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.
The proportion of births occurring at healthcare facilities is rising globally, yet healthcare facilities in low-income settings have been found to be highly contaminated with bacterial pathogens, including antibiotic resistant pathogens. There is a need for effective strategies to reduce contamination in healthcare facilities in order to reduce infection risks among facility-born neonates. In this trial, medium-sized public health facilities will be randomized to control or to receive an intervention consisting of passive chlorination for water supply treatment and a reliable supply of chlorine disinfectant. Reliable supply is randomized as either (a) an electrochlorinator for on-site production or (b) bulk chlorine delivery. This cluster randomized controlled trial will enroll 36 health facilities to generate rigorous evidence on the maternal and neonatal health benefits of chlorinated water supply paired with reliable supplies of chlorine disinfectant. This study has the following aims: 1) determine the impact of the intervention on pathogenic and antibiotic resistant bacterial contamination in water supplies, on high-touch surfaces, and on healthcare worker hands, 2) quantify intervention effects on gut colonization of mothers and neonates by a panel of pathogenic and antibiotic resistant bacteria species linked to serious infection, using molecular and culture-based methods, and 3) follow up with mother-neonate dyads to measure intervention effects on symptoms of possible serious bacterial infection in the week following birth. Data collection will be for a duration of 24 months. Infection prevention through effective water, sanitation, and hygiene (WASH) has been cited by national action plans as a key tool in the fight against antimicrobial resistance and, while global data show dire WASH conditions in low- and middle-income (LMIC) health facilities, there exists very little guidance for implementing effective interventions. The overarching goal is to generate actionable evidence to inform investments in chlorination at health facilities to improve maternal and neonatal health and reduce the threat of antibiotic resistant infections.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
45,450
* Installation of inline chlorine doser(s) for automated water disinfection. * Provision of chlorine solution for water and surface disinfection (half of treatment facilities randomized to receive electrochlorinator, half receive bulk chlorine solution deliveries). * Provision of mop(s), bucket(s), and spray bottles for surface cleaning.
Infection prevention and control guidance and messaging
University of California, Berkeley
Berkeley, California, United States
ACTIVE_NOT_RECRUITINGKenya Medical Research Institute
Nairobi, Kenya
RECRUITINGPossible serious bacterial infection in neonate
Incidence of one or more of the following severe infection symptoms of neonates based on WHO criteria for possible serious bacterial infection: 1. Not able to feed at all or not feeding well 2. Convulsions 3. Severe chest indrawing 4. Fever - High body temperature (38°C\* or above) 5. Low body temperature (less than 35.5°C\*) 6. Movement only when stimulated or no movement at all 7. Fast breathing (60 breaths per minute or more)
Time frame: From birth to 7 days post birth
Possible maternal sepsis
Any of the following listed with fever or hypothermia: 1. fast heartbeat 2. low blood pressure 3. respiratory distress 4. jaundice 5. decreased urination/dysuria 6. altered mental status
Time frame: From birth to 7 days post birth
Neonatal infection with at least one bacterial pathogen
Detection of any pre-specified bacterial pathogen detected by qPCR in infant rectal swabs (among swab subset of participants) Includes: ETEC, STEC, EPEC, EAEC, EIEC, EHEC O157:H7, Escherichia coli/Shigella, Shigella spp, Shigella flexneri, Salmonella spp., Salmonella enteritidis, Salmonella typhi, Campylobacter jejuni/coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus agalactiae (Group B strep), Serratia marcescens, Pseudomonas aeruginosa, Acinetobacter baumannii, Clostridium difficile, Vibrio cholerae
Time frame: 7 days after birth
Any symptom or sign of infection in neonate
One or more of the following symptoms: Difficulty feeding, Hyperthermia/fever, Hypothermia, Tachypnea, Severe chest indrawing, Convulsions, Movement only when stimulated/no movement, Bulging fontanel, Labored breathing, Skin infection, Umbilical redness, Oozing ears, Diarrhea, Three or more loose or watery stools in a 24 hour period, Vomiting, Cyanosis, Cough, Runny nose or congestion, Tachycardia (\>160 bpm at rest)
Time frame: From birth until 7 days post birth
Any symptom or sign of infection in mother
One or more of the following symptoms: Hypothermia, Fever, Foul smelling vaginal discharge, Fits/convulsions, Tachycardia (\>100 bpm at rest), Low blood pressure, Diarrhea (self-defined), Difficulty breathing, Jaundice, Decreased urination or difficult or painful urination, Confusion or altered mental state, Mastitis, Chills, Body aches, Low appetite, Lower abdominal pain, Three or more loose or watery stools in a 24 hour period, Vomiting, Cough, Runny nose or congestion, Chest pain, Bloody stool, Skin infection
Time frame: From birth to 7 days post birth
Clinical diagnosis of sepsis in neonate
Abstracted diagnosis from medical charts OR self-reported diagnosis confirmed by clinician
Time frame: From birth to 7 days post birth
Clinical diagnosis of sepsis in mother
Abstracted diagnosis from medical charts OR self-reported diagnosis confirmed by clinician
Time frame: From birth to 7 days post birth
Neonatal mortality
Report of neonatal death up to 28 days
Time frame: From birth to 28 days after birth
Maternal mortality
Report of maternal death
Time frame: From birth to 28 days after birth
Neonatal rectal colonization with at least one bacterial pathogen by culture
Detection of any pre-specified bacterial pathogen detected by culture in neonate rectal swabs (among swab subset of participants) Includes: Acinetobacter spp., Pseudomonas spp., Salmonella spp., Shigella, Staphylococcus aureus, Group B streptococcus
Time frame: 7 days after birth
Maternal rectal colonization with at least one bacterial pathogen by culture-based method
Detection of any pre-specified bacterial pathogen detected by culture in maternal rectal swabs (among swab subset of participants) Acinetobacter spp., Pseudomonas spp., Salmonella spp., Shigella spp., Staphylococcus aureus, Group B streptococcus
Time frame: 7 days postpartum
Number of clinically relevant antibiotic resistance genes (ARGs) detected in neonatal rectal swabs
Measured by qPCR. Includes: resistance to quinolone, macrolide, sulfonamide, tetracycline, vancomycin, aminoglycoside, beta-lactams (cephalosporin, penicillin, ampicillin) , carbapenem, colistin
Time frame: 7 days post birth
Rectal colonization with one or more antibiotic resistant bacteria (neonates)
Detection of ESBL enterobacteriaceae by culture in rectal swabs Includes: Klebsiella spp./Enterobacter/Citrobacter spp. (KEC), Acinetobacter spp., Pseudomonas spp., E. coli
Time frame: 7 days post birth
Rectal colonization with one or more antibiotic resistant bacteria (mothers)
Detection of ESBL enterobacteriaceae by culture in rectal swabs Includes: Klebsiella spp./Enterobacter/Citrobacter spp. (KEC), Acinetobacter spp., Pseudomonas spp., E. coli
Time frame: 7 days postpartum
Number of bacterial pathogens in rectal swabs (neonates)
Number of unique bacterial pathogens (see pre-specified list above) detected by qPCR
Time frame: 7 days post birth
Number of bacterial pathogens in rectal swabs (mothers)
Number of unique bacterial pathogens (see pre-specified list above) by culture
Time frame: 7 days postpartum
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.