Siqueira CM, Homsani F, da Veiga VF, et al. Homeopathic medicines for prevention of influenza and acute respiratory tract infections in children: blind, randomized, placebo-controlled clinical trial. Homeopathy. 2016;105(1):71-77.
This parallel clinical trial was a randomized, triple-blind, placebo-controlled study. It was conducted between April 2009 and March 2010.
Study included 600 children (ages 1-5 years) from the Brazilian Public Health System in Petropolis (BPHSP), Rio de Janeiro. The inclusion criteria were: male or female patients with no apparent disease. Children who lived in geographical areas that were difficult to monitor and those with the following characteristics were excluded: history of wheezing and asthma, HIV infection, immunodeficiency, type I diabetes, malignancies, corticosteroid treatment, congenital anomalies, liver disease, history of at least 1 episode of respiratory infection in the previous 30 days.
Study Medication and Dosage
The children were randomized into 3 intervention groups with 200 patients in each group: homeopathic complex, placebo, and InfluBio.
The InfluBio solution was prepared by serially diluting a sample of purified influenza virus [A/Victoria/3/75 (H3N2)] in 1:10 ratio with sterile water to a 30x dilution according to the Brazilian Homeopathic Pharmacopea employing mechanical succession 100 times between each dilution.
The homeopathic complex used was composed of bacterial strains (Streptococcus and Staphylococcus) and inactivated influenza virus, prepared following the same homeopathic procedures of serial dilution and succession to a 30x dilution. This medicine is used routinely in Brazil for the prophylaxis and treatment of upper respiratory tract infections. The placebo consisted of 30% alcohol in a sterile water solution, which was the same composition used to dilute the homeopathic agents prepared in this study.
The child’s tutor administered the test solutions twice a day for 30 days.
During the study, neither the families nor the healthcare providers knew which solution was being given to each child.
The number of episodes of flu and acute respiratory infection during a 1-year period, as well as the duration of flu or acute respiratory infection, was tracked using a standardized questionnaire.
To characterize the number of flu and acute respiratory infection episodes, at least 2 of the following symptoms had to be present: fever (temperature > 37.8 deg. C), nasal discharge, prostration, myalgia, headache, and cough.
Of the 600 children selected, 445 (74.17%) children completed the study (149: homeopathic complex; 151: placebo; 145: InfluBio) and 155 (25.83%) children dropped out during the research period. Of the children who completed the entire study period, the mean age was 2.4 years without differences among groups.
Most of the children were classified as Caucasian or mixed-race living in the urban area. In the year before the study, most children had at least 1 episode of either flu or acute respiratory infection. In general, the number of flu and acute respiratory infections detected was low. The incidence of flu and acute respiratory infection episodes in the group that received placebo was higher compared to the groups that received homeopathic medications. The difference between homeopathic and placebo groups was statistically significant (P<0.001), whereas the difference between the homeopathic medicine groups was not (P=0.99).
In the first year post-intervention, 46 of 151 (30.5%) in the placebo group developed 3 or more flu and acute respiratory infection episodes, while there was no episode out of 149 children who used homeopathic complex and only 1 out of 145 (1%) in children who received InfluBio.
The results reported by Siqueira et al in this paper are incredible, but as in the true meaning of the word, unbelievable. They seem just too good to be true.
Our belief as naturopathic physicians in the efficacy of homeopathic medicines in which the active agent employed has been diluted to the point of extinction contradicts logic and generally accepted scientific understanding. Despite the logic-defying premise of homeopathy, experience of apparent clinical efficacy leaves many of us in a quandary. How does one justify the use of a medical practice that in the opinion of most scientists should not work? As a result we are particularly attentive to scientific research that supports the use of this type of medicine.
It has been 2 decades since David Reilly’s Lancet articles, which showed homeopathic preparations of airborne allergens had significant impact on allergy symptoms, which prompted the editors of the Lancet to write “either there is something amiss with the clinical trial as conventionally conducted, or the effects of homoeopathic immunotherapy differ from those of placebo … carefully done work of this sort should not be denied the attention of Lancet readers.”1,2
Homeopathy was incorporated into Brazil’s Public Health Service in 2006. Petropolis was one of the first cities in Brazil to actively implement homeopathy. Petropolis was also the home of Roberto Costa and the Roberto Costa Institute.
The homeopathic medicines used in this study are somewhat unique. Roberto Costa, a homeopathic physician from Petropolis, developed a method of preparing nosodes using living organisms and reported they produced dramatic results compared to standard nosodes that are prepared from dead organisms.3 Costa’s reported results prompted an in vitro study published in 2013, which demonstrated that living nosodes prepared from influenza A virus had measurable effects—in particular stimulating macrophage cells and inducing an increase in tumor necrosis factor-alpha.4 These results motivated the present clinical trial to be conducted in the Brazilian Public Health System. These living nosodes are designated as “RC nosodes” after Roberto Costa.
These results seem too good. While almost a third of the children in the placebo group had 3 or more episodes of flu per year, use of either one of the homeopathic preparations tested in this study reduced episodes dramatically to just 1 episode in almost 300 children.
The timing of the study is another detail that makes the results seem implausible. This study was conducted during a year when Brazil was in the midst of the worldwide H1N1 flu pandemic. The pandemic reached Brazil between 2009 and 2010, but did so unevenly. The positive outcomes reported in this study occurred during a time when increased infection rates should have been expected.
We are thus obliged to look hard for potential errors in methodology that might account for misleading data.
Two states (out of a total of 23) were responsible for 73% of all influenza cases reported in Brazil that year.5 Could the children who received placebo have lived in an area of higher infection rates than those receiving the homeopathic medicines? The authors state that the treatment groups were randomized so that geographic location would not confound the data.
The most obvious weakness in this study was that there was no actual laboratory examination of ill patients to confirm influenza infection. It would be more accurate to say that the children had something similar to an upper respiratory infection (URI) or influenza-like illness (ILI). It would be presumptive to state that these children actually had legitimate influenza infections based only on their questionnaires.
This lack of laboratory confirmation is shared by many complementary and alternative medicine trials and has been listed as a prime methodological consideration for investigating homeopathic treatment of influenza. Unless laboratory testing is employed to confirm the nature of a reported illness, the term ILI should have been used instead of influenza in discussing findings.
According to Paul Herscu, ND, DHANP, MPH, of the New England School of Homeopathy, studies are easily discredited when they claim to be about influenza but rely only on symptoms for diagnosis. This kind of criticism may sink a paper’s credibility.6,7 Whichever terms are ultimately chosen, the reader is nevertheless left with the fact that the treatment groups experienced far fewer episodes of apparent illness.
Another weakness in this Brazilian study is that it was dependent on, and may be weakened by, recall bias for the inclusion criterion, as well as recall bias during the actual trial. This is important since the actual time period during which the trial was conducted coincided with the 2009 H1N1 epidemic, a time when there would have been increased surveillance and increased reported incidence, not less.
Another factor that possibly affected recall bias is the Hawthorne Effect. The Hawthorne Effect is the positive change in the performance of a group taking part in an experiment or study due to their perception of being singled out for special consideration. Given the young age of the study participants, we might assume they would be far less sensitive to this effect, but perhaps their family or care providers who reported on symptoms of illness were influenced. Even so, this study was well blinded: Neither children, family, teachers, doctors, nor pharmacists knew whether the participant was singled out to received active homeopathic medication or placebo.
Rates of actual influenza and illnesses are incredibly heterogeneous in Brazil, with a great deal of moveable pieces and fluctuating demographic changes to illnesses, making a trial difficult to understand, which is why we hope for laboratory confirmation.
In another paper describing the 2009 Brazilian flu epidemic, Oliveira et al reported, “There were 2,651 (45.6 % of 5,817 acute febrile illness patients) ILI cases with a mean annual incidence of 60 cases/1,000 population (95 % CI 58-62). Risk of ILI was highest among 5–9 year olds with an annual incidence of 105 cases/1,000 population in 2009.”8
In Siquerira’s homeopathy study, 46 of the 151 children who had received placebo developed 3 or more flu or acute respiratory infection episodes. If this were only 1 episode per child, the incidence would equal 305 cases per 1,000. This would still be nearly 3 times the highest rate, or 7 times the average rate of illness that Oliveira et al report. These numbers are so far above the general infection rates reported elsewhere that it raises questions and cause for concern.
If the children in the homeopathic treatment groups were to have become ill at the same rate as those who received placebo, there should have been approximately 90 children who became ill (0.305 x 294=90), but apparently only 1 did. Siquerira et al are not just proposing homeopathic prophylaxis lowered risk of infection, but that it prevented 99% of the expected cases.
In contrast, the CDC reports that this year’s flu vaccine (2016) has been “highly effective” at a 59% reduction.9
Even applying Oliveira’s reported incidence rate of 105 cases out of 1,000 to the 294 children who received homeopathic treatment and completed the study, we would extrapolate that 31 should have fallen ill during the year. Again, reporting that only 1 child became ill seems incredible.
Siqueira et al do not report vaccination rates among their study participants and whether rates varied among treatment versus placebo groups. More than 89 millions doses of H1N1 vaccine were administered during the course of this study in Brazil.10 While one assumes that randomization created subgroups that were equally vaccinated, this missing information raises the possibility that lower vaccination rates among the placebo group might be linked with higher incidence of infectious episodes.
The nature of the questionnaire Siqueira et al used to measure the effectiveness of the homeopathic interventions allowed for tracking frequency of perceived illness but not severity. It is typical to report these 2 measures together as a way to judge the effectiveness of an intervention. One way to do so is by reporting the number of severe acute respiratory infections (SARIs), as in the paper cited below. Missing this more quantifiable measure of illness leaves the door open for conjecture; for example, is it possible that those individuals treated with homeopathic medicine had fewer episodes but that each episode was more severe or life threatening? Another possibility is that the placebo group had more frequent illnesses but of less severity.11 The authors did report that the children receiving the homeopathic preparation were more likely to have mild flulike symptoms in the month following initial treatment, while those children receiving placebo were more likely to have flulike symptoms about 3 months after treatment and then repeatedly. One might argue that this was a “homeopathic proving” or an immunological response to the treatments. If the latter, it would be curious to have looked for changes in viral antibody titers pre- and post-interventions.
Future trials like this would benefit from tracking symptoms and illness severity—and using lab testing to confirm flu infection.
Science, good or bad, rarely stands in the way of public belief, and we will likely see this paper being used as justification for homeopathic influenza prophylaxis treatments this coming winter. Given the low side effect risk of these medicines, there is little reason to dissuade people from engaging in such practices. Whether these RC nosodes become available in North America is another question. Perhaps as we gain clinical experience using these products, my initial doubts about these incredible results will change.
- Reilly D, Taylor MA, Beattie NG, Campbell JH, McSharry C, Aitchison TC, Carter R, et al. Is evidence for homoeopathy reproducible? Lancet. 1994;344(8937):1601-1606.
- Taylor MA, Reilly D, Llewellyn-Jones RH, McSharry C, Aitchison TC. Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. BMJ. 2000 Aug 19; 321(7259): 471–476.
- Costa RA. Nosodios Vivos. 1st edn. Rio de Janeiro: Farmacia Homeopatica Atomo Ltda., 2002.
- Siqueira CM, Costa B, Amorim AM, et al. H3N2 homeopathic influenza virus solution modifies cellular and biochemical aspects of MDCK and J774G8 cell lines. Homeopathy. 2013;102:31e40.
- Codeço CT, Cordeiro JD, Lima AW, et al. The epidemic wave of influenza A (H1N1) in Brazil. Cadernos de Saúde Pública. 2009;28(7):1325-1336.
- Kirkby R, Calabrese C, Kaltman L, Monnier J, Herscu P. Methodological considerations for future controlled influenza treatment trials in complementary and alternative medicine. J Altern Complement Med. 2010;16(3):275-283.
- Kirkby R, Herscu P. Homeopathic trial design in influenza treatment. Homeopathy. 2010;99(1):69-75.
- Oliveira CR, Costa GSR, Paploski IAD, et al. Influenza-like illness in an urban community of Salvador, Brazil: incidence, seasonality and risk factors. BMC Infectious Diseases. 2016;16:125.
- Centers for Disease Control and Prevention. Flu vaccine nearly 60 percent effective. http://www.cdc.gov/media/releases/2016/flu-vaccine-60-percent.html. Accessed August 29, 2016.
- Domingues CM, de Oliveira WK; Brazilian andemic Influenza Vaccination Evaluation Team. Uptake of pandemic influenza (H1N1)-2009 vaccines in Brazil, 2010. Vaccine. 2012;30(32):4744-4751.
- Oliveira W, Carmo E, Penna G, et al. Pandemic H1N1 influenza in Brazil: analysis of the first 34,506 notified cases of influenza-like illness with severe acute respiratory infection (SARI). Euro Surveill. 2009;14(42).