Viral Shedding and Transmission Potential of Asymptomatic and Paucisymptomatic Influenza Virus Infections in the Community.

Background: Influenza virus infections are associated with a wide spectrum of disease. However, few studies have investigated in detail the epidemiological and virological characteristics of asymptomatic and mild illness with influenza virus infections. Methods: In a community-based study in Hong Kong from 2008 to 2014, we followed up initially healthy individuals who were household contacts of symptomatic persons with laboratory-confirmed influenza, to identify secondary infections. Information from daily symptom diaries was used to classify infections as symptomatic (≥2 signs/symptoms, including fever ≥37.8°C, headache, myalgia, cough, sore throat, runny nose and sputum), paucisymptomatic (1 symptom only), or asymptomatic (none of these symptoms). We compared the patterns of influenza viral shedding between these groups. Results: We identified 235 virologically confirmed secondary cases of influenza virus infection in the household setting, including 31 (13%) paucisymptomatic and 25 (11%) asymptomatic cases. The duration of viral RNA shedding was shorter and declined more rapidly in paucisymptomatic and asymptomatic than in symptomatic cases. The mean levels of influenza viral RNA shedding in asymptomatic and paucisymptomatic cases were approximately 1-2 log10 copies lower than in symptomatic cases. Conclusions: The presence of influenza viral shedding in patients with influenza who have very few or no symptoms reflects their potential for transmitting the virus to close contacts. These findings suggest that further research is needed to investigate the contribution of persons with asymptomatic or clinically mild influenza virus infections to influenza virus transmission in household, institutional, and community settings.

The Dynamic Relationship Between Clinical Symptomatology and Viral Shedding in Naturally Acquired Seasonal and Pandemic Influenza Virus Infections.

BACKGROUND: Although the pattern of viral shedding over time has been documented in volunteer challenge studies, understanding of the relationship between clinical symptomatology and viral shedding in naturally acquired influenza infections in humans remains limited. METHODS: In a community-based study in Hong Kong from 2008 to 2014, we followed up initially healthy individuals and identified 224 secondary cases of natural influenza virus infection in the household setting. We examined the dynamic relationship between patterns of clinical symptomatology and viral shedding as quantified using reverse transcription polymerase chain reaction and viral culture in 127 cases with a clinical picture of acute respiratory infection. RESULTS: Viral shedding in influenza A virus infections peaked on the first 1-2 days of clinical illness, and decreased gradually to undetectable levels by day 6-7, matching closely with the dynamics of clinical illness. Viral shedding in influenza B virus infections rose up to 2 days prior to symptom onset and persisted for 6-7 days after onset with a bimodal pattern. CONCLUSIONS: Our results suggest that while clinical illness profiles may serve as a proxy for clinical infectiousness in influenza A virus infections, patients may potentially be infectious even before symptom onset or after clinical improvement in influenza B virus infections.

Heterogeneity in viral shedding among individuals with medically attended influenza A virus infection.

Compared with the average transmissibility of human influenza A virus, much less attention has been paid to the potential variability in its transmissibility. We considered viral shedding as a proxy for infectiousness and explored the heterogeneity of infectiousness among patients with medically attended seasonal influenza A virus infection. The analysis revealed that viral shedding is more heterogeneous in children than in adults. The top 20% most infectious children and adults were estimated to be responsible for 89%-96% and 78%-82%, respectively, of the total infectiousness in each age group. Further investigation is required to correlate the substantial variations in viral shedding with heterogeneity in actual transmissibility.

Comparative epidemiology of pandemic and seasonal influenza A in households.

BACKGROUND: There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and cocirculating seasonal influenza A viruses in community settings. METHODS: We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses. RESULTS: Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for the pandemic influenza virus (8%; 95% confidence interval [CI], 3 to 14) and seasonal influenza viruses (9%; 95% CI, 5 to 15). The patterns of viral shedding and the course of illness among index patients were also similar for the pandemic and seasonal influenza viruses. In a subgroup of patients for whom baseline and convalescent serum samples were available, 36% of household contacts who had serologic evidence of pandemic influenza virus infection did not shed detectable virus or report illness. CONCLUSIONS: Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting.

A systematic review and meta-analysis comparing the efficacy and surgical outcomes of total thyroidectomy between harmonic scalpel versus ligasure.

BACKGROUND: Both ultrasonic coagulation (Harmonic Scalpel) (HS) and bipolar coagulation (Ligasure) (LS) are new energy devices commonly used in open thyroidectomy. This systematic review aimed at comparing the efficacy and surgical outcomes of total thyroidectomy (TT) between HS and. LS. METHODS: A systematic review of the literature was performed to identify studies comparing HS and LS. Intraoperative outcomes, surgically related complications, overall morbidity, and hospital stay were evaluated. Meta-analysis was performed using a fixed-effects model. RESULTS: There were 8 studies that matched the selection criteria. Of the 963 patients who underwent TT, 433 (45.0 %) used HS (HS group) while 530 (55.0 %) used LS (LS group). Compared with LS, the HS group had significantly less volume of blood loss by 2.22 ml (95 % CI = 0.26-4.23 ml) (standardized mean difference [SMD] = -0.2, 95 % CI = -0.38 to -0.02) and reduced total operating time by 3.32 minutes (95 % CI = 1.62-5.03 minutes) (SMD = -0.28, 95 % CI = -0.42 to -0.15). There was no significant difference in temporary postoperative hypocalcemia (OR = 1.29, 95 % CI = 0.88-1.90), permanent postoperative hypocalcemia (OR = 1.45, 95 % CI = 0.23-9.26), temporary recurrent laryngeal nerve (RLN) injury (OR = 1.34; 95 % CI = 0.66-2.71), permanent RLN injury (OR = 1.00; 95 % CI = 0.25-4.03), hematoma (OR = 1.00; 95 % CI = 0.3-3.31), overall morbidity (OR = 1.21, 95 % CI = 0.87-1.69), and hospital stay (SMD = -0.03; 95 % CI = -0.07 to 0.01). CONCLUSIONS: Compared with LS, using HS in TT significantly reduced the volume of blood loss and operating time. However, the clinical significance of these findings remained questionable because the overall mean difference appeared small. There was no significant difference in the rate of complications, overall morbidity, and hospital stay between the two devices.

Household transmission of 2009 pandemic influenza A (H1N1): a systematic review and meta-analysis.

BACKGROUND: During the 2009 influenza A (H1N1) pandemic, household transmission studies were implemented to better understand the characteristics of the transmission of the novel virus in a confined setting. METHODS: We conducted a systematic review and meta-analysis to assess and summarize the findings of these studies. We identified 27 articles, around half of which reported studies conducted in May and June 2009. RESULTS: In 13 of the 27 studies (48%) that collected respiratory specimens from household contacts, point estimates of the risk of secondary infection ranged from 3% to 38%, with substantial heterogeneity. Meta-regression analyses revealed that a part of the heterogeneity reflected varying case ascertainment and study designs. The estimates of symptomatic secondary infection risk, based on 20 studies identifying febrile acute respiratory illness among household contacts, also showed substantial variability, with point estimates ranging from 4% to 37%. CONCLUSIONS: Transmission of the 2009 pandemic virus in households appeared to vary among countries and settings, with differences in estimates of the secondary infection risk also partly due to differences in study designs.

Viral shedding and clinical illness in naturally acquired influenza virus infections.

BACKGROUND: Volunteer challenge studies have provided detailed data on viral shedding from the respiratory tract before and through the course of experimental influenza virus infection. There are no comparable quantitative data to our knowledge on naturally acquired infections. METHODS: In a community-based study in Hong Kong in 2008, we followed up initially healthy individuals to quantify trends in viral shedding on the basis of cultures and reverse-transcription polymerase chain reaction (RT-PCR) through the course of illness associated with seasonal influenza A and B virus infection. RESULTS: Trends in symptom scores more closely matched changes in molecular viral loads measured with RT-PCR for influenza A than for influenza B. For influenza A virus infections, the replicating viral loads determined with cultures decreased to undetectable levels earlier after illness onset than did molecular viral loads. Most viral shedding occurred during the first 2-3 days after illness onset, and we estimated that 1%-8% of infectiousness occurs prior to illness onset. Only 14% of infections with detectable shedding at RT-PCR were asymptomatic, and viral shedding was low in these cases. CONCLUSIONS: Our results suggest that "silent spreaders" (ie, individuals who are infectious while asymptomatic or presymptomatic) may be less important in the spread of influenza epidemics than previously thought.

Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1).

BACKGROUND: After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission. METHODS: We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case. RESULTS: Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays. CONCLUSIONS: Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.

Social trust and health seeking behaviours: A longitudinal study of a community-based active tuberculosis case finding program in the Philippines.

INTRODUCTION: Social trust is an important driver of health seeking behaviours and plays a particularly important role for diseases that have a high degree of stigma associated with them, such as tuberculosis (TB). Individuals experiencing poverty also face additional social and financial barriers in accessing care for TB. We examined an active case finding (ACF) initiative embedded in a program targeting those living in poverty (Transform) implemented by International Care Ministries (ICM), a Philippine-based non-governmental organization (NGO), and analyzed how different forms of social trust may affect the initial uptake of ACF. METHODS: Program monitoring data and a cross-sectional survey conducted at the beginning of Transform included six dimensions of social trust: satisfaction with family life, satisfaction with friendships, and level of trust in relatives, neighbours, pastor or religious leader, and local government officials. Amongst individuals suspected of having TB who received referrals post-screening, multilevel modelling examined the effects of social trust on rural health unit (RHU) attendance. RESULTS: Among the subset of 3350 individuals who received TB screening in 51 communities, 889 (26.5%) were symptom positive and required referral to the RHU, but only 24.1% of those who received referrals successfully attended the RHU. Multilevel regression analysis showed that for each unit increase on the Likert scale in baseline level of family satisfaction and level of trust in relatives, the odds of attending an RHU was 1.03 times (95% CI: 0.99, 1.07) and 1.06 times greater (95% CI: 1.00, 1.11), respectively, independent of other factors. CONCLUSION: These results suggest that social trust in family members could play a valuable role in addressing stigma and rejection, both cited as barriers to higher screening rates. It is recommended that ACF programs that target TB, or other diseases that are stigmatized, prioritize trust-building as an important component of their intervention.

Household Transmission of Influenza Virus.

Human influenza viruses cause regular epidemics and occasional pandemics with a substantial public health burden. Household transmission studies have provided valuable information on the dynamics of influenza transmission. We reviewed published studies and found that once one household member is infected with influenza, the risk of infection in a household contact can be up to 38%, and the delay between onset in index and secondary cases is around 3 days. Younger age was associated with higher susceptibility. In the future, household transmission studies will provide information on transmission dynamics, including the correlation of virus shedding and symptoms with transmission, and the correlation of new measures of immunity with protection against infection.

A systematic review and meta-analysis of prophylactic central neck dissection on short-term locoregional recurrence in papillary thyroid carcinoma after total thyroidectomy.

BACKGROUND: Prophylactic central neck dissection (pCND) at the time of total thyroidectomy (TT) remains controversial in clinically node-negative (cN0) papillary thyroid carcinoma (PTC). Despite occult central lymph node metastases being common, it is unclear if removing these metastases initially would reduce future locoregional recurrence (LRR). This systematic review and meta-analysis aimed at comparing the short-term LRR between patients who underwent TT with pCND and those who underwent TT alone. METHODS: A systematic review of the literature was performed to identify studies comparing LRR between patients with PTC who underwent TT + pCND (group A) and those who underwent TT alone (group B). Inclusion criteria were cN0 patients, with each comparative group containing > 10 patients, and with the number of LRR and mean follow-up duration available. The pooled incidence rate ratio (IRR) was used for calculating the LRR rate between the two groups. Other parameters evaluated included postoperative radioiodine (RAI) ablation, surgically related complications, and overall morbidity. Meta-analysis was performed using a fixed-effects model. RESULTS: Fourteen studies matched the selection criteria. Of the 3331 patients, 1592 (47.8%) belonged to group A, while 1739 (52.2%) belonged to group B. Relative to group B, group A was significantly more likely to have postoperative RAI ablation (71.7% vs. 53.1%; odds ratio [OR] = 2.60 [95% confidence interval (CI) = 2.12-3.18]), temporary hypocalcemia (26.0% vs. 10.8%; OR = 2.56 [CI = 2.04-3.21]), and overall morbidity (33.2% vs. 17.7%; OR = 2.12 [CI = 1.75-2.57]). When temporary hypocalcemia was excluded, overall morbidity was similar between the two groups (7.3% vs. 6.8%; OR = 1.07 [CI = 0.78-1.47]). Group A had a significantly lower risk of LRR than group B (4.7% vs. 8.6%; IRR = 0.65 [CI = 0.48-0.86]). CONCLUSIONS: Group A was more likely to have postoperative RAI ablation, temporary hypocalcemia, and overall morbidity than group B. Temporary hypocalcemia was the major surgical morbidity in pCND and, when excluded, the overall morbidity appeared similar between the two groups. Although our meta-analysis would suggest that those who undergo TT + pCND may have a 35% reduction in risk of LRR than those who undergo TT alone in the short term (< 5 years), it remains unclear how much of this risk reduction is related to increased use of RAI ablation and potential selection bias in some of the studies examined.

Seroprevalence of pandemic H1N1 antibody among health care workers in Hong Kong following receipt of monovalent 2009 H1N1 influenza vaccine.

BACKGROUND: Healthcare workers in many countries are recommended to receive influenza vaccine to protect themselves as well as patients. A monovalent H1N1 vaccine became available in Hong Kong in December 2009 and around 10% of local healthcare workers had received the vaccine by February 2010. METHODS: We conducted a cross-sectional study of the prevalence of antibody to pandemic (H1N1) 2009 among HCWs in Hong Kong in February-March 2010 following the first pandemic wave and the pH1N1 vaccination campaign. In this study we focus on the subset of healthcare workers who reported receipt of non-adjuvanted monovalent 2009 H1N1 vaccine (Panenza, Sanofi Pasteur). Sera collected from HCWs were tested for antibody against the pH1N1 virus by hemagglutination inhibition (HI) and viral neutralization (VN) assays. RESULTS: We enrolled 703 HCWs. Among 104 HCWs who reported receipt of pH1N1 vaccine, 54% (95% confidence interval (CI): 44%-63%) had antibody titer ≥1∶40 by HI and 42% (95% CI: 33%-52%) had antibody titer ≥1∶40 by VN. The proportion of HCWs with antibody titer ≥1∶40 by HI and VN significantly decreased with age, and the proportion with antibody titer ≥1∶40 by VN was marginally significantly lower among HCWs who reported prior receipt of 2007-08 seasonal influenza vaccine (odds ratio: 0.43; 95% CI: 0.19-1.00). After adjustment for age, the effect of prior seasonal vaccine receipt was not statistically significant. CONCLUSIONS: Our findings suggest that monovalent H1N1 vaccine may have had suboptimal immunogenicity in HCWs in Hong Kong. Larger studies are required to confirm whether influenza vaccine maintains high efficacy and effectiveness in HCWs.