To the Editors: Rapid influenza diagnostic tests (RIDTs) are often used at point-of-care due to their ease of use and rapidly available results. Most tests are lateral flow immunoassays that detect chromatographic changes if an influenza antigen is present in the respiratory specimen. These tests have high specificity (therefore, a positive is almost certainly a true positive) but low sensitivity (therefore, will often miss true cases).1,2 A newer immunofluorescence assay, Sofia A+B FIA (Quidel, San Diego, CA), demonstrated increased sensitivity but maintained high specificity.3 However, on December 3, 2012, Quidel issued a voluntary recall of certain lots of Sofia A+B because of false positive results.4 In August 2011, we began a prospective cohort study of children aged ≤36 months at Queen Sirikit National Institute of Child Health, the largest pediatric referral hospital in Thailand. Children (equal numbers of high risk and healthy) are followed for 2 years and parents contacted weekly to inquire about whether their child had acute respiratory illness. Ill children came to the hospital and had a combined nasal and throat swab collected and tested for influenza viruses by realtime reverse transcription polymerase chain reaction (rRT-PCR).5 In addition, a separate nasal swab was taken and tested using 1 of 2 RIDTs made by Quidel (QuickVue A+B during August 2011 to January 20, 2013; Sofia A+B during January 21, 2013 to May 2013). Of the 1152 specimens tested with QuickVue A+B, 59 (5.1%) were positive by rRT-PCR. Compared with rRT-PCR, QuickVue A+B had a sensitivity of 55.9% (33/59; 95% confidence interval (CI): 42.4–68.8%) and a specificity of 99.4% (1086/1093; 95% CI: 98.7–99.7%). Seven (0.6%) were false positive on QuickVue A+B. Of the 370 specimens tested with Sofia A+B, 12 (3.2%) were positive by rRT-PCR. Compared with rRT-PCR, Sofia had a sensitivity of 100% (12/12; 95% CI: 73.5–100.0%) and a specificity of 61.2% (219/358; 95% CI: 55.9–66.3%). One-hundred thirty nine (38.8%) were false positive on Sofia. Of the 139 false positives, 123 (88.5%) were influenza B and 16 were influenza A. There was no difference in the time between illness onset and specimen collection date between true and false positives (median days = 2; P = 0.96), nor was there a difference between the prevalence of influenza during the 2 periods (5.1% vs. 3.2%, P = 0.1). Two lots of the Sofia assay were used and both had poor specificity (data not shown). We learned that the assay lots we purchased were made after the recognized problem that led to the recall was corrected. Nevertheless, our data suggest that continuing problems exist. We share these data to alert others using this assay to the risk of false positives. Our findings further support the limitations in using RIDTs for clinical decision making.6 In Thailand, the Clinical Practice Guidelines recommend oseltamivir treatment for 2 groups of patients: (1) patients with complicated or severe influenza (ie, pneumonia, alteration of conscious, loss of appetite or dehydration and symptoms worsening after 48 hours of illness) and (2) patients with a high risk of having severe influenza (ie, pregnancy, obesity or chronic medical conditions). They also state that oseltamivir should also be considered in children <2 years of age or persons >65 years of age. In Thailand, the use of RIDTs is not recommended for deciding on a course of treatment. Further, we caution that newer RIDTs using immunofluorescence may need additional field evaluations. Sonja J. Olsen, PhD Influenza Division Centers for Disease Control and Prevention Atlanta, GA Influenza Program Thailand MOPH – US CDC Collaboration Nonthaburi, Thailand Wanitchaya Kittikraisak, PhD Influenza Program Thailand MOPH – US CDC Collaboration Nonthaburi, Thailand Stefan Fernandez, PhD Armed Forces Research Institute of Medical Sciences Bangkok, Thailand Piyarat Suntarattiwong, MD Tawee Chotpitayasunondh, MD Queen Sirikit National Institute of Child Health Bangkok, Thailand
We compared cord blood antibody titers in unvaccinated pregnant women to those vaccinated with seasonal influenza vaccine during the 2nd and the 3rd trimesters.Pregnant women had cord blood collected at delivery for hemagglutination inhibition assay against vaccine reference viruses: A/California/07/2009 (H1N1)pdm09, A/Switzerland/9715293/2013 (H3N2), and B/Phuket/3073/2013 (Yamagata lineage). Geometric mean titer (GMT) ratios were calculated comparing vaccinated versus unvaccinated pregnant women, and women vaccinated in the 2nd and the 3rd trimesters. Proportions of women achieving defined titers were compared using the χ2 test.Of 307 women, 190 (62%) were unvaccinated. Fifty and 67 were vaccinated during the 2nd and the 3rd trimesters, respectively. Median enrollment age was 29 years (interquartile range 24-34). Sixteen (5%) women had pre-existing conditions, but none were immunocompromised. GMT ratios comparing vaccinated and unvaccinated women were 5.90 (95% confidence interval [CI] 5.06-6.96) for influenza A/California, 5.39 (95% CI 4.18-6.08) for influenza A/Switzerland, and 5.05 (95% CI 4.43-5.85) for influenza B/Phuket. Similarly, the GMT ratios comparing the 3rd and the 2nd trimester vaccinated women were 2.90 (95% CI 2.54-3.39), 2.82 (95% CI 2.56-3.13), and 2.83 (95% CI 2.56-3.14), respectively. The proportions of women with defined titers for the three vaccine reference viruses did not differ between 2nd and 3rd trimester vaccinated women (titers ≥40: 68-92% versus 70-93%; ≥110: 32% versus 33-63%; and ≥330: 4-10% versus 3-21%).Pregnant women vaccinated against influenza had more placental transfer of influenza antibodies to their infants than unvaccinated women. Placental transfer of antibodies was higher among those vaccinated in the 3rd trimester than in the 2nd trimester. There was no difference in the proportions of women achieving antibody titers corresponding to protection against influenza in children. Findings support the current World Health Organization's recommendation that pregnant women may be vaccinated in either 2nd or 3rd trimester of pregnancy.
In Asia, patients increasingly seek tuberculosis (TB) treatment in the private sector; however, few private sector practices follow international TB management guidelines. We conducted a study to measure the frequency and predictors of seeking TB diagnosis in the private sector among 756 HIV-infected TB patients in four Thai provinces during 2005-2006. Of enrolled patients, 97 (13%) first sought care at a private provider and 83 (11%) at a pharmacy. In multivariable analysis, the only factor independently associated with seeking care at a private provider was having a high TB stigma score. Factors independently associated with seeking care at a pharmacy included not knowing that TB can be cured and that TB care can be provided close to home. Patients reported that the most influential factor in choosing a provider was confidentiality (468; 62%). Further research is needed to evaluate whether educating the community about the confidentiality, availability, and success of curing TB at government health facilities can promote prompt utilization of public TB treatment services by HIV-infected patients in Thailand.
Background Each year, an influenza B strain representing only one influenza B lineage is included in the trivalent inactivated influenza vaccine ( IIV 3); a mismatch between the selected lineage and circulating viruses can result in suboptimal vaccine effectiveness. We modeled the added potential public health impact of a quadrivalent inactivated influenza vaccine ( IIV 4) that includes strains from both influenza B lineages compared to IIV 3 on influenza‐associated morbidity and mortality in Thailand. Methods Using data on the incidence of influenza‐associated hospitalizations and deaths, vaccine effectiveness, and vaccine coverage from the 2007–2012 influenza seasons in Thailand, we estimated rates of influenza‐associated outcomes that might be averted using IIV 4 instead of IIV 3. We then applied these rates to national population estimates to calculate averted illnesses, hospitalizations, and deaths for each season. We assumed that the influenza B lineage included in IIV 3 would provide a relative vaccine effectiveness of 75% against the other B lineage. Results Compared to use of IIV 3, use of IIV 4 might have led to an additional reduction ranging from 0·4 to 14·3 influenza‐associated illnesses per 100 000 population/year, <0·1 to 0·5 hospitalizations per 100 000/year, and <0·1 to 0·4 deaths per 1000/year. Based on extrapolation to national population estimates, replacement of IIV 3 with IIV 4 might have averted an additional 267–9784 influenza‐associated illnesses, 9–320 hospitalizations, and 0–3 deaths. Conclusion Compared to use of IIV 3, IIV 4 has the potential to further reduce the burden of influenza‐associated morbidity and mortality in Thailand.
Despite recommendations, few children aged 6-35 months in Thailand receive seasonal influenza vaccination. Using previously estimated incidence and vaccine effectiveness data from the period 2012-2014, we estimate that up to 121 000 medical visits could be prevented each year with 50% coverage and expanded recommendations to children aged <5 years.
A case study from the Katine parish in Uganda where the challenge of accessing antiretroviral drugs is exacerbated by abject poverty in the region. The article highlights the needs of the community members with HIV / AIDS in the region and the response of AMREF (the NGO working in the region) to addressing these issues.
The World Health Organization (WHO) recommends case definitions for influenza surveillance that are also used in public health research, although their performance has not been assessed in many risk groups, including pregnant women in whom influenza may manifest differently. We evaluated the performance of symptom-based definitions to detect influenza in a cohort of pregnant women in India, Peru, and Thailand.
The HIV and multi-drug resistant tuberculosis (MDR-TB) epidemics are closely linked. In Thailand as part of a sentinel surveillance system, we collected data prospectively about pulmonary TB cases treated in public clinics. A subset of HIV-infected TB patients identified through this system had additional data collected for a research study. We conducted multivariate analysis to identify factors associated with MDR-TB. Of 10,428 TB patients, 2,376 (23%) were HIV-infected; 145 (1%) had MDR-TB. Of the MDR-TB cases, 52 (37%) were HIV-infected. Independent risk factors for MDR-TB included age 18-29 years old, male sex, and previous TB treatment, but not HIV infection. Among new patients, having an injection drug use history was a risk factor for MDR-TB. Of 539 HIV-infected TB patients in the research study, MDR-TB was diagnosed in 19 (4%); the only significant risk factors were previous TB treatment and previous hepatitis. In Thailand, HIV is common among MDR-TB patients, but is not an independent risk factor for MDR-TB. Populations at high risk for HIV-young adults, men, injection drug users - should be prioritized for drug susceptibility testing.
Background: We examined SARS-CoV-2 anti-spike 1 IgG antibody levels following COVID-19 vaccination (AstraZeneca [AZ], Sinovac [SV], Pfizer-BioNTech [PZ]) among Thai healthcare providers. Methods: Blood specimens were tested using enzyme-linked immunosorbent assay. We analyzed seven vaccination regimens: a) one dose of AZ or SV, b) two doses of homologous (2AZ, 2SV) or heterologous (1AZ+1PZ) vaccines, and c) three doses of heterologous vaccines (2SV+1AZ, 2SV+1PZ). Differences in antibody levels were assessed using Kruskal-Wallis statistic, Mann-Whitney test, or Wilcoxon matched-pairs signed-rank test. Antibody kinetics were predicted using fractional polynomial regression. Findings: The 563 participants had median age of 39 years; 92% were female; 74% reported no underlying medical condition. Antibody levels peaked at 22-23 days in both 1AZ and 2SV vaccinees and dropped below assay’s cutoff for positive (35·2 binding antibody units/mL [BAU/mL]) in 55 days among 1AZ vaccinees compared to 117 days among 2SV vaccinees. 1AZ+1PZ vaccination regimen was highly immunogenic (median 2,279 BAU/mL) 1-4 weeks post vaccination. 2SV+1PZ vaccinees had significantly higher antibody levels than 2SV+1AZ vaccinees four weeks post vaccination (3,423 vs. 2,105 BAU/mL; p-value<0·01), and during weeks 5-8 (3,656 vs. 1,072 BAU/mL; p-value<0·01). Antibodies peaked at 12-15 days in both 2SV+1PZ and 2SV+1AZ vaccinees, but those of 2SV+1AZ declined more rapidly and dropped below assay’s cutoff in 228 days while those of 2SV+1PZ remained detectable. Interpretation: 1AZ+1PZ, 2SV+1AZ, and 2SV+1PZ vaccinees had substantial IgG levels, suggesting that these individuals likely mounted sufficient anti-S1 IgG antibodies for possible protection against SARS-CoV-2 infection. Funding Information: U.S. Centers for Disease Control and Prevention.Declaration of Interests: All authors have no conflicts of interests or funding to disclose.Ethics Approval Statement: This study was approved by the Institutional Review Boards (IRBs) of PMK; BIDI; PH; RY; Department of Disease Control of the Thai MOPH (Thailand); and Walter Reed Army Institute of Research (USA). The IRB of the U.S. Centers for Disease Control and Prevention (USA) and Mahidol University (Thailand) relied on the determinations of PMK’s and MOPH’s IRBs, respectively. All participants provided written informed consent.
BackgroundWe evaluated molecular-based point-of-care influenza virus detection systems in a laboratory prior to a field evaluation of on-site specimen testing.MethodsThe performance characteristics of 1) insulated isothermal polymerase chain reaction (PCR) on a POCKIT™ device and 2) real-time reverse transcription-PCR (rRT-PCR) on a MyGo Mini™ device were evaluated using human clinical specimens, beta-propiolactone-inactivated influenza viruses, and RNA controls. The rRT-PCR carried out on a CXF-96™ real-time detection system was used as a gold standard for comparison.ResultsBoth systems demonstrated 100% sensitivity and specificity and test results were in 100% agreement with the gold standard. POCKIT™ only correctly identified influenza A (M gene) in clinical specimens due to the unavailability of typing and subtyping reagents for human influenza viruses, while MyGo Mini™ had either a one log higher or the same sensitivity in detecting influenza viruses in clinical specimens compared to the gold standard. For inactivated viruses and/or viral RNA, the analytic sensitivity of POCKIT™ was shown to be comparable to, or more sensitive, than the gold standard. The analytic sensitivity of MyGo Mini™ had mixed results depending on the types and subtypes of influenza viruses.ConclusionsThe performance of the two systems in a laboratory is promising and supports further evaluation in field settings.
