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Challenges in Implementation of the ANISA Protocol at the Odisha Site in India

Satpathy, Radhanath MD; Nanda, Pritish MPH; Nanda, Nimai C. MD; Bal, Himadri B. PhD; Mohanty, Ranjita BDS; Mishra, Archana MSc; Swain, Tapoja MSc; Pradhan, Keshab C. MBA; Panigrahi, Kalpana PhD; Dutta, Ambarish PhD; Misra, Pravas R. MVSc; Parida, Sailajanandan MD; Panigrahi, Pinaki MD

The Pediatric Infectious Disease Journal: May 2016 - Volume 35 - Issue 5 - p S74–S78
doi: 10.1097/INF.0000000000001112
ANISA Supplement

Background: The Aetiology of Neonatal Infection in South Asia (ANISA) study is being carried out at 5 sites across Bangladesh, India and Pakistan, generating in-depth information on etiologic agents in the community setting. Pregnancies are identified, births are registered and young infants are followed up to 59 days old with regular assessments for possible serious bacterial infection following a generic protocol. Specimens are collected from suspected cases. This article describes the challenges in implementing the generic ANISA protocol and modifications made to accommodate the Odisha site, India.

Challenges: Primary challenges in implementing the protocol are the large geographic area, with a population of over 350,000, to be covered; assessing young infants at home and arranging timely transport of sick young infants to study hospitals for physician confirmation of illness; and specimen collection and treatment. A large workforce is deployed in a 3-tier system in the field, while clinical, microbiology, laboratory and data management teams collaborate dynamically. Mobile phones with text message capability, integration with the Odisha State government’s health system, involvement of local communities and strict monitoring at different levels have been critical in addressing these challenges.

Conclusion: This article describes the challenges and modalities adopted to collect complex and accurate data on etiology, timing of disease and associated factors for community-acquired neonatal infections. Attention to local culture and customs, training and employing community level workers and supervisors, involving existing government machinery, using technology (cell phones), and uninterrupted systematic monitoring are critical for implementing such complex protocols that aim to collect population-based data to drive policy.

From the *Asian Institute of Public Health, Bhubaneswar, Odisha, India; Ispat General Hospital, Rourkela, Odisha, India; Center for Global Health and Development, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska; and §Sri Ramachandra Bhanj Medical College, Cuttack, Odisha, India.

Accepted for publication January 10, 2016.

The ANISA study is funded by the Bill & Melinda Gates Foundation (Grant No. OPPGH5307). The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Pinaki Panigrahi, MD, PhD, Center for Global Health and Development, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska 68198. E-mail: ppanigrahi@unmc.edu.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially.

The Aetiology of Neonatal Infection in South Asia (ANISA) study aims to identify the incidence, timing, etiologic agents, antibiotic resistance and risk factors for neonatal infections. The first phase of the study involves establishment of community-based pregnancy, birth and neonatal surveillance for identifying cases of possible serious bacterial infection (pSBI) in the 0–59 day age group and collecting specimens for etiologic evaluation using blood culture and state-of-the-art molecular techniques. Crucially, controls are also enrolled to identify natural colonizers that do not produce disease.1,2

The Odisha state site research hubs are located in Rourkela and Bhubaneswar in eastern India, areas that continue to record very high infant and neonatal mortality.3 The 2 sites were chosen to participate in ANISA because of their diversity, including coastal, rural, tribal, mining and periurban areas, as well as neonatal disease prevalence. The site investigators have previous experience conducting large-scale community and hospital-based surveillance and intervention studies among neonates.4–8 Established rapport with the state government health systems and availability of a trained workforce in the community, along with facilities for data management, microbiological analyses and long-term storage of biological specimens, were considered major strengths of the site. This article outlines the diverse nature of the communities and the associated operational, socio-cultural and scientific challenges faced while implementing the ANISA protocol at Rourkela and Bhubaneswar in Odisha.

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STUDY SITES AND POPULATION

The state of Odisha, home to 3.4% of India’s population, records the second-highest infant mortality rate (62/1000 live births) among the 29 states and 11 union territories in the country.3 Odisha is divided into 30 districts and each district is divided into blocks, with a population of approximately 100,000 in each block. Odisha’s population density is 265/km2, and its birth rate is 20/1000 population.9 The 2 study hubs are located in the major cities of Rourkela, in Sundargarh District, and Bhubaneswar, in Khordha District, where the neonatal mortality rates are 39 and 46/1000 live births, respectively (Fig. 1 and Table 1).9 These 2 areas are about 500 km apart, and their inhabitants are diverse in ethnic, socio-cultural, environmental, occupational and economic characteristics. The study area in Rourkela covers about 480 km2 and in Bhubaneswar 161 km2. The 105 study units in the Rourkela site have a total population of 204,000, and the 75 study units at the Bhubaneswar site have a population of 156,000. These units comprise 3 to 7 villages with populations of 600–1200 each. At the time of study initiation, there were 36,718 and 25,677 married women of reproductive age (13–49 years) in Rourkela and Bhubaneswar, respectively, for a total of 62,395 women eligible for enrollment in ANISA.

TABLE 1

TABLE 1

FIGURE 1

FIGURE 1

Villages around the Rourkela site are spread over hilly and mining areas of Lathikata and Kuarmunda Blocks, with indigenous tribes predominating in the population. Many small villages are dispersed in the study area, with the population living a traditional lifestyle with minimal outside interaction. The villagers earn their livelihood from forestry, rearing animals and raising arid crops. Some of those who live close to townships work for daily wages, and others have salaried employment in local coal and iron mines. In contrast, inhabitants of Balianata and Balipatana Blocks in Khordha District in the Bhubaneswar site depend on irrigated agriculture and work in government offices and small industries. They are relatively more affluent and live in densely populated villages that are close to each other. Apart from primary and community health centers, each site has one tertiary care municipal hospital that provides most health care for free. Capital Hospital, a large multispecialty government facility in the city of Bhubaneswar, and Ispat General Hospital, an Indian government undertaking with the steel industry in Rourkela, serve as the research hubs for ANISA.

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TRAINING AND RECRUITMENT OF PERSONNEL

Anganwadi (meaning “courtyard shelter”) Centers have been functional for more than 4 decades in our study areas, providing preschool mid-day meals, assessing nutritional status of children, and acting as a common place for health education, immunization, minor health check-ups and referral services. Female, high-school (or higher) educated Anganwadi workers are from the same or nearby villages and have been critical partners in the implementation of ANISA in Odisha, particularly in building rapport with families and birth registration. A new cadre of village-level workers, Accredited Social Health Activists (ASHAs), has been introduced in the area and they are also part of the existing community health structure. The ASHAs and the Anganwadi workers were incorporated into the ANISA project design to help maintain regular surveillance and facilitate bringing pregnant women to facilities for delivery. Both the Anganwadi workers and ASHAs work in concert with our dedicated community health volunteers (CHVs).

We follow a 3-tier reporting and monitoring system that we designed and have been using for the past 12 years. Considering the significant distance between the study units, an extra tier of block coordinators is utilized in Rourkela. Otherwise, each study site has 1 CHV, a woman from the same village. About 10 CHVs are supervised by 1 area coordinator, who reports either through block coordinators (in Rourkela only) or directly to program managers. A senior program officer is in charge of overall field operations (Fig. 2)

FIGURE 2

FIGURE 2

After receiving centralized training at the Child Health Research Foundation (CHRF) in Dhaka, senior clinicians, microbiologists and senior program officers trained 185 CHVs, 25 area coordinators, 6 block coordinators and 2 program managers on site. The training lasted 6 or 7 days and included common protocols, use of the ANISA text messaging system, and a 1-day clinical observation (newborn assessment, identification of pSBI cases admitted to hospital and other neonatal ailments). Three months after study initiation, we conducted a retraining at the district-level ANISA field offices. Pre- and post-training tests were conducted using pretested questions, and all personnel showed proficiency by the end of the pilot phase.

During January and May, 2013, additional rooms were made available by study hospital authorities for clinical and data management activities. The microbiology operations required many major changes, including controlled airflow in culture areas. Experts from CHRF and the US Centers for Disease Control and Prevention (CDC), Atlanta, as well as University of Nebraska-based investigators, provided hands-on training through troubleshooting and establishing different steps of specimen collection, analyses, storage and shipment. Information technology (IT) staff from CHRF helped the local IT manager in Bhubaneswar to install software remotely and conducted a site visit to provide further training and troubleshooting in various procedures for logging and tracking the text message report generation and other ancillary IT-related activities.

The Odisha field sites started piloting in June 2012 and graduated to the main study activities in August 2013 based upon satisfactory fulfillment of performance indicators.10 Healthy control selection also began at that time.

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ETHICAL CLEARANCE AND OTHER APPROVALS

The study protocol was approved by the Ethical Review Committee of the Asian Institute of Public Health which is responsible for the overall implementation of the study protocol at Odisha. Approval was also obtained from the Ispat General Hospital Ethical Review Committee. Since government health systems were utilized, we obtained additional approval from the Department of Health and Family Welfare of the Government of Odisha. The protocol was then reviewed (including an external peer review) by the Foreign Projects Department of the Indian Council of Medical Research. Final clearance from the Health Ministry Screening Committee of the Government of India was received along with approval from the Department of Home Affairs.

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CHALLENGES IN THE ADOPTION OF THE ANISA PROTOCOL AND REMEDIAL ACTIONS

Field Activities

Reaching Newborns Within 24 Hours of Birth

Although 88%–94% of all births in the Odisha site now take place in hospitals, we faced the initial challenge of capturing these births early. A majority (55%–62%) of mothers live far from hospitals, so it was difficult for CHVs and supervisors to reach the hospitals in time to collect initial information to enroll newborns within 24 hours. During the first 3 months of the study, we captured only about half of all births within this time frame (Fig. 3). Although this rate improved to some extent after retraining, it was inconsistent and dropped during the cold season (December). We then employed nurses to cover both day and night shifts at the hospitals where most deliveries took place. January and February, 2014, showed an increase in reporting in the first 6 hours after birth. A second round of refresher training was conducted in April 2014, and helped to maintain this high level in the first 6 hours of life, with most other births recorded within the first 24 hours (Fig. 3).

FIGURE 3

FIGURE 3

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Ensuring Accurate Newborn Assessments and Referral of pSBI Cases to Study Hospitals from Villages

Our second biggest challenge was identification of pSBI cases by CHVs at the community level and timely referral to study hospitals. Initially the identification rate was very low (2%–4%). A field office for each site was opened in the community for rigorous reinforcement of the protocol and training every fortnight. Utilization of our 3-tiered monitoring system using the mother-baby card (described below) along with routine use of mobile phones to call supervisory staff increased the rate to a steady 20% of all births (Fig. 4). During this transition and improvement, we worked hard to prevent unnecessary referral. The regular presence of study physicians in the field for confirmation or rejection of a diagnosis of pSBI made by the CHVs and comonitoring by area coordinators and program managers provided an additional level of confidence to the field workers to discern milder ailments while not missing any pSBI cases. We are now able to maintain specificity without losing sensitivity; about half of the referred cases are admitted after evaluation by a study physician (Fig. 5).

FIGURE 4

FIGURE 4

FIGURE 5

FIGURE 5

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Large Study Area, Difficult Terrain, Delay in Case Identification and Transport

The distance to be covered by CHVs and area coordinators in a 480 km2 area with forest and hills was a challenge in Rourkela. The recruitment of 15 additional CHVs permitted strict home monitoring. While each CHV sometimes visited only 3 or 4 homes (compared with more than 15 by others) because of the terrain, the time involved was necessary and the only way to conduct true population-based surveillance in areas where many deaths occur due to lack of communication and timely transport of sick young infants to hospitals. Even in coastal areas, the time taken for transportation of sick young infants and their parents was a challenge. Instead of utilizing one study vehicle in each area, we introduced a system where local owners of 3-wheeled auto-rickshaws provided transport upon receiving a phone call and received immediate payment at the study hospital according to set rates.

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Enrolling Healthy Controls

The enrollment of healthy controls was considered to be of paramount importance in the study to rule out normal colonizers that do not cause disease. The local institutional review board wanted study participants to perceive specific benefits apart from rigorous health monitoring in the most critical period of infancy. Since metabolic screens were still not part of routine care, we offered free thyroid screening to rule out congenital hypothyroidism that can cause serious morbidity. The offer of this screening, along with counseling by field personnel and study physicians, allowed our site to recruit the required number of controls for this study.

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Hospital and Laboratory Activities

QA/QC of Blood Culture

There were initial problems with contamination of blood cultures which needed to be addressed (Fig. 6). Allocation of a dedicated clean room for blood draws as well as training of nurses and completion of a physician-observed checklist helped maintain a contamination level below 5%. However, to achieve this level required constant vigilance. We found that even a small decrease in monitoring by laboratory staff resulted in increased contamination at both locations. We continue to have problems of contamination in cases where the young infant requires immediate oxygen and other life support in the crowded pediatric ward and cannot be brought to the research sampling room.

FIGURE 6

FIGURE 6

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Uninterrupted Power Supply and Maintenance of Major Equipment

We installed generators for freezers and automated blood culture machines, and uninterruptible power sources for all data management equipment. Although there are maintenance contracts at each site, we have faced time lags for factory-approved technicians to repair equipment. Our proactive measure was to provide a second −80°C freezer at each site which prevented thawing of valuable specimens when one of the freezers was out of order for nearly a week.

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International Shipment of Specimens

While there are multiple air couriers, it was difficult to find ones that allowed dry ice shipments and assured refilling during transit. In fact, our first shipment arrived at CDC when Atlanta was experiencing an unusual ice storm, resulting in flight cancellations and road traffic problems. However, due to the availability of storage facilities and the ability of the courier to refill the shipment with dry ice, all specimens were maintained at the required temperature until delivery.

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Unique Activities at the Odisha Site

Mother-baby Card and Manual of Newborn Care

A mother-baby card written in the local language, Odia, is given to the mother in the last trimester of pregnancy for follow-up. This card is kept with the mother throughout the study period. It bears a serial number (for internal tracking by field staff) and the ANISA study identification number. There are spaces for recording health status and the signatures of the CHV, area coordinator and a third-level supervisor/study physician. These signatures, with dates and times, in conjunction with scheduled and surprise visits by supervisors, provide a strict monitoring system for field workers. This card also serves as identification for the mother and infant when they come to the study hospital for treatment.

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SUMMARY AND CONCLUSION

Implementing ANISA in a population of over 350,000 spread across a large area with diverse geographic, socio-cultural and economic backgrounds was a formidable task. Involvement and assistance from state health department personnel, hiring local full-time study staff, enhancing individual family contacts, motivating marginal and minority communities and providing direct support to needy cases at health service points played important roles in attaining the necessary quality for our site to graduate from piloting to the main study phase in a relatively short time period. Implementation was a team effort with field staff, clinicians, microbiologists and data management staff working together on a regular basis. The ability of all our field staff to use mobile phones and text messaging was invaluable. The assistance provided by skilled domain experts at CHRF and CDC at every step was instrumental in addressing deficiencies in a timely fashion. Although the site is halfway into the main study, reaching sick young infants and transporting them to our study hospitals (and not to other private care providers or village doctors) will continue to be a challenge as we attempt to track and collect biological specimens from every young infant with pSBI for bacterial and viral analyses.

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ACKNOWLEDGMENTS

The authors thank the officials at the Indian Council of Medical Research for reviewing this protocol. This study could not have been implemented without the ownership and keen interest of the Cabinet Minister and Principal Secretary, Department of Health and Family Welfare, Government of Odisha. We are grateful to Mahendra Pradhan, Ranjan K. Raul, Basil Kullu, Karunakar Panda, Sunita Patel, Sabita Behera, Janaki Shaw and Jyoti R. Mohanty for their support in the data center, field and hospital. Our thanks are also due to over 250 field staff, including the CHVs and supervisory staff, and all the Anganwadi workers and ASHAs in the districts of Rourkela and Bhubaneswar for their sincere discharge of the duties assigned to them, as well as to the parents of the infants enrolled in this important study for their cooperation. We are grateful to Meghan Scott for her assistance in developing the manuscript.

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REFERENCES

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3. Directorate of Census Operations, Orissa. Provisional Population Totals – Orissa - Data Sheet: 2011.Accessed September 19, 2014 New Delhi, India Office of the Registrar General and Census Commissioner; 2011 Available at: http://censusindia.gov.in/2011-prov-results/data_files/orissa/Data%20Sheet-%20Orissa-Provisional.pdf
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6. Carlo WA, Goudar SS, Jehan I, et al. Newborn-care training and perinatal mortality in developing countries. N Engl J Med. 2010;362:614–623
7. Panigrahi P, Parida S, Pradhan L, et al. Long-term colonization of a Lactobacillus plantarum synbiotic preparation in the neonatal gut. J Pediatr Gastroenterol Nutr. 2008;47:45–53
8. McClure EM, Wright LL, Goldenberg RL, et al. The global network: a prospective study of stillbirths in developing countries. Am J Obstet Gynecol. 2007;197:247.e1–e5
9. Registrar General & Census Commissioner, India. Annual Health Survey Bulletin 2011–12, Odisha. 2012Accessed September 19, 2014 New Delhi, India Office of the Registrar General and Census Commissioner Available at: http://censusindia.gov.in/vital_statistics/AHSBulletins/files2012/Odisha_Bulletin%202011–12.pdf
10. Connor NE, Islam MS, Arvay ML, et al. Methods employed in monitoring and evaluating field and laboratory systems in the ANISA study: ensuring quality. Pediatr Infect Dis J. 2016;35(Suppl 1):S39–S44
Keywords:

neonatal; surveillance; pSBI; etiology; ANISA; Odisha; Rourkela; Bhubaneswar

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