INTRODUCTIONCrimean Congo Hemorrhagic Fever (CCHF) is a tick-borne disease caused by Nairovirus of the familyBunyaviridae. The major reservoirs of this infection areboth wild and domestic animals. The virus is transmittedto humans through either tick bite or body fluids of theinfected animals. Human-to-human transmission hasalso been reported amongst those in close contact withbody fluids of infected persons.1

CCHF typically courses through four phases: incubation,pre-hemorrhagic, hemorrhagic and convalescenceperiods.2 The incubation period usually depends on themode of transmission of the virus and viral dose. Pre-hemorrhagic phase presents with a fever and other flu-like symptoms.2 Additional symptoms of non-bloodydiarrhea, abdominal pain, vomiting, depression andlassitude may be present.2,3 Signs such as conjunctivitis,pharyngitis, cutaneous flushing, hypotension, brady-cardia, tachypnea and hepatomegaly may also benoted.2,3 The hemorrhagic period is generally short,lasting 2 - 3 days, and begins 3 - 7 days after disease.1,2

Progressive hemorrhagic diathesis rapidly develops inthe form of petechial bleeding, mucosal bleeding,hematuria, hematemesis or melena.1,2 This may befollowed by Disseminated Intravascular Coagulation(DIC) and circulatory shock in severe cases. Deathusually occurs in this phase. If the patient survives, hebegins convalescing 10-20 days after disease onset.1

Here, we describe a case of CCHF that presented withprolonged hemorrhage.

CASE REPORTA 62-year male patient without any comorbid conditionswas admitted to JPMC, Karachi in December 2014 witha history of fever, chills, cough and flu-like symptomssince 6 days and bleeding gums since 3 days. He wasreferred to JPMC from a private hospital in the city,where he had been managed supportively for 2 daysand a complete blood count (CBC), coagulation profileand liver function tests were ordered. He belonged to anurban neighbourhood but had the history of exposure toa small flock of lambs that he reared at home. However,he could not recall a tick bite. He reported no previoushistory of bleeding diathesis.

Upon admission, his blood picture revealed a droppinghemoglobin (Hb) from 12 mg/dl to 9.7 mg/dl whileplatelet count rose from 10 x 109 to 30 x 109 since initialpresentation at the private hospital. The rise occurredfollowing transfusion of 12 units of platelets during hisstay at that hospital. His Total Leukocyte Count (TLC)was also noted to be significantly decreased at 1.86x109 (neutrophils 46%, lymphocytes 44%). Other workup revealed activated partial thromboplastin time=59seconds, international normalized ratio=1.01, alaninetransaminase=107 U/I, creatinine=1.0 mg/dl, andurea=32 mg/dl. Dengue serology for acute infection andblood smear for malarial parasite were negative. Twounits of packed red cells and 4 units of Fresh FrozenPlasma (FFP) were arranged and transfused the sameday. A clinical picture typical of hemorrhagic fever, apositive history of contact with domestic animals, andawareness of an ongoing CCHF epidemic promptedsuspicion for CCHF. His blood sample was sent on theadmission day, for a Polymerase Chain Reaction (PCR)test for CCHF virus RNA, to a laboratory in Karachi.Based on high suspicion, a loading dose of 2 gm of oralribavirin was initiated before CCHF virus RNA wasdetected.

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CASE REPORT

An Unusual Case of Crimean Congo Hemorrhagic Fever:Prolonged Bleeding with Successful RecoveryQurban Hussain1, Bilal Hussain Shaikh1, Ali Raza Bhutto2 and Muneebah Sohaib3

ABSTRACTCrimean Congo Hemorrhagic Fever (CCHF) is a tick-borne viral disease with a major reservoir in both domestic and wildanimals. In Pakistan, it is endemic largely in rural areas and most cases occur in spring and autumn. Recently, cases arebeing reported throughout the year, including winter months, with some even from urban areas. Death from CCHF is mostlikely to occur during the hemorrhagic phase. We report a case presenting from an urban locality in December. Clinicalpresentation was characterized by a prolonged hemorrhagic phase and a delayed normalization of platelet counts.

Key Words: Crimean Congo hemorrhagic fever. Prolonged bleeding. Early ribavirin therapy. Delayed normalization of platelets.

1 Department of Medicine, Jinnah Postgraduate Medical Centre(JPMC), Karachi.

2 Department of Medicine, The Indus Hospital, Karachi.3 Department of Medicine, Civil Hospital, Karachi.

Correspondence: Dr. Qurban Hussain, Assistant Professor ofMedicine, Department of Medicine, Jinnah PostgraduateMedical Centre (JPMC), Karachi.E-mail: drqurbanhussain@gmail.com

Received: June 22, 2015; Accepted: November 20, 2015.

Following the confirmation of CCHF the next day,ribavirin was continued at 4 gm/day in four divided dosesfor the next 6 days and subsequently at 2 gm/day in 4divided doses for another 6 days. The patient was keptisolated with barrier nursing. Antibiotic treatment withAmoxicillin-clavulanate 625 mg/125 mg orally BD, wasinitiated for prophylaxis of chest infections. Over thecourse of four days following admission and ribavirintherapy, the patient had two prominent fever spikes(102°F) and continued to bleed through gums with largevolumes of blood collecting repeatedly in the oral cavity.Oral hygiene was noted to be poor and regular anti-septic mouthwash use was begun. Prolonged bleedingwas also witnessed through puncture sites, but nohematuria, hematemesis or melena was reported. Hisblood counts monitored through daily CBC worsenedprogressively. Hb/Hct decreased to 7.2 mg/dl/21.4% andplatelets declined to a minimum 11 x 109 on the fourthday while TLC rose to 9.1 mg/dl with neutrophilia (75%).This was managed aggressively with replacement of twounits of packed cells and a single mega unit of platelets,following which platelet count and Hb improvedtransiently to 83 x 109 and 8.2 g/ dl, respectively. Anothermarked drop in Hb (7.1g/dl) was witnessed on CBCperformed on the 9th day post-admission whilst moresmall oral bleeds continued. Thereon no further bleedsoccurred, and platelets gradually rose to 179 x 109 on12th day post-admission at JPMC. Dosing of ribavirinwas stopped on 12th day, coinciding with a stableplatelet count.

Throughout admission, the patient was kept in anisolation unit and strict barrier nursing protocols werefollowed, involving use of gloves, gowns and N-95respirators at each patient encounter. The patient wasdischarged on the 12th day of admission.

DISCUSSIONPakistan, along with neighbouring Iran and Afghanistan,is endemic to CCHF with the first confirmed caseoccurring in the country in 1976.4,5 Seasonal variationsin incidence have been witnessed in the region.Traditionally, more cases are seen in rural areas in a bi-annual pattern between March and May and againbetween August and October.4,6 Recently, however,cases have been reported throughout the year.4 Theindex case was one of 7 CCHF cases that presented atJPMC, Karachi between November 2014 - January 2015and belonged to an urban neighbourhood. This supportsthe slowly changing geographical and epidemiologicalpatterns with some cases being reported from urbanareas and throughout the year.

CCHF is a severe hemorrhagic disease with frequentextensive bleeding, DIC and multiorgan failure. A widerange of case fatality rate ranging from 10 - 40% has

been reported.3 CCHF has been shown to besusceptible to ribavirin in vitro but controlled trials havefailed to establish any benefit. A number of uncontrolledstudies have reported good response to oral orparenteral ribavirin in CCHF patients.7,8

Patients usually present in the pre-hemorrhagic phasewith flu-like symptoms, or just after the first bleedingepisode. This case presented relatively later; oncegingival bleeding had begun while diagnosis andantiviral treatment were further delayed by 2 days as thepatient underwent transfer of care. While this patientsurvived, the most unusual aspect of this case was theduration of bleeding. While it is rare for bleeding to lastmore than 3 - 4 days with platelet counts rising over150 x 109 by the 7th day, this patient took twice that timeto reach those platelet counts and stop bleeding.2,8 Thiswas despite the ribavirin dosage as recommended in theupdated WHO/NIH guidelines.9 The total hospital stayfor this patient was 14 days compared to the meanlength of stay of 8 days for all CCHF patients whopresented during the same period and survived. In astudy conducted by Tasdelen et al., earlieradministration of ribavirin to CCHF patients (< 4 dayssince onset of symptoms) resulted in significantly highermean platelet counts at days 5 - 10 of disease onsetwhen compared to later administration (> 4 days sinceonset).10 While the authors are uncertain about whatcaused the slower improvement of platelet counts andprolonged bleeding, it is possible this could have beenprevented by earlier initiation of ribavirin.

In a background of changing geographical andepidemiological patterns as well as year-roundoccurrence, it is imperative that a high index of suspicionof CCHF is maintained when managing viral fevers.Attempts for earlier diagnosis and initiation of ribavirintherapy should be made to improve mortality fromhemorrhagic episodes in CCHF.

REFERENCES1. Ergönül O. Crimean-Congo haemorrhagic fever. Lancet Infect

Dis 2006; 6:203-14

2. Hoogstraal H. The epidemiology of tick-borne Crimean-Congohemorrhagic fever in Asia, Europe, and Africa. J Med Entomol1979; 15:307-417.

3. World Health Organization. Crimean-Congo hemorrhagicfever [Internet]. 2013. Available from: http://www.who.int/mediacentre/factsheets/fs208/en/

4. World Health Organization: Crimean-Congo haemorrhagicfever in Pakistan. 2013. Available from: http://applications.emro.who.int/dsaf/epi/2013/Epi_Monitor_2013_6_40.pdf

5. Ince Y, Yasa C, Metin M, Sonmez M, Meram E, Benkli B et all.Crimean-Congo hemorrhagic fever infections reported byProMED. Int J Infect Dis 2014; 26:44-6.

6. Sheikh AS, Sheikh AA, Sheikh NS, Rafi US, Asif M, Afridi F,

Qurban Hussain, Bilal Hussain Shaikh, Ali Raza Bhutto and Muneebah Sohaib

152 Journal of the College of Physicians and Surgeons Pakistan 2016, Vol. 26 (2): 151-153

et al. Bi-annual surge of Crimean-Congo hemorrhagic fever(CCHF): a five-year experience. Int J Infect Dis 2005; 9:37-42.

7. Fisher-Hoch SP, Khan JK, Rehman S. Crimean-Congohemorrhagic fever treated with oral ribavirin. Lancet 1995;346:472-5.

8. Ergonul, O, Celikbas, A, Dokuzoguz, B, Eren, S, Baykam, N,and Esener, H. The characteristics of Crimean-Congohemorrhagic fever in a recent outbreak in Turkey and the

impact of oral ribavirin therapy. Clin Infect Dis 2004; 39:285-9.

9. National Institute of Health, World Health Organization.Guidelines for Crimean-Congo Hemorrhagic fever (CCHF).Islamabad: WHO; 2013.

10. Tasdelen Fisgin N, Ergonul O, Doganci L, Tulek N. The role ofribavirin in the therapy of crimean-congo hemorrhagic fever:early use is promising. Eur J Clin Microbiol Infect Dis 2009;28:929-33.

An unusual case of crimean congo hemorrhagic fever: prolonged bleeding with successful recovery

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