Dag Hvidsten

RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study

BackgroundPneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries.MethodsFrom July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay.ResultsWe identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (rs= 0.40, P = 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (rs= 0.55, P = 0.0005).ConclusionRespiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.

Respiratory viruses in Nepalese children with and without pneumonia: a case-control study.

Background: The causative role of respiratory viruses detected in upper airway secretions in childhood pneumonia needs further investigation. Objective: To measure the association between infection with respiratory RNA viruses and pneumonia in children. Methods: From March 2006 to July 2007, we conducted a case-control study of 680 pneumonia cases (WHO criteria) and 680 randomly selected, concurrently sampled age-matched controls among children aged 2–35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each child was examined for 7 respiratory viruses using reverse transcription polymerase chain reaction. We calculated the matched odds ratios (MORs) for the detection of the individual viruses from a case compared with a control as measures of pathogenicity using conditional logistic regression. Results: At least 1 virus was recovered in 248 (36.5%) cases and 48 (7.1%) controls. The MOR varied from 2.0 to 13.0; the highest associations were observed for parainfluenza virus type 3 (MOR 13.0; 95% confidence interval [CI] 6.0–28.0), respiratory syncytial virus (MOR 10.7; CI 4.6–24.6), and influenza A (MOR 6.3; CI 1.9–21.4). We observed that the association was lower for children age 2–5 months compared with older children for parainfluenza virus type 3 (P value for interaction 0.002). Conclusions: All of the 7 respiratory viruses were associated with pneumonia, but their pathogenicity varied. Parainfluenza type 3, RSV, and influenza A were most strongly associated with pneumonia.

Clinical Presentation and Severity of Viral Community-acquired Pneumonia in Young Nepalese Children

Background: Most deaths from pneumonia in children <5 years of age occur in developing countries, where information about the clinical impact and severity of viral causes of respiratory infections is limited. Methods: From June 29, 2004 to June 30, 2007 we evaluated 2230 cases of pneumonia (World Health Organization criteria) in children aged 2 to 35 months in Bhaktapur, Nepal. A nasopharyngeal aspirate from each case was examined for 7 respiratory viruses using reverse-transcription polymerase chain reaction. We compared illness duration, severity, and treatment failure between cases positive and negative for the individual viruses in multiple regression models. Results: A total of 2219 cases had a valid polymerase chain reaction result and were included in the analyses. Overall, 46.1% of cases were 2 to 11 months of age. Being infected with respiratory syncytial virus (RSV) was associated with lower chest indrawing (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.42–3.30) and, among infants, oxygen saturation <93% (OR: 1.88; CI: 1.32–2.69). Among the 2088 nonsevere pneumonia cases, those positive for RSV had a longer time to recovery (hazard ratio 0.82; CI 0.75–0.90; P < 0.001) and an increased risk of treatment failure (OR: 1.75; CI: 1.34–2.28; P < 0.001) than the RSV negative cases. Conclusions: Being infected with RSV was associated with a more severe clinical presentation of pneumonia, longer illness duration, and increased risk of treatment failure. The severity of RSV infection was age related, infants being more severely affected.

Chlamydophila pneumoniae diagnostics : importance of methodology in relation to timing of sampling

The diagnostic impact of PCR-based detection was compared to single-serum IgM antibody measurement and IgG antibody seroconversion during an outbreak of Chlamydophila pneumoniae in a military community. Nasopharyngeal swabs for PCR-based detection, and serum, were obtained from 127 conscripts during the outbreak. Serum, drawn many months before the outbreak, provided the baseline antibody status. C. pneumoniae IgM and IgG antibodies were assayed using microimmunofluorescence (MIF), enzyme immunoassay (EIA) and recombinant ELISA (rELISA). Two reference standard tests were applied: (i) C. pneumoniae PCR; and (ii) assay of C. pneumoniae IgM antibodies, defined as positive if >or=2 IgM antibody assays (i.e. rELISA with MIF and/or EIA) were positive. In 33 subjects, of whom two tested negative according to IgM antibody assays and IgG seroconversion, C. pneumoniae DNA was detected by PCR. The sensitivities were 79%, 85%, 88% and 68%, respectively, and the specificities were 86%, 84%, 78% and 93%, respectively, for MIF IgM, EIA IgM, rELISA IgM and PCR. In two subjects, acute infection was diagnosed on the basis of IgG antibody seroconversion alone. The sensitivity of PCR detection was lower than that of any IgM antibody assay. This may be explained by the late sampling, or clearance of the organism following antibiotic treatment. The results of assay evaluation studies are affected not only by the choice of reference standard tests, but also by the timing of sampling for the different test principles used. On the basis of these findings, a combination of nasopharyngeal swabbing for PCR detection and specific single-serum IgM measurement is recommended in cases of acute respiratory C. pneumoniae infection.

Benign meningococcemia with IgG and IgM antimeningococcal antibodies measured by ELISA

Six patients with benign meningococcemia are presented. The clinical picture was typically intermittent fever with chills, skin eruptions, maculopapules (often hemorrhagic) and arthritis/arthralgia in a person in good general condition. Meningococci of serogroup B were isolated from the blood of 3 patients, from the cerebrospinal fluid of 1 patient and from the nasopharynx of the remaining 2 patients. In 4 patients we assayed the levels of IgG and IgM antibodies against meningococcus serogroup B in an enzyme-linked immunosorbent test (ELISA), using whole bacteria as the antigen. All of them had higher antibody levels than the geometric means for healthy controls of both IgG and IgM, except for 1 patient who did not develop IgG antibodies.

Borrelia burgdorferi sensu lato-infected Ixodes ricinus collected from vegetation near the Arctic Circle.

This is the first study to determine the density of questing Ixodes ricinus in northern Norway. It was performed at two sites in Brønnøy, which has been known for its tick permissive habitats for decades and is one of the northernmost habitats with an abundant I. ricinus population in the world. From April to November 2011, all stages of host-seeking I. ricinus were collected from the two sites. The overall prevalence of nymphs infected with Borrelia burgdorferi sensu lato was 21% and that of adult ticks 46%. The rates of the genospecies Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana were similar to findings in most other studies in Scandinavia, with B. afzelii by far the most prevalent at 76%. The high Borrelia-infection prevalence in ticks from Brønnøy may explain the high incidence rate of reported Lyme borreliosis in the municipality.

Blood donor Borrelia burgdorferi sensu lato seroprevalence and history of tick bites at a northern limit of the vector distribution

In order to study the antibody seroprevalence of the causal agent of Lyme borreliosis, Borrelia burgdorferi sensu lato (s.l.), and the history of tick bites at a geographical distribution limit of Ixodes ricinus, we compared healthy blood donors in geographically extreme regions: the borreliosis‐endemic Vestfold County (59°N) and the region of northern Norway. Blood samples were screened using IgG/VlsE ELISA, and positive/borderline samples were confirmed using C6 ELISA and immunoblot assays. Also, donors completed a questionnaire consisting of several items including the places they have lived, and whether they owned any pets. The seroprevalence was 0.48% (5/1048) in northern Norway and 9.25% (48/519) in Vestfold County. Seven donors (of 1048) had experienced a single tick bite in the southern part of Nordland County (65°N) in northern Norway. This first study on B. burgdorferi s.l. antibody seroprevalence and tick bites on humans and pets in northern Norway showed that the seroprevalence of B. burgdorferi s.l. infection and the risk of tick bite in northern Norway are insignificant; the fact that only five positive IgG samples were detected underscores the very low background seroprevalence. These results suggest that so far I. ricinus has not expanded north of the previously established geographical distribution limit.