Chlorination for Infections

(CLEAN Trial)

Recruiting at 1 trial location

Overseen By Amy J Pickering, PhD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Berkeley

Disqualifiers: Miscarriage, Stillbirth, Consent, Distance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

45450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The CLEAN (ChLorine to reduce Enteric and Antibiotic resistant infections in Neonates) cluster randomized controlled trial in western Kenya will evaluate the impact of a multi-component chlorination intervention in health care facilities on maternal and neonatal health. Intervention facilities will receive a passive chlorination technology for water supply treatment and a reliable supply of sodium hypochlorite disinfectant. Both intervention and treatment facilities will receive infection prevention and control messaging. The goal of the study is to evaluate the impact of the intervention on bacterial contamination of water supply, on staff hands, and on high-touch surfaces in maternity wards, and the following outcomes among facility-born neonates and their mothers: (1) gut carriage of bacterial pathogens associated with sepsis one week post-birth, (2) gut carriage of antibiotic resistant bacteria one week post-birth, and (3) symptoms of possible serious bacterial infection one week following birth.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

Is chlorination generally safe for humans?

Chlorination has been used for water disinfection for many years and is effective in preventing waterborne diseases. However, it can produce by-products that may pose health risks, such as respiratory and eye irritation, and potential links to cancer and birth defects. While these risks exist, they are generally considered low compared to the benefits of preventing infectious diseases. ^{1 2 3 4 5}

How does chlorination for infections differ from other treatments?

Chlorination is unique because it focuses on disinfecting water and surfaces to prevent infections, rather than treating infections directly. It works by killing pathogens in water, which helps reduce the spread of diseases like typhoid fever and viral infections, making it different from treatments that target infections after they occur. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Chlorination for water disinfection and surface disinfection in preventing infections?

Chlorination has been shown to effectively inactivate viruses and reduce the incidence of water-borne viral diseases, making it a valuable method for disinfecting water and preventing infections. Additionally, chlorination has historically been important in controlling waterborne diseases like typhoid fever, cholera, and hepatitis A, highlighting its role in infection prevention. ^{7 8 11 12 13}

Who Is on the Research Team?

Lillian Musila, PhD

Principal Investigator

Walter Reed Army Institute of Research-Africa

Amy J Pickering, PhD

Principal Investigator

University of California, Berkeley

Phelgona Otieno, PhD

Principal Investigator

Kenya Medical Research Institute

Are You a Good Fit for This Trial?

The CLEAN trial is for newborns and their mothers in western Kenya. It aims to reduce infections, including those resistant to antibiotics, by improving hygiene in healthcare facilities with chlorination interventions.

Inclusion Criteria

Facility: Public health care facility with 25 live births or more per month and infrastructure compatible with inline chlorination device

I am pregnant or a new parent at the enrolled facility.

Exclusion Criteria

Facility: Existing facility-level chlorination

Participant: Miscarriage (<28 weeks gestation)

Participant: Stillbirth (for neonatal analysis only)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Implementation of multi-component chlorination intervention in health care facilities, including passive chlorination technology and sodium hypochlorite disinfectant supply

24 months

Quarterly visits for data collection

Follow-up

Participants are monitored for symptoms of possible serious bacterial infection and other health outcomes

7 days post birth for neonates, 28 days post birth for mothers

Data Collection

Quarterly data collection on water quality, surface contamination, and healthcare worker hand hygiene

24 months

Quarterly visits

What Are the Treatments Tested in This Trial?

Interventions

• Chlorination for water disinfection and surface disinfection
• Infection prevention and control messaging

Trial Overview This study tests whether using chlorine for water treatment and surface disinfection in health care settings can lower bacterial contamination and infection rates among newborns and mothers.

How Is the Trial Designed?

Group I: Multi-component chlorine intervention Experimental Treatment 2 Interventions

Health care facilities will receive one or more inline chlorine dosers that will automatically chlorinate all water accessed by the maternity wards. Intervention facilities will also be randomized to either receive an electrochlorinator for on-site production of liquid chlorine solution or to receive bulk chlorine deliveries. Chlorine will be use to refill the chlorine dosers and for surface disinfection. Facilities will also receive hardware to facilitate surface disinfection.

Group II: Control Active Control 1 Intervention

Control group. At the conclusion of the trial, facilities will receive a chlorine doser.

Who Is Running the Clinical Trial?

University of California, Berkeley

Lead Sponsor

Trials

193

Recruited

716,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Kenya Medical Research Institute

Collaborator

Trials

186

Recruited

1,408,000+

Walter Reed Army Institute of Research (WRAIR)

Collaborator

Trials

111

Recruited

108,000+

Published Research Related to This Trial

Chlorination of water is an effective method for inactivating enteroviruses, which are a significant concern as enteral pathogens in the environment.

Using chlorination for water disinfection has been shown to reduce the incidence of water-borne viral diseases, highlighting its importance for public health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Conditions of inactivation of viruses in water with chlorination]. Nestor, I.[2013]

Healthcare-associated infections (HAIs) are a significant issue, causing approximately 1.7 million infections and 99,000 deaths annually in the U.S., highlighting the urgent need for effective disinfection practices in healthcare settings.

The systematic review of 181 studies revealed that current guidelines for disinfectant use are largely based on laboratory data rather than real-world efficacy, indicating a need for improved research on the actual effectiveness of disinfection practices in reducing pathogen load in critical care environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence Map and Systematic Review of Disinfection Efficacy on Environmental Surfaces in Healthcare Facilities. Christenson, EC., Cronk, R., Atkinson, H., et al.[2023]

Chlorination has been a crucial method for disinfecting drinking water, significantly reducing waterborne diseases like typhoid fever, but interruptions in chlorination can lead to outbreaks, highlighting the ongoing need for effective disinfection.

While chlorine remains the primary disinfectant, alternatives like ozone, chlorine dioxide, and chloramines are being evaluated due to concerns about carcinogenic byproducts from chlorination, with ozone being the most effective biocide among them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Waterborne outbreak control: which disinfectant? Akin, EW., Hoff, JC., Lippy, EC.[2018]

Hospitals using monochloramine for drinking water disinfection had significantly fewer outbreaks of Legionnaires' disease compared to those using free chlorine, with an odds ratio of 10.2, indicating a strong protective effect.

The study suggests that if monochloramine had been used instead of free chlorine, up to 90% of Legionnaires' disease outbreaks could have been prevented, highlighting the potential for monochloramine to be a cost-effective solution for reducing these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of monochloramine disinfection of municipal drinking water on risk of nosocomial Legionnaires' disease. Kool, JL., Carpenter, JC., Fields, BS.[2016]

Combining UV treatment with chlorine or chlorine dioxide significantly reduces Escherichia coli levels in drinking water systems more effectively than using chlorine-based disinfectants alone, as shown in a study using eight reactors.

Despite the effectiveness of UV and chlorine combinations, E. coli can adapt and persist under certain conditions, highlighting the need for improved disinfection strategies to ensure safe drinking water.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential UV- and chlorine-based disinfection to mitigate Escherichia coli in drinking water biofilms. Murphy, HM., Payne, SJ., Gagnon, GA.[2013]

Chlorination of public drinking water significantly reduced waterborne diseases since the early 1900s, but it also led to the formation of harmful chlorinated by-products, such as chloroform, which prompted regulatory measures.

Recent studies have identified numerous other chlorinated by-products, including the potent bacterial mutagen MX and chlorinated acetic acids, raising concerns about their potential health risks and the need for thorough risk assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in research on carcinogenic and genotoxic by-products of chlorine disinfection: chlorinated hydroxyfuranones and chlorinated acetic acids. Daniel, FB., Meier, JR., Deangelo, AB.[2012]

From 1993 to 2000, there was a decline in chlorine release events, but these incidents were significantly more likely to cause harm, requiring evacuations and decontaminations compared to other hazardous substance releases.

Most victims of chlorine exposure experienced respiratory and eye irritation, with the main causes being equipment failure and human error, highlighting the need for ongoing employee training and maintenance to prevent such incidents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The public health consequences from acute chlorine releases, 1993-2000. Horton, DK., Berkowitz, Z., Kaye, WE.[2019]

A population-based case-control study using Arkansas birth records found no significant increase in the risk of hypospadias associated with exposure to disinfection by-products (DBPs) like trihalomethanes (THM) and haloacetic acids (HAA) during pregnancy.

While some intermediate exposure levels showed a potential association with hypospadias, the overall evidence was weak, highlighting the importance of individual-level data in assessing the risks of DBP exposure during gestation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal exposure to water disinfection by-products during gestation and risk of hypospadias. Luben, TJ., Nuckols, JR., Mosley, BS., et al.[2013]

Chlorination has been a highly effective public health measure for controlling waterborne diseases for nearly a century, but it produces disinfection by-products (DBPs) that raise safety concerns, particularly trihalomethanes (THMs) and haloacetates.

Alternatives to chlorination exist, but their safety and effectiveness are less understood, which could lead to greater public health risks if not applied correctly; thus, the hazards of chlorination must be carefully evaluated against these alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Water chlorination: essential process or cancer hazard? Bull, RJ., Birnbaum, LS., Cantor, KP., et al.[2019]

Chlorination has been the standard method for disinfecting drinking water in the U.S. for 75 years, but it can produce potentially harmful trihalomethanes (THMs) like chloroform, raising health concerns.

Chlorine dioxide is a potential alternative that does not generate THMs, but while it has shown some toxicity in animal studies, there is currently no clear evidence of adverse health effects in humans, including those undergoing hemodialysis, suggesting that with proper precautions, risks may be minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chlorine dioxide and hemodialysis. Smith, RP., Willhite, CC.[2019]

Chlorination of drinking water has significantly reduced typhoid fever mortality since its introduction, but it is not sufficient alone to prevent water-mediated disease outbreaks, as pathogens can still survive in fecal particles.

Filtration is essential for effectively removing pathogens from drinking water, as disinfection alone cannot ensure safety from fecal contamination; both methods should be used together for optimal water hygiene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of disinfection in suppressing the spread of pathogens with drinking water: possibilities and limitations. Schoenen, D.[2019]

Higher concentrations of disinfectants are required to effectively degrade Legionella biofilms and prevent their formation on plastic surfaces compared to the concentrations needed to kill Legionella bacteria in culture.

The study used monospecies biofilms of three strains of Legionella pneumophila grown on plastic plates, highlighting the importance of testing disinfectants in conditions that mimic real-world biofilm scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Assessment of bactericidal activity of disinfectants against Legionella on the biofilm model]. Dronina, IuE., Panteleeva, LG., Karpova, TI., et al.[2020]

Enterobacter cloacae, when attached to drinking water distribution particles, showed increased resistance to chlorination, highlighting a potential risk for water safety.

The degree of protection from disinfection was influenced by the chlorine concentration and the duration of attachment, suggesting that longer attachment times could enhance the risk of coliform outbreaks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attachment as a factor in the protection of Enterobacter cloacae from chlorination. Herson, DS., McGonigle, B., Payer, MA., et al.[2021]

Citations

1. Romania pubmed.ncbi.nlm.nih.gov

[Conditions of inactivation of viruses in water with chlorination]. [2013]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Evidence Map and Systematic Review of Disinfection Efficacy on Environmental Surfaces in Healthcare Facilities. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Waterborne outbreak control: which disinfectant? [2018]

4. England pubmed.ncbi.nlm.nih.gov

Effect of monochloramine disinfection of municipal drinking water on risk of nosocomial Legionnaires' disease. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Sequential UV- and chlorine-based disinfection to mitigate Escherichia coli in drinking water biofilms. [2013]

6. Italy pubmed.ncbi.nlm.nih.gov

Advances in research on carcinogenic and genotoxic by-products of chlorine disinfection: chlorinated hydroxyfuranones and chlorinated acetic acids. [2012]

7. United States pubmed.ncbi.nlm.nih.gov

The public health consequences from acute chlorine releases, 1993-2000. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Maternal exposure to water disinfection by-products during gestation and risk of hypospadias. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Water chlorination: essential process or cancer hazard? [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Chlorine dioxide and hemodialysis. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Role of disinfection in suppressing the spread of pathogens with drinking water: possibilities and limitations. [2019]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Assessment of bactericidal activity of disinfectants against Legionella on the biofilm model]. [2020]

13. United States pubmed.ncbi.nlm.nih.gov

Attachment as a factor in the protection of Enterobacter cloacae from chlorination. [2021]