Background Self‐collection of nasal swabs could improve the timeliness of influenza virus detection in older adults. Objectives Measure the acceptability, adequacy, timeliness, and validity of self‐collected nasal swabs among adults > 65 years in Thailand. Methods Our evaluation consisted of two parts: a one‐month study among randomly selected, community‐dwelling older adults to simulate community‐based surveillance for acute respiratory infections ( ARI ); and a clinic study of older adults with ARI to evaluate the sensitivity and specificity of self‐collected nasal swabs for influenza virus infection compared with healthcare worker ( HCW )‐collected nasal and nasopharyngeal swabs. Results In the community study, 24% of participants experienced an ARI during the observation period. All (100%) participants with an ARI self‐collected nasal swabs within 72 hours of symptom onset of which 92% were considered adequate samples. In the clinic study, 45% of patients with ARI presented within 72 hours of symptom onset. The sensitivity of self‐collected nasal swabs for detection of influenza virus infection was 78% (95% CI 40‐97) compared to nasopharyngeal and 88% (95% CI 47‐100) compared to nasal swabs collected by HCW s. Specificity was 100% (95% CI 97‐100) compared to both methods. Self‐collection of nasal swabs was found acceptable by 99% of participants in both studies. Conclusions Self‐collection of nasal swabs was acceptable to older adults in Thailand who were able to take adequate samples. Self‐collection of nasal swabs may improve the timeliness of sample collection but lower sensitivity will need to be considered.
Background Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) for the prevention of malaria has shown promising results in six trials. However, resistance to SP is rising and alternative drug combinations need to be evaluated to better understand the role of treatment versus prophylactic effects. Methods Between March 2004 and March 2008, in an area of western Kenya with year round malaria transmission with high seasonal intensity and high usage of insecticide-treated nets, we conducted a randomized, double-blind placebo-controlled trial with SP plus 3 days of artesunate (SP-AS3), 3 days of amodiaquine-artesunate (AQ3-AS3), or 3 days of short-acting chlorproguanil-dapsone (CD3) administered at routine expanded programme of immunization visits (10 weeks, 14 weeks and 9 months). Principal Findings 1,365 subjects were included in the analysis. The incidence of first or only episode of clinical malaria during the first year of life (primary endpoint) was 0.98 episodes/person-year in the placebo group, 0.74 in the SP-AS3 group, 0.76 in the AQ3-AS3 group, and 0.82 in the CD3 group. The protective efficacy (PE) and 95% confidence intervals against the primary endpoint were: 25.7% (6.3, 41.1); 25.9% (6.8, 41.0); and 16.3% (−5.2, 33.5) in the SP-AS3, AQ3-AS3, and CD3 groups, respectively. The PEs for moderate-to-severe anaemia were: 27.5% (−6.9, 50.8); 23.1% (−11.9, 47.2); and 11.4% (−28.6, 39.0). The duration of the protective effect remained significant for up to 5 to 8 weeks for SP-AS3 and AQ3-AS3. There was no evidence for a sustained beneficial or rebound effect in the second year of life. All regimens were well tolerated. Conclusions These results support the view that IPTi with long-acting regimens provide protection against clinical malaria for up to 8 weeks even in the presence of high ITN coverage, and that the prophylactic rather than the treatment effect of IPTi appears central to its protective efficacy. Trial Registration ClinicalTrials.gov NCT00111163
Abstract Background Detection of malaria parasitaemia in samples that are negative by rapid diagnostic tests (RDTs) requires resource-intensive molecular tools. While pooled testing using a two-step strategy provides a cost-saving alternative to the gold standard of individual sample testing, statistical adjustments are needed to improve accuracy of prevalence estimates for a single step pooled testing strategy. Methods A random sample of 4670 malaria RDT negative dried blood spot samples were selected from a mass testing and treatment trial in Asembo, Gem, and Karemo, western Kenya. Samples were tested for malaria individually and in pools of five, 934 pools, by one-step quantitative polymerase chain reaction (qPCR). Maximum likelihood approaches were used to estimate subpatent parasitaemia (RDT-negative, qPCR-positive) prevalence by pooling, assuming poolwise sensitivity and specificity was either 100% (strategy A) or imperfect (strategy B). To improve and illustrate the practicality of this estimation approach, a validation study was constructed from pools allocated at random into main (734 pools) and validation (200 pools) subsets. Prevalence was estimated using strategies A and B and an inverse-variance weighted estimator and estimates were weighted to account for differential sampling rates by area. Results The prevalence of subpatent parasitaemia was 14.5% (95% CI 13.6–15.3%) by individual qPCR, 9.5% (95% CI (8.5–10.5%) by strategy A, and 13.9% (95% CI 12.6–15.2%) by strategy B. In the validation study, the prevalence by individual qPCR was 13.5% (95% CI 12.4–14.7%) in the main subset, 8.9% (95% CI 7.9–9.9%) by strategy A, 11.4% (95% CI 9.9–12.9%) by strategy B, and 12.8% (95% CI 11.2–14.3%) using inverse-variance weighted estimator from poolwise validation. Pooling, including a 20% validation subset, reduced costs by 52% compared to individual testing. Conclusions Compared to individual testing, a one-step pooled testing strategy with an internal validation subset can provide accurate prevalence estimates of PCR-positivity among RDT-negatives at a lower cost.
Summary Early diagnosis of malaria followed by appropriate treatment can help reduce related morbidity and mortality as well as interrupt transmission. Previous studies of household responses to malaria have tended to focus on endemic areas where the burden of this disease is greatest. With the apparent increasing frequency of epidemics in African highlands, a better understanding of treatment behaviours in areas of unstable transmission may be important to future public health interventions. This study was undertaken following a serious epidemic of malaria in the highlands of south‐western Uganda. Our objectives were to characterize actions taken by both adults and caretakers of children ≤5 years old during their most recent episode of self‐diagnosed malaria, and to identify factors that were associated with prompt treatment at a health facility. A survey of 300 households selected in a 2‐stage cluster sampling procedure produced 453 adult respondents and 133 caretakers of children ≤5 years old. We found that almost 65% of adults and 62% of children who had experienced an episode of malaria in the last year (most during the epidemic) had sought treatment from a health facility first as opposed to self‐treatment. Most of these people had visited the health facility within 1 day of symptom onset. By the end of their malaria episode, over 87% of adults and 80% of children had visited a health facility at least once. Factors associated with prompt presentation at a health facility included severity of illness, household proximity to a health facility, and knowledge of malaria prevention methods. Our results indicate that there is an important role for the formal health care system in mitigating morbidity and mortality and reducing transmission during malaria epidemics in Uganda.
ABSTRACT. The basis for an evidence-based recommendation is a well-conducted systematic review that synthesizes the primary literature relevant to the policy or program question of interest. In 2020, the WHO commissioned 10 systematic reviews of potential interventions in elimination or post-elimination settings to summarize their impact on malaria transmission. This paper describes the general methods used to conduct this series of systematic reviews and notes where individual reviews diverged from the common methodology. The paper also presents lessons learned from conducting the systematic reviews to make similar future efforts more efficient, standardized, and streamlined.
Acute gastroenteritis (AGE) is a leading infectious cause of morbidity worldwide, particularly among children in developing countries. With the decline of rotavirus disease rates following introduction of rotavirus vaccines, the relative importance of norovirus will likely increase. Our objectives in this study were to determine the incidence and clinical profile of norovirus disease in Guatemala.We analyzed data from a population-based surveillance study conducted in Guatemala from 2008 through 2013. Demographic information, clinical data, and stool samples were collected from patients who presented with AGE (≥3 liquid stools within 24 hours that initiated 7 days before presentation). Estimated incidence of hospitalized, outpatient, and total community norovirus disease was calculated using surveillance data and household surveys of healthcare use.We included 999 AGE hospitalizations and 3189 AGE outpatient visits at facilities, of which 164 (16%) and 370 (12%), respectively, were positive for norovirus. Severity of norovirus was milder than of rotavirus. Community incidence of norovirus ranged from 2068 to 4954 per 100000 person-years (py) in children aged<5 years. Children aged <5 years also had higher incidence of norovirus-associated hospitalization (51-105 per 100000 py) compared with patients aged ≥5 years (0-1.6 per 100000 py and 49-80 per 100000 py, respectively).This study highlights the burden of norovirus disease in Guatemala, especially among young children. These data can help prioritize development of control strategies, including the potential use of vaccines, and provide a baseline to evaluate the impact of such interventions.
Physicians play a major role in influencing acceptance and uptake of vaccines. However, little is known about physicians' perspectives on influenza vaccination of pregnant women in Thailand, for whom vaccine coverage is estimated at <1%.In 2013, a self-administered questionnaire on physicians' perceptions, attitudes and practices related to influenza vaccination for pregnant women was distributed to 1,134 hospitals with an antenatal care clinic (ANC) in Thailand. At each hospital, one physician working at the ANC completed the survey. Predictors of routine recommendation of influenza vaccine were analyzed utilizing log-binomial regression.A total of 580 (51%) complete responses were received from physicians practicing at ANCs. A favorable attitude towards vaccination was expressed by 436 (75%) physicians, however only 142 (25%) reported routinely recommending influenza vaccine to pregnant women in their current practice. Physicians were more likely to recommend influenza vaccine routinely when they had more than three years of practice (prevalence ratio [PR] 1.9, 95% CI 1.2-2.3), had treated pregnant women for influenza (PR 1.8, 95% CI 1.3-2.7), perceived the influenza vaccine to be effective (moderate level: PR 1.6, 95% CI 1.1-2.4; high level: PR 1.9, 95% CI 1.3-2.9) and were aware of the Ministry of Public Health's (MOPH) recommendation of influenza vaccination in pregnancy (PR 1.3, 95% CI 1.1-1.7). Vaccine not being available, perception that policy was ambiguous and lack of awareness of MOPH recommendations were the most commonly cited barriers to routine recommendation of influenza vaccine.Despite a national policy to vaccinate pregnant women for influenza, only 25% of Thai physicians working in ANCs routinely recommend vaccination. Strategies are needed to increase vaccine availability and free vaccine services, address clinician concerns over vaccine effectiveness and expand healthcare provider awareness of MOPH recommendations.
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.
Severe malaria has a case fatality rate of 10-20 %; however, few studies have addressed the quality of severe malaria case management. This study evaluated the diagnostic and treatment practices of malaria patients admitted to inpatient health facilities (HF) in Malawi. In July–August 2012, a nationwide, cross-sectional survey of severe malaria management was conducted in 36 HFs selected with equal probability from all eligible public sector HFs in Malawi. Patient records from all admissions during October 2011 and April 2012 (low and high season, respectively) were screened for an admission diagnosis of malaria or prescription of any anti-malarial. Eligible records were stratified by age (< 5 or ≥ 5 years). A maximum of eight records was randomly selected within each age and month stratum. Severe malaria was defined by admission diagnosis or documentation of at least one sign or symptom of severe malaria. Treatment with intravenous (IV) quinine or artesunate was considered correct. Patients without documentation of severe malaria were analysed as uncomplicated malaria patients; treatment with an artemisinin-based combination therapy (ACT) or oral quinine based on malaria test results was considered correct. All analyses accounted for HF level clustering and sampling weights. The analysis included 906 records from 35 HFs. Among these, 42 % (95 % confidence interval [CI] 35–49) had a severe malaria admission diagnosis and 50 % (95 % CI 44–57) had at least one severe malaria sign or symptom documented. Severe malaria patients defined by admission diagnosis (93, 95 % CI 86–99) were more likely to be treated correctly compared to patients defined by a severe sign (82, 95 % CI 75–89) (p < 0.0001). Among uncomplicated malaria patients, 26 % (95 % CI 18–35) were correctly treated and 53 % (95 % CI 42–64) were adequately treated with IV quinine alone or in combination with an ACT or oral quinine. A majority of patients diagnosed with severe malaria received the recommended IV therapy in accordance with national treatment guidelines. However, the inconsistencies between diagnosis of severe malaria and documentation of severe signs and symptoms highlight the need to improve healthcare worker recognition and documentation of severe signs and symptoms.
The escalating level of mosquito resistance to pyrethroid insecticides threatens the effectiveness of insecticide-treated nets (ITNs) for malaria control in Malawi. An evaluation of the effectiveness of ITNs for preventing malaria in children aged 6–59 months old, after 1 year of mass distribution of LLINs was conducted in Machinga District, Malawi, an area of moderate pyrethroid resistance. A facility-based, case–control study among children 6–59 months was conducted in an area of pyrethroid resistance between March and September 2013 in Machinga District. Cases and controls were children with fever who sought care from the same hospital and tested positive and negative, respectively, for malaria parasites by microscopy. A high proportion of both cases (354 of 404 or 87.6 %) and controls (660 of 778 or 84.8 %) slept under an ITN the night before the survey. In univariable logistic regression, older age (24–59 months versus 6–23 months, p < 0.001), sleeping on the floor versus a mattress (p < 0.001), and open versus closed house eaves (p = 0.001) were associated with increased odds of malaria, whilst secondary education of the caretaker, having windows on multiple walls, and being in the least poor wealth quintile (p < 0.001 for each) reduced the odds of malaria; ITN use was not associated with malaria (p = 0.181). In multivariable analysis, older age (p < 0.001) and secondary education of the caregiver (p = 0.011) were the only factors significantly associated with malaria. This study did not find a significant personal protective effect of ITNs. However, high use of ITNs in the community and recent findings of lower malaria incidence in ITN users compared to bed net non-users from a cohort study in the same area suggest that ITNs provide community protection to both users and non-users alike in this area.
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