Transactions of the Royal Society of Tropical Medicine and Hygiene (2009) 103, 455—460

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Epidemiological features of pneumonic plagueoutbreak in Himachal Pradesh, India

Kamlesh Joshia, J.S. Thakura, Rajesh Kumara,∗, A.J. Singha, Pallab Rayb,Sanjay Jainc, S. Varmac

a Department of Community Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, Indiab Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, Indiac Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Received 14 July 2006; received in revised form 24 November 2008; accepted 25 November 2008Available online 10 February 2009

KEYWORDSPlague;Yersinia pestis;Epidemic;Epidemiology;Surveillance;India

Summary Four people admitted to a tertiary care hospital during February 2002 had similarrespiratory symptoms; they belonged to one family residing in a village in Himachal Pradesh,India. The clustering of these cases in space and time led to the suspicion that it could be a pneu-monic plague outbreak. A standard case definition, and treatment and prophylaxis guidelineswere prepared. Active surveillance identified 30 cases. The incubation period ranged from 3 to 7days. Among the affected people, 53.3% were males, and 90% were >15 years of age. Fever withcough was the most common presenting feature (43.3%). The diagnosis of pneumonic plaguewas confirmed from blood cultures using conventional biochemical tests, phage susceptibilityof the identified organisms, and F1 antigen ELISA and PCR for the pla gene. Five patients diedgiving a case—fatality ratio of 16.6%. The other cases recovered following treatment. Earlyidentification of cases and prompt institution of control measures, particularly among closefamily members, relatives and health care contacts is essential for containing outbreaks. To

prevent future outbreaks, known endemic foci should be identified and essential informationshould be gathered on the epizoology of plague.© 2008 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rightsreserved.

∗ Corresponding author. Present address: School of Public Health,Postgraduate Institute of Medical Education and Research, Chandi-garh 160 012, India. Tel.: +91 172 2755216;fax: +91 172 2744993, 2744401.

E-mail address: dr.rajeshkumar@gmail.com (R. Kumar).

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0035-9203/$ — see front matter © 2008 Royal Society of Tropical Medicindoi:10.1016/j.trstmh.2008.11.026

. Introduction

n India, plague has occurred since the sixteenth century.t caused nearly 13 000 000 deaths between the last pan-

1

emic year of 1898 and 1994. As a result of effectiveontrol measures, plague was brought under control in the950s.4 Since 1980, suspected plague cases have occurredn various states, i.e. Himachal Pradesh, Bihar, Karnataka,amil Nadu, Andhra Pradesh, Maharashtra and Gujarat.1—4

e and Hygiene. Published by Elsevier Ltd. All rights reserved.

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he 1994 Surat plague epidemic attracted worldwidettention.5

Himachal Pradesh, a hilly state in the northern part ofndia, is known to be enzootic for plague. Plague outbreaksccurred at short intervals during the late 1950s and early960s.4 Evidence of plague activity was observed in this staten 1972 when plague bacilli were isolated from rodents. In983, an outbreak of pneumonic plague that had occurredollowing the handling of a wild rat by the index casenvolved human-to-human transmission in 22 cases and ledo 17 deaths. However, the disease could not be confirmedue to inadequate laboratory facilities. In February 2002, aplague-like mysterious disease’ was reported in Himachalradesh, and an investigation team was formed promptlyo investigate and take measures to control the reportedutbreak.

. Case reports and methods

he index case was a 35-year-old male who was residing inatkoti village of Shimla district in Himachal Pradesh withis wife, son, mother and a brother. A few days beforehe onset of illness he had visited his brother-in-law atelvi hamlet where they went hunting in a nearby forestn 25 January 2002 and reportedly killed a wild animal.he dead animal was brought to the brother-in-law’s househere skinning was done by his two children. The index case

eturned to his home on 2 February, and on the same day heeveloped fever with chills and rigors. Gradually, he devel-ped chest pain and the illness continued to progress withnset of haemoptysis. He was taken to the Civil Hospitalhere he was diagnosed as suffering from pneumonia andas given some injections and oral medications. As thereere no signs of recovery he was taken to a sub-divisionalospital where he developed haematuria and gradually pro-ressed into a state of shock and died on 5 February 2002.ater, several family members and relatives, who had comento contact with the index case and/or his wife during theirllness at home, hospital or during cremation activities, weredmitted to Postgraduate Institute of Medical Education andesearch (PGIMER), Chandigarh between 9 and 13 February002 (Table 1).

On 12 February 2002, we received information about fourf these cases, who belonged to one family and had similarymptoms. Active surveillance was carried out to update thenformation on the admitted cases and to review the hospi-al records for admission of any new cases. A line list ofhe cases was prepared to estimate the probable incubationeriod, secondary attack rate and case—fatality rate.

On 13 February 2002 the outbreak was diagnosed as‘highly communicable disease (secondary attack rate of

5%) with a short incubation period (1—4 days) and highase fatality spreading through droplet transmission’ andcore committee was formed to prepare guidelines for

iagnosis, treatment, prophylaxis and control measures.ontrol measures included advice on use of protective gear

nd chemoprophylaxis (broad-spectrum antibiotics for allontacts). A ‘control room’ was established to provide infor-ation to the general public about preventive measures and

hemoprophylaxis so as to avoid any panic. Based on thepidemiological and clinical characteristics, a differential

sibit

K. Joshi et al.

iagnosis was made in decreasing order of probability: pneu-onic plague, tularaemia, anthrax, hanta virus syndrome.fter the bacteriological confirmation of the diagnosis on6 February 2002, the National Health Authority formallyeclared it as a plague outbreak on 20 February 2002.

A house-to-house survey was also carried out in theffected villages by the State Health Services to detect anyew cases among those who had interacted with the indexase or his family members or those who participated in theuneral of the index case. State health authorities prohibitedntry of outsiders to the two affected hamlets and fumiga-ion of the affected houses was carried out. All educationalnstitutions in the sub-division were closed until 22 February002.

The second wave of transmission occurred when a 28-ear-old male visitor of a patient admitted to the Emergencyoom of PGIMER, reportedly came in to contact with the rel-tives of the index case on 10 February 2002. On 17 February002, he developed fever with chills and chest pain. Nextay, he had haemoptysis along with episodes of vomiting.e sought treatment from a government hospital, as wells a private clinic and a private nursing home in Chandigarhity. On 19 February 2002, he was brought to the Emergencyoom of PGIMER in a critical condition where he died in thearly morning of 20 February 2002. It seems that during theourse of his illness and cremation he transmitted the dis-ase to his family members, neighbours, relatives, as wells a staff nurse in Chandigarh city, thus extending the chainf transmission (Table 1).

As soon as transmission to the resident of Chandigarh wasuspected, local health authorities were alerted to take pre-entive actions that were also reviewed by the Chandigarhdministrator. Since this person had acquired infection fromases initially admitted to the Emergency Room of PGIMER,he possibility of transmission to other exposed patients andttendants in adjoining beds was considered. Therefore, aist of 51 patients who were admitted to the Emergencyoom on 19 and 20 February 2002, with their addresses,nd/or other patients who were in the vicinity of the patientas made available to the Director of Health Services in

he respective states. Those residing in Chandigarh wereontacted overnight by telephone and were advised aboutrophylactic treatment. It was decided that any suspectedases arriving at the Emergency Room should be isolatednd managed in the communicable diseases ward, other-ise it would be difficult to break the transmission cycle of

he disease.A rapid house-to-house survey was carried out in the vil-

age from where the local resident of Chandigarh had beenrought to the Emergency Room with plague-like illness.lood samples of those who were found to have fever withhills, chest pain or haemoptysis, and a history of contactere taken. Thereafter, surveillance was also conducted by

he State Health Services in all the villages of Mansa districtf Punjab State, where the dead body of the Chandigarhesident was brought for cremation.

An assessment of the mode of transmission and a pos-

ible chain of transmission of illness was made from thenformation available in the line list. The treatment-seekingehaviour and mobility history of the cases was investigatedn order to obtain detailed information about possible con-acts (Table 1).

Pneumonic

plagueoutbreak

inIndia

457

Table 1 Characteristics of plague outbreak cases in northern India, 2002

Patientno.

Age/sex Place ofresidence

Relationship Contact date(with patientno.)

Contactplace

Date ofillness onset

Hospitalization/date

Symptomsand signs

Outcome/date Diagnosis ofplaguea

Transmission in Himachal Pradesh State1 35/M Hatkoti Index case 25—26 Jan 2002 Forest 2 Feb Yes/4 Feb Fever,

cough,chest pain,haemopty-sis,haematuria

Died/5 Feb Probable

2 28/F Hatkoti Wife 2—5 Feb (1) Home 5 Feb Yes/9 Feb Fever,cough,chest pain,haemopty-sis,haematuria

Died/14 Feb Probable

3 45/M Kilvi Brother-in-law

4—5 Feb (1) Home 9 Feb Yes/12 Feb Fever, chestpain,haemopty-sis,vomiting

Recovered/20Feb

Probable

4 60/F Shimla Father’ssister

5 Feb (2 & 3) Homevisiting

11 Feb Yes/11 Feb Fever, chestpain,haemoptysis

Recovered/17Feb

Probable

5 27/M Hatkoti Brother 2—5 Feb (1 & 2) Home 5 Feb Yes/12 Feb Fever, chestpain,haemoptysis

Recovered/21Feb

Confirmed

6 31/F Shimla Sister 5 Feb (2 & 3) Home 10 Feb Yes/12 Feb Fever, chestpain,haemoptysis

Died/18 Feb Confirmed

7 38/F Guntu Wife’s sister 4—5 Feb (1 & 2) Home 10 Feb Yes/12 Feb Fever,cough,hemoptysis

Recovered/19Feb

Confirmed

8 35/M Kotgarh Brother-in-law

5 Feb (2 & 3) Home 12 Feb Yes/13 Feb Fever, chestpain,hemoptysis

Recovered/20Feb

Probable

9 25/F Kotgarh Sister 5 Feb (2 & 3) Home 12 Feb Yes/13 Feb Fever, chestpain,haemoptysis

Recovered/19Feb

Probable

10 35/M Darkoti Brother-in-law

5 Feb (2 & 3) Home 12 Feb Yes/13 Feb Fever, chestpain

Recovered/17 Feb

Probable

458K.

Joshietal.

Table 1 (Continued )

Patientno.

Age/sex Place ofresidence

Relationship Contact date(with patientno.)

Contactplace

Date ofillness onset

Hospitalization/date

Symptomsand signs

Outcome/date

Diagnosis ofplaguea

11 60/F Shimla Father’ssister

5 Feb (2) Homevisiting

11 Feb No Fever Recovered/18Feb

Suspect

12 26/M Hatkoti Cousin 5 Feb (1) Home 5 Feb No Fever,vomiting

Recovered/9Feb

Suspect

13 ?/F Hatkoti Cousin 5 Feb (?) Home ? No Fever Recovered/? Suspect14 25/M Shimla Related to

mother8 Feb (2) Home 12 Feb No Cough,

chest painRecovered/16Feb

Suspect

15 43/F JubbalTehsil

Related towife’s sister

5 Feb (1 & 2) Home 9 Feb Yes/9 Feb Fever, chestpain,haemoptysis

Died/16 Feb Probable

16 45/F JubbalTehsil

Mother’ssister

5 Feb (1 & 2) Home 10 Feb No Fever Recovered/13Feb

Suspect

17 54/F Hatkoti Aunt 5 Feb (1 & 2) Home 12 Feb Yes/12 Feb Fever Recovered/15Feb

Suspect

18 6/M Hatkoti Son 2—5 Feb (1 & 2) Home 15 Feb Yes/16 Feb Vomiting,epigastricpain

Recovered/17Feb

Suspect

19 6/M Loga Nephew 5 Feb (1 & 2) Homevisiting

15 Feb Yes/16 Feb Vomiting,epigastricpain

Recovered/18Feb

Suspect

Transmission in Chandigarh Union Territory and Punjab State20 28/M Kansal

ChandigarhNot related 10—13 Feb (3,

5—10)Hospital 17 Feb Yes/18 Feb Fever,

cough,dyspnea,chest pain,haemoptysis

Died/20 Feb Probable

21 30/F Kansal Wife of no.20

17—19 Feb (20) Home 20 Feb Yes/21 Feb Fever,dyspnea,chest pain,haemoptysis

Recovered/26Feb

Probable

22 4/F Kansal Daughter ofnos 20 & 21

17—20 Feb (20 &22)

Home 21 Feb Yes/22 Feb Fever,dyspnea,chestindrawing

Recovered/25Feb

Probable

23 45/F Kansal Neighbourof no. 20

18—19 Feb (21) Hospital 20 Feb No Fever Recovered/23Feb

Probable

24 22/M Kansal Neighbourof no. 20

19 Feb (21) Hospital 21 Feb No Fever, bodyache

Recovered/24 Feb

Probable

Pneumonic plague outbreak in India 459

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igure 1 Occurrence of plague cases according to date ofnset of illness, northern India, 2002.

Two peaks of occurrence of cases were noted (Figure 1);he first on 12 February with five cases as a result of theutbreak of plague in Himachal Pradesh and the second peakn 22 February with four cases following the transmission tohe resident of Chandigarh city.

In this outbreak, most of those affected were adults over5 years (90%). Fever with cough was the most common pre-enting feature (43.3%), followed by fever, chest pain andaemoptysis in 30% of the cases (Table 1). None of the casesresented with glandular enlargement/swelling. Most of theases recovered from their illness following treatment. Thease—fatality rate was 16.6% (5/30).

Standard case definitions of suspected, probable andonfirmed pneumonic plague were adopted from theHO manual.1 Blood and sputum specimens were taken

rom each case admitted to PGIMER, and three samplesf tracheal aspirates were also collected from patientsho had been intubated. Blood was collected by asep-

ic venepuncture, and 2—5 ml of blood added to each ofwo 4-oz bottles containing 45 ml of tryptone soy brothHi-Media Laboratories, Mumbai, India) and bile broth (Hi-edia Laboratories, India). The bottles were incubated at7 ◦C for up to 7 days and subcultures made on sheeplood agar (SBA) and McConkey agar (MA) plates aftervernight, 48 h and 7 days, or in between whenever visi-le turbidity appeared. Sputum specimens were examinedicroscopically for a Q score by a Gram-stained smear for

ppropriateness of specimen and cultured on SBA, choco-ate agar (CA) and MA plates incubated at 37 ◦C aerobicallynd anaerobically (except MA) with 5% CO2 in a carbon diox-de incubator. Other specimens, such as tracheal swabs,ere subjected to Gram stain microscopy and culturedn SBA, CA and MA plates and incubated at 37 ◦C aer-bically and anaerobically, as above. Significant isolatesrom the cultures were identified by conventional bio-hemical tests, and confirmed by the phage susceptibilityest followed by F1 antigen ELISA and PCR for the plaene.

The autopsy of the wife of the index case revealed bilat-ral pleural effusion and pericardial effusion; her lungs wereolid and heavy with the cut surface showing walled off areas

esembling abscess cavities. Her spleen was septicaemic,nd the liver and kidneys were enlarged. Three blood spec-mens of one patient (collected on the same day) and twolood specimens of two other patients grew non-lactose-

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ermenting gram-negative bacilli after overnight incubation.ll five isolates were presumptively identified as Yersiniaestis by conventional biochemical tests and confirmed byhage susceptibility test, F1 antigen ELISA and PCR for plaene.

. Discussion

imachal Pradesh has witnessed several suspected plagueutbreaks. Based on the findings of past epidemics it appearshat the plague bacilli are ‘zonal’ in nature, and the diseasereaks out in cycles of 10—15 years. This area experiencedlague in early 1971 and 1983 and the February 2002 out-reak conforms to this cyclic trend. The bacteria evidentlyemain dormant in the remote forest areas during the inter-ening period. The organism is active in the months betweeneptember and April, when temperatures are conducive forroliferation. Plague outbreaks in Himachal Pradesh haveeen observed during the months from September to Febru-ry, whereas the plague season in West Bengal provinceccurs generally from March to June, and two seasonal peaksave been noticed in Mumbai, Central India, Mysore andamil Nadu.6

Humans are at risk of acquiring plague whenever theyisit infected areas as hunters, trappers or nomads. Theebruary 2002 outbreak in Hatkoti occurred when the indexase hunted in the high-risk forest area of Rohru subdivi-ion. The fact that rat deaths during this outbreak wereot reported, and even the vector (rat flea) responsible forransmission of plague was not identified, suggests the pos-ibility of acquiring plague bacilli through inhalation by thendex case from the hunted wild animal. Primary pneumoniclague results from close contact (within 2 m) with a per-on or animal expelling fine droplets of Y. pestis. Wild andomestic cats are infected easily by eating infected preynd serve as a source of Y. pestis. People can be infectedirectly from a plague-infected rodent or other animal whileandling, skinning or cutting up the meat.

John2 lamented the lack of expertise in the bacteriologyf Y. pestis in the public health laboratory network in India.uring the plague outbreak in Surat city in 1994, samplesere sent to the laboratory for diagnosis, but the laboratoryould not diagnose promptly. This created confusion, uncer-ainty and panic, which was fanned by the mass media anded to over-reaction by national and international adminis-rators. Gani and Leach7 developed mathematical modelssing historical outbreak data that showed an average of.3 (variance = 3.1) secondary cases per primary case. Theirork suggested that transmission tends to be zero followingutbreak detection.

In the February 2002 outbreak in Himachal Pradesh, onlylose relatives of the index case were initially affected andhe chain of transmission was only extended when a closeontact acquired infection from patients in the health careetting. This outbreak was detected early, an aetiological

K. Joshi et al.

iagnosis was established, and early initiation of epidemi-logical investigation and control measures contained theutbreak at an early stage. Plague pneumonia is known toe invariably fatal when antibiotic therapy is delayed forore than 20 h after the onset of illness.4 In this outbreak

he case—fatality rate was 16.6%. Early initiation of treat-ent may have led to lower case fatality. The case—fatality

ate in another recent outbreak of bubonic plague in Uttarashi district of Uttranchal state (India) was 38% (3/8).3

To prevent future outbreaks known endemic foci shoulde identified and essential information should be gatheredn the epidemiology and epizoology of the infection. Earlydentification of cases and prompt institution of controleasures, particularly among close family members, rel-

tives and health care contacts is essential for containingutbreaks.

uthors’ contributions: KJ, JS, AJS and RK collected andnalysed the epidemiological data; PR conducted laboratorynvestigations; SJ and SV collected and analysed the clini-al data; All authors contributed to data interpretation andriting of the manuscript and read and approved the finalersion. RK is guarantor of the paper.

cknowledgements: We thank the Microbiology Divisionf the Defense Research and Development Organization,walior, for providing assistance in the bacteriophage lysisest, F1 antigen ELISA and PCR for pla gene.

unding: None.

onflicts of interest: None declared.

thical approval: Not required; the study is based on theetrospective surveillance data.

eferences

1. WHO. Plague manual: epidemiology, distribution, surveil-lance and control. Geneva: World Health Organization; 1999.WHO/CSR/EDC/99.2.

2. John TJ. Emerging and re-emerging bacterial pathogens in India.Indian J Med Res 1996;103:4—18.

3. Mittal V, Rana UV, Jain SK, Kumar K, Pal IS, Arya RC, IchhpujaniRL, Lal S. Quick control of bubonic plague oubreak in Uttal Kashi.India J Commun Dis 2004;36:333—9.

4. Sehgal S, Bhatia R. Plague in India. Delhi: National Institute ofCommunicable Diseases; 1991.

5. Clem A, Galwankar S. Plague: a decade since the 1994 outbreaksin India. J Assoc Physicians India 2005;53:457—64.

6. Seal SC. Epidemiology of plague with reference to the presentCalcutta outbreak. Calcutta Med J 1949;46:167.

7. Gani R, Leach S. Epidemiologic determinants of modellingpneumonic plague outbreaks. Emerg Infect Dis 2004;10:608—14.