Global public health intelligence: World Health Organization operational practices.

Early warning and response are key to tackle emerging and acute public health risks globally. Therefore, the World Health Organization (WHO) has implemented a robust approach to public health intelligence (PHI) for the global detection, verification and risk assessment of acute public health threats. WHO's PHI operations are underpinned by the International Health Regulations (2005), which require that countries strengthen surveillance efforts, and assess, notify and verify events that may constitute a public health emergency of international concern (PHEIC). PHI activities at WHO are conducted systematically at WHO's headquarters and all six regional offices continuously, throughout every day of the year. We describe four interlinked steps; detection, verification, risk assessment, and reporting and dissemination. For PHI operations, a diverse and interdisciplinary workforce is needed. Overall, PHI is a key feature of the global health architecture and will only become more prominent as the world faces increasing public health threats.

Performance and utility of more highly sensitive malaria rapid diagnostic tests.

BACKGROUND: A new more highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium falciparum malaria (Alere™/Abbott Malaria Ag P.f RDT [05FK140], now called NxTek™ Eliminate Malaria Ag Pf) was launched in 2017. The test has already been used in many research studies in a wide range of geographies and use cases. METHODS: In this study, we collate all published and available unpublished studies that use the HS-RDT and assess its performance in (i) prevalence surveys, (ii) clinical diagnosis, (iii) screening pregnant women, and (iv) active case detection. Two individual-level data sets from asymptomatic populations are used to fit logistic regression models to estimate the probability of HS-RDT positivity based on histidine-rich protein 2 (HRP2) concentration and parasite density. The performance of the HS-RDT in prevalence surveys is estimated by calculating the sensitivity and positive proportion in comparison to polymerase chain reaction (PCR) and conventional malaria RDTs. RESULTS: We find that across 18 studies, in prevalence surveys, the mean sensitivity of the HS-RDT is estimated to be 56.1% (95% confidence interval [CI] 46.9-65.4%) compared to 44.3% (95% CI 32.6-56.0%) for a conventional RDT (co-RDT) when using nucleic acid amplification techniques as the reference standard. In studies where prevalence was estimated using both the HS-RDT and a co-RDT, we found that prevalence was on average 46% higher using a HS-RDT compared to a co-RDT. For use in clinical diagnosis and screening pregnant women, the HS-RDT was not significantly more sensitive than a co-RDT. CONCLUSIONS: Overall, the evidence presented here suggests that the HS-RDT is more sensitive in asymptomatic populations and could provide a marginal improvement in clinical diagnosis and screening pregnant women. Although the HS-RDT has limited temperature stability and shelf-life claims compared to co-RDTs, there is no evidence to suggest, given this test has the same cost as current RDTs, it would have any negative impacts in terms of malaria misdiagnosis if it were widely used in all four population groups explored here.

Clinical and hospitalisation predictors of COVID-19 in the first month of the pandemic, Portugal.

COVID-19 mainly presents as a respiratory disease with flu-like symptoms, however, recent findings suggest that non-respiratory symptoms can occur early in the infection and cluster together in different groups in different regions. We collected surveillance data among COVID-19 suspected cases tested in mainland Portugal during the first wave of the pandemic, March-April 2020. A multivariable logistic-regression analysis was performed to ascertain the effects of age, sex, prior medical condition and symptoms on the likelihood of testing positive and hospitalisation. Of 25,926 COVID-19 suspected cases included in this study, 5,298 (20%) tested positive. Symptoms were grouped into ten clusters, of which two main ones: one with cough and fever and another with the remainder. There was a higher odds of a positive test with increasing age, myalgia and headache. The odds of being hospitalised increased with age, presence of fever, dyspnoea, or having a prior medical condition although these results varied by region. Presence of cough and other respiratory symptoms did not predict COVID-19 compared to non-COVID respiratory disease patients in any region. Dyspnoea was a strong determinant of hospitalisation, as well as fever and the presence of a prior medical condition, whereas these results varied by region.

A longitudinal study on symptom duration and 60-day clinical course in non-hospitalised COVID-19 cases in Berlin, Germany, March to May, 2020.

BackgroundDetailed information on symptom duration and temporal course of patients with mild COVID-19 was scarce at the beginning of the COVID-19 pandemic.AimWe aimed to determine the longitudinal course of clinical symptoms in non-hospitalised COVID-19 patients in Berlin, Germany.MethodsBetween March and May 2020, 102 confirmed COVID-19 cases in home isolation notified in Berlin, Germany, were sampled using total population sampling. Data on 25 symptoms were collected during telephone consultations (a maximum of four consultations) with each patient. We collected information on prevalence and duration of symptoms for each day of the first 2 weeks after symptom onset and for day 30 and 60 after symptom onset.ResultsMedian age was 35 years (range 18-74), 57% (58/102) were female, and 37% (38/102) reported having comorbidities. During the first 2 weeks, most common symptoms were malaise (94%, 92/98), headache (71%, 70/98), and rhinitis (69%, 68/98). Malaise was present for a median of 11 days (IQR 7-14 days) with 35% (34/98) of cases still reporting malaise on day 14. Headache and muscle pain mostly occurred during the first week, whereas dysosmia and dysgeusia mostly occurred during the second week. Symptoms persisted in 41% (39/95) and 20% (18/88) of patients on day 30 and 60, respectively.ConclusionOur study shows that a significant proportion of non-hospitalised COVID-19 cases endured symptoms for at least 2 months. Further research is needed to assess the frequency of long-term adverse health effects in non-hospitalised COVID-19 patients.

Severe Acute Respiratory Syndrome Coronavirus 2 Outbreak Related to a Nightclub, Germany, 2020.

We report an outbreak of coronavirus disease with 74 cases related to a nightclub in Germany in March 2020. Staff members were particularly affected (attack rate 56%) and likely caused sustained viral transmission after an event at the club. This outbreak illustrates the potential for superspreader events and corroborates current club closures.

The Relationship Between Blood Sample Volume and Diagnostic Sensitivity of Blood Culture for Typhoid and Paratyphoid Fever: A Systematic Review and Meta-Analysis.

Background: Blood culture is the standard diagnostic method for typhoid and paratyphoid (enteric) fever in surveillance studies and clinical trials, but sensitivity is widely acknowledged to be suboptimal. We conducted a systematic review and meta-analysis to examine sources of heterogeneity across studies and quantified the effect of blood volume. Methods: We searched the literature to identify all studies that performed blood culture alongside bone marrow culture (a gold standard) to detect cases of enteric fever. We performed a meta-regression analysis to quantify the relationship between blood sample volume and diagnostic sensitivity. Furthermore, we evaluated the impact of patient age, antimicrobial use, and symptom duration on sensitivity. Results: We estimated blood culture diagnostic sensitivity was 0.59 (95% confidence interval [CI], 0.54-0.64) with significant between-study heterogeneity (I2, 76% [95% CI, 68%-82%]; P < .01). Sensitivity ranged from 0.51 (95% CI, 0.44-0.57) for a 2-mL blood specimen to 0.65 (95% CI, 0.58-0.70) for a 10-mL blood specimen, indicative of a relationship between specimen volume and sensitivity. Subgroup analysis showed significant heterogeneity by patient age and a weak trend towards higher sensitivity among more recent studies. Sensitivity was 34% lower (95% CI, 4%-54%) among patients with prior antimicrobial use and 31% lower after the first week of symptoms (95% CI, 19%-41%). There was no evidence of confounding by patient age, antimicrobial use, symptom duration, or study date on the relationship between specimen volume and sensitivity. Conclusions: The relationship between the blood sample volume and culture sensitivity should be accounted for in incidence and next-generation diagnostic studies.

Seasonal dynamics of typhoid and paratyphoid fever.

Typhoid and paratyphoid fever may follow a seasonal pattern, but this pattern is not well characterized. Moreover, the environmental drivers that influence seasonal dynamics are not fully understood, although increasing evidence suggests that rainfall and temperature may play an important role. We compiled a database of typhoid, paratyphoid, or enteric fever and their potential environmental drivers. We assessed the seasonal dynamics by region and latitude, quantifying the mean timing of peak prevalence and seasonal variability. Moreover, we investigated the potential drivers of the seasonal dynamics and compared the seasonal dynamics for typhoid and paratyphoid fever. We observed a distinct seasonal pattern for enteric and typhoid fever by latitude, with seasonal variability more pronounced further from the equator. We also found evidence of a positive association between preceding rainfall and enteric fever among settings 35°-11°N and a more consistent positive association between temperature and enteric fever incidence across most regions of the world. In conclusion, we identified varying seasonal dynamics for enteric or typhoid fever in association with environmental factors. The underlying mechanisms that drive the seasonality of enteric fever are likely dependent on the local context and should be taken into account in future control efforts.

Case Fatality Rate of Enteric Fever in Endemic Countries: A Systematic Review and Meta-analysis.

Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR) of 1% is assumed when evaluating the global burden of enteric fever. Until now, no meta-analysis has been conducted to summarize mortality from enteric fever. Therefore, we conducted a systematic review and meta-analysis to aggregate all available evidence. We estimated an overall CFR of 2.49% (95% confidence interval, 1.65%-3.75%; n = 44), and a CFR in hospitalized patients of 4.45% (2.85%-6.88%; n = 21 of 44). There was considerably heterogeneity in estimates of the CFR from individual studies. Neither age nor antimicrobial resistance were significant prognostic factors, but limited data were available for these analyses. The combined estimate of the CFR for enteric fever is higher than previously estimated, and the evaluation of prognostic factors, including antimicrobial resistance, urgently requires more data.

Explaining ethnic disparities in lung function among young adults: A pilot investigation.

BACKGROUND: Ethnic disparities in lung function have been linked mainly to anthropometric factors but have not been fully explained. We conducted a cross-sectional pilot study to investigate how best to study ethnic differences in lung function in young adults and evaluate whether these could be explained by birth weight and socio-economic factors. METHODS: We recruited 112 university students of White and South Asian British ethnicity, measured post-bronchodilator lung function, obtained information on respiratory symptoms and socio-economic factors through questionnaires, and acquired birth weight through data linkage. We regressed lung function against ethnicity and candidate predictors defined a priori using linear regression, and used penalised regression to examine a wider range of factors. We reviewed the implications of our findings for the feasibility of a larger study. RESULTS: There was a similar parental socio-economic environment and no difference in birth weight between the two ethnic groups, but the ethnic difference in FVC adjusted for sex, age, height, demi-span, father's occupation, birth weight, maternal educational attainment and maternal upbringing was 0.81L (95%CI: -1.01 to -0.54L). Difference in body proportions did not explain the ethnic differences although parental immigration was an important predictor of FVC independent of ethnic group. Participants were comfortable with study procedures and we were able to link birth weight data to clinical measurements. CONCLUSION: Studies of ethnic disparities in lung function among young adults are feasible. Future studies should recruit a socially more diverse sample and investigate the role of markers of acculturation in explaining such differences.

The impact of migration and antimicrobial resistance on the transmission dynamics of typhoid fever in Kathmandu, Nepal: A mathematical modelling study.

BACKGROUND: A substantial proportion of the global burden of typhoid fever occurs in South Asia. Kathmandu, Nepal experienced a substantial increase in the number of typhoid fever cases (caused by Salmonella Typhi) between 2000 and 2003, which subsequently declined but to a higher endemic level than in 2000. This epidemic of S. Typhi coincided with an increase in organisms with reduced susceptibility against fluoroquinolones, the emergence of S. Typhi H58, and an increase in the migratory population in Kathmandu. METHODS: We devised a mathematical model to investigate the potential epidemic drivers of typhoid in Kathmandu and fit this model to weekly data of S. Typhi cases between April 1997 and June 2011 and the age distribution of S. Typhi cases. We used this model to determine if the typhoid epidemic in Kathmandu was driven by heightened migration, the emergence of organisms with reduced susceptibility against fluoroquinolones or a combination of these factors. RESULTS: Models allowing for the migration of susceptible individuals into Kathmandu alone or in combination with the emergence of S. Typhi with reduced susceptibility against fluoroquinolones provided a good fit for the data. The emergence of organisms with reduced susceptibility against fluoroquinolones organisms alone, either through an increase in disease duration or increased transmission, did not fully explain the pattern of S. Typhi infections. CONCLUSIONS: Our analysis is consistent with the hypothesis that the increase in typhoid fever in Kathmandu was associated with the migration of susceptible individuals into the city and aided by the emergence of reduced susceptibility against fluoroquinolones. These data support identifying and targeting migrant populations with typhoid immunization programmes to prevent transmission and disease.

Birth Weight and Lung Function in Adulthood: A Systematic Review and Meta-analysis.

RATIONALE: There is evidence suggesting that birth weight may influence lung function in adulthood, but it is unclear whether it might differentially affect restrictive (FVC) and obstructive (FEV1/FVC) patterns. OBJECTIVES: To summarize evidence available on the association of birth weight, weight at 1 year, and weight gain in the first year of life with FVC and FEV1/FVC in adulthood. METHODS: We performed a systematic review of the literature by searching MEDLINE, EMBASE, and Web of Science through January 2015. Data were combined using inverse-variance weighted meta-analysis with random effects models and between-study heterogeneity evaluated. We conducted a priori subgroup or sensitivity analyses by age, country wealth, ethnicity, sex, and smoking. We evaluated risk of bias using the Newcastle Ottawa Scale and reporting bias using funnel plots. RESULTS: Eighteen articles were included in the review and 13 in the meta-analyses. Most studies were from high-income countries, and all had a low risk of bias. We found strong evidence of an association of birth weight with adult FVC, a 59.4 ml higher FVC in adulthood per kilogram increase in birth weight (95% confidence interval, 43.3-75.5), with no evidence of heterogeneity. Evidence of an association of birth weight with FEV1/FVC was weaker and showed some inconsistency across studies. Only one study investigated weight at 1 year, and another one reported weight gain in the first year. CONCLUSIONS: Our meta-analyses show strong and consistent evidence of an association of birth weight with adult FVC, a measure of restrictive impairment, with much weaker evidence for airflow obstruction.

Doing science: How to submit a successful funding application.

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