https://orcid.org/0000-0002-8242-1911
Figures
Abstract
Background
In India, under-five children with Severe Acute Malnutrition (SAM) are referred to Nutritional Rehabilitation Centers (NRCs). NRCs screen the causes of SAM including tuberculosis (TB). The national TB programme recommends upfront testing with a rapid molecular test if TB is suspected in children.
Objective
We estimated the yield of and adherence to the TB diagnostic guidelines (clinical assessment and assessment for microbiological confirmation) among under-five children with SAM admitted at NRCs (six in district Sagar and four in district Sheopur) of Madhya Pradesh, India in 2017. We also explored the challenges in screening from the health care providers’ perspective.
Methods
It was an explanatory mixed method study. The NRC records were reviewed This was followed by three key informant interviews and three focus group discussions among staff of NRC and TB programme. Manual descriptive thematic analysis was performed.
Results
Of 3230, a total of 2665(83%) children underwent Mantoux test, 2438(75%) underwent physical examination, 2277(70%) were asked about the symptoms suggestive of TB, 1220(38%) underwent chest radiograph and 485(15%) were asked for recent contact with TB. A total of 547(17%) underwent assessment for microbiological confirmation. Of 547, a total of 229 gastric aspirate specimens underwent rapid molecular test (24% positive) and 318 underwent sputum microscopy (44% positive). A total of 223 were diagnosed as TB (195 microbiologically and 28 clinically confirmed) and 209 were initiated on anti-TB treatment. The treatment outcome was favourable (cure or treatment completed) for 70(31%) and not recorded for 121(54%). The main perceived challenges in screening for TB were poor team skills, lack of diagnostic facilities and poor understanding of the guidelines due to inadequate training.
Citation: Singh AR, Kumar A, Shewade HD, Dhingra B (2021) Poor adherence to TB diagnosis guidelines among under-five children with severe acute malnutrition in central India: A missed window of opportunity? PLoS ONE 16(3): e0248192. https://doi.org/10.1371/journal.pone.0248192
Editor: Frederick Quinn, The University of Georgia, UNITED STATES
Received: September 27, 2020; Accepted: February 19, 2021; Published: March 12, 2021
Copyright: © 2021 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files. The data can also be accessed on following URL Quantitative data: https://www.dropbox.com/home/NRC%20paper/PloS%20resubmission_V2?preview=S2+Annex.xlsx Qualitative data: https://www.dropbox.com/home/NRC%20paper/PloS%20resubmission_V2?preview=S3+Annex.docx
Funding: This project was funded by National Health Mission, Government of Madhya Pradesh, India (Child Health-Nutrition/NHM/2017/25383).
Competing interests: The authors have declared that no competing interests exist.
Introduction
Globally in 2017, an estimated 10% of the total diagnosed tuberculosis (TB) patients were children (<15 years) but in India this was six percent among reported TB [1]. It is both under-diagnosed and under-reported. The major reasons include poor access to rapid diagnostic tests with high sensitivity and specificity, paucibacillary nature of childhood TB, and difficulty in obtaining quality specimen for microbiological confirmation. Hence, the majority of childhood TB is clinically diagnosed [2–6].
TB in children is an inevitable consequence of its presence in any community [7]. Childhood TB is an indicator of recent and ongoing transmission of Mycobacterium tuberculosis [8]. Thirty to forty percent of childhood TB is extrapulmonary and can present in a wide variety of anatomical sites [9, 10]. In infants, the time between infection and disease can be shorter than in older children, and the presentation may be more severe [11].
In India, among under-five children, 38% are stunted, 21% are wasted (a sign of acute undernutrition), while 36% are underweight [12, 13]. The Integrated Child Development Scheme of India guidelines identifies Severe Acute Malnutrition (SAM) as weight-for-height/length Z- score below 3SD of the median World Health Organization (WHO) child growth standards or a mid-upper arm circumference (MUAC) <115 mm or the presence of nutritional edema [13, 14]. SAM can be an indirect cause of child death by increasing the case fatality rate in children suffering from common illnesses including TB [13, 15]. As per WHO guideline for facility based management of children with SAM, they should be referred to Nutritional Rehabilitation Centres (NRCs at sub-district and district level). NRCs screen the causes of SAM including infectious causes like TB [13, 16].
Globally, studies have reported that 4–20% of children with SAM have active TB [17–19]. In India, studies form NRCs have reported a variable prevalence of TB among children with SAM, ranging from 22% to as low as <1% [20–25]. This could be due to the extent to which TB screening is implemented and the adherence to the diagnostic algorithm and this has not been assessed in India [25]. In 2016, India’s national TB programme introduced a new pediatric TB diagnostic algorithm. This included up-front testing of gastric aspirate with a rapid molecular test if TB was suspected among children [26].
In order to understand the TB diagnosis gaps in children with SAM, our study aimed to determine the yield of and adherence to the TB diagnostic guidelines (clinical assessment and assessment for microbiological confirmation) among under-five children with SAM admitted at NRCs of Madhya Pradesh, India in 2017. We also explored the challenges in screening from the health care providers’ perspective.
Methods
Study design
An explanatory type of mixed methods study design was used [27]. The descriptive quantitative phase involving secondary data collection was followed by a descriptive qualitative phase.
Study setting
General setting.
Madhya Pradesh is a state in central India and has one of the largest networks of community and facility-based centers for the management of malnutrition. In 2017, the state had 8,465 Anganwadi centres (AWCs), 12,670 mini-AWCs, 315 operational NRCs and two severe malnutrition treatment units (SMTUs). In 2017, a total of 70,859 SAM children were admitted at the NRCs and SMTUs [16]. The guidelines for the screening, diagnosis and treatment of TB are same at NRCs & SMTUs so SMTUs are described as any other NRC in the study.
The study was conducted in two districts: Sagar and Sheopur. Sagar district had six and Sheopur has four operational NRCs. As per operational guideline for a 10 bedded NRC, the human resource required is one medical officer, four nursing staff, one nutritional counsellor, one cook cum care taker, one attendant or cleaner and one medical social worker [28]. Most of the NRCs have three permanent staff; these are feeding demonstrator, staff nurse and a cook. The in-charge of these NRCs is preferably a Pediatrician or a medical Officer as per their availability in the health facility where the NRC is housed.
Care pathway for identification of TB cases among children admitted at NRCs.
Under-five children with SAM along with medical complications get referred to NRC by a community health worker or may come directly (self-referral). This child is screened for medical complications and causes of SAM [13]. TB might be one of the possible etiology or complication of SAM [29]. Hence, initial clinical assessment of every child for TB is done using these five criteria: i) history suggestive to TB; ii) history of contact with sputum smear positive TB in the family; iii) physical examination for the signs of TB disease; iv) chest radiograph and v) Mantoux test. The national TB programme recommends that children with presumptive TB should be screened by a rapid molecular test (cartridge-based nucleic acid amplification test (CBNAAT) also known as Xpert MTB/RIF©) for confirmation of TB [30]. There must be every effort to demonstrate Mycobacterium tuberculosis, in any of the biological specimens of the patient [31]. Hence, the gastric lavage (preferably) or induced sputum should be obtained for every admitted child in the NRC. In case, microbiological confirmation of TB cannot be established by this method, the in-charge pediatrician or medical officer can also make a clinical diagnosis depending on the initial assessment and further investigations. If the child is diagnosed as TB disease (either microbiologically or clinically) they get registered and directly observed treatment (DOT) is commenced as per their weight band.
Study population
In the quantitative phase, under-five children with SAM, who were admitted to the NRCs of district Sagar and Sheopur between 1 January and 31 December 2017, were included. The selection of district Sagar and Sheopur was purely purposive. This was followed by qualitative phase in district Sagar. Concerned staff members were not available in Sheopur district because of strike during the qualitative study period (June 2018) and limited funds were available under the project, hence only one district was selected. For this, the representatives of the stakeholders involved in the care pathway of TB screening were selected if they were vocal, knowledgeable, and ready to participate in interviews. Selection was done to ensure maximum heterogeneity in the responses.
Data collection and sources of data
In the quantitative phase, between February and May 2018, information related to screening, diagnosis and treatment was extracted and captured in a mobile based data collection tool [32]. The source was records of NRCs (admission register, case records, NRC SAM register), laboratory register of designated microscopic centers (DMC) and treatment cards of the children. In case of ambiguity/unavailability/unclear information, it was clarified with the staff present over the facility. Results of quantitative phase fed into the development of interview guide for the qualitative phase (see S1 Annex for interview guide).
In the qualitative phase (June 2018), we conducted three focus group discussions (FGDs), one with NRC staff (feeding demonstrators/auxiliary nurse midwife posted at NRC, n = 7), second with staff of DMCs (TB laboratory technician and TB health visitor, n = 7) and third with senior treatment supervisors (n = 6) of the district. The representation of every NRC and DMC of the district was ensured while inviting the participants for FGDs. For key informant interviews, the stakeholders who were involved in the care pathway were identified: pediatrician-in-charge of NRC (n = 1), staff nurse of the NRC (n = 1) and district TB officer (n = 1).
The qualitative enquiry was conducted in Hindi at the date and time convenient to participants. Two investigators carried out all the qualitative interviews, among them one was trained in conducting the qualitative study. Before the start of interview, participants were informed about the purpose of the study. An interview guide with broad open-ended questions was prepared, pilot-tested and used to conduct these interviews/discussions. Audio recording (after consent) and verbatim notes were taken. The time duration of key informant interviews ranged from 32 to 55 minutes and the FGDs ranged from 42 to 65 minutes. Translation and transcription (in English) was done within a week by the investigators. Field notes of observations during visits/interviews were also made.
Data analysis
In the quantitative phase, data was extracted in Microsoft Excel 2010 (Microsoft, Redmond, WA, USA) and analyzed using STATA (version 12.1 STATA Corp., College Station, TX, USA). Key analytic outputs were the number (proportion) of children that were clinically assessed (each criteria presented separately) and the number (proportion) that underwent smear microscopy or rapid molecular tests to establish microbiological confirmation. It was operationally decided to include sputum microscopy for the assessment of microbiological confirmation. The STROBE guideline was followed for reporting the quantitative component of the study [33].
In the qualitative phase, transcripts obtained were compiled and discussed among investigators to become familiar with the data. Manual descriptive thematic analysis was used [34]. Codes and themes were reviewed to reduce bias and interpretive credibility. The decision on coding rules and theme generation was done by using standard procedures and with consensus among investigators. Both inductive and deductive codes were generated. Similar codes were combined into themes. To ensure that the results as true reflection of data, the codes/themes were reverted back to the original data. The themes were described and de-identified as representative statements were included in the results to illustrate the themes. The findings were reported by using COnsolidated criteria for REporting Qualitative research (COREQ) [35].
Ethics.
The study was approved by Institutional Human Ethics Committee of the All India Institute of Medical Sciences, Bhopal, India (IHEC-LOP/2018/EF0076, dated 02/02/2018). Administrative approval was also obtained before starting the study. As the quantitative phase was based on record review, waiver for written informed consent was requested and approved by the ethics committee. For the qualitative phase, written informed consent was taken (separately for audio recording) and the process was approved by the ethics committee. The data pertaining to the study participants (quantitative as well as qualitative) were fully anonymized.
Results
Quantitative phase
Of 3230 under-five children with SAM admitted at NRCs, 1552 (48%) were in Sagar and 1678 (52%) in Sheopur. Of 3230 children, 2263(70%) were identified by the Integrated Child Development Scheme services, 204 (6%) got admitted through healthcare delivery system, 85(3%) were self-referred and the source of referral was not recorded for 678 (21%) children (Fig 1).
ICDS: Integrated Child Development Services; AWC; Anganwadi Center, SAM; Severely Malnourished children, AFB; Acid Fast Bacilli, NRC; Nutritional Rehabilitation Center, $; Others: Healthcare system/Self-referred/Not recorded, CBNAAT; Cartridge-Based Nucleic Acid Amplification Test, ATT; Antituberculosis treatment.
As part of clinical assessment, 2665(83%) children underwent Mantoux test, of them 176 (6%) had a positive test; 2438(75%) underwent physical examination, of them one was suggestive of TB; 2277(70%) were asked about the symptoms suggestive of TB, of them 202 (6%) had symptoms suggestive of TB; 1220(38%) underwent chest radiograph, of them 159 (5%) had features suggestive of pulmonary TB; and 485(15%) were asked for recent contact with TB, of them 12 (0.4%) reported recent contact. (Table 1)
Gastric aspirate was obtained from 229(7%) children for CBNAAT and of them 55 (24%) were positive. Gastric aspirate specimen was obtained from 318(10%) for smear microscopy and of them 140 (44%) were positive. It was also revealed that in certain cases, where specimen was being sent for CBNAAT, smear microscopy was not being done. Of 3230, a total of 547 (17%) were tested either by smear microscopy or CBNAAT. A total of 223 (7%) were diagnosed as TB: 195 (6%) microbiologically confirmed and 28 (1%) clinically confirmed. (Fig 1)
The proportion being assessed for microbiological confirmation and the proportion diagnosed as TB, stratified by NRCs in the two districts is depicted in Table 2. The extent of screening varied across NRCs in Sagar while it was consistently low in Sheopur.
Of the 223 children with TB, anti-TB treatment was initiated for 209 (94%). Of 209, the treatment outcome was favourable for 70 (34%) (cured or treatment completed). Treatment was still going on for 17(8%), outcome was not recorded for 121(58%) and one child failed the treatment (Fig 1).
Qualitative phase
Qualitatively, the barriers for poor screening of under-five children with SAM at NRCs were explored and five themes were identified (Fig 2).
ICDS: Integrated Child Development Services; AWC; Anganwadi Center, Sputum smear microscopy, AFP; Acid Fast Bacilli, NRC; Nutritional Rehabilitation Center, CBNAAT; Cartridge-Based Nucleic Acid Amplification Test, ATT; Antituberculosis treatment.
Poor record keeping.
Among the children reaching the NRCs, the source of referral was not documented in one-fourth of cases. Even for children referred to higher facilities from NRCs, this information was poorly recorded. The NRC staff did not perceive this as an important job responsibility. (Field notes)
Lack of training.
There was lack of training of peripheral health workers and if they had received training, most did not remember the training content. The NRC staff (feeding demonstrator) stated during an FGD.
No, we have not gone through any training pertaining to screening/diagnosis of TB at NRCs
Reluctance for invasive procedure.
NRC staff perceived that obtaining biological specimen like gastric aspirate from children was a difficult task. One NRC staff (staff nurse) with more than five years’ experience, when asked about the gastric aspirate, described her problem,
No! Nobody in the hospital is trained to do it [gastric aspirate]. They have never been trained for this.
Poor team skills.
Poor team skills were observed in the form of lack of motivations of the in-charge pediatricians. This could be due to poor understanding of guidelines, lack of diagnostic facilities or non-feasibility of diagnostic tests. It eventfully led to poor adherence to the diagnostic guidelines.
The situation is different at different NRCs. We do not have facility for chest radiograph, CBNAAT and better guidance is needed to facilitate all the diagnostic tests. Considering all this the mainstay of diagnosis of TB is the Mantoux test barring at the NRC at district hospital. (DMC staff)
An NRC in-charge felt that lack of collection of gastric aspirate of CBNAAT was due to the poor motivation of staff nurse.
We used to write [investigation request] for gastric aspirate, but our staff nurse cannot do this. The challenge here is to motivate them for gastric Aspirate. (Pediatrician of an NRC)
Ambiguity in diagnostic algorithm.
CBNAAT was not available in all facilities. The screening and diagnostic guidelines were not explicit regarding what was to be done when certain tests/facilities were either not available or not feasible due to lack of assured specimen transport; therefore the screening guidelines were not consistently followed across the NRCs.
Children admitted at Sagar NRC undergo for CBNAAT, but for other places, it mainly depends on the wisdom of the doctor and feasibility of the tests. In most places, the availability of pediatrician is not confirmed and it is difficult for other staff members to diagnose or decide. (FGD, DMC staff)
At Sagar NRC, we use to send gastric aspirate of almost every child for CBNAAT since last few months. But for other NRCs, the decision of treatment is solely based on the result of Mantoux test, as no other tests are available. (DMC staff)
Discussion
Key findings
NRCs provide a unique window of opportunity for the screening of TB among under-five children with SAM, the utilization of this opportunity remained suboptimal. In the context of poor implementation of TB screening, the yield of smear microscopy and CBNAAT in the small subgroup of children who underwent testing cannot be extrapolated to all the children admitted at NRC (n = 3230). The diagnostic guidelines implemented at different NRCs were different. According to our findings, adherence to screening for TB was low because of poor team skills which may be due to busy schedule of in-charge pediatrician or their involvement in other programmes; non-availability of diagnostic facilities and poor knowledge of these guidelines. Furthermore, the treatment outcomes of more than half were not available. Because of poor adherence to diagnostic guidelines and suboptimal initial assessment, we are missing a lot of TB among under-five children with SAM.
Poor record keeping was consistently seen. Information related to source of referral of children to NRC, tests advised and date of testing was not consistently recorded. It appeared that there was a poor understanding of the denominator and a lack of cohort-wise tracking. High positivity rates among those tested indicates that those who were tested were retrospectively entered in the records.
During the initial assessment, less than three-fourth children were asked about the history suggestive of TB and history of contact to TB case was investigated in less than one-fourth children. Despite being simple to evaluate and hardly time-consuming, they were missed. The staff either undermined the importance or did not record the details in the case sheets. Similarly, few children had a record of physical examination. Only one child was found with signs suggestive of TB. This is surprising considering tubercular lymphadenitis is most common manifestation of extrapulmonary TB in children [7]. Studies from central India reported 0.4 to 22% prevalence of tubercular lymphadenitis among children (age less than 15 years) [36, 37]. Despite the fact that these studies did not address the particular age group of under-five children but still the proportion is very low in our study especially among children with SAM. Only about one-third children underwent chest radiograph and three-fourth underwent Mantoux test. This affects clinical diagnosis. It might be due to poor team skills that might have led to erratic usage of these diagnostics and poor coordination of NRC staff with concerned departments.
Although both gastric lavage and induced sputum are complementary to each other with comparative yield, it was interesting to note that gastric aspirate was preferred [38]. Induced sputum is cumbersome and more time-consuming process than gastric aspirate. Therefore, it is difficult to perform induced sputum at NRC attached health facilities at a regular basis.
A similar study carried out in 2012 in six sub-district level administrative units of Karnataka (a state in south India) reported bottlenecks in the diagnosis of TB at NRC. These were non-availability of full-time pediatrician, non-availability of diagnostic facilities and poor adherence to the diagnostic algorithm because of its non-feasibility [22]. This is similar to the findings of our study. The studies from other high burden countries also suggest the screening of childhood TB is always difficult and mostly delayed [39–46].
Recommendations
The following are our recommendations i) focus on reforming and reinforcement of result oriented quality training methods of NRC staff ii) ensure sustained availability and functionality of diagnostic equipment required for the screening iii) providing an assured specimen transport mechanism iv) standardized and simplified mechanism of record keeping and v) close integration between NRC and TB programme for treatment adherence during follow up visits at NRC.
Various studies have suggested capacity building of TB programme staff can significantly improve the TB outcomes [47–51]. Despite increase in expenditure towards training programmes in middle and low income countries, its robust evaluation is needed [52]. Ensuring sustained availability of diagnostic equipment will definitely improve the screening and diagnosis process of TB [40–44]. There are obvious reasons to believe that good record keeping process and close integration between NRC and TB programme will yield better results.
Strengths and limitations
The major strength of this study was its mixed methods design which proved invaluable in complementing and supplementing quantitative and qualitative findings. However, few limitations of the study are worth noting. First, the selection of two districts restricts the generalization of the findings of the quantitative phase. Second, the qualitative phase was undertaken only in one district. Qualitative systematic enquiry did not yield details about TB treatment adherence and high proportion of children with non-evaluated TB treatment outcomes.
Conclusion
To conclude, present study documented poor adherence to initial assessment and TB diagnostic guidelines among under-five children with SAM admitted at NRCs of two districts in central India. The main challenges perceived by the healthcare providers are poor team skills and poor understanding of relevant guidelines due to ambiguity in the diagnostic algorithm. Study recommends quality training to NRC staff, sustained availability of diagnostic equipment, uniform and simplified mechanism of record keeping and assured specimen transport mechanism.
Acknowledgments
The authors thank the National TB Elimination Programme and National Health Mission of Madhya Pradesh (India) for providing support and necessary guidance. We express our gratitude for our data collection team, comprising of Mrs. Seema Gotiwale (Project Coordinator), Mr. Saurabh Singh and Mr. Saurabh Rajak (both Field Data Collector).
Disclaimer: The contents of this paper do not necessarily reflect the views of the institutions the authors are affiliated to.
References
- 1. Corbett EL, Watt CJ, Walker N, Maher D, Williams BG, Raviglione MC, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med. 2003;163: 1009–1021. pmid:12742798
- 2. Lonnroth K, Williams BG, Cegielski P, Dye C. A consistent log-linear relationship between tuberculosis incidence and body mass index. Int J Epidemiol. 2010;39: 149–155. pmid:19820104
- 3. Udwadia ZF, Pinto LM, Uplekar MW. Tuberculosis management by private practitioners in Mumbai, India: has anything changed in two decades? PLoS One. 2010;5: e12023. pmid:20711502
- 4. Pandey R, Singh AR, Kabirpanti V, Mishra R. Barriers of Treatment-Supporters for DOTS under RNTCP in District Shahdol, India: A Mix-Method Study. Int Arch Biomed Clin Res. 2018;4: 80–85.
- 5. Pandey R, Singh A, Kabirpanthi V, ShubhashChandra Diwedi JB K., Mishra R. Challenges perceived by the private practitioners in TB notification at district Shahdol, Madhya Pradesh: A mixed-method study. Glob J Res Anal. 2018;7: 1–4.
- 6. G Meintjes H Schoeman, C Morroni, D Wilson GM. Patient and provider delay in Tuberculosis suspects from communities with a high HIV prevalence in South Africa: a cross sectional study. BMC Infect Dis. 2008;8: 72. pmid:18501019
- 7.
Starke JR, Donald PR, editors. Handbook of Child & Adolescent Tuberculosis. London (United Kingdom): Oxford University Press; 2016.
- 8. Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Starke JJ, et al. The natural history of childhood intra-thoracic tuberculosis: A critical review of literature from the pre-chemotherapy era. International Journal of Tuberculosis and Lung Disease. International Union Against Tuberculosis and Lung Disease; 2004. pp. 392–402. Available: https://www.ingentaconnect.com/content/iuatld/ijtld/2004/00000008/00000004/art00002
- 9. Pulmonary Zimmerman M. and osseous tuberculosis in an Egyptian mummy. Bull NY Acad Med. 1979;55: 604–8.
- 10. Marais BJ. Childhood turberculosis: reflections from the front line. Pediatr Ann. 2004;33: 695–698. Available: http://www.ncbi.nlm.nih.gov/pubmed/15515356 pmid:15515356
- 11. Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B. Paediatric tuberculosis. Lancet Infect Dis. 2008;8: 498–510. pmid:18652996
- 12.
International Institute for Population Sciences (IIPS) and ICF. National Family Health Survey (NFHS-4), 2015–16: India. Mumbai:IIPS; 2017.
- 13.
National Rural Health Mission(NRHM). Operational Guidelines on Facility Based Management of Children with Severe Acute Malnutrition. New Delhi: Ministry of Health and Family Welfare Government of India; 2011. p. 35. Available: http://rajswasthya.nic.in/MTCGuideline- MOHFW.pdf
- 14.
World Health Organization (WHO), UNICEF. WHO child growth standards and the identification of severe acute malnutrition in infants and children; A Joint Statement by the World Health Organization and the United Nations Children’s Fund. Switzerland & Newyork; 2009.
- 15. Padmapriyadarsini C, Shobana M, Lakshmi M, Beena T, Swaminathan S. Undernutrition & tuberculosis in India: Situation analysis & the way forward. Indian Journal of Medical Research. Indian Council of Medical Research; 2016. pp. 11–20. pmid:27834321
- 16.
Ministry of Women and Child Development. Integrated Child Development Services Scheme. In: Government of Madhya Pradesh [Internet]. 2017 [cited 12 Dec 2018]. Available: https://mpwcdmis.gov.in
- 17. De Maayer T, Saloojee H. Clinical outcomes of severe malnutrition in a high tuberculosis and HIV setting. Arch Dis Child. 2011;96: 560–564. pmid:21310895
- 18. LaCourse SM, Chester FM, Preidis G, McCrary LM, Arscott-Mills T, Maliwichi M, et al. Use Of Xpert For The Diagnosis Of Pulmonary Tuberculosis In Severely Malnourished Hospitalized Malawian Children. Pediatr Infect Dis J. 2014;33: 1200–1202. pmid:25361410
- 19. Sunguya B. Effects of infections on severely malnourished children in Kilifi-Mombasa and Dar es Salaam: a comparative study. Dar Es Salaam Med Students’ J. 2010;14: 27–35.
- 20. Prashanth MR, Savitha MR, Raju HNY, Shanthi M. Clinical spectrum of severe acute malnutrition among children admitted to nutritional rehabilitation centre of a tertiary care hospital with special reference to incidence of bilateral pitting pedal oedema in children with severe acute malnutrition. Int J Contemp Pediatr. 2018;5: 1928–32.
- 21. Natrajan E, Chhaya Valvi. Risk factors for acute malnutrition in infants under 6 months in a public hospital in Maharashtra- cross sectional observational study. Int J Sci Res. 2019;8: 19–21.
- 22. Bhat PG, Kumar AM V., Naik B, Satyanarayana S, KG D, Nair SA, et al. Intensified Tuberculosis Case Finding among Malnourished Children in Nutritional Rehabilitation Centres of Karnataka, India: Missed Opportunities. Lee YL, editor. PLoS One. 2013;8: e84255. pmid:24358350
- 23. Arya AK, Lal P, Pramod Kumar . Co-morbidities in Children with Severe Acute Malnutrition—A Tertiary Care Centre Experience. Int J Contemp Med Res. 2017;4: 10896–8.
- 24. Satpathy DM, Sahoo BK, Jena D. Socioclinical profile of SAM children admitted to a Nutritional Rehabilitation Center in South Odisha. INDIAN J Res. 2019;8: 223–5.
- 25. Anil Kumar Tiwari, Anil Kumar Jaiswal, Saurabh Kumar, Priyanka . A study of clinical profile and outcome of SAM children admitted in nutritional rehabilitation centre, Patna Medical College and Hospital, Patna, Bihar, India. Int J Contemp Pediatr. 2018;5: 1497–1504. Available: https://pdfs.semanticscholar.org/8e65/ebfef6f484ef6bf350d28a9e9b485620bcfc.pdf
- 26.
Revised National TB Control Programme (RNTCP), Pediatrics IA of. RNTCP Updated Pediatric TB Guidelines 2019. New Delhi: Central TB Division (CTD), Directorate General of Health Services, Ministry of Health and Family Welfare; 2019.
- 27. Creswell JW, Clark VLP. Designing and conducting mixed methods research. 2007.
- 28.
National Rural Health Mission(NRHM). Operational Guidelines on Facility Based Management of Children with Severe Acute malnutrition. Minist Heal Fam Welf Gov India. New Dehi; 2011. Available: http://www.who.int/lep/resources/SEAGLP20062.pdf
- 29. Lönnroth K, Corbett E, Golub J, Godfrey-Faussett P, Uplekar M, Weil D, et al. Systematic screening for active tuberculosis: rationale, definitions and key considerations [State of the art series. Active case finding/screening. Number 1 in the series]. Int J Tuberc Lung Dis. 2013;17: 289–298. pmid:23407219
- 30.
Revised National Tuberculosis Control Programme. Guidelines on Programmatic Management of Drug Resistant TB (PMDT) in India. Central TB Division, editor. New Delhi: Directorate General of Health Services, Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi– 110011; 2017. p. 23. Available: http://tbcindia.gov.in/WriteReadData/l892s/8320929355Guidelines for PMDT in India—May 2012.pdf
- 31.
Chilld Health and Nutrition. Circulars and Guidelines, Nutrition Rehabilitation Centers (M.P.) Management Information System Version 3.0. In: National Heallth Mission (Madhya Pradesh) [Internet]. 2013 [cited 19 Oct 2017]. Available: http://nrcmis.mp.gov.in/Circulars/29/Guideline 2.pdf
- 32.
ONA Systems: Make Data Count Reliable mobile data collection. Accessible visualization. Seamless collaboration. 2017 [cited 5 Jun 2017]. Available: https://enketo.ona.io/x/#poev
- 33. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370: 1453–1457. pmid:18064739
- 34.
Saldana J. The Coding Manual for Qualitative Research. Los Angeles: Sage Publication; 2010.
- 35. Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Heal Care. 2007;19: 349–357. pmid:17872937
- 36. Narang P, Narang R, Narang R, Mendiratta D, Sharma S, Tyagi N. Prevalence of tuberculous lymphadenitis in children in Wardha district, Maharashtra State, India. Int J Tuberc Lung Dis. 2005;9: 188–94. pmid:15732739
- 37. Shrivastav PS, Woike P, Tripathi L, Gaur R, Mangal K. Profile of Nodal Tuberculosis at a Tertiary Care Centre, Gwalior, India. J Med Sci Clin Res. 2015;03: 7970–6.
- 38. Singh S, Singh A, Prajapati S, Kabra SK, Lodha R, Mukherjee A, et al. Xpert MTB/RIF assay can be used on archived gastric aspirate and induced sputum samples for sensitive diagnosis of paediatric tuberculosis. BMC Microbiol. 2015;15: 191. pmid:26420261
- 39. Adejumo OA, Daniel OJ, Adebayo BI, Adejumo EN, Jaiyesimi EO, Akang G, et al. Yield of Screening for TB and HIV among Children Failing to Thrive in Botswana. J Trop Pediatr. 2016;62: 27–32.
- 40. Chiang SS, Roche S, Contreras C, Alarcón V, Castillo HD, Becerra MC, et al. Barriers to the diagnosis of childhood tuberculosis: A qualitative study. Int J Tuberc Lung Dis. 2015;19: 1144–1152. pmid:26459524
- 41. Sullivan BJ, Esmaili BE, Cunningham CK. Barriers to initiating tuberculosis treatment in sub-Saharan Africa: A systematic review focused on children and youth. Global Health Action. Taylor and Francis Ltd.; 2017. p. 1290317. pmid:28598771
- 42. Marais BJ. Improving access to tuberculosis preventive therapy and treatment for children. International Journal of Infectious Diseases. Elsevier B.V.; 2017. pp. 122–125. pmid:27993688
- 43. Marais BJ, Obihara CC, Warren RM, Schaaf HS, Gie RP, Donald PR. The burden of childhood tuberculosis: a public health perspective [Review Article].
- 44. Frieze JB, Yadav RP, Sokhan K, Ngak S, Khim TB. Examining the quality of childhood tuberculosis diagnosis in Cambodia: A cross-sectional study. BMC Public Health. 2017;17: 1–9. pmid:28049454
- 45. Pantha S, Aguinaldo MJ, Hasan-Ul Bari SM, Das Gupta R, Bari R, Sarker M. Facilitators and Barriers to Implementation of Childhood Tuberculosis Control Program in Bangladesh: A Mixed-Methods Study from BRAC Urban DOTS Centres in Dhaka. [cited 3 Aug 2020].
- 46. Chiang SS, Cruz AT, del Castillo H, Contreras C, Becerra MC, Lecca L. Evaluation of health-care providers’ knowledge of childhood tuberculosis in Lima, Peru. Paediatr Int Child Health. 2015;35: 29–35. pmid:25161060
- 47. Uwimana J, Zarowsky C, Hausler H, Jackson D. Training community care workers to provide comprehensive TB/HIV/PMTCT integrated care in KwaZulu-Natal: lessons learnt. Trop Med Int Heal. 2012;17: 488–496. pmid:22296235
- 48. Lewin S, Dick J, Zwarenstein M, Lombard CJ. Staff training and ambulatory tuberculosis treatment outcomes: A cluster randomized controlled trial in South Africa. Bull World Health Organ. 2005;83: 250–259. pmid:15868015
- 49. Raftery P, Ködmön C, van der Werf MJ, Nikolayevskyy V. Barriers to the diagnosis of childhood tuberculosis: A qualitative study. BMC Health Serv Res. 2020;20: 2–9.
- 50. Delai MY, Gounder S, Tayler-Smith K, Van den Bergh R, Harries AD. Relationship between education and training activities and tuberculosis case detection in Fiji, 2008–2011 [Short communication]. Public Heal Action. 2012;2: 142–144. pmid:26392973
- 51. Islama S, Harries AD, Malhotra S, Zaman K, Husain A, Islam A, et al. Training of community healthcare providers and TB case detection in Bangladesh. Int Health. 2013;5: 223–227. pmid:24030273
- 52.
Wu S, Roychowdhury I, Khan M. Evaluating the impact of healthcare provider training to improve tuberculosis management: a systematic review of methods and outcome indicators used. International Journal of Infectious Diseases. Elsevier B.V.; 2017. pp. 105–110. https://doi.org/10.1016/j.ijid.2016.11.421 pmid:27979785