|Year : 2019 | Volume
| Issue : 3 | Page : 182-186
A case of coinfection with (H1N1) 2009 influenza and scrub typhus with CNS involvement
Suneeta Sahu1, Rani Sahu1, Manoj Chhotray2, Sharmili Sinha3, Banambar Ray3
1 Department of Clinical Microbiology and Immuno Serology, Apollo Hospital, Bhubaneswar, Odisha, India
2 Department of Medicine, Apollo Hospital, Bhubaneswar, Odisha, India
3 Department of Critical Care, Apollo Hospital, Bhubaneswar, Odisha, India
|Date of Submission||25-Jun-2019|
|Date of Acceptance||26-Jul-2019|
|Date of Web Publication||11-Sep-2019|
Department of Clinical Microbiology and Immuno Serology, Apollo Hospitals, Bhubaneswar, Odisha
Source of Support: None, Conflict of Interest: None
Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications, and in turn reduces morbidity and mortality due to rickettsial diseases. Febrile patients with thrombocytopenia and MODS should be investigated for more than one tropical infection. Therefore, there is a distinct need for physicians and health-care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy of these infections.
Keywords: Coinfection, H1N1, scrub typhus
|How to cite this article:|
Sahu S, Sahu R, Chhotray M, Sinha S, Ray B. A case of coinfection with (H1N1) 2009 influenza and scrub typhus with CNS involvement. Apollo Med 2019;16:182-6
| Introduction|| |
Acute onset of fever, chills, myalgia, and fatigue are common features of many infections that are endemic in India. In many areas of developing countries, where diagnostic facilities are limited, etiologies of acute undifferentiated febrile illness (AUFI) remain largely unknown. Physicians often diagnose patients presumptively based on clinical features and assumptions regarding prevalent pathogens. These AUFIs that include scrub typhus, dengue fever, malaria, enteric fever, and leptospirosis among others cause significant mortality and morbidity. These infections may be indistinguishable clinically, and the choice of empiric antibiotics depends on the etiologic profile which is variable and is region specific. Some infectious diseases may mimic H1N1 viral infection, especially scrub typhus, dengue, Leptospira, and malaria-like diseases.
A spurt of H1N1 (seasonal) influenza outbreak coincided with the typical scrub typhus season, in the month of August 2017. This could have led to diagnostic difficulties due to their similar and nonspecific symptoms. However, due to robust diagnostic microbiology laboratory facilities and good clinical acumen, timely diagnosis and hence treatment was possible. Here, we describe a case of laboratory-confirmed coinfection of (H1N1) 2009 influenza and scrub typhus and discuss the similarities of the two illnesses.
Rickettsial diseases have been documented in India since the 1930s with reports of scrub typhus from Kumaon region, in soldiers during the second world war in Assam,, of scrub and murine typhus from Jabalpur area in Madhya Pradesh, and of murine typhus from Kashmir.
| Case Report|| |
A 44-year-old male from the western part of Odisha presented in the emergency department of our hospital for fever under evaluation in the month of August 2017. He had a history of irregular fever with chills and rigor for the past 5 days along with irritating cough for 3 days which was associated with anorexia, nausea, vomiting for 3 days, burning sensation, and constipation. There was no history of type 2 diabetes mellitus and hypertension. On examination, the patient was febrile (temperature: 100° F) tachycardic with pulse 92/min, was suspected to be icteric, and blood pressure (BP) was 110/60 mmHg. He had breathing difficulty. The chest had bilateral vesicular breath sounds (BS), and the patient was delirious. Crepitations were present over the right base. Cardiovascular system s1s2s3 was normal. Per abdomen was mildly distended. The patient was shifted to the ward from the emergency department and started on piperacillin-tazobactam 4.5 g IV TID, azithromycin 500 mg OD, and antimalarial artesunate 60 mg OD and the patient was nebulized as palliative treatment.
Blood investigation showed raised leukocytes (18100/mm 3), arterial blood gas analysis decreased partial pressure of carbon dioxide, decreased partial pressure of oxygen, Hyponatremia (sodium 129 Mmol/L), hypochloremia (Cl 103 Mmol/L), increased lactate (lactic acidosis of 4.3 Mmol), potassium 4.9, Base 8.4, tachycardia (pulse 110/min, regular). Tachypneic with respiratory rate of 25/min, oxygen saturation of 95% Cardiovascular system was normal, Glasgow Coma Scale (GCS) was E4V6M5. Per abdomen was soft.
On the 2nd day early morning, the patient was shifted from the ward to the intensive care unit in view of decreased saturation and delirious mental state and was difficult to manage. Although the patient was conscious, afebrile but had breathing difficulty and oxygen saturation was 92% with six litres of oxygen. The pulse rate was 141 per min, respiratory rate was 23 per minute and blood pressure was 103/63 per minute. Chest findings had bilateral vesicular breath sounds. Cardiovascular system was normal. The partial pressure of carbon di oxide was 25.7, partial pressure of oxygen was 71.9. Urine output was measured to be 2500 ml 4 times which was voided by self. Malarial antigen by malarial parasite immunochromatographic test and Dengue Ns1, IgM and IgG was negative. Hyponatremia continued. There was moderate elevation of total bilirubin to 1.8. As the day advanced, the patient remained febrile and confused and complained of pain abdomen. Ultrasound showed no abdominal pathology, but the abdomen was slightly distended, and the patient continued having tachycardia. Therefore, the patient was advised to remain nil by mouth.
On thorough clinical examination, eschar [Figure 1] was found in the lower abdomen, and the index of suspicion was toward scrub typhus. Clinical suspicion of scrub typhus was confirmed with laboratory diagnosis of scrub typhus serology positive (scrub typhus IgM: 1.901). Moreover, our hospital has been experiencing an increasing number of scrub typhus patients over the recent years, perhaps due to both global re-emergence of the disease and the increasing index of suspicion in our hospital. Therefore, doxycycline 100 mg IV BD was started. On further examination, he had deranged liver function test, febrile, tachycardic with heart rate of 142/min. Since patient continued to be irritable clinician advised for lumbar puncture which was done and cerebrospinal fluid (CSF) sent for investigations like adenosine deaminase (ADA), biochemical, cytology study. CSF glucose was 39, protein 136, cell count was 1, and Glasgow Coma Scale (GCS) was E4V4M6. CSF Gram's stain showed no pus cells, and organism cultures were negative. Ziehl–Neelsen stain was negative for acid fast bacilli, polymerase chain reaction (PCR) for tuberculosis was negative, and ADA was negative. PCR for herpes simplex virus was also negative.
On CNS examination, vertigo was mildly positive. On auscultation of the chest, BS were vesicular with occasional crepitations. Therefore, the patient was investigated for H1N1 and Leptospira in the evening of the 2nd day. Ct 29 is Cycle threshold was 29. The same sample was sent to RMRC (ICMR), Bhubaneswar, who also reaffirmed the presence of H1N1. Oseltamivir was started at 150 mg BD. On later part of second day. HR is Heart rate SPO2 is Oxygen saturation 96% with 0.5 litres of Oxygen and bilateral crepitations. The patient passed motion. With this downhill parameter, antibiotics were escalated to meropenem 1 g IV BD.
Observing the delirious condition on the 3rd day, computed tomography (CT) scan without contrast was done which was reported as no significant abnormality detected. Cerebral parenchyma showed normal attenuation. There was no evidence of any diffuse or focal lesion. Posterior fossa structures such as cerebellum and brain stem were normal. Ventricular system and cistern spaces showed normal configuration and attenuation. Sellar, suprasellar, and parasellar legion appeared normal.
Lumbar puncture was done and cerebrospinal fluid had increased protein 136 Mg/dL (normal value: 15–45 Mg/dL), Adenosine Deaminase (CSF) 7.95 U/L, CSF white blood cells was 53/mm 3. CSF cytology read moderate cellular smear showing numerous lymphocytes, plasma cells, few polymorph and occasional red blood cells which indicated moderate chronic inflammation.
Patient's N- terminal prob-type natriuretic peptide (NTproBNP) was 8682. Two-Dimensional; Echocardiography (2D Echo) had Left Ventricular Hypertrophy (com LVH) and Atrioventricular (sd AV cum output). Heart Rate (HR) 115/min, BP 107/62 mmHg Oxygen saturation (SPO2) 92% at 6 Litres (L) oxygen (O2), Respiratory Rate (RR) 21/min, chest Bilateral (B/L) Vesicular Breath Sounds (VBS) Per Abdomen (P/A) firm, mild ly distended. Oral liquid diet was started with extra salt of 2 g BD for in view of decreased Na +.
On the fourth day, the patient was afebrile, less irritable. Pulse started settling to 98/min, BP stabilized to 134/73 mm Hg, ABG also settled to Partial pressure of Carbon Di Oxide (PCO2) 93% with 6L O2. Meropenem 1 gm 8 hourly, oseltamivir continued 150 mg twice daily. Tablet azithral 500 mg once daily and nebulization continued. Contrast-enhanced CT of the brain was advised because the patient complained of headache.
Fifth day morning, he was stable and comfortable, conscious, a febrile Input/Output (I/O ) 2500/2315, Motion passed 5 times. HR – 67/min, SPO298%, RR17/min chest Bilateral (B/L) Vesicular Breath sounds (VBS) Cardiovascular system (CVS) normal. GCS: E4 V5 M6. P/A: Bowel sounds (BS) positive.
The patient was shifted to the ward from day 6. Clinical parameters from day 6 to 11 remained within normal limits. The patient was afebrile, BP was maintained at an average of 126/80 mm Hg, pulse was 80/min, and the chest was clear and CVS NAD.
Ultrasound whole abdomen
No evidence of any free fluid in the peritoneal cavity.
| Discussion|| |
Scrub typhus is the most common rickettsial disease in India. It is caused by Orientia tsutsugamushi and is spread by chiggers. It is considered some of the most covert emerging and re-emerging diseases and serious re-emerging threat as untreated cases may have 30%–35% mortality. Rickettsial infections are generally incapacitating and difficult to diagnose. The vast variability and nonspecific presentation of this infection have often made it difficult to diagnose clinically. The eschar is characteristic of scrub typhus; however, differences in the skin immunity and possible previous exposure to the Rickettsia in endemic populations may be the cause of the absence of eschar in many patients., Our case had an eschar. The Writing Committee of the DHR-ICMR Guidelines for the diagnosis and management of rickettsial diseases in India has recommended doxycycline as the drug of choice in rickettsial infection in adults above 45 kg 2. Hence, in our case, initial empirical treatment was started with doxycycline 200 mg/day in two divided doses for a duration of 7 days.
However, Phimda et al. showed azithromycin and doxycycline to be similarly efficacious. The symptoms of scrub typhus are similar to symptoms of many other diseases. Early recognition of scrub typhus is important for prompt initiation of appropriate antibiotics. Common symptoms in both groups included breathlessness, dry cough, nausea, vomiting, headache, myalgia, altered sensorium, abdominal pain, and bleeding.
Saleem et al. reported 15 cases of scrub typhus coinfection with dengue in adults, whereas Rajendran reported one case of coinfection in the pediatric age group. Previous infection with any one of the agents in the recent past can render a false-positive IgM ELISA in the present episode. However, our case did not have any febrile illness in the past 4 months. The abdominal pain in our patient could be due to vasculitis-induced mesenteric ischemia  which may occur in scrub typhus. It is well known that the third spacing of fluid (due to capillary leak) and polyserositis are possible in scrub typhus fever as the basic pathogenic mechanism scrub typhus infections are vasculitis and increased vascular permeability.,
Some other complications such as thrombocytopenia and seizure can occur in scrub typhus infections and hence should be kept in mind during a coinfection. Seizures have been reported both in children with scrub typhus  and dengue. Besides, high fever can also precipitate febrile seizure in children and should be taken into account. Thus, it becomes profoundly important to look for features which might alert the clinician to look for a coinfection, even after having diagnosed one. Basheer et al. found that the coinfection cases have greater tachycardia, hypotension, transaminitis, and hypoalbuminemia, alteration in activated partial thromboplastin time and hospital stay compared to either infection alone. Our case also had tachycardia, hypotension, hypoalbuminaemia.
The nadir platelet count was lower (mean platelet count in coinfection was 2.17 × 109/cm 3 as opposed to 63.8 × 109/cm 3 in scrub typhus and 44.5 × 109/cm 3 in dengue alone), and the time needed to achieve the nadir platelet count was higher (median duration for coinfection was 3 days as compared to 4.5 days in scrub typhus and 5 days in dengue) in cases of coinfection. Iqbal et al. reported a case of pancreatitis with multiorgan dysfunction syndrome (MODS) in dengue–scrub typhus coinfection and noted that coinfection should always be investigated in doubtful cases of infective pancreatitis. All patients in the case series published by Venkategowda et al. had required mechanical ventilation and renal replacement therapy; as such, they concluded that any febrile patient with thrombocytopenia and MODS should be investigated for more than one tropical infection.
Febrile respiratory symptoms represent the most common clinical manifestations of infection with 2009 H1N1 virus and are in general mild and self-limited. The organism infects vascular endothelium with subsequent vascular injury in organs such as the skin, liver, kidneys, meninges, and brain resulting in multiorgan manifestations. Incubation period varies from 1 to 3 weeks, and clinical features are fever, headache and myalgia, breathing difficulty, delirium, vomiting, cough, jaundice, and eschar. Complications usually are overwhelming pneumonia with acute respiratory distress syndromes such as presentation, hepatitis, aseptic meningitis, myocarditis, and disseminated intravascular coagulation.
The incubation period for H1N1 appears to be approximately 1.5–3 days, which is similar to that of seasonal influenza. In a minority of patients, the period may extend to 7 days.
Infection with the 2009 H1N1 virus causes a broad spectrum of clinical syndromes, ranging from afebrile upper respiratory illness to fulminant viral pneumonia. Mild illness without fever has been reported in 8%–32% of infected persons. Most of the patients presenting for care have a typical influenza-like illness with fever and cough, symptoms that are sometimes accompanied by sore throat and rhinorrhea. Systemic symptoms are frequent. Gastrointestinal symptoms (including nausea, vomiting, and diarrhea) occur more commonly than in seasonal influenza, especially in adults. Dyspnea, tachypnea in children, chest pain, hemoptysis or purulent sputum, prolonged or recurrent fever, altered mental status, manifestations of dehydration, and reappearance of lower respiratory tract symptoms after improvement are signs of progression to more severe disease or complications. Laboratory findings at presentation in patients with severe disease typically include normal or low-normal leukocyte counts with lymphocytopenia and elevations in levels of serum aminotransferases, lactate dehydrogenase, creatine kinase, and creatinine. Myositis and rhabdomyolysis have occurred in severe cases. [Table 1] shows the detailed laboratory parameters of the patient admitted to our hospital. A poor prognosis is associated with increased levels of creatine kinase, creatinine, and perhaps lactate dehydrogenase, as well as with the presence of thrombocytopenia and metabolic acidosis. Sporadic cases of neurologic manifestations (confusion, seizures, unconsciousness, acute or postinfectious encephalopathy, quadriparesis, and encephalitis and myocarditis have been reported, including some fulminant cases.
| Conclusion|| |
Physicians should maintain a high index of suspicion in cases of febrile illnesses not responding in the conventional way. This case report delineates that scrub typhus coinfection with H1N1, though rare, may occur in adults.
Since we have a high prevalence of Scrub typhus and this disease is associated with morbidity and mortality if left undiagnosed, has overlapping clinical findings with H1N1 infection there is a need for awareness and early diagnosis and empirical treatment.
To the best of our knowledge, this is the first reported case of scrub typhus and H1N1 coinfection in an adult 44-year-old male patient in Odisha, admitted with C/O abdominal pain from 4 days and fever and vomiting for 3 days. In view of continuous fever. Patient RPP test was done, which was suggestive of H1N1 influenza infection. The patient was also Scrub typhus IgM positive. The patient was managed symptomatically on IV antibiotics, proton pump inhibitor, and other supportive measures. The patient clinically improved and was discharged in a medically stable condition.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Our sincere thanks to Dr. B Dwibedi, Scientist E, In charge VRDL RMRC (ICMR), Bhubaneswar, for confirming the H1N1 sample sent from our laboratory.
Financial support and sponsorship
Conflicts for interest
There are no conflicts for interest.
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