Volume 09 · Issue 03 · 2020

随着2019年新型冠状病毒病（COVID-19）疫情在全球迅速蔓延，许多关于该疾病的基本生物学和流行病学的未解问题阻碍了我们的应对策略，并限制了我们实现控制和防止反弹或所谓“第二波”的能力。其中一个至关重要的问题是：无症状病例在多大程度上有助于传播？关于这一主题的早期小型研究发现了对无症状携带者患病率的广泛估计，迄今为止只有少数研究记录了无症状病例的病毒脱落[1].我们最近重新检查了中国的新冠肺炎病例报告数据来调查这个问题[2].这篇社论旨在描述无症状病例如何导致传播，以及对控制策略的影响。

The outbreak of coronavirus disease 2019 (COVID-19) has become a pandemic causing global health problem. We provide estimates of the daily trend in the size of the epidemic in Wuhan based on detailed information of 10 940 confirmed cases outside Hubei province.

In this modelling study, we first estimate the epidemic size in Wuhan from 10 January to 5 April 2020 with a newly proposed model, based on the confirmed cases outside Hubei province that left Wuhan by 23 January 2020 retrieved from official websites of provincial and municipal health commissions. Since some confirmed cases have no information on whether they visited Wuhan before, we adjust for these missing values. We then calculate the reporting rate in Wuhan from 20 January to 5 April 2020. Finally, we estimate the date when the first infected case occurred in Wuhan.

We estimate the number of cases that should be reported in Wuhan by 10 January 2020, as 3229 (95% confidence interval [CI]: 3139–3321) and 51 273 (95% CI: 49 844–52 734) by 5 April 2020. The reporting rate has grown rapidly from 1.5% (95% CI: 1.5–1.6%) on 20 January 2020, to 39.1% (95% CI: 38.0–40.2%) on 11 February 2020, and increased to 71.4% (95% CI: 69.4–73.4%) on 13 February 2020, and reaches 97.6% (95% CI: 94.8–100.3%) on 5 April 2020. The date of first infection is estimated as 30 November 2019.

In the early stage of COVID-19 outbreak, the testing capacity of Wuhan was insufficient. Clinical diagnosis could be a good complement to the method of confirmation at that time. The reporting rate is very close to 100% now and there are very few cases since 17 March 2020, which might suggest that Wuhan is able to accommodate all patients and the epidemic has been controlled.

A cluster of pneumonia cases were reported by Wuhan Municipal Health Commission, China in December 2019. A novel coronavirus was eventually identified, and became the COVID-19 epidemic that affected public health and life. We investigated the psychological status and behavior changes of the general public in China from January 30 to February 3, 2020.

Respondents were recruited via social media (WeChat) and completed an online questionnaire. We used the State-Trait Anxiety Inventory, Self-rating Depression Scale, and Symptom Checklist-90 to evaluate psychological status. We also investigated respondents’ behavior changes. Quantitative data were analyzed by t-tests or analysis of variance, and classified data were analyzed with chi-square tests.

In total, 608 valid questionnaires were obtained. More respondents had state anxiety than trait anxiety (15.8% vs 4.0%). Depression was found among 27.1% of respondents and 7.7% had psychological abnormalities. About 10.1% of respondents suffered from phobia. Our analysis of the relationship between subgroup characteristics and psychological status showed that age, gender, knowledge about COVID-19, degree of worry about epidemiological infection, and confidence about overcoming the outbreak significantly influenced psychological status. Around 93.3% of respondents avoided going to public places and almost all respondents reduced Spring Festival-related activities. At least 70.9% of respondents chose to take three or more preventive measures to avoid infection. The three most commonly used prevention measures were making fewer trips outside and avoiding contact (98.0%), wearing a mask (83.7%), and hand hygiene (82.4%).

We need to pay more attention to public psychological stress, especially among young people, as they are likely to experience anxiety, depression, and psychological abnormalities. Different psychological interventions could be formulated according to the psychological characteristics of different gender and age groups. The majority of respondents followed specific behaviors required by the authorities, but it will take time to observe the effects of these behaviors on the epidemic.

As COVID-19 makes its way around the globe, each nation must decide when and how to respond. Yet many knowledge gaps persist, and many countries lack the capacity to develop complex models to assess risk and response. This paper aimed to meet this need by developing a model that uses case reporting data as input and provides a four-tiered risk assessment output.

We used publicly available, country/territory level case reporting data to determine median seeding number, mean seeding time (ST), and several measures of mean doubling time (DT) for COVID-19. We then structured our model as a coordinate plane with ST on the x-axis, DT on the y-axis, and mean ST and mean DT dividing the plane into four quadrants, each assigned a risk level. Sensitivity analysis was performed and countries/territories early in their outbreaks were assessed for risk.

Our main finding was that among 45 countries/territories evaluated, 87% were at high risk for their outbreaks entering a rapid growth phase epidemic. We furthermore found that the model was sensitive to changes in DT, and that these changes were consistent with what is officially known of cases reported and control strategies implemented in those countries.

Our main finding is that the ST/DT Model can be used to produce meaningful assessments of the risk of escalation in country/territory-level COVID-19 epidemics using only case reporting data. Our model can help support timely, decisive action at the national level as leaders and other decision makers face of the serious public health threat that is COVID-19.

Coronavirus disease 2019 (COVID-19) is now a global public threat. Given the pandemic of COVID-19, the economic impact of COVID-19 is essential to add value to the policy-making process. We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China, and also assess the factors affecting their costs.

This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020. The total direct medical expenditures were analyzed by cost factors. We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income. Differences between groups were tested by student t test and Mann-Whitney test when appropriate. A multiple logistic regression model was built to determine the risk factors associated with high cost.

A total of 70 COVID-19 patients were included in the analysis. The overall mean cost was USD 6827 per treated episode. The highest mean cost was observed in drug acquisition, accounting for 45.1% of the overall cost. Total mean cost was significantly higher in patients with pre-existing diseases compared to those without preexisting diseases. Pre-existing diseases and the advanced disease severity were strongly associated with higher cost. Around USD 0.49 billion were expected for clinical manage of COVID-19 in China. Among rural households, the proportions of health insurance coverage should be increased to 70% for severe cases, and 80% for critically ill cases to avoid catastrophic health expenditure.

Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance. The cost for drug acquisition is the major contributor to the medical cost, whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19. Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.

A steady progress on schistosomiasis control in the Peoples’ Republic of China (P.R. China) was achieved and broadened into the twelve-year medium and long term national plan (MLNP) which marled the implementation of an integrated control strategy across all endemic areas in P.R. China in 2004. To understand the endemic trends of schistosomiasis to assess the effectiveness of an integrated strategy, we conducted an analysis of schistosomiasis surveillance data spanned from 2005 to 2015.

The schistosomiasis sentinel surveillance data from sentinel sites were collected and analyzed from 2005 to 2015. In these sentinel sites, residents aged 6 years or above were screened annually by indirect hemagglutination assay (IHA), while only antibody positives were followed by stool examination either Kato-katz method (KK) and/or hatching technique (HT). Domestic animals raised in sentinel sites were examined by HT for confirming the infection of schistosomes. Snail investigation was conducted each year through systematic sampling method combined with environmental sampling method. The snails collected from field were tested by microscopic dissection method. The infection rates of schistosomes in residents, domestic animals and snails, as well as the indicators reflecting the snails’ distribution were calculated and analyzed. ANOVA analysis was used to examine the changes of the number of eggs per gram feces in population and Chi-square test was used to examine any change in proportions among groups.

A total of 148 902 residents from sentinel sites attended this study and 631 676 blood samples were examined by IHA test during the 11 covered years. The annual average antibody positive rates presented a significant decrease trends, from 17.48% (95% CI: 17.20–17.75%) in 2005 to 5.93% (95% CI: 5.71–6.15%) (χ²= 8890.47, P < 0.001) in 2015. During 2005–2015, the average infection rate of schistosomes in residents declined from 2.07% (95% CI: 1.96–2.17%) to 0.13% (95% CI: 0.09–0.16%), accompanied by significant decrease of infection intensity in population. In 2015, the stool positives were only found in farmers, fishermen and boatmen with infection rate of 0.16% (95% CI: 0.11–0.20%), 0.17% (95% CI: 0–0.50%) respectively. The infection rate of schistosomes in domestic animals dropped from 9.42% (538/5711, 95% CI: 8.66–10.18%) to 0.08% (2/2360, 95% CI: 0–0.20%) from 2005 to 2015. Infections were found in eight species of domestic animals at the beginning of surveillance while only two cattle were infected in 2015. Totally 98 ha of new snail habitats were found, while 94.90% (93/98) distributed in lake and marshland regions. The percentage of frames with snails decreased from 16.96% (56 884/33 5391, 95% CI: 16.83–17.09%) in 2005 to 4.28% (18 121/423 755, 95% CI: 4.22–4.34%) in 2014, with a slightly increase in 2015. Meanwhile, the infection rate of schistosomes in snails was decreased from 0.26% (663/256 531, 95% CI: 0.24–0.28%) to zero during 2005–2015.

The infection rate of schistosomes declined significantly, providing evidence that the goal of the MLNP was achieved. Elimination of schistosomiasis as a public health problem defined as WHO was also reached in P.R. China nationwide. Surveillance-response system should be improved and strengthened to realize the final goal of schistosomiasis elimination.

China still suffers heavily from rabies, although reported human cases continue to decrease year over year. There are far fewer laboratory-confirmed human cases than clinically diagnosed cases, which is a big problem that needs to be addressed. In this report, we summarize analyses of all specimens from human cases tested in our laboratory over the past 15 years, in order to promote laboratory diagnosis of rabies.

From 2005 to 2019, a total of 271 samples from 164 suspected rabies cases were collected from local hospitals by the local Centers for Disease Control and Prevention (CDCs) in China. Saliva, cerebrospinal fluid (CSF), serum (blood) and urine were collected for ante-mortem diagnosis, and brain tissue, neck skin tissue and cornea were collected for post-mortem diagnosis. All of the specimens were tested by reverse transcription-polymerase chain reaction (RT-PCR), and brain tissues were also tested using fluorescent antibody test (FAT). The number of positive test results obtained using different fluids or tissues, and at different stages of the disease, were compared using a chi-square test and a more effective sampling program is recommended.

As the national reference laboratory for rabies surveillance in China, our laboratory has tested 271 samples from 164 suspected rabies cases collected by local CDCs since 2005. We found that saliva gave the highest number of positive test results (32%), compared with CSF and other fluids. We also found that serum or blood specimens collected in the last 3 days of life can test positive by RT-PCR.

Serum or blood samples collected in the last 3 days of a patient’s life can be used to measure viral RNA, which means that serum samples, as well as saliva and CSF, can be used to detect viral RNA for anti-mortem diagnosis of rabies. Because of our findings, we have modified our "National Surveillance Project for Human Rabies", by adding the collection and testing of serum samples from the end of the survival period. This will improve our national surveillance and laboratory diagnosis of human rabies.

Multidrug-resistant tuberculosis (MDR-TB) is on the rise in China. This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative control measures.

Eight states of tuberculosis transmission were set up in the Markov model using a hypothetical cohort of 100 000 people. The prevalence of MDR-TB and bacteriologically confirmed drug-susceptible tuberculosis (DS-TB⁺) were simulated and MDR-TB was stratified into whether the disease was treated with the recommended regimen or not.

Without any intervention changes to current conditions, the prevalence of DS-TB⁺ was projected to decline 67.7% by 2050, decreasing to 20 per 100 000 people, whereas that of MDR-TB was expected to triple to 58/100 000. Furthermore, 86.2% of the MDR-TB cases would be left untreated by the year of 2050. In the case where MDR-TB detection rate reaches 50% or 70% at 5% per year, the decline in prevalence of MDR-TB would be 25.9 and 36.2% respectively. In the case where treatment coverage was improved to 70% or 100% at 5% per year, MDR-TB prevalence in 2050 would decrease by 13.8 and 24.1%, respectively. If both detection rate and treatment coverage reach 70%, the prevalence of MDR-TB by 2050 would be reduced to 28/100 000 by a 51.7% reduction.

MDR-TB, especially untreated MDR-TB, would rise rapidly under China’s current MDR-TB control strategies. Interventions designed to promote effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics.

After the scale-up of antiretroviral therapy (ART) for HIV infected people, increasing numbers of patients have pretreatment drug resistance (PDR). In this study, the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China.

Blood samples were obtained from 1943 patients who initiated antiretroviral therapy (ART) in 2017 from 13 provinces or cities in China. Pol sequences were used to analyze drug resistance and construct transmission networks. Logistic regression model was used to estimate the potential factors associated with PDR.

In total, 1711 eligible patients (76.0% male; 87.8% aged ≥ 25 years) were included, of which 117 (6.8%) had PDR. The highest rates of PDR were 12.2% in Liangshan Prefecture of Sichuan and 9.3 and 8.9% in Dehong and Lincang Prefecture of Yunnan. A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users (adjusted Odds Ratio (aOR) = 2.64, 95% CI: 1.57–4.44) and individuals from Liangshan, Dehong, and Lincang (aOR= 2.04, 95% CI: 1.26–3.30). In total, 754 sequences were used to generate 164 transmission networks. Five transmission networks had two or three sequences containing the same mutations, two networks contained subjects from Liangshan, and one network contained subjects from Dehong.

Overall, the PDR prevalence was moderate, with a particularly high prevalence in areas with severe HIV epidemics. These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.

Soil-transmitted helminthiases (STH) are part of the group of neglected tropical diseases traditionally treated with preventive chemotherapy interventions. In recent years, drug donations have been essential to expanding preventive chemotherapy and achieving progressive control of morbidity from STH. This study aims to evaluate the need for anthelminthic medicines during 2020–2030.

To estimate the need for anthelminthic medicines, we considered three different scenarios: (1) the control programmes continues to expand coverage and maintains the frequency of drug administration established at baseline; (2) the programmes continues to expand coverage but adapts the frequency of drug administration when the STH prevalence is reduced and (3) the STH programme becomes self-sustainable in some endemic countries.

We estimate that the number of anthelmintic medicines needed to treat school-aged children will increase by 40% by 2025 and by 52% by 2030 if countries do not change the frequency of preventive chemotherapy (scenario 1); that the number of tablets needed will reduce by 32.4% by 2025 and by 49.1% in 2030 if endemic countries reduce the frequency of preventive chemotherapy (scenario 2); and drug donations could be reduced by 54.4% by 2025 and 74.4% by 2030 if some endemic countries could become independent in drug procurement (scenario 3).

The number of anthelmintic medicines needed to achieve elimination of morbidity due to STH in school-aged children will decline during 2020–2030. The decline will be substantial if a number of "upper-middle income" countries in which STH are endemic procure, as expected, anthelminthic medicines independently.

The incidence of brucellosis, which is caused by the Brucella species of bacteria, is rapidly rising worldwide; however, few studies have investigated the immune response to this pathogen and clinical biochemical features. In this paper, we examined the levels of various cytokines and inflammatory factors as well as clinical course characteristics in patients with brucellosis, in order to provide evidence for the diagnosis, assessment, and prognosis of this infectious disease.

A total of 191 brucellosis inpatients (50 acute cases and 141 chronic cases), as well as 60 healthy control subjects, were included in the analysis. We investigated changes in the levels of six cytokines (IL-4, IL-6, IL-10, IL-17, TNF-α, INF-γ) and related clinical biochemical markers in patients with acute and chronic brucellosis in Xinjiang, China. Possible factors were statistically analyzed using the t test, χ² test, z test and a multivariate logistic stepwise regression test.

We found that IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α levels were higher in those with brucellosis than in controls (P < 0.05). With regard to disease progression, procalcitonin (PCT) and C-reactive protein (CRP) levels were significantly higher in those with an acute infection compared to chronic cases (P < 0.05). We found that the expression of all six cytokines tested was closely related to the degree of brucellosis using univariate logistic regression; however, only IL-6 and INF-γ levels were independent factors associated with the severity of brucellosis.

Assessing cytokine levels in patients with acute and chronic brucellosis is not only useful for detecting the immune response, but can also be indicative of the severity of brucellosis. In particular, we propose IL-6 and INF-γ levels may be useful independent predictive factors in the clinical evaluation and diagnosis of brucellosis.

Practitioners and researchers in the midst of overwhelming coronavirus disease 2019 (COVID-19) outbreaks are calling for new ways of looking at such pandemics, with an emphasis on human behavior and holistic considerations. Viral outbreaks are characterized by socio-behaviorally-oriented public health efforts aimed at reducing exposure and prevention of morbidity/mortality once infected. These efforts involve different points-of-view, generally, than do those aimed to understand the virus' natural history. Rampant spread of SARS-CoV-2infection in cities clearly signals that urban areas contain conditions favorable for rapid transmission of the virus.

The Critical Medical Ecology model is a multidimensional, multilevel way of viewing pandemics comprehensively, rooted simultaneously in microbiology and in anthropology, with shared priority for evolution, context, stressors, homeostasis, adaptation, and power relationships. Viewing COVID-19 with a Critical Medical Ecological lens suggests three important interpretations: 1) COVID-19 is equally — if not more — a socially-driven disease as much as a biomedical disease, 2) the present interventions available for primary prevention of transmission are social and behavioral interventions, and 3) wide variation in COVID-19 hospitalization/death rates is not expected to significantly be attributable to a more virulent and rapidly-evolving virus, but rather to differences in social and behavioral factors — and power dynamics — rather than (solely) biological and clinical factors. Cities especially are challenged due to logistics and volume of patients, and lack of access to sustaining products and services for many residents living in isolation.

In the end, SARS-CoV-2 is acting upon dynamic social human beings, entangled within structures and relationships that include but extend far beyond their cells, and in fact beyond their own individual behavior. As a comprehensive way of thinking, the Critical Medical Ecology model helps identify these elements and dynamics in the context of ecological processes that create, shape, and sustain people in their multidimensional, intersecting environments.

Several studies highlighted the impact of community-based interventions whose purpose was to reduce the vectors’ breeding sites. These strategies are particularly interesting in low-and-middle-income countries which may find it difficult to sustainably assume the cost of insecticide-based interventions. In this case study we determine the spatial distribution of a community-based intervention for dengue vector control using different entomological indices. The objective was to evaluate locally where the intervention was most effective, using spatial analysis methods that are too often neglected in impact assessments.

Two neighbourhoods, Tampouy and Juvenat in Ouagadougou, Burkina Faso, were chosen among five after a survey was conducted, as part of an assessment related to the burden of dengue. As part of the community-based intervention conducted in Tampouy between August and early October 2016, an entomological survey was implemented in two phases. The first phase consisted of a baseline entomological characterization of potential breeding sites in the neighbourhood of Tampouy as well as in Juvenat, the control area. This phase was conducted in October 2015 at the end of the rainy season. The mosquito breeding sites were screened in randomly selected houses: 206 in Tampouy and 203 in Juvenat. A second phase took place after the intervention, in October 2016. The mosquito breeding sites were investigated in the same yards as during the baseline phase. We performed several entomological analyses to measure site productivity as well as before and after analysis using multilevel linear regression. We used Local Indicators of Spatial Association (LISAs) to analyse spatial concentrations of larvae.

After the intervention, it is noted that LISAs at Tampouy reveal few aggregates of all types and the suppression of those existing before the intervention. The analysis therefore reveals that the intervention made it possible to reduce the number of concentration areas of high and low values of pupae.

The contribution of spatial methods for assessing community-based intervention are relevant for monitoring at local levels as a complement to epidemiological analyses conducted within neighbourhoods. They are useful, therefore, not only for assessment but also for establishing interventions. This study shows that spatial analyses also have their place in population health intervention research.

To detect acute schistosomiasis, low-intensity infections, or to verify the success of treatment with praziquantel, highly sensitive test methods are required. The aim of this study was therefore to demonstrate the performance of Schistosoma mansoni specific DNA detection in serum and urine using real-time polymerase chain reaction (PCR) in an endemic area before and after treatment.

The study pursued a 1-week and 20-weeks longitudinal design with a treatment intervention among 36 study participants aged 18 to 70 years in the community of Kayenze, a fishing village in Ilemela district on the southern shore of Lake Victoria in north-western Tanzania between February and June 2018. Blood, urine and stool samples were collected from each participant to diagnose Schistosoma mansoni infection before and two times after treatment with praziquantel using serum-and urine based real-time PCR, point-of-care circulating cathodic antigen (POC-CCA) rapid diagnostic test and the microscopic Kato-Katz (KK) method. Kappa coefficient (κ) was used to estimate the agreement between these diagnostic tests compared to a combined "gold standard" of positive results by serum-based real-time PCR and/or positive egg counts determined by KK. Kendall’s Tau rank correlation was used to examine the relationship between cycle threshold (Ct)-values and egg counts and the Wilcoxon signed-rank test was used to compare the median Ct-values of the different examination time points.

By using the combined "gold standard" of the parasitological Kato-Katz test and/or serum-based real-time PCR, a S. mansoni prevalence of 77.1% could be determined at baseline. In terms of sensitivity, serum-based realtime PCR (96.3%) and POC-CCA assay (77.8%) showed the highest results. The detection of DNA from urine samples showed the lowest sensitivity (33.3%). Treatment with praziquantel resulted in a significantly reduced prevalence of S. mansoni. No infection could be detected by Kato-Katz, with the POC-CCA test only 33.3%. The analysis of the median Ct values over time (which were determined by the serum-based real-time PCR) showed that the Ct decreases significantly shortly after treatment (from 30.3 to 28) and increases above baseline level (34.9) three months later.

The data presented here show that the serum-based real-time PCR exhibits excellent diagnostic accuracy, in contrast to the use of urine as sample material for S. mansoni DNA detection. However, as circulating DNA does not necessarily reflect the persistence of living worms in schistosomiasis, this method is less well suited to verify the success of treatment with praziquantel.