Direct and indirect costs for hospitalized patients with dengue in Southern Sri Lanka.

BACKGROUND: The Southern Province of Sri Lanka is endemic with dengue, with frequent outbreaks and occurrence of severe disease. However, the economic burden of dengue is poorly quantified. Therefore, we conducted a cost analysis to assess the direct and indirect costs associated with hospitalized patients with dengue to households and to the public healthcare system. METHODS: From June 2017-December 2018, we prospectively enrolled children and adults with acute dengue hospitalized at the largest, public tertiary-care (1800 bed) hospital in the Southern Province, Sri Lanka. We administered a structured questionnaire to obtain information regarding direct costs spent by households on medical visits, medications, laboratory testing, and travel for seeking care for the illness. Indirect costs lost by households were estimated by identifying the days of work lost by patients and caregivers and school days lost by children. Direct hospital costs were estimated using gross costing approach and adjusted by multiplying by annual inflation rates in Sri Lankan rupees and converted to US dollars. RESULTS: A total of 1064 patients with laboratory-confirmed dengue were enrolled. The mean age (SD) was 35.9 years (15.6) with male predominance (66.2%). The mean durations of hospitalization for adults and paediatric patients were 3.86 (SD = 1.51) and 4 (SD = 1.32) days, respectively. The per-capita direct cost borne by the healthcare system was 233.76 USD, and was approximately 14 times greater than the per-capita direct cost borne by households (16.29 USD, SD = 14.02). The per-capita average number of loss of working days was 21.51 (SD = 41.71), with mean per-capita loss of income due to loss of work being 303.99 USD (SD = 569.77), accounting for over 70% of average monthly income. On average, 10.88 days (SD = 10.97) of school days were missed due to the dengue episode. School misses were expected to reduce future annual income of affected children by 0.44%. CONCLUSIONS: Dengue requiring hospitalization had a substantial economic burden on the public healthcare system in Sri Lanka and the affected households. These findings emphasize the importance of strengthening dengue control activities and improved use of hospital-based resources for care to reduce the economic impact of dengue in Sri Lanka.

Differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.

Exposure to influenza virus triggers a complex cascade of events in the human host. In order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2), and then had serial peripheral blood samples drawn and tested for the presence of 25 major human cytokines. Nine of 17 (53%) inoculated subjects developed symptomatic influenza infection. Individuals who will go on to become symptomatic demonstrate increased circulating levels of interleukin (IL)-6, IL-8, IL-15, monocyte chemotactic protein (MCP)-1 and interferon (IFN) gamma-induced protein (IP)-10 as early as 12-29 h post-inoculation (during the presymptomatic phase), whereas challenged patients who remain asymptomatic do not. Overall, the immunological pathways of leucocyte recruitment, Toll-like receptor (TLR)-signalling, innate anti-viral immunity and fever production are all over-represented in symptomatic individuals very early in disease, but are also dynamic and evolve continuously over time. Comparison with simultaneous peripheral blood genomics demonstrates that some inflammatory mediators (MCP-1, IP-10, IL-15) are being expressed actively in circulating cells, while others (IL-6, IL-8, IFN-α and IFN-γ) are probable effectors produced locally at the site of infection. Interestingly, asymptomatic exposed subjects are not quiescent either immunologically or genomically, but instead exhibit early and persistent down-regulation of important inflammatory mediators in the periphery. The host inflammatory response to influenza infection is variable but robust, and evolves over time. These results offer critical insight into pathways driving influenza-related symptomatology and offer the potential to contribute to early detection and differentiation of infected hosts.

Repeat endocarditis: analysis of risk factors based on the International Collaboration on Endocarditis - Prospective Cohort Study.

Repeat episodes of infective endocarditis (IE) can occur in patients who survive an initial episode. We analysed risk factors and 1-year mortality of patients with repeat IE. We considered 1874 patients enrolled in the International Collaboration on Endocarditis - Prospective Cohort Study between January 2000 and December 2006 (ICE-PCS) who had definite native or prosthetic valve IE and 1-year follow-up. Multivariable analysis was used to determine risk factors for repeat IE and 1-year mortality. Of 1874 patients, 1783 (95.2%) had single-episode IE and 91 (4.8%) had repeat IE: 74/91 (81%) with new infection and 17/91 (19%) with presumed relapse. On bivariate analysis, repeat IE was associated with haemodialysis (p 0.002), HIV (p 0.009), injection drug use (IDU) (p < 0.001), Staphylococcus aureus IE (p 0.003), healthcare acquisition (p 0.006) and previous IE before ICE enrolment (p 0.001). On adjusted analysis, independent risk factors were haemodialysis (OR, 2.5; 95% CI, 1.2-5.3), IDU (OR, 2.9; 95% CI, 1.6-5.4), previous IE (OR, 2.8; 95% CI, 1.5-5.1) and living in the North American region (OR, 1.9; 95% CI, 1.1-3.4). Patients with repeat IE had higher 1-year mortality than those with single-episode IE (p 0.003). Repeat IE is associated with IDU, previous IE and haemodialysis. Clinicians should be aware of these risk factors in order to recognize patients who are at risk of repeat IE.

Development of necrotizing enterocolitis in premature infants receiving thickened feeds using SimplyThick®.

SimplyThick(®)(ST) has been safely used as a thickener to treat adults who have dysphagia, but the safety of this product has not been studied in premature infants. Xanthan gum is the ingredient in ST that results in thickening and also is an effective laxative. We recently began using ST to treat premature infants with dysphagia and/or gastroesophageal reflux. We describe three cases of premature infants who developed necrotizing enterocolitis (NEC) after they were fed ST. Unlike classic NEC, all three cases presented with late-onset colonic NEC.

Community-associated Clostridium difficile infection: experience of a veteran affairs medical center in southeastern USA.

BACKGROUND: There is increasing recognition of the importance of community-associated Clostridium difficile infection (CA-CDI) despite little being known about its epidemiology. METHODS: We performed routine, active laboratory surveillance for CDI at the Durham Veterans Affairs Medical Center between January and December 2005 and extracted data from the electronic medical record for this investigation. Bivariable analyses were performed using the chi-square test, and continuous variables were compared using two sample t test and Wilcoxon rank sums. RESULTS: We identified 108 CDI cases during the study period; 38 (35%) had onset of disease in the community and, of these, 31 (82%) met the definition for CA-CDI. A comparison of CA- versus healthcare facility-associated (HCFA)-CDI revealed that CA-CDI patients were younger (median age 58 vs. 69 years, respectively; p = 0.01), with the majority being <65 years, but had similar co-morbidities to HCFA-CDI patients. CA-CDI patients were reportedly exposed less frequently to an antimicrobial or a proton pump inhibitor than HCFA-CDI patients, while the latter showed a trend towards a higher 60-day all-cause mortality (3 vs. 17%, respectively; p = 0.06). CONCLUSIONS: CA-CDI is the primary reason for community-onset CDI in our community. Compared to patients with HCFA-CDI, those with CA-CDI were younger, had fewer reported exposures to antimicrobials or PPIs, and had lower mortality. Further study is needed to identify unrecognized risk factors of CDI in the community.

Bartonella sp. bacteremia in patients with neurological and neurocognitive dysfunction.

We detected infection with a Bartonella species (B. henselae or B. vinsonii subsp. berkhoffii) in blood samples from six immunocompetent patients who presented with a chronic neurological or neurocognitive syndrome including seizures, ataxia, memory loss, and/or tremors. Each of these patients had substantial animal contact or recent arthropod exposure as a potential risk factor for Bartonella infection. Additional studies should be performed to clarify the potential role of Bartonella spp. as a cause of chronic neurological and neurocognitive dysfunction.

Survival after lung transplantation of cystic fibrosis patients infected with Burkholderia cepacia complex.

Within the Burkholderia cepacia complex (Bcc), B. cenocepacia portends increased mortality compared with other species. We investigated the impact of Bcc infection on mortality and re-infection following lung transplant (LT). Species designation for isolates from Bcc-infected patients was determined using 16S rDNA and recA gene analyses. Of 75 cystic fibrosis patients undergoing LT from September 1992 to August 2002, 59 had no Bcc and 16 had Bcc (including 7 B. cenocepacia) isolated in the year before LT. Of the latter, 87.5% had Bcc recovered after transplantation, and all retained their pretransplant strains. Survival was 97%, 92%, 76% and 63% for noninfected patients; 89%, 89%, 67% and 56% for patients infected with Bcc species other than B. cenocepacia; and 71%, 29%, 29% and 29% for patients with B. cenocepacia (p = 0.014) at 1 month, 1 year, 3 years and 5 years, respectively. Patients infected with B. cenocepacia before transplant were six times more likely to die within 1 year of transplant than those infected with other Bcc species (p = 0.04) and eight times than noninfected patients (p < 0.00005). Following LT, infection with Bcc species other than B. cenocepacia does not significantly impact 5-year survival whereas infection with B. cenocepacia pretransplant is associated with decreased survival.

Leptotrichia endocarditis: report of two cases from the International Collaboration on Endocarditis (ICE) database and review of previous cases.

Leptotrichia species typically colonize the oral cavity and genitourinary tract. We report the first two cases of endocarditis secondary to L. goodfellowii sp. nov. Both cases were identified using 16S rRNA gene sequencing. Review of the English literature revealed only two other cases of Leptotrichia sp. endocarditis.

Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database.

Infective endocarditis due to coagulase-negative staphylococci is increasingly recognized as a difficult-to-treat disease associated with poor outcome. The aim of this report is to describe the characteristics and outcome of patients with prosthetic valve endocarditis (PVE) due to coagulase-negative staphylococci versus those of patients with PVE due to Staphylococcus aureus and viridans streptococci. Patients were identified through the International Collaboration on Endocarditis Merged Database. A total of 54 cases of coagulase-negative staphylococci PVE, 58 cases of S. aureus PVE, and 63 cases of viridans-streptococci-related PVE were available for analysis. There was no difference between the three groups with respect to the type of valve involved or the rate of embolization. However, heart failure was encountered more frequently with coagulase-negative staphylococci (54%) than with either S. aureus (33%; p=0.03) or viridans streptococci (32%; p=0.02). In addition, valvular abscesses complicated 39% of infections due to coagulase-negative staphylococci compared with 22% of those due to S. aureus (p=0.06) and 6% of those due to viridans streptococci (p<0.001). Mortality was highest in patients with S. aureus and coagulase-negative staphylococcal endocarditis (47 and 36%, respectively; p=0.22) and was considerably lower in patients with viridans streptococcal endocarditis (p=0.002 compared to patients with coagulase-negative staphylococcal endocarditis). The results of this analysis demonstrate the aggressive nature of coagulase-negative staphylococcal PVE and the substantially greater morbidity and mortality associated with this infection compared to PVE caused by other pathogens.

Controlled clinical comparison of the BacT/ALERT FN and the standard anaerobic SN blood culture medium.

To determine the optimal anaerobic companion bottle to pair with the BacT/ALERT (bioMerieux, Durham, N.C.) nonvented aerobic FA (FA) medium for recovery of pathogenic microorganisms from adult patients with bacteremia and fungemia, we compared the BacT/ALERT FN (FN) anaerobic bottle with the standard BacT/ALERT SN (SN) anaerobic bottle. Each bottle, FA, FN, and SN, was filled with 8 to 12 ml of blood. Of 11,498 blood culture sets received in the clinical microbiology laboratories at two university medical centers, 7,945 sets had all three bottles filled adequately and 8,569 had both anaerobic bottles filled adequately. Of 686 clinically important (based on previously published criteria) isolates detected in one or both adequately filled anaerobic bottles, more staphylococci (P < 0.001), including Staphylococcus aureus (P < 0.001); members of the family Enterobacteriaceae (P < 0.001); and all microorganisms combined (P < 0.001) were detected in FN bottles. In contrast, more Pseudomonas aeruginosa isolates (P < 0.01) and yeasts (P < 0.001) were detected in SN bottles. More Bacteroides fragilis group bacteremias were detected only in the FN (six) than in the SN (one) anaerobic bottle (P = not significant). Overall, the mean time to detection was shorter with FN (16.8 h) than with SN (18.2 h). This difference in time to detection was greatest for the B. fragilis group: FN, 28 h, versus SN, 60.0 h. Many of the facultative microorganisms recovered in either FN or SN were also found in the companion FA. When microorganisms found in the companion FA bottle were omitted from the analysis, significantly more staphylococci (P < 0.001), including S. aureus (P < 0.001), and Enterobacteriaceae (P < 0.005) still were detected in FN bottles, whereas there were no significant differences for P. aeruginosa and yeasts, which were found as expected in FA bottles. We conclude that the companion anaerobic FN bottle detects more microorganisms than does the anaerobic SN bottle when used in conjunction with the nonvented aerobic FA bottle in the BacT/ALERT blood culture system.

Mycobacterium bovis peritonitis mimicking ovarian cancer in a young woman.

We describe a 27-year-old woman with peritonitis due to Mycobacterium bovis that initially appeared to be ovarian cancer. Clinicians should include this disease in the differential diagnosis of ovarian cancer and should consider laparoscopic diagnosis in the appropriate epidemiologic setting.

Testis ecdysiotropin, an insect gonadotropin that induces synthesis of ecdysteroid.

Testes of lepidoptera synthesized ecdysteroid in a somewhat different temporal pattern than the prothoracic glands that release ecdysteroid to the hemolymph. Brain extracts from Heliothis virescens and Lymantria dispar induced testes to synthesize ecdysteroid, but did not affect prothoracic glands. The testis ecdysiotropin (LTE) was isolated from L. dispar pupal brains by a series of high-pressure chromatography steps. Its sequence was Ile-Ser-Asp-Phe-Asp-Glu-Tyr-Glu-Pro-Leu-Asn-Asp-Ala-Asp-Asn-Asn-Glu-Val-Leu-Asp-Phe-OH, of molecular mass 2,473 Daltons. The predominant signaling pathway for LTE was via G(i) protein, IP3, diacylglycerol and PKC; a modulating pathway, apparently mediated by an angiotensin II-like peptide, was controlled via G(s) protein, cAMP, and PKA. Testis ecdysteroid caused isolated testis sheaths to also synthesize a growth factor that induced development of the male genital tract. The growth factor appeared to be a glycoprotein similar to vertebrate alpha-1-glycoprotein. A polyclonal antibody to LTE indicated LTE-like peptide in L. dispar brain medial neurosecretory cells, the suboesophageal, and other ganglia, and also in its target organ, the testis sheath. LTE immunoreactivity was also seen in testis sheaths of Rhodnius prolixus. LTE-like immunoactivity was also detected in developing optic lobes, antennae, frontal ganglia, and elongating spermatids of developing L. dispar pupae. This may indicate that LTE has a role in development as well as stimulation of testis ecdysteroid synthesis. Published 2001 Wiley-Liss, Inc.

Marijuana use and social networks in a community outbreak of meningococcal disease.

BACKGROUND: We examined the role of social networks and marijuana smoking in a community outbreak of infections due to Neisseria meningitidis. METHODS: We interviewed all patients and their contacts. Isolates were tested by pulsed field electrophoresis and multilocus enzyme electrophoresis. RESULTS: Nine cases of meningococcal disease occurred in the outbreak; isolates from seven cases with positive cultures were identical. Multiple overlapping social networks were found for case-patients and their contacts. All case-patients were linked by the marijuana-related activities of their contacts. CONCLUSION: Investigation of social networks and marijuana exposure might help identify close contacts of patients with meningococcal disease and help prevent secondary infections.

Meningococcemia in a patient coinfected with hepatitis C virus and HIV.

We describe the first reported case of meningococcemia in a patient coinfected with hepatitis C virus and HIV. Hypocomplementemia secondary to hepatic dysfunction may have enhanced the patient's susceptibility to meningococcal infection.

Coccidioidomycosis in human immunodeficiency virus-infected persons in Arizona, 1994-1997: incidence, risk factors, and prevention.

From 1 January 1995 through 31 June 1997, 153 cases of coccidioidomycosis in human immunodeficiency virus (HIV)-infected persons were identified in Arizona (incidence, 41/1000 persons living with AIDS). A case-control study was conducted to evaluate risk factors for coccidioidomycosis in HIV-infected persons. A case was defined as laboratory-confirmed, incident coccidioidomycosis in a person infected with HIV for > or =3 months, and each case patient had 3 control patients matched by county, age group, sex, HIV/AIDS status, and CD4 lymphocyte count. Multivariable analysis identified black race and a history of oropharyngeal or esophageal candidiasis to be associated with increased risk of coccidioidomycosis; protease inhibitor therapy was associated with a reduced risk. In persons with previous history of oropharyngeal or esophageal candidiasis, having received an azole drug was associated with a reduced risk (odds ratio, 0.4; 95% confidence interval, 0.2-0.9; P=.04). Physicians may need to consider azole chemoprophylaxis for HIV-infected persons who live in areas of endemicity, have CD4 cell counts <200/microL, are black, or have a history of thrush.

Emergency vaccination against epidemic meningitis in Ghana: implications for the control of meningococcal disease in West Africa.

BACKGROUND: Recurrent epidemics of meningococcal disease have been reported throughout the African meningitis belt since description of the disease in 1912. Meningooccal polysaccharide vaccines can effectively prevent disease but the optimum strategy for their use in this setting has been controversial. We used data from an outbreak of meningococcal disease in northern Ghana in 1997 to assess the potential effect of different vaccination strategies. METHODS: We identified all reported cases of meningococcal meningitis and estimated the number of cases and deaths that could have been prevented by vaccination through use of a simple mathematical model. We then assessed the potential effect of different vaccination strategies and the burden of these strategies on the public-health system. FINDINGS: In the three affected regions in northern Ghana there were 18703 cases and 1356 deaths reported between November, 1996, and May, 1997. Vaccination began in the third week of February and continued to April, reaching 72% of the at-risk population and preventing an estimated 23% of cases and 18% of deaths. A strategy of routine childhood and adult immunisation would have prevented 61% of cases had this same rate of vaccine coverage been achieved and maintained before the epidemic. If vaccination had started after the onset of the epidemic in January, as currently advocated by WHO guidelines, a similar proportion (61%) of cases could have been prevented. INTERPRETATION: Prevention of epidemics of meningococal disease in west Africa will be difficult until long-lasting conjugate vaccines capable of interrupting transmission of Neisseria meningitidis can be incorporated into routine infant-immunisation schedules. Until then, the strategy of surveillance and response advocated by WHO is as effective and more practical than a strategy of routine childhood and adult vaccination with currently available polysaccharide vaccines.

PIP: This study assessed the potential effects of different vaccination strategies using data from the 1997 meningococcal outbreak in northern Ghana. Since the description of the disease in 1912, recurrent epidemics of meningococcal disease have been reported throughout the African meningitis belt. The use of meningococcal polysaccharide vaccines has been proven to effectively prevent the disease, although the method of vaccine distribution was disputable. Using a simple mathematical model, meningococcal meningitis cases and deaths, which could have been forestalled by vaccination, were identified, and the effect of developed vaccination strategies on the public health system was analyzed. About 18,703 cases and 1356 deaths were reported in 3 regions of northern Ghana between November 1996 and May 1997. Vaccination was conducted between February and April, which covered 72% of the high-risk population and prevented approximately 23% of cases and 18% of deaths. Routine childhood and adult immunization would have prevented 61% of cases had this same rate of vaccine coverage been achieved and maintained before the epidemic. This study suggests that the prevention of the meningococcal disease epidemic in West Africa would be difficult unless long-lasting conjugate vaccines are incorporated into routine infant immunization schedules. For now, the surveillance and response strategies advocated by the WHO serve as an effective and practical intervention.

Structure-function analysis of Lymantria testis ecdysiotropin: a search for the active core.

A structure-function study was performed on the synthetic 21 residue neuropeptide, Lymantria testis ecdysiotropin (LTE), originally isolated from brains of Lymantria dispar pupae. The peptide induces ecdysteroid synthesis by testis sheaths of various lepidopteran species. LTE, as well as synthetic LTE 1-11, 11-21, and 11-15, stimulated synthesis in larval and pupal testes of Lymantria dispar at concentrations of 10(-9) to 10(-15) M; LTE 16-21 was weakly active, and an elongated LEU-LTE was inhibitory to synthesis at all but extremely low concentrations (10(-15) M). Since the sequence and polarity of residues in LTE 1-11, 11-15, and 11-21 are quite different, several parts of the molecule must activate receptors which initiate the cascade, resulting in ecdysiogenesis in Lepidopteran testes.