Effect of training of frontline health workers on tuberculosis: a cluster randomized control trial in South Nigeria [version 2; peer review: 1 approved]

Background: Intensified efforts to improve tuberculosis (TB) diagnosis, treatment, and prevention are needed to meet global EndTB targets. Community health workers’ (CHWs) knowledge with respect to case finding is vital in tuberculosis elimination. This study aimed to determine the effect of tuberculosis training on the knowledge of community health workers in Nigeria. Methods: As part of a larger multicomponent intervention study, a randomised control trial was conducted with CHWs in 18 primary health care (PHC) clusters in Nigeria. The clusters were allocated to three arms: training and cash incentive (A), training only (B), and control (C) arms. Arms (A) and (B) received training on tuberculosis symptoms, prevention, score (83.1%) when compared to the control group (93.1%). These were, however, not statistically significant. Conclusions: An improvement in the CHWs’ knowledge of symptoms, prevention, diagnosis and treatment of tuberculosis was observed after a training intervention was done. Integration of routine tuberculosis training is recommended to improve tuberculosis case finding in high burden communities. This was a randomized control trial to study the effect of training and or incentive on the knowledge of community health workers. The participants were health workers in formal (community health workers) and informal (patent medicine vendors, PMVs) settings. The title could be amended to read “Effects of training of frontline health workers’ on tuberculosis: a cluster-randomized control trial in South Nigeria”.


Introduction
One of the United Nations' Sustainable Development Goals (SDG) as contained in the SDG target 3.3 is to end the tuberculosis epidemic by the year 2030. This End TB Strategy defines as a target for 2030, a 90% reduction in the number of TB deaths and an 80% reduction in the TB incidence rate (new cases per 100 000 population per year) compared with levels in 2015. 1 Progress in global TB elimination which has been inconsistent in recent years has led to intensified efforts to improve TB diagnosis, treatment, and prevention required to meet global targets for 2020-2035. 2 To achieve these set targets, there's a need for various national tuberculosis programs to have agendas set and implemented towards meeting goals. In 2019 alone, an estimated 1.4 million people died from TB-related illnesses and of the estimated 10 million cases that year, some 3 million went undiagnosed, or were not officially reported to national authorities. 3 Diagnosis, treatment and prevention of tuberculosis rests largely on the healthcare workers. Health care workers knowledge and attitude with respect to diagnosis, treatment and prevention of TB is vital in TB elimination. 4 In Nigeria, the treatment of TB is free at all public health facilities. Successful implementation of directly observed treatment short course (DOTS) is dependent on the ability of the health care system to identify and properly manage TB cases which requires active involvement of the health workers in TB diagnosis and management. TB treatment should include counselling regarding progression of disease and the importance of treatment adherence. 5 Countries with good TB knowledge scores have been shown to have better TB indices with respect to treatment and prevention. In Iran, 98.4% of healthcare workers had a 'good' score for knowledge of TB with 98.2% who correctly answered that TB transmission is through the respiratory tract, 90% acknowledged TB is a treatable disease, and only 12.6% of them were oblivious that it is caused by a bacterium. 6 In South India, accurate knowledge of TB was displayed by 86% of healthcare workers. 7 Good and fair level of knowledge of TB was possessed by 56% and 43.9% of healthcare workers in Thailand. 8 Studies in South Africa and Mozambique also reported satisfactory level of knowledge of TB among health care workers. 4,9 In Mozambique, higher knowledge scores were seen among those with greater educational attainment. Knowledge scores were also affected by profession with medical doctors having the greatest knowledge score and midwives having the lowest knowledge scores. 4 A study in Vietnam also showed that an increased level of TB knowledge among the health staff is correlated with participation in TB training and higher medical education. 10 In South Africa, the mean percentage of correct answers to the 98-item questionnaire administered was 59.5% pre-training and rose to 66.5% after training. Post-training, nurses, doctors and TB support staff showed significant improvements in total mean knowledge scores. 11 A study in China that assessed knowledge retention of multidrug-resistant tuberculosis (MDR-TB) health practitioners 1 year after training, also reported an overall positive long-term impact of the training on participants' knowledge. 12 Akande et al., in a study in Nigeria reported a significant increase in the knowledge of TB infection control after the health workers had been trained. 13 Training of frontline health workers is an important strategy for TB control as efficient human resources development is crucial for facilitating tuberculosis control. In an ideal setting, training on TB should be integrated into the general education of health workers and into health systems. However, in a tuberculosis-endemic and resource-poor country like Nigeria, these systems are too weak to support routine effective tuberculosis control and training services. 14 This study therefore aims to determine the effect of TB training on the knowledge of community health workers in Akwa Ibom state. This will aid in policy making and program designing with regard to TB control in the state.

Methods
This study was registered as a clinical trial with the Pan African Clinical Trial Registry (PACTR202010691865364 on 14 th October 2020). This article is reported in line with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. 27 Setting Akwa Ibom State is located in the Southern part of Nigeria, with a population of about 5.4 million people. 15 It has 31 local governments across three senatorial districts. It has 368 primary health centers, unevenly distributed across the local REVISED Amendments from Version 1 In answer to the reviewer's query on trainer qualifications, we have provided the necessary information on trainers' qualifications. We have also modified the topic to reflect the reviewer's comment.
Any further responses from the reviewers can be found at the end of the article government areas (LGAs). Akwa Ibom state has a high burden of TB and human immunodeficiency viruses (HIV). At the time of this study, the USAID was carrying out TB control activities in 15 LGAs and TB Reach had projects in 3 of the remaining 16 LGAs. The study population was the 13 LGAs that were not covered by the ongoing TB programs.

Study design
The study was designed as a three-arm parallel cluster randomized control study. We evaluated the effect of cash incentives and training on community health workers' knowledge of TB. The PHCs were grouped in three clusters as shown in Figure 1.
A panel survey was planned but this was not possible as there was large in-and out migration of the patent medicine vendors (PMVs), especially those who originally sent their apprentices to the training. All the HCWs trained in the clusters were followed up for the duration of the study. At endline, we deployed the same method used in recruitment at baseline, targeting all HCWs in the study clusters. This design was used to minimize sampling error and take into account the design effect and prevent contamination across the three study arms. Therefore, participants were selected as two independent cross-sectional samples.
The interest in evaluating both training and cash incentives concurrently informed the choice of a multi-arm cluster randomized trial. It is also documented that sharing a control arm reduces the sample size relative to performing separate 2-arm trials. 16 Cluster randomization was used in this study because the target of intervention was not individual health workers, but the PHC clusters. Each PHC cluster consisted of the PHC facility and its catchment communities. The RCT was conducted in six high TB burden LGAs in the state. The LGAs were selected from the sampling frame of 13 LGAs, with the aid of the State Tuberculosis and Leprosy Control Officer (STBLCO). In each participating LGA, 3 PHC facilities offering DOTS treatment and services were selected by simple random sampling and included in the study, each LGA has 3 clusters. Each PHC plus the catchment communities served as a cluster for this study. All community Health workers (CHWs) (PHC workers and patent medicine vendors) in each cluster were recruited into the study.

The selected
LGAs were randomized to one of the three experimental arms by three researchers. Each researcher represented an intervention arm and picked from a box containing the names of the LGAs. Each LGA was assigned to the intervention arm picked by the researcher. All CHWs in the study clusters in each LGA were automatically assigned an intervention arm based on this randomization. Training with cash incentives was study cluster arm A and training only was arm B. The CHWs were recruited with the aid of the facility focal persons, working with the Chairman of the PMVs. All CHWs in the catchment were given an invitation to the training. The Field Coordinator conducted visits to the Facility Heads and Chair of PMV for each cluster. Formal letters were served to the Head of facility in each cluster. He was requested to mobilize all the CHWs in the catchment. He thus directed the Field Coordinator to the Chair of the PMVs who subsequently mobilized all the PMVs for the study. No exclusions were made, except if the person declined to participate. All CHWs in each cluster who participated in the workshop and gave consent were enrolled for the study under Arm A or B depending on their cluster.
Blinding of participants to their allocated arms was not possible. To ensure that participants were blinded to the intervention, the LGAs chosen were spread apart and not contiguous to reduce contamination. Blinding of assessors to the different arms was also not possible.  Interventions A one-day training session was carried out for each of the arms separately. The sessions lasted about 6 hours. The allocation ratio for the three clusters was 1:1:1 as shown in Figure 2.
The training was conducted by the researchers in collaboration with the State Tuberculosis Leprosy and Buruli ulcer Control Program (STBLCP) office. The research team comprised four consultant physicians: one cardiologist, one respiratory medicine physician and two community medicine physicians; three medical officers; and the STBLCP is a physician with post graduate training in tuberculosis. One of the medical officers has specialist training in tuberculosis. Qualifications of the trainers have been included. Prior to the workshop, a Training of Trainers was conducted by the Lead Researcher and the STBLBCP State Coordinator and researchers. The Workshop facilitators were trained on the course contents. This was to develop a shared understanding of the aims of the workshop and familiarize them with the contents of the workshop materials. Training manuals were developed specifically for the research and distributed to participants. Facilitators used both the training manuals and power point presentations developed from the manuals. Facilitators used participatory learning methods to deliver the course contents. The contents of the training were based on the module developed for active TB case finding through house-to-house search for community-based organizations (CBOs) and CHWs by the National Tuberculosis and Leprosy Control Program (NTBLCP). 17 The sessions included training on basic symptoms, misconceptions diagnosis and treatment of TB, identification of presumptive TB cases, sputum collection and transportation and linking TB patients to care and treatment.
Participants were also taught how to collect sputum samples by the State Laboratory Focal Person for TB. Sputum cups were donated by the STBLCP program, the researchers procured transportation media (plastic bowls that could contain 4 sputa cups). At the end of the training, each participant was given a container for transporting sputum, 4 sputa cups, a presumptive case referral booklet and information, education and communication (IEC) materials to be used in educating clients.
Participants were instructed to carry out community education campaigns, identify presumptive TB cases in communities, collect sputum and make referrals to the PHC for treatment. The control Arm C had 41 CHWs. They were also requested to organize outreach health education campaigns in the communities. The participants in intervention arm A (85) received a cash incentive of two hundred naira (USD0.78) for every presumptive case referred for screening.
The interventions were carried out between April 2019 and March 2020. The trial ended as scheduled after one year.

Data collection
Data collection was carried out for a period of 12 months starting in April 2019 and ended in March 2020. Data collection was done via quarterly supportive supervisory visits (SSV) made to the trained Community Health Extension Workers (CHEWs), PMVs and CPs. During the quarterly SSVs, data was collected from the CHWs and compared with the facility TB register. The number of presumptive cases referred, and number of outreaches conducted during the quarter were documented.
A pre-intervention assessment of CHWs knowledge on TB was done using a pre-tested self-administered structured questionnaire. 27 This was a standardized and validated questionnaire used by the national TB program for the 2017 TB Prevalence survey in Nigeria. The questionnaires were administered just before the training workshop for study arms A and B. However, they were administered at the six PHC facilities for the control arm as there was no training conducted for them.
A post-intervention assessment was also done using the same tool after 12 months, in the PHC facilities in each of the clusters.

Outcome variables
Knowledge of TB was a secondary outcome variable for this study. The total knowledge score was 21. Good knowledge was taken as scores above 11, and poor scores below 11. Knowledge of TB was assessed at individual level and at cluster level. The focus of this paper was the secondary outcome. The secondary outcome measure of knowledge was assessed and analysed both at the individual participant level and cluster level.

Data analysis
Data was collected and entered into a Microsoft excel spreadsheet, version 2013, then collated and analyzed using STATA version 13 and GraphPad Prism version 8. R is an alternative open access software that could be used. The statistician was blinded to the study allocation until the data set was ready for final analysis. Descriptive statistics were carried out using frequencies and percentages and presented using tables. Chi square/Fischer's exact test was used to compare the groups. And mean difference as effect size within each group. A p value of less than 0.05 was taken as statistically significant.

Results
A total of 240 CHWs were recruited at baseline and 153 trained, 85 in arm A and 73 in arm B, while 82 were recruited in the control arm 26 . At the end of the trial 72, 77 and 72 were analysed in arms A, B and C, respectively, to give a total of 221. Over the 12-month period of intervention, some CHWs retired, relocated and transferred out of the catchment area intention-to-treat analysis was done.
Most of the CHWs in this study were female (62.5%), aged 30 years or less (47.9%), and had secondary level of education (64.6%). PMVs made up the majority of the health workers (78.8%), and over half (69.2%) worked at patent medicine shops. Most had worked at their current position for 1-4 years (32.1%). There was statistically significant difference in the duration at current position (P = 0.035) and type of facility of CHWs (P = 0.000) across the three arms. Also, a significantly higher proportion of CHWs in the control group (43.9%) had previously attended a TB workshop and had access to TB guidelines (31.7%) compared to their counterparts in other groups (Table 1). Table 2 shows the sociodemographic characteristics across the three arms post-intervention. Most participants were aged 31-40 years (44.3%), female (53.4%), had secondary level of education (64.3%) and had worked for 1-4 years at their current position (38.0%). The majority were PMVs (77.4%), and worked at patent medicine stores (52.9%). There was a statistically significant difference in the duration of current job of the CHWs across the three arms (P 0.006), and in the type of health facility across the three arms (P 0.001).
There was a significant increase in the total knowledge score of the respondents at end line (P 0.0001), with the respondents at baseline having a mean knowledge score of 11.8 (3.2) and at end line 16.8 (2.5). There was also statistically significant difference in the different categories of knowledge tested at baseline and at end line (Table 3). Table 4 compares the knowledge of tuberculosis across the three arms of the study. There was statistically significant relationship seen between respondents' knowledge of diagnosis (P 0.0001), knowledge of prevention (P 0.014) and the total knowledge score (P 0.0480); and the different study arms. Post-intervention, a higher proportion of the respondents in the control group had good knowledge of diagnosis and treatment (75%) and prevention (93.1%) compared to the training and cash incentives group (55.6% and 76.4%, respectively). These were statistically significant at P 0.0224 and 0.0096 respectively (Table 5).
At endline, a higher proportion of the respondents in the control group had good knowledge of diagnosis and treatment (75%) and prevention (93.1%) compared to the training only group (42.9% and 77.1%, respectively). These were statistically significant at p=0.0109 and 0.0001, respectively (Table 6).       At baseline, CHWs who were in the training and CCT arm had a mean total knowledge score of 13.8 (2.4), and at end line, 14.5 (2.1), and this difference was statistically significant (P 0.0001). The difference in mean general knowledge score at pre-and post-intervention was also statistically significant (P 0.0430) ( Table 7). Table 8 shows the knowledge score of the health care workers that were in the training only arm at baseline and at endline. The mean general knowledge score, prevention score and total knowledge score showed a statistically significant increase at the end of the study compared to baseline (P 0.0001, 0.0353 and 0.0001, respectively).
In the control arm, the mean total knowledge score increased by 2.1 (95% CI:1.3-2.9) at endline, and this increase was statistically significant (P 0.0001). Significant increases were also noticed in the different categories of knowledge assessed for at endline compared to baseline (Table 9).

Discussion
This randomized control trial aimed to assess the effect of tuberculosis training on community health workers knowledge on TB in Akwa Ibom state. Overall, there was improvement in the respondents' knowledge post-intervention, compared to the baseline knowledge. The CHWs were comparable in their socio-demographic characteristics at baseline and at endline. It is worthy of note that a significant proportion of CHWs in the control arm had previously received training on TB, and had access to TB guidelines. This may be due to the attention the state has been receiving as a result of the high prevalence of HIV/AIDS, and consequently TB.
This study found a significant increase in CHW's TB knowledge post intervention when compared to the baseline. The highest increase was noticed in knowledge of prevention, followed by knowledge of general symptoms. At baseline, the mean knowledge score of the CHWs was just above the average, increasing by a score of three at end line assessment. This corroborates with others studies that found an increase in knowledge of TB immediately after training and even long after training was done. 13,18,19 Training was found in Abia state, Nigeria, to not only improve knowledge among Health workers, but to also improve all indicators of the Finding TB cases Actively, Separating safely, and Treating effectively (FAST) strategy which include the time to diagnosis (the time between when patient presents to the health facility to when a diagnosis of TB is made), time to treatment which the time between making a diagnosis and commencement of TB treatment, number of presumptive TB and Drug Resistant TB (DRTB) cases identified and number of TB and DRTB cases commenced on treatment. 20 Comparing the three arms of the study post-intervention, it was observed that knowledge of diagnosis, prevention and the total knowledge score was significantly different across the three arms. Furthermore, the control arm was seen to have a higher mean knowledge score when compared to the arms that received training. This may have been an effect of previous training that the health workers in the control arm had received, as well as the fact that they reported having more access to TB guidelines. This finding was noticed during data analysis, despite earlier attempts to control for such contamination in the study. In a similar study among HIV infected people in Minna, training was shown to significantly improve the knowledge of the participants in the intervention group compared to the control group. 21 In contrast, a similar study by Rakhshani et al. reported a significant increase in end line knowledge of malaria in the intervention group when compared to the control group. 22 More participants from the training and cash incentives arm in the present study however had good knowledge scores when compared with those in the control arm, though this finding was not statistically significant.
This study compared the knowledge of CHWs in each arm at baseline and at endline. Among the participants in the training and cash incentives arm and in the training only arm, there was a significant increase in the mean total score between the baseline and post intervention. This is similar to results obtained in Turkey where training intervention increased the primary healthcare workers' knowledge on immunization. Furthermore, the study reported a significant increase in the vaccination coverage rate in the community after the training intervention. 23 Training intervention is therefore be effective in increasing knowledge and effecting behavior change. This is corroborated by other studies. 21,22 Training community health workers on TB is essential to achieving TB control as they are the frontline health workers in the communities and are at a better position to identify TB cases. In a study in Southern Mozambique, health workers were seen to have poor knowledge of TB, and consequently low practice competency. 24 Wu et al. found a decline in health workers knowledge one year post intervention, compared to the immediate post intervention period, though it was still higher than the pre-intervention knowledge. 18 This therefore implies that training of health care workers should not be a one-time event, but a continuous process if TB control is to be achieved. Experiences in Kyrgyzstan 14 and the Democratic Republic of Congo show that periodic training and supervision in the field can improve healthcare workers' TB knowledge and skills. 25

Limitations
This study had some limitations. Firstly, though this study was planned as a panel survey, this could not be carried out. This is because some of health workers in the different communities may have resigned or moved away, while others took up these positions. Therefore, not all those that were trained at baseline could participate in the post intervention assessment. Also, a few CHWs were transferred in and were part of the post intervention assessment since it was a cluster sampling.
Another limitation was the selection bias seen in the study. The control arm had more exposure to TB training as evidenced by the baseline characteristics like exposure to workshops and access to TB guidelines were significantly higher among the control group. The control arm was likely to have had previous trainings on TB and had access to TB guidelines which may have affected the study results. This is because random allocation of PHCs to the different arms was carried out prior to the pre-intervention assessment.

Conclusion
This study was conducted to determine the effect of TB training on the knowledge of community health workers in Akwa Ibom state, Nigeria. Patent Medicine Vendors formed two thirds of the CHWs mobilized, indicating they were readily available in the communities. We found a significant improvement in the CHWs knowledge of symptoms, prevention, diagnosis and treatment of TB after the training intervention was done. We thus recommend the integration and use of PMVs in the delivery of interventions in the community. Furthermore, integration of routine TB training for all categories of CHWs will improve TB case finding and notification, improving TB indices in the communities and the country.   Table 4 is not necessary as the data have been presented in subsequent tables that compare the different interventions with the control.

3.
Table 7 has a title implying the comparison is between intervention and control arms but it is actually pre-and post-comparison; let this be corrected.

4.
It is implied in the discussion that the observed impact in the control was from "contamination". It is rather a selection error than contamination. The statement should be deleted.

5.
Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Public health
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.