Dengue haemorrhagic fever after living donor renal transplantation

Felicia Li-Sher Tan, Dale L. S. K. Loh and K. Prabhakaran

Department of Pediatric Surgery, National University of Hospital, Singapore

Correspondence and offprint requests to: Felicia Li-Sher Tan, Department of Pediatric Surgery, National University of Hospital, Singapore. Email: feliciates{at}hotmail.com



   Introduction
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 Introduction
 Case report
 Discussion
 References
 
The transmission of infection from donor to recipient in solid organ transplantation can result in loss of the allograft and in severe cases, death of the recipient. The occurrence of dengue virus infection in an immunocompromised renal transplant patient can have many detrimental effects, the most life-threatening of these is development of dengue shock syndrome. We present a case of possible transmission of dengue infection from donor to recipient after living donor renal transplantation, resulting in a fulminant course of dengue haemorrhagic fever (DHF).



   Case report
 Top
 Introduction
 Case report
 Discussion
 References
 
A 23-year-old male with end-stage renal failure due to lupus nephritis underwent a living donor renal transplantation. The donor was his mother, who was healthy except for a significant past history of dengue fever 6 months prior. Early post-operative recovery was uncomplicated with immediate graft function and serum creatinine of 67 µmol/l on post-operative day 2. His immunosuppressive medication consisted of mycophenolate mofetil, tacrolimus and methylprednisolone.

On the 5th post-operative day, he spiked a temperature of 39°C. He was asymptomatic and physical examination did not reveal a source of infection. In view of a previous history of dengue infection in the donor, blood was analysed for dengue virus using real-time polymerase chain reaction (RT-PCR). This was positive for Dengue virus Serotype 1.

Over the next week, he continued to spike high temperatures with a fall in platelet count and a deterioration of his general clinical condition. On the 12th post-operative day, he developed upper gastrointestinal bleeding, gross haematuria and tachycardia. Investigations revealed that his haemoglobin had dropped to 4.6 g/dl, leucocyte count was 0.86 x 109/l, platelet count was 71 x 109/l, serum lactate dehydrogenase was 1322 U/l (normal: 300–700 U/l) and albumin was 14 g/l (normal: 38–49 g/l). His mycophenolate mofetil dose was discontinued and granulocyte-colony stimulating factor was commenced for his profound leucopenia. He required multiple packed cell and platelet transfusions. Chest X-ray revealed a right sided pleural effusion. On the 15th post-operative day, he complained of left flank pain and abdominal distension. One litre of blood was drained from his Tenckoff catheter. Computed tomography of his abdomen revealed a large retroperitoneal haematoma arising from the bed of the transplanted kidney. Emergency laparotomy was undertaken for surgical haemostasis and evacuation of the haematoma. Intra-operatively, 1.5 l of blood was drained from the retroperitoneal space. A generalized ooze was seen from the tissue bed of the allograft and this was treated with packing. There was a perforation seen in the peritoneum, which allowed communication between the retroperitoneal and intraperitoneal spaces. The transplanted kidney appeared healthy. A repeat dengue RT-PCR was negative.

Post-operative recovery was uneventful with resolution of fever and recovery of thrombocytopenia within the next week. Haemorrhagic tendencies ceased spontaneously with resolution of haemetemesis and haematuria. His graft function remained excellent. Figure 1 depicts the course and progression of his illness.



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Fig. 1. Trend of temperature and platelet count correlated to clinical findings during period of illness. Dotted line represents normal values: normal body temperature taken as 37°C; lower limit of normal for platelet count taken as 130 x 109 g/l. PCR, polymerase chain reaction; BGIT, bleeding gastrointestinal tract. Minus sign indicates negative results, plus sign indicates positive result.

 


   Discussion
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 Introduction
 Case report
 Discussion
 References
 
The pathophysiological mechanisms underlying DHF remains controversial. There is strong evidence to suggest an increased risk of DHF with secondary dengue virus infection [1]. The presence of pre-exisiting antidengue antibodies increases viraemia titres by a phenomenon known as antibody-dependent enhancement of infection (ADE) [2].

Having lived in a dengue-endemic region, our patient may have been infected previously but was asymptomatic or had subclinical infection. A large proportion of the adult population in Singapore have been exposed to dengue as reflected by a high prevalence of dengue seropositivity (45%) [3]. Transplantation of the dengue-infected allograft can cause secondary infection and development of DHF. It is not known whether donor organs remain infected after apparent resolution of viraemia. Alternatively, secondary transmission could have been via the usual route, the bite of a mosquito. However, there was no active transmission of dengue in our area during this period, making hospital-acquired infection less likely.

Clinical presentation and course of the illness in this immunosuppressed patient is similar to that in the immunocompetent, except for a longer period of illness. Our patient experienced a prolonged course of illness (19 days) as well as prolonged duration of thrombocytopenia (12 days). The mean duration of illness is 2–7 days and duration of thrombocytopenia 3.6 days (±1.6 days) [4]. The critical stage in DHF is usually around the time of defervescence, with circulatory failure of haemorrhagic manifestations occurring about 24 h before to 24 h after the temperature falls to normal or below. This was the case for our patient with shock and haemoperitoneum occurring on the same day as defervescence of fever (Figure 1).

DHF occurring early post-operatively poses a potential danger to the transplant patient. Bleeding diathesis resulting from thrombocytopenia, dysfunctional surviving platelets and increased fibrinolysis result in persistent haemorrhage especially from cut tissue surfaces. In our patient, profuse, persistent bleeding from the tissue bed of the transplanted kidney led to circulatory collapse and a need for surgical drainage of haematoma and haemostasis. In addition, he also had other haemorrhagic manifestations with gastrointestinal bleeding and haematuria. Hypovolaemia poses a risk of damage to the allograft. Hypoalbuminaemia secondary to leakage of plasma aggravates the problem of poor wound healing in the immunosuppressed transplant recipient. No specific therapy or vaccine exists for DHF. Management is supportive, with correction of hypovolaemia and coagulation abnormalities.

This case illustrates the severity of DHF after renal transplantation of an infected allograft. In dengue-endemic regions, clinicians should have a high index of suspicion for DHF in patients with viral haemorrhagic fevers. Screening donors of organs and blood products may be beneficial, although sensitivity, feasibility and cost benefits of screening need to be assessed.

Conflict of interest statement. None declared.



   References
 Top
 Introduction
 Case report
 Discussion
 References
 

  1. Rothman AL. Dengue: defining protective versus pathologic immunity. J Clin Invest 2004; 113: 946–951[Abstract/Free Full Text]
  2. Morens DM, Halstead SB. Measurement of antibody-dependent infection enhancement of four dengue virus serotypes by monoclonal and polyclonal antibodies. J Gen Virol 1990; 71: 2909–2914[Abstract]
  3. Wilder-Smith A, Foo W, Earnest A, Sremulanthan S, Paton NI. Seroepidemiology of dengue in the adult population of Singapore. Trop Med Int Health 2004; 9: 305–308[CrossRef][ISI][Medline]
  4. Tai DYH, Chee YC, Chan KW. The natural history of dengue illness based on a study of hospitalized patients in Singapore. Singapore Med J 1999; 40: 238–242[Medline]
Received for publication: 31. 7.04
Accepted in revised form: 19.10.04





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