A case report of Typhoid Fever with Severe Pancytopenia

Abstract

Typhoid fever, an acute febrile illness caused by Salmonella enterica serovar Typhi (S. Typhi) remains an important etiology of fever in developing countries like Myanmar. According to a WHO report, an estimated 11–21 million typhoid fever cases and 148,000–161,000 associated deaths occurred worldwide in 2015.¹ The course of typhoid fever can range from an uncomplicated febrile illness to life-threatening sepsis with multiorgan involvement. We report a previously healthy male with severe typhoid fever complicated by sepsis and severe pancytopenia. A 14-year-old novice presented with fever, loose motions, abdominal pain and cough for 10 day’s duration. Clinically, severe anemia presented but his vitals were stable with mild tenderness around the umbilicus. Blood tests revealed Hb/4.1g/dL, WBC/3×10³/ul, Plt/33×10³/ul with features of DIC, mild hyponatremia Na 123 mmol/L, high CRP 158 ug/ml and high procalcitonin 20 ng/ml. Typhoid fever was confirmed by Widal test +1/640 (O Ag), 1/160 (H Ag) with blood culture reported multidrug resistant organism which was ESBL MDR Salmonella ser. Typhi. To find out cause of persistent severe pancytopenia, bone marrow examination was proceeded and it concluded that active marrow in both bone marrow aspiration and trephine biopsy.(see Pic 2) Intravenous antibiotics were given according to sensitivity for a total of 14 days and after treatment all the abnormal hematological parameters returned to normal and he was discharged from hospital uneventfully.

Introduction

Typhoid fever is a systemic infection caused by Salmonella typhi. A definite diagnosis of typhoid fever is achieved by culture of blood and bone marrow. Positive blood cultures are seen in 60-80% of cases. Possibility of blood culture positivity decreases after the first week and becomes negative in the fourth week. ^2,3 Clinical presentation and severity of the disease is varied. The most common clinical presentation is high fever in the first week, diarrhoea in the second week, and splenomegaly, encephalopathy, intestinal hemorrhage and perforation are typical findings seen in the third week.^4,5 Leucopenia and relatively normal leucocyte count is common in typhoid fever while bone marrow depression in the form of pancytopenia is less common and was seen in 5%only.⁶ In Joseph et al report, in many typhoid cases concurrent bone marrow suppression was not found at the time of pancytopenia in peripheral blood suggesting a peripheral mechanism might be responsible for the blood dyscrasia in those cases.⁷ However, in other studies the patients suffering from typhoid fever with pancytopenia, bone marrow examination revealed extensive haemophagocytosis. Therefore, clinicians need to be aware of bone marrow suppression in a severe typhoid fever especially due to multi drug resistant organism.

Case report

A 14-year-old previously healthy novice from Yangon presented to our hospital with 10 day’s duration of high fever, abdominal discomfort and loose motions. On examination, he was febrile and had severe anaemia. There were some crepitations in the right lower lobe, and tenderness around the umbilicus but there was no active bleeding and he was hemodynamically stable. Investigations on admission revealed Hb 4.3 g/dL Hct 10 ,MCV 45, WBC 3x 10³/ul, Plt 33x 10³/ul ,peripheral blood film stated hypochromic microcytic anemia with anisopoikiocytosis, leucopenia and showed thrombocytopenia, CRP 158 ug/ml, procalcitonin 20ng/ml, AST 181U/L, ALT 57U/L, GGT 43U/L, serum bilirubin 62mg/dl, INR 1.8, APTT 63, Ddimer 11.5 mg/L, fibrinogen 95mg/dL, ferritin 22037ng/ml, Na 126 mmol/l with normal renal function. Dengue serology and malaria (ICT, film) were negative. Enteric fever was confirmed by Widal + 1/640 (O Ag), 1/160 (H Ag) with Salmonella Typhi (ESBL MDR) grew from blood culture. (Pic 1) Hb electrophoresis was also done and consistent with Hb H disease. CT (chest and abdomen) revealed chest infection in posterior basal segment of right lower lobe, minimal right pleural effusion, moderate pelvic ascites and mild hepatosplenomegaly. Severe anaemia was corrected by blood transfusion and intravenous meropenem was given according to sensitivity for 14 days. Due to persistent pancytopenia, bone marrow examination was proceeded to exclude hemophagocytic lymphohistiocytosis (HLH) due to severe typhoid infection. Bone marrow aspiration and trephine biopsy reported only active marrow which conclude that peripheral destruction of blood cells due to septicemia. (Pic 2) After 2 weeks of antibiotic, he became afebrile and pancytopenia returned to normal. (table 1)

Fig.1 Blood culture result of patient

Table 1. Serial full blood count result of patient

Fig 1. Bone marrow result of patient

Discussion

The Yangon General Hospital is a 2000-bedded major public hospital in Myanmar. Typhoid fever is one of the important cause of fever admitted to the hospital. The clinical spectrum of admitted typhoid fever varies widely from mild illness to severe sepsis. Getta et alhad done bone marrow study in all typhoid fever with pancytopenia in 2018, they reported that majority of cases had active marrow like our case, 43% had increased histocyte activity and only 13% had haemophagocytosis features.⁸ In our case, his underlying haemoglobinopathy ( Hb H disease) also contribute to severe anemia during his illness. Some studies also reported mild hyponatremia can be associated with multi drug resistant cases in typhoid fever.⁹ Persistent mild hyponatremia was also presented in our case which finally grew multidrug resistant organism in blood culture. So we need to aware of multidrug resistant organism in clinical care of typhoid fever if patient has hyponatremia in blood tests.

Conclusion

Typhoid fever is still important infectious disease in South East Asia region including Myanmar. Bone marrow involvement in typhoid fever is uncommon but not rare in typhoid patients. To find out the cause of pancytopenia in typhoid fever, the bone marrow examination is invasive and discomfortable procedure so we can postpone it until pancytopenia is persistent. Therefore, close follow up of the blood parameters during the treatment is the best choice as an alternative to the bone marrow examination. However, persistent of pancytopenia is indication for bone marrow examination to exclude other possibility like hemophagocytic lymphohistio cytosis syndrome.

Reference

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Author Information

Aye-Mya-Theingi-Win¹, May-Zabe², Khin-Rupar-Ko³, Aye-Aye-Win⁴, Nyunt Thein⁵

1. Consultant physician, Tropical and Infectious Diseases Department, Yangon General Hospital
2. Consultant physician, Tropical and Infectious Diseases Department, Yangon General Hospital
3. Professor, Tropical and Infectious Diseases Department, Yangon General Hospital
4. Associate Professor, Tropical and Infectious Diseases Department, University of Medicine (1), Yangon
5. Senior Consultant physician, Former Head of Department of Medicine, Emeritus Professor of Medicine, University of Medicine (1), Yangon