Harare, Zimbabwe — Zimbabwe has recorded new cases of cholera several months after declaring the end of an outbreak that killed more than 700 people over an 18-month period.  On Wednesday, Zimbabwe confirmed a new outbreak of cholera has been recorded in the district of Kariba — on the border with Zambia — where 21 cases have been confirmed and one person died.  Dr. Godfrey Muza, the Kariba district medical officer, said the government is working to contain the situation:  "We have set up cholera equipment camp and also some oral rehydration points within the affected villages," said Muza. "We are getting assistance from our local and regional partners like MSF [Medecins Sans Frontieres, also known as Doctors Without Borders] and UNICEF. And our teams are on the ground doing risk communication and community engagement activities on health promotion, hygiene promotion and assisting the community in terms of improving sanction."   In August, the Zimbabwe government declared that the 18-month long cholera outbreak was over. The outbreak  affected up to 35,000 people and claimed more than 700 lives. Zimbabwe has dealt with cholera outbreaks in the past.  In 2008, an outbreak resulted in more than 98,000 cases and more than 4,000 reported deaths.   Independent health experts such as Dr. Norman Matara of Zimbabwe Doctors for Human Rights said the government needs to address the conditions that enable the waterborne disease to spread.  "In public health, we often say cholera is a disease of poverty which mainly affects people with inadequate access to safe water and basic sanitation," said Matara. "In Zimbabwe, we have witnessed perennial cholera outbreaks in recent years and these outbreaks are being caused by a lack of safe drinking water supply and a broken-down sanitation system which leaves residents in densely populated communities surrounded by flowing sewer. This sewer will then contaminate alternative sources of water such as shower wells, streams, rivers and even boreholes resulting in people drinking or eating food contaminated with the cholera bacteria."  He said that those conditions have been chronic over the years in Zimbabwe, contributing to the repeated outbreaks.  How does Zimbabwe get out of this cycle of recurring cholera outbreaks?  "We need to make sure that our hospitals are well-supposed with the real addressing solutions and medicines so that people can be assisted," said Matara. " ... Also, those high-risk communities, especially in towns and urban cities, we may give them the oral cholera vaccine so that they may be protected. In the long term, the government needs to invest more in proper sanitation facilities and infrastructure as well as making sure that people are provided with clean safe water for drinking and cooking."  Matara said he hopes the current outbreak is contained quickly and does not spread to other parts of Zimbabwe.  But with raw sewage flowing in some streets of Harare, it might be a question of time.  

[VOA] Harare, Zimbabwe -- Zimbabwe has recorded new cases of cholera several months after declaring the end of an outbreak that killed more than 700 people over an 18-month period.

Bharat Biotech announced the release of an medlinkoral cholera vaccine/medlink (OCV), a significant public health issue in regions with inadequate sanitation (!--ref1--).

Mumbai-based drug maker i TechInvention Lifecare /i in partnership with South Korean Eubiologics, has launched an oral cholera vaccine in India

The United Nations humanitarian agency has intensified its efforts to address the medlinkcholera/medlink (!--ref1--) outbreak in Somalia, as the death toll has risen to 120 since January.

Hopkinson, Deborah, author

Surge in cholera cases renews attention on the need to fortify public health

Princeton University researchers have discovered that the bacteria behind the life-threatening disease cholera initiates infection by coordinating a wave of mass shapeshifting that allows them to more effectively penetrate their victims' intestines. The researchers also identified the protein that allows Vibrio cholerae to morph, and found that it's activated through quorum sensing. The findings could lead to new treatments for cholera that target the bacteria's ability to change shape or penetrate the gut.

Several pathogenic bacteria utilize sialic acid, including host-derived N-acetylneuraminic acid (Neu5Ac), in at least two ways: they use it as a nutrient source and as a host-evasion strategy by coating themselves with Neu5Ac. Given the significant role of sialic acid in pathogenesis and host-gut colonization by various pathogenic bacteria, including Neisseria meningitidis, Haemophilus influenzae, Pasteurella multocida and Vibrio cholerae, several enzymes of the sialic acid catabolic, biosynthetic and incorporation pathways are considered to be potential drug targets. In this work, findings on the structural and functional characterization of CMP-N-acetylneuraminate synthetase (CMAS), a key enzyme in the incorporation pathway, from Vibrio cholerae are reported. CMAS catalyzes the synthesis of CMP-sialic acid by utilizing CTP and sialic acid. Crystal structures of the apo and the CDP-bound forms of the enzyme were determined, which allowed the identification of the metal cofactor Mg2+ in the active site interacting with CDP and the invariant Asp215 residue. While open and closed structural forms of the enzyme from eukaryotic and other bacterial species have already been characterized, a partially closed structure of V. cholerae CMAS (VcCMAS) observed upon CDP binding, representing an intermediate state, is reported here. The kinetic data suggest that VcCMAS is capable of activating the two most common sialic acid derivatives, Neu5Ac and Neu5Gc. Amino-acid sequence and structural comparison of the active site of VcCMAS with those of eukaryotic and other bacterial counterparts reveal a diverse hydrophobic pocket that interacts with the C5 substituents of sialic acid. Analyses of the thermodynamic signatures obtained from the binding of the nucleotide (CTP) and the product (CMP-sialic acid) to VcCMAS provide fundamental information on the energetics of the binding process.

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Brian Waller questions the lack of political will when it comes to preventable deaths across Asia and sub-Saharan Africa, while Tony Haynes reveals how artists can explore attitudes to disease

Neil Singh’s powerful long read (Cholera and coronavirus: why we must not repeat the same mistakes, 1 May) tellingly compares the way in which the world is reacting to Covid-19 with how it has handled cholera, especially in developing countries. He states: “There is no biological or environmental reason why cholera can’t be eradicated … It is not the knowhow that is lacking, but rather the political will.”

Exactly the same conclusion can be reached in respect of the 5 million-plus children under five who are dying every year. According to the World Health Organization, many of these early child deaths are preventable or can be easily treated, but there is nothing remotely like the effort being put into this as in the response to Covid-19. Might the reason for that inaction be that more than 80% of these deaths involve children in central and south Asia, and sub-Saharan Africa?
Brian Waller
Otley, North Yorkshire

Antimicrobial peptides play an important role in host defense against Vibrio cholerae. Generally, the V. cholerae O1 classical biotype is polymyxin B (PB) sensitive and El Tor is relatively resistant. Detection of classical biotype traits like the production of classical cholera toxin and PB sensitivity in El Tor strains has been reported in recent years, including in the devastating Yemen cholera outbreak during 2016-2018. To investigate the factor(s) responsible for the shift in the trend of sensitivity to PB, we studied the two-component system encoded by carRS, regulating the lipid A modification of El Tor vibrios, and found that only carR contains a single nucleotide polymorphism (SNP) in recently emerged PB-sensitive strains. We designated the two alleles present in PB-resistant and -sensitive strains carR^r and carR^s alleles, respectively, and replaced the carR^s allele of a sensitive strain with the carR^r allele, using an allelic-exchange approach. The sensitive strain then became resistant. The PB-resistant strain N16961 was made susceptible to PB in a similar fashion. Our in silico CarR protein models suggested that the D89N substitution in the more stable CarR^s protein brings the two structural domains of CarR closer, constricting the DNA binding cleft. This probably reduces the expression of the carR-regulated almEFG operon, inducing PB susceptibility. Expression of almEFG in PB-sensitive strains was found to be downregulated under natural culturing conditions. In addition, the expression of carR and almEG decreased in all strains with increased concentrations of extracellular Ca²⁺ but increased with a rise in pH. The downregulation of almEFG in CarR^s strains confirmed that the G265A mutation is responsible for the emergence of PB-sensitive El Tor strains.

Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 x 10⁸ CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 x 10⁹ CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 x 10⁸-CFU standard dose (n = 50) or a ≥2 x 10⁹-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ~2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.)

Third Cholera Epidemic poses as a new health threat to Yemen people who are still recovering from the war. World health organization has warned the government

Cholera outbreak kills six people in Cameroon, Yaounde capital, Central Africa. Cases of this outbreak have been documented since May 2018 in four districts

Strategic changes need to be made to government response teams to stop the cholera epidemic in Yemen. By the implementing these suggested changes the