International Journal of Infectious Diseases 33 (2015) e67–e70

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International Journal of Infectious Diseases

jou rnal homepage: www.elsevier.com/locate/ijid

Case Report

Primary case of human pneumonic plague occurring in a Himalayan

marmot natural focus area Province,

a,1 a,1 b,1 c,1 a,1 a,1

Pengfei Ge , Jinxiao Xi , Jun Ding , Fachang Jin , Hong Zhang , Limin Guo ,

c c b a d d,

Jie Zhang , Junlin Li , Zhiqiang Gan , Bin Wu , Junrong Liang , Xin Wang *, a,

Xinhua Wang **

a

Gansu Provincial Centre for Disease Control and Prevention, 230 Donggang West Road, Chengguan , , China

b

Jiuquan Municipal Centre for Disease Control and Prevention, , China

c

Yumen Municipal Centre for Disease Control and Prevention, Yumen, China

d

National Institute for Communicable Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, State Key Laboratory for Infectious

Disease Prevention and Control, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, 155 Changbai Road, Changping District,

102206 , China

A R T I C L E I N F O S U M M A R Y

Article history: A case of primary pneumonic plague (PPP) caused by Yersinia pestis is reported. This case occurred in the

Received 27 October 2014

largest plague area in China. The patient died after contact with a dog that had captured an infected

Received in revised form 19 December 2014

marmot. Three of 151 contacts were shown to be positive for antibody against F1 antigen by indirect

Accepted 22 December 2014

hemagglutination assay, but none had clinical symptoms. There was no secondary case.

Corresponding Editor: Eskild Petersen,

ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Aarhus, Denmark

This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by- nc-sa/4.0/).

Keywords:

Primary pneumonic plague Dogs

Marmota himalayana

Indirect hemagglutination test

Epidemiological investigation

1. Introduction brother then dismembered the marmot and fed the meat to five

dogs, including the dog that had captured it. The man began to

1

China has faced plague throughout history. With efficient have a fever on July 13. On July 14, he went to and

prevention and control, human cases are significantly reduced; talked with his sister-in-law and neighbours. His condition

however sporadic cases still emerge. deteriorated rapidly on July 15 and he went to the village clinic.

The – plateau natural plague focus area is the largest From there he was transferred to the local hospital where a

in China. The primary reservoir is the Himalayan marmot Marmota preliminary diagnosis of upper respiratory infection was made;

himalayana (and rodents), with annual outbreaks in animals this was treated with antipyretics, anti-inflammatory agents, and

2,3

occasionally spreading to humans. Capturing and flaying marmots clindamycin. However, his condition worsened and he was

is the main cause of human infection. With increased awareness, transferred to Yumen People’s Hospital.

fewer people are flaying marmots and human cases are decreasing. Examinations showed a pathology of both lungs; he had a partially

dilated intestine, pleural effusion in the left lung, and a pericardial

effusion. The diagnosis of severe pneumonia was made and he was

2. Case report

given anti-inflammatories, fluid replacement, and cefoperazone

sodium. At 10:30 p.m., blood, sputum, and a throat swab were taken

The index case was a 38-year-old male shepherd. On July 11,

for serological tests and strain isolation. The serum was collected to

2014, he seized a marmot from a dog while grazing sheep. His older

determine the F1 antibody concentration via indirect hemagglutina-

4,5

* Corresponding author. Tel.: +8610 58900758; fax: +8610 58900070. tion assay (IHA). A reverse IHA was used to detect the Yersinia pestis

2

** Corresponding author. Tel.: +86931 8270001. F1 antigen from sputum and throat samples.

E-mail addresses: [email protected] (X. Wang),

At 11:30 p.m. on July 15, sputum and blood smears showed a

[email protected] (X. Wang).

1 Gram-negative bacillus with rounded darker ends. The patient was

P. G., J. X., J. D., F. J., H. Z., and L. G. contributed equally to this study.

http://dx.doi.org/10.1016/j.ijid.2014.12.044

1201-9712/ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-SA

license (http://creativecommons.org/licenses/by-nc-sa/4.0/).

e68 P. Ge et al. / International Journal of Infectious Diseases 33 (2015) e67–e70

diagnosed as a suspected plague case and was reported to the Among 151 contacts, 63 were close contacts in the outpatient

Infectious Disease Reporting System. and inpatient departments and their escorts, and these contacts

At 00:10 a.m. on July 16, the patient’s blood pressure decreased were immediately quarantined; the other 88 were indirect

and he became short of breath and produced red frothy sputum. contacts and visitors, and they were isolated in their homes

The breath was low in the left lung and there was a wet rattle in (Figure 1). Examination of paired sera of the 151 contacts using the

both lungs. He was treated with 1 g streptomycin intramuscular IHA (on July 16 and 20) showed the sister-in-law to have an F1

(IM), 8 mg gentamicin intravenous (IV), and dopamine. At 5:00 antibody titre that increased from 1:16 to 1:64; two of the

a.m., there were signs of dysphoria, polypnea, and cardiac arrest; outpatients transfused in the same room had F1 antibody titres of

he immediately received assisted respiration, external cardiac 1:16. The remaining contacts were negative.

massage, and electric defibrillation. The patient died at 5:57 a.m. At Five dogs fed with the marmot were positive for F1 antibody

1:30 a.m. on July 16, antibody to F1 antigen was detected at a titre with titres of 1:32 (n = 1) and 1:128 (n = 4; including the dog that

of 1:40 (serum); the reverse IHA showed titres of 1:6400 (throat) had captured the marmot). One dog that had not eaten the marmot

6,7

and 1:12 800 (sputum). PCR for Y. pestis fra and pla was positive. was F1-negative.

On July 18, Y. pestis strains were isolated from sputum, blood, and Beginning on July 16, preventive medications were given to the

8

throat swab samples, and identified by bacteriophage lysis test 151 contacts: streptomycin IM (0.75 g on July 16) and oral

and PCR. sulfadiazine (2 g per day from July 17 to 21, in three doses per day).

Experts including epidemiologists, bacteriologists, and doctors All contacts were quarantined for 9 days under professional

diagnosed the case as one of primary pneumonic plague (PPP). medical observation. At 9 a.m. on July 17, the corpse and

Figure 1. Epidemiology of the case of primary pneumonic plague (PPP).

P. Ge et al. / International Journal of Infectious Diseases 33 (2015) e67–e70 e69

Table 1

Occurrence of plague in humans in the Qinghai–Tibet plateau natural plague foci, from 2000 to 2012

Date Location Cause No. of patients Clinical diagnosis

(County/ Province)

2000/9/29 Akesai/ Gansu Flayed marmots 1 death Pneumonic plague

2001/5/17 Tongde/ Qinghai Flayed fox 1 death Pneumonic plague

2003/9/20 Qilian/ Qinghai Flayed marmots 1 death Pneumonic plague

2004/5/6 Sunan/ Gansu Flayed marmots 1 case Pneumonic plague

2004/7/10 Qilian/ Qinghai Flayed marmots 1 death Pneumonic plague

2004/9/16 Nangqian/ Qinghai Flayed marmots 14 cases (6 deaths) The first case was pneumonic plague; the

13 contacts were all infected by the first-episode

patient

2004/9/19 Huangyuan/ Qinghai Flayed marmots 3 cases (2 deaths) Two pneumonic plague, one bubonic plague

2004/9/30 Wulan/ Qinghai Flayed marmots 2 cases (1 death) One pneumonic plague, one bubonic plague

2005/6/10 Huangyuan/ Qinghai Dog captured an 1 death Pneumonic plague

infected marmot

2005/6/27 Zhiduo/ Qinghai Flayed marmots 1 death Pneumonic plague

2006/9/13 Huangyuan/ Qinghai Flayed marmots 1 death Pneumonic plague

2007/9/25 Asubei/ Gansu Flayed marmots 1 case Bubonic plague

2007/11/11 Subei/ Gansu Fed marmot to dogs 1 death Pneumonic plague

2009/7/29 Xinghai/ Qinghai Buried infected dog 12 cases (3 deaths) Primary pneumonic plague

2010/9/23 Lang/ Tibet Autonomous Flayed marmots 5 cases (1 death) The first case was bubonic plague advancing to

Region pneumonic plague; the four contacts were all

pneumonic plague

2010/6/12 Akesai/ Gansu Flayed marmots 1 death Bubonic plague advancing to septicaemic plague

2011/9/28 Huangyuan/ Qinghai Flayed marmots 1 death Bubonic plague advancing to septicaemic plague

2012/9/2 Dege/ Sichuan Flayed marmots 1 death Bubonic plague advancing to septicaemic plague

contaminated objects were sent to a biosafety disposal unit and the however the one that did not eat the marmot was negative. Dogs are

area of contamination was sterilized. The five dogs with F1 used as an indicator animal for plague surveillance, and measuring

antibody were destroyed. Marmot depopulation was performed in the antibody to F1 in dog serum can predict the plague outbreak

10

the grazing location. risk. In the Qinghai–Tibet plague focus area, 25.71% (27/105) of

dogs were found to be positive for F1 antibody in Gansu Province and

9

18.18% (22/121) in Qinghai Province.

3. Discussion

All contacts underwent on-site isolation and all were under

medical observation and took prophylactic medication. Three

This PPP index case died, and three of 151 contacts were

clinically asymptomatic contacts had F1 antibody, but there were

positive for F1 without clinical symptoms. Because ineffective

no secondary cases. This shows that prophylactic medication can

antibiotics were given, the PPP progressed before detection;

efficiently control the spread of plague. In contrast, in the PPP

therefore the patient missed the treatment window. The local

outbreak reported in 2009 in Qinghai Province, all 11 close contacts

village clinic and local hospital where the patient was misdiag- 2

were infected as no efficient timely control occurred.

nosed had limited medical facilities; Y. pestis was not identified

F1 antibody was detected in people who had been in contact

until microscopic examination was performed. When streptomy-

with the patient for a long period of time: the sister-in-law and two

cin was used, large amounts of endotoxin entered the bloodstream

outpatients who had undergone infusions at the same time as the

leading to shock and a more rapid progression to death. This case

case patient. Contamination may depend on the duration of the

suggests that early accurate diagnosis and the use of the correct

exposure. However, the older brother-in-law who dismembered

antibiotic treatment are of the highest importance for a plague

the marmot and the patient’s wife who accompanied him until his

patient. Doctors need to improve awareness and obtain a contact

death were negative for F1 antibody. We found that better health

history to identify the possibility of plague infection in order to

may effectively prevent PPP among contacts. In addition, no F1

avoid misdiagnosis.

antibody was detected in the serum of the doctors and this may be

The case was initiated by a dog capturing an infected marmot. The

related to the wearing of masks. This simple countermeasure may

primary cause of the PPP was exposure to Y. pestis aerosols because

provide a basic form of defence when facing unknown risks for

Y. pestis strains were isolated from sputum and throat samples.

infection.

This case occurred in Yumen County, Gansu Province, located in

the Qinghai–Tibet natural plague area. Animal and human cases

Acknowledgements

have recently been increasing; a case of human plague occurs

almost every year (Table 1). There have been two human plague

This work was supported by the National Sci-Tech Key Project

cases reported in Yumen County. The epidemic risk has recently

(2012ZX10004-208, 2012ZX10004201, 2013ZX10004203-002,

become higher. In 2012, the isolation of Y. pestis from dead

and 201202021). We thank Jim Nelson for critical reading and

marmots was 1.94% and from fleas was 4.17%, and an average

helpful comments on our manuscript.

4.55% of dogs were positive for F1 antibody. In 2013, the isolation

Conflict of interest: There are no conflicts of interest to declare.

was higher: 40.7% and 3.74% for dead marmots and fleas,

respectively, and 10% of dogs F1 antibody-positive. From May

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