Title- Combination drug therapy for prevention and treatment of

•Recommendations:
• From the above research it is clear that the impact of the tuberculosis as a disease is extremely
high on the paediatric populations. Similarly, there is acute need for better treatment modalities,
especially for drug susceptible to multidrug resistant strains of the disease (Cruz and Starke
2014). The above research had been successful in identification of the combination drug therapy
to be extremely effective for treatment and symptom control along with prevention of
tuberculosis in latent infection stage of the children. The two drugs that have been the focus of
the research studies investigating the impact of combination drug therapy include rifapentine
and isozianid. There are a few recommendations on integrating the use of both rifapentine and
isozianid as a combination therapy in the treatment modalities for children.
• First and foremost, the combination therapy is the best effective in the latent infection stage, as
the pathogen has not yet spread enough inside the body if the host and is much easier to be
controlled by the combination therapy of both the drugs. Hence, the first recommendations is to
carry out better assessment of the latent stage infection among the target children group and
implement the medication therapy immediately to control the infection in the latent stage itself.
• Secondly, Pease et al. (2017) had stated that shorter or three-month regimen of the combination
drug therapy had been far more effective for preventing the onset of the disease and offer better
symptomatic control for the spread. Hence, it is recommended for the combination therapy to be
inoculated in a three month or similar regimen to ensure better, safer, and faster results.
• Thirdly, as discussed by Borisov et al. (2018) has stated that long term treatment of combination
therapy using both rifapentine and isoniazid can result in subtherapeutic concentrations of
antiretroviral drugs. The authors compared the benefit of using efavirenz as another conjuncture
medicine to counteract this effect. The data findings suggest four weeks of daily rifapentine plus
isoniazid can be co-administered with efavirenz without clinically meaningful reductions in
efavirenz mid-dosing concentrations or virologic suppression. Hence, for HIV positive or
immune-compromised children with risk of tuberculosis, the additional administration of
efavirenz is effective.
• The empirical evidence base is minimal and there is need for more research to identify the
exact mode of combination therapy and exact dosages that are going to be optimal for
controlling the infection beforehand. There is also need for better staff education on how to
recognize and control the manifestation of the disease in the latent stage itself. Educational
Background
 The topic of this research poster is the instance of tuberculosis (TB) among the children. The statistical data suggests that, an estimated number of 1
million children under the age group of 15 years have been reported to be suffering with tuberculosis. It has to be acknowledged that the total count of
people dying from tuberculosis has escalated to 239,000 people per year (Who.int, 2019). Furthermore, the statistics also suggests that 70-80% of the
children that have been reported to be suffering from tuberculosis have pulmonary tuberculosis. Along with that, for high burden Tuberculosis settings,
at least 15-20% of the total burden of TB is found in children. The rate of children developing multidrug resistant tuberculosis is also very high with
more than 30000 children falling sick every year with various strains of multidrug- resistant TB. Hence, undoubtedly tuberculosis is a grave issue in the
paediatric health care setting and the need for more advanced integrated therapies and treatment modalities for better and more effective management of
TB in children (Teo et al. 2015).
 Combination drug therapy is a more or less novel addition to the pharmacological treatment for serious diseases. There is mounting evidence that
suggests that for drug susceptible tuberculosis, the regular and conventional treatment modalities are not effective any longer. Hence, the need for
combination drug therapy for the diseases such as the tuberculosis has been reported to be very effective for the children, especially for the risk of drug
resistant tuberculosis (Majdoub et al. 2016). One of the greatest contributing factors leading to high rate of tuberculosis among the children is the latent
infection, for which the combination drug therapy has been found to be very effective to limit the probability of the children developing the disease.
Hence, the topic of this research poster is chosen as combination drug therapy for treating tuberculosis in children using two very potent medication for
tuberculosis, rifampicin and isoniazid.
Relevant Key Messages from your research
• The latent infection stage of the tuberculosis is the best period for treatment management with combination drug therapy.
• Tuberculosis can be defined as the ongoing chronic infection which affects the children that is caused by the different pathogenic
strains of Mycobacterium, which generally affects the lungs of the patient but often the kidneys, spine or brain can also be affected. There are
three stages to the development of tuberculosis, the exposure stage, which is when the child has been in first contact with any infected
person. The next stage is the latent infection, where the child begins to carry the pathogen in the body however there is no onset of
symptoms. The third and final stage of the development of the disease is the development of the clinical manifestation of the infection with
the onset and establishment of the symptoms of the disease. As discussed by Fox et al. (2017), the latent stage of tuberculosis is
asymptomatic due to the acclimatization of the pathogen in the body, as a result the stage is very easy for the treatment to affect and limit the
spread of infection before it can manifest successfully in the body of the host. Prevention of TB remains of component of a comprehensive
control strategy for controlling the spread of the disease and the combination therapy of multiple drugs can be extremely helpful for
controlling the spread of the infection.
• Single drug therapies are not as effective against drug susceptible tuberculosis in children.
• The concept of multidrug resistant tuberculosis is that the pathogen develops a significant resistance to the common antibiotic strains that are
regularly used for the treatment of tuberculosis and is not affected by the regular medication anymore. As discussed by the Villarino et al.
(2015), the impact of fixed dose tuberculosis drug treatment with only a singular TB drug fails to have a statistically significant impact on
managing the symptoms. However, similarly the impact of combination drug therapy is associated with better control of the diseases and
better symptomatic management. As a result the impact of fixed dose treatment of therapeutic drugs with more than one drugs used have
been reported to have better effects on treatment and management of the disease among the children. Triasih et al. (2016) has been successful
in describing the fact that fixed dose combination of drugs as compared to single drug formulations are associated with treating pulmonary
tuberculosis in the latent stage as well as in early onset of the disease. Hence, it can be easily stated that the impact of combination drug
therapies with more than one systemic antimicrobial products in the treatment and management of tuberculosis has been reported to be very
effective and for better prevention and management of tuberculosis in the children is a novel technique.
• The combination therapy with rifapentine and isoniazid as two systemic drugs as the treatment of tuberculosis and prevention of the
manifestation of the disease.
• Villarino et al. (2015) has suggested that the combination drug therapy using Rifapentine and Isoniazid for tuberculosis treatment has been
reported to be extremely effective for the children with onset of tuberculosis. This randomized controlled trial has explained the usage of a 3
month 12 dose regimen of a combination of rifapentine and isoniazid drug therapy and the safety and efficacy of the non-inferiority treatment
effectiveness has been very effective as compared to 9 month treatment of just isoniazid for latent TB infection among the children. The
combination drug therapy effects was far safer and had better completion rate than the single drug treatment effect, and treatment with the
combination of rifapentine and isoniazid was more effective for prevention of tuberculosis in children aged 2 to 17 years as well. Borisov et
al. (2018) identified latent tuberculosis infection treatment as a critical element to control and eliminate the disease among the children. In
this systematic review and meta-analysis study, the combination of rifapentine and isoniazid drug regimen have been updated for large scale
use among the paediatric tuberculosis patient group. Sterling et al. (2016) has mentioned that the three month weekly administration of
rifapentine and isozianid has been very effective in treating the tuberculosis infection in even HIV co-infected patients. It is needed to be
highlighted here that the rate of tuberculosis infection is also extremely high among the HIV positive children, and due to the immune-
compromised state of the students, treating or controlling the infection becomes extremely difficult for them. Hence, this combination of
rifapentine and isoniazid has been found to be effective to treat and perform symptomatic control of tuberculosis for HIV positive children as
well. Hence, undoubtedly this combination therapy can have many potential benefits associated with it and there is need for large scale
implementation of this therapeutic treatment for the target patient group.
•
Discuss implementation of your results to improve clinical practice,
and/or education:
• Discussing the implementation of this treatment recommendation in the clinical setting, the
initial challenges in wide acceptance of this as a better alternative to isoniazid preventative
therapy or similar conventional single drug treatment modalities will be difficult. As
discussed by Fox et al. (2017), latent stage is the most susceptible stage of the disease
progression of TB, and combination therapy with potent drugs can be extremely helpful.
The exploration of the literature has indicated at the undeniable benefits of using this
particular treatment regime for children, which will not only provide better symptomatic
control, but will also be extremely effective in nipping the issue in the bud, the latent
infection stage. Hence, with active advocacy and consistent efforts can help in large scale
implementation of the regimen into clinical practice. Similarly, voluntary pilot projects on
the effectiveness of the medication regimen carried out on smaller scales can be of extreme
help to gather the confidence of the public and authorities on the benefits of this technique.
• Similarly, it also needs to be discussed that this treatment modality is more cost effective
along with being highly effective. The article by Villarino et al. (2015) and Triasih et al.
(2016) has stated that single drug therapy with a fixed dose regimen is ineffective in
controlling the disease. Elaborating further, Johnson et al. (2018) stated that in high burden
settings, the implementation of the combination drug therapy including rifapentine with
isoniazid is considerably higher as compared to isoniazid preventive therapy. As the high
burden setting of tuberculosis represents higher rate of paediatric tuberculosis as well, the
implementation of the recommended combination therapy can also be cost effective
providing additional safety in lesser costs.
• As discussed by Villarino et al. (2015), the combination therapy using both Rifapentine and
Isoniazid in a 3-month twelve regimen can help paediatric patients evade manifestation of
the disease radically. In support, Sterling et al. (2016) has also confirmed that a 3-month
weekly administration of the medication can help stop the spread of the infection in the
latent stage in even HIV co-infected patients. Hence, clinical implementation must take
insight from the reviewed evidence in terms of both dosage and time period of
administration.
• Hence, there are both positive and negative implications of the implementation of the
recommended treatment regimen using both rifapentine and isoniazid, however as evident
from previously published literature here, the benefits of the regimen outweighs the
possible negative implications. Although, there is need for better empirical investigation
and research on how to adequately and systematically integrate this treatment regimen in
clinical practice and how to optimize the benefits for the target group.
•
Title- Combination drug therapy for prevention and treatment of
Tuberculosis in children aged 5-15 against single drug therapy
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