The Global Use of Mobile Based Applications in Tuberculosis (TB) Care: A Systematic Review Protocol

Background: Tuberculosis remains one of the world’s deadliest communicable diseases despite being preventable and curable. The use of mobile phones has increased worldwide over the past decade and this has created opportunities to use mobile phones as intervention tools in health care including in promoting prevention, treatment and adherence monitoring and evaluation. However, the potential of information and communication technologies (ICTs) to ght TB remains largely untapped. Many countries are still researching further on how to use eHealth and mHealth effectively in the ght against TB. This systematic review protocol seeks to explore the mobile based applications that are being used in TB care globally and will provide crucial information to inform programming for the national TB programme, bringing the focus on interventions that really inuence improving TB outcomes. Methods: A systematic review will be conducted through online searches using comprehensive Medical Subject Headings (MeSH) terms in various combinations. Information sources will include the Cochrane Central Register of Controlled Trials, Medline, Google Scholar and PubMed. The review will be done by 2 reviewers who will resolve discrepancies through consensus. Narrative data synthesis will be done. Discussion: Analysis of the selected studies will provide information on the use of the mobile applications in TB care globally. Conclusions will be based on the best available scientic evidence. The results will provide crucial information to inform programming for the national TB programme, bringing the focus on interventions that really inuence improving TB outcomes. This will result in the effective use of resources by channelling them where there is the greatest impact in terms of reducing morbidity and mortality due to TB in Zimbabwe.

reviewers who will resolve discrepancies through consensus. Narrative data synthesis will be done.
Discussion: Analysis of the selected studies will provide information on the use of the mobile applications in TB care globally. Conclusions will be based on the best available scienti c evidence. The results will provide crucial information to inform programming for the national TB programme, bringing the focus on interventions that really in uence improving TB outcomes. This will result in the effective use of resources by channelling them where there is the greatest impact in terms of reducing morbidity and mortality due to TB in Zimbabwe.
Systematic review protocol registration: PROSPERO CRD42020154793 Background Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Although the bacteria usually affect the lungs, they can also attack any part of the body such as the kidney, spine, and brain [1]. Tuberculosis that affects the lungs is referred to as pulmonary TB whilst TB affecting other parts of the body is known as extra pulmonary TB. Pulmonary TB is spread by droplet infection when an infected sputum positive infected person sneezes or coughs. The symptoms of TB infection include a cough that lasts 3 weeks or longer, pain in the chest, coughing up blood or sputum (mucus from deep inside the lungs), weakness or fatigue, weight loss, loss of appetite, chills, fever and night sweats [2,3] According to the World Health Organisation (WHO) sputum smear microscopy is the widely used methods to diagnose Tuberculosis worldwide. However, this method only detects half the number of TB cases and does not detect drug resistance. On the other hand, the use of the rapid test Xpert which provides results within 2 hours has been on the increase since 2010. This test detects TB and Rifampicin resistance. Currently this test is being recommended by WHO as the initial diagnostic test for all people with signs and symptoms of TB [1]. Tuberculosis is treatable and curable, with active drug susceptible TB treated with a standard 6-month course of 4 antimicrobial medicines. However, adherence is always an issue during treatment and patients require lots of support in terms of information and monitoring [1].
According to the Global TB Report 2018, TB is still one of the top ten causes of death and is now the leading cause from a single infectious agent, ahead of HIV and AIDS [4].In addition, an estimated 9.6 million people developed TB and 1.5 million died from the disease in 2014 [2.3].Tuberculosis is a leading killer of people living with HIV resulting in a third of all HIV-related deaths globally [1].People with HIV are 19 times more likely to develop active TB disease than people without [1].This is because the combination of HIV and TB is deadly, with each speeding the others progression. In 2018 approximately 251 000 people died of HIV associated TB and 862 000 new cases of TB among HIV positive people were recorded, with 72% of these living in Africa. In 2015 TB was ranked alongside HIV as a leading cause of death [1,2,3]. It is estimated that worldwide about 10 million people developed TB in 2017. The majority of these were men (5.8 million) followed by women [3.2] and the remaining 1 million were children. Africa had the largest burden of TB with 281 cases per 100 000 population compared with a global average of 133 cases per 100 000 population [1].
In Zimbabwe TB is among the top 10 diseases of public health importance and is a leading cause of death among adults. The country had an estimated TB incident rate of 278 per 100 000 population in 2015 [3]. The treatment success rate of 80% in 2015 (2), is still below the global target of 87%. Main challenges faced by the country in TB control are the emergence of drug resistant TB (DR), high TB death rates, high defaulter rates and non-evaluation of treatment outcomes for TB patients [5,6].
Several treatment adherence interventions for TB exist to support patients. These include the provision of education and counselling on the disease and treatment ; offering a package of treatment adherence intervention for patients on TB treatment in conjunction with the selection of a suitable treatment administration option; material support to patients (for example food, transport, living allowance, housing or nancial bonus); psychological support to patients (for example counselling sessions or peer-group support); communication with patients (for example home visit, SMS or phone call); digital medication monitor (a device to measure time between openings of the pill box and/or send SMS or audio reminders) ; staff education (e.g. education, chart or visual reminder, educational tool and desktop aid for decisionmaking and reminder). In addition, effective treatment options for each patient may be offered and these include community or home-based treatment, over facility-based treatment or unsupervised treatment; treatment administered by trained lay providers or health-care workers and the use of digital health technology such as SMS or phone calls, medication monitors, and video observed treatment -as a replacement for in-person directly observed treatment -when conditions of technology and operation allow [7].
The World Health Organisation has noted that the potential of information and communication technologies (ICTs) to ght TB remains largely untapped. Many countries are still researching further on how to use eHealth and mHealth effectively in the ght against TB. A lot of work still needs to be done to maximise the impact of these methods for monitoring treatment in people with TB [8].
The use of mobile phones has increased worldwide over the past decade and this has created opportunities to use mobile phones as intervention tools in health care including in promoting prevention, treatment and adherence monitoring and evaluation [9,10]. The effectiveness of such client centred applications needs to be known as it will improve client care. A systematic review of the effectiveness of such patient centred applications in TB Care is important to inform future programming for the national TB programme, bringing the focus on interventions that really in uence improving TB outcomes. This will result in the effective use of resources by channelling them where there is the greatest impact in terms of reducing morbidity and mortality due to TB in Zimbabwe.
The research question seeks to explore the mobile based applications that are being used in TB care globally and the implications of their use. The systematic review aims to summarize the literature on mobile based applications used in TB care globally, with speci c objectives to: Determine the types, the scope, the target users and the effectiveness of the mobile TB applications in TB Care globally.

Methods
The new Cochrane guidelines for systematic reviews of Interventions will be followed [12].
A comprehensive online search will be conducted to identify potentially eligible studies. Studies not found in the online domain will not be included. The eligibility criteria for the review will include:

Search Strategy and Screening
The search will be performed by 2 reviewers, the rst author and another doctoral student who will have co-authorship of the paper. A wide range of medical subject heading (MeSH) terms will be used in various combinations and these include: 'mobile based applications', 'mobile apps', 'digital apps', 'Tuberculosis Care', 'TB Care' and 'Tuberculosis'. The rst-stage screening of titles and abstracts will identify potentially eligible studies for original research in which the title and abstract suggest the use of mobile based TB applications to eliminate articles not within the scope of the systematic review. Reasons for excluding potentially eligible studies will be listed. The second stage screening will entail review of full texts if selected studies using pre speci ed eligibility criteria. Reference lists of full text studies assessed for inclusion will be used to identify more studies. If the two reviewers disagree, discussion and consensus will be employed to reconcile the differences. A Preferred reporting items for systematic reviews and meta analyses (Prisma) ow diagram will be developed at the beginning of the data search.

Data Extraction, Management and Synthesis
References will be managed using Zotero or Endnote. The 2 reviewers will independently extract data using an electronic excel form designed by the rst author to collate information on selected variables.
Data variables are shown in Table 1. The rst author will enter the data and the second reviewer will check for errors. Discrepancies will be settled through discussion and consensus. All the data obtained via database searches will be taken as is, no follow-up will be done with authors. Narrative synthesis will be done in accordance with the Cochrane Handbook of Systematic Reviews for Interventions [11].

Assessment of Quality of Selected Studies
A standard quality appraisal checklist for randomised controlled trials and qualitative studies adapted from the Critical Appraisal Skills Programme (CASP) will be used to assess the overall quality of the selected studies [12]. Each study will be evaluated by looking at its: Methodological quality-the extent to which the design and conduct of the study are likely to have prevented systematic errors (bias) ; Precision-a measure of the likelihood of random errors ; External validity-the extent to which the results are generalisable or applicable to a particular target population .

Assessment of Risk of Bias in Selected Studies
The Cochrane Risk of Bias Assessment tool [13] will be used to assess the risk of bias in the selected studies as follows: Selection bias: evaluation of the random sequence generation (RCTs) and allocation concealment (RCTs) Performance bias: assessing the blinding of study participants and/or investigators (all studies) Detection/Outcome bias: Assessment of who was aware of the intervention Attrition bias: Assessment of availability of outcome data for all Outcome reporting bias: Assessment of the extent to which the data was reported based on the protocol (all studies) The studies will be scored as having high, low or unclear risk of bias.

Discussion
The results of the systematic review will provide crucial information to inform programming for the national TB programme, bringing the focus on interventions that really in uence improving TB outcomes. This will result in the effective use of resources by channelling them where there is the greatest impact in terms of reducing morbidity and mortality due to TB in Zimbabwe.