Placebo-controlled Field Trial Research Articles

HYSSOP and POLIUM could help to prevent COVID-19 in high-risk population: The results of a parallel randomized placebo-controlled field trial

This study was conducted to evaluate the effect of HYSSOP (composed of Hyssopus officinalis, Echium amoenum, and Glycyrrhiza glabra L) and POLIUM (contained Teucrium polium L, Cuscuta epithymum Murr, and Cichorium intybus L) combined distilled herbal medicines compared to placebo in prevention of COVID-19. This is a double-blind parallel placebo-controlled field trial conducted on 751 asymptomatic individuals who one of the family members recently had a positive RT-PCR test for COVID-19. They were divided into three groups including POLIUM, HYSSOP, and placebousing random blocks with a 1:1:1 allocation ratio. Participants received daily 5 cc (under 12 years) or 10 cc (over 12 years) of allocated oral medications for 20 days. The primary outcome was the frequency of positive RT-PCR test among participants who became symptomatic. The mean age of participants was 36.6. Nineteen participants get infected by COVID-19 during the intervention; fifteen of them belonged to the placebo and four to the POLIUM group. Fisher's exact test indicated significant differences between HYSSOP and placebo (p<0.001) as well as POLIUM and placebo (p=0.009) groups in terms of COVID-19 confirmed by PCR test. Cox regression model adjusted for confounders illustrated that the hazard of getting infection by COVID-19 in POLIUM and HYSSOP groups decreased by 66% (OR (95% CI): 0.34 (0.12 to 0.94); p=0.038) and 93% (OR (95% CI): 0.07 (0.01to 0.56); p=0.012) respectively, compared to placebo. Oral administration of HYSSOP and POLIUM with the other supportive health care could decrease the risk of getting COVID-19.

A randomized placebo-controlled trial of the efficacy and safety of a terbinafine, florfenicol and betamethasone topical ear formulation in dogs for the treatment of bacterial and/or fungal otitis externa

BackgroundTreatment of infected otitis externa (OE) relies on the topical application of specific formulations that most often contain an antibiotic, an antifungal and a glucocorticoid. This study is to report the results of a randomized, placebo-controlled field trial evaluating the efficacy and safety of OSURNIA™ (Elanco Animal Health, a division of Eli Lilly and Company, Greenfield, IN), a novel topical ear medication containing florfenicol, terbinafine and betamethasone acetate in an adaptable gel. The study includes 284 dogs with bacterial and/or fungal OE who were randomly assigned to receive two doses of Osurnia or its vehicle, one week apart. Dogs were evaluated at various time points through Day 45, and a total clinical score (TCS) was calculated based on pain, erythema, exudate, swelling, odor and ulceration. The primary outcome measure was the rate of treatment success (RTS), defined as a TCS of 0, 1 or 2 on Day 45. Before and after treatment, a “clap test” was performed to subjectively assess hearing, and blood and urine were collected for routine clinical pathology.ResultsThe RTS was significantly higher in ears treated with Osurnia (64.78%) than with placebo (43.42%). There was no significant interaction between efficacy and duration of history, recurrence of otitis or body weight. Adverse events were similar between groups. All dogs treated with Osurnia maintained their hearing, and there were no relevant clinical pathology changes.ConclusionsThe application of two doses of Osurnia, one week apart, is effective and safe to treat microbial otitis externa in dogs.

Systemic inflammatory response to shoulder ulcers and lack of preventive effect of postpartum pain medication with ketoprofen in sows

Shoulder lesions are common in lactating sows and can affect their welfare. We assessed the systemic inflammatory response to shoulder ulcers and monitored the preventive effect of postpartum administration with non-steroidal anti-inflammatory medication (ketoprofen) on their prevalence. In a double-blind placebo-controlled field trial, 144 YxL hybrid sows farrowing in crates with a cast-iron floor received either ketoprofen (3 mg/kg) or placebo as an intramuscular injection on days 0-1 after parturition. During the lactation period (weeks 1–4) all sows were assessed weekly for the presence of shoulder ulcers (0 = no ulcer, 1 = unilateral ulcer, 2 = bilateral ulcers; in all cases at least epithelial damage). From a subset of 37 sows, haptoglobin (Hp), albumin (ALB) and cortisol (COR) were measured from blood samples taken 10 to 12 days after farrowing. Results were analyzed according to a linear regression model for associations between Hp, ALB, COR and shoulder ulcers. A random ordered logistic model was used to assess risk factors (body condition score (BCS), back and shoulder fat, decrease in BCS or fat layer thickness during lactation, parity, number of live born and stillborn piglets, piglets weaned, shoulder ulcer scar) and the effect of ketoprofen treatment. Total prevalence of shoulder ulcers at lactation weeks 1–4 was 26.4%, 33.3%, 38.2% and 38.9%, respectively. Prevalences of unilateral shoulder ulcers at lactation weeks 1–4 were 16.7%, 19.4%, 20.8% and 18.8%, and prevalences of bilateral shoulder ulcers were 9.7%, 13.9%, 17.4%, and 20.1%. There was a decrease in albumin and an increase in Hp levels in sows with bilateral shoulder ulcers compared with sows without shoulder ulcers (P < 0.001) or unilateral shoulder ulcers (P = 0.014 for ALB, P = 0.021 for Hp). Changes in COR levels were not statistically significant but sows with bilateral shoulder ulcers tended to have lower cortisol levels than sows without ulcers (P = 0.061) and sows with unilateral shoulder ulcers (P = 0.089). Ketoprofen failed to protect against shoulder ulcers, but instead the treated sows had an increased number of shoulder lesions at the second and third lactation week (P = 0.023 and P = 0.049). Previous shoulder ulcer was a predisposing factor for shoulder ulcers at all lactation weeks (P < 0.001). Higher body condition score (BCS) and a thicker back and shoulder fat layer protected against shoulder ulcers. The results indicate that bilateral shoulder ulcers trigger a systemic response and should therefore be regarded as a significant finding in clinical evaluation. Postpartum administration of ketoprofen was ineffective in shoulder ulcer prevention.

The longitudinal effect of a multi-strain probiotic on the intestinal bacterial microbiota of neonatal foals.

The microbiota plays a key role in health and disease. Probiotics are a potential way to therapeutically modify the intestinal microbiota and prevent disease. The aim of this study was to investigate the effects of probiotics on the bacterial microbiota of foals during and after administration. Randomised placebo controlled field trial. Thirty-eight healthy neonatal foals enrolled in a previous study were selected. The foals had received a multi-strain probiotic (four Lactobacillus spp. 3-4 × 103 colony-forming units (cfu)/g each, Bifidobacterium animalis spp. lactis, 1 × 103-4 cfu/g) or placebo once daily for 3 weeks. A total of 3 faecal samples were collected from each foal at 2-week intervals and assessed via metagenomic sequencing. The Wilcoxon test was used to compare data between treatment groups. There were no changes on the phylum, order or class level between treatment groups at any age (all P>0.05) but some significant changes in relative abundance of families. Probiotic administration did not result in an increased relative abundance of lactobacilli or bifidobacteria at any age (Lactobacillus: P = 0.9, P = 0.1 and P = 0.2, Bifidobacterium: P = 0.3, P = 0.6 and P = 0.1 for Weeks 2, 4 and 6, respectively). Lactobacillus was enriched in the probiotic group at Week 6 on LEfSe analysis (linear discriminant analysis score 0.34, P = 0 .02). There was no effect on alpha diversity (all P>0.2) or community structure when parsimony and unifrac analysis were applied (all P>0.6). There were limited effects of probiotic treatment on the bacterial microbiota of foals. The studied probiotic based on lactobacilli and bifidobacteria has a limited potential for therapeutic modification of the gastrointestinal microbiota.

The Effect of Zinc Supplementation on Cognitive Performance in Schoolchildren

Introduction Zinc is a vital micronutrient in humans and its deficiency in children can thwart their growth and development, compromise their immunity and cognitive function. However, there is a paucity of studies about the effect of zinc supplementation on cognitive functions. This study is an attempt to quantify the impact of zinc supplementation on cognitive performance of schoolchildren. Materials and Methods This randomized, double-blind, placebo-controlled field trial was carried out in public elementary school in Mashhad- Iran to investigate the effect of Zinc on cognition of 45 healthy children. The cognitive test used in the trial was Raven IQ (Intelligence Quotient) test. A total of 45 first grade children aged 6 to 8 years were enrolled and divided into two experiment and control groups. The cases group, received 20 mg of zinc sulfate syrup vs. the control group received a placebo each day for 6 months. Raven IQ test was administered under basal conditions before and after the supplementation of zinc or placebo. Results The memory and intellectual development in the experimental group was significantly more than in the control group (P < 0.05). Conclusion The results of the study demonstrate the positive relationship between zinc administration and some aspects of intellectual development and personality features, emphasizing the significance of this element in the normal psychological status of children.

The effect of ketoprofen on feeding behavior of tail-bitten pigs

No research has been reported on the effect of intramuscular ketoprofen administration on the feeding behavior of tail-bitten pigs. In order to investigate this, a longitudinal, double blind, placebo-controlled field trial was conducted with a total of 77 pigs from a finishing herd. Pigs received either ketoprofen (KET) or a placebo (PLAC) intramuscularly for three days and procaine penicillin for five days after the tail was first observed to be damaged. Pigs were followed from day −2 to day 3 with respect to a noted tail wound. Only new incidence of tail biting was included. Nine to 11 pigs per pen were reared with a single automatic feeder. A transponder attached to the ear of each pig recorded times of entrance and exit to the feeder and feed consumed. To calculate average daily weight gain (ADG), pigs were weighed at days 0, 6 and 13. Time spent at the feeder by visit and on a daily basis, and mean daily intervals between feeder visits per pig were computed in minutes. Daily feeding rate (FR) was calculated from the feeder data (consumed feed (g) / time at the feeder (s)). Placebo pigs consumed more feed and spent more time at the feeder on day 1 than KET pigs (P < 0.05). For all pigs, FR increased from day 1 to day 3 (P < 0.05). Feeder visit intervals were longer and frequency lower on day 0 compared with other days (P < 0.05). Average feed consumption and time spent at the feeder per day decreased on day 0 and returned to the initial level on day 1 (P < 0.05 for both). No effect on ADG was recorded. Intramuscular administration of ketoprofen induced little change in feeding behavior and had no effect on weight gain. Placebo-treated pigs may have used feed as an analgesic and calming substance to some degree, leading to temporarily increased feed consumption.

Efficacy and safety of a combined Porcine Circovirus and Mycoplasma hyopneumoniae vaccine in finishing pigs

The safety and protective efficacy of a new one dose combination vaccine containing Porcine Circovirus type 2 (PCV2) and M. hyopneumoniae antigens – Porcilis® PCV M Hyo - was evaluated in laboratory studies and under field conditions. Vaccination resulted in a moderate temperature increase on the day of vaccination and mild systemic and local reactions were found in only a low percentage of the vaccinated pigs. The local reactions observed were small (max. 2 cm) and transient (max. 1 day). In short term (onset of immunity) and long term (duration of immunity) challenge studies with the individual pathogens, the vaccine significantly reduced the PCV2 load in lymphoid tissue and lungs and M. hyopneumoniae-induced lung lesions. In a placebo-controlled field trial on a farm where both PCV2 and M. hyopneumoniae were present, vaccination of piglets at 3 weeks of age resulted in a reduction of PCV2 viremia and shedding and lower lung lesion scores at slaughter. In addition, a positive effect on the average daily weight gain (+ 34 g/day) in the finishing phase was observed. It can therefore be concluded that this new ready to use combination vaccine is safe and efficacious against PCV2 and M. hyopneumoniae single and combined infections.

Multi‐Centre Field Trial to Evaluate the Effectiveness of Clodronic Acid for Navicular Syndrome

Reasons for performing studyClodronic acid (CA) is a bisphosphonate which inhibits bone resorption through inhibition of formation/dissolution of hydroxyapatite crystals and by direct cellular effects on osteoclasts. The study was conducted to assess the short‐ and long‐term effectiveness of CA for the control of lameness associated with navicular syndrome.ObjectivesTo demonstrate the effectiveness of CA in navicular syndrome.Study designRandomised, multi‐centre, double‐masked, placebo controlled field trial in client‐owned horses.MethodsHorses with unilateral or bilateral forelimb lameness (AAEP lameness scale grade ≥2); positive anaesthesia of the distal palmar digital nerve(s); radiographic evidence of navicular syndrome and the absence of other causes of lameness were eligible for enrolment. Horses were randomised to treatment groups in a 3:1 ratio of CA to saline control. Treatment was administered once via intramuscular injection at 1.2 mg/kg bwt (maximum 765 mg CA or 15 ml saline). Efficacy was assessed by comparing lameness grades before and after treatment.Results146 horses of various breeds were enrolled at 6 sites in Germany and US. At 8 weeks, horses in the CA group had a significantly higher success rate than horses in the control group (least squares mean 74.72% vs. 3.30%; P = 0.0028). Efficacy was sustained through 180 days in 66% of horses. Adverse events were few and considered to be mild and transient.ConclusionsClodronic acid was safe and effective in navicular syndrome.Ethical animal research: Owners gave informed consent for their horses’ inclusion in the study. Sources of funding: Dechra Ltd. Competing interests: The late Dr Frevel was a consultant to Omnimedic GbR, which has applied for a patent for the use of clodronic acid for navicular syndrome. Dr Poole is employed by Dechra.

Efficacy and safety of a patch vaccine containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase 3, randomised, double-blind, placebo-controlled field trial in travellers from Europe to Mexico and Guatemala

Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the efficacy and safety of a skin-patch vaccine containing the pathogen's heat-labile toxin (LT) in a population of travellers to Mexico and Guatemala. In this phase 3, randomised, double-blind, placebo-controlled field trial, healthy adults (aged 18-64 years) travelling from Germany or the UK to Mexico or Guatemala were assigned in a 1:1 ratio by a dynamic electronic randomisation system to receive transcutaneous immunisation with a patch containing 37.5 μg of ETEC LT or a placebo patch. Participants, site staff, and the investigators who did the analyses were masked to group assignment. Participants were vaccinated before travel, with two patches given 14 days apart. In the destination country, participants tracked stool output in a diary and provided stool samples for pathogen identification if diarrhoea occurred. The primary endpoint was the proportion of participants with at least one episode of moderate-to-severe diarrhoea (defined as four or more unformed stools in a 24 h period) in which either or both ETEC enterotoxins (LT and heat-stable toxin [ST]) were detected. The study is registered at ClinicalTrials.gov, number NCT00993681. 2036 participants were recruited and randomly assigned between Oct 14, 2009, and Aug 13, 2010, with 1016 allocated to receive the LT patch and 1020 the placebo patch. 821 participants in the LT-patch group and 823 in the placebo group received both vaccinations and were analysed in the per-protocol population. 30 (3.7%, 95% CI 2.5-5.2) participants in the LT-patch group and 46 (5.6%, 4.1-7.4) in the placebo group had moderate or severe ETEC diarrhoea (vaccine efficacy 34.6%, -2.2 to 58.9; p=0.0621). 9333 local (ie, patch-site) adverse events (including erythema, rash, pruritus, hyperpigmentation, pain, hypopigmentation, and oedema) occurred in 943 (93%) of 1015 participants in the LT-patch group, compared with 1444 local adverse events in 574 (56%) of 1019 participants in the placebo group (p<0.0001). Serious adverse events occurred in 25 participants (14 in the LT-patch group and 11 in the placebo group), with all regarded as either unrelated or possibly related to treatment. Vaccine-induced hyperpigmentation persisted for at least 180 days after vaccination in 150 (18%) of the 849 participants who received both vaccinations and returned for final assessment in the LT-patch group, compared with none of the 842 participants in the placebo group. The vaccine was immunogenic, with a post-vaccination geometric mean titre of LT-specific serum immunoglobulin G of 3400.29, compared with 315.41 in the placebo group. Although the LT antigen was delivered effectively by the skin patch, the vaccine did not protect travellers against diarrhoea caused by ETEC or other organisms. Future vaccines against travellers' diarrhoea might need to include several antigens against various diarrhoeal pathogens, and might need to be able to generate mucosal and higher systemic immunity.

A double-blind controlled field trial of doxycycline and albendazole in combination for the treatment of bancroftian filariasis in India

In a placebo controlled field trial, the effects of doxycycline (200mg/day) for 23 days followed by doxycycline (200mg/day) in combination with albendazole (ABZ) (400mg/day) for 7 days on depletion of Wolbachia endobacteria from Wuchereria bancrofti and microfilaricidal activity were studied in 68 patients (34 males and 34 females) from West Bengal, India. The drugs in combination (i.e., doxycycline+ABZ) provided the best efficacy by totally eliminating the circulating microfilaria (mf) (in 42% cases) on day 365 with (99.8%, P<0.05) suppression even on day 365 post-treatment compared to both exclusive doxycycline (69%, P<0.05) and ABZ (89%, P<0.05) groups. Thus, our results have established that a 30-day course of doxycycline in combination with a 7-day course of ABZ is sufficient to ensure long-term reduction in mf level by depleting Wolbachia from worm tissues. Doxycycline combined with ABZ led to a greater reduction in mf density in blood at 4 months (post-treatment) in comparison to doxycycline or ABZ alone. There were significant differences between the three treatments after 12 months (post-treatment). Further, the impact of a 7-day regimen of ABZ was surprisingly good in reducing mf compared to doxycycline-alone group. Adverse reactions were mild. A 30-day course of doxycycline and ABZ in combination is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against microfilaremia.

Patient-related factors predicting the effectiveness of rifampicin chemoprophylaxis in contacts: 6 year follow up of the COLEP cohort in Bangladesh

The COLEP trial in Bangladesh showed a 57% reduction in leprosy incidence among contacts of newly diagnosed patients in the first 2 years after chemoprophylaxis with single dose rifampicin (SDR). We assessed the impact of this intervention after 6 years and identified characteristics of the leprosy index patients predicting the effectiveness of this intervention. The cohort of 1037 patients and their 28 092 contacts that participated in the randomised placebo controlled field trial with single dose rifampicin was followed for 6 years. The leprosy status of contacts was established at 2, 4 and 6 years after the intervention. We assessed the association between characteristics of the index leprosy patients and the development of clinical leprosy among their contacts using logistic regression. The protective effect of SDR was seen only in the first 2 years, with no additional effect after 4 and 6 years. However, the total impact of the intervention was still statistically significant (P = 0.025) after 6 years and no excess cases were observed in the SDR arm at a later stage. The intervention prevented leprosy in contacts that actually received SDR, but did not offer protection to members of the same contact group who did not take chemoprophylaxis. The intervention was most effective in contact groups of female index patients, an enhanced effect was also observed in contact groups of patients belonging to a cluster of two or more leprosy patients at intake as well. These easy to recognise patient characteristics indicate a possible enhanced risk of transmission of Mycobacterium leprae to contacts in the vicinity of patients and are useful for deciding about preventive measures, such as early detection or chemoprophylaxis.

Probiotics, Enteric and Diarrheal Diseases, and Global Health

Enteric and diarrheal diseases are a major worldwide cause of death among children under the age of 5. In this age group, diarrhea occurs 2.5 billion times per year [1] and causes 15% of childhood deaths.[2] Diarrheal diseases claim 59 million disability-adjusted life years (DALYs), nearly all from children in low- and middle-income countries.[3] Despite this enormous burden, these numbers fail to capture the full impact of enteric and diarrheal diseases. Early and frequent exposure to intestinal pathogens begins a cycle (Figure 1A) that affects digestion, nutrient absorption, growth, and immunity.[4] Repeated infections, with either overt diarrhea or subclinical enteropathy, produce acute and chronic undernutrition,[5] which leads to more frequent and severe infections.[6] Undernutrition contributes to 53% of childhood deaths [7] and is the leading risk factor for poor health outcomes in childhood;[8] survivors are at risk for developmental deficits in growth, fitness, and cognition that persist into adulthood with devastating consequences.[4] These consequences have a multiplicative effect on calculations of DALYs from diarrheal disease.[9] Open in a separate window Figure 1 The vicious cycle of diarrhea and undernutrition in susceptible children (A) The devastating synergy between enteric infections and undernutrition is influenced by the environment, the human genome, host nutrition, and the human microbiome. Various interventions (red boxes) may inhibit progression to the next step in the cycle, minimizing both acute and chronic morbidities. (B) Employing a spectrum of disease outcome measures would lend greater insight into the pathology underlying enteric and diarrheal diseases, while providing a more complete understanding of interventions targeting basic steps of enteric and diarrheal disease pathogenesis. Adapted with permission from Wiley: Nutrition Reviews,4 copyright 2008. http://www.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1753-4887.

Probiotics in Perspective

Probiotics in Perspective

Role of probiotic in preventing acute diarrhoea in children: a community-based, randomized, double-blind placebo-controlled field trial in an urban slum

Acute diarrhoea remains a major public health challenge in developing countries. We examined the role of a probiotic in the prevention of acute diarrhoea to discover if there was an effect directed towards a specific aetiology. A double-blind, randomized, controlled field trial involving 3758 children aged 1-5 years was conducted in an urban slum community in Kolkata, India. Participants were given either a probiotic drink containing Lactobacillus casei strain Shirota or a nutrient drink daily for 12 weeks. They were followed up for another 12 weeks. The primary outcome of this study was the occurrence of first episodes of diarrhoea. We assessed this during 12 weeks of intake of study agent and also for 12 weeks of follow-up. There were 608 subjects with diarrhoea in the probiotic group and 674 subjects in the nutrient group during the study period of 24 weeks. The level of protective efficacy for the probiotic was 14% (95% confidence interval 4-23, P<0·01 in adjusted model). The reduced occurrence of acute diarrhoea in the probiotic group compared to nutrient group was not associated with any specific aetiology. No adverse event was observed in children of either probiotic or nutrient groups. The study suggests that daily intake of a probiotic drink can play a role in prevention of acute diarrhoea in young children in a community setting of a developing country.

Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial

Enterotoxigenic Escherichia coli (ETEC) is a major cause of travellers' diarrhoea. We investigated the rate of diarrhoea attacks, safety, and feasibility of a vaccine containing heat-labile enterotoxin (LT) from ETEC delivered to the skin by patch in travellers to Mexico and Guatemala. In this phase II study, healthy adults (aged 18-64 years) who planned to travel to Mexico or Guatemala and had access to a US regional vaccination centre were eligible. A centralised randomisation code was used for allocation, which was masked to participants and site staff. Primary endpoints were to investigate the field rate of ETEC diarrhoea, and to assess the safety of heat-labile toxins from E coli (LT) delivered via patch. Secondary endpoints included vaccine efficacy against travellers' diarrhoea and ETEC. Participants were vaccinated before travel, with two patches given 2-3 weeks apart. Patches contained either 37.5 mug of LT or placebo. Participants tracked stool output on diary cards in country and provided samples for pathogen identification if diarrhoea occurred. Diarrhoea was graded by the number of loose stools in 24 h: mild (three), moderate (four or five), and severe (at least six). Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT00516659. Recruitment closed after 201 participants were assigned patches. 178 individuals received two vaccinations and travelled and 170 were analysed. 24 (22%) of 111 placebo recipients had diarrhoea, of whom 11 (10%) had ETEC diarrhoea. The vaccine was safe and immunogenic. The 59 LT-patch recipients were protected against moderate-to-severe diarrhoea (protective efficacy [PE] 75%, p=0.0070) and severe diarrhoea (PE 84%, p=0.0332). LT-patch recipients who became ill had shorter episodes of diarrhoea (0.5 days vs 2.1 days, p=0.0006) with fewer loose stools (3.7 vs 10.5, p<0.0001) than placebo. Travellers' diarrhoea is a common ailment, with ETEC diarrhoea illness occurring in 10% of cases. The vaccine patch is safe and feasible, with benefits to the rate and severity of travellers' diarrhoea.

Safety of Upper-Room Ultraviolet Germicidal Air Disinfection for Room Occupants: Results from the Tuberculosis Ultraviolet Shelter Study

We evaluated the safety of room occupants in the Tuberculosis Ultraviolet Shelter Study (TUSS), a double-blind, placebo-controlled field trial of upper-room ultraviolet germicidal irradiation (UVGI) at 14 homeless shelters in six U.S. cities from 1997 to 2004. Data collection involved administering questionnaires regarding eye and skin irritation to a total of 3,611 staff and homeless study subjects. Among these subjects, there were 223 reports of eye or skin symptoms. During the active UV period, 95 questionnaires (6%) noted such symptoms, and during the placebo period, 92 questionnaires (6%) did so. In the 36 remaining cases, either the UV period when symptoms took place was unknown or the symptoms spanned both periods. There was no statistically significant difference in the number of reports of symptoms between the active and placebo periods. One definite instance of UV-related keratoconjunctivitis occurred, resulting from a placement of a bunk bed in a dormitory where a single bed had been used when the UV fixtures were first installed. These findings demonstrate that careful application of upper-room UVGI can be achieved without an apparent increase in the incidence of the most common side effects of accidental UV overexposure.

Iron and/or Zinc Supplementation Did Not Reduce Blood Lead Concentrations in Children in a Randomized, Placebo-Controlled Trial

There is increasing interest in the interaction of nutritional deficiencies with toxic metals. Iron deficiency and elevated blood lead concentrations (PbB) reportedly occur together, and zinc also plays an important role in lead metabolism. The objective was to evaluate the effect of zinc and/or iron supplementation on PbB of children attending schools in the neighborhood of a smelter complex for 6 mo. We conducted a double-blind, placebo-controlled field trial in 9 elementary schools located within a 3.5-km radius of a metal foundry in Torreón, Mexico. Of the 602 first-graders enrolled, 517 completed supplementation and had initial and final PbBs. Children were given either 30 mg of iron, 30 mg of zinc, both, or a placebo daily for 6 mo. Baseline and final measures included nutritional status and PbB. The overall prevalence of iron and zinc deficiencies was 12.1 and 30.3%, respectively, and 10.3% were anemic. The PbB concentration decreased in all experimental groups (P < 0.05). After controlling for initial PbB, groups administered zinc and/or iron did not have lower PbB concentrations than the placebo group (P < 0.05). In conclusion, iron supplementation of lead-exposed children significantly improved iron status but did not reduce PbBs. Zinc supplementation did not reduce PbBs independently of zinc nutritional status. Neither iron nor zinc can be recommended as the sole treatment for lead-exposed school children.

Efficacy of Iron and/or Zinc Supplementation on Cognitive Performance of Lead-Exposed Mexican Schoolchildren: A Randomized, Placebo-Controlled Trial

Lead exposure in children has been associated with both global and specific cognitive deficits. Although chelation therapy is advised for children with blood lead concentrations of >44 microg/dL, treatment options for children with lower blood lead values are limited. Because lead absorption is related to children's nutritional status, micronutrient supplements may be 1 strategy for combating low-level, chronic lead exposure. This study was designed to test the efficacy of iron and zinc supplementation for lowering blood lead concentrations and improving cognitive performance in schoolchildren who live in a lead-contaminated city. This randomized, double-blind, placebo-controlled field trial was conducted in public elementary schools in Torreón, an industrialized city in northern Mexico. A metal foundry, located close to the city center and within 3.5 km of 9 schools, was the main source of lead exposure. A total of 602 children who were aged 6 to 8 years and regularly attending first grade in the study schools were enrolled. Children were given 30 mg of iron, 30 mg of zinc, both, or a placebo daily for 6 months. A total of 527 completed the treatment, and 515 were available for long-term follow-up, after another 6 months without supplementation. Eleven cognitive tests of memory, attention, visual-spatial abilities, and learning were administered at baseline and each follow-up. There were no consistent or lasting differences in cognitive performance among treatment groups. Daily supplementation with iron and/or zinc may be of limited usefulness for improving cognition in lead-exposed schoolchildren. However, these treatments may be effective in settings with higher prevalence of nutritional deficiencies or in younger children.

Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial

Wolbachia endosymbionts of filarial nematodes are vital for larval development and adult-worm fertility and viability. This essential dependency on the bacterium for survival of the parasites has provided a new approach to treat filariasis with antibiotics. We used this strategy to investigate the effects of doxycycline treatment on the major cause of lymphatic filariasis, Wuchereria bancrofti. We undertook a double-blind, randomised, placebo-controlled field trial of doxycycline (200 mg per day) for 8 weeks in 72 individuals infected with W bancrofti from Kimang'a village, Pangani, Tanzania. Participants were randomly assigned by block randomisation to receive capsules of doxycycline (n=34) or placebo (n=38). We assessed treatment efficacy by monitoring microfilaraemia, antigenaemia, and ultrasound detection of adult worms. Follow-up assessments were done at 5, 8, 11, and 14 months after the start of treatment. Analysis was per protocol. One person from the doxycycline group died from HIV infection. Five (doxycycline) and 11 (placebo) individuals were absent at the time of ultrasound analysis. Doxycycline treatment almost completely eliminated microfilaraemia at 8-14 months' follow-up (for all timepoints p<0.001). Ultrasonography detected adult worms in only six (22%) of 27 individuals treated with doxycycline compared with 24 (88%) of 27 with placebo at 14 months after the start of treatment (p<0.0001). At the same timepoint, filarial antigenaemia in the doxycycline group fell to about half of that before treatment (p=0.015). Adverse events were few and mild. An 8-week course of doxycycline is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia.

A placebo-controlled trial of two intranasal vaccines to prevent tracheobronchitis (kennel cough) in dogs entering a humane shelter

A placebo-controlled field trial was conducted to compare the effectiveness of intranasal (IN) vaccines containing Bordetella bronchiseptica and canine-parainfluenza virus, with (IN-BPA) or without (IN-BP) canine-adenovirus type 2, for prevention of kennel cough at a humane shelter. Dogs were examined on admission to the shelter and those without respiratory signs of disease were assigned daily, on a rotating basis, to receive one of three vaccines. We enrolled 972 healthy dogs. Dogs were monitored for up to 30 days post-vaccination for coughing and other clinical signs of respiratory disease. Thirty-three (10.7%; 95% confidence interval (CI): 7.2, 14.2) dogs in the IN-BP group, 36 (10.2%; 95% CI: 7.0, 13.4) dogs in the IN-BPA group, and 42 (13.5%; 95% CI: 9.7, 17.3) dogs in the IN-P group coughed spontaneously for ≥1 day within 30 days of vaccination ( P=0.37). The IN-BP and IN-BPA vaccines were 20.7 and 24.4% effective, respectively, in reducing coughing compared with a placebo vaccine. The strongest prognostic factor for coughing (regardless of vaccine group) was the number of days spent at the shelter, with each additional day increasing the risk of coughing by 3% (95% CI: 0.5, 6.3). The low incidence of coughing in the shelter during this study precluded observation of differences in vaccine effectiveness. No differences in vaccine-associated adverse events (coughing, sneezing, nasal or ocular discharge) were noted during the first 3 days post-administration or thereafter.