key: cord-0077155-fham67ww
authors: Li, Haiyan; Zhang, Chao
title: Research Progress and Analysis of Moxibustion in Prevention and Treatment of Acute Infectious Diseases
date: 2020-09-22
journal: nan
DOI: 10.4103/cmac.cmac_28_20
sha: e529cb162202938256fdc7e2bd57a5becf9b1c65
doc_id: 77155
cord_uid: fham67ww

To introduce and evaluate current research progress of moxibustion in the prevention and treatment of acute infectious diseases, related literature in CNKI, Wanfang Data, and SinoMed was retrieved and analyzed by the present study. Results showed abundant studies on the mechanism of action of moxibustion in the prevention and treatment of acute infectious diseases with remarkable clinical efficacy. The present study also summarizes the commonly-occurring problems and found out the deficiencies in existing studies in hope of providing more reference for further research.

experiment on moxibustion for the prevention and treatment of acute infectious diseases; (3) clinical observation of moxibustion in the prevention and treatment of acute infectious diseases; and (4) studies on the mechanism of action of moxibustion in the prevention and treatment of acute infectious diseases.

(1) Literature review; (2) studies with unspecified diagnosis of disease; (3) studies that used acupuncture combined with moxibustion and had only pre-and post-treatment comparison and no intergroup comparison; and (4) moxibustion studies that used sulfur or medicated threads instead of moxa.

The above databases were searched for and full-text literature that met the inclusion criteria was read, and 25 eligible papers were obtained after screening by the exclusion criteria. Study subjects and methods are shown in Table 1 . One of the papers involved two kinds of studies, namely case studies and clinical case series observation. [2] Twelve diseases were identified, with EHF occurring frequently.

In terms of study subjects, there were a total of 9 papers about the mechanism of action of moxibustion in intervention of acute infectious diseases that included EHF, leptospirosis, dysentery and influenza virus pneumonia, and all of the studies were animal randomized controlled trials. After full-text reading, the authors analyzed and summarized the pathways at different levels in the mechanism of action of moxibustion in the prevention and treatment of acute infectious diseases.

In an experimental study by Song Xiaoge on moxibustion in the treatment of rats with EHF, [3] the activity of erythrocyte C3b receptor rosette (E-C3bRR) was investigated. 33 Wister rats were used in the study. The number of yeast rosettes in 200 erythrocytes observed under a microscope was counted experimentally, converted to percentages and used as indicator of the erythrocyte C 3 b receptor activity. Virus inoculation and treatment were not performed for rats in the blank group, and EHF virus was inoculated in both the infection group and the treatment group. Moxibustion was not given in the infection group. Animals in the treatment group were treated as follows: At day 2 after EHF virus inoculation, moxibustion was performed at the kidney acupoint area for 30 min, once daily for 7 days. At 14 days after inoculation of EHF virus, the E-C3bRR rate was calculated as shown above.

The E-C3bRR rate (`X ± standard deviation [SD]) was 4.23 nda. 07, 6.55 nda. 76 and 9.13 nda. 67 in the normal (blank) group, infection (control) group and treatment (moxibustion) group, respectively. It was higher in the infection group than in the normal group (P < 0.05) and was higher in the treatment group than in the infection group (P < 0.02), indicating that the activity of E-C3bRR was increased in the rats infected with EHF virus compared to that in the healthy rats, and moxibustion was effective in enhancing the activity of E-C3bRR.

In a study of the same type by the same authors, [4] percentage of peritoneal macrophage (PM) phagocytosis was used as another indicator. Twenty-two rats were used in the study. With exactly the same experimental design with the previous study, 120-160 macrophages were obtained experimentally and counted under a microscope at 14 days after viral inoculation, and the percentage of PM phagocytosis was calculated.

The percentage of PM phagocytosis (`X ± SD) was 27.63 goc. 78, 19.00 goc. 20 and 29.8 dgo. 20 in the normal (blank) group, infection (control) group and treatment (moxibustion) group, respectively. It was higher in the treatment group than in the infection group (P < 0.05), indicating that moxibustion could significantly enhance the phagocytic function of PMs in rats infected with EHF virus.

The E-C3bRR rate was one of the indicators reflecting erythrocyte immune function, and PMs themselves participated in cell immunity. Moxibustion improved the activity of E-C3bRR and the phagocytic function of PMs, suggesting its potential in boosting immunity of the body.

There was a total of 4 papers on this subject and all studies were animal randomized controlled trials that used EHF virus as the challenge virus. Immunofluorescence assay and radioimmunoassay were performed. There were a normal (blank) group, an infection (control) group and a treatment (moxibustion) group in the trials, with 10 rats in each group. Except for the number of animals and the indicators, the study design was the same with the previous studies. Comparison of indicators in the three groups was described below with the following data.

In a study with norepinephrine (NE) and dopamine (DA) as indicators (`X ± s, ng/ml), [5] Animal randomized controlled trial infection group; and 194.74 ± 56.12 and 816.50 ± 56o. 91 respectively in the treatment group. The levels of NE and DA were significantly higher in the infection group than in the normal group (P NE < 0.01, P DA < 0.001) and they were significantly lower in the treatment group than in the infection group (P NE < 0.05, P DA < 0.001), with no significant difference between treatment and normal groups (P > 0.05). The above data indicated that the levels of NE and DA increased in rats infected with EHF virus, and moxibustion reduced the levels, hence able to promote the levels of NE and DA to return to normal.

In a study with 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) used as indicators, [6] the data also suggested that the levels of 5-HT and 5-HIAA were significantly higher in the infection group than in the normal group (P 5-HT < 0.05, P 5-HIAA < 0.001), and the levels were significantly lower in the treatment group than in the infection group (P 5-HT < 0.001, P 5-HIAA < 0.05). The level of 5-HT was not significantly different (P 5-HT > 0.05) and the level of 5-HIAA was significantly different (P 5-HIAA < 0.05) between treatment and normal groups. In addition, it was shown in a related study [7] that the level of 5-HT had the same pattern of changes in lung and kidney tissues as in the above plasma samples. These data indicated that the level of 5-HT in plasma increased in rats infected with EHF virus, and moxibustion reduced the level, hence able to promote the level of 5-HT in plasma and lung and kidney tissues to return to normal.

The same pattern of changes was revealed in studies using the metabolite (TXB 2 ) of thromboxane (TXA 2 ), the metabolite (6-K-PGF 1 ) of prostacyclin (PGI 2 ), and the TXB 2 /6-K-PGF 1 ratio as indicators as in the above studies.

Studies under this category were performed by Tang Zhaoliang et al. In these studies, the roles of the two catecholamine adrenergic neurotransmitters -NE and DA, the two monoamine neurotransmitters -5-HT and 5-HIAA, and the two prostaglandins -TXB 2 and 6-K-PGF 1 in the body were described in detail. Results of the studies suggested that in the treatment of experimental animals with EHF, moxibustion had the effects of correcting fluid disorders and stabilizing the inner environment of the body, but there were few descriptions of the correlation between moxibustion and the disease course of EHF. Whether this mechanism of action can be supported in the treatment of other acute infectious diseases is to be further investigated.

There was a total of 3 papers on antiviral effects of moxibustion in the treatment of acute infectious diseases. The diseases in question were influenza, leptospirosis, and bacillary dysentery, and the studies were animal randomized experimental studies.

In one of the studies, [8] there were four groups, namely acupuncture group, treatment group, infection (control) group and blank control group. Potency of serum interferon in mice was used as the indicator and microdose cytopathogenic effect inhibition assay [9] was carried out to determine serum interferon in mice. Animals in the moxibustion group were treated as follows: The Guanyuan point was selected for direct moxibustion with a 10-15 mg moxa cone, 4 cones at a time, once daily for 3 days. At day 3, mice were anesthetized lightly with ether after moxibustion, and under this condition, the nasal cavity of mice was attacked with influenza virus PR 8 . Then, mice were treated with moxibustion for 3 times using the same method as above. Blood was collected from the mice after 48 h for the detection of serum interferon. It is worth mentioning that in the studies on mechanism of action that were included in this review, the experimental method in this study was one of the few methods in which moxibustion was carried out before viral inoculation for animals, and its results were significant for explaining the mechanism of action of moxibustion in the prevention of infection with influenza virus.

Based on experimental results, the potency of interferon (`X ± SD) was 4.22 erf. 23, 2.63 erf. 22 and 2.93 erf. 19 in the moxibustion, infection and blank control groups, respectively. It was lower in the infection group than in the blank control group (P < 0.05), and was significantly higher in the moxibustion group than in the infection group (P < 0.001), indicating that moxibustion increased the potency of interferon in mice.

It is well-known that as a cytokine, serum interferon has broad-spectrum antiviral activity. [10] Inducing production of interferons is an important approach of moxibustion to exert its antiviral effects. In this paper, the phagocytic function of PMs in mice was also investigated experimentally, and a possibility was proposed that interferons activated macrophages to improve immune function, thus it can be reasonably inferred that further investigation of the correlation between the antiviral effects of moxibustion in the prevention and treatment of acute infectious diseases and the mechanism of immune response is another approach to studying the mechanism of action of moxibustion. In mechanism studies on moxibustion exerting antiviral effects in intervention in other infectious diseases, there were also studies with other indicators demonstrating the antiviral mechanism of moxibustion, including studies on indicators of antibody titer [11] and on endotoxins. [12] Although further mechanism studies were not as definite as studies on interferons, they affirmed the antiviral effects of moxibustion in the prevention and treatment of acute infectious diseases.

In terms of study subjects, there were a total of 15 papers on efficacy evaluation of moxibustion in the prevention and treatment of acute infectious diseases and the study designs were clinical randomized controlled trial, clinical case study, clinical case series observation, and animal randomized controlled trial. Eleven diseases were involved, including EHF, [13] viral hepatitis, [14] hand-foot-and-mouth disease, [15] malaria, [16] rubella, [17] hepatic echinococcosis, [2] COVID-19, [18] severe acute respiratory syndrome (SARS), amoebic dysentery, epidemic parotitis, [19] and leptospirosis. [20] It can be seen that moxibustion had a broad spectrum of disease in the prevention and treatment of acute infectious diseases.

In clinical observations included in the review, the total effective rate of moxibustion was 88.07% in the treatment of diseases. The effects mainly included improving symptoms and shortening the course of disease (Take a study on moxibustion in the treatment of 6 patients with acute amoebic dysentery as an example), [21] as well as reducing sequelae (Take a study on moxibustion in the treatment of SARS as an example. In this study by Zhao Hong, moxibustion was used to treat 9 SARS patients in recovery, and it was shown that moxibustion significantly improved sequelae of SARS, including low fever, chest tightness, fatigue, head and body aches, chest and abdominal distension pain, anorexia, constipation). [22] In treatment of diseases, functions of the respiratory, digestive and urinary systems were improved, especially those of the digestive system, accounting for 66.67% [ Table 2 ].

According to preliminary classification of literature, there were only 6 clinical randomized controlled trials, accounting for 42.86% in clinical studies. In nonrandomized controlled studies, there were narrative reports of small-scale case series and case studies, and one of the papers were about two types of studies, namely case series observation and case study. Diseases involved are shown in Table 3 . The study design was assessed considering several elements by further analyzing the literature.

of the clinical trials included in the review, only 42.86% of the trials had definite criteria of disease diagnosis and efficacy indicator judgment, among which the trials on COVID-19 accounted for 50%. In most of the trials, there were shortcomings as follows: lack of diagnostic criteria; lack of standardization in efficacy indicator judgment, i.e., using subjective indicators and not using current reference standards formulated in guidelines or by international conferences. Table 4 . There were mainly a moxibustion group, a Western medicine group, and a group of moxibustion combined with Western medicine. It can be seen from the study conclusions that apart from efficacy, the superiority of the combined therapy was demonstrated in the treatment of acute infectious diseases. However, in the studies with a Western medicine group, there was a common problem that there was various but no specifically described treatment with Western medicine.

Besides, in all of the designs of moxibustion, treatment based on syndrome differentiation was performed in only 2 of the studies, and there was a lack of explanation for acupoint selection, so it was difficult to make a further conclusion on TCM treatment.

In addition, there was also an animal randomized controlled trial that was one of the few studies included in the review in which moxibustion was carried out before attack of pathogens. The disease studied was leptospirosis and expression of the c-Fos gene in the medulla oblongata of guinea pigs infected with leptospira was used as an indicator to show the degree of injury in the animals (expression of the c-Fos gene indicates noxious stimulation in the central and peripheral nervous system).

OmpL39 antigen injection was performed in the trial except for moxibustion (The Zusanli and Guanyuan points were selected. The Zusanli point was used for grain-sized moxibustion, 3 moxa cones at a time, 0.5 mg per cone; and the Guanyuan point was used for suspended moxibustion for 5 min. Moxibustion was carried out once every other day). There were a group of moxibustion + OmpL39 antigen injection, an OmpL39 antigen injection group, a moxibustion group and a control group. The effect of different prevention methods Renal functions (oliguria, dysuria, and proteinuria) Epidemic hemorrhagic fever 3 (25.00) SARS: Severe acute respiratory syndrome was observed on visceral bleeding and c-Fos expression in guinea pigs attacked by viable leptospira. Results showed that visceral bleeding and c-Fos expression were reduced in the moxibustion group, the group of moxibustion + OmpL39 antigen injection and the OmpL39 antigen injection group compared to the control group (P < 0.05); they were reduced in the group of moxibustion + OmpL39 antigen injection and the OmpL39 antigen injection group compared to the moxibustion group (P < 0.05); expression of the c-Fos gene was significantly reduced in the group of moxibustion + OmpL39 antigen injection compared to the OmpL39 antigen injection group (P < 0.05). It was suggested that therapy with moxibustion alone was effective and moxibustion combined with antigen injection was more effective in reducing the noxious manifestations in the course of leptospirosis. However, since it was an animal trial that could not provide evidence for clinical efficacy, it could only support the therapeutic effect of moxibustion in the treatment of animals infected with leptospira and provide reference for further clinical study.

Although it was revealed that [23] infectious disease was not the high-frequency disease in the spectrum of disease intervened by moxibustion, it was found out in the studies included in this review that there was a wide scope of acute infectious diseases intervened by moxibustion, and moxibustion showed effect generally in the treatment of these diseases. According to this review, there were still shortcomings in the studies on moxibustion in the treatment of acute infectious diseases as follows: (1) There were few homogeneous studies evaluating the efficacy of moxibustion in treating certain disease, making it difficult to thoroughly evaluate the efficacy of moxibustion in the prevention and treatment of acute infectious diseases and to obtain evidence for evidence-based treatment of each disease. (2) There was almost no study on different diseases that elaborated the same mechanism of action, making it difficult to show universality of the epidemic prevention mechanism. There is currently no solution to the above two problems, thus apart from the approaches proposed in this paper, new methodology is needed concerning this subject for more objective and reliable data evaluation on existing studies.

Moreover, the studies on the diseases involved in this review were still isolated except those wide-scope and standard studies on EHF. Therefore, the authors believe that studies on other diseases may learn from the experience as follows. (1) After selection of a disease, the study protocol is designed based on an evaluation indicator with high disease relevance or commonly used in guidelines. (2) In performance of a mechanism study, efficacy indicators can also be used. For instance, in a study on the effect of moxibustion on 5-HT in lung tissue of rats infected with EHF virus, evaluation on pulmonary index can be included to explore the relevance between the therapeutic effect and the mechanism of action, so that the epidemic prevention mechanism of moxibustion can be more convincing. (3) In performance of related studies, correlation study can be performed on several indicators for which satisfactory effect has been obtained. For instance, evaluation indicators of relevance between different mechanisms can be added, or, further study can be carried out on current study results about the prevention mechanism of moxibustion for a certain disease (EHF), in hope of elaborating the relationship among and the focus in the antiviral mechanism, neurohumoral regulatory effect, and immunity-enhancing effect. After outbreak of the COVID-19, papers discussing the feasibility of using moxibustion to prevent and treat this disease proposed that the immunity-enhancing effect might be the basis of the antiviral effect of moxibustion. As is known to all, the nervous, endocrine, and immune systems have an impact on each other, but it can be seen from this review that there was no correlation study on such mechanism in specific infectious disease, warranting further investigation.

In addition, it is noticed that in previous studies, although various diseases were involved in clinical studies on moxibustion in the prevention and treatment of infectious diseases, high-quality studies with efficacy observation were few, thus, it is difficult to provide a reliable and systematic study basis for a persuasive result. The reasons lie in inadequate Moxibustion group and group of moxibustion combined with Western medicine Viral hepatitis 1 (7.14) EHF: Epidemic hemorrhagic fever emphasis on methodology and nonstandard study design that were common to these studies. Most studies included in this review were observations on symptom improvement and statistics about cure rate, and few of them included prevention observations, which indicates that clinical study on moxibustion in the prevention of acute infectious diseases is still a challenge.

Nil.

There are no conflicts of interest.

Translator: Shuna Zhang (张淑娜) reFerences

Protective effect of acupuncture and moxibustion on mice infected with influenza virus

Interferons and their clinical application Overview, definition and classification of interferons

Overview of animal interferon studies

Promotional effect of moxibustion on OmpL39 immune protection against leptospira

Effect of moxibustion on vanishing speed of phosphorus~(32) labelled dysentery endotoxins in rabbit blood

Observation on effect of moxibustion on renal function in EHF

Application and care of moxibustion in treatment of viral hepatitis

Analysis of therapeutic effect on hand-foot-mouth disease treated with pricking moxibustion combined with medicine

Efficacy observation of moxibustion in treatment of enuresis and malaria

Treatment of rubella with moxibustion

Moxibustion in adjuvant treatment of 7 cases of COVID-19

Moxibustion in treatment of 100 cases of epidemic parotitis

Effect of moxibustion on c-Fos expression in medulla oblongata of guinea pigs infected with leptospira

Moxibustion in treatment of 6 cases of acute amoebic dysentery

Clinical Observation of Moxibustion in Treatment of 9 SARS Patients in Recovery. Paper Presented at: National Symposium on the Prevention and Treatment of SARS with Chinese Medicine

Evidence-Based Medicine Review of Moxibustion in Intervening Alone a Spectrum of Disease and High-Frequency Diseases

Reflection on prevention and treatment of COVID-19 with moxibustion in ancient literature and modern research

Clinical experience in treatment of 23 cases of hepatic echinococcosis with moxibustion in Tibetan medicine

Effect of moxibustion on formation rate of erythrocyte C3b receptor rosette in rats infected with EHFV. Anhui Zhongyiyao Daxue Xuebao

Effect of moxibustion on immune and antiviral functions of rats infected with EHFV

Effect of moxibustion on plasma catecholamine in rats infected with EHFV. Anhui Zhongyiyao Daxue Xuebao

Effect of moxibustion on humoral factors in rats infected with EHFV

Effect of moxibustion on 5-HT in plasma and lung and kidney tissues in rats infected with EHFV. Anhui Zhongyiyao Daxue Xuebao