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This article presents the WHO recommendations on the use of cholera vaccines excerpted from the recently published Cholera vaccines: WHO position paper. This document replaces the WHO position paper on Cholera vaccines published in the Weekly Epidemiological Record in April 2001. Footnotes to this paper provide a limited number of core references; their abstracts as well as a more comprehensive list of references may be found at http://www.who.int/immunization/documents/positionpapers/en/index.html. Grading tables which assess the quality of scientific evidence for key conclusions are also available through this link and are referenced in the position paper. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This updated paper reflects the recent recommendations of WHO's Strategic Advisory Group of Experts on immunization (SAGE)., (Copyright 2010. Published by Elsevier Ltd.. All rights reserved.)

Background Global estimates for cholera annually approximate 4 million cases worldwide with 95,000 deaths. Recent outbreaks, including Haiti and Yemen, are reminders that cholera is still a global health concern. Cholera outbreaks can rapidly induce high death tolls by overwhelming the capacity of health facilities, especially in remote areas or areas of civil unrest. Recent studies demonstrated that stool specimens preserved on filter paper facilitate molecular analysis of Vibrio cholerae in resource limited settings. Specimens preserved in a rapid, low-cost, safe and sustainable manner for sequencing provides previously unavailable data about circulating cholera strains. This may ultimately contribute new information to shape public policy response on cholera control and elimination. Methodology/Principal findings Whole genome sequencing (WGS) recovered close to a complete sequence of the V. cholerae O1 genome with satisfactory genome coverage from stool specimens enriched in alkaline peptone water (APW) and V. cholerae culture isolates, both spotted on filter paper. The minimum concentration of V. cholerae DNA sufficient to produce quality genomic information was 0.02 ng/μL. The genomic data confirmed the presence or absence of genes of epidemiological interest, including cholera toxin and pilus loci. WGS identified a variety of diarrheal pathogens from APW-enriched specimen spotted filter paper, highlighting the potential for this technique to explore the gut microbiome, potentially identifying co-infections, which may impact the severity of disease. WGS demonstrated that these specimens fit within the current global cholera phylogenetic tree, identifying the strains as the 7th pandemic El Tor. Conclusions WGS results allowed for mapping of short reads from APW-enriched specimen and culture isolate spotted filter papers. This provided valuable molecular epidemiological sequence information on V. cholerae strains from remote, low-resource settings. These results identified the presence of co-infecting pathogens while providing rare insight into the specific V. cholerae strains causing outbreaks in cholera-endemic areas., Author summary Cholera affects more than 4 million people globally every year; people predominantly living in poverty or in resource-constrained conditions including political crises or natural disasters. Cholera’s typical presentation is characterized by rapid onset of acute watery diarrhea and vomiting which can progress from watery stool to shock in as little as four hours. Laboratory conditions needed for culture confirmation and strain preservation are rarely to never present in these affected areas. In fact, many cholera endemic areas in Sub-Saharan African are so remote that even treatment response alone is often challenging. Here we present the genomic analysis of DNA extracted from dried filter paper, which is a low-cost, low-tech and sustainable method. Previously this method has facilitated cholera confirmation by PCR, but we demonstrate that this method is also suitable for whole genome sequencing and subsequent strain characterization by presenting the analysis of samples from an outbreak in a remote area of Cameroon. This method will facilitate the understanding of the molecular epidemiology in cholera-prone areas, which were previously too challenging to attempt. It also introduces a method that can be used on a broader scale for diarrheal disease surveillance, including providing a window into co-infection and microbiome analyses.

Cholera is now considered to be endemic in Haiti, often with increased incidence during rainy seasons. The challenge of cholera surveillance is exacerbated by the cost of sample collection and laboratory analysis. A diagnostic tool is needed that is low cost, easy-to-use, and able to detect and quantify Vibrio cholerae accurately in water samples within 18-24h, and perform reliably in remote settings lacking laboratory infrastructure and skilled staff. The two main objectives of this study were to develop and evaluate a new culture medium embedded in a new diagnostic tool (PAD for paper based analytical device) for detecting Vibrio cholerae from water samples collected in Haiti. The intent is to provide guidance for corrective action, such as chlorination, for water positive for V. cholerae epidemic strains. For detecting Vibrio cholerae, a new chromogenic medium was designed and evaluated as an alternative to thiosulfate citrate bile salts sucrose (TCBS) agar for testing raw water samples. Sensitivity and specificity of the medium were assessed using both raw and spiked water samples. The Vibrio cholerae chromogenic medium was proved to be highly selective against most of the cultivable bacteria in the water samples, without loss of sensitivity in detection of V. cholerae. Thus, reliability of this new culture medium for detection of V. cholerae in the presence of other Vibrio species in water samples offers a significant advantage. A new paper based device containing the new chromogenic medium previously evaluated was compared with reference methods for detecting V. cholerae from spiked water sample. The microbiological PAD specifications were evaluated in Haiti. More precisely, a total of 185 water samples were collected at five sites in Haiti, June 2014 and again in June 2015. With this new tool, three V. cholerae O1 and 17 V. cholerae non-O1/O139 strains were isolated. The presence of virulence-associated and regulatory genes, including ctxA, zot, ace, and toxR, was confirmed using multiplex PCR. The three V. cholerae O1 isolates were positive for three of the four virulence-associated and regulatory genes. Twelve of the V. cholerae non-O1/O139 isolates were found to carry toxR, but none were ctxA+, zot+, or ace+. However, six of the V. cholerae non-O1/O139 isolates were resistant to penicillin, ampicillin, trimethoprim/sulfamethoxazole, nalidixic acid, and ciprofloxacin. The paper based analytical device (PAD) provides advantages in that standard culture methods employing agar plates are not required. Also, intermediary isolation steps were not required, including transfer to selective growth media, hence these steps being omitted reduced time to results. Furthermore, experienced technical skills also were not required. Thus, PAD is well suited for resource-limited settings.

Confirmation of a cholera epidemic is based on bacteriological identification of the agent and requires the sending of samples to a culture laboratory, often in countries with limited resources. Comparison of the use of filter paper with the use of Cary-Blair reference medium for stool transport showed that this simple transport medium is appropriate for the recovery of Vibrio cholerae .

This article presents the World Health Organization's (WHO) recommendations on the use of cholera vaccines excerpted from the Cholera vaccines: WHO position paper, August 2017, published in the Weekly Epidemiological Record (Cholera vaccine, 2017) [1]. This position paper replaces the 2010 WHO position paper on cholera vaccines (Cholera vaccine, 2010) [2]. It incorporates the most recent evidence on cholera vaccination and provides revised recommendations on the target populations for cholera immunization. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of cholera vaccines were discussed by the Strategic Advisory Group of Experts (SAGE) in April 2017; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2017/April/presentations_background_docs/en/.

Dear Sir: We read with great interest the recent article by Debes and others1 concerning simplified cholera surveillance methods performed in the Far North Region of Cameroon in 2013–2014. The authors described the novel use of filter paper to preserve DNA specimens for polymerase chain reaction (PCR) confirmation of cholera. In another recent article,2 they used the same sampling method to genotype Vibrio cholerae using multiple loci variable number tandem repeat (VNTR) analysis (MLVA), in the same resource-constrained area. In both studies, stool specimens were initially enriched for 6–8 hours in alkaline peptone water (APW). One to two drops of the enrichment were subsequently aliquoted onto Whatman 903 Protein Saver Cards (GE Healthcare Limited, Chalfont St.Giles, UK) and allowed to air-dry. While investigating the origin of a cholera epidemic in the Republic of Guinea3 in September 2012, we experimented direct dried stool sampling on filter paper in the neighboring Sierra Leone, without prior enrichment in APW. Indeed, analysis of surveillance data and field investigations suggested a recent importation of cholera from Sierra Leone. However, lacking laboratory capacities in this country impaired the inclusion of samples for genetic comparison with Guinean culture isolates.4 Dried blood or saliva specimens on filter paper are relatively easy to collect, store, and transport, as they are not subject to United Nations biosafety regulations for transport of category B infectious substances.5 Moreover, direct PCR detection of V. cholerae on stool samples has been shown to represent a successful diagnosis method for cholera.6 With official authorization of Sierra Leonean health authorities, 17 suspected cholera patients were thus anonymously sampled in cholera treatment units in several coastal districts (Supplemental Figure 1). One or two drops of their watery diarrhea were directly collected from nonchlorinated buckets below cholera cots and then deposited onto each sample area of Whatman FTA Elute Micro Cards (GE Healthcare Limited, Chalfont St. Giles, UK). Each sample was air-dried for approximately 5 minutes in a shaded area, sealed with a Desiccant Packet (GE Healthcare Limited, Chalfont St. Giles, UK) into individual Multi-Barrier Pouches (GE Healthcare Limited, Chalfont St. Giles, UK), transported to Marseille, France, and stored at ambient temperature. For technical reasons, DNA extraction was performed only in June 2015. Using a scalpel, a 1-cm2 area of the filter paper was removed and suspended in 500 μL NucliSENS® easyMAG® lysis buffer (bioMerieux, Marcy l'Etoile, France) overnight at 4°C. The DNA was then extracted using a NucliSENS® easyMAG® platform (bioMerieux, Marcy l'Etoile, France) as previously described,7 and the supernatants were stored at −20°C for downstream PCR assays. To check for conserved DNA, a 16S ribosomal DNA PCR was performed as previously described.8 Six previously described VNTRs7 were independently genotyped for each sample. All primer pairs were verified to be specific for V. cholerae using National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST), and one primer set was located within the cholera toxin A subunit promoter region. MLVA results of the Sierra Leonean samples were included within the genotype panel of 35 Guinean isolates isolated via conventional culture in February–September 2012 (Supplemental Figure 1) and genotyped using the same method.7 The presence of amplifiable bacterial DNA was confirmed by 16S PCR in all 17 filter paper samples (Supplemental Table 1). Toxigenic V. cholerae was confirmed and MLVA genotyping was completed for nine of them. All VNTR-specific PCRs were negative for the eight remaining samples, which suggest that the corresponding patients may have been affected by noncholera acute watery diarrhea. The panel of nine genotyped samples from Sierra Leone displayed four distinct MLVA types (1, 5, 6, and 7). Together with the samples from Guinea, these MLVA types formed a single clonal complex of 13 closely related MLVA types (Supplemental Figure 1). Two MLVA types (5 and 6) were common to both Sierra Leonean and Guinean samples (Supplemental Figure 1). We thus confirm that filter paper is a very convenient, inexpensive, and efficient tool to sample suspected cholera cases for delayed molecular studies, including V. cholerae MLVA genotyping, even after several years of storage at room temperature. Moreover, we demonstrate that prior stool enrichment in APW is not necessary to perform specific V. cholerae PCRs, which renders sampling even easier. Further experiments are required to determine whether this method of DNA collection and conservation is sufficient for V. cholerae whole-genome single nucleotide polymorphism–based phylogenetics. In addition, MLVA genotyping of these cholera filter paper samples further bolsters the initial conclusion that Sierra Leone and the Republic of Guinea were affected in 2012 by the same transborder cholera epidemic,3 which was genetically related to outbreaks in Togo between 2010 and 2012.7 Such genotyping results can provide valuable insight to optimize control and prevention strategies. Direct stool sampling on filter papers should therefore be included in the rapid response package to investigate cholera epidemics, especially when V. cholerae culture and strain storage facilities are not available or biosafety shipping to specialized genotyping laboratories is too complicated.

The "View now" link directs to the finding aid only. Please email wvrhcref@westvirginia.libanswers.com or call 304-293-3536 for more information about accessing collection A&M 1563 Alfred Beckley (1802-1888) Papers, 1832-1856. Correspondence of General Alfred Beckley and his wife Emily Craig. Several of the letters are by Beckley's mother from Lexington, Kentucky and comment on the Presidential election of 1832 in that state, the reception of President Jackson's in Lexington, 1832 the Cholera scourge, and local social affairs. The rest of the letters are concerned with family matters.

Through his consideration of responses to 19th-century cholera outbreaks in the United States, Whooley explores interplay among science, medicine, and society.