Table 3: Non-Cochrane reviews with some evidence of effectiveness of CAM treatments of infections.

Treatment and indicationMain conclusionsStudy characteristics

Respiratory tract infections (RTIs)

Andrographis paniculata for symptomatic relief of acute respiratory tract infections in adults and children [48]A. paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity.
Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. paniculata are warranted
33 RCTs with a total of 7.175 patients were included. Most trials evaluating A. paniculata (as a monotherapy and as a herbal mixture) provided commercially but seldom reported manufacturing or quality control details. A. paniculata improved cough (n = 596, standardised mean difference SMD: -0.39, 95% CI: -0.67 to -0.10) and sore throat (n = 314, SMD: -1.13, 95% CI: -1.37 to -0.89) when compared with placebo. A. paniculata (alone or plus usual care) has a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. paniculata (alone or plus usual care) shortened the duration of cough, sore throat, and sick leave/time to resolution when compared with usual care. The methodological quality of included trials was overall poor.

Pelargonium sidoides preparation (EPS 7630) for acute bronchitis, acute rhinosinusitis and acute tonsillopharyngitis [49]Superiority of EPS 7630 to placebo in reducing both symptom severity and time until complete recovery for all indications investigated13 trials with a total of 3.392 participants were included, 10 of which could be entered into meta-analyses of efficacy (AB: 6/8 trials; ARS: 2/2 trials; ATP: 2/3 trials). In ARS, all trials included adults only, whereas studies in ATP had been conducted with children only.
EPS 7630 was superior to placebo in reducing
both symptom severity and time until complete recovery for all indications investigated.
Significant advantages for the herbal drug were also observed for time until the onset of a meaningful treatment effect, global therapy outcome, and days off work, school, or kindergarten.
In AB, efficacy could also be shown for both subsets defined by age.

Pelargonium sidoides for acute rhinosinusitis [50]Positive evidenceSeven trials on P. sidoides (EPs 7630, Umckaloabo®), Myrtol (GeloMyrtol® forte), BNO 1016 (Sinupret® extract), BNO 101
(Sinupret®), Cyclamen europaeum (Nasodren®), and Esberitox® were included.
Risk of bias was heterogeneous.
EPs 7630 appeared to be useful in the treatment of ARS. Myrtol showed benefits against a placebo compound, and BNO 1016 and BNO 101 might be helpful; however, there was little evidence for the effectiveness of Cyclamen europaeum and Esberitox® (p-values not presented).

Echinacea and Pelargonium sidoides for treatment of RTIs in children [51]
Because of conflicting evidence in the included studies, no concrete conclusion on effects of Echinacea could be drawn so far. In the case of P. sidoides, there is moderate evidence for efficacy and safety in the treatment of RTIs in childrenEleven trials with 2.181 participants were included. No clear evidence for Echinacea (4 trials) or an herbal compound preparation (1 trial) in preventing RTI symptoms was found. Meta-analysis revealed evidence for efficacy (responder rates: RR: 2.56; 95% CI: 1.54 – 4.26; p < .01) and safety (patients with adverse events: RR: 1.06, 95% CI: 0.42 – 2.66; p = .9) of P. sidoides in treating RTI symptoms compared with placebo (6 trials).

Probiotics for prevention of upper respiratory tract infections (URTIs) in children [52]Probiotics decrease the incidence of URTIs23 trials with a total of 6.269 children (age: 0 -18).
None of the trials showed a high risk of bias. The quality of the evidence of outcomes was moderate.
Probiotic consumption significantly decreased the number of subjects having at least 1 RTI episode (17 RCTs, 4.513 children, RR: 0.89, 95% CI: 0.82–0.96, p=0.004). Children supplemented with probiotics had fewer numbers of days of RTIs per person compared with children who had taken a placebo (6 RCTs, 2.067 children, MD: −0.16, 95% CI: −0.29 to 0.02, p=0.03) and had fewer numbers of absence days from day care/school (8 RCTs, 1.499 children, MD: −0.94, 95% CI: −1.72 to −0.15, p=0.02). However, there was no statistically significant difference of illness episode duration between probiotic intervention group and placebo group (9 RCTs, 2.817 children, MD: −0.60, 95% CI: −1.49 to 0.30, p=0.19).

Probiotics for prevention of URTIs in immunocompetent children [53]Modest effect both in diminishing the incidence of URTIs and the severity of the infection symptoms14 RCTs applied to a pediatric population with high-quality methodology.
At least one beneficial effect of prophylactic probiotic was observed in the majority of RCTs.
The long-term administration of probiotics appeared to have a good safety profile in childhood and none of the studies reported any serious adverse events related to the probiotic strain.
Probiotics in immunocompetent children have a modest effect in diminishing both the incidence of URTIs (number of subjects having at least 1 respiratory symptom episode (RR: 0.89, 95% CI: 0.82 – 0.96, p = 0.004); children supplemented with probiotics had fewer number of days of RTIs per person compared with children who had taken a placebo (weighted MD: 0.16, 95% CI: 0.29-0.02, p = 0.03)) and the severity of the infection symptoms.

Sanren Decoction (made of almonds,
Amomum cardamomum, barley, talc, tetrapanax papyrifera, folia bambosae, Magnolia officinalis, Pinellia ternate) for URTIs [54]
Higher cure rate and effectiveness rate than control group
High quality evidence is required
Seven studies with 571 URTI patients.
The cure rate (OR = 3.51, 95% CI: 2.19-5.15, p < 0.001) and effectiveness rate (OR = 3.91, 95% CI: 2.58-5.90, p < 0.001) of Sanren Decoction’s treatment on URTI were significantly higher than those of control group.

Shuanghuanglian injection for URTIs [55]Better effect than common antibiotics on helping relieve some symptoms and decrease the course of acute upper respiratory tract infections
High quality evidence is required
Eight trials with 857 participants.
SHL injection showed significant effect on reducing the time to resolution of fever (3 trials, 297 patients; MD: 0.82 day, 95% CI: 0.6-1.04, p < 0.00001) and the resolution time of cough (2 trials, 209 patients; MD: 0.9 day, 95% CI: 0.58-1.23, p < 0.00001), when compared with ribavirin and/or lincomycin.
SHL injections had significant effect on reducing the resolution time of sore throat (1 trial, 79 patients; MD: 1.39 day, 95% CI: 0.88-1.9) and nasal congestion and discharge (1 trial, 130 patients; MD: 0.74 day, 95% CI: 0.11-1.37) (p-values not presented).

Homeopathy for URTIs [56, 57]Positive results29 studies of different designs (17 RCTs) with 5.062 patients on the domain ‘Upper Respiratory Tract Infection/Allergy’ (URTI/A) showed an overall positive result in favour of homeopathy. 6 out of 7 of the controlled studies demonstrated at least equivalence with conventional medical interventions and 8 out of 16 placebo controlled studies significance in favour of homeopathy. This positive trend was maintained in the evaluation of subgroups.

Individualized homeopathy for children with URTI, tonsillitis and acute sinusitis [58]Homeopathy is a more or at least not inferior cost-effective method than placebo or conventional and antibiotic treatmentsSix clinical trials (N= not presented).
A significant difference in the median total symptom score in patients receiving homeopathy compared to the recipients of placebo in control groups (p = 0.026). Homeopathic strategies yielded significantly better results compared to antibiotic strategies in terms of medical efficacy (p ≤ 0.001).

Herbal medicine for cough [59]Strong evidence for Andrographis paniculata and ivy/primrose/thyme-based preparations
Moderate evidence for Pelargonium sidoides
34 RCTs (N = 7.083) on P. sidoides (11 RCTs), Echinacea (8 RCTs), A. paniculata (6 RCTs), ivy/primrose/thyme (4 RCTs), essential oils (4 RCTs) and bakumondoto (1 RCT) were included. Controls were mainly placebo. Most studies had a low risk of bias. The meta-analysis revealed strong evidence for A. paniculata (SMD = -1.00, 95% CI: -1.85 to -0.15; p < 0.001) and ivy/primrose/thyme (RR = 1.40, 95% CI: 1.23-1.60; p < 0.001) in treating cough; moderate evidence for P. sidoides (RR = 4.60; 95% CI: 2.89-7.31; p < 0.001), and limited evidence for Echinacea (SMD = -0.68; 95% CI: -1.32 to -0.04; p = 0.04).

Chinese herbal medicine for postinfectious cough [60]Improvement of core symptoms of postinfectious cough
Enhancement of quality of life
12 RCTs with moderate-to-high levels of evidence. Methodological quality was considered high in three trials, while in the other nine studies the unclear risk of bias was in the majority. Findings suggested that, compared with western conventional medicine or placebo, Chinese herbal medicine could effectively improve core symptoms of postinfectious cough, act better and have earlier antitussive effect, and enhance patients’ quality of life. No serious adverse event was reported.

Chinese medicine for respiratory diseases [61]Chinese medicine was more effective than anti-viral medicineSix economic evaluations and cost studies were included, of which 4 studies’ quality was low, 1 was high and 1 was medium. All studies adequately documented effectiveness of interventions. However, the costs of interventions were not well reported in 2 studies. 2 studies inadequately conducted sensitivity analysis and discounting. The diseases of 6 studies included bronchitis (2 studies), upper respiratory tract infection, herpangina, hand-foot-and-mouth disease and viral pneumonia. The studies results showed that cost-effectiveness of Xiyanping injection is poorer than Tanreqing injection and has more adverse reaction in 2 studies, and it is poorer than Yanhuning injection, but with less adverse reaction in 2 studies. Xiyanping injection is better than anti-viral medicine in 2 studies. 1 study indicated that Xiyanping is more cost-effective by atomized than intravenous drip.

Urinary tract infections (UTIs)

Cranberry for UTIs [62]Evidence supporting clinical efficacy of cranberry product UTI prophylaxis exists in the following populations: women with rUTI, women with rUTI over 49 years old, children, rUTI, post-gynecological surgery patients, patients carrying a double-J ureteral stent, high-UTI-risk long-term care facility (LTCF) patients, prostatic adenocarcinoma patients treated with radiotherapy, and renal transplant patients with rUTI.
An absence of clinical efficacy for cranberry product UTI prophylaxis exists in populations of women with rUTI (other studies), elderly males and females, neuropathic bladder/spinal injury patients, pregnant women, children (other studies), radiotherapy patients, low-UTI-risk LTCF patients, and MS patients with neurogenic bladder.
22 relevant articles: three SRs, two SRs with MAs, eight RCTs, five NRSs, and four guidelines with relevant recommendations.

Antibiotic-associated diarrhoea

Probiotics for antibiotic-associated diarrhoea (AAD) [63]Reduction of AADA total of 82 RCTs met inclusion criteria. The majority used Lactobacillus-based interventions alone or in combination with other genera; strains were poorly documented. The pooled relative risk in a DerSimonian-Laird random-effects meta-analysis of 63 RCTs, which included 11.811 participants, indicated a statistically significant association of probiotic administration with reduction in AAD (relative risk: 0.58; 95% CI: 0.50-0.68; p < .001; I(2), 54%; [risk difference: -0.07; 95% CI, -0.10 to -0.05], [number needed to treat: 13; 95% CI: 10.3-19.1]) in trials reporting on the number of patients with AAD. This result was relatively insensitive to numerous subgroup analyses. However, there exists significant heterogeneity in pooled results and the evidence is insufficient to determine whether this association varies systematically by population, antibiotic characteristic, or probiotic preparation.

Probiotics for prevention of AAD [64]Preventive effects on AAD in adults (18–64 years) but not the elderly (> 65 years)30 RCTs met the predefined inclusion criteria and were included in the meta-analysis.
There was considerable heterogeneity among the trials (p < .001); thus, subgroup analyses were performed. The meta-analysis resulted in a pooled relative risk (RR) of AAD of 0.69 (95% CI: 0.62-0.76) in a fixed effects model and 0.58 (95% CI: 0.48-0.71) in a random effects model, as compared with placebo. The positive association between intake of probiotic and reduced risk of AAD was observed in adults (RR: 0.47; 95% CI: 0.4-0.56). In contrast, in elderly patients, there was no positive effect (RR: 0.94; 95% CI: 0.76-1.15) of probiotic use and AAD.