- Email: [email protected]
SCRUB TYPHUS: A SERIOUS PUBLIC HEALTH ISSUE IN NEPAL
Journal Pre-proof SCRUB TYPHUS: A SERIOUS PUBLIC HEALTH ISSUE IN NEPAL Krishna Prasad Acharya, Niran Adhikari, Muhammad Tariq PII:
S2213-3984(20)30042-7
DOI:
https://doi.org/10.1016/j.cegh.2020.02.006
Reference:
CEGH 502
To appear in:
Clinical Epidemiology and Global Health
Received Date: 13 December 2019 Accepted Date: 14 February 2020
Please cite this article as: Acharya KP, Adhikari N, Tariq M, SCRUB TYPHUS: A SERIOUS PUBLIC HEALTH ISSUE IN NEPAL, Clinical Epidemiology and Global Health, https://doi.org/10.1016/ j.cegh.2020.02.006. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of INDIACLEN.
SCRUB TYPHUS: A SERIOUS PUBLIC HEALTH ISSUE IN NEPAL Krishna Prasad Acharya1*, Niran Adhikari2, Muhammad Tariq3 1
Ministry of Agriculture and Livestock Development (MoALD), Kathmandu, Nepal
2
Animal Health Training and Consultancy Services (AHTCS), Pokhara, Nepal
3
Department of Livestock Management, University of Agriculture, Faisalabad Sub-Campus Toba
Tek Singh, Pakistan
*Correspondence: Dr. Krishna Prasad Acharya; Ministry of Agriculture and Livestock Development (MoALD), Kathmandu, Nepal; Email: [email protected]; [email protected]
1
Letter to the Editor SCRUB TYPHUS: A SERIOUS PUBLIC HEALTH ISSUE IN NEPAL
2 3
Abstract
4
The agro-climatic conditions, socio-economic situation, poor sanitation, low hygiene and health
5
standards in Nepal are major contributing factors to the emergence of scrub typhus in Nepal.
6
These outbreaks, along with poor diagnostic facilities, can lead to severe economic losses in a
7
resource-limited country like Nepal. Diseases like avian influenza, leptospirosis, brucellosis,
8
tuberculosis and rabies, that cause heavy socio-economic burden, have received huge attention of
9
Government of Nepal and hence are among the top ten priority diseases. However, until now,
10
scrub typhus is not considered a priority disease in Nepal, despite having severe outbreaks time
11
to time. In order to diagnose and treat scrub typhus infection, low budget diagnostic tests such as
12
Weil Felix are less efficient and poor in screening, and highly advanced & efficient tests are less
13
likely to be available and are expensive. Nepal needs to explore appropriate and applicable test
14
settings in primary health centers and referral laboratories in the country. Moreover, focus should
15
be made on effective surveillance programs and public awareness campaigns, mice/rat control
16
strategies, and improving sanitation, public health and hygiene measures for the people at most
17
risk. In addition, health workers and professionals should be trained on early case detection,
18
personal protection, proactive rodent control strategies, habitat destruction and good sanitation
19
and hygiene practices.
20
Keywords: Scrub typhus; diagnosis; rodent control; public health and hygiene, Nepal
21 22
Scrub typhus, also known as bush typhus, is an acute, endemic, febrile, zoonotic rickettsial
23
infectious disease. Scrub typhus is caused by Orientia tsutsugamushi, an obligatory intracellular
24
gram negative proteo-bacterium1 transmitted by the blood sucking larvae, chigger, of arthropod
25
(Trombiculadae family) mites. These mites are highly prevalent in certain regions of Nepal and
26
are endemic to neighboring countries like Pakistan, India, Indonesia, Maldives, Myanmar, Sri
27
Lanka, Thailand and other islands in the region 2. The onset of disease condition is characterized
28
by the fever of unknown origin (FUO), headache, body aches (Myalgia), rashes, cough and
29
gastro-intestinal problems. Usually the eschar or scab is developed at the site of chigger bite.
30
However, detection of eschar is rare in South-East Asian patients and is usually reported with
31
less severe form of illness often without the eschar or rash. The other symptoms may include
32
lymphadenopathy and hypotension 3.
33
In Nepal, the vast majority (approximately 80%) of the population lives in rural areas with
34
agriculture as their mainstay of household economy. While involving in agricultural activities as
35
well as household chores, they daily come in direct contact with rodents, ticks, and mites 4.
36
Likewise in urban areas, where waste disposal is a major issue, and also provides flourishing
37
environment for rodents and pests especially rats, mice and mite 5. The seasonal flooding in
38
Nepal predisposes to the poor sanitary and hygienic conditions and increases the number of
39
rodents that eventually increase the risk of disease transmission. In addition, during the wetter
40
months of the year more chiggers are attached to a rodent which may cause scrub typhus burdens
41
in rainy seasons 6. The recurrent outbreaks of scrub typhus in Nepal could have been thus,
42
substantiated by occupational status, poor sewage and agro-climatic condition of the country.
43
Acute febrile illness is the most common problem in Nepal and most of the cases FUO are often
44
misdiagnosed
45
suspected to be salmonella enterica serovar typhi and paratyphi-A9,10 and treated as per
46
Most of the cases of febrile illness are mostly treated based on the clinical suspicion rather than
47
the epidemiological studies and identification of causative pathogens
48
the possible reason behind those febrile illnesses could be rickettsial infection of spotted fever
49
group or typhus group type (scrub typhus) or mixed infection of both. These two forms of
50
rickettsial infection (spotted fever group and scrub typhus) have varying degree of clinical
51
manifestations. Though both rickettsial infections have different geographical distribution,
52
seasonal patterns, and clinical indications, they share some clinical features.
53
A study by Kalal et al., with ELISA shows that skin rash and leukocytosis was more associated
54
with spotted fever group and thrombocytopenia with scrub typhus infection
55
unidentified fever or FUO, without neglecting potential diseases with similar symptoms, must be
56
distinguished with an appropriate diagnostic test.
57
Scrub typhus was first reported in Nepal in 1981 as a cause of FUO 15. Serological investigation
58
of scrub typhus was carried out in 2004, in Patan Hospital (one of the largest hospitals in Nepal)
59
in a small number of febrile patients (876) admitted to the same hospital
60
were made before 2014 to determine the prevalence of scrub typhus in Nepal 17.
7,8
. These febrile illness cases, characterized by high body temperature, are
11,13
16
11,12
.
. Chances exist that
14
. Therefore,
. Very few attempts
61
In 2015, the number of recurrent outbreaks of scrub typhus increased in Nepal in the people
62
living in temporary shelters following a devastating 7.8-magnitude earthquake and the
63
subsequent aftershocks with history of increased rodent infestation in the environment18. Since
64
then, several episodes of outbreak of scrub typhus have been reported (Table 1).
65
This all has been speculated most likely to be due to creation of favorable niche due to aftermath
66
and debris created by the earthquake, overcrowding in temporary makeshift camps, poor
67
sanitation and health hygiene,
68
population dislocation that resulted in rats abandoning their underground habitat
69
close proximity of human dwellings and thus, breeding sites of vectors and reservoirs, and
70
altered epidemiological behavior of vectors/reservoirs.
71
The outbreaks alarmed health authority and hence Epidemiology and Disease Control Division
72
(EDCD) developed an interim guideline on Prevention and Control of Scrub Typhus in Nepal 24.
73
However, the public have poorly opted and implemented these guidelines as evidenced by recent
74
rise on the cases of scrub typhus in Nepal
75
diagnosis of this condition. Weil Felix test and ELISA test are among these most frequently used
76
tests in Nepal 29. Weil-Felix is less sensitive test characterized by low efficiency, which can be
77
referred in primary health centers and hospitals. However, more simple and rapid tests like
78
dipstick can be arranged in primary hospital which is more efficient, sensitive and specific than
79
Weil-Felix test. In the reference laboratory, tests like IgM ELISA and gold standard tests like
80
Immuno-fluorescent Assay (IFA) and Indirect Immuno-peroxidase assay (IIPA) could be
81
conducted. Real time PCR (RT-PCR) which is highly specific, if feasible could be employed to
82
antigen detection. But, high technical savviness and expenses [23], hinders its application in
83
Nepalese condition. Real time PCR (RT-PCR) is highly specific, but it is costly and varies with
84
sample test and type and its timing.
85
Currently, scrub typhus is not considered a priority disease in Nepal. Diseases like avian
86
influenza, leptospirosis, brucellosis, rabies and other similar zoonotic infection that cause heavy
87
socio-economic burden, have received attention of Government of Nepal and hence are among
88
the top ten priority zoonotic diseases
89
disease control and prevention is used up for the prevention and control of these prioritized
90
diseases. With the availability of limited budget and resource allocation in health sector, the
large scale human and rat/mice habitat destruction, and
3031
28
27
, coming in
. A number of tests have been developed for
. Almost all health sector budget, allocated for the
91
government is unable to spend financial resources for prevention and control of every disease
92
with equal emphasis.
93
Putting the facts together, medical and para-medical staff training and education, availability of
94
cost effective diagnostic methods and an effective program to assure prompt treatment, should be
95
initiated as there is always an ever existing danger of disease re-emergence. The situation could
96
also be handled in a better way by proactive management strategies for mice/rat control and
97
improving sanitation, public health and hygiene conditions for the people at most risk. Last but
98
not least, primary health workers and medical professionals should be trained on early case
99
detection, personal protection, proactive rodent control strategies, habitat destruction and good
100
sanitation/ hygiene practices. Thus, a nationwide study is needed to identify the niche and track
101
scrub typhus, an important issue of high public health concern while emphasizing on its future
102
epidemiological characterization and ecological studies in Nepal.
103 104 105
List of abbreviations FUO Fever of unknown origin
106
ELISA
Enzyme linked immuno sorbent Assay
107
IFA
Immuno-fluorescence Assay
108
IIPA
Indirect Immuno-peroxidase assay
109
EDCD
Epidemiology and Disease Control Division
110
RT-PCR
Real time polymerase chain reaction
111
NHRC
Nepal Health Research Council
112 113 114 115 116 117 118 119 120 121 122 123
Declarations: Ethics approval and consent to participate: Not applicable (NA) Consent for publication Not applicable (NA) Availability of data and material All data generated or analyzed during this article preparation from published articles are referenced in author & ref. column of table.
124 125 126 127 128 129 130 131 132 133 134 135 136 137 138
Competing interests No competing interest Funding No funding was available. Authors' contributions KPA designed study, KPA and NA did literature review and prepared the manuscript, KPA, NA and MT extensively revised the manuscript, read and approved the final manuscript. Acknowledgements The author is thankful to the Dr. Prerana Sedhain Bhattarai, Dr. Krishna Kaphle for their inputs and valuable suggestions. Thanks are also due to two reviewers for their constructive comments without which this paper would not have been in the present shape
139 140
References
141
1.
Taylor AJ, Paris DH, Newton PN. A Systematic Review of Mortality from Untreated
142
Scrub Typhus (Orientia tsutsugamushi). Walker DH, ed. PLoS Negl Trop Dis.
143
2015;9(8):e0003971. doi:10.1371/journal.pntd.0003971
144
2.
Dermatology. Vol 62. Medknow Publications; 2017:478-485. doi:10.4103/ijd.IJD_388_17
145 146
3.
4.
Xu G, Walker DH, Jupiter D, Melby PC, Arcari CM. A review of the global epidemiology of scrub typhus. PLoS Negl Trop Dis. 2017. doi:10.1371/journal.pntd.0006062
149 150
Chakraborty S, Sarma N. Scrub typhus: An emerging threat. In: Indian Journal of Dermatology. Vol 62. Medknow Publications; 2017:478-485. doi:10.4103/ijd.IJD_388_17
147 148
Chakraborty S, Sarma N. Scrub typhus: An emerging threat. In: Indian Journal of
5.
Santos N de J, Sousa E, Reis MG, Ko AI, Costa F. Infestação por roedores associada a
151
fatores ambientais numa comunidade carente com alto risco de transmissão da
152
leptospirose. Cad Saude Publica. 2017;33(2). doi:10.1590/0102-311X00132115
153
6.
Gurung S, Pradhan J, Bhutia PY. Outbreak of scrub typhus in the North East Himalayan
154
region-Sikkim: an emerging threat. Indian J Med Microbiol. 31(1):72-74.
155
doi:10.4103/0255-0857.108729
156 157
7.
Murdoch DR, Woods CW, Zimmerman MD, et al. The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal. Am J Trop Med Hyg. 2004;70(6):670-
675. http://www.ncbi.nlm.nih.gov/pubmed/15211012. Accessed March 28, 2018.
158 159
8.
Blacksell SD, Bryant NJ, Paris DH, Doust JA, Sakoda Y, Day NPJ. Scrub Typhus
160
Serologic Testing with the Indirect Immunofluorescence Method as a Diagnostic Gold
161
Standard: A Lack of Consensus Leads to a Lot of Confusion. Clin Infect Dis.
162
2007;44(3):391-401. doi:10.1086/510585
163
9.
Puran Sharma ଝ K, Ramakrishnan R, Hutin Y, et al. ARTICLE IN PRESS +Model Scrub
164
typhus in Darjeeling, India: opportunities for simple, practical prevention measures. Trans
165
R Soc Trop Med Hyg. 2009. doi:10.1016/j.trstmh.2009.02.006 Murdoch DR, Woods CW, Zimmerman MD, et al. The etiology of febrile illness in adults
166
10.
167
presenting to Patan hospital in Kathmandu, Nepal. Am J Trop Med Hyg. 2004;70(6):670-
168
675.
169
11.
Blacksell SD, Bryant NJ, Paris DH, Doust JA, Sakoda Y, Day NPJ. Scrub Typhus
170
Serologic Testing with the Indirect Immunofluorescence Method as a Diagnostic Gold
171
Standard: A Lack of Consensus Leads to a Lot of Confusion. Clin Infect Dis.
172
2007;44(3):391-401. doi:10.1086/510585
173
12.
Puran Sharma ଝ K, Ramakrishnan R, Hutin Y, et al. ARTICLE IN PRESS +Model Scrub
174
typhus in Darjeeling, India: opportunities for simple, practical prevention measures. Trans
175
R Soc Trop Med Hyg. 2009. doi:10.1016/j.trstmh.2009.02.006
176
13.
2016;4(8):e516-7. doi:10.1016/S2214-109X(16)30094-8
177 178
Basnyat B. Typhoid versus typhus fever in post-earthquake Nepal. Lancet Glob Heal.
14.
Kalal BS, Puranik P, Nagaraj S, Rego S, Shet A. Scrub typhus and spotted fever among
179
hospitalised children in South India: Clinical profile and serological epidemiology. Indian
180
J Med Microbiol. 2016;34(3):293-298. doi:10.4103/0255-0857.188315
181
15.
Soc Trop Med Hyg. 1981;75(4):586-587. doi:10.1016/0035-9203(81)90210-8
182 183
Brown GW, Shirai A, Gan E, Bernthal P. Antibodies to typhus in Eastern Nepal. Trans R
16.
Murdoch DR, Woods CW, Zimmerman MD, et al. The etiology of febrile illness in adults
184
presenting to Patan Hospital in Kathmandu, Nepal. Am J Trop Med Hyg. 2004;70(6):670-
185
675. doi:10.4269/ajtmh.2004.70.670
186
17.
Bahadur Karki K, Prasad Acharya B, Dhimal M, et al. Descriptive Epidemiology of Scrub
187
Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive
188
Epidemiology of Scrub Typhus in Nepal, 2017 Authors. 2017. http://nhrc.gov.np/wp-
content/uploads/2017/11/Final_Scrub.pdf. Accessed April 12, 2018.
189 190
18.
doi:10.3126/nje.v6i2.15162
191 192
Nayak N. Scrub Typhus in Nepal. Nepal J Epidemiol. 2016;6(2):563-564.
19.
Sah RK, Chapagain RH, Shrestha SM, Rai GK. Clinico-laboratory Profile and
193
Therapeutic Outcome of Serologically Confirmed Scrub Typhus in Children in Tertiary
194
Care Children ’ s Hospital of iMedPub Journals Clinico-laboratory Profile and
195
Therapeutic Outcome of Serologically Confirmed Scrub Typhus in. 2019;(January).
196
doi:10.21767/2573-0282.100065
197
20.
Upadhyaya BP, Shakya G, Adhikari S, et al. Scrub Typhus: An Emerging Neglected
198
Tropical Disease in Nepal. J Nepal Health Res Counc. 2016;14(33):122-127.
199
http://www.ncbi.nlm.nih.gov/pubmed/27885295. Accessed March 28, 2018.
200
21.
Chitwan Med Coll. 2017;6(4):1. doi:10.3126/jcmc.v6i4.16707
201 202
22.
23.
24.
EDCD interim Guideline on Prevention and Control of Scrub Typhus September 2015 (Updated in August 2016).
207 208
Bastola A, Pant N. An outbreak of scrub typhus in nepal following the 2015 Gorkha earthquake. Int J Infect Dis. 2016;53:55. doi:10.1016/j.ijid.2016.11.141
205 206
Upadhyaya BP, Shakya G, Adhikari S, et al. Scrub Typhus: An Emerging Neglected Tropical Disease in Nepal. J Nepal Health Res Counc. 2016;14(33):122-127.
203 204
Thapa S, Sapkota LB, Hamal P. Threat of scrub typhus in post-earthquake Nepal. J
25.
Bahadur Karki K, Prasad Acharya B, Dhimal M, et al. Descriptive Epidemiology of Scrub
209
Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive
210
Epidemiology of Scrub Typhus in Nepal, 2017 Authors. 2017.
211
26.
Pathak S, Chaudhary N, Dhakal P, et al. Clinical profile, complications and outcome of
212
scrub typhus in children: A hospital based observational study in central Nepal. PLoS
213
One. 2019;14(8):e0220905. doi:10.1371/journal.pone.0220905
214
27.
Chitwan Med Coll. 2017;6(4):1. doi:10.3126/jcmc.v6i4.16707
215 216
28.
219
Cases of scrub typhus on the rise. https://thehimalayantimes.com/nepal/cases-of-scrubtyphus-on-the-rise/. Accessed October 26, 2019.
217 218
Thapa S, Sapkota LB, Hamal P. Threat of scrub typhus in post-earthquake Nepal. J
29.
Sedhain A, Bhattarai GR. Clinical presentation of scrub typhus during a major outbreak in central Nepal. Asian J Med Sci. 2017;8(4):27-31. doi:10.3126/ajms.v8i4.17163
220
30.
Zoonotic Disease Control Programme.
221
https://www.mohp.gov.np/eng/program/communicable-disease/zoonotic-disease-control-
222
programme. Accessed October 26, 2019.
223 224 225
31.
EDCD|Home. http://www.edcd.gov.np/. Accessed October 26, 2019.
Table 1: Studies/Reports on Scrub Typhus in Nepal
Author Murdoch et al.,[10]
Study Year 2003
Blacksell et al.,[11]
2007
Shah et al., [19]
2019
Upadhyay et al., [20]
2016
Thapa et al., [21]
2016
Upadhyay et al., [22]
2016
Bastola and Pant [23]
2016
Epidemiology and Disease Control Division (EDCD), Nepal [24]
2016
Location
Test Used
Prevalence %
Type of study
Different Hospitals of Kathmandu
INDx Multitest dipstickSDLST
3.2% ( 28/876)
Prospective
22.33% (23/103)
Retrospective
Different Hospitals of Kathmandu Kanti Children Hospital Dhading
ELISA
2016: 37.1% Retrospective 2017: 61.3% 2018: 1.6% 35.3% (36/102) Prospective
Kailali
ELISA
60.4% (32/53)
Kanchanpur
ELISA
54.2% (13/24)
Ramechhap
ELISA
81.3% (13/16)
Khotang Patient admitted to Chitwan Medical College 30 districts of Nepal
ELISA ELISA
61.5% (8/13) 44.1% (181/410)
ELISA
52.4%(175/434) Retrospective
PCR IFA ELISA
29.4% (5/17) 70.6% (12/17) 23 cases
Prospective
ELISA
6 cases
Retrospective
Patients admitted to the Sukraraj Tropical and Infectious Disease Hospital, Ktm Eastern Nepal
Serological tests
Prospective
Epidemiology and Disease Control Division (EDCD), Nepal[24] Nepal Health Research Council (NHRC)[25] Nepal Health Research Council (NHRC)[25] Nepal Health Research Council (NHRC)[25]
2016
Nepal Health Research Council (NHRC)[25] Pathak et al.,[26]
All over the Nepal 25 districts of Nepal
ELISA
> 400 cases
Retrospective
ELISA
>500 cases
Retrospective
IFA
2016
From Rodents population
PCR
22.2% (2/9)
Prospective
2016
Chiggers mite samples
PCR
33.3% (1/3)
Prospective
2016
ELISA
60.0% (30/50)
Prospective
IFA
52.0% (26/50)
Prospective
2016
National Public Health Laboratory, Kathmandu Chitwan
IFA
27.3% (3/11)
Prospective
2019
Chitwan
ELISA
24.4% (76/312)
Retrospective
S2213-3984(20)30042-7
DOI:
https://doi.org/10.1016/j.cegh.2020.02.006
Reference:
CEGH 502
To appear in:
Clinical Epidemiology and Global Health
Received Date: 13 December 2019 Accepted Date: 14 February 2020
Please cite this article as: Acharya KP, Adhikari N, Tariq M, SCRUB TYPHUS: A SERIOUS PUBLIC HEALTH ISSUE IN NEPAL, Clinical Epidemiology and Global Health, https://doi.org/10.1016/ j.cegh.2020.02.006. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of INDIACLEN.
SCRUB TYPHUS: A SERIOUS PUBLIC HEALTH ISSUE IN NEPAL Krishna Prasad Acharya1*, Niran Adhikari2, Muhammad Tariq3 1
Ministry of Agriculture and Livestock Development (MoALD), Kathmandu, Nepal
2
Animal Health Training and Consultancy Services (AHTCS), Pokhara, Nepal
3
Department of Livestock Management, University of Agriculture, Faisalabad Sub-Campus Toba
Tek Singh, Pakistan
*Correspondence: Dr. Krishna Prasad Acharya; Ministry of Agriculture and Livestock Development (MoALD), Kathmandu, Nepal; Email: [email protected]; [email protected]
1
Letter to the Editor SCRUB TYPHUS: A SERIOUS PUBLIC HEALTH ISSUE IN NEPAL
2 3
Abstract
4
The agro-climatic conditions, socio-economic situation, poor sanitation, low hygiene and health
5
standards in Nepal are major contributing factors to the emergence of scrub typhus in Nepal.
6
These outbreaks, along with poor diagnostic facilities, can lead to severe economic losses in a
7
resource-limited country like Nepal. Diseases like avian influenza, leptospirosis, brucellosis,
8
tuberculosis and rabies, that cause heavy socio-economic burden, have received huge attention of
9
Government of Nepal and hence are among the top ten priority diseases. However, until now,
10
scrub typhus is not considered a priority disease in Nepal, despite having severe outbreaks time
11
to time. In order to diagnose and treat scrub typhus infection, low budget diagnostic tests such as
12
Weil Felix are less efficient and poor in screening, and highly advanced & efficient tests are less
13
likely to be available and are expensive. Nepal needs to explore appropriate and applicable test
14
settings in primary health centers and referral laboratories in the country. Moreover, focus should
15
be made on effective surveillance programs and public awareness campaigns, mice/rat control
16
strategies, and improving sanitation, public health and hygiene measures for the people at most
17
risk. In addition, health workers and professionals should be trained on early case detection,
18
personal protection, proactive rodent control strategies, habitat destruction and good sanitation
19
and hygiene practices.
20
Keywords: Scrub typhus; diagnosis; rodent control; public health and hygiene, Nepal
21 22
Scrub typhus, also known as bush typhus, is an acute, endemic, febrile, zoonotic rickettsial
23
infectious disease. Scrub typhus is caused by Orientia tsutsugamushi, an obligatory intracellular
24
gram negative proteo-bacterium1 transmitted by the blood sucking larvae, chigger, of arthropod
25
(Trombiculadae family) mites. These mites are highly prevalent in certain regions of Nepal and
26
are endemic to neighboring countries like Pakistan, India, Indonesia, Maldives, Myanmar, Sri
27
Lanka, Thailand and other islands in the region 2. The onset of disease condition is characterized
28
by the fever of unknown origin (FUO), headache, body aches (Myalgia), rashes, cough and
29
gastro-intestinal problems. Usually the eschar or scab is developed at the site of chigger bite.
30
However, detection of eschar is rare in South-East Asian patients and is usually reported with
31
less severe form of illness often without the eschar or rash. The other symptoms may include
32
lymphadenopathy and hypotension 3.
33
In Nepal, the vast majority (approximately 80%) of the population lives in rural areas with
34
agriculture as their mainstay of household economy. While involving in agricultural activities as
35
well as household chores, they daily come in direct contact with rodents, ticks, and mites 4.
36
Likewise in urban areas, where waste disposal is a major issue, and also provides flourishing
37
environment for rodents and pests especially rats, mice and mite 5. The seasonal flooding in
38
Nepal predisposes to the poor sanitary and hygienic conditions and increases the number of
39
rodents that eventually increase the risk of disease transmission. In addition, during the wetter
40
months of the year more chiggers are attached to a rodent which may cause scrub typhus burdens
41
in rainy seasons 6. The recurrent outbreaks of scrub typhus in Nepal could have been thus,
42
substantiated by occupational status, poor sewage and agro-climatic condition of the country.
43
Acute febrile illness is the most common problem in Nepal and most of the cases FUO are often
44
misdiagnosed
45
suspected to be salmonella enterica serovar typhi and paratyphi-A9,10 and treated as per
46
Most of the cases of febrile illness are mostly treated based on the clinical suspicion rather than
47
the epidemiological studies and identification of causative pathogens
48
the possible reason behind those febrile illnesses could be rickettsial infection of spotted fever
49
group or typhus group type (scrub typhus) or mixed infection of both. These two forms of
50
rickettsial infection (spotted fever group and scrub typhus) have varying degree of clinical
51
manifestations. Though both rickettsial infections have different geographical distribution,
52
seasonal patterns, and clinical indications, they share some clinical features.
53
A study by Kalal et al., with ELISA shows that skin rash and leukocytosis was more associated
54
with spotted fever group and thrombocytopenia with scrub typhus infection
55
unidentified fever or FUO, without neglecting potential diseases with similar symptoms, must be
56
distinguished with an appropriate diagnostic test.
57
Scrub typhus was first reported in Nepal in 1981 as a cause of FUO 15. Serological investigation
58
of scrub typhus was carried out in 2004, in Patan Hospital (one of the largest hospitals in Nepal)
59
in a small number of febrile patients (876) admitted to the same hospital
60
were made before 2014 to determine the prevalence of scrub typhus in Nepal 17.
7,8
. These febrile illness cases, characterized by high body temperature, are
11,13
16
11,12
.
. Chances exist that
14
. Therefore,
. Very few attempts
61
In 2015, the number of recurrent outbreaks of scrub typhus increased in Nepal in the people
62
living in temporary shelters following a devastating 7.8-magnitude earthquake and the
63
subsequent aftershocks with history of increased rodent infestation in the environment18. Since
64
then, several episodes of outbreak of scrub typhus have been reported (Table 1).
65
This all has been speculated most likely to be due to creation of favorable niche due to aftermath
66
and debris created by the earthquake, overcrowding in temporary makeshift camps, poor
67
sanitation and health hygiene,
68
population dislocation that resulted in rats abandoning their underground habitat
69
close proximity of human dwellings and thus, breeding sites of vectors and reservoirs, and
70
altered epidemiological behavior of vectors/reservoirs.
71
The outbreaks alarmed health authority and hence Epidemiology and Disease Control Division
72
(EDCD) developed an interim guideline on Prevention and Control of Scrub Typhus in Nepal 24.
73
However, the public have poorly opted and implemented these guidelines as evidenced by recent
74
rise on the cases of scrub typhus in Nepal
75
diagnosis of this condition. Weil Felix test and ELISA test are among these most frequently used
76
tests in Nepal 29. Weil-Felix is less sensitive test characterized by low efficiency, which can be
77
referred in primary health centers and hospitals. However, more simple and rapid tests like
78
dipstick can be arranged in primary hospital which is more efficient, sensitive and specific than
79
Weil-Felix test. In the reference laboratory, tests like IgM ELISA and gold standard tests like
80
Immuno-fluorescent Assay (IFA) and Indirect Immuno-peroxidase assay (IIPA) could be
81
conducted. Real time PCR (RT-PCR) which is highly specific, if feasible could be employed to
82
antigen detection. But, high technical savviness and expenses [23], hinders its application in
83
Nepalese condition. Real time PCR (RT-PCR) is highly specific, but it is costly and varies with
84
sample test and type and its timing.
85
Currently, scrub typhus is not considered a priority disease in Nepal. Diseases like avian
86
influenza, leptospirosis, brucellosis, rabies and other similar zoonotic infection that cause heavy
87
socio-economic burden, have received attention of Government of Nepal and hence are among
88
the top ten priority zoonotic diseases
89
disease control and prevention is used up for the prevention and control of these prioritized
90
diseases. With the availability of limited budget and resource allocation in health sector, the
large scale human and rat/mice habitat destruction, and
3031
28
27
, coming in
. A number of tests have been developed for
. Almost all health sector budget, allocated for the
91
government is unable to spend financial resources for prevention and control of every disease
92
with equal emphasis.
93
Putting the facts together, medical and para-medical staff training and education, availability of
94
cost effective diagnostic methods and an effective program to assure prompt treatment, should be
95
initiated as there is always an ever existing danger of disease re-emergence. The situation could
96
also be handled in a better way by proactive management strategies for mice/rat control and
97
improving sanitation, public health and hygiene conditions for the people at most risk. Last but
98
not least, primary health workers and medical professionals should be trained on early case
99
detection, personal protection, proactive rodent control strategies, habitat destruction and good
100
sanitation/ hygiene practices. Thus, a nationwide study is needed to identify the niche and track
101
scrub typhus, an important issue of high public health concern while emphasizing on its future
102
epidemiological characterization and ecological studies in Nepal.
103 104 105
List of abbreviations FUO Fever of unknown origin
106
ELISA
Enzyme linked immuno sorbent Assay
107
IFA
Immuno-fluorescence Assay
108
IIPA
Indirect Immuno-peroxidase assay
109
EDCD
Epidemiology and Disease Control Division
110
RT-PCR
Real time polymerase chain reaction
111
NHRC
Nepal Health Research Council
112 113 114 115 116 117 118 119 120 121 122 123
Declarations: Ethics approval and consent to participate: Not applicable (NA) Consent for publication Not applicable (NA) Availability of data and material All data generated or analyzed during this article preparation from published articles are referenced in author & ref. column of table.
124 125 126 127 128 129 130 131 132 133 134 135 136 137 138
Competing interests No competing interest Funding No funding was available. Authors' contributions KPA designed study, KPA and NA did literature review and prepared the manuscript, KPA, NA and MT extensively revised the manuscript, read and approved the final manuscript. Acknowledgements The author is thankful to the Dr. Prerana Sedhain Bhattarai, Dr. Krishna Kaphle for their inputs and valuable suggestions. Thanks are also due to two reviewers for their constructive comments without which this paper would not have been in the present shape
139 140
References
141
1.
Taylor AJ, Paris DH, Newton PN. A Systematic Review of Mortality from Untreated
142
Scrub Typhus (Orientia tsutsugamushi). Walker DH, ed. PLoS Negl Trop Dis.
143
2015;9(8):e0003971. doi:10.1371/journal.pntd.0003971
144
2.
Dermatology. Vol 62. Medknow Publications; 2017:478-485. doi:10.4103/ijd.IJD_388_17
145 146
3.
4.
Xu G, Walker DH, Jupiter D, Melby PC, Arcari CM. A review of the global epidemiology of scrub typhus. PLoS Negl Trop Dis. 2017. doi:10.1371/journal.pntd.0006062
149 150
Chakraborty S, Sarma N. Scrub typhus: An emerging threat. In: Indian Journal of Dermatology. Vol 62. Medknow Publications; 2017:478-485. doi:10.4103/ijd.IJD_388_17
147 148
Chakraborty S, Sarma N. Scrub typhus: An emerging threat. In: Indian Journal of
5.
Santos N de J, Sousa E, Reis MG, Ko AI, Costa F. Infestação por roedores associada a
151
fatores ambientais numa comunidade carente com alto risco de transmissão da
152
leptospirose. Cad Saude Publica. 2017;33(2). doi:10.1590/0102-311X00132115
153
6.
Gurung S, Pradhan J, Bhutia PY. Outbreak of scrub typhus in the North East Himalayan
154
region-Sikkim: an emerging threat. Indian J Med Microbiol. 31(1):72-74.
155
doi:10.4103/0255-0857.108729
156 157
7.
Murdoch DR, Woods CW, Zimmerman MD, et al. The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal. Am J Trop Med Hyg. 2004;70(6):670-
675. http://www.ncbi.nlm.nih.gov/pubmed/15211012. Accessed March 28, 2018.
158 159
8.
Blacksell SD, Bryant NJ, Paris DH, Doust JA, Sakoda Y, Day NPJ. Scrub Typhus
160
Serologic Testing with the Indirect Immunofluorescence Method as a Diagnostic Gold
161
Standard: A Lack of Consensus Leads to a Lot of Confusion. Clin Infect Dis.
162
2007;44(3):391-401. doi:10.1086/510585
163
9.
Puran Sharma ଝ K, Ramakrishnan R, Hutin Y, et al. ARTICLE IN PRESS +Model Scrub
164
typhus in Darjeeling, India: opportunities for simple, practical prevention measures. Trans
165
R Soc Trop Med Hyg. 2009. doi:10.1016/j.trstmh.2009.02.006 Murdoch DR, Woods CW, Zimmerman MD, et al. The etiology of febrile illness in adults
166
10.
167
presenting to Patan hospital in Kathmandu, Nepal. Am J Trop Med Hyg. 2004;70(6):670-
168
675.
169
11.
Blacksell SD, Bryant NJ, Paris DH, Doust JA, Sakoda Y, Day NPJ. Scrub Typhus
170
Serologic Testing with the Indirect Immunofluorescence Method as a Diagnostic Gold
171
Standard: A Lack of Consensus Leads to a Lot of Confusion. Clin Infect Dis.
172
2007;44(3):391-401. doi:10.1086/510585
173
12.
Puran Sharma ଝ K, Ramakrishnan R, Hutin Y, et al. ARTICLE IN PRESS +Model Scrub
174
typhus in Darjeeling, India: opportunities for simple, practical prevention measures. Trans
175
R Soc Trop Med Hyg. 2009. doi:10.1016/j.trstmh.2009.02.006
176
13.
2016;4(8):e516-7. doi:10.1016/S2214-109X(16)30094-8
177 178
Basnyat B. Typhoid versus typhus fever in post-earthquake Nepal. Lancet Glob Heal.
14.
Kalal BS, Puranik P, Nagaraj S, Rego S, Shet A. Scrub typhus and spotted fever among
179
hospitalised children in South India: Clinical profile and serological epidemiology. Indian
180
J Med Microbiol. 2016;34(3):293-298. doi:10.4103/0255-0857.188315
181
15.
Soc Trop Med Hyg. 1981;75(4):586-587. doi:10.1016/0035-9203(81)90210-8
182 183
Brown GW, Shirai A, Gan E, Bernthal P. Antibodies to typhus in Eastern Nepal. Trans R
16.
Murdoch DR, Woods CW, Zimmerman MD, et al. The etiology of febrile illness in adults
184
presenting to Patan Hospital in Kathmandu, Nepal. Am J Trop Med Hyg. 2004;70(6):670-
185
675. doi:10.4269/ajtmh.2004.70.670
186
17.
Bahadur Karki K, Prasad Acharya B, Dhimal M, et al. Descriptive Epidemiology of Scrub
187
Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive
188
Epidemiology of Scrub Typhus in Nepal, 2017 Authors. 2017. http://nhrc.gov.np/wp-
content/uploads/2017/11/Final_Scrub.pdf. Accessed April 12, 2018.
189 190
18.
doi:10.3126/nje.v6i2.15162
191 192
Nayak N. Scrub Typhus in Nepal. Nepal J Epidemiol. 2016;6(2):563-564.
19.
Sah RK, Chapagain RH, Shrestha SM, Rai GK. Clinico-laboratory Profile and
193
Therapeutic Outcome of Serologically Confirmed Scrub Typhus in Children in Tertiary
194
Care Children ’ s Hospital of iMedPub Journals Clinico-laboratory Profile and
195
Therapeutic Outcome of Serologically Confirmed Scrub Typhus in. 2019;(January).
196
doi:10.21767/2573-0282.100065
197
20.
Upadhyaya BP, Shakya G, Adhikari S, et al. Scrub Typhus: An Emerging Neglected
198
Tropical Disease in Nepal. J Nepal Health Res Counc. 2016;14(33):122-127.
199
http://www.ncbi.nlm.nih.gov/pubmed/27885295. Accessed March 28, 2018.
200
21.
Chitwan Med Coll. 2017;6(4):1. doi:10.3126/jcmc.v6i4.16707
201 202
22.
23.
24.
EDCD interim Guideline on Prevention and Control of Scrub Typhus September 2015 (Updated in August 2016).
207 208
Bastola A, Pant N. An outbreak of scrub typhus in nepal following the 2015 Gorkha earthquake. Int J Infect Dis. 2016;53:55. doi:10.1016/j.ijid.2016.11.141
205 206
Upadhyaya BP, Shakya G, Adhikari S, et al. Scrub Typhus: An Emerging Neglected Tropical Disease in Nepal. J Nepal Health Res Counc. 2016;14(33):122-127.
203 204
Thapa S, Sapkota LB, Hamal P. Threat of scrub typhus in post-earthquake Nepal. J
25.
Bahadur Karki K, Prasad Acharya B, Dhimal M, et al. Descriptive Epidemiology of Scrub
209
Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive
210
Epidemiology of Scrub Typhus in Nepal, 2017 Authors. 2017.
211
26.
Pathak S, Chaudhary N, Dhakal P, et al. Clinical profile, complications and outcome of
212
scrub typhus in children: A hospital based observational study in central Nepal. PLoS
213
One. 2019;14(8):e0220905. doi:10.1371/journal.pone.0220905
214
27.
Chitwan Med Coll. 2017;6(4):1. doi:10.3126/jcmc.v6i4.16707
215 216
28.
219
Cases of scrub typhus on the rise. https://thehimalayantimes.com/nepal/cases-of-scrubtyphus-on-the-rise/. Accessed October 26, 2019.
217 218
Thapa S, Sapkota LB, Hamal P. Threat of scrub typhus in post-earthquake Nepal. J
29.
Sedhain A, Bhattarai GR. Clinical presentation of scrub typhus during a major outbreak in central Nepal. Asian J Med Sci. 2017;8(4):27-31. doi:10.3126/ajms.v8i4.17163
220
30.
Zoonotic Disease Control Programme.
221
https://www.mohp.gov.np/eng/program/communicable-disease/zoonotic-disease-control-
222
programme. Accessed October 26, 2019.
223 224 225
31.
EDCD|Home. http://www.edcd.gov.np/. Accessed October 26, 2019.
Table 1: Studies/Reports on Scrub Typhus in Nepal
Author Murdoch et al.,[10]
Study Year 2003
Blacksell et al.,[11]
2007
Shah et al., [19]
2019
Upadhyay et al., [20]
2016
Thapa et al., [21]
2016
Upadhyay et al., [22]
2016
Bastola and Pant [23]
2016
Epidemiology and Disease Control Division (EDCD), Nepal [24]
2016
Location
Test Used
Prevalence %
Type of study
Different Hospitals of Kathmandu
INDx Multitest dipstickSDLST
3.2% ( 28/876)
Prospective
22.33% (23/103)
Retrospective
Different Hospitals of Kathmandu Kanti Children Hospital Dhading
ELISA
2016: 37.1% Retrospective 2017: 61.3% 2018: 1.6% 35.3% (36/102) Prospective
Kailali
ELISA
60.4% (32/53)
Kanchanpur
ELISA
54.2% (13/24)
Ramechhap
ELISA
81.3% (13/16)
Khotang Patient admitted to Chitwan Medical College 30 districts of Nepal
ELISA ELISA
61.5% (8/13) 44.1% (181/410)
ELISA
52.4%(175/434) Retrospective
PCR IFA ELISA
29.4% (5/17) 70.6% (12/17) 23 cases
Prospective
ELISA
6 cases
Retrospective
Patients admitted to the Sukraraj Tropical and Infectious Disease Hospital, Ktm Eastern Nepal
Serological tests
Prospective
Epidemiology and Disease Control Division (EDCD), Nepal[24] Nepal Health Research Council (NHRC)[25] Nepal Health Research Council (NHRC)[25] Nepal Health Research Council (NHRC)[25]
2016
Nepal Health Research Council (NHRC)[25] Pathak et al.,[26]
All over the Nepal 25 districts of Nepal
ELISA
> 400 cases
Retrospective
ELISA
>500 cases
Retrospective
IFA
2016
From Rodents population
PCR
22.2% (2/9)
Prospective
2016
Chiggers mite samples
PCR
33.3% (1/3)
Prospective
2016
ELISA
60.0% (30/50)
Prospective
IFA
52.0% (26/50)
Prospective
2016
National Public Health Laboratory, Kathmandu Chitwan
IFA
27.3% (3/11)
Prospective
2019
Chitwan
ELISA
24.4% (76/312)
Retrospective