- Ivermectin and malaria control. [Journal Article]
- MJMalar J 2017 Apr 24; 16(1):172
- As the world begins to realize the very real prospect of eliminating malaria as a public health problem globally, the scientific community is acutely aware that novel and innovative new tools will be...
As the world begins to realize the very real prospect of eliminating malaria as a public health problem globally, the scientific community is acutely aware that novel and innovative new tools will be required if that lofty goal is to be accomplished. Moreover, the need for comprehensive, integrated products and interventions is being recognized in order for the critical 'final steps' toward elimination to be taken successfully. Failure to take these crucial last steps have dogged all past global disease elimination programmes, except for smallpox. The success of ivermectin in driving two of the most devastating and disfiguring neglected tropical diseases (NTD) to the brink of elimination has been well documented. The drug also bestows immeasurable non-target benefits, increasing the health and socioeconomic prospects of all communities where mass drug administration (MDA) has been carried out. Ivermectin kills a variety of parasites and insects, including the Anopheline vectors of malaria parasites. In view of long-standing MDA programmes, increasing attention is now being paid to the potential offered by re-formulating and re-purposing ivermectin to function as a feed-though mosquitocidal tool. This will provide a comprehensively beneficial weapon, for the anti-malarial armamentarium, as well as for probably improving the impact on existing target diseases. Prospects currently look highly promising, especially as the drug is already proven to be extremely safe for human use. However, for maximum impact, detailed analysis of various analogues of the unique ivermectin, as well as the parent avermectin compounds, will need to be undertaken. 'Ivermectin' comprises an imprecise mix of two compounds, both of which are potent anthelmintics. Yet recently, it has been confirmed that only the minor of the two component compounds is molluscicidal. Further structure activity relationship studies may well identify the analogue, analogues or combination thereof best suited for use in a concerted initiative to simultaneously tackle malaria and other NTD in poly-parasitized communities.
- Review of poxvirus: emergence of monkeypox. [Journal Article]
- MSMed Sante Trop 2017 Feb 01; 27(1):29-39
- This article reviews the different types of poxvirus infections. Smallpox, although eradicated, must continue to be monitored because of the potential risk of accidental or voluntary (by bioterrorism...
This article reviews the different types of poxvirus infections. Smallpox, although eradicated, must continue to be monitored because of the potential risk of accidental or voluntary (by bioterrorism) reintroduction. Monkeypox and cowpox viruses are considered to be emergent today ; their high risk of dissemination is due to the increase in international transport as well as trends for new animals as pets and the loss of vaccinal protection against smallpox. Molluscum contagiosum (molluscipoxvirus) causes mild infections, is particularly frequent in children ; in adults it is a marker of the risk of sexually transmitted infections and can, in cases with profuse lesions, reveal AIDS.
- Preparing for biological threats: Addressing the needs of pregnant women. [Review]
- BDBirth Defects Res 2017 Mar 15; 109(5):391-398
- Intentional release of infectious agents and biological weapons to cause illness and death has the potential to greatly impact pregnant women and their fetuses. We review what is known about the mate...
Intentional release of infectious agents and biological weapons to cause illness and death has the potential to greatly impact pregnant women and their fetuses. We review what is known about the maternal and fetal effects of seven biological threats: Bacillus anthracis (anthrax); variola virus (smallpox); Clostridium botulinum toxin (botulism); Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis); Yersinia pestis (plague); Francisella tularensis (tularemia); and Rickettsia prowazekii (typhus). Evaluating the potential maternal, fetal, and infant consequences of an intentional release of an infectious agent requires an assessment of several key issues: (1) are pregnant women more susceptible to infection or illness compared to the general population?; (2) are pregnant women at increased risk for severe illness, morbidity, and mortality compared to the general population?; (3) does infection or illness during pregnancy place women, the fetus, or the infant at increased risk for adverse outcomes and how does this affect clinical management?; and (4) are the medical countermeasures recommended for the general population safe and effective during pregnancy? These issues help frame national guidance for the care of pregnant women during an intentional release of a biological threat. Birth Defects Research 109:391-398, 2017.© 2017 Wiley Periodicals, Inc.
- Relocating Pastorian Medicine: Accommodation and Acclimatization of Pastorian Practices against Smallpox at the Pasteur Institute of Chengdu, China, 1908-1927. [Journal Article]
- SCSci Context 2017; 30(1):33-59
- Argument Revising the diffusionist view of current scholarship on the Pasteur Institutes in China, this paper demonstrates the ways in which local networks and circumstances informed the circulation ...
Argument Revising the diffusionist view of current scholarship on the Pasteur Institutes in China, this paper demonstrates the ways in which local networks and circumstances informed the circulation and construction of knowledge and practices relating to smallpox prophylaxis in the Southwest of China during the early twentieth century. I argue that the Pasteur Institute of Chengdu did not operate in a natural continuity with the preceding local French medical institutions, but rather presented an intentional break from them. This Institute, as the first established by the French in China, strove for political and administrative independence both from the Chinese authority and from the Catholic Church. Yet, its operation realized political independence only partially. The founding of this Institute was also an attempt to satisfy the medical demand for local vaccine production. However, even though the Institute succeeded at producing the Jennerian vaccine locally, its production needed to accommodate local conditions pertaining to the climate, vaccine strains, and animals. Furthermore, vaccination had to conform to Chinese variolation, including its social and medical practices, in order to achieve the collaboration of local Chinese traditional practitioners with French colonial physicians, who were Pastorian-trained and worked at the Pasteur Institute of Chengdu. Thus the nature of the Pastorian work in Chengdu was not an imposition of foreign standards and practices, but rather a mutual compromise and collaboration between the French and the Chinese.
- Efficacy of delayed brincidofovir treatment against a lethal rabbitpox virus challenge in New Zealand White rabbits. [Journal Article]
- ARAntiviral Res 2017 Apr 06
- In the event of a bioterror attack with variola virus (smallpox), exposure may only be identified following onset of fever. To determine if antiviral therapy with brincidofovir (BCV; CMX001) initiate...
In the event of a bioterror attack with variola virus (smallpox), exposure may only be identified following onset of fever. To determine if antiviral therapy with brincidofovir (BCV; CMX001) initiated at, or following, onset of fever could prevent severe illness and death, a lethal rabbitpox model was used. BCV is in advanced development as an antiviral for the treatment of smallpox under the US Food and Drug Administration's 'Animal Rule'. This pivotal study assessed the efficacy of immediate versus delayed treatment with BCV following onset of symptomatic disease in New Zealand White rabbits intradermally inoculated with a lethal rabbitpox virus (RPXV), strain Utrecht. Infected rabbits with confirmed fever were randomized to blinded treatment with placebo, BCV, or BCV delayed by 24, 48, or 72 h. The primary objective evaluated the survival benefit with BCV treatment. The assessment of reduction in the severity and progression of clinical events associated with RPXV were secondary objectives. Clinically and statistically significant reductions in mortality were observed when BCV was initiated up to 48 h following the onset of fever; survival rates were 100%, 93%, and 93% in the immediate treatment, 24-h, and 48-h delayed treatment groups, respectively, versus 48% in the placebo group (p < 0.05 for each vs. placebo). Significant improvements in clinical and virologic parameters were also observed. These findings provide a scientific rationale for therapeutic intervention with BCV in the event of a smallpox outbreak when vaccination is contraindicated or when diagnosis follows the appearance of clinical signs and symptoms.
- [The advent of a newborn specialty: 19th century pediatrics]. [Journal Article]
- PMPresse Med 2017 Apr 05
- Pediatrics began under the most unfavorable conditions that are difficult to imagine nowadays. Children at the start of the 19th century were considered as negligible. The death rate was tremendous, ...
Pediatrics began under the most unfavorable conditions that are difficult to imagine nowadays. Children at the start of the 19th century were considered as negligible. The death rate was tremendous, increased by the work of children in factories as soon as 6 years of age in textile industries. In upper classes, infants were fed by a wet nurse, far from their parents and death rate was high as well. The emergence of pediatrics was the result of work carried out in adult medicine in the first half of the 19th century: clinical anatomic method, knowledge of contagious diseases even before the discovery of bacteria, birth of bacteriology. During the whole century, infectious diseases contributed in a large part to children mortality, as that of adults, by cholera, typhus, variola, diphtheria, measles and tuberculosis. Progresses noted during the 2nd part of the century resulted from beginning of hygiene, antisepsis, nutrition improvement, taking consideration of children as human being asking for protection. In contrast, therapeutics as serotherapy, vaccinations at the break of the 20th century played a secondary role.
- Generation and Production of Modified Vaccinia Virus Ankara (MVA) as a Vaccine Vector. [Journal Article]
- MMMethods Mol Biol 2017; 1581:97-119
- The smallpox vaccine based on the vaccinia virus was successfully used to eradicate smallpox, but although very effective, it was a very reactogenic vaccine and responsible for the deaths of one to t...
The smallpox vaccine based on the vaccinia virus was successfully used to eradicate smallpox, but although very effective, it was a very reactogenic vaccine and responsible for the deaths of one to two people per million vaccinated. Modified Vaccinia virus Ankara (MVA) is an attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer. MVA can encode one or more foreign antigens and thus can function as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant properties, and induces humoral and cellular immune responses. Many clinical trials of these new vaccines have been conducted, and the safety of MVA is now well documented. Immunogenicity is influenced by the dose and vaccination regimen, and information on the efficacy of MVA-vectored vaccines is now beginning to accumulate. In this chapter, we provide protocols for generation, isolation, amplification, and purification of recombinant MVA for preclinical and clinical evaluation.
- Vaccinia virus evasion of regulated cell death. [Review]
- ILImmunol Lett 2017 Mar 30
- Regulated cell death is a powerful anti-viral mechanism capable of aborting the virus replicative cycle and alerting neighbouring cells to the threat of infection. The biological importance of regula...
Regulated cell death is a powerful anti-viral mechanism capable of aborting the virus replicative cycle and alerting neighbouring cells to the threat of infection. The biological importance of regulated cell death is illustrated by the rich repertoire of host signalling cascades causing cell death and by the multiple strategies exhibited by viruses to block death signal transduction and preserve cell viability. Vaccinia virus (VACV), a poxvirus and the vaccine used to eradicate smallpox, encodes multiple proteins that interfere with apoptotic, necroptotic and pyroptotic signalling. Here the current knowledge on cell death pathways and how VACV proteins interact with them is reviewed. Studying the mechanisms evolved by VACV to counteract host programmed cell death has implications for its successful use as a vector for vaccination and as an oncolytic agent against cancer.
- The origins of the vaccine cold chain and a glimpse of the future. [Review]
- VVaccine 2017 Apr 19; 35(17):2115-2120
- International efforts to eradicate smallpox in the 1960s and 1970s provided the foundation for efforts to expand immunization programmes, including work to develop immunization supply chains. The nee...
International efforts to eradicate smallpox in the 1960s and 1970s provided the foundation for efforts to expand immunization programmes, including work to develop immunization supply chains. The need to create a reliable system to keep vaccines cold during the lengthy journey from the manufacturer to the point of use, even in remote areas, was a crucial concern during the early days of the Expanded Programme on Immunization. The vaccine cold chain was deliberately separated from other medical distribution systems to assure timely access to and control of vaccines and injection materials. The story of the early development of the vaccine cold chain shows how a number of challenges were overcome with technological and human resource solutions. For example, the lack of methods to monitor exposure of vaccines to heat during transport and storage led to many innovations, including temperature-sensitive vaccine vial monitors and better methods to record and communicate temperatures in vaccine stores. The need for appropriate equipment to store and transport vaccines in tropical developing countries led to innovations in refrigeration equipment as well as the introduction and widespread adoption of novel high performance vaccine cold-boxes and carriers. New technologies also helped to make injection safer. Underlying this work on technologies and equipment was a major effort to develop the human resources required to manage and implement the immunization supply chain. This included creating foundational policies and a management infrastructure; providing training for managers, health workers, technicians, and others. The vaccine cold chain has contributed to one of the world's public health success stories and provides three priority lessons for future: the vaccine supply chain needs to be integrated with other public health supplies, re-designed for efficiency and effectiveness and work is needed in the longer term to eliminate the need for refrigeration in the supply chain.
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- Variola minor in coalfield areas of England and Wales, 1921-34: Geographical determinants of a national smallpox epidemic that spread out of effective control. [Journal Article]
- SSSoc Sci Med 2017; 180:160-169
- This paper uses techniques of binary logistic regression to identify the spatial determinants of the last national epidemic of smallpox to spread in England and Wales, the variola minor epidemic of 1...
This paper uses techniques of binary logistic regression to identify the spatial determinants of the last national epidemic of smallpox to spread in England and Wales, the variola minor epidemic of 1921-34. Adjusting for age and county-level variations in vaccination coverage in infancy, the analysis identifies a dose-response gradient with increasing odds of elevated smallpox rates in local government areas with (i) medium (odds ratio [OR] = 5.32, 95% Confidence Interval [95% CI] 1.96-14.41) and high (OR = 11.32, 95% CI 4.20-31.59) coal mining occupation rates and (ii) medium (OR = 16.74, 95% CI 2.24-125.21) and high (OR = 63.43, 95% CI 7.82-497.21) levels of residential density. The results imply that the spatial transmission of variola virus was facilitated by the close spatial packing of individuals, with a heightened transmission risk in coal mining areas of the country. A syndemic interaction between common respiratory conditions arising from exposure to coal dust and smallpox virus transmission is postulated to have contributed to the findings. We suggest that further studies of the geographical intersection of coal mining and acute infections that are transmitted via respiratory secretions are warranted.