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Background Acute undifferentiated fever (AUF) ranges from self-limiting illness to life-threatening infections, such as sepsis, malaria, dengue, leptospirosis and rickettsioses. Similar clinical presentation challenges the clinical management. This study describes risk factors for death in patients hospitalized with AUF in India. Methods Patients aged ≥5 y admitted with fever for 2–14 d without localizing signs were included in a prospective observational study at seven hospitals in India during 2011–2012. Predictors identified by univariate analysis were analyzed by multivariate logistic regression for survival analysis. Results Mortality was 2.4% (37/1521) and 46.9% (15/32) died within 2 d. History of heart disease (p=0.013), steroid use (p=0.011), altered consciousness (p<0.0001), bleeding (p<0.0001), oliguria (p=0.020) and breathlessness (p=0.015) were predictors of death, as were reduced Glasgow coma score (p=0.005), low urinary output (p=0.004), abnormal breathing (p=0.006), abdominal tenderness (p=0.023), leucocytosis (p<0.0001) and thrombocytopenia (p=0.001) at admission. Etiology was identified in 48.6% (18/37) of fatal cases. Conclusions Bleeding, cerebral dysfunction, respiratory failure and oliguria at admission, suggestive of severe organ failure secondary to systemic infection, were predictors of death. Almost half of the patients who died, died shortly after admission, which, together with organ failure, suggests that delay in hospitalization and, consequently, delayed treatment, contribute to death from AUF. [ABSTRACT FROM AUTHOR]

Abstract Background Nested PCR is a commonly used technique in diagnosis of malaria owing to its high sensitivity and specificity. However, it is time-consuming, open to considerable risk of contamination and has low cost-efficiency. Using amplification targets presented in multiple copies, such as rRNA 18S, or mitochondrial targets with an even higher copy number, might increase sensitivity. Methods The sensitivity and specificity of two newly designed Plasmodium genus-specific single-round amplification PCR programmes, based on previously published primers targeting 18S and mitochondrial genome, were compared with a widely used nested 18S PCR. Analyses of dilution series from Plasmodium falciparum reference material were performed, as well as retrospective analyses of 135 blood samples, evaluated by routine microscopy, from 132 fever patients with potential imported malaria. Sequencing of the 220 bp mitochondrial PCR products was performed. Results At the threshold dilution 0.5 parasites/μl, the sensitivity of the mitochondrial PCR was 97% (29/30 parallels), that of the single-round 18S PCR 93% and the reference nested 18S PCR 87%. All three assays detected as low as 0.05 p/μl, though not consistently. In the patient cohort, malaria was diagnosed in 21% (28/135) samples, defined as positive by at least two methods. Both single-round amplification assays identified all malaria positives diagnosed by nested PCR that had sensitivity of 96% (27/28). The mitochondrial PCR detected one additional sample, also positive by microscopy, and was the only method with 100% sensitivity (28/28). The sensitivity and specificity of the mitochondrial PCR were statistically non-inferior to that of the reference nested PCR. Microscopy missed two infections detected by all PCR assays. Sequencing of the genus-specific mitochondrial PCR products revealed different single nucleotide polymorphisms which allowed species identification of the 28 sequences with following distribution; 20 P. falciparum, six Plasmodium vivax, one Plasmodium ovale and one Plasmodium malariae. Conclusions In this study, design of PCR programmes with suitable parameters and optimization resulted in simpler and faster single-round amplification assays. Both sensitivity and specificity of the novel mitochondrial PCR was 100% and proved non-inferior to that of the reference nested PCR. Sequencing of genus-specific mitochondrial PCR products could be used for species determination.

Abstract Background A Giardia outbreak was associated with development of post-infectious functional gastrointestinal disorders (PI-FGID) and chronic fatigue syndrome (PI-CFS). Markers of immune dysfunction have given conflicting results in CFS and FGID patient populations. The aim of this study was to evaluate a wide selection of markers of immune dysfunction in these two co-occurring post-infectious syndromes. Methods 48 patients, reporting chronic fatigue in a questionnaire study, were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS (n=19) and idiopathic chronic fatigue (n=5) and Rome II criteria for FGIDs (n=54). 22 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Results In peripheral blood we found significantly higher CD8 T-cell levels in PI-FGID, and significantly lower NK-cell levels in PI-CFS patients. Severity of abdominal and fatigue symptoms correlated negatively with NK-cell levels. A tendency towards lower T-cell CD26 expression in FGID was seen. Conclusion Patients with PI-CFS and/or PI-FGID 5 years after Giardia lamblia infection showed alterations in NK-cell and CD8-cell populations suggesting a possible immunological abnormality in these conditions. We found no significant changes in other markers examined in this well-defined group of PI-CFS and PI-FGID elicited by a gastrointestinal infection. Controlling for co-morbid conditions is important in evaluation of CFS-biomarkers.

Abstract Background Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. Methods Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients. Results In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients. Conclusions Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.

Abstract Background A high rate of post-infectious fatigue and abdominal symptoms two years after a waterborne outbreak of giardiasis in Bergen, Norway in 2004 has previously been reported. The aim of this report was to identify risk factors associated with such manifestations. Methods All laboratory confirmed cases of giardiasis (n = 1262) during the outbreak in Bergen in 2004 received a postal questionnaire two years after. Degree of post-infectious abdominal symptoms and fatigue, as well as previous abdominal problems, was recorded. In the statistical analyses number of treatment courses, treatment refractory infection, delayed education and sick leave were used as indices of protracted and severe Giardia infection. Age, gender, previous abdominal problems and symptoms during infection were also analysed as possible risk factors. Simple and multiple ordinal logistic regression models were used for the analyses. Results The response rate was 81% (1017/1262), 64% were women and median age was 31 years (range 3-93), compared to 61% women and 30 years (range 2-93) among all 1262 cases. Factors in multiple regression analysis significantly associated with abdominal symptoms two years after infection were: More than one treatment course, treatment refractory infection, delayed education, bloating and female gender. Abdominal problems prior to Giardia infection were not associated with post-infectious abdominal symptoms. More than one treatment course, delayed education, sick leave more than 2 weeks, and malaise at the time of infection, were significantly associated with fatigue in the multiple regression analysis, as were increasing age and previous abdominal problems. Conclusion Protracted and severe giardiasis seemed to be a risk factor for post-infectious fatigue and abdominal symptoms two years after clearing the Giardia infection.