Smallpox Prevention and Public Healthcare in China in the 1920s and 1930s: Focusing on the Cases of Shanghai and Beijing.

Beijing and Shanghai, representative modern cities in China, witnessed the development of various urban infrastructures and quarantine systems in the 1920s and 1930s. Both cities established Health Demonstration Stations in the 1930s, as part of their implementation of modern health administration. This foundation played a pivotal role for making health administration more practical. Huang Zi-fang (1899-1940) and Hu Hung-ji (1894-1932), the inaugural directors of the health bureau in the respective cities, were both graduates of the Johns Hopkins University School of Public Health in the United States. They shared a similar view of public health. Active exchanges occurred between the heads of the health administration in the two cities who were the leading forces in the health reform, encompassing various health experiments including the Health Demonstration Station. During the 1930s in China, state medicine gained prominence as the most ideal medical model for constructing a modern state. As such, the quarantine activities they promoted were also considered the most ideal model. The public health care centered on Health Demonstration Stations in the 1920s and 1930s that developed in large Chinese cities such as Beijing and Shanghai pursued similar goals by strengthening quarantine administration through free medical treatment and modern spatial control. Nonetheless, each city exhibited differences in terms of the subjects and targets of quarantine, as well as the primary bases of quarantine, which were either Health Demonstration Stations or hospitals. Both municipal governments and the civilian sector led the sanitary infrastructure development. While Shanghai showed stronger development in terms of the number of vaccinations, Shanghai's dualized quarantine system did not necessarily create a better health environment than Beijing in terms of spatial control. In the 1940s, the Japanese occupation government implemented measures to inherit and further develop existing health administrations in Beijing and Shanghai. Existing international settlements were incorporated into the Japanese occupation government, and the occupation government pursued homogenization of urban space and tried to maintain the existing urban policy as much as possible to preserve the status quo. However, the intensification of the Anti-Japanese War and the Chinese Civil War brought an end to the health experiment centered around the Health Demonstration Station in China in the first half of the twentieth century.

Mpox: Aspectos epidemiológicos, imunopatogênicos e manejo pré e pós-infecção / Mpox: Epidemiological, immunopathogenic aspects and pre- and post-infection management

Mpoxou Varíola M é uma zoonose causada por vírus do gênero Orthopoxvirus, causadores também da varíola comum. É uma doença considerada rara e autolimitada, sendo endêmica em países africanos. Entretanto, no ano de 2022 ganhou destaque devido ao surto global que se iniciou, quando o mundo ainda se recuperava da pandemia da COVID-19. Dessa forma, por se tratar de uma doença emergente, a presente revisão visa pontuar aspectos gerais do que se sabe até o momento sobre a Mpox, desde sua imunopatogenia até as formas atuais de prevenção e cuidados pós-infecção

Mpox or Variola M is a zoonosis caused by viruses of the genus Orthopoxvirus, which also cause smallpox. It is a disease considered rare and self-limiting, being endemic in African countries. However, in 2022, it gained prominence due to the global outbreak that began when the world was still recovering from the COVID-19 pandemic. Thus, as it is an emerging disease, this review aims to point out general aspects of what is known so far about Mpox, from its immunopathogenesis to current forms of prevention and post-infection care

Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study.

BACKGROUND: In May, 2022, several European countries reported autochthonous cases of monkeypox, which rapidly spread globally. Early reports suggest atypical presentations. We aimed to investigate clinical and virological characteristics of cases of human monkeypox in Spain. METHODS: This multicentre, prospective, observational cohort study was done in three sexual health clinics in Madrid and Barcelona, Spain. We enrolled all consecutive patients with laboratory-confirmed monkeypox from May 11 to June 29, 2022. Participants were offered lesion, anal, and oropharynx swabs for PCR testing. Participant data were collected by means of interviews conducted by dermatologists or specialists in sexually transmitted infections and were recorded using a standard case report form. Outcomes assessed in all participants with a confirmed diagnosis were demographics, smallpox vaccination, HIV status, exposure to someone with monkeypox, travel, mass gathering attendance, risk factors for sexually transmitted infections, sexual behaviour, signs and symptoms on first presentation, virological results at multiple body sites, co-infection with other sexually transmitted pathogens, and clinical outcomes 14 days after the initial presentation. Clinical outcomes were followed up until July 13, 2022. FINDINGS: 181 patients had a confirmed monkeypox diagnosis and were enrolled in the study. 166 (92%) identified as gay men, bisexual men, or other men who have sex with men (MSM) and 15 (8%) identified as heterosexual men or heterosexual women. Median age was 37·0 years (IQR 31·0-42·0). 32 (18%) patients reported previous smallpox vaccination, 72 (40%) were HIV-positive, eight (11%) had a CD4 cell count less than 500 cells per µL, and 31 (17%) were diagnosed with a concurrent sexually transmitted infection. Median incubation was 7·0 days (IQR 5·0-10·0). All participants presented with skin lesions; 141 (78%) participants had lesions in the anogenital region, and 78 (43%) in the oral and perioral region. 70 (39%) participants had complications requiring treatment: 45 (25%) had a proctitis, 19 (10%) had tonsillitis, 15 (8%) had penile oedema, six (3%) an abscess, and eight (4%) had an exanthem. Three (2%) patients required hospital admission. 178 (99%) of 180 swabs from skin lesions collected tested positive, as did 82 (70%) of 117 throat swabs. Viral load was higher in lesion swabs than in pharyngeal specimens (mean cycle threshold value 23 [SD 4] vs 32 [6], absolute difference 9 [95% CI 8-10]; p<0·0001). 108 (65%) of 166 MSM reported anal-receptive sex. MSM who engaged in anal-receptive sex presented with proctitis (41 [38%] of 108 vs four [7%] of 58, absolute difference 31% [95% CI 19-44]; p<0·0001) and systemic symptoms before the rash (67 [62%] vs 16 [28%], absolute difference 34% [28-62]; p<0·0001) more frequently than MSM who did not engage in anal-receptive sex. 18 (95%) of 19 participants with tonsillitis reported practising oral-receptive sex. The median time from onset of lesions to formation of a dry crust was 10 days (IQR 7-13). INTERPRETATION: In our cohort, monkeypox caused genital, perianal, and oral lesions and complications including proctitis and tonsillitis. Because of the variability of presentations, clinicians should have a low threshold for suspicion of monkeypox. Lesion swabs showed the highest viral loads, which, combined with the history of sexual exposure and the distribution of lesions, suggests close contact is probably the dominant transmission route in the current outbreak. FUNDING: None.

Proteomic assessment of humoral immune responses in smallpox vaccine recipients.

The availability of effective smallpox vaccines was a critical element of the successful eradication of smallpox in 1980. Antibody responses play a primary role in protective immunity and neutralizing antibody is an established correlate of protection against smallpox. In this study we used a poxvirus proteome array to assess the antibody response to individual viral proteins in a cohort of 1,037 smallpox vaccine recipients. Several statistically significant differences were observed in the antibody response to immunodominant proteins between men and women, including B5R-a major target of neutralizing antibody in vaccinia immune globulin, and the membrane proteins D8L and A27L, both of which have been used as vaccine antigens providing protection in animal models. We also noted differences across racial/ethnic groups. In this cohort, which consisted of both ACAM2000 and Dryvax recipients, we noted minute differences in the antibody responses to a restricted number of viral proteins, providing additional support for the use of ACAM2000 as a replacement smallpox vaccine. Furthermore, our data indicate that poxvirus proteome microarrays can be valuable for screening and monitoring smallpox vaccine-induced humoral immune responses in large-scale serologic surveillance studies and prove useful in the guidance of developing novel smallpox candidate vaccines.

Benefit-risk assessment for brincidofovir for the treatment of smallpox: U.S. Food and Drug Administration's Evaluation.

The development and approval of brincidofovir for the treatment of smallpox, a disease that was eradicated from the world over 40 years ago, has resulted in the second antiviral approved via the Medical Countermeasure Initiative (MCMi) to combat this disease. Approval of brincidofovir required a unique regulatory approach based on the FDA Animal Rule, and development was supported by many years of research and collaboration among academic investigators, the pharmaceutical industry and multiple government agencies. This article summarizes the FDA regulatory pathway and describes the challenges involved.

Las epidemias en La Pampa (Argentina), en perspectiva histórica* / The epidemics in La Pampa (Argentina), from a historical perspective

Resumen Este artículo describe el inicio de las preocupaciones sanitarias vinculadas a las epidemias ocurridas durante el siglo XX en La Pampa, provincia argentina. Las epidemias, como las de la viruela, fueron un estímulo para estas políticas que frecuentemente tuvieron origen en Buenos Aires, la capital del país. El contagio de muchas epidemias dependía de carencias de infraestructura: agua, desagüe y desecho adecuado de basuras, de la ausencia de un número suficiente de trabajadores de salud, de la presencia de vectores transmisores de enfermedades como los mosquitos y, en última instancia, de la pobreza. La experiencia histórica descrita en este texto resalta la importancia de analizar el impacto del SARS-CoV-2 más allá de las grandes ciudades.

Abstract This article describes the emergence of health concerns relating to the epidemics that occurred during the twentieth century in La Pampa, a province in Argentina. Epidemics such as smallpox drove such policies, which frequently originated in Buenos Aires, the country's capital. The spread of many epidemics was due to shortages: water, sewage and adequate refuse disposal, an insufficient number of health care workers, the presence of disease transmission vectors such as mosquitos, and, ultimately, poverty. The historical experience described in this text highlights the importance of analyzing the impact of SARS-CoV-2 beyond the big cities.

[The epidemics in La Pampa (Argentina), from a historical perspective]. / Las epidemias en La Pampa (Argentina), en perspectiva histórica.

This article describes the emergence of health concerns relating to the epidemics that occurred during the twentieth century in La Pampa, a province in Argentina. Epidemics such as smallpox drove such policies, which frequently originated in Buenos Aires, the country's capital. The spread of many epidemics was due to shortages: water, sewage and adequate refuse disposal, an insufficient number of health care workers, the presence of disease transmission vectors such as mosquitos, and, ultimately, poverty. The historical experience described in this text highlights the importance of analyzing the impact of SARS-CoV-2 beyond the big cities.

Este artículo describe el inicio de las preocupaciones sanitarias vinculadas a las epidemias ocurridas durante el siglo XX en La Pampa, provincia argentina. Las epidemias, como las de la viruela, fueron un estímulo para estas políticas que frecuentemente tuvieron origen en Buenos Aires, la capital del país. El contagio de muchas epidemias dependía de carencias de infraestructura: agua, desagüe y desecho adecuado de basuras, de la ausencia de un número suficiente de trabajadores de salud, de la presencia de vectores transmisores de enfermedades como los mosquitos y, en última instancia, de la pobreza. La experiencia histórica descrita en este texto resalta la importancia de analizar el impacto del SARS-CoV-2 más allá de las grandes ciudades.

In Honor of Dr. Abdul Hussein Taba: Iranian Physician and Former Director of the Eastern Mediterranean Region of the World Health Organization.

The honorable Abdul Hussein Tabatabaei was born in 1911 in Iran and received his medical education in the United Kingdom. Famously known as Dr. A.H. Taba, he was a well-respected man for his significant impact on the improvement of the national and global healthcare services and support for social justice. Before joining the World Health Organization (WHO), he was twice elected to the Iranian national assembly and served as the under-secretary of health services in Iran. Later, he joined the WHO and was elected as the Director of the Eastern Mediterranean Region (EMRO) in Alexandria in 1957 - a position he maintained for 25 years. During his tenure as the Regional Director, he rendered valuable assistance to the development and expansion of major health issues such as development and expansion of the health workforce, improvement of the national health services and controlling of various communicable diseases in the member countries and across the WHO regional offices.

Recalibration of the Grunow-Finke Assessment Tool to Improve Performance in Detecting Unnatural Epidemics.

Successful identification of unnatural epidemics relies on a sensitive risk assessment tool designed for the differentiation between unnatural and natural epidemics. The Grunow-Finke tool (GFT), which has been the most widely used, however, has low sensitivity in such differentiation. We aimed to recalibrate the GFT and improve the performance in detection of unnatural epidemics. The comparator was the original GFT and its application in 11 historical outbreaks, including eight confirmed unnatural outbreaks and three natural outbreaks. Three steps were involved: (i) removing criteria, (ii) changing weighting factors, and (iii) adding and refining criteria. We created a series of alternative models to examine the changes on the parameter likelihood of unnatural outbreaks until we found a model that correctly identified all the unnatural outbreaks and natural ones. Finally, the recalibrated GFT was tested and validated with data from an unnatural and natural outbreak, respectively. A total of 238 models were tested. Through the removal of criteria, increasing or decreasing weighting factors of other criteria, adding a new criterion titled "special insights," and setting a new threshold for likelihood, we increased the sensitivity of the GFT from 38% to 100%, and retained the specificity at 100% in detecting unnatural epidemics. Using test data from an unnatural and a natural outbreak, the recalibrated GFT correctly classified their etiology. The recalibrated GFT could be integrated into routine outbreak investigation by public health institutions and agencies responsible for biosecurity.

Best practice assessment of disease modelling for infectious disease outbreaks.

During emerging disease outbreaks, public health, emergency management officials and decision-makers increasingly rely on epidemiological models to forecast outbreak progression and determine the best response to health crisis needs. Outbreak response strategies derived from such modelling may include pharmaceutical distribution, immunisation campaigns, social distancing, prophylactic pharmaceuticals, medical care, bed surge, security and other requirements. Infectious disease modelling estimates are unavoidably subject to multiple interpretations, and full understanding of a model's limitations may be lost when provided from the disease modeller to public health practitioner to government policymaker. We review epidemiological models created for diseases which are of greatest concern for public health protection. Such diseases, whether transmitted from person-to-person (Ebola, influenza, smallpox), via direct exposure (anthrax), or food and waterborne exposure (cholera, typhoid) may cause severe illness and death in a large population. We examine disease-specific models to determine best practices characterising infectious disease outbreaks and facilitating emergency response and implementation of public health policy and disease control measures.

Treacle and Smallpox: Two Tests for Multicriteria Decision Analysis Models in Health Technology Assessment.

Multicriteria decision analysis (MCDA) is rightly receiving increasing attention in health technology assessment. Nevertheless, a distinguishing feature of the health domain is that technologies must actually improve health, and good performance on other criteria cannot compensate for failure to do so. We argue for two reasonable tests for MCDA models: the treacle test (can a winning intervention be incompletely ineffective?) and the smallpox test (can a winning intervention be for a disease that no one suffers from?). We explore why models might fail such tests (as the models of some existing published studies would do) and offer some suggestions as to how practice should be improved.

Modelling and Bayesian analysis of the Abakaliki smallpox data.

The celebrated Abakaliki smallpox data have appeared numerous times in the epidemic modelling literature, but in almost all cases only a specific subset of the data is considered. The only previous analysis of the full data set relied on approximation methods to derive a likelihood and did not assess model adequacy. The data themselves continue to be of interest due to concerns about the possible re-emergence of smallpox as a bioterrorism weapon. We present the first full Bayesian statistical analysis using data-augmentation Markov chain Monte Carlo methods which avoid the need for likelihood approximations and which yield a wider range of results than previous analyses. We also carry out model assessment using simulation-based methods. Our findings suggest that the outbreak was largely driven by the interaction structure of the population, and that the introduction of control measures was not the sole reason for the end of the epidemic. We also obtain quantitative estimates of key quantities including reproduction numbers.

Genome sequencing rated top advance of past 40 years.

The sequencing of the human genome represents the most significant breakthrough in healthcare over the past 40 years, according to Modern Healthcare readers. That achievement, capping a 13-year, $3 billion international effort funded by the federal government, drew the most votes from the 728 respondents to a survey that listed 60 healthcare milestones achieved since Modern Healthcare was founded in 1976. The survey asked readers to pick their top five choices from each of three categories: science and technology; healthcare delivery; and politics and policy.

Benefits of lethal pandemics: direct impact of contagious diseases on public administration in Hungary (1867-1914).

The reconciliation of 1867 between Austria and Hungary brought great changes to Hungarian public administration: the way towards the building up of a modern public administration had been opened. Although there was a functioning public health system and a related legislation from the late 18th century, major issues - such as balanced geographical distribution of medical personnel, fair access to medical services even in the poorer regions of the country, and the effective protection against some contagious diseases - were not resolved for decades. During the reform work of public administration since the 1870s, the lawmakers touched repeatedly the framework and functioning of the public health as well. Although the general conditions of the domain depended traditionally on the municipalities and counties due to the national importance of the matter, the government made efforts to make the functioning of the public health more efficient through centralisation. The contagious diseases continuously endangered the population, revealing the weak points in the existing public health system, thereby giving a momentum to the reforms and helping the government in its organization of prevention and clearly contributing to the legislation work.

Economic considerations for the eradication endgame.

An infectious disease will be eradicated only if it is eliminated everywhere, including in the hardest-to-reach, most vaccine-wary communities. If eradication is successful, it promises a dividend in the form of avoided infections and vaccinations. However, success is never certain unless and until eradication is achieved, and claiming the dividend means bearing the possibly great risk of re-emergence. Economic analysis of eradication evaluates these risks and rewards relative to the alternative of 'optimal control', and also exposes the incentives for achieving and capitalizing on eradication. Eradication is a 'game', because some countries may be willing to eliminate the disease within their borders only if assured that all others will eliminate the disease within their borders. International financing is also a game, because each country would rather free ride than contribute. Finally, for diseases such as polio, capitalizing on eradication is a game, for should any country continue to vaccinate in the post-eradication era using the live-attenuated polio vaccine, the countries that stop vaccinating will be exposed to the risk of vaccine-derived polioviruses. In the framework developed in this paper, eradication is a seductive goal, its attainment fraught with peril.