Cause Of Acute Febrile Illness Research Articles

Epidemiology of Zika Virus Infection.

Long known to be endemic in Africa and Southeast Asia and a rare cause of acute febrile illness, Zika virus (ZIKAV) arose from obscurity when an Asian genotype ZIKAV caused an outbreak of mild febrile illness in 2007 in Yap State, Federated States of Micronesia. Subsequent viral spread in the Pacific led to a large outbreak in French Polynesia commencing in 2013. After its recognition in the Americas through March 2017, the Pan American Health Organization has received reports of >750000 suspected and laboratory-confirmed cases of autochthonous ZIKAV transmission. Outbreaks in most countries in the Americas peaked in early to mid-2016. Increased surveillance in several Southeast Asian counties has led to increased case recognition, including an outbreak in Singapore, and the first reports of birth defects linked to ZIKAV in the region. As of April 2017, the World Health Organization reported 84 countries or territories with current or previous ZIKAV transmission.

Emerging and reemerging arboviruses: A new threat in Eastern Peru.

BackgroundArboviral diseases are one of the most common causes of acute febrile illness (AFI) and a significant health problem in South America. In Peru, laboratory etiologic identification of these infections occurs in less than 50% of cases, leading to underdiagnoses of important emerging arboviruses.AimTo assess the prevalence of the Dengue (DENV), Oropouche (OROV), Chikungunya (CHIKV), Mayaro (MAYV) and Zika (ZIKV) viruses in patients with acute febrile illness from Puerto Maldonado (Peru).MethodologySerum samples were obtained from patients with AFI during January 2016 to March 2016. A total of 139 specimens were analyzed for the presence of DENV, OROV, CHIKV, MAYV, and ZIKV using polymerase chain reaction (PCR).ResultsCHIKV in 9.4% and OROV in 8.6% were the most prevalent arboviruses, followed by DENV and ZIKV, with a prevalence of 6.5% and 5%, respectively. Among all patients, the most common symptoms accompanying fever were headaches 79.9%, muscle pain 65.5% and joint pain 63.3%.ConclusionsDuring this short 3-month period, 4 arboviruses were detected by PCR, CHIKV and OROV being the most common arboviruses in Puerto Maldonado (Peru). Thus, it is crucial to include OROV detection in the national health surveillance. Furthermore, the etiologic clinical diagnosis of arboviral infections is not possible due to the low specificity of symptoms; therefore an increase of cases confirmed by molecular diagnostic methods will enhance arboviral surveillance in Peru.

Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012-2015.

Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1–4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1–4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3–5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.

Epididymo: Orchitis in an Adult with Scrub Typhus

Introduction: Scrub typhus is a re-emerging Rickettsial infection presenting with protean manifestations and increasingly reported from all over the country. It is an important cause of acute febrile illness. Case Report: A middle aged adult male presented with complaints of fever, abdominal pain and pain in the testes of about two weeks duration. On examination patient was toxic, icteric, had inguinal and cervical lymphadenopathy, hepatosplenomegaly and unilateral tender testes and epididymis. All common causes of FUO (viz) Malaria, Typhoid fever; Dengue and Brucellosis were ruled out by laboratory tests. Serology for Scrub typhus was positive. The patient responded in 24 hours to Doxycycline thus clinching the diagnosis. Conclusion: This case is reported because of the unusual complication of epididymo orchitis in an adult due to Scrub typhus.

Reducing Uncertainty for Acute Febrile Illness in Resource-Limited Settings: The Current Diagnostic Landscape.

AbstractDiagnosing the cause of acute febrile illness in resource-limited settings is important-to give the correct antimicrobials to patients who need them, to prevent unnecessary antimicrobial use, to detect emerging infectious diseases early, and to guide vaccine deployment. A variety of approaches are yielding more rapid and accurate tests that can detect more pathogens in a wider variety of settings. After decades of slow progress in diagnostics for acute febrile illness in resource-limited settings, a wave of converging advancements will enable clinicians in resource-limited settings to reduce uncertainty for the diagnosis of acute febrile illness.

Scrub Typhus Complicated by Pneumonia and Acute Kidney Injury: Still an Underecognized Scenario in West Bengal

Scrub typhus is an emerging and remerging disease in India and increasingly important cause of acute febrile illness. It is usually complicated by various organ dysfunctions, and is diagnosed by serology. We are reporting a case of 34 years old man resident of West Bengal presented to us with complaints of fever for 7 days with features of pneumonitis and Acute Kidney Injury (AKI). He received doxycyline after positive serology of IgM Scrub typhus, and responded very well. In tropical region any short duration fever with pneumonia, AKI with leukocytosis scrub typhus should be kept in differential as it is a fairly treatable and significantly under diagnosed condition.

Emergence of Epidemic Dengue-1 Virus in the Southern Province of Sri Lanka.

BackgroundDengue is a frequent cause of acute febrile illness with an expanding global distribution. Since the 1960s, dengue in Sri Lanka has been documented primarily along the heavily urbanized western coast with periodic shifting of serotypes. Outbreaks from 2005–2008 were attributed to a new clade of DENV-3 and more recently to a newly introduced genotype of DENV-1. In 2007, we conducted etiologic surveillance of acute febrile illness in the Southern Province and confirmed dengue in only 6.3% of febrile patients, with no cases of DENV-1 identified. To re-evaluate the importance of dengue as an etiology of acute febrile illness in this region, we renewed fever surveillance in the Southern Province to newly identify and characterize dengue.Methodology/Principal FindingsA cross-sectional surveillance study was conducted at the largest tertiary care hospital in the Southern Province from 2012–2013. A total of 976 patients hospitalized with acute undifferentiated fever were enrolled, with 64.3% male and 31.4% children. Convalescent blood samples were collected from 877 (89.6%). Dengue virus isolation, dengue RT-PCR, and paired IgG ELISA were performed. Acute dengue was confirmed as the etiology for 388 (39.8%) of 976 hospitalizations, with most cases (291, 75.0%) confirmed virologically and by multiple methods. Among 351 cases of virologically confirmed dengue, 320 (91.2%) were due to DENV-1. Acute dengue was associated with self-reported rural residence, travel, and months having greatest rainfall. Sequencing of selected dengue viruses revealed that sequences were most closely related to those described from China and Southeast Asia, not nearby India.Conclusions/SignificanceWe describe the first epidemic of DENV-1 in the Southern Province of Sri Lanka in a population known to be susceptible to this serotype because of prior study. Dengue accounted for 40% of acute febrile illnesses in the current study. The emergence of DENV-1 as the foremost serotype in this densely populated but agrarian population highlights the changing epidemiology of dengue and the need for continued surveillance and prevention.

Advances in diagnosis, treatment, and prevention of invasive Salmonella infections.

Typhoidal and nontyphoidal Salmonella enterica serotypes are among the most common bacterial causes of acute febrile illnesses in the developing world. In this review, we discuss new advances in understanding of the burden, diagnostic approaches, treatment and vaccines for invasive Salmonella infections. Recent estimates of the global burden of typhoidal and nontyphoidal Salmonella not only affirm the importance of these infections but also highlight the paucity of systematic incidence data from many regions. New data from Africa indicate that typhoidal Salmonella may be more common than previously considered. Novel diagnostic techniques for Salmonella include new serologic, molecular and metabolomic approaches, but blood culture - although slow and insensitive - remains the primary means of establishing a diagnosis. Antibiotic resistance, particularly to fluoroquinolones, continues to emerge and threatens to undermine treatment success for these infections. New vaccines for typhoid, including conjugate vaccines with longer duration of immunity than prior vaccines, represent a promising tool for prevention of enteric fever. Invasive Salmonella infections are a major cause of morbidity and mortality worldwide. Increasing antibiotic resistance in Salmonella is concerning, and empiric oral options are being rapidly eroded. Where new effective antimicrobials are lacking, developments in vaccines offer hope for reducing the burden of Salmonella infections globally.

Concurrent malaria and arbovirus infections in Kedougou, southeastern Senegal.

BackgroundMalaria is one of the leading causes of acute febrile illness (AFI) in Africa. With the advent of malaria rapid diagnostic tests, misdiagnosis and co-morbidity with other diseases has been highlighted by an increasing number of studies. Although arboviral infections and malaria are both vector-borne diseases and often have an overlapping geographic distribution in sub-Saharan Africa, information about their incidence rates and concurrent infections is scarce.MethodsFrom July 2009 to March 2013 patients from seven healthcare facilities of the Kedougou region presenting with AFI were enrolled and tested for malaria and arboviral infections, i.e., yellow fever (YFV), West Nile (WNV), dengue (DENV), chikungunya (CHIKV), Crimean Congo haemorrhagic fever (CCHFV), Zika (ZIKV), and Rift Valley fever viruses (RVFV). Malaria parasite infections were investigated using thick blood smear (TBS) and rapid diagnostics tests (RDT) while arbovirus infections were tested by IgM antibody detection (ELISA) and RT-PCR assays. Data analysis of single or concurrent malaria and arbovirus was performed using R software.ResultsA total of 13,845 patients, including 7387 with malaria and 41 with acute arbovirus infections (12 YFV, nine ZIKV, 16 CHIKV, three DENV, and one RVFV) were enrolled. Among the arbovirus-infected patients, 48.7 % (20/41) were co-infected with malaria parasites at the following frequencies: CHIKV 18.7 % (3/16), YFV 58.3 % (7/12), ZIKV 88.9 % (8/9), DENV 33.3 % (1/3), and RVF 100 % (1/1). Fever ≥40 °C was the only sign or symptom significantly associated with dual malaria parasite/arbovirus infection.ConclusionsConcurrent malaria parasite and arbovirus infections were detected in the Kedougou region from 2009 to 2013 and need to be further documented, including among asymptomatic individuals, to assess its epidemiological and clinical impact.

Scrub Typhus and Leptospirosis: The fallacy of Diagnosing with IgM Enzyme Linked Immunosorbant Assay

Introduction: Leptospirosis and scrub typhus are important causes of acute febrile illness in India. IgM Enzyme Linked Immunosorbant Assay (ELISA) is the most common diagnostic modality used for their diagnosis. The common epidemiology of both the diseases creates an opportunity of dual infections with these diseases. Therefore, the objective of the study was to detect and evaluate the cases of serological and molecular dual infections. Methodology: A cross sectional diagnostic study from October 2013 to October 2015 was conducted on 258 patients with acute febrile illness. All the samples were subjected to IgM ELISA for scrub typhus and leptospirosis. The samples that were positive for both scrub typhus and leptospirosis were subjected to serological tests for other infections. They were also subjected to PCR assays to find out the cases of molecular dual infections. Results: A total of twenty serum samples were positive by IgM ELISA for leptospirosis while thirty five serum samples were positive by IgM ELISA for scrub typhus. Among these, ten samples were positive for both the serological tests. These dual positives were additionally positive by serology for some other infections [Dengue (n = 2), Mycoplasma pneumoniae (n = 1), Malaria (n = 1), Chlamydia pneumoniae (n = 6), Typhoid (n = 2) and Legionella pneumophila (n = 1)]. Only one case of molecular dual infection was confirmed. Conclusion: The possibility of serological co-infections should be investigated in endemic areas. In a case of serological dual infection, since there are high chances of serological cross reactivity, molecular confirmation should be sought for. The choice of therapy in inconclusive cases should include those drugs that cover for both the infections.

Serological Evidence of Scrub Typhus among Cases of PUO in the Kashmir Valley- A Hospital Based Study.

Rickettsial infections are being increasingly recognized as a cause of acute febrile illnesses and should be considered a distinct possibility in patients presenting with suggestive clinical features. Their diagnosis remains a challenge in a country like ours where tests like immunofluorescence assay cannot be routinely done. Results of serological tests, when correlated with patients clinical profile can aid in the timely diagnosis of scrub typhus. To find out the extent to which scrub typhus contributes to Pyrexia of Unknown Origin (PUO) in patients admitted to or attending the OPD of our hospital using simple tests like Weil-Felix Agglutination Test (WFT) and Enzyme Linked Immunosorbent Assay (ELISA). A cross-sectional study was carried out in the Department of Microbiology, Government Medical College and Hospital, Srinagar, over a period of eight months (1(st) March to 31(st) October 2015). Serum samples from patients suffering from Pyrexia of Unknown Origin (PUO) were processed for the detection of Scrub typhus. A total of 162 samples were included in the study. These were subjected to WFT using OX-K strain. The serum samples were diluted 1/20 to 1/640 and a titre of ≥ 1:160 was considered as positive. The samples were also tested for IgM and IgG antibodies for scrub typhus by ELISA and tube agglutination test was done to detect typhoid fever and brucellosis. Of the 162 serum samples tested 22.8% tested positive scrub typhus by WFT. IgM ELISA and IgG was positive in 8 (4.9%) and 15 (9.3%) samples respectively. Sensitivity, specificity, positive and negative predictive values of WFT; taking IgM ELISA as a reference standard were 75%, 79.9%, 16.2% and 98.4% respectively. Scrub typhus is prevalent in our state and the results of WFT supplemented by those of ELISA can aid in its diagnosis. However the results of these tests should always be regarded in light of the clinical condition of the patient.

Hemothorax in scrub typhus: A rare clinical manifestation

Scrub typhus is one of the most common causes of acute febrile illness in South India. The clinical features vary from mild illness to severe complications such as gastrointestinal bleed, acute respiratory distress syndrome, meningoencephalitis, and acute kidney injury. The pathological findings are characterized by vasculitis of small vessels of the involved organs. We report probably the first case of scrub typhus-related hemothorax in a 72-year-old diabetic male who presented with acute febrile illness with shortness of breath and acute kidney injury. The patient improved with azithromycin and hemodialysis.

The impact of HIV on presentation and outcome of bacterial sepsis and other causes of acute febrile illness in Gabon.

PurposeHIV, bacterial sepsis, malaria, and tuberculosis are important causes of disease in Africa. We aimed to determine the impact of HIV on the presentation, causes and outcome of bacterial sepsis and other acute febrile illnesses in Gabon, Central Africa.MethodsWe performed a prospective observational study in new adult admissions with fever or hypothermia (≥38 or <36 °C). Blood cultures, as well as HIV and malaria testing were performed in all patients.ResultsWe enrolled 382 patients, including 77 (20.2 %) with HIV infection. Malaria was the most frequent diagnosis (n = 130, 34 %), and was associated with a more severe presentation in HIV patients. Sepsis was also common (n = 107, 28 %), including 29 (7.6 %) patients with culture confirmed bacterial bloodstream infection. Bacterial bloodstream infections were more frequent in HIV patients, in particular with S. pneumoniae. Tuberculosis was observed in 29 (7.6 %) patients, and was also more common in HIV patients. The majority of HIV patients was newly diagnosed, and only 15 (19.5 %) were using combination antiretroviral therapy.ConclusionsOur findings illustrate the impact of HIV co-infection on the burden of sepsis, malaria and tuberculosis in Gabon, as well as the need to scale up HIV counseling, testing and treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s15010-015-0753-2) contains supplementary material, which is available to authorized users.

Common Infectious Etiologies of Acute Febrile Illness in a Remote Geographical Location: Could Scrub Typhus be the Most Common Cause?

Background: Disease burden of acute febrile illness due to infectious etiologies is under reported in various parts of India including Sikkim due to lack of laboratory confirmation. Undifferentiated febrile illnesses common in tropical areas of Asia are dengue, chikungunya, malaria, leptospirosis, enteric fever, chikungunya, rickettsia, Japanese encephalitis and scrub typhus. Aims: This study was conducted to determine various infectious etiologies of acute febrile illness with their clinical presentations, complications and mortality with special emphasis to scrub typhus. Setting and Design: This was a cross-sectional study and 205 patients including paediatric patients admitted with acute febrile illness were evaluated. Materials and Methods: A detailed history was taken and complete physical examination was done in all patients. Basic laboratory tests were done in all cases along with confirmatory tests. Results: In our study the most common cause of acute febrile illness was found to be scrub typhus

Scrub Typhus Seroprevalence in Healthy Indian Population.

Scrub typhus, a zoonosis caused by Orientia tsutsugamushi, is an important cause of acute febrile illness in India. This preliminary study determines the seroprevalence of scrub typhus in healthy Indian adults by measuring IgM and IgG antibodies to scrub typhus by ELISA in 100 healthy blood donors. Our study demonstrates a 15% seroprevalence of scrub typhus in adults. Further studies are needed to confirm these findings especially in children.

Multiplex PCR analysis of clusters of unexplained viral respiratory tract infection in Cambodia.

BackgroundFevers of unknown origin constitute a substantial disease burden in Southeast Asia. In majority of the cases, the cause of acute febrile illness is not identified.MethodsWe used MassTag PCR, a multiplex assay platform, to test for the presence of 15 viral respiratory agents from 85 patients with unexplained respiratory illness representing six disease clusters that occurred in Cambodia between 2009 and 2012.ResultsWe detected a virus in 37 (44%) of the cases. Human rhinovirus, the virus detected most frequently, was found in both children and adults. The viruses most frequently detected in children and adults, respectively, were respiratory syncytial virus and enterovirus 68. Sequence analysis indicated that two distinct clades of enterovirus 68 were circulating during this time period.ConclusionsThis is the first report of enterovirus 68 in Cambodia and contributes to the appreciation of this virus as an important respiratory pathogen.

Dengue and Chikungunya fever among viral diseases in outpatient febrile children in Kilosa district hospital, Tanzania.

IntroductionViral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria.MethodsA cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2–13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used.ResultsA total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35–3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus.ConclusionOur results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended.

Investigating an outbreak of acute fever in Chuuk, Federated States of Micronesia.

In September 2012, there was an unexpected increase of acute febrile illness (AFI) in Chuuk State of the Federated States of Micronesia. At the same time, dengue outbreaks were occurring in two of the Federated States of Micronesia's other three states. The cause of AFI was suspected to be dengue; however, by the end of October, only one of 39 samples was positive for dengue. The objective of the investigation was to establish the cause of the outbreak. A line list was created and data analysed by time, place, person and clinical features. Reported symptoms were compared with the published symptoms of several diagnoses and laboratory testing undertaken. Of the 168 suspected cases, 62% were less than 20 years of age and 60% were male. The clinical features of the cases were not typical for dengue but suggestive of respiratory illness. Nasopharyngeal swabs were subsequently collected and found to be positive for influenza. Public health measures were undertaken and the AFI returned to expected levels. Clinical diagnosis of acute febrile illness (AFI) can often be difficult and misleading. This can mean that opportunities for preventive measures early on in an outbreak are missed. In any outbreak, descriptive epidemiological analyses are valuable in helping to ascertain the cause of the outbreak.

Serological evidence of flaviviruses infection among acute febrile illness patients in Afghanistan.

Current published reports on the causative agents of acute febrile illness (AFI) in Afghanistan are scarce, and the burden of disease due to flaviviruses is unknown. A hospital-based surveillance study for AFI was established in 2008 through 2010 to determine the seroepidemiology of West Nile virus (WNV), tick-borne encephalitis virus (TBEV) and dengue viruses (DENV) using commercial ELISA kits. Due to major logistical challenges, only acute sera were collected. Serological analysis for IgG were as follows: WNV 30.4% (277/913); TBEV 23.4% (214/913); DENV 19.7% (180/913). Single positive IgG reactions for WNV, TBEV and DENV were noted in 11% (100/913), 7.2% (66/913), and 5% (47/913), respectively. Reactivity for all three screened flaviviruses was detected in 44.5% (406/913) of sera. IgM positivity was uncommon, with only 0.5% (5/913), 2.2% (20/913) and 2.6% (8/312) of samples positive for WNV, TBEV, and DENV, respectively. Serological findings were confirmed in random positive samples by neutralization assay. These serological results suggest circulation of WNV, TBEV, and DENV within Afghanistan, with evidence of current or prior infection noted in a significant proportion of patients seeking care for AFI. Obtaining additional information on the prevalence of these and other causes of AFI is paramount for improving the distribution of available limited syndromic treatment and improving the existing health protection policy in Afghanistan.

Borrelia crocidurae infection in acutely febrile patients, Senegal.

As malaria cases in Africa decline, other causes of acute febrile illness are being explored. To determine incidence of Borrelia crocidurae infection during June 2010–October 2011, we collected 1,566 blood specimens from febrile patients in Senegal. Incidence was high (7.3%). New treatment strategies, possibly doxycycline, might be indicated for febrile patients.