Risk factors for Group B Streptococcus colonisation and disease in Gambian women and their infants

Journal of Infection, Volume 72, No. 3, Year 2016

Interpretation

Objectives: To determine risk factors for GBS colonisation in Gambian mothers and in their infants from birth to day 60-89 of age. Methods: Swabs and breastmilk from mothers/infant pairs were collected and cultured on selective agar. Negative samples were analysed for GBS DNA via real-time PCR. Positive isolates were serotyped using multiplex PCR and gel-agarose electrophoresis. Results: Seven hundred and fifty women/infant pairs were recruited. 253 women (33.7%) were GBS-colonised at delivery. The predominant serotypes were: V (55%), II (16%), III (10%), Ia (8%) and Ib (8%). 186 infants were colonised (24.8%) at birth, 181 (24.1%) at 6 days and 96 at day 60-89 (14%). Infants born before 34 weeks of gestation and to women with rectovaginal and breastmilk colonisation at delivery had increased odds of GBS colonisation at birth. Season of birth was associated with increased odds of persistent infant GBS colonisation (dry season vs. wet season AOR 2.9; 95% CI 1.6-5.2). Conclusion: GBS colonisation is common in Gambian women at delivery and in their infants to day 60-89 and is dominated by serotype V. In addition to maternal colonisation, breastmilk and season of birth are important risk factors for infant GBS colonisation. We undertook a prospective longitudinal cohort study in two government health centres offering antenatal care to women in the Fajara area of costal Gambia, a low-income country with an annual birth rate of 43.1/1000 population, neonatal sepsis rate of 4.42/1000 live births7 and neonatal mortality rate of 28/1000 live births.8 The combined birth rate of these two health centres is approximately 12,500 births annually. The health centres were selected to be representative of the level of care usually available to Gambian women. The eligibility criteria for maternal participation in the study included all pregnant women over the age of 18 years who had a negative HIV test and were deemed to be at low risk for pregnancy complications (no evidence of pre-eclampsia, cardiomyopathy, maternal gestational diabetes, placenta praevia, twin pregnancy). Women were invited to deliver at the health centre and offered a confirmatory HIV test prior to enrolment. Women found to be HIV positive were referred for specialist ongoing care. Mothers were excluded if they were not planning to breastfeed or were unable to remain in the Fajara area for the first three months postpartum. Healthy infants over 32 weeks of gestation assessed using the Ballard score and weighing over 2.5 kg were included. Infants were excluded if they had obvious congenital abnormalities or required resuscitation at the time of delivery requiring transfer to a neonatal unit. Mother and infant pairs were recruited to the study between 1st January 2014 and 31st December 2014 if both mother and infant met the inclusion criteria. All eligible women and infants were recruited until the pre-defined sample size was reached. Participants were followed up daily at home until day 6 and then asked to return to clinic when the infant 60−89 days old for final follow up visit and vaccinations. If an infant died during the study a verbal autopsy was carried out to assess the potential cause of death. Field workers explained the purpose of the study to eligible participants in their local language (Mandinka, Wolof, Fula, Jolla, Mangago) and each participant signed an informed consent form, or in case of illiteracy, thumb-printed and the consent form was signed by an impartial witness. The study was approved by the joint Gambian Government/Medical Research Council Research Ethics Committee, SCC 1350 V4. Rectovaginal swabs were taken from enrolled women presenting in labour to one of the health centres and cord blood was taken after delivery but prior to separation of the placenta. A screening questionnaire was completed after four hours postpartum and the infant checked for any abnormalities requiring medical intervention. The questions included ethnic origin, gravida, parity, maternal weight, blood pressure, haemoglobin concentration, use of medication/traditional medicines/antibiotics and vaccination in pregnancy, any illnesses in pregnancy, number of antenatal attendances, HIV status, education, diet, compound location and presence of cattle at the compound. Nasopharyngeal and rectal swabs were taken from all eligible infants at four hours after birth. Mothers were provided with soap and asked to wash their hands and wipe their breasts with alcohol wipes before hand expressing colostrum/milk within the first 12 h after birth, at day 6 and between days 60 and 89. Nasopharyngeal and rectal swabs were also taken from infants at day 6 of life and again at 60–89 days of life. Infants who were unwell before day 6 were assessed at home and referred for treatment as necessary. All sick infants had a blood culture taken on admission to hospital. At each visit a standardized questionnaire was completed in the local language documenting infant anthropometry, feeding, vaccinations, signs and symptoms of infant illnesses, use of antibiotic/traditional medicine and vital signs. Copan (for rectal and rectovaginal samples) and Dacron (for nasopharyngeal samples) swabs were collected in skim-milk tryptone glucose glycerol (STGG) transport medium, stored at 4 °C and transported to the Medical Research Council laboratories, The Gambia within 4 h of collection. On arrival the samples were vortexed briefly and immediately frozen at −70 °C until processing. All swab specimens were inoculated into Todd–Hewitt broth supplemented with colistin and nalidixic acid and were processed for isolation of GBS using standard laboratory procedures.1 Presumptive positive GBS samples were identified by latex agglutination (Oxoid). Five colonies from positive samples were harvested into phosphate buffered saline (PBS) and subjected to real-time polymerase chain reaction (PCR).9 Negative samples were also subjected to confirmation by real-time PCR. All GBS positive isolates were then serotyped using conventional PCR and identified using gel PCR and agarose electrophoresis.10 The primary outcome was prevalence of ST-specific GBS colonisation in mothers and infants at birth, six days and between days 60–89 using microbiological culture and molecular techniques. Secondary outcomes were detection of GBS in breastmilk; infant acquisition and loss of GBS colonisation during the study follow up period and infant GBS disease (sample obtained from sterile site), as ascertained by positive microbiological culture and confirmatory PCR. Swabs were considered negative if no GBS was evident by culture and PCR and positive if GBS was found on culture and PCR. If swabs were negative on culture but positive on PCR, conventional PCR was performed to determine serotype. If the second PCR resulted in the identification of a GBS serotype the samples were deemed positive. If no serotype was identified or the DNA did not amplify, samples were deemed negative. Calculated on the basis of the previously observed 24% colonisation rate,11 the intended sample size was 750 mothers, to provide at least 180 colonised women for serotype analysis (95% confidence interval (CI) 150–202 women) and 90 colonised infants (95% CI 72–107 infants). The sample size of 180 colonised women was chosen to ensure at least 10 samples of the least prevalent ST based on historical data from The Gambia (ST III (6%)),11 in order to allow longitudinal colonisation analysis. Statistical analyses were completed using STATA version 12 (StataCorp 2013, Texas) and GraphPad Prism version 6.0 (GraphPad Software Inc, La Jolla, California). Descriptive statistics included the prevalence of colonisation at individual time points expressed as a proportion of the total number of participants. Odds ratios and 95% confidence intervals (CI) were calculated to determine risk of maternal and infant colonisation at birth in a single variable analysis. Adjusted odds ratios were then calculated using any variables from the single variable analysis with a p-value <0.2 using a backwards-stepwise procedure. Analyses of the changes in infant colonisation over time were undertaken using longitudinal logistical regression. Adjusted odds ratios were then calculated using any variables from the single variable analysis with a p-value <0.2 using a backwards-stepwise procedure. New acquisition of GBS was defined as detection of a new serotype by culture or PCR that was not previously present. Clearance of colonisation was defined as a negative GBS culture or PCR for a specific serotype following a positive sample at the previous visit for the same ST. The log-rank test was used to examine differences in duration of colonisation between serotypes. Using an expected vertical transmission rate of 50%1 we calculated observed vs. expected statistics for risk of infant colonisation by ST. For comparison between our study and the study conducted in 1994, we calculated 95% confidence intervals for both studies. P-values <0.05 were considered significant. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data and the corresponding author had final responsibility for the decision to submit for publication.

AI Digest

Study Justification:

The study aimed to determine the risk factors for Group B Streptococcus (GBS) colonization in Gambian mothers and their infants. This research was important because GBS colonization can lead to serious infections in newborns, including sepsis and meningitis. Understanding the risk factors for colonization can help inform prevention strategies and improve maternal and infant health outcomes.

Study Highlights:

– 750 women and infant pairs were recruited for the study.
– 33.7% of women were GBS-colonized at delivery.
– The most common GBS serotypes were V (55%), II (16%), III (10%), Ia (8%), and Ib (8%).
– 24.8% of infants were colonized at birth, 24.1% at 6 days, and 14% at day 60-89.
– Infants born before 34 weeks of gestation and to women with rectovaginal and breastmilk colonization at delivery had increased odds of GBS colonization at birth.
– Season of birth was associated with increased odds of persistent infant GBS colonization.

Recommendations for Lay Reader:

Based on the study findings, it is recommended that pregnant women and healthcare providers take steps to reduce the risk of GBS colonization and infection in infants. This includes:

1. Ensuring proper hygiene practices, such as handwashing and cleaning the breast before breastfeeding.
2. Identifying and treating GBS colonization in pregnant women to reduce the risk of transmission to infants.
3. Monitoring infants born prematurely or to mothers with GBS colonization more closely for signs of infection.
4. Considering the season of birth as a potential risk factor for GBS colonization in infants.

Recommendations for Policy Maker:

To address the risk factors for GBS colonization and disease in Gambian women and their infants, the following actions are recommended:

1. Implement educational programs for pregnant women and healthcare providers to raise awareness about GBS and prevention strategies.
2. Strengthen antenatal care services to include routine screening and treatment for GBS colonization in pregnant women.
3. Improve access to healthcare facilities for high-risk infants, such as those born prematurely or to mothers with GBS colonization.
4. Conduct further research to understand the impact of seasonality on GBS colonization and develop targeted interventions.

Key Role Players:

1. Healthcare providers: Responsible for implementing prevention strategies, screening pregnant women, and providing appropriate care to infants.
2. Public health officials: Involved in developing and implementing educational programs, monitoring GBS colonization rates, and evaluating the effectiveness of interventions.
3. Researchers: Conducting further studies to expand knowledge on GBS colonization and inform evidence-based interventions.
4. Community leaders: Engaging with the community to raise awareness, promote hygiene practices, and encourage participation in prevention programs.

Cost Items for Planning Recommendations:

1. Training and education materials for healthcare providers and pregnant women.
2. Screening tests and laboratory equipment for GBS colonization.
3. Additional healthcare staff to support increased screening and monitoring efforts.
4. Development and implementation of educational campaigns.
5. Research funding for further studies on GBS colonization and prevention strategies.
6. Infrastructure improvements to enhance access to healthcare facilities for high-risk infants.
Please note that the cost items provided are for planning purposes and do not reflect actual costs.

Strength of Evidence

The strength of evidence for this abstract is 8 out of 10.
The evidence in the abstract is strong because it is based on a prospective longitudinal cohort study with a large sample size. The study collected swabs and breastmilk from 750 women/infant pairs and analyzed them using selective agar, real-time PCR, and serotyping. The study found that GBS colonization is common in Gambian women and their infants, with serotype V being the most predominant. The study also identified risk factors for GBS colonization, such as maternal colonization, breastmilk colonization, and season of birth. To improve the evidence, the study could have included a control group for comparison and conducted a follow-up study to assess the long-term effects of GBS colonization on infants.

Abstract

We undertook a prospective longitudinal cohort study in two government health centres offering antenatal care to women in the Fajara area of costal Gambia, a low-income country with an annual birth rate of 43.1/1000 population, neonatal sepsis rate of 4.42/1000 live births7 and neonatal mortality rate of 28/1000 live births.8 The combined birth rate of these two health centres is approximately 12,500 births annually. The health centres were selected to be representative of the level of care usually available to Gambian women. The eligibility criteria for maternal participation in the study included all pregnant women over the age of 18 years who had a negative HIV test and were deemed to be at low risk for pregnancy complications (no evidence of pre-eclampsia, cardiomyopathy, maternal gestational diabetes, placenta praevia, twin pregnancy). Women were invited to deliver at the health centre and offered a confirmatory HIV test prior to enrolment. Women found to be HIV positive were referred for specialist ongoing care. Mothers were excluded if they were not planning to breastfeed or were unable to remain in the Fajara area for the first three months postpartum. Healthy infants over 32 weeks of gestation assessed using the Ballard score and weighing over 2.5 kg were included. Infants were excluded if they had obvious congenital abnormalities or required resuscitation at the time of delivery requiring transfer to a neonatal unit. Mother and infant pairs were recruited to the study between 1st January 2014 and 31st December 2014 if both mother and infant met the inclusion criteria. All eligible women and infants were recruited until the pre-defined sample size was reached. Participants were followed up daily at home until day 6 and then asked to return to clinic when the infant 60−89 days old for final follow up visit and vaccinations. If an infant died during the study a verbal autopsy was carried out to assess the potential cause of death. Field workers explained the purpose of the study to eligible participants in their local language (Mandinka, Wolof, Fula, Jolla, Mangago) and each participant signed an informed consent form, or in case of illiteracy, thumb-printed and the consent form was signed by an impartial witness. The study was approved by the joint Gambian Government/Medical Research Council Research Ethics Committee, SCC 1350 V4. Rectovaginal swabs were taken from enrolled women presenting in labour to one of the health centres and cord blood was taken after delivery but prior to separation of the placenta. A screening questionnaire was completed after four hours postpartum and the infant checked for any abnormalities requiring medical intervention. The questions included ethnic origin, gravida, parity, maternal weight, blood pressure, haemoglobin concentration, use of medication/traditional medicines/antibiotics and vaccination in pregnancy, any illnesses in pregnancy, number of antenatal attendances, HIV status, education, diet, compound location and presence of cattle at the compound. Nasopharyngeal and rectal swabs were taken from all eligible infants at four hours after birth. Mothers were provided with soap and asked to wash their hands and wipe their breasts with alcohol wipes before hand expressing colostrum/milk within the first 12 h after birth, at day 6 and between days 60 and 89. Nasopharyngeal and rectal swabs were also taken from infants at day 6 of life and again at 60–89 days of life. Infants who were unwell before day 6 were assessed at home and referred for treatment as necessary. All sick infants had a blood culture taken on admission to hospital. At each visit a standardized questionnaire was completed in the local language documenting infant anthropometry, feeding, vaccinations, signs and symptoms of infant illnesses, use of antibiotic/traditional medicine and vital signs. Copan (for rectal and rectovaginal samples) and Dacron (for nasopharyngeal samples) swabs were collected in skim-milk tryptone glucose glycerol (STGG) transport medium, stored at 4 °C and transported to the Medical Research Council laboratories, The Gambia within 4 h of collection. On arrival the samples were vortexed briefly and immediately frozen at −70 °C until processing. All swab specimens were inoculated into Todd–Hewitt broth supplemented with colistin and nalidixic acid and were processed for isolation of GBS using standard laboratory procedures.1 Presumptive positive GBS samples were identified by latex agglutination (Oxoid). Five colonies from positive samples were harvested into phosphate buffered saline (PBS) and subjected to real-time polymerase chain reaction (PCR).9 Negative samples were also subjected to confirmation by real-time PCR. All GBS positive isolates were then serotyped using conventional PCR and identified using gel PCR and agarose electrophoresis.10 The primary outcome was prevalence of ST-specific GBS colonisation in mothers and infants at birth, six days and between days 60–89 using microbiological culture and molecular techniques. Secondary outcomes were detection of GBS in breastmilk; infant acquisition and loss of GBS colonisation during the study follow up period and infant GBS disease (sample obtained from sterile site), as ascertained by positive microbiological culture and confirmatory PCR. Swabs were considered negative if no GBS was evident by culture and PCR and positive if GBS was found on culture and PCR. If swabs were negative on culture but positive on PCR, conventional PCR was performed to determine serotype. If the second PCR resulted in the identification of a GBS serotype the samples were deemed positive. If no serotype was identified or the DNA did not amplify, samples were deemed negative. Calculated on the basis of the previously observed 24% colonisation rate,11 the intended sample size was 750 mothers, to provide at least 180 colonised women for serotype analysis (95% confidence interval (CI) 150–202 women) and 90 colonised infants (95% CI 72–107 infants). The sample size of 180 colonised women was chosen to ensure at least 10 samples of the least prevalent ST based on historical data from The Gambia (ST III (6%)),11 in order to allow longitudinal colonisation analysis. Statistical analyses were completed using STATA version 12 (StataCorp 2013, Texas) and GraphPad Prism version 6.0 (GraphPad Software Inc, La Jolla, California). Descriptive statistics included the prevalence of colonisation at individual time points expressed as a proportion of the total number of participants. Odds ratios and 95% confidence intervals (CI) were calculated to determine risk of maternal and infant colonisation at birth in a single variable analysis. Adjusted odds ratios were then calculated using any variables from the single variable analysis with a p-value <0.2 using a backwards-stepwise procedure. Analyses of the changes in infant colonisation over time were undertaken using longitudinal logistical regression. Adjusted odds ratios were then calculated using any variables from the single variable analysis with a p-value <0.2 using a backwards-stepwise procedure. New acquisition of GBS was defined as detection of a new serotype by culture or PCR that was not previously present. Clearance of colonisation was defined as a negative GBS culture or PCR for a specific serotype following a positive sample at the previous visit for the same ST. The log-rank test was used to examine differences in duration of colonisation between serotypes. Using an expected vertical transmission rate of 50%1 we calculated observed vs. expected statistics for risk of infant colonisation by ST. For comparison between our study and the study conducted in 1994, we calculated 95% confidence intervals for both studies. P-values <0.05 were considered significant. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data and the corresponding author had final responsibility for the decision to submit for publication.

Materials

https://efashare.b-cdn.net/materials/8d5e908b5f9479dc8a8fae1968c8e0605a31e6ae49927b265aa46dd84bedc8da/mmc1.docx

Innovations

Based on the provided information, here are some potential innovations that can be used to improve access to maternal health:

1. Mobile Health (mHealth) Applications: Develop mobile applications that provide information and resources related to maternal health, including risk factors for Group B Streptococcus (GBS) colonization and disease. These apps can be easily accessible to pregnant women and healthcare providers, providing them with accurate and up-to-date information.

2. Telemedicine: Implement telemedicine services to allow pregnant women in remote areas to have virtual consultations with healthcare providers. This can help overcome geographical barriers and ensure that women receive timely and appropriate care, including screening and management of GBS colonization.

3. Community Health Workers: Train and deploy community health workers who can educate pregnant women about GBS colonization and provide support and guidance throughout their pregnancy. These workers can also collect samples for GBS testing and facilitate access to healthcare services.

4. Point-of-Care Testing: Develop and deploy rapid diagnostic tests for GBS colonization that can be performed at the point of care, such as in health centers or even at home. This can help identify GBS colonization early and enable prompt interventions to reduce the risk of transmission to infants.

5. Health Education Campaigns: Conduct targeted health education campaigns to raise awareness about GBS colonization and its associated risks. These campaigns can include community workshops, radio broadcasts, and informational materials in local languages to ensure widespread understanding and adoption of preventive measures.

6. Improved Antenatal Care: Strengthen antenatal care services by ensuring that all pregnant women have access to regular check-ups, including GBS screening. This can help identify and manage GBS colonization early in pregnancy, reducing the risk of transmission to infants.

7. Enhanced Postnatal Care: Provide comprehensive postnatal care services that include GBS screening and follow-up visits to monitor the health of both mothers and infants. This can help identify and address any complications or infections related to GBS colonization.

It is important to note that the implementation of these innovations should be context-specific and tailored to the local healthcare system and resources available in the Gambian setting.

AI Innovations Description

Based on the provided description, the following recommendation can be developed into an innovation to improve access to maternal health:

Implement a comprehensive maternal health program in low-income countries, such as The Gambia, that focuses on preventing and managing Group B Streptococcus (GBS) colonization in mothers and infants. This program should include the following components:

1. Antenatal care: Strengthen antenatal care services in government health centers to ensure early identification and management of risk factors for GBS colonization. This can include regular screening for GBS colonization during pregnancy and providing appropriate treatment to colonized mothers.

2. Education and awareness: Develop educational materials and conduct awareness campaigns to educate pregnant women and their families about the risks of GBS colonization and the importance of preventive measures. This can include information on proper hygiene practices, breastfeeding, and the benefits of early detection and treatment.

3. Screening and testing: Establish a systematic screening and testing program for GBS colonization in pregnant women and infants. This can involve collecting swabs and conducting real-time PCR tests to detect GBS DNA. Positive cases can be further analyzed for serotyping using multiplex PCR and gel-agarose electrophoresis.

4. Treatment and management: Provide appropriate treatment to GBS-colonized mothers during labor and delivery to reduce the risk of transmission to the infant. This can include administering intravenous antibiotics and promoting safe delivery practices.

5. Postpartum follow-up: Implement a postpartum follow-up program to monitor the health of both mothers and infants. This can involve regular check-ups, vaccinations, and counseling on breastfeeding and infant care.

6. Capacity building: Train healthcare providers on the prevention, diagnosis, and management of GBS colonization. This can include workshops, seminars, and ongoing education programs to ensure healthcare professionals have the necessary knowledge and skills to provide quality care.

7. Data collection and research: Establish a robust data collection system to monitor the prevalence of GBS colonization and the effectiveness of the program. This can help identify trends, evaluate the impact of interventions, and guide future improvements.

By implementing this comprehensive maternal health program, access to maternal health services can be improved, and the risk of GBS colonization and related complications can be reduced, ultimately leading to better maternal and infant health outcomes.

AI Innovations Methodology

Based on the provided information, here are some potential recommendations for improving access to maternal health:

1. Strengthen Antenatal Care: Enhance antenatal care services in government health centers by providing comprehensive screenings and assessments for pregnant women, including regular testing for Group B Streptococcus (GBS) colonization. This can help identify high-risk individuals and provide appropriate interventions.

2. Education and Awareness: Implement educational programs to raise awareness among pregnant women about the risk factors and consequences of GBS colonization. This can include information on hygiene practices, breastfeeding, and the importance of seeking timely medical care.

3. Improved Testing and Diagnosis: Invest in the development and implementation of rapid and accurate diagnostic tests for GBS colonization in both mothers and infants. This can help identify cases early and facilitate prompt treatment.

4. Strengthen Postpartum Care: Enhance postpartum care services to ensure continued monitoring and support for mothers and infants. This can include regular follow-up visits, vaccinations, and screening for GBS colonization.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could include the following steps:

1. Baseline Data Collection: Gather data on the current access to maternal health services, including antenatal care utilization, GBS screening rates, and maternal and infant outcomes related to GBS colonization.

2. Define Key Indicators: Identify key indicators to measure the impact of the recommendations, such as the percentage increase in antenatal care utilization, the percentage decrease in GBS colonization rates, and improvements in maternal and infant health outcomes.

3. Develop a Simulation Model: Create a simulation model that incorporates the baseline data and the potential impact of the recommendations. This model should consider factors such as population demographics, healthcare infrastructure, and resource availability.

4. Run Simulations: Run multiple simulations using different scenarios, varying the implementation of the recommendations. This can help determine the potential impact of each recommendation individually and in combination.

5. Analyze Results: Analyze the simulation results to assess the potential impact of the recommendations on improving access to maternal health. This can include evaluating the changes in key indicators and identifying the most effective strategies.

6. Refine and Implement: Based on the simulation results, refine the recommendations and develop an implementation plan. This may involve prioritizing certain recommendations based on their potential impact and feasibility.

7. Monitor and Evaluate: Implement the refined recommendations and establish a monitoring and evaluation system to track progress and measure the actual impact on access to maternal health. This can help identify any adjustments needed and ensure continuous improvement.

By following this methodology, stakeholders can gain insights into the potential impact of the recommendations and make informed decisions to improve access to maternal health.

Author

Dima Health

Statistics:

Citations: 51

Identifiers:

DOI: 10.1016/j.jinf.2015.12.014

ISSN: 01634453

Research Areas:

Community Interventions, Genetics and Genomics, Health System and Policy, Infectious Diseases, Maternal Access, Maternal and Child Health, Noncommunicable Diseases, Sexual and Reproductive Health, Social Determinants, Substance Abuse

Study Countries:

Gambia

Study Design:

Cohort Study, Cross Sectional Study, Grounded Theory, randomised-control-trial

Study Approach:

Quantitative

Participants Gender:

Female