Treatment coverage of mass administration of azithromycin among children aged 1–11 months in 21 districts of Kebbi state, Nigeria

Abstract

Background

The WHO recommends mass drug administration (MDA) as a strategy to deliver safe and cost-effective medicines to prevent and treat diseases. The antibiotic, azithromycin, has been used during MDA for the treatment and prevention of trachoma in Nigeria. Azithromycin has recently been shown to reduce infant mortality in communities receiving it for trachoma-elimination purposes in sub-Saharan Africa. This article reports on the implementation strategies for the safety and antimicrobial resistance of mass administration of azithromycin to children aged 1–11 mo using the trachoma programme platform in Kebbi state.

Methods

The mass administration of azithromycin among 1–11-mo-olds in Kebbi was implemented in three phases: (i) the preimplementation phase, during which specific activities were conducted to achieve government and community buy-in, ownership and capacity building; (ii) the implementation phase, which included the mass administration of azithromycin carried out by community volunteers (also known as community-directed distributors [CDDs]), monitoring (by health workers and independent monitors) and reporting of the distribution by all personnel; and (iii) the postimplementation phase, which included the validation of community data, where each item of community summary data is verified and checked for completeness and accuracy before uploading to the District Health Information System platform, where data are visualised, analysed and stored.

Results

In total, 97% of the target population received treatment; the remaining 3% were not treated due to signs of ill health, history of allergy to antibiotics, parental refusal or absence at the time of MDA. Children aged 1–11 mo accounted for 17% of the under-5 population, with females constituting 56% of the target population. In communities that were monitored, reports showed that only 5% lacked distribution materials (scales, slings or registers), >80% correctly entered data into community registers and 5% of children were not treated due to inadequate azithromycin provided to the CDDs for distribution.

Conclusion

The implementation of azithromycin MDA for children aged 1–11 mo in Kebbi, utilising the trachoma platform, exhibited commendable coverage due to existing programme platform, healthcare and community structures, intensive advocacy and social mobilisation, real-time monitoring and progress-tracking strategies. It also demonstrated that the trachoma platform is suitable for implementing public health interventions, even after the elimination of trachoma in previously endemic districts.

Introduction

Nigeria has one of the youngest populations globally, with children aged <5 y (under-5) making up to 16% of its population; it is one of the highest contributors to the burden of child mortality, accounting for 10% of all under-5 deaths globally.¹ Mass drug administration (MDA) is a strategy designed to deliver safe and cost-effective medicines to prevent and treat diseases.²

Recently, the sub-Saharan tri-country study (Macrolides Oraux pour Réduire les Décès avec un-Oeil sur la Résistance—MORDOR),³ showed a cumulative 13.5% reduction in mortality among children under-5 who received azithromycin (AZT), with the highest impact among infants.⁴ Based on this evidence, the WHO provided conditional recommendations to conduct AZT MDA to children aged 1–11 mo for the prevention of childhood mortality (infant mortality rate [IMR] and under-5 mortality rate [U5MR]) in sub-Saharan African settings that include areas with high mortality (of IMR>60/1000 or/and U5MR>80/1000). The WHO also recommends that child survival interventions are available and leveraged on for the AZT MDA for the prevention of childhood mortality, and concurrent actions taken to strengthen their effective implementation. Because there is limited information on the safety and efficacy of AZT in children aged <6 mo, pharmacovigilance for mortality, adverse reactions and antimicrobial resistance should also be instituted.⁵

Nigeria, with a U5MR of 71 and IMR of 111 per 1000 live births,⁶ is certainly a priority country in sub-Saharan Africa for IMR reduction. Childhood deaths are mainly caused by acute respiratory tract infection, diarrhoeal diseases, malaria, sepsis and nutritional problems. High-impact, cost-effective interventions with safe, low-cost medicines can prevent most of these deaths. With northern Nigeria accounting for the most significant burden of childhood morbidity and mortality,⁷ the Federal Ministry of Health (FMoH) has instituted several health interventions to improve child survival. These interventions include the seasonal malaria chemoprophylaxis programme, routine immunisation, the polio eradication initiative and the neglected tropical diseases (NTDs) elimination and control programme, in which the mass administration of AZT is used for the treatment and prevention of trachoma. With these interventions available, the implementation of the AZT MDA for the prevention of childhood mortality was instituted in 2021; it was called Safety and Antimicrobial Resistance of Mass Administration of Azithromycin in 1–11 months in Nigeria (SARMAAN). The aim of the SARMAAN project is to enable the FMoH, together with the Nigerian Institute of Medical Research (NIMR), to administer AZT through MDA platforms and evaluate the benefits of improving child survival in Nigeria. The SARMAAN project is being implemented across six states (Abia, Akwa Ibom, Jigawa, Kano, Kebbi and Sokoto). In Kebbi state, SARMAAN implementation is scheduled to occur biannually over a period of 24 mo, leveraging on the already existing trachoma programme of the NTD platform, with the NIMR responsible for monitoring the safety and antimicrobial resistance of the project in addition to the pharmacovigilance measures normally conducted on the trachoma platform.

For >10 y, AZT, a broad-spectrum macrolide, has been used in Nigeria for the treatment of a variety of bacterial infections causing acute respiratory illness, soft tissue infections, rheumatic heart diseases, diarrhoeal illness and even malaria. It is also commonly used in the management of NTDs like trachoma by the FMoH NTD elimination and control programme. The FMOH currently uses AZT for trachoma MDA from the age of ≥6 mo, with tetracycline ointment used for children aged 0–5 mo and pregnant women. For research purposes, AZT has been authorised for children aged 1–11 mo in the selected SARMAAN project states. At the time of implementing the SARMAAN project in Kebbi state, the trachoma intervention had commenced its surveillance stage in the endemic local government areas (LGAs), hence there were was no ongoing trachoma MDA. This paper aims to highlight that the trachoma platform not only provides an avenue for the generation of evidence for the MORDOR trial, but also demonstrates the suitability of the trachoma platform for successful delivery of SARMAAN in Kebbi state with strategic adaptations.

Methods

Ethical clearance for the SARMAAN study project was obtained from The National Health Research Ethics Committee of Nigeria. Eligibility criteria for the MDA included children aged 1 mo (at least 30 d old) to <12 mo on the week of the MDA. Also, these children were residents of the community and the child's parent/caregiver gave consent for the child to be administered AZT. Exclusion criteria from the MDA included any child with body weight <3.0 kg, any child who appears ill or weak, any child unable to swallow liquid delivered either from a cup or using a spoon because of physical limitations and any child with a known allergy to antibiotics, particularly AZT, or the antibiotic group to which AZT belongs: macrolides.

The SARMAAN standard operating procedure, training manual and data tools for the NTD platform were developed at the national level by the national NTD elimination and control unit of the FMoH with the technical support of the implementing partners. The MDA, which was conducted from April to June 2022 in Kebbi state for children aged 1–11 mo on the trachoma elimination programme platform, had the following phases: preimplementation, implementation and postimplementation.

• 1. Preimplementation: Preimplementation phase activities undertaken included advocacy visits to state policymakers, traditional leaders and religious leaders to secure their support and buy-in. Other awareness campaigns included community mobilisation meetings, radio campaigns and the use of town announcers. These activities were continuous and took place throughout the preimplementation and implementation phases. Key stakeholders were actively engaged, and planning meetings were conducted to formulate a comprehensive work plan. These meetings established a consensus on the proposed strategy and timeline for the implementation process. Community sensitisation and mobilisation meetings were also held to secure community ownership. The preimplementation phase was completed with capacity building for health workers on MDA implementation (census and treatment) for children aged 1–11 mo, the process of reporting, reverse logistics of medicine balances and supportive supervision to community-directed distributors (CDDs) under their catchment communities.

The training was conducted at the state level for the state NTD team and the LGA NTD teams. This training was facilitated by the FMoH with technical assistance from the implementing partner: Sightsavers. At the LGA level, the trained state and LGA teams stepped down the training to health workers in charge of frontline health facilities in each LGA. These health workers went on to train the community volunteers known as CDDs to conduct the house-to-house census (to collect names, the gender and ages of each household member, starting with the head of household) and administer AZT. The training of CDDs was carried out in the facility that serves the community to which the CDDs belong. The training of CDDs was practical and participatory and the content aimed to build CDDs’ capacity to complete the community treatment register for census and, during treatment, weigh each child with a handheld scale (to which a sling large enough to hold the child was fitted), reconstitute the powdered Zithromax solution before use, chart the child's weight to determine the correct amount of Zithromax to administer and to correctly administer the medicine to each eligible child. The dose charts were based on a calculation of a dose of 20 mg/kg body weight and showed the quantity in ml that should be administered to a child at a given weight.

Lastly, the CDDs were also trained on the various signs of adverse and severe adverse reactions during MDA with the corresponding actions they should take if any of these occurred. Being resident members of the community, the CDDs were taught to provide parents and caregivers with this information during MDA and to also document any adverse reactions reported, while they immediately referred severe adverse reactions to their catchment health facilities.

• 2. Implementation: The implementation phase commenced in each community with a house-to-house census that was conducted by trained CDDs. Using the data-capturing tool called the community treatment register, children aged 0–11 mo were documented in months, while the ages of the other members of the household from 12 mo and older were documented in years (this register has both the census and treatment segments with a summary at the bottom of each segment). The census data obtained not only revealed the number of eligible children for the MDA but also guided the health worker to quantify the medicines that was given to the CDDs for treatment in each community. Following the census, the retrieved community registers were collated by the health worker and submitted to the LGA through the ward focal persons for validation, then the CDDs were provided with the required quantity of AZT for their communities by the health workers.

Prior to the administration of AZT by the CDDs, consent was obtained from each parent or caregiver (depending on which was applicable) at the time of the visit. Children aged 1–11 mo, documented in the community register, received a weight-based dose of AZT, and this administration was duly documented in the community register. To achieve the correct weight-based dose for each child, a calibrated handheld weighing scale was used to weigh each child. The child was placed in a cloth sling that was hung on the hook on the scale, to obtain a reading indicating the weight of the child after the scale is tared (a button on the scale designed to take off or subtract the weight of the cloth sling from the weight of the child). The CDD then referred to the comprehensive weight-based dose chart provided, to administer the dose indicated for the child's weight. Other entries into the registers included the quantity of AZT given to each child, and reasons why the eligible population were not offered the medicines or were not accepting the medicines. The reasons for not being treated included being severely ill (at the time of the visit), being <3 kg of weight (i.e. underweight as a sign of being malnourished, stunted and general sickness), known allergy to antibiotics, being absent during MDA and parents not consenting to the treatment.

The MDA activity was supervised by the state and the LGA NTD health workers. Because they were responsible for the training of the CDDs, they provided monitoring and supportive supervision (based on criteria such as difficult-to-reach areas, complex/urban/mixed population areas or areas shown to have previous MDA challenges), as well as on-the-job capacity building and other support when necessary, along with supplying medicines and materials (where insufficient) during MDA implementation. Also, independent monitors (IMs) were engaged for quality assurance and to ensure adherence to guidelines and standard protocols. The IMs and supervisors used standard checklists (CommCare) that were preinstalled on their Android devices to complete monitoring and supervision data. Daily monitoring reports were presented to all key implementing stakeholders and other partners at evening review meetings, where challenges were addressed and the progress of MDA was tracked.

• 3. Postimplementation: This phase focused on the validation of community data, where each item of community summary data was verified and checked for completeness and accuracy. The data were entered into the District Health Information System platform where the data were visualised, downloaded, analysed and stored. Reported MDA data were analysed using data tools and formulae in Microsoft Excel (Redmond, Washington, USA, http://microsoft.com/en-us/microsoft-365/excel). The analysis focused on identifying strengths and gaps in the MDA implementation, such as coverage in terms of percentage of community reached and percentage of the location (usually LGA or state) reached with medicines. In this paper, treatment coverage refers to the percentage of the eligible population in a particular location who were offered, accepted and took the medicines as recorded in treatment registers and reported by programme data-reporting tools. Other postimplementation activities included retrieval of unused drugs (and empty bottles), analysis of treatment, post-MDA monitoring and validation reports.

Results

• 1. MDA—Census data for under-5-y-olds in Kebbi, 2022.

In Figure 1, the census data collected showed that the target population (children aged 1–11 mo) accounted for 17% (180 842) of the under-5 children population (1 037 932).

Figure 1.

Age distribution of under-5 children, Kebbi, 2022.

• 2. Treatment coverage

Table 1 shows the overall census and treatment of children aged 1–11 mo (180 842). Three LGAs reported treatment coverage of 100% of the census, while five out of 21 LGAs reported <95% treatment coverage. Overall, the state had treatment coverage of 97% (175 638) of the total number of 180 842 eligible children in the communities where the census took place. More female children (99 182) were treated compared with males (76 454).

Table 1.

MDA treatment coverage of 1–11-month-olds in Kebbi state

Census			Treatment
Female (1–11 mo) census	Male (1–11 mo) census	Total census (1–11 mo)	Female 1–11 mo treated	Male 1–11 mo treated	Total treated (1–11 mo)	Coverage (%)
102 026	78 816	180 842	99 182	76 454	175 638	97%

In Table 2, the community data also showed that 10 communities in two LGAs had no eligible children (aged 1–11 mo) during treatment. Out of 3577 communities expected at the time of MDA, 23 communities across three LGAs had no census or treatment due to insecurity.

Table 2.

Community coverage data of 1–11-mo-olds in Kebbi state

LGA	Communities	Communities visited	Communities treated	Communities without treatment	Reasons for not treating
Aliero	105	105	104	4	No eligible child
Arewa	175	175	175
Argungu	197	197	197
Augie	162	162	162
Bagudo	319	315	315	18	Insecurity
Birnin Kebbi	197	197	192	6	No eligible child
Bunza	126	126	126
Dandi	163	163	163
Danko Wasagu	365	365	365
Fakai	249	249	249
Gwandu	136	136	136
Jega	134	134	134
Kalgo	85	85	85
Koko Besse	123	123	123
Maiyama	137	137	137
Ngaski	196	196	196	3	Insecurity
Sakaba	170	151	151	2	Insecurity
Shanga	149	149	149
Suru	189	189	189
Yauri	147	147	147
Zuru	231	231	231
Total	3650	3732	3726	33

A total of 5204 (3%) children from the censused population were not treated during the MDA. The reasons for non-treatment are categorised in Figure 2.

Figure 2.

Reasons for non-treatment of children (aged 1–11 mo), Kebbi, 2022.

In four LGAs, parents and caregivers of 74 (0.042%) children aged 1–11 y who were given AZT reported that they showed signs of an adverse reaction, which was either vomiting or mild fever lasting for a few hours. No cases of severe adverse effects were reported during this round of treatment.

• 3. Monitoring of MDA

As described in the MDA methodology, state and LGA health personnel and IMs conducted the monitoring of selected communities. Table 3 shows key indicators that were monitored.

Table 3.

Indicators for monitoring MDA among 1–11-mo-olds, Kebbi, 2022

MDA monitoring indicators	Number	Percentage
Communities visited	571
Number of communities monitored with trained CDDs	533	93%
Number of communities reporting a census completed before MDA	513	90%
Number of communities reporting an absence of MDA materials: registers	63	11%
Number of communities reporting an absence of MDA materials: scales	26	5%
Number of communities reporting an absence of MDA materials: dose chart	25	4%
Number of communities reporting an absence of MDA materials: slings	24	4%
Number of communities reporting correct entries in the register	464	81%
Number of communities monitored with at least one child missed due to unavailability of medicines	31	5%
Number of communities reporting adverse events	39	7%
Number of communities supporting CDDs with cash or in kind	26	5%

A total of 571 communities were visited by the IMs while MDA was ongoing. Of the communities visited, 533 (90%) had trained CDDs conducting the MDA and 513 (90%) had reported a census in the registers. Only 31 (5%) of these communities reported having children who were not treated because the medicines given were inadequate, while adverse events were reported in 39 (7%) communities monitored.

Discussion

Mass distribution and administration of AZT among children aged 1–11 mo is necessary to reduce infant and child mortality in Nigeria. The 1–11-mo population targeted was derived by calculating 4% of the total projected population for Kebbi. The community census of children aged <1 y was 19% lower than the expected projection of the 2006 National Population Census.⁸ This may be attributed to insecurity experienced in some communities, resulting in the migration of families to safer communities outside the state. While it was important for us to ensure that no child was left behind during the MDA, 23 communities across three LGAs could not be accessed during the census and treatment as a result of insecurity. In northern Nigeria, insecurity is one of the major external factors that affect implementation of health interventions.^9,10

In this study, 97% of children aged 1–11 mo took the AZT dose. AZT treatment coverage is >80% of the threshold for trachoma effective coverage recommended by the WHO.¹¹ This AZT treatment coverage among children aged 1–11 mo is consistent with what was achieved in the 2020 trachoma MDA with AZT conducted in Augie LGA (unpublished,¹² NTD snapshot). However, it surpasses the coverage reported in 2013 in Plateau state, Nigeria, which reported a coverage of 60.3%.¹³ Alshamahi et al.¹⁴ also reported lower coverage of 90% for the trachoma MDA coverage in seven selected districts in Yemen. The Kebbi SARMAAN coverage results are also higher than those reported by Keenan et al.,³ where in the total of 1533 communities that were randomised, 190 238 children censused at baseline and 323 302 person-years monitored had a mean antibiotic coverage of >4 biannual distributions of 90.4% (SD 10.4%) of the censused population during the MORDOR trial.

The mass administration of AZT to 1–11-mo-olds in Kebbi being a pilot intervention, leveraged on the existing trachoma and NTD platform structures with targeted advocacy and social mobilisation effort for community acceptability. Community ownership through the selection of CDDs, real time monitoring of MDA and daily monitoring team reviews, which helped to identify gaps that were addressed immediately, also contributed to the high coverage achieved. The assumption is that high coverage then the prevalence of respiratory tract and gastrointestinal infections is expected to decrease until the next round of MDA commences. This is due to the beneficial antibiotic effects of AZT on these types of infections.¹⁵

The children that were not treated accounted for 3% of the censused population, and the reasons for non-treatment included being absent during MDA, refusals/non consent by caregivers, antibiotic allergy and signs of ill health. Children that exhibited signs of ill health such as malnourishment, underweight and stunted growth were referred to health facilities within their catchment area for proper management of their health conditions. Some of these referrals would have remained unidentified or resulted in serious complications.

During monitoring, some communities without trained CDDs were either missed during selection and did not send representatives for training or were trained but did not conduct the distribution due to several reasons, including having other competing activities (school, farm work, trading), or they were not provided with adequate support or incentives. Technical support, social support and incentives have been identified as problems implementers face during MDA and the need to address them is important for successful MDA.¹⁶ In some instances, the communities selected other volunteers who were not trained to conduct the MDA, which explains why some CDDs did not have distribution materials like registers, dose charts and slings.

Although this report generates findings that will help improve coverage for future rounds of AZT MDA among 1–11-mo-olds, the result of this report should be interpreted considering the following limitations. This report only provides information on the implementation of the first round of AZT MDA to children aged 1–11 mo in Kebbi state using the trachoma platform; the impact of MDA on child mortality cannot be assessed after one round of treatment. Also, this report does not include information on the safety and antimicrobial resistance of the SARMAAN project, which can demonstrate the impact (or not) of AZT on infant mortality in Kebbi state. Although this report details the programmatic processes and findings of the first round of MDA in this novel project in Nigeria, a comparison with subsequent rounds of MDA will be more beneficial due to the maturity of the project.

Conclusion

The implementation of AZT MDA for children aged 1–11 mo in Kebbi, utilising the trachoma platform, exhibited commendable coverage of 97% due to the collaborative effort of government officials, healthcare professionals, community leaders and CDDs, adaptative real time monitoring and daily progress tracking. The trachoma platform has proved its usefulness in delivering the SARMAAN project and could be used for implementing similar public health interventions, even after the elimination of trachoma as a public health problem in previously endemic districts.

Although further studies and more rounds of MDA will be required to provide information on the impact of this MDA in reducing infant and under-5 mortality in Kebbi state, the very good coverage recorded in this MDA might be an indication that this may be achieved.

Authors' contributions

All authors contributed to either one or more aspects of the design, implementation, reporting and/or analysis of this article. Each author also contributed to the writing of this manuscript and has read and approved the final version.

Acknowledgements

The authors wish to acknowledge and thank Folake Aliu, Godwin Tarbo, Eunice Dogo, Abrak Gimba and Folake Ibrahim for supporting aspects of monitoring, supervision and data handling. We also acknowledge the Departments of family medicine and Neglected Tropical Diseases, FMoH, Nigeria, the NTD unit of Kebbi state SMoH, the Kebbi SPHCDA, Local Government Area NTD coordinators in Kebbi state, both state and LGA data officers in Kebbi state and Sightsavers staff in Kebbi state.

Funding

SARMAAN and the production of this manuscript was funded by a consortium of donors to Sightsavers' Accelerate programme, including Bill and Melinda Gates Foundation, Children's Investment Fund Foundation, The ELMA Foundation, Virgin Unite, and an Anonymous donor. The funders had no role in the writing of the manuscript or the decision to submit it for publication. The azithromycin POS was donated by Pfizer.

Competing interests

None

Ethical approval

Ethical clearance for the SARMAAN study project was obtained from The National Health Research Ethics Committee of Nigeria (NHREC).

Data availability

The data that support the findings for this study are available from DHIS and Sightsavers. Access is subject to certain restrictions and require permission from FMOH and Sightsavers. Researchers interested in obtaining this data can submit request to FMOH tor Sightsavers.