Acute Febrile Illness Patients Research Articles

Identification of Bacteria and Viruses Associated with Patients with Acute Febrile Illness in Khon Kaen Province, Thailand.

The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we conducted molecular pathogen screening and serological analyses in patients who sought treatment in Chum Phae Hospital, Khon Kaen province, during the period from 2015 to 2016. Through integrated approaches, we successfully identified the etiology in 25.5% of cases, with dengue virus infection being the most common cause, noted in 17% of the study population, followed by scrub typhus in 3.8% and rickettsioses in 6.8%. Further investigations targeting viruses in patients revealed the presence of Guadeloupe mosquito virus (GMV) in four patients without other pathogen co-infections. The characterization of four complete genome sequences of GMV amplified from AFI patients showed a 93-97% nucleotide sequence identity with GMV previously reported in mosquitoes. Nucleotide substitutions resulted in amino acid differences between GMV amplified from AFI patients and mosquitoes, observed in 37 positions. However, these changes had undergone purifying selection pressure and potentially had a minimal impact on protein function. Our study suggests that the GMV strains identified in the AFI patients are relatively similar to those previously reported in mosquitoes, highlighting their potential role associated with febrile illness.

Scrub typhus among patients with acute febrile illness in a tertiary health care centre

Scrub typhus, caused by Orientia tsutsugamushi and transmitted by bite of larval trombiculid mite of the Leptotrombidium genus and is a vector borne zoonotic disease. It has been predominantly reported from Southeast Asia, the Asian Pacific Rim, and Australia. The incidence of this disease is increased in India. These patients show an acute undifferentiated febrile illness and laboratory confirmation is essential. Delay in diagnosis may be fatal. : To assess the Scrub typhus burden among acute febrile illness patients. This Cross-sectional study, conducted in Dept. of Microbiology, Basaveshwara Medical College & Hospital, Chitradurga, Karnataka, India. Study duration was from August 2020 to January 2021. In this study, a total of 100 febrile illness patients were involved. Among them, 66 were males and 34 females. Under aseptic conditions, venous blood samples were collected from all subjects. Serum was separated by centrifugation, aliquoted, and stored at −20°C for further testing. The serum sample was tested for scrub typhus IgM ELISA using the INBIOS kit. Samples were also checked for dengue fever, typhoid fever, leptospirosis, and malaria. The serum samples that tested positive for any other infectious disease mentioned above (with or without detectable rickettsial antibodies) were excluded from the study. Data was represented in numbers and percentages. : In this study, out of 100 samples 30 were seropositive. Of the 30 seropositive scrub typhus cases, women were 11 (37%) and men were 19 (63%), suggesting that seropositivity was more in men than women. Among the seropositive cases, maximum number of the cases were in 16-30 years (33%) of age, followed by 31–45 years (23%). In this study, more number of positive cases 17 (56.6%) were found during the post-monsoon season i.e., October and November 2020. Fever, the most common symptom (100%). Headache, reported in (70 %) of cases, myalgia (40%), abdominal pain (37%), cough (23%), vomiting (20%), lymphadenopathy (17%), rashes (13%), hepato-spleenomegaly (10%), eschar (3%). The study results may conclude that Scrub typhus seropositivity rate was higher in males than females and also to be included in differential diagnosis of fever of unknown origin.

Clinical Evaluation of Hospitalized Cases of Acute Febrile Illness with Thrombocytopenia in North - West Zone of Rajasthan

Background: Thrombocytopenia has been recognized as an important manifestation of acute febrile illness caused by various types of. Early diagnosis of aetiology is very important to reduce morbidity and mortality. This study was planned to evaluate clinical profile, aetiology, differential diagnosis, clinical course and outcome of such patients. Methods: Present prospective cross-sectional study was conducted on 400 consecutive patients of fever with thrombocytopenia admitted during 1st May 2022 to 31st October 2022 in the Department of Medicine, S.P. Medical College & Associated Group of P.B.M. Hospitals, Bikaner. All patients were evaluated as per proforma including detail clinical history and physical examination. Laboratory evaluation including CBC, RFT, LFT, blood sugar, LDH, Rapid diagnostic test for malaria, PBF for MP, test for dengue, HBsAg, Anti HCV, HIV, PBF detail, Blood culture, D–dimer, test for Scrub typhus and leptospirosis, Ultrasonography and chest X-Ray was done in all cases. Other investigations were done as per requirement. All patients were treated as per guidelines and followed-up during hospitalization. Results: Out of 400 patients 227 were males (age ranging 15-87 years, mean 35.46 ±15.63) and 173 females (age ranging 15-92 years, mean 39.75 ± 17.36). Dengue fever was found to be the commonest cause (29.5%) followed by Malaria, COVID-19 infection (0.75%) and one each HIV and Hepatitis B. In 54.25% of the cases definite etiological diagnosis could not be ascertained. 14.25% patients were having life threatening thrombocytopenia, 45% severe grade, 21.75% moderate and 19% mild thrombocytopenia. Severity of thrombocytopenia was associated with longer duration of illness (p<0.02). Bleeding manifestations were observed in 5.75% but did not corelated with severity of thrombocytopenia. Mean duration of hospital stay was found to be inversely proportion to total platelet count on admission. Conclusion: Acute Febrile illness patients should be investigated for platelet count irrespective of the bleeding manifestations as decreased platelet count could be severe without external manifestations and could be an indicator of bad prognosis.

2241. Antibiotic Use Before and After Hospital Admission Among Hospitalized Patients with Acute Febrile Illness in Bangladesh

Abstract Background The inappropriate use of antibiotics is common in Bangladesh, contributing to the significant burden of antimicrobial resistance. The WHO has categorized Access, Watch, and Reserve groups of antibiotics (AWaRe classification) to promote optimal use. We explored antibiotic use among hospitalized patients with acute febrile illness (AFI) at five tertiary-level hospitals in Bangladesh. Methods From September 2021 to February 2023, 1544 patients were randomly selected among all hospitalized patients with measured fever (≥100.4°F) or a history of fever in the past 14 days. Blood and urine culture isolates were analyzed for antibiotic sensitivity using the VITEK-2 system. Results Of enrolled AFI patients, 835 (54%) reported the use of antibiotics prior to hospitalization, with 79% of reported antibiotics from the Watch group, 16% from the Access group, and none from the Reserve group. Five percent of the antibiotics prescribed were not recommended by WHO for clinical practice. The top five frequently reported antibiotics before hospitalization were cefixime (24%), azithromycin (19%), ceftriaxone (16%), amoxicillin (6%), and cefuroxime (5%). Bacterial infection was diagnosed among 205 patients (13% of all enrollees) through Rapid diagnostic tests, culture and Rt-PCR. In-hospital, 1385 (90%) patients received at least one antibiotic. The most frequently prescribed antibiotics were from the Watch group (84%), followed by the Access group (15%) and none from the Reserve group. The top five antibiotics prescribed in-hospital were ceftriaxone (64%), amoxiclav (7%), ceftazidime (3.4%), clarithromycin (2.8%), and moxifloxacin (2.6%). Antibiotic susceptibility testing (AST) results from blood and urine culture isolates showed high resistance pattern to ceftriaxone (45% and 56%) and ceftazidime (63% and 50%). Of blood culture isolates 80% were sensitive to amoxiclav, while 46% of urine culture isolates were resistant to amoxiclav. At least one bacterial organism was identified in only 13% of enrolled patients. List of antibiotics that were reported to be received by the enrolled AFI patients before Hospitalization Before hospitalization, 132 patients reported receiving antibiotics from Access group, while 662 patients received antibiotics from WATCH group List of antibiotics received by the enrolled AFI patients during hospitalization During hospitalization, 211 patients received antibiotics from Access group and 1169 patients received antibiotics from Watch Group List of 235 bactrial organisms which were identified from clinical samples of 205 AFI patients (some patient had co-infection) Conclusion In conclusion, antibiotics were used in nine of ten patients. The frequent and inappropriate use of Watch group antibiotics in outpatient settings likely contributes to decreased effectiveness and demonstrates the need for improved antimicrobial stewardship. Disclosures All Authors: No reported disclosures

Changing Trends in the Clinical Suspicion of Scrub Typhus in Acute Febrile Illness Patients

Abstract Introduction: Scrub typhus is an important and widespread cause of acute febrile illness (AFI), which can be diagnosed easily by serological assay. Methods: All cases of AFI were sent for Scrub Typhus serology by rapid Enzyme Linked Immuno-Sorbent Assay (ELISA) method. Anyone found positive was admitted for further evaluation. Results: In this series 80 % had liver abnormality, 80 % had ARDS, 40 % had renal failure, 40 % had eschar and 80 % of them had MODS. Only 20 % had clinical features of encephalitis with MRI brain haemorrhagic transformation of infarct. All patients responded well to treatment with Doxycycline with hospitalization of around 7-10 days. Conclusion: This case series highlights the importance of keeping a high index of clinical suspicion to exclude scrub typhus in all AFI patients.

Role of TaqMan array card in determining causative organisms of acute febrile illness in hospitalized patients.

Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor quality of clinical diagnosis. TaqMan array card (TAC) can detect up to 35 AFI-associated organisms in 1.5 h, addressing diagnostic demands. In this study, we aimed to evaluate the role of TAC in determining the causative organisms in hospitalized AFI patients. The study had a cross-sectional design and enrolled 120 admitted patients with persistent fever for three or more days from the medicine ward of Chittagong Medical College Hospital (CMCH) and Bangladesh Institute of Tropical and Infectious Diseases Hospital (BITID). Blood samples were collected and then subjected to automated BacT/Alert blood culture, microbial culture, TAC assay, and typhoid/paratyphoid test. The total number of study participants was 120, among them 48 (40%) samples showed a positive result in TAC card, 29 (24.16%) were TP positive and nine (7.51%) were culture positive. The number of organisms detected by the TAC card was 13 bacteria, three viruses, one protozoan, and one fungus. The sensitivity and specificity of the TAC assay for different bacterial pathogen compared to blood culture was 44.44%, and 90.99%, respectively. In contrast, the TP test had a sensitivity and specificity of 100% and 80%, respectively, compared to the blood culture test. TAC can be a handful tool for detecting multiple organisms in AFI with high specificity which can facilitate early diagnosis of different pathogens contributing to AFI.

Assessment of the Utility of Point-of-Care Testing Incorporating Ultrasound and Arterial Blood Gas in Patients with Acute Febrile Illness in the Emergency Department to Determine Disease Severity, Disposition, Need for Ventilation and Renal Replacement Therapy.

Acute febrile illness (AFI) patients present to the emergency department (ED), with fever to multi-organ dysfunction. There is a lack of early point-of-care-based disposition criteria in AFI patients regarding the need for intensive care unit (ICU) or high dependency unit (HDU) care. We enrolled 100 patients with AFI presenting to the ED and evaluated using point-of-care ultrasound with two-dimensional echocardiography (ECHO), lung ultrasound score (LUS), renal arterial resistive index (RRI), and arterial blood gas. The need for ICU/HDU admission, ventilation (either noninvasive or invasive), and renal-replacement therapy (RRT) within 48 h of hospitalization was noted. Ninety-five patients were included in the analysis. 72 (75.8%) patients required either ICU or HDU admission, 45 (47.4%) required ventilatory support (either noninvasive or invasive), and 32 (33.7%) required RRT. After logistic regression, LUS ≥16, and arterial lactate ≥12 mg/dL were independent predictors of the need for ICU or HDU admission. The respiratory rate (RR) ≥28/minute, LUS ≥16 and RRI ≥61 were the independent predictors of the need for ventilation. The MAP ≤73 mmHg, LUS (≥16), and RRI (≥67) were the predictors of the need for RRT. In AFI patients presenting to the ED, the MAP, LUS, and lactate are predictors of the need for ICU/HDU admission. The LUS and RRI were predictors of the need for RRT whereas the RR, LUS, and RRI were the predictors of the need for ventilation.

Comparative Study of Antigen Detection and Viral Nucleic Acid Assay for Early Detection of Dengue Infection

Background : Differentiating dengue patients from other acute febrile illness patients is a great challenge among physicians. Thus early and rapid diagnosis of dengue virus infection is of top most importance. The present study was designed to establish an early and rapid diagnosis of dengue virus infection from single serum samples with comparison between two methods-antigen detection by Immunochromatographic test (ICT) and nucleic acid assay by Real time RT –PCR.
 Materials and methods : This cross sectional study was carried out in the Department of Microbiology, Chittagong Medical College and Chevron Laboratory in Chattogram during the period of January 2012 to December 2012. A total 115 clinically suspected dengue patient of all ages and both sexex from indoor and Out Patient Department (OPD) of Chittagong Medical College Hospital were enrolled in this study.
 Results : These test were done in 2-7 days of fever. Blood samples from 115 clinically suspected dengue cases had been taken. Among them, NS1 antigen by ICT were found positive in 78(67.8 %) cases and DENV RNA by realtime RT-PCR in 64 (55.7% ) cases. Among 64 dengue PCR positive cases, dengue ICT was found positive in 61 (95.30%) cases & not detectable in 03 (4.65%) cases and in 51 PCR negative cases, 17 were found positive by ICT. The difference in diagnosing dengue by ICT and PCR was found highly significant, p < 0.001. Highest positivity of both test were observed in 2nd to 4th days. In this study, dengue ICT was detected 19 (70%) cases in • 5 days of fever where as PCR was detected only 02 (6.80%) cases. The sensivity , specificity , positive predictive value , negative predictive value of ICT in comparison to PCR were found 95.3% , 66.7%, 78.2 %, 91.9% respectively.
 Conclusion : In the comparative evaluation, NS1 Antigen was found to be far more sensitive than Real time RT-PCR 1.
 IAHS Medical Journal Vol 4(2), December 2021; 60-65

Development and validation of a simple tool composed of items on dyspnea, respiration rates, and C-reactive protein for pneumonia prediction among acute febrile respiratory illness patients in primary care settings

BackgroundAcute febrile respiratory illness (AFRI) patients are susceptible to pneumonia and suffer from significant morbidity and mortality throughout the world. In primary care settings, the situation is worse. Limited by computerized tomography resources and physician experiences, AFRI patients in primary care settings may not be diagnosed appropriately, which would affect following treatment. In this study, we aimed to develop and validate a simple prediction model to help physicians quickly identify AFRI patients of pneumonia risk in primary care settings.MethodsA total of 1977 AFRI patients were enrolled at two fever clinics in Shanghai, China, and among them, 727 patients who underwent CT scans were included in the analysis. Acute alveolar or interstitial infiltrates found on CT images were diagnosed with pneumonia. Characteristics and blood parameters were compared between pneumonia and non-pneumonia patients. Then a multivariable model for pneumonia prediction was developed through logistic regression analysis. Its value for pneumonia prediction was prospectively assessed in an external multi-center population, which included 1299 AFRI patients in primary settings from 5 different provinces throughout China.ResultsIn the model development population, pneumonia patients (n = 227) had a longer duration of fever; higher frequencies of purulent sputum, dyspnea, and thoracic pain; and higher levels of respiration rates and C-reactive protein (CRP) than non-pneumonia patients (n = 500). Logistic regression analysis worked out a model composed of items on dyspnea, respiration rates > 20/min, and CRP > 20 mg/l (DRC) for pneumonia prediction with an area under curve (AUC) of 0.8506. In the external validation population, the predictive accuracy of the DRC model was the highest when choosing at least one positive item (1 score) as a cut-off point with a sensitivity of 87.0% and specificity of 80.5%. DRC scores increased with pneumonia severity and lung lobe involvement and showed good performance for both bacterial and viral pneumonia. For viral pneumonia, dyspnea plus respiration rates > 20/min had good predictive capacity regardless of CRP concentration.ConclusionsDRC model is a simple tool that predicts pneumonia among AFRI patients, which would help physicians utilize medical resources rationally in primary care settings.

Acute febrile illness among outpatients seeking health care in Bangladeshi hospitals prior to the COVID-19 pandemic.

Understanding the distribution of pathogens causing acute febrile illness (AFI) is important for clinical management of patients in resource-poor settings. We evaluated the proportion of AFI caused by specific pathogens among outpatients in Bangladesh. During May 2019-March 2020, physicians screened patients aged ≥2 years in outpatient departments of four tertiary level public hospitals. We randomly enrolled patients having measured fever (≥100.4°F) during assessment with onset within the past 14 days. Blood and urine samples were tested at icddr,b through rapid diagnostic tests, bacterial culture, and polymerase chain reaction (PCR). Acute and convalescent samples were sent to the Centers for Disease Control and Prevention (USA) for Rickettsia and Orientia (R/O) and Leptospira tests. Among 690 patients, 69 (10%) had enteric fever (Salmonella enterica serotype Typhi orSalmonella enterica serotype Paratyphi), 51 (7.4%) Escherichia coli, and 28 (4.1%) dengue detected. Of the 441 patients tested for R/O, 39 (8.8%) had rickettsioses. We found 7 (2%) Leptospira cases among the 403 AFI patients tested. Nine patients (1%) were hospitalized, and none died. The highest proportion of enteric fever (15%, 36/231) and rickettsioses (14%, 25/182) was in Rajshahi. Dhaka had the most dengue cases (68%, 19/28). R/O affected older children and young adults (IQR 8-23 years) and was detected more frequently in the 21-25 years age-group (17%, 12/70). R/O was more likely to be found in patients in Rajshahi region than in Sylhet (aOR 2.49, 95% CI 0.85-7.32) between July and December (aOR 2.01, 1.01-5.23), and who had a history of recent animal entry inside their house than not (aOR 2.0, 0.93-4.3). Gram-negative Enterobacteriaceae were the most common bacterial infections, and dengue was the most common viral infection among AFI patients in Bangladeshi hospitals, though there was geographic variability. These results can help guide empiric outpatient AFI management.

Beyond arboviruses: A multicenter study to evaluate differential diagnosis of rash diseases and acute febrile illness cases in Rio de Janeiro, Brazil.

IntroductionA wide variety of viruses can cause rash diseases (RDs) or acute febrile illness (AFIs) in children, adolescents and adults; however, approximately 19% of RD cases and 40% of AFI cases remain without a defined etiology. Parvovirus B19 (B19V) and herpesvirus infection can also cause RD and/or AFI, and in some risk groups, these infections can become persistent (or latent) and may require hospital treatment. Since these infections do not have mandatory reporting, they can be hidden by other diseases, such as those caused by arboviruses (e.g., dengue virus). In this context, the aim of this study was to pursue the differential laboratory diagnoses of B19V and herpesvirus infections in patients with RD and AFI, without a defined etiology, seen in hospitals and/or reference centers for infectious diseases in Rio de Janeiro.MethodsA total of 114 participants were enrolled in the study, including 54 children and 60 adults. B19V infection was assessed by real-time PCR (qPCR) and ELISA (anti-B19V IgM and IgG). EBV was assessed through qPCR, and betaherpesviruses (HCMV, HHV-6 and HHV-7) were assessed through multiplex qPCR. Sociodemographic and clinical data were obtained from the medical record data of these participants.ResultsThe median age of children with RD was 2 years (interquartile range (IQR): 5), and 55.6% were male. Among adults with AFI, the median age was 38 years (IQR: 21), and 56.7% were female. Regarding RD patients, viral prevalence (and load) were 5.5%(104IU/mL), 3.4%(104IU/mL), 5.5%(104IU/mL) and 11.1%(105IU/mL) for B19V, EBV, HCMV and HHV-6 infection, respectively, and in AFI patients they were 6.6%(105IU/mL), 1.6%(103IU/mL), 3.3%(104IU/mL) for B19V, HCMV and HHV-6, respectively. HHV-7 was not detected in RD or AFI patients.ConclusionThese results suggest the importance of including B19V and herpesviruses in the differential laboratory diagnoses for patients with RD and AFI, not only for epidemiological purposes but also for the proper management of the patient.

Study of thrombocytopenia in patients of acute febrile illness

Introduction: Many viral and bacterial infections result in thrombocytopenia and are most common non-iatrogenic cause of thrombocytopenia. Infections can affect both platelet production and platelet survival. In addition, immune mechanisms can also be a cause, as in immune-mediated thrombocytopenia (ITP) in children following viral infection. In our setup, tropical infections like malaria, dengue and leptospirosis formed the most common and important causes of thrombocytopenia. Objectives: To correlate the bleeding manifestations of thrombocytopenia with platelet count in patients with acute febrile illness and to document the incidence of thrombocytopenia and most common cause of thrombocytopenia among patients with acute febrile illnesses. Methodology: A minimum of 200 patients admitted to tertiary care center with documented fever of >37.50C and platelet count <1,50,000/µL were selected using purposive sampling techniques. They were followed from admission till recovery, discharge or death. Correlation of bleeding manifestations like petechiae, gum bleeding, hematuria, menorrhagia, epistaxis in relation with lowest platelet count was done along with categorization of patients according to different platelet count ranges. Results: Out of total 200 patients 65% were male and 35% were female.

The expression of circulating hsa-miR-126-3p in dengue-infected Thai pediatric patients

ABSTRACT Circulating hsa-miRNA-126 (CmiR-126) has been reported to involve in the pathogenesis of many infectious diseases including dengue virus infection. However, no prior study has been conducted to describe more details in dengue-infected pediatric patients. This study aimed to describe CmiR-126-3p in dengue-infected pediatric patients during the febrile and convalescent phases. Additionally, the correlations between CmiR-126-3p and other relevant clinical laboratory factors were investigated. Sixty paired-serum specimens collected during febrile and convalescent phases were retrieved from patients with dengue fever (DF) (n = 30) and dengue hemorrhagic fever (DHF) (n = 30). Thirty paired-serum specimens collected from non-dengue acute febrile illness patients (AFI) were included as the control group. CmiR-126-3p was determined using reverse transcription quantitative real-time polymerase-chain reaction (RT-qPCR). Relative miRNA expression was calculated as 2−ΔCt using CmiR-16-5p for data normalization. CmiR-126-3p expression during febrile and convalescent phases in dengue-infected patients was significantly lower than AFI (p < 0.05). However, miRNA levels were not different (p > 0.05) compared between DF and DHF and between primary and secondary infection. CmiR-126-3p levels in DF in the convalescent were significantly higher than in the febrile phase (p = 0.025). No association between CmiR-126-3p and hematocrit, WBC level, platelet count, WBC differential count or dengue viral load was observed (p > 0.05). The data suggest that hsa-miR-126-3p involved in pathogenesis of dengue infection and may be a promising early and late biomarker for DENV infection. However, hsa-miR-126-3p alone cannot be used as a predictor for dengue severity.

Cardiac Manifestations of Acute Febrile Illness Amongst Intensive Care Unit Patients

Background: There are various incidences of cardiac involvement in acute febrile illness (AFI). As the acute febrile illnesses are spreading, there is an increase in atypical cardiac manifestations ranging from asymptomatic bradycardia to life threatening manifestations like myocarditis and pericardial effusion. Objective: To determine cardiac manifestations of AFI amongst intensive care unit patients in rural populations. Methods: Twenty patients of AFI were studied between January 2021 to June 2021. Echocardiography (ECG), and cardiac enzymes were evaluated. Patients were from either gender from 15 to 60 years and were willing to sign consent. patients admitted with fever and on examination were found abnormal cardiac functions like hypotension, arrhythmia, hypertension, cardiac enzyme changes and reduced ejection fraction on 2D Echo. Patients with preexisting heart disease, cardioactive drugs affecting the heart rate were not involved in this study. Results: In total, 20 patients having cardiac manifestations with AFI were studied, out of which 9 cases presented with bradycardia, 3 cases presented with asymptomatic pericardial effusion, and 8 cases presented with ECG abnormalities such as narrow QRS complex, ST, and T changes. Conclusion: Cardiac Manifestations in adults with AFI were common, ranging from elevated cardiac biomarkers to myocarditis. Persistent shock despite adequate fluid resuscitation can be a crucial cardiac manifestation and should guide the treating physician towards underlying cardiac involvement such as systolic or diastolic dysfunction.

A retrospective analysis of serological & molecular testing data on dengue fever in Kolkata & adjacent districts during 2016-2019.

Regional Virus Research and Diagnostic Laboratory established at ICMR-National Institute of Cholera and Enteric Diseases (NICED) regularly receives samples for dengue screening and serotyping from patients of acute febrile illness (AFI) from Kolkata and adjacent districts. In this study, data over a three year period (August 2016-July 2019) was retrospectively analyzed to provide insight into the epidemiological trends of dengue fever in this region. Serological screening of dengue was performed by detection of NS1 antigen and/or immunoglobulin M (IgM) antibody. Dengue serotyping was done by conventional or real-time reverse transcriptase-PCR. The data were analyzed to describe the distribution of dengue with respect to age of patient, duration of fever on the day of blood collection and month of the year. Zip codes were used for spatial plotting. Out of the 24,474 samples received from Kolkata and its adjacent districts (Hooghly, Howrah, North and South 24 Parganas), 38.3 per cent (95% confidence interval: 37.7-38.9%) samples were screened positive for dengue. The correlation between age and dengue positivity was found to be weak. A combination of dengue NS1 antigen and dengue IgM antibody detection may be a better option for detecting dengue positivity compared to a single test. Most AFI cases were tested from August to November during the study period, with maximum dengue positivity noted during September (45.9%). The predominant serotype of 2016, dengue virus serotype 1 (DENV-1), was almost entirely replaced by DENV-2 in 2017 and 2018. Dengue continues to be an important cause of AFI in the region and round-the-year preventive measures are required for its control. Serotype switching is alarming and should be monitored routinely.

Evaluation of a genus-specific rGroEL1-524 IgM-ELISA and commercial ELISA kits during the course of leptospirosis in Thailand

In the present study, we developed a genus-specific rGroEL1-524 IgM-ELISA assay for use in screening diagnosis of suspected leptospirosis among acute undifferentiated febrile illness patients during acute fever. The diagnostic accuracies of the rGroEL1–524 IgM-ELISA, commercial Panbio IgM-ELISA, and Virion-Serion Classic IgG-ELISA were evaluated using 133 Thai leptospirosis sera and 210 controls. Sensitivities were 91.7%, 59.6%, and 17.7% for acute infection, and the specificities were 92.6%, 90.2%, and 88.3% for the non-leptospirosis control, respectively. The rGroEL1-524 IgM-ELISA had high sensitivity, at 92.3% and 91.7%, among culture-positive and MAT-negative cases at 1–3 days post-onset of symptoms (DPO1–3), respectively. Impaired specificity on scrub typhus was found, possibly from antibody cross-reaction to ortholog GroEL. Commercial Panbio IgM-ELISA had sensitivities at DPO1–3 of 30.8% and 41.7% for culture-positive and MAT-negative cases whereas Virion-Serion IgG-ELISA showed sensitivities of 5.9% and 13.3%, respectively. The rGroEL1-524 IgM-ELISA could be useful as a screening test for early diagnosis. The performance of the commercial ELISA suggests the applicability of IgM-ELISA for diagnosis, while IgG-ELISA is useful for seroprevalence surveys. However, confirmation by reference tests is recommended.

Infection Manager System (IMS) as a new hemocytometry-based bacteremia detection tool: A diagnostic accuracy study in a malaria-endemic area of Burkina Faso

New hemocytometric parameters can be used to differentiate causes of acute febrile illness (AFI). We evaluated a software algorithm-Infection Manager System (IMS)-which uses hemocytometric data generated by Sysmex hematology analyzers, for its accuracy to detect bacteremia in AFI patients with and without malaria in Burkina Faso. Secondary aims included comparing the accuracy of IMS with C-reactive protein (CRP) and procalcitonin (PCT). In a prospective observational study, patients of ≥ three-month-old (range 3 months- 90 years) presenting with AFI were enrolled. IMS, blood culture and malaria diagnostics were done upon inclusion and additional diagnostics on clinical indication. CRP, PCT, viral multiplex PCR on nasopharyngeal swabs and bacterial- and malaria PCR were batch-tested retrospectively. Diagnostic classification was done retrospectively using all available data except IMS, CRP and PCT results. A diagnosis was affirmed in 549/914 (60.1%) patients and included malaria (n = 191) bacteremia (n = 69), viral infections (n = 145), and malaria-bacteremia co-infections (n = 47). The overall sensitivity, specificity, and negative predictive value (NPV) of IMS for detection of bacteremia in patients of ≥ 5 years were 97.0% (95% CI: 89.8-99.6), 68.2% (95% CI: 55.6-79.1) and 95.7% (95% CI: 85.5-99.5) respectively, compared to 93.9% (95% CI: 85.2-98.3), 39.4% (95% CI: 27.6-52.2), and 86.7% (95% CI: 69.3-96.2) for CRP at ≥20mg/L. The sensitivity, specificity and NPV of PCT at 0.5 ng/ml were lower at respectively 72.7% (95% CI: 60.4-83.0), 50.0% (95% CI: 37.4-62.6) and 64.7% (95% CI: 50.1-77.6) The diagnostic accuracy of IMS was lower among malaria cases and patients <5 years but remained equal to- or higher than the accuracy of CRP. IMS is a new diagnostic tool to differentiate causes of AFI. Its high NPV for bacteremia has the potential to improve antibiotic dispensing practices in healthcare facilities with hematology analyzers. Future studies are needed to evaluate whether IMS, combined with malaria diagnostics, may be used to rationalize antimicrobial prescription in malaria endemic areas. ClinicalTrials.gov (NCT02669823) https://clinicaltrials.gov/ct2/show/NCT02669823.

Evaluation of Clinical and Hematological Parameters of Acute Febrile Illness Patients: A Dengue Predictive Model

Objectives: In tropical and subtropical nations dengue is a main public health matter. We try to find to analyze the clinical and hematological factors from a Complete Blood Count (CBC) which differentiate dengue infection. The purpose of the study was to categorize clinical features and hematological parameters and develop predictive model of high fever patients was treated as early marker and possible prognosticator factors of dengue. Methods: Demographic data analysis with variables like gender, place, age and clinical data analysis of clinical parameters with dengue confirmation test have been done develop predictive model factors to differentiate Dengue Infection (DI) from CBC data of Acute Febrile Illness (AFI) patients in Delhi-NCR, Sonepat region from 2015 to 2018. Results: Among 223 patients, 167 were confirmed with 100 primary and 67 secondary DI of maximum number male patients in the age group of 10-30 years from 2015 to 2018 while 56 had negative results. Badhkhalsa, Jakholi, Sewli and Rai were high dengue reported area in Delhi-NCR, Sonepat. There was a statistically significant value (p<0.05) of Total Leukocytes Count (TLC) cells/cmm during AFI phase from 2015 to 2018 using logistic regression and ROC graph. TLC (cells/cmm) had a higher area ± SE value from 2015 to 2018 (0.66 ± 0.07, 0.76 ± 0.10, 0.68 ± 0.07 and 0.79 ± 0.06) respectively which were statistically significant (p<0.05). Dengue diagnosis test of mean value of TLC (<4000 cells/cmm) from 2015 to 2018 were evaluated with a prevalence of dengue disease of 35.09%- 58.06%, sensitivity of 41.03%-100%, specificity of 24.10%-93.10% and accuracy rate of diagnosis evaluation of 62.07%-70.97% were related to danger sign DI in Delhi-NCR, Sonepat area. Conclusion: As per our study we can conclude that due to non-specific clinical features and delayed of confirmation test, among the clinical parameters TLC could be the useful feature for quick finding of DI which is unique, simple, easily available, cost effective approach mainly in rural area.

Determination of cut-off of diagnostic ELISA for Scrub typhus in endemic setup: Central India.

Serology remains the mainstay for diagnosis of scrub typhus. In central India, diagnosis of this neglected emerging zoonotic disease suffers due to lack of standardized region-specific cutoff value and diagnostic test. Henceforth, standardized region-specific cutoff value for diagnostic ELISA play a significant role in initial treatment of patients and to differentiate other febrile diseases in endemic setup. A total of 144 patients of all age groups with acute undifferentiated febrile illness patients, forty healthy controls, dengue and chikungunya positive thirty-five samples in each category, respectively were enrolled in the study and subjected to IgM ELISA (InBioS, International, Inc.). Samples showing OD value more than 0.5 in IgM ELISA, were subjected to nested PCR. Both, receiver operating characteristic (ROC) curve and healthy volunteer samples mean with +3 SD were considered to generate region specific cutoff OD value. A total of 48 patients were diagnosed as cases of scrub typhus through IgM ELISA. Out of 48 samples, 30 were positive by nested PCR. The ROC curve analysis revealed a diagnostic ELISA cutoff value of 0.73 with sensitivity and specificity of 95% and 100%, respectively. The cut off arrived from healthy volunteer is mean OD + 3 SD is 0.72. Considering the significance of scrub typhus diagnosis for treatment and to understand disease dynamics in region wise, the cutoff value of >0.72 for diagnostic ELISA for Madhya Pradesh in central India can be used.

Scrub typhus associated acute kidney injury: An emerging health problem in Odisha, India.

Acute kidney injury associated with scrub typhus is an emerging health problem in the tropics including India. This study intended to find out the incidence, clinical outcome, cytokine response and genotypes of Orientia tsutsugamushi associated with AKI patients in Odisha, a state in eastern India. Acute febrile illness or history of acute fever with various degrees of kidney involvement admitted to SCB Medical College Hospital, Cuttack were included in the study. A detailed demographic characteristics and clinical features were recorded with pre-tested questionnaire at the time of admission. Scrub Typhus was detected by 'IgM ELISA' test (OD > 0.5) and PCR. Routine urine, haematological and biochemical tests were performed. Genotyping of the Orientia tsutsugamushi was done using 56-kDa gene for Orientia species and phylogenetic tree by neighbor-joining method. The plasma level of the IFN-γ (pro-inflammatory cytokine) and IL10 (anti-inflammatory) were measured by commercially available ELISA kit. The statistical analysis was performed using Graph Pad Prism software (version 4). Out of 140 acute febrile illness or history of acute febrile illness patients with AKI admitted to hospital, 32.14% were confirmed to be scrub typhus positive; eschar was seen in 17.8% of them. Of the total scrub typhus positive cases, 24.4% were having multi organ dysfunction. Majority of the AKI patients (60%) were in the "failure" category under RIFLE criteria. The mortality rate was 20.0%. Risk of dialysis requirement and mortality increases with RIFLE classification. "Karp" was the predominant circulating genotype. IFN-γ and IL10 level was high among the scrub typhus associated AKI patients. The study shows a high incidence of scrub typhus associated AKI and high case fatality rate. Hence, emphasis should be given on differential diagnosis. RIFLE classification is applicable with increment risk of dialysis requirement and death. An in-depth study is required to determine the role of O. tsutsugamuchi KARP strain and INF-γ/ IL-10 in disease severity so as to identify a prognostic marker.