate) consisting of 1 Suncus murinus
     and 11 R. tanezumi. The rats trapping results are shown in Figure 1.

                               Figure 1. Rats trapping in Purworejo District

                                     7
             7
                                                          6
             6
                                             5
             5

             4
                       3                                                    Rattus tanezumi
             3
                                                                            Suncus murinus
             2
                                                   1
             1

             0
                     male        female     male        female
                           Pituruh               Purwodadi

     The results of Polymerase Chain Reaction on the rats and shrew kidney samples showed one
     male R. tanezumi in Pituruh was Leptospira infected (prevalence 4.76%). The positive rat was
     trapped at the neighbour’s house ofthe leptospirosis patients that died in a distance between 9m
     (metres).

2.   Interview
           Interview showed that the jobs of all the patients that had risk of leptospirosis was related
     with farming. The other risk factors for the transmission of this disease include those related to
     flooding (at home or place of work), injury on the feet by snails in the farm, contact with puddle
     and well water, and not using personal protective equipment (PPE).
           History showed that the initial treatment of leptospirosis was by a medical practitioner or
     taking drugs from a shop. The whole patients experienced delays in early clinical detection of

  Annals of Tropical       Medicine & Public Health http://doi.org/10.36295/ASRO.2021.241105
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021   Vol. 24 Issue 01

       leptospirosis, thus the patients came to the hospital too late and were in an advanced stage
       already (all appeared icteric), which lead to not getting antibiotics on time.

3.     Environmental Survey
             During dry season, environmental survey was carried out to ensure there were no puddles
       filled with water around the patient’s environment, but cases generally occurred when it was
       rainy or after flooding either on the farm or at home. The results of the activity were obtained
       using six (6) water samples from the home and rice fields, and the PCR method showed that all
       of them were Leptospira negative.
             All of leptospirosis patients that died have environment close to the Bogowonto river or
       irrigation canals. The condition of the houses or rice fields was nearness to animals / livestock
       such as cows, goats and dogs. In fact, at one of the rat trapping locations, there were many dogs
       roaming around. This condition made it possible for the transmission of Leptospira bacteria from
       livestock to human through their wastes.

     Figure 2. Environmental survey on leptospirosis cases who died in Pituruh and Purwodadi

             Observations on the environment’s          condition are that the houses were in a humid
       condition ranging from 52-69% and relatively dark. There was a part of the homes that had soil
       floors, while the location of the infective items was irregular. There was presence of garbage with
       uncovered containers that were not discarded daily, open waste disposal and the houses were
       not rats proof.

     Annals of Tropical   Medicine & Public Health http://doi.org/10.36295/ASRO.2021.241105
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021     Vol. 24 Issue 01

Discussion
      The success rate of rats trapping in Purworejo Regency was about 7-9%, indicating that it is still
in relatively normal condition. The population density of rat species fluctuates depending on
environmental conditions, thus influencing transmission of the pathogens they carry.8 The trapped
rats were R. tanezumi, because of their wide habitats that ranged from primary and secondary forest,
tropical rainforest, plantations, office buildings to rural and residential areas or at an altitude of 0-2000
m.9 Rattus tanezumi is mostly found indoors and it is a subspecies of Rattus-rattus which is common
in people's homes on Java island. The movement of rats between houses to survive and breed tends
to also be one of the causes of wider spread of leptospirosis.
      In this study, the prevalence of Leptospira bacteria in rat found in Purworejo was 4.76% which
is low, the same as the results of the 2015 special study on Vector and Disease Reservoir in
Purworejo. The results of PCR examinations on 71 rats from three (3) ecosystems (forest, non-forest
and coastal) showed Leptospira infection in R. tanezumi (1 rat’s head) and R. tiomanicus (3 heads).9
The prevalence of Leptospira bacteria in R. tanezumi in this region is similar to that of R. norvegicus
in Maumere City which was 4.4%.10 Rats are the main reservoir for leptospirosis because they are
able to excrete Leptospira bacteria in a long time and have high concentrations in their urine without
clinical symptoms. Many of the findings of leptospirosis was in rats found in urban or rural areas
around human settlements, even though the Leptospira positive animals is also detectable in distant
places such as forests.11 Cosson states that the genus Rattus and Bandicota are the most important
hosts for leptospirosis.12 Transmission between rats occurs both in ecosystems close to and far from
settlements. The study in three (3) districts in Central Sulawesi Province showed that Rattus sp was
positive for Lesptospira bacteria in primary, secondary, and coastal forest habitats, settlements, yards,
gardens, rice fields, beaches, and fields.13
      Leptospira bacteria were not found in the water samples, possibly because this study was
carried out during dry season. Therefore, it was less supportive to Leptospira transmission in the rats
population, due to the fact that water plays an important role in the transmission of these bacteria. Dry
air, hot sunshine and an inappropriate pH make up an unfavorable atmosphere for the life of
Leptospira.14 The prevalence of these bacteria in rats is influenced by several factors, including type
of environment (habitat and altitude) and sex.8The swimming ability of reservoir animals and minimum
temperature is also associated with leptospira infection.8
      The presence of Leptospira positive rats often contaminates the soil, environment, humans and
livestock around them. There was an outbreak of leptospirosis in Sleman, Bantul and Kulon Progo
several years ago. In a study conducted on the Progo River throughout these two districts (Sleman
and Kulon Progo) in Yogyakarta, the risk of leptospirosis on cows with 1-5 tails of rats was 2.67 times
compared to those that were rat-free. Stables with a waste disposal distance of
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021     Vol. 24 Issue 01

javanica, 4.5% canicola, 4.5% pyrogenes, 2% tarrasovi and 2% celledoni.14 The prevalence of
leptospirosis on sheep in Kulon Progo was 3.33% with ichterohaemorrhagiae serovar.15
      The existence of R. tanezumi that was infected by Leptospira in this study proved that R. diardii
/ R. tanezumi, R. norvegicus, and R. exulans as well as Suncus murinus were the most common
species that often become a reservoir for leptospirosis.16 Himsel stated that mice infected with the
Leptospira bacteria near settlements have the potential to transmit the bacteria to humans around
them when there is poor environmental sanitation, littering and improper food storage. But, Aulia study
proved that clean and healthy living habits of the people are important in the household, where sewer
conditions, the presence of rats, stagnant water, facilities of         waste and garbage disposal have
                                                            13
correlated with the incidence of leptospirosis in humans.
      The leptospirosis patients that died in this study lived close to the rivers / irrigation. Furthermore,
areas close to the rivers are more likely to be exposed to overflow during floods in the rainy season.
Irrigation canals are suitable places for the growth of Leptospira bacteria, while the people that live
close to dirty drains have 5.15 greater risk of suffering from leptospirosis. 17 Cases of leptospirosis at
the borders of Bantul, Sleman and Kulon Progo show groupings based on the distance of the houses
of those infected from rice fields, rivers and roads according to the pattern of planting and early rainy
season which tends to increase yearly. This needs to be a concern to ensure that it is able to
anticipate an increase in leptospirosis cases in the following years.
      In March 2019 there were floods in 4 sub-districts in Purworejo District, which were Bagelen,
Purwodadi, Ngombol and Bayan18, while another happened in other sub-districts on the previous
January. Also, floods occurred due to the overflowing of the Kaliwawar and Bogowonto rivers which
experienced high sedimentation.19       Leptospirosis outbreaks often follow floods, storms or other
disasters in the tropical countries. The incidence of leptospirosis in tropical countries is higher than in
subtropical and cold climates.20    Leptospirosis associated with this flood occurred in many areas
including Cengkareng Sub District, West Jakarta, and 26 cases were reported with 15.3% CFR. 21
There is possibility that Leptospira bacteria comes from livestock found around the leptospirosis
cases. Sources of this disease’s transmission in animals include rats, pigs, cows, goats, sheep,
horses, dogs, cats, insects, birds, insectivores (hedgehogs, bats, squirrels) and foxes which tend to
become Leptospira careers. Bacteria are transmitted to other animals directly or indirectly through
urine or other body fluids containing Leptospira. The results of study in Demak showed that livestock
such as goats, sheep, cats and cows tested positive for the bacteria by PCR examination. 22
      The results of Ramadhani's study showed that the presence of puddle water that contaminated
with rat or pet urine facilitates the entry of Leptospira bacteria into the human body due to direct or
indirect contact with rats or intermediate hosts.23 These bacteria enter the human body through
injured skin / blisters, especially around the feet, mucous membranes on the eye, nose, and of the
mouth.24 Leptospira spp are able to persist in moist soil and natural water bodies despite cold and
nutrient-poor acidic conditions, but do not survive in dry condition.1
      Leptospirosis control in Purworejo District and generally, encountered the same obstacles in
this course. Most of the leptospirosis patients come for health services in a delayed state. Commonly,

  Annals of Tropical    Medicine & Public Health http://doi.org/10.36295/ASRO.2021.241105
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021   Vol. 24 Issue 01

the patients and their families do not know whether the symptoms they feel before are leptospirosis
and capable to endanger their lives.25
        The patients that died in the course of this study were not detected as leptospirosis positive
from the onset. The atypical early symptoms of the disease make many health workers forget to
diagnose leptospirosis and this supports the associated high fatality rate.26 Approximately 10-15% of
leptospirosis fatality was due to pulmonary hemorrhage, arrhythmia, renal and heart failure due to
myocarditis. In the study on leptospirosis cases in Bantul District for 5 years, there were 32 of 128
patients that died (CFR 25%), which showed that those with shortness of breath, headache, myalgia,
jaundice and thrombocytopenia had 82.12% probability of experiencing death.26 Mild leptospirosis
was estimated as 90% of all cases of the disease with symptoms of fever, headache and myalgia and
only 10% severe leptospirosis with renal failure, jaundice and bleeding.16
        The study in Bantul suggested giving antibiotics in all phases, both acute (fever) and severe
leptospirosis. There is need for supportive therapy with attention to fluid and electrolyte balance in
severe leptospirosis. Cases with renal failure were treated for hemodialysis and it is recommended
that early transfusion of platelets be performed when these blood cells are less than 50,000 / mm3 or
drop drastically in a relatively fast time.26
        In 2019, the high Case Fatality Rate of leptospirosis in Purworejo District needs attention about
the importance of promoting leptospirosis to health workers and the community. There is need for
early detection and warning, together with availability of leptospirosis diagnostic tools at first-level
health facilities to anticipate more severe symptoms, especially in flooding areas and communities
with risk factors such as farming. Attention to leptospirosis is expected to reduce the fatality rate,
which is observable from the number of cases that are six (6) without death record in Purworejo as at
June 2020.27
        Transmission of diseases through rats needs to be watched out because these animals are able
to adapt to various types of climates, extreme conditions and have a wide space for movement both in
residential and swampy areas, markets, grasslands, gardens and forest edges. The importance of
rodent-borne disease surveillance in Purworejo is not only about leptospirosis but also including
another type of infection, because the results of other studies found that 8 of 57 R. tanezumi were
hanta virus positive as detected by serology. 28

Acknowledgement
The author is grateful to the Head of Banjarnegara Research and Development Unit and colleagues
for the implementation of this activity. The author is also grateful to the Head of Purworejo District
Health Office and staff for the good cooperation to ensure that this activity was completed smoothly.
Conflict of Interest
The authors have no conflict of interest associated with the material presented in this paper.

References
1.       Mayer-Scholl A, Teifke JP, Huber N, et al. Leptospira spp. in Rodents and Shrews from
         Afghanistan. J Wildl Dis. 2018;55(2):477-481. doi:10.7589/2018-05-122

     Annals of Tropical   Medicine & Public Health http://doi.org/10.36295/ASRO.2021.241105
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021   Vol. 24 Issue 01

2.       Kementerian Kesehatan RI. Profil Kesehatan Indonesia Tahun 2019. Vol 53. (Hardhana B,
         Sibuea F, Widiantini W, eds.). Jakarta: Kementerian Kesehatan RI; 2020.
         doi:10.1017/CBO9781107415324.004
3.       Kementrian Kesehatan RI. Profil Kesehatan Indonesia 2018. (Kurniawan R, Yudianto,
         Hardhana B, Siswanti T, eds.). Jakarta: Kementerian Kesehatan RI; 2019.
         http://www.depkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/Data-dan-
         Informasi_Profil-Kesehatan-Indonesia-2018.pdf.
4.       Ningsih DP, Sholichah Z. Kajian Reservoir Leptospira di Daerah Sporadis Leptospirosis
         Kabupaten Purworejo , Jawa Tengah. MKMI. 2018;14(1):61-67.
5.       Seksi Pencegahan Penyakit Menular Dinkes Kabupaten Purworejo. Data Kasus Leptospirosis
         Kabupaten Purworejo. Purworejo; 2019.
6.       Yuliadi B, Muhidin, S. I. Tikus Jawa: Teknik Survei Di Bidang Kesehatan. 1st ed. (Ristiyanto,
         Ahmadi AS, eds.). Jakarta: Lembaga Penerbit Badan Penelitian dan Pengembangan
         Kesehatan; 2016.
7.       Suyanto A. Penuntun Identifikasi Tikus di Jawa. Fauna Indones. 2001;5(1):7-25.
8.       Joharina AS, Pujiyanti A, Nugroho A, Martiningsih I, Handayani FD. Peran Tikus Sebagai
         Reservoir Leptospira di Tiga Ekosistem di Kabupaten Bantul , Yogyakarta. Bul Penelit Kesehat.
         2019;47(3):191-198.
9.       Khariri. Survei keanekaragaman tikus sebagai hewan pembawa bakteri Leptospira di Provinsi
         Jawa Tengah. Pros Semin Nas Masy Biodivers Indones. 2019;5(1):42-45.
         doi:10.13057/psnmbi/m050109
10.      Mulyono A, Ristiyanto, Putro DBW. Infeksi Ganda Leptospira dan Hantavirus pada Rattus
         norvegicus di Maumere Flores , Nusa Tenggara Timur. BALA. 2017;13(2):93-104.
11.      Ardanto A, Yuliadi B, Martiningsih I, Putro DBW, Joharina AS, Nurwidayati A. Leptospirosis
         pada Tikus Endemis Sulawesi (Rodentia: Muridae) dan Potensi Penularannya Antar Tikus dari
         Provinsi Sulawesi Selatan. Balaba. 2018:135-146. doi:10.22435/blb.v14i2.196
12.      Cosson JF, Picardeau M, Mielcarek M, et al. Epidemiology of Leptospira Transmitted by
         Rodents in Southeast Asia. PLoS Negl Trop Dis. 2014;8(6). doi:10.1371/journal.pntd.0002902
13.      Widjajanti W, Anastasia H, Rosmini R, Veridiana NN, Yuana WT. Kewaspadaan Dini Kasus
         Leptospirosis di Provinsi Sulawesi Tengah. VEKTORA. 2017;9(2):59-68.
14.      Mulyani GT, Sumiarto B, Artama WT, et al. Kajian Leptospirosis Pada Sapi Potong Di Daerah
         Aliran Sungai Progo Daerah Istimewa Yogyakarta. J Kedokt Hewan - Indones J Vet Sci.
         2016;10(1). doi:10.21157/j.ked.hewan.v10i1.3374
15.      Mulyani GT, Sulistyadi E, Kirwanto A, et al. Prevalensi dan Serovar Penyebab Leptospirosis
         pada Domba di Kabupaten Kulon Progo. J Sa. 2016;34(1):70-75. doi:10.22146/jsv.22817
16.      Direktorat Jenderal Pencegahan dan Pengendalian Penyakit. Petunjuk Teknis Pengendalian
         Leptospirosis. Cetakan Ke. Jakarta: Kementerian Kesehatan RI; 2017.
17.      Nurbeti M, Kusnanto H, Nugroho WS. Analisis Spasial Kasus Leptospirosis di Perbatasan
         Kabupaten Bantul, Sleman dan Kulon Progo. J Kesehat Masy. 2016;10(1):1-10.
18.      Heksantoro R. Belasan Desa di Purworejo Kebanjiran, Ratusan Warga Ngungsi.
         https://news.detik.com/berita-jawa-tengah/d-4472075/.  https://news.detik.com/berita-jawa-
         tengah/d-4472075/. Published 2019. Accessed September 13, 2020.
19.      Budi T. Biang Banjir Purworejo Akibat Pendangkalan Kaliwawar dan Bogowonto.
         https://news.okezone.com/.        https://news.okezone.com/read/2019/03/20/512/2032400/.
         Published 2019. Accessed September 14, 2020.
20.      Ristiyanto, Wibawa T, Budiharta S, Supargiono. Prevalensi tikus terinfeksi Leptospira
         interogans di Kota Semarang, Jawa Tengah. VEKTORA. 2015;7(2):85-92.
21.      Erviana A. Studi Epidemiologi Kejadian Leptospirosis Pada Saat Banjir di Kecamatan
         Cengkareng Periode Januari-Februari 2014. 2014.
22.      Putro DBW, Ristiyanto, Mulyono A. Deteksi Leptospira Patogenik Secara Molekuler Pada
         Hewan Ternak dan Peliharaan di Daerah Endemis Leptospirosis Kota Semarang, Jawa
         Tengah. http://repository.uksw.edu/.
23.      Ramadhani T. Serovar Bakteri Leptospira Pada Lingkungan (Air Dan Tanah) Dan Reservoir Di

     Annals of Tropical   Medicine & Public Health http://doi.org/10.36295/ASRO.2021.241105
Wijayanti et al (2021): Case Analysis of Leptospirosis in Purworejo District , Jan 2021   Vol. 24 Issue 01

       Daerah Dengan Kejadian Leptospirosis Di Provinsi Jawa Tengah.; 2013.
24.    Kusmiyati, Noor S, Supar. Leptospirosis Pada Hewan Dan Manusia di Indonesia. Wartazoa.
       2005;15:213-220.
25.    Meilani RAR, Sakundarno M, Yuliawati S. Gambaran keterlambatan mencari pengobatan ke
       pelayanan kesehatan pada penderita leptospirosis dan faktor-faktor terkait di Kota Semarang.
       J Kesehat Masy. 2016;4(4):448-453.
26.    Depo M, Kusnanto H. Risiko Kematian pada Kasus-kasus Leptospirosis: Data dari Kabupaten
       Bantul 2012-2017. Ber Kedokt Masy. 2018;34(6):236-241. doi:10.22146/bkm.34878
27.    Seksi Pencegahan Penyakit Menular. Data Penderita Penyakit Leptospirosis. Purworejo; 2020.
28.    Mulyono A, Ristiyanto, Handayani FD, Susanti L, Raharjo J. Catatan Baru Reservoir
       Hantavirus Dari Provinsi Jawa Tengah, Indonesia. Vektora. 2017;9(2):51-59.
       file:///C:/Users/user/Downloads/6955-19833-2-PB.pdf.

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