Small Group Discussions
Breakout Group 1 was chaired by Stuart MacLeod, British Columbia Research Institute for Children’s and Women’s Health, Vancouver, Canada; and Bo Sun, Children’s Hospital of Fudan University, Shanghai, China.
Group 1 was comprised of approximately 10 participants who were asked to discuss antibiotic therapy and drug resistance in the treatment of neonatal infections in mid- and low-income countries. Specifically, they considered research needed to determine the appropriate use of antibiotics and the prevention of practices that lead to drug resistance in mid- and low-income countries; and research that is needed on problems related to accessibility and availability of drugs in mid- and low-income countries.
In the final plenary session Dr. MacLeod presented the following major points on behalf of Group 1:
1. Resistance to antibiotics is a major problem; in order to study this further there is need to define resistance since there may be a difference between in vivo and in vitro resistance. For example, in Zambia over 70% of bacterial strains are resistant to Cotrimoxasole however it is thought to be effective in vivo.
2. In China, aminoglycosides are not to be used for newborns. Evidently the fear is the complication of deafness. The data presented by Dr. Van Anker at this symposium supported the safety of gentamycin in newborns. Accordingly there is a need to study this problem to provide health authorities with information about the safety of this drug for effective therapy of bacterial infections in newborns. A study is necessary in order to be certain that either the Chinese drug is different or the response of newborns to this drug is different.
3. The role of PGPR internationally in studies of neonatal infections was considered. It was agreed that PGPR serves a catalytic role in making issues clearly understood, providing recommendations concerning the need and directions of research and communicating those recommendations to the community of researchers and government health systems. It is also PGPR’s role to bring together groups to carry out those studies and provide those recommendations.
4. Accessibility and availability of drugs is a major problem in many countries. Accordingly, recommendations of ideal therapy must also consider the availability of the agents recommended. The group discussed problems, especially bacterial resistance, arising from free availability of drugs.
5. There are still a large number of deaths due to tetanus in many countries. The actual numbers are difficult to determine but in countries where there is a problem an active program of tetanus immunization should be implemented.
6. The cost effectiveness of programs was discussed. It was concluded that the availability of a laboratory to provide accurate diagnosis could well be cost effective and certainly would provide better therapy. The program described by Dr. Saha suggested that this could be done in developing countries.
7. A policy of developing comprehensive algorithms (a step by step process) should lead to effective treatment and may reduce the problem of resistance development.
Breakout Group 2 was chaired by Zulfiqar Bhutta, The Aga Khan University, Karachi, Pakistan; and Jack Sinclair, Cochrane Neonatal Review Group, Hamilton, Canada.
Group 2 was comprised of 11 participants who were asked to discuss diagnosis and treatment of neonatal infections in rural communities in mid- and low-income countries. Specifically, they considered research needed concerning the diagnosis of neonatal infection, both in hospital and community settings; research needed on therapy, both in hospital and community settings (including the benefits and risks associated with such therapy and whether there are research needs surrounding long-term morbidity from infection).
Dr. Bhutta presented for Group 2 and began by pointing out that the diagnosis of bacterial infections is difficult in developed countries as well as in low and mid income countries. There is need for a specific and sensitive test for bacterial infection but none is known at this point. Bacterial culture is not a gold standard for several reasons: The first is that infection can occur without a positive bacterial isolates. Second, bacteria in the blood is not, alone, diagnostic of infection since asymptomatic bacteremias occur.
The work of Abhay Bang was discussed by Group 2. The studies of his group were outlined in detail in Dr. Bang’s symposium presentation. Dr. Bang and his team determined the clinical criteria for infection and then trained health workers to use these criteria to diagnose infections. Those same workers were also trained to treat infections with parenteral gentamycin and co-trimoxazole.
From Dr. Bang’s studies, it was recommended that diagnosis and treatment of bacterial infections in a community was dependent on:
- Types of bacteria causing infection in the community
- Availability of diagnostic resources
- Availability of antibiotics
- Cost effectiveness of diagnostic and therapeutic procedures
- Safety of agents used
- Also, if possible, oral therapy should be used and a single daily dose is preferable to repeated dosage
Group 2 felt that an algorithim for optimal diagnostic and therapeutic procedures in each community should be developed. The above criteria should be used in formulating the algorithm.
There is no proven data on the duration of therapy necessary for treatment.
The following recommendations were made by Group 2:
1. There is need for a better definition of clinical and laboratory criteria for diagnosing serious neonatal infections in developing countries using a setting-specific standard against which test results could be compared.
2. Rapid diagnostic tests (clinical and/or laboratory) for neonatal infections are needed.
3. Diagnostic and therapeutic algorithm applicable to particular settings should be developed.
4. The following specific issues should be considered for inclusion in the algorithim:
- Oral therapy
- Single daily parenteral regimen (including Uniject® devices and switch therapy)
- Optimal combinations
- Duration of therapy
- Research on strategies for adoption of evidence-based practices for the treatment of neonatal infections within health systems
- Research needs on the impact on potential emergence of antibiotic resistance following community-based approaches
- The role of various categories of health workers in health system settings (community health workers and first & second level facilities).
5. Long-term outcomes of survivors of neonatal asphyxia should be done.
6. Outcomes studies should include: survival, morbidity, growth, and neuro-development.
Breakout Group 3 was chaired by Philip Fischer, Mayo Clinic, Rochester, U.S.A. and Demissie Habte, BRAC University, Dhaka, Bangladesh
Group 3 was comprised of 11 participants who were asked to discuss the development of research infrastructure for the study of neonatal infections in mid- and low-income countries.
Dr. Fischer, presenting for Group 3, began by outlining the Potential Principles to Guide Action; He indicated that of greatest importance is the presence of local, trained personnel on site who can champion the need for resource infrastructure and focus on locally identified problems. "Infrastructure” includes personnel, laboratories, financial management, information technology and resources and government support.
Specific Questions Discussed:
What research will help determine the need for and feasibility of establishing diagnostic facilities in mid- and low-income countries?
1. Each country should survey the existing diagnostic laboratory facilities.
2. Each country should determine the basic epidemiology of neonatal infections using a representative sampling of microbial etiology and susceptibility patterns.
3. Algorithms of management should be implemented and tested.
4. Cost-effective analysis is needed to determine in which communities/hospitals microbiology testing at various levels (basic culture, susceptibility, complex/antigen testing) should be available.
What research issues surround training of personnel who will remain on site?
1. Proper selection and training of personnel is essential; training should be focused on in-country training as much as possible. However, mentors and trainees must be carefully linked during and after training.
2. Training should include collaborative research on projects relevant to the home country.
3. Trainees who assume responsibility for programs in their country should be supported by continuation grants to assist in research.
4. Initial training should be followed by continuing collaborative research between mentors and trainees working in the home country.
5. Those who are already experienced and committed to their home country should be selected for foreign training.
6. Trainees should benefit from both local and international support, including networking, as they return to their countries of origin.
7. Foreign training is of value in providing an enlarged world view in addition to the specific training received.
8. The projects done during foreign training should be relevant and potentially portable back to home countries.
Breakout Group 4 was chaired by Gary Darmstadt, Johns Hopkins University, Baltimore, U.S.A.; and Margaret Nakakeeto, Mulago Hospital, Kampala, Uganda
Group 4 was comprised of approximately 17 participants. Dr. Darmstadt presented the notes from their discussion.
The group addressed both nosocomial and environmental infections. This demanded consideration of problems originating in the hospital and in the community. Initially Group 4 considered prevention measures that were effective but operational research was required to fully implement them. Examples were tetanus vaccination and breast feeding. They then concluded that there are measures that still require clinical and basic research as well as operational research.
There are many known, effective procedures that are applicable both in the hospital and in the community. However what is central and critical in implementing all these measures which can prevent infection is education to make behavioural and operational changes. This includes families in the communities, health workers in the communities and in the hospital and in health programs of the government. Procedures such as hand hygiene, clean deliveries, skilled birth attendance, post natal care of hands, breasts, skin to skin care and so forth are effective, however there is a need for them to be implemented; operational research to implement these changes requires education to effect behavioural changes. Research should determine the best way of establishing basic relationships for effective education and change.
The group then considered specific research that is required in the hospital and in the community.
1. Vaginal and skin cleansing should be “unbundled” and evaluated separately to ensure the effectiveness of each component.
2. The antiseptic agent (chlorhexidine) is effective; however the method of application should be studied as well as the concentration of the agent and whether other agents might be preferable.
3. Cord cleansing has been applied in community settings where it appears to be effective in reducing the 15% incidence of cord infections. There is need to determine the incidence of cord infections in hospital deliveries and thereby determine whether cord cleansing is required.
4. Vernix is an important contributor to innate skin immunity with distinct antibacterial properties. It is necessary to study traditional practices of cleansing the baby and removing vernix, and developing communications to promote leaving vernix on the skin as a protective barrier. Also, the role of emollients has to be studied further to determine not only its effectiveness in reducing the incidence of nosocomial infections but also whether it has any long term effect on the infant (e.g. its skin flora).
5. Emollients have been proven to be of value in premature infants. There is a need for research to determine their effectiveness in full term infants.
1. All the above issues should be studied in community settings.
2. Effectiveness studies should be implemented in community settings.
3. Effectiveness of infection control packages should be studied.
4. Effectiveness of educational programs in changing behaviour of mothers and traditional birth attendants for effective infection control should be studied.
5. Use of hand cleansing products to substitute for hand washing where water quality is bad should be studied.