Amodiaquine and malaria prophylaxis

In 1985 the WHO and the United States Centers for Disease Control recommended that amodiaquine (400 mg weekly) could be used as a first-line malaria prophylactic in areas of the world with chloroquine resistance. Recently both the WHO and the CDC have withdrawn this recommendation. In this article, Tim Peto and Charles Gilks discuss the reasons behind the original recommendation and the events that led to the sudden change.     

Is the United States country zero for the First-World AIDS epidemic?

The incidence for AIDS per hundred thousand is several times higher in the United States than in the rest of the First World. Earlier work by Thompson (1984, 1989a, b, 1990, 1998) indicated that a relatively small proportion of gay males frequenting the bathhouses in the United States, drove AIDS over the epidemiological threshold in the U.S. It is shown that the rate of growth of AIDS is essentially the same for the United States and other First-World countries. An argument is advanced, based on WHO AIDS data, to the effect that it is contact with the pool of infectives in the United States that drives the epidemic in other First-World Countries.     

Cyanotoxins in inland lakes of the United States: Occurrence and potential recreational health risks in the EPA National Lakes Assessment 2007

A large nation-wide survey of cyanotoxins (1161 lakes) in the United States (U.S.) was conducted during the EPA National Lakes Assessment 2007. Cyanotoxin data were compared with cyanobacteria abundance- and chlorophyll-based World Health Organization (WHO) thresholds and mouse toxicity data to evaluate potential recreational risks. Cylindrospermopsins, microcystins, and saxitoxins were detected (ELISA) in 4.0, 32, and 7.7% of samples with mean concentrations of 0.56, 3.0, and 0.061 μg/L, respectively (detections only). Co-occurrence of the three cyanotoxin classes was rare (0.32%) when at least one toxin was detected. Cyanobacteria were present and dominant in 98 and 76% of samples, respectively. Potential anatoxin-, cylindrospermopsin-, microcystin-, and saxitoxin-producing cyanobacteria occurred in 81, 67, 95, and 79% of samples, respectively. Anatoxin-a and nodularin-R were detected (LC/MS/MS) in 15 and 3.7% samples (n = 27). The WHO moderate and high risk thresholds for microcystins, cyanobacteria abundance, and total chlorophyll were exceeded in 1.1, 27, and 44% of samples, respectively. Complete agreement by all three WHO microcystin metrics occurred in 27% of samples. This suggests that WHO microcystin metrics based on total chlorophyll and cyanobacterial abundance can overestimate microcystin risk when compared to WHO microcystin thresholds. The lack of parity among the WHO thresholds was expected since chlorophyll is common amongst all phytoplankton and not all cyanobacteria produce microcystins.     

浅谈WHO国家疫苗监管体系评估及其上市许可板块要求

通过卫生组织国家疫苗监管体系(National Regulatory Authority)评估是一个国家疫苗具备参与联合国全球采购资格的必要条件。本文对WHO国家疫苗监管体系评估整体加以简述,重点对上市许可板块指标进行归纳,通过探讨WHO国家疫苗监管体系评估上市许可部分的管理理念,以期为疫苗监管相关部门加强自身管理提升监管质量和效率有所提示。     

Changes to International Nonproprietary Names for antibody therapeutics 2017 and beyond: of mice,men and more

Active pharmaceutical substances require an International Nonproprietary Name (INN) assigned by the World Health Organization (WHO) to obtain market authorization as a medicinal product. INNs are selected to represent a unique, generic name for a drug enabling unambiguous identification by stakeholders worldwide. INNs may be requested after initiating clinical development of an investigational drug. Pharmaceutical classes are indicated by a common stem or suffix. Currently, INNs for monoclonal antibody-based drugs are recognized by the suffix, -mab, preceded by a source infix such as -xi- (chimeric), -zu- (humanized) or -u- (human) designating the species from which the antibody was derived. However, many technological advances have made it increasingly difficult to accurately capture an antibody's source in its name. In 2014, the WHO and the United States Adopted Names (USAN) Council approached this challenge by implementing changes to antibody source infix definitions. Unfortunately, gaps and ambiguities in the definitions and procedures resulted in inconsistent source category assignments and widespread confusion. The Antibody Society, extensively supported by academic and industry scientists, voiced concerns leading to constructive dialog during scheduled consultations with WHO and USAN Council representatives. In June 2017, the WHO announced that use of the source infix will be discontinued for new antibody INNs effective immediately. We fully support this change as it better aligns antibody INNs with current and foreseeable future innovations in antibody therapeutics. Here we review the changes implemented. Additionally, we analyzed antibody INNs recently assigned under the previous 2014 definitions and provide recommendations for further alignment.     

Technology and malaria control, 1930-1960: the career of Rockefeller Foundation engineer Frederick W. Knipe

Frederick W. Knipe was a malaria-control engineer with the Rockefeller Foundation, serving in Bulgaria, Albania, India, Mexico, Italy, and the United States. There were two phases to his career: from 1930 to 1943 he focused on drainage works that reduced or eliminated mosquito habitat, and from 1944 to 1960 he supervised DDT spraying programs. His appointments to the WHO Expert Committee on Insecticides, 1948-55, demonstrate that his contributions to malaria-control were highly regarded by his peers.     

International programme on chemical safety (IPCS) environmental health criteria on boron human health risk assessment

The International Program on Chemical Safety (IPCS), a collaborative program of the United Nations Environment Program, the International Labour Organization (ILO), and the World Health Organization (WHO), includes the Environmental Health Criteria (EHC) Program inaugurated in 1973 by WHO. These EHC are integrated evaluations of the human health and environmental risks from exposure to specific chemicals carried out by a group of international scientists. Boron (B) was evaluated at an IPCS Task Group (TG) convened in November 1996. All TGs are convened under WHO rules and procedures. These procedures relate the overall process used to prepare an EHC including transparency of the process, conflict of interest, the roles of Members and Observers, and the conduct of the TG. The scope and purpose of an EHC, for an element such as B, and its possible role in national and international chemical safety programs will be discussed. In the early 1990s, countries asked that IPCS request TGs to prepare, where data permit, health-based guidance values (GVs) (both total daily intake and to recommend health-based guidelines for various environmental media). This final evaluation in an EHC reflects the collective consensus view of the TG Members. To foster the use of consistent methodology by TGs, IPCS prepared in 1994 an EHC on the methodology for the preparation of GVs for human exposure limits (EHC 170). In developing their final evaluation, TGs have been asked to consider using this methodology. This was done by the TG on B, and a total daily intake for humans of 0.4 mg/kg body wt was derived from animal studies of reproductive and developmental effects in rodents and pharmacokinetic data from both animals and humans. The application of the methodology described in EHC 170 regarding choice of critical effect and uncertainty factors will be discussed.     

Visual problems in the elderly population and implications for services.

OBJECTIVE--To determine the prevalence of visual disability and common eye disease among elderly people in inner London. DESIGN--Cross sectional random sample survey. SETTING--Inner London health centre. SUBJECTS--Random sample of people aged 65 and over taken from practice''s computerised age-sex register. MAIN OUTCOME MEASURES--Presenting binocular Snellen 6 m distance acuity and best monocular 3 m Sonksen-Silver acuity to classify prevalence of blindness by World Health Organisation criteria (less than 3/60 in better eye) and American criteria for legal blindness (better eye equal to 6/60 or less) and of low vision by WHO criteria (best acuity 6/18) and visual impairment by American criteria (less than 6/12 or 20/40 but greater than 6/60 or 20/200 in better eye). Principal cause of visual loss by diagnosis, referral indication by cause to hospital eye service, and proportion of cases known to primary care. RESULTS--207 of 288 (72%) eligible people were examined. 17 (8%) housebound subjects were examined at home. The prevalence of blindness was 1% by WHO criteria and 3.9% by American criteria. The prevalence of low vision (WHO criteria) was 7.7%. The prevalence of visual impairment (American criteria) was 10.6%. Cataract accounted for 75% of cases of low vision. Only eight out of 16 patients with low vision were known by their general practitioner to have an eye problem. 56 subjects (27%) would probably have benefited from refraction. Comparisons with studies in the United States and Finland suggested higher rates in this sample, mainly due to the prevalence of disabling cataract. CONCLUSION--There seems to be a considerable amount of undetected ocular disease in elderly people in the community.     

Availability and Use of HIV Monitoring and Early Infant Diagnosis Technologies in WHO Member States in 2011–2013: Analysis of Annual Surveys at the Facility Level

BackgroundThe Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 targets have reinforced the importance of functioning laboratory services to ensure prompt diagnosis and to assess treatment efficacy. We surveyed the availability and utilization of technologies for HIV treatment monitoring and early infant diagnosis (EID) in World Health Organization (WHO) Member States.ConclusionThis is the first attempt to comprehensively gather information on HIV testing technology coverage in WHO Member States. The survey results suggest that major operational changes will need to be implemented, particularly in low- and middle-income countries, if the 90-90-90 targets are to be met.     

Screening Level Assessment of Risks Associated with Dietary Exposure to Selected Heavy Metals,Polycyclic Aromatic Hydrocarbons,and Radionuclides in Kuwait

To assess the health risks associated with dietary exposure of the Kuwait population, two market baskets comprising 146 food items, which represented the diets of various age groups of the Kuwaiti population, were collected twice, once in the winter of 1997 and again in the summer of 1998, to account for seasonal variation. These food items were analyzed for their heavy metals, polycyclic aromatic hydrocarbons (PAHs) and selected radionuclides contents. Probabilistic risk assessments using the Monte Carlo simulation technique were conducted for Cd, Pb, PAHs, ¹³⁷Cs, ⁹⁰Sr, and ²²⁶Ra. The data obtained showed that high Cd and Pb exposures, which exceeded the World Health Organization's (WHO's) standards are encountered among young children. Exposures to PAHs of the different age groups of the Kuwaiti population were not unusually high at the higher percentiles. On the other hand, dietary exposures to ⁹⁰Sr were all below WHO standards for all percentile and age groups. Exposures to ¹³⁷Cs were slightly above the WHO standard at the 90^th percentile for most age groups, and ²²⁶Ra exposures were all well above WHO standards at the upper percentiles for all age groups, but still below the United States Food and Drug Administration's (USFDA's) intervention levels.     

甲型H1N1流感病毒快速核酸检测技术的建立

美国、墨西哥等国家相继发生甲型H1N1流感疫情后,即刻引起全球关注。WHO日前宣布目前为流感大流行第五期,预示又一次流感大流行可能逼近。正确检测和鉴定病毒是必须解决的首要问题。我们开展了甲型H1N1流感病毒快速核酸检测技术的研制工作,目前已经建立了甲型H1N1流感病毒核酸RT-PCR检测技术,并将其及时用于临床样本的检测。     

Construction of a Preclinical Multimodality Phantom Using Tissue-mimicking Materials for Quality Assurance in Tumor Size Measurement

World Health Organization (WHO) and the Response Evaluation Criteria in Solid Tumors (RECIST) working groups advocated standardized criteria for radiologic assessment of solid tumors in response to anti-tumor drug therapy in the 1980s and 1990s, respectively. WHO criteria measure solid tumors in two-dimensions, whereas RECIST measurements use only one-dimension which is considered to be more reproducible ^{1, 2, 3,4,5}. These criteria have been widely used as the only imaging biomarker approved by the United States Food and Drug Administration (FDA) ⁶. In order to measure tumor response to anti-tumor drugs on images with accuracy, therefore, a robust quality assurance (QA) procedures and corresponding QA phantom are needed.To address this need, the authors constructed a preclinical multimodality (for ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) phantom using tissue-mimicking (TM) materials based on the limited number of target lesions required by RECIST by revising a Gammex US commercial phantom ⁷. The Appendix in Lee et al. demonstrates the procedures of phantom fabrication ⁷. In this article, all protocols are introduced in a step-by-step fashion beginning with procedures for preparing the silicone molds for casting tumor-simulating test objects in the phantom, followed by preparation of TM materials for multimodality imaging, and finally construction of the preclinical multimodality QA phantom. The primary purpose of this paper is to provide the protocols to allow anyone interested in independently constructing a phantom for their own projects. QA procedures for tumor size measurement, and RECIST, WHO and volume measurement results of test objects made at multiple institutions using this QA phantom are shown in detail in Lee et al. ⁸.     

Canadian recommendations underestimate energy needs of women over fifty years as determined by doubly-labelled water

Accurate estimations of energy requirements at the population level are crucial because of disease processes associated with energy imbalance. The present objective was to compare energy expenditure with existing Recommended Nutrient Intakes for Canadians (RNIC) and determine whether the RNIC provides a true index of energy requirement in middle-aged and elderly Canadian women. A second objective was to compare energy expenditure and the RNIC to Food and Agriculture Organization, World Health Organization, United Nations University (FAO/WHO/UNU) predictions. Seventy-six women were recruited for the study (67.3 +/- 11.5 y, 63 +/- 11.7 kg, BMI 24.8 +/- 4.4 kg x m(-2)). The two-point doubly-labelled water (DLW) method was used over 13 days to assess energy expenditure while subjects carried out their routine activities. Subjects were stratified to enable age specific requirements for middle-aged and elderly women. At weight maintenance, energy needs were underestimated using the RNIC (7.1 +/- 1.6 MJ x d(-1), 1698 +/- 391 kcal x d(-1)) compared to total energy expenditure (10.0 +/- 3.2 MJ x d(-1), 2395 +/- 746 kcal x d(-1)) as determined by DLW as a whole and for each age group. The RNIC recommendations were lower than the FAO/WHO/UNU estimations even for light activity. Results indicate that mean energy expenditure was 29% greater than the RNIC recommendations created using formulas based on age and weight, whereas the FAO/WHO/ UNU estimations closely approximated energy expenditure based on heavy activity in women 49-79 y and light activity in women over 80 y old. These data suggest a systematic underestimation of Canadian energy recommendations for women.     

Eradication of Yaws: Historical Efforts and Achieving WHO's 2020 Target

Background

Yaws, one of the 17 neglected tropical diseases (NTDs), is targeted for eradication by 2020 in resolution WHA66.12 of the World Health Assembly (2013) and the WHO roadmap on NTDs (2012). The disease frequently affects children who live in poor socioeconomic conditions. Between 1952 and 1964, WHO and the United Nations Children''s Fund (UNICEF) led a global eradication campaign using injectable benzathine penicillin. Recent developments using a single dose of oral azithromycin have renewed optimism that eradication can be achieved through a comprehensive large-scale treatment strategy. We review historical efforts to eradicate yaws and argue that this goal is now technically feasible using new tools and with the favorable environment for control of NTDs. We also summarize the work of WHO''s Department of Control of Neglected Tropical Diseases in leading the renewed eradication initiative and call on the international community to support efforts to achieve the 2020 eradication goal. The critical factor remains access to azithromycin. Excluding medicines, the financial cost of yaws eradication could be as little as US$ 100 million.

Conclusions

The development of new tools has renewed interest in eradication of yaws; with modest support, the WHO eradication target of 2020 can be achieved.     

Deep within the filarial genome: progress of the filarial genome project.

Four years ago, a WHO/United Nations Development Programme/World Bank-sponsored genome project to study the filarial lymphatic nematode parasite Brugia malayi was initiated. The project took as its aims gene discovery for drug target and vaccine candidate identification, genome mapping, dissemination of genomic data to the world community and training of endemic country partners in genomic research. In this article, the principal investigators in the laboratories behind the project describe the background to the project, the data now emerging and goals for the future. Open access to filarial genome data is emphasized.     

Baby food industry lobbies WHO on breast feeding advice

In the existing WHO guidelines, complementary feeding at 4-6 months is advocated. However, many nutrition specialists believe that these guidelines lead to complementary foods being offered from the age of 3 months, or even earlier, subsequently suggesting that the WHO should change its recommendations to about 6 months. To this effect, the International Association of Infant Food Manufacturers lobbied the WHO to delay any change to its recommendations on the optimal length of exclusive breast-feeding. Their message states that any action dealing with Infant and Young Child Nutrition should be delayed until the World Health Assembly 2002. Supporting facts to justify the message argue the importance of an international study on infant growth being carried out by the WHO, which should be finished by 2002. Nevertheless, several nutrition specialists believe that the scientific evidence to support a change in the WHO policy already exists and that such a study was not set up to determine the optimal length of exclusive breast-feeding.     

WHO/KFDA joint workshop on implementing WHO guidelines on evaluating similar biotherapeutic products, Seoul, Republic of Korea 24-26 August, 2010

In August 2010, the World Health Organization and the Korea Food & Drug Administration jointly organized the first implementation workshop of WHO guidelines on evaluating similar biotherapeutic products (SBPs) at the global level. The objective of the Workshop was to facilitate implementation of the newly adopted WHO Guidelines into the practice of national regulatory authorities (NRAs). WHO Guidelines were recognized by the workshop participants as a tool for harmonizing regulatory requirements worldwide. By reviewing and practicing several case studies, better understanding and consensus on the principles of clinical trial designs were reached. However, variations in terms of the national requirements for quality, safety and efficacy of these products revealed diversity in the regulatory expectations in different countries and regions. In addition, lack of terminology for the products developed as copy products (so called "me too" products) with a partial comparability to an RBP, led to a great diversity in evaluating as well as naming these products. The workshop participants proposed the following actions: a) NRAs should make efforts to build their capacities for regulation of SBPs; b) WHO should revise WHO Guidelines for assuring the quality of products prepared by recombinant DNA technology (WHO TRS 814) and continue monitoring progress with the implementation of the Guidelines on evaluating SBPs. Publication of the outcome of the Workshop was recognized as another action that WHO should coordinate.     

Manufacturing and supply of monovalent oral polio vaccines.

A new polio vaccine was developed, produced and licensed by sanofi pasteur at the request of the World Health Organization (WHO) for mass immunization campaigns in endemic countries such as Egypt. The new vaccine, monovalent oral polio vaccine 1 or mOPV1, is currently used in Egypt as a critical part of a new WHO strategy to end polio type 1 transmission by the end of the year 2005 (types 2 and 3 polioviruses have already been eliminated from Egypt). To answer this specific need, an urgent program was mounted by Sanofi pasteur to manufacture 50million doses for Egypt, in close collaboration with WHO and National Regulatory Agencies (France and Egypt). The joint efforts between manufacturer, regulators and the WHO resulted in the quickest ever vaccine development and licensure and WHO pre-qualification. The production of mOPV was based on existing tOPV but with appropriate "change control" procedures to assure the quality of the product, and to distinguish mOPV from tOPV. Key success factors included clear and careful definition of the project; close collaboration between manufacturer, regulators and WHO; and commitment and motivation of staff. As a result, development and production of mOPV1 vaccine were carried out in a drastically reduced time period, leading to the release and delivery of the first 15 million doses of mOPV1 in April 2005.     

Design and development of oral drugs for the prophylaxis and treatment of smallpox infection

Smallpox was eradicated by the World Health Organization (WHO) vaccination campaign in the 1970s and the variola virus was restricted to repositories in the United States and Russia. Recently, however, concerns have arisen about the possible existence of variola outside these sites and the potential for using the virus as a weapon of bioterror. The world population now has little residual immunity to smallpox and supplies of the smallpox vaccine are being reconstituted. Large numbers of individuals with various skin diseases or immunosuppression owing to AIDS or organ transplantation medications, or who are pregnant or have heart disease might not be ideal candidates for vaccination with the current live vaccines. It would be useful to have an orally active drug that could be self-administered in case of an outbreak of smallpox.     

Quantitative risk assessment of Listeria monocytogenes in ready-to-eat foods: the FAO/WHO approach

Quantitative microbiological risk assessment is a very new and unique scientific approach able to link, for the first time, data from food (in the farm-to-fork continuum) and the various data on human disease to provide a clear estimation of the impact of contaminated food on human public health. The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) have recently launched risk assessment studies of a number of pathogen-food commodity combinations (Salmonella in eggs and in broiler chickens, Listeria monocytogenes in ready-to-eat foods, Campylobacter in broiler chickens, Vibrio in seafood) to be used to lower the risk associated with these food-borne diseases and ensure fair practices in the international trade of food. The FAO/WHO Listeria risk assessment was undertaken in part to determine how previously developed risk assessments done at the national level could be adapted or expanded to address concerns related to L. monocytogenes in ready-to-eat foods at an international level. In addition, after initiation of the risk assessment, the risk assessors were asked by the Codex Committee on Food to consider three specific questions related to ready-to-eat foods in general, which are: (1). estimate the risk for consumers in different susceptible populations groups (elderly, infants, pregnant women and immunocompromised patients) relative to the general population; (2). estimate the risk for L. monocytogenes in foods that support growth and foods that do not support growth under specific storage and shelf-life conditions; (3). estimate the risk from L. monocytogenes in food when the number of organisms ranges from absence in 25 g to 1000 colonies forming units per gram or milliliter, or does not exceed specified levels at the point of consumption. To achieve these goals, new dose-response relationships and exposure assessments for ready-to-eat foods were developed. Preliminary data indicate that eliminating the higher dose levels at the time of consumption has a large impact on the number of predicted cases.