Introduction

An estimated 2.5 million neonates died in 2018, accounting for about 47% of all deaths among children under five years of age [1,2]. Though global neonatal mortality decreased from 31 deaths per 1000 live births in 2000 to 19 per 1000 live births in 2015, the higher rate of 29 per 1000 observed in Central and Southern Asia and sub-Saharan Africa remains a concern [3,4]. While a large number of neonatal deaths were related to prematurity and birth asphyxia, a substantial number were due to serious bacterial infections such as neonatal sepsis and pneumonia [2,5]. The ANISA study from South-East Asia reported that among babies with possible serious bacterial infection (PSBI) who died with an attributable cause, 92% were bacterial [6]. In the Democratic Republic of the Congo (DRC), the neonatal mortality rate was estimated to be 29 per 1000 live births in 2018 [7].

The World Health Organization (WHO) recommends that infants with signs of a serious bacterial infection or neonatal sepsis be referred to a hospital and treated with injectable antibiotics, as it is estimated that most deaths are bacterial in origin [8]. Referral in low-resource settings may not be feasible or may not be accepted by families because of the cost of care in a hospital, lack of available or suitable transportation to a hospital, lack of hospital services, perceived low quality of care, or cultural beliefs about the inevitable mortality among hospitalized infants [9–13]. Studies from Southeast Asia have shown that when referral is not possible, sick young infants can be treated in the community or on an outpatient basis [14–16]. These studies were followed by randomized controlled trials comparing various simplified antibiotic regimens conducted in Bangladesh, the DRC, Kenya, Nigeria and Pakistan, which confirmed the safety and efficacy of outpatient treatment for these infants [17–20]. Using this evidence, WHO developed a guideline for managing PSBI in sick young infants when referral was not feasible [21]. The implementation of this guideline should result in increasing access to treatment for more sick young infants, which could result in neonatal mortality reduction.

Before the implementation and scale-up of this guideline in the DRC, public health officials required a test of the feasibility and practicality of implementing the WHO guideline within the local programme context. This paper describes the feasibility and implementation of the WHO PSBI management guideline by the health authorities in one region of the DRC. Our objectives were: i) all health facilities provide management of PSBI; ii) at least 80% of all the expected number of infants with PSBI to be identified and treated; and iii) among treated infants, at least 80% should receive adequate treatment.

Methods

Policy dialogue phase

In February 2015, a national orientation and policy dialogue meeting was organized by the DRC Ministry of Health (MOH) in collaboration with WHO. Participants included programme managers from newborn- and child health-related programmes, MOH Technical Advisory Group members, international partners (UNICEF, Save the Children, United States Agency for International Development), and academic institutions. At that meeting, the lack of a standard protocol for treating young infants with PSBI when a referral is not feasible, high newborn mortality, challenges of referral in rural areas and the need for action were discussed along with the results of the African Neonatal Sepsis Trial (AFRINEST) [19,20]. Table 1 summarizes the recommendations of the participants and agreements reached during the meeting. Recommendations regarding treatment were consistent with the WHO guidelines.

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Table 1. Decisions made during the policy dialogue meeting for the management of sick young infants with possible serious bacterial infection (PSBI)^* when a referral is not feasible.

https://doi.org/10.1371/journal.pone.0268277.t001

A second policy dialogue meeting was held at the provincial level to provide additional orientation and ensure buy-in from local authorities. The Provincial Minister of Health and the Directors of the Division of Health of North and South Ubangi Provinces and members of a Technical Support Unit (TSU) attended this meeting. The group decided to implement the PSBI guideline in five health areas selected as a convenience sample for early learning.

Barriers to health care seeking

Prior to implementation, we used qualitative methods to identify barriers to health care seeking. We held 20 focus groups with mothers, fathers, traditional birth attendants, and CHWs and 15 in-depth interviews with opinion leaders (physicians, political and administrative authorities, nurses and religious leaders). In each FGD 8 to 10 people participated. The discussion took place at the health center where people were convened. The selection of participants for the FGDs was guided by the health center nurses and the information provided by the CHWs. The criteria of homogeneity of residence, age, marital status, and level of education were also taken into account. These interviews were conducted under the guidance of two study physicians and two anthropologists from the University of Kinshasa. A total of 220 individuals, including 110 women and 95 men, participated in the FGDs, and 15 men in the in-depth interviews. The interviews recorded in Lingala and Ngbaka were translated into French and transcribed before being grouped and coded by theme and analyzed using ATLAS.ti version 7 software.

Our implementation strategy was informed by the major themes that emerged from the focus group discussions (Table 2).

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Table 2. Major themes of the barriers to healthcare seeking for young infants with PSBI identified during focus group discussions and interviews.

https://doi.org/10.1371/journal.pone.0268277.t002

Results

From April 2016 to March 2017, 3162 births were recorded at the participating health areas, of which we identified 3050 live births. CHWs visited 2909 (95%) young infants on day 1, 2680 (88%) on day 3, and 2656 (87%) on day 7 after birth.

We identified 285 young infants who resided in the study area and who had signs of PSBI, instead of 305 expected cases during the study period, based on an estimated 10% incidence of PSBI among 3050 live births [6,19]. Of these, 256 young infants received treatment for PSBI, thus the coverage of treatment was 83.9% (256/305). During the study period, based on the parents’ addresses, we also determined that an additional 426 young infants came from outside the study area, thus a total of 711 young infants up to 2 months of age were identified with signs of PSBI. Over half (365/711, 51.3%) of these infants were brought by family members to the health centres. Of 426 (60%) who required referral to a hospital, two-thirds (282/426, 66.2%) refused the referral advice (Table 3).

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Table 3. Identification and confirmation of infants with signs of possible serious bacterial infection by health centre nurses (n = 711).

https://doi.org/10.1371/journal.pone.0268277.t003

Pneumonia was identified in 285 infants; 90.1% received outpatient treatment at a health centre (Table 3), and 99.2% took at least 13 doses of oral amoxicillin (Table 4). Treatment failure was identified in 3.1% with no deaths (Table 4).

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Table 4. Treatment outcomes among sick young infants who received outpatient treatment at health centres.

https://doi.org/10.1371/journal.pone.0268277.t004

Severe pneumonia was identified in 141 infants, who were referred to a hospital, but 90.8% of families refused referral advice and accepted treatment at the health centre level (Table 3). All of them received at least 13 doses of oral amoxicillin. Treatment failure was reported in 7.8% of these infants with no deaths (Table 4).

CSI was identified in 233 infants who were referred to a hospital; 63.1% of families refused referral advice and accepted treatment at the health centres (Table 3). All completed two injections of gentamicin, and 97.9% received at least 13 doses of oral amoxicillin (Table 4). Among those treated as outpatients, 17.0% failed treatment, and one died (Table 4).

Health centre nurses classified 52 infants as critical illness, referred them to a hospital, and 86.5% of families accepted referral advice (Table 3). Seven infants whose families refused referral completed seven days of treatment with injectable gentamicin and injectable ampicillin. Treatment failure occurred in 28.6% of infants, and all survived (Table 4).

Among the 539 infants with PSBI who received outpatient treatment, 99.2% completed seven days of treatment, 8.3% failed treatment, and one died.

Among infants who were hospitalized, 7.7% with severe pneumonia died, 23.3% with signs of CSI died, and 40.0% with any sign of critical illness died within two weeks of the initial assessment. The overall case fatality ratio (CFR) among hospitalized infants with PSBI was 27%.

Challenges and solutions during implementation

We encountered several challenges related to the weak health system and governance during implementation (Table 5). We implemented the PSBI intervention using the existing infrastructure and health care force to ensure the smooth implementation of the programme and to respond to the needs of the community. We used study funds to overcome the main challenges. The challenges were regular topics for discussion during the meetings between the TSU and local health authorities.

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Table 5. Challenges and solutions during implementation.

https://doi.org/10.1371/journal.pone.0268277.t005

Discussion

We demonstrated the feasibility of the successful implementation of the WHO PSBI management guideline [21] in a programme setting during a one-year study period. All five health centres in the study area were able to provide outpatient treatment of PSBI. The coverage of treatment was 84% at either the first level facility health centre or a hospital. Nearly, all of the sick young infants treated on an outpatient basis received adequate treatment according to the WHO guideline [8,21]. Those young infants whose families were unable to accept referral advice were treated with the WHO recommended simplified antibiotic regimens [21] at the health centres on an outpatient level with high treatment success and low mortality rates. Young infants 7–59 days of age with only fast breathing represented two-fifths of all sick young infants and were treated on an outpatient basis without referral to a hospital.

In general, the nurses at the health centres were able to correctly assess, classify and manage sick infants with PSBI. They were able to correctly follow the national guideline for management, including the provision of injectable antibiotics when the referral was not feasible. There was only one death amongst all the sick young infants with PSBI signs treated on an outpatient basis, suggesting that treatment was effective. Also, spot checks for antibiotic dosage did not find any problems in our study, whereas 23% errors in dose calculation and 15% classification errors on assessment were reported from the MaMoni project, Bangladesh [24]. The training that health centre staff received and the oversight and handholding by supervisors and the TSU staff contributed to reinforcing the skills of the health workers and building their confidence. The critical role of technical support, mentoring and supervision of health care providers, has also been reported previously from PSBI implementation research studies in the MaMoni project and Kushtia, Bangladesh, Ntcheu, Malawi and Zaria, Nigeria [10,11,25,26].

In our study, treatment adherence was very high in those treated on an outpatient basis. Nearly all young infants treated on an outpatient basis completed their treatment. Such high rates have also been reported from other PSBI implementation research sites [10,11,13,26]. This may have resulted from the high-quality training, supervision and motivation of health workers as well as the acceptance of simplified treatment on an outpatient basis by the families [13]. Whereas, in India [12], the adherence rates were lower than those seen in our study.

During the study period, we identified over 3000 live births, and we expected that around 10% of young infants would develop signs of PSBI [6,19,20]. The number of young infants living in the study area who were identified with PSBI represented about 9% of live births, which was close to the published data and suggested that almost all potential cases of PSBI were identified and brought to the health centres for appropriate treatment. Our coverage of treatment was a bit less than that reported from Zaria, Nigeria (96%) [10]; but higher than those reported from Kushtia, Bangladesh (31%) [26]; Lucknow, India (53%) [12]; and Ntcheu, Malawi (64%) [11]. However, in our study, the overall number of PSBI patients were much higher than expected during the study period. Review of the addresses showed that only two-fifths of these sick infants were from the study area, whereas the majority were from the neighbouring villages. Families living near the participating health centres and even from further away found out about the free essential medicines and other supplies through word of mouth and came to seek care at these facilities.

Two-third of families whose sick young infants needed hospital care refused referral advice and accepted simplified antibiotic treatment on an outpatient basis. This is nearer to the median of 74% (range 34–97%) reported in the systematic review of community-to-facility neonatal referral completion rates in Africa and Asia [9]. Other PSBI implementation research sites have also reported high referral refusal rates i.e., 97% in Zaria, Nigeria [10]; 93% in Ntcheu, Malawi [11]; 81% in Lucknow, India [12]; and 83% in Sylhet and Lakshmipur, Bangladesh [13].

We observed 27% CFR among those who received treatment in a hospital compared to 0.2% CFR among those treated at the health centres. Higher CFR among infants receiving hospital care is likely to have resulted from greater severity of illness among this cohort. Alternate or additional explanations for higher CFR among infants receiving hospital care include delays in reaching the hospital due to the family decision-making process, distance to the hospital, lack of suitable transport, or poor quality of care at the hospital. The latter may be due to poor infrastructure, or lack of essential equipment and medicines at district hospitals in the study area. Both referral hospitals lacked oxygen, incubators and blood bank services, and sometimes essential medicines. Their laboratories are not equipped to perform cultures. In comparison, another PSBI implementation research site from Lucknow, India, reported 13% CFR among those treated at a hospital [12], compared to 2.6% CFR among those treated on an outpatient basis at the government health centres by trained health workers, whereas CFR was 25% among those sick young infants whose families refused treatment at any government facility and sought only private treatment.

In our study, we observed a higher treatment failure rate of 17% in young infants with signs of CSI compared to 5% reported in the AFRINEST severe infection study [19], which may be explained by the real-life setting of our study which was different from a controlled trial. Other PSBI implementation research studies have reported variable but generally, low treatment failure rates in CSI cases i.e., 3.5% in Malawi [11], 1.3% in Zaria, Nigeria [10]; and 5.8% in Lucknow, India [12]. However, our treatment failure rate of 3% for infants with pneumonia was lower than 19% reported in the AFRINEST pneumonia trial [20]. But, the AFRINEST study treatment failure definition also included persistence of fast breathing on day 4, which if excluded would result in a failure rate of 3.7% [20]. Other PSBI implementation research studies have reported variable but low treatment failure rates in fast breathing pneumonia cases i.e., none in Zaria, Nigeria [10]; 2.2% in Malawi [11], and 4.8% in Lucknow, India [12].

There are several programme implications of our results. First, although we have demonstrated that it is possible to implement the WHO guideline for PSBI treatment [21] using existing infrastructure, additional investments were needed to ensure success. Health workers were provided with quality training, incentives and additional supervision, and facilities were supplied with essential medicines. Families were receptive to advice by CHWs on home care, including referral when needed, when they knew that quality services were available and affordable. We believe that the feasibility of implementation depends upon the provision of these resources. Second, we demonstrated to the national and local health authorities that it is possible to provide simplified antibiotic regimens to sick infants with PSBI at the primary level of care, thereby, contributing to a reduction in young infant deaths in the DRC. However, for this intervention to be part of the overall national strategy for the elimination of preventable deaths, investments must be made in strengthening the health system. Third, the success of using a model with oversight and consultative support provided by a consortium of government and non-governmental technical experts (i.e. the TSU) suggests the importance of the partnership between technical experts and programme implementers. The TSU played an important role in capacity-building and problem-solving, which may have provided programme staff with confidence for implementation. The TSU participated in planning, training/capacity strengthening, supervision and monitoring, quality control and problem-solving aspects of the study. To scale up this intervention, some technical support to the health system in the future would be needed. Technical members of the TSU may also have benefitted from their role by gaining an understanding of the potential contributions they can make to build a responsive and resilient health system.

The key lessons learned from this implementation research that may be of use to policy-makers include the value of government commitment and substantial external support and partnership. Uninterrupted delivery of essential commodities is critical for maintaining the quality of services and confidence of communities. Technical support, mentoring and supervision are important to sustain the quality of care of services. The need for health system strengthening for achieving and sustaining high coverage of PSBI treatment is essential. Poor quality of care at hospitals may result in low acceptability of referral advice and preference for outpatient treatment.

Our study had some strengths. First, the MOH played a vital role in the implementation of the study. MOH staff from central, district and health zone levels were actively engaged in the study and were looking forward to the eventual integration of the findings into the routine health system. This strong support is crucial not only for generating community buy-in and ownership but also for promoting quality assurance of the intervention. Second, this study was implemented in a programme setting. People who work in the real world (health centre nurses) were used to assess infants with danger signs and provide appropriate treatment. Although support to acquire various commodities, including antibiotics, was provided through study funding, all medicines were purchased from the regional distribution centre, used by all government health facilities for the purchase of medicines and health supplies. The existing health system monitoring, evaluation and supervision system was used and strengthened, thus ensuring the sustainability of the process. Finally, community buy-in was promoted as part of the implementation. Village leaders sensitized the community for timely care-seeking and facilitated referral by CHWs.

Our study also had some limitations. Although we demonstrated that community-based identification and treatment of PSBI was feasible, we cannot necessarily infer feasibility and sustainability on a larger scale because of some aspects of our strategy. First, we had to fill gaps in areas of usual responsibility of the district and national health authorities. Staff salaries and provision of essential medicines and supplies are core functions of any government, and unless these are addressed sustainably, it will be difficult for the DRC to scale up this strategy and make progress towards the achievement of the Sustainable Development Goals [27]. The DRC has committed to universal health coverage and needs to take lessons learned from this implementation research to identify sustainable solutions for scaling-up. Second, CHWs are village volunteers and, as such, are not entitled to payment. However, in this study, CHWs received a small monetary incentive and bicycles. We do not know what their performance might have been without this incentive. Also, health centre nurses received a small monetary incentive. This may have generated extra motivation that would not exist under scale-up conditions. Third, almost all critical supplies (thermometers, respiratory rate timers, weighing scales, medicines) were provided by the study and an international agency. The success of scale-up would not be possible without this level of assistance. Finally, due to limited resources, we could not increase the capacity of the district hospitals. We collected limited outcome data from hospitalized patients, but couldn’t collect detailed clinical data.

In conclusion, our study provides policy-makers and programme implementers with strategies for addressing the management of sick young infants with PSBI when the referral is not feasible. Implementing the PSBI guideline in a programme setting is feasible but will require appropriate investments and external support. Treatment protocols can be standardized, and trained health care providers can manage sick young infants with simplified antibiotic regimens, which in turn will save lives. Health system challenges need to be addressed to successfully implement the strategy. Community sensitization and improvements in quality of care at the referral level are complementary strategies that the MOH needs to strengthen to prevent deaths and improve survival. This implementation research has identified critical areas for action and has shown the roadmap for innovative strategies for addressing the needs of sick young infants and for leaving no one behind in the context of universal health coverage.

Supporting information