Efficacy of 5-nitroimidazole compounds for giardiasis in Cuban children: systematic review and meta-analysis.

Five-nitroimidazole (5-NI) compounds are among the most commonly used medications in the treatment of giardiasis. However, after more than five decades of their initial indication for such treatment, there are some concerns about the efficacy of 5-NIs in giardiasis. This study sought to compare the efficacy of any 5-NI with any other antigiardial drug for the treatment of Cuban children with giardiasis. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched CUMED, EBSCOhost and PubMed databases. Two reviewers independently assessed trial eligibility, trial quality and extracted appropriate data. The primary outcome was the parasitological cure. The effect estimate was the pooled relative risk (RR) with 95% confidence intervals (CI). We included seven RCTs in the systematic review, involving a total of 1046 children. When the effect of 5-NIs was compared with that of benzimidazole compounds, the pooled effect was significant and favored 5-NIs [the relative risk (RR) is 1.35, 95% CI =1.05 to 1.75], with high heterogeneity (4 studies, I2 =79%). Compared with chloroquine, the pooled effects of the 5-NIs were not significant [RR is 0.96, 95% CI=0.79 to 1.18, (2 studies, I2=68%)]. Our results support the use of 5-NIs (mainly tinidazole) as first-line therapy for Cuban pediatric patients infected with Giardia and may continue being used as reference drugs in future RCTs of giardiasis. These data could help inform policy decisions in Cuba. Caution is needed in extrapolating such data in other settings.

Treatment of refractory paediatric giardiasis using secnidazole plus albendazole: a case series.

Giardia lamblia, the aetiological agent of human giardiasis, is a frequently identified protozoan infection of the upper small intestine. It mainly affects children and has a wide range of clinical manifestations, from asymptomatic carriage to acute or chronic diarrhoea with dehydration, abdominal pain, nausea, vomiting, excessive flatulence and weight loss. Standard treatment for giardiasis is commonly with 5-nitroimidazole (5-NI) compounds, or nitazoxanide; however, some individuals experience treatment failure. For such patients, a combination of two or more drugs may be a viable approach. We report our experience with 11 paediatric patients with drug-refractory giardiasis, for whom therapy with a combination of secnidazole (SNZ) (30 mg/kg/day, divided into 2 doses, for 3 days) and albendazole (ABZ) (400 mg daily for 5 days) resulted in cure for 9 of the 11 (82%) patients. This combination of drugs was well tolerated; only mild, transient, and self-limited side effects were reported and these did not require discontinuation of treatment. These results support the use of SNZ plus ABZ as an alternative treatment for paediatric patients with giardiasis who have failed conventional treatments. Further research is needed to establish the safety of this combination and how it compares to other combination strategies.

Efficacy of mebendazole in paediatric patients with giardiasis: A systematic review and meta-analysis.

Mebendazole (MBZ), a benzimidazole compound, has received attention in treating patients with giardiasis because it has shown beneficial effects both in vitro and in vivo. The aim of this study was to assess with a systematic review and meta-analysis of randomized controlled trials (RCTs) the efficacy of MBZ compared to other antigiardial agents in children. We searched RCTs of MBZ for the treatment of Giardia infections published in PubMed and EBSCOhost. Application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality were independently performed in duplicate. The primary outcome was the parasitological cure. We included 7 RCTs in the systematic review (639 patients). There was no clinical difference in the parasitological cure between MBZ and metronidazole (MTZ). The relative risk (RR) was 0.81 [95% Confidence Interval 0.61-1.09], with high heterogeneity (4 trials, I2 = 81%). The prediction interval expected to cover the results of a new trial was wide enough (0.22-2.96) to support both a clinically relevant difference favouring either MBZ or MTZ. The decision to support any treatment should be based not only on efficacy but also safety and cost. Although our results suggest that MBZ may be an effective treatment option for children with Giardia infection, they should also be interpreted and translated into clinical practice with caution, as the evidence is based on a limited number of RCTs presenting high heterogeneity.

Potential sexual transmission of Giardia in an endemic region: a case series.

We present four cases in which probable sexual transmission of Giardia lamblia was suspected. Diagnosing this mode of transmission in endemic areas is often difficult and should be considered only as possible, because exposure to poor sanitation and a potentially contaminated environment are always latent. However, as patients reported, there was no history of drinking tap water, exposure to recreational water, eating contaminated food, or other potential sources of infection but anilingus with an infected partner. We consider that in endemic countries, even when other more frequent modes of transmission could be playing the main role, the possibility of (re)infection due to sexual transmission should not be forgotten. Talking openly with patients, strengthening patient-specific preventive measures and counselling appear to be needed to reduce risks of Giardia infection transmission due to this often neglected route.

Giardiasis: a diagnosis that should be considered regardless of the setting.

Although Giardia, the aetiological agent of giardiasis, is one of the most prevalent intestinal parasitic infections world-wide, for industrialised countries, it is mainly appreciated as an imported disease with the minimal local transmission. However, the current evidence challenges this perception; Giardia has relevance beyond the high prevalence areas. This infection may be asymptomatic or cause gastrointestinal complains and long-term sequelae, including irritable bowel syndrome, chronic fatigue and impaired child growth and cognitive development. Its detection and diagnosis present a challenge to physicians who may not be familiar with this infection. To improve interventions to control this parasitosis, it is necessary to maintain a high index of suspicion and remain vigilant in finding cases at risk for infection. A better understanding of the characteristics of populations importing infections alongside improved methods to reliably classify infections as imported or acquired locally will help to ensure early and accurate diagnosis. The evidence shows that public health problems like giardiasis are global issues that need to be addressed collectively by both high and low prevalence countries.

Combination therapy in the management of giardiasis: What laboratory and clinical studies tell us, so far

Treatment failures in patients suffering from giardiasis are not uncommon feature. The most frequent approach in these cases is to treat these patients with longer repeated courses and/or higher doses of the primary therapy, or using drugs from a different class to avoid potential cross-resistance. However, a higher rate of adverse events may limit this strategy. In this context, combination therapy (CT) is emerging as a valuable option against refractory giardiasis. In the attempt to evaluate the benefits of CT, a number of experimental studies, clinical series, and randomized clinical trials (RCTs), as well as several veterinary studies have been performed, with varying results. Here, we present a critical analysis of the available information regarding CT for the treatment of Giardia infection, as well as the authors' opinion with respect to its use. RCTs of combination therapy are limited and the optimal combinations and administration strategies need yet to be clarified. Analyses of the cost-effectiveness and RCTs of CTs for Giardia infection are required to assess the role of these drugs for the control of giardiasis, mainly in the case of treatment failures linked to suspected drug tolerance are the case

Combination therapy in the management of giardiasis: What laboratory and clinical studies tell us, so far.

Treatment failures in patients suffering from giardiasis are not uncommon feature. The most frequent approach in these cases is to treat these patients with longer repeated courses and/or higher doses of the primary therapy, or using drugs from a different class to avoid potential cross-resistance. However, a higher rate of adverse events may limit this strategy. In this context, combination therapy (CT) is emerging as a valuable option against refractory giardiasis. In the attempt to evaluate the benefits of CT, a number of experimental studies, clinical series, and randomized clinical trials (RCTs), as well as several veterinary studies have been performed, with varying results. Here, we present a critical analysis of the available information regarding CT for the treatment of Giardia infection, as well as the authors' opinion with respect to its use. RCTs of combination therapy are limited and the optimal combinations and administration strategies need yet to be clarified. Analyses of the cost-effectiveness and RCTs of CTs for Giardia infection are required to assess the role of these drugs for the control of giardiasis, mainly in the case of treatment failures linked to suspected drug tolerance are the case.

A meta-analysis of the efficacy of albendazole compared with tinidazole as treatments for Giardia infections in children.

Metronidazole is frequently used against Giardia infection; however, it has been associated with significant failure rates in clearing parasites from the gut; additionally, as it should be taken for 5 to 10 days, it is associated with poor compliance, probably due to side effects. Other drugs, including tinidazole (TNZ) and albendazole (ABZ) have been included in the antigiardial armamentarium. Our aim was to assess the efficacy of ABZ compared with TNZ in Giardia infections in children. A systematic review and a meta-analysis were carried out. PubMed, Medline, EMBASE, CENTRAL, and LILACS were searched electronically until February 2015. Also relevant journals and references of studies included therein were hand-searched for randomised controlled trials (RCTs). The meta-analysis was limited to RCTs evaluating the use of ABZ compared with TNZ in children with Giardia infection. The assessed outcome was parasitological efficacy. Prediction intervals (PI) were computed to better express uncertainties in the effect estimates. Five RCTs including 403 children were included. Overall, TNZ significantly outperformed ABZ without differences between subgroups defined by ABZ dosages [relative risk, (RR) 1.61 (95% CI): (1.40-1.85); P<0.0001]. The 95% prediction interval range is 1.28-2.02. There was no significant heterogeneity (I(2)=0%; Q-test of heterogeneity P=0.4507. The number-needed-to-treat, the average number of patients who need to be treated with TNZ to gain one additional good outcome as compared with ABZ was 4, 95% CI: 3-5. Our results show that TNZ outperforms ABZ in the treatment of Giardia infections in children from developing countries.

Chloroquine: An Old Drug with New Perspective Against Giardiasis.

The occurrence of treatment failures to first-line treatment for giardiasis, one of the most widespread although neglected parasitic disease, has long been recognised. Nowadays, it starts to represent a great challenge to clinicians, especially in endemic countries. This requires the introduction of new drug interventions, but the development of novel drugs is a time and money consuming effort with most of the compounds never reaching the market. Consequently, alternative strategies are needed, especially for the treatment of giardiasis. Chloroquine (CQ), a synthetic drug developed as antimalarial agent, has been shown to also exert antigiardial activity. Here, we present a mini-research summarizing results on the treatment of human clinical cases with CQ, going through in vitro research, case report, and case series to human clinical trials, highlighting the benefits and mentioning possible adverse effects.

A bibliometric study of international scientific productivity in giardiasis covering the period 1971-2010.

INTRODUCTION: Despite years of relative neglect, interest in Giardia infection seems to be recently growing, perhaps in part due to its inclusion into the World Health Organization's Neglected Diseases Initiative since 2004. The purpose of this study was to provide an overview of Giardia and giardiasis research over time, as represented by the quantity of published papers. METHODOLOGY: Data for this study were collected from the electronic PubMed/Medline database of National Library of Medicine's (NLM), due to it is easily accessibility and wide use. It was accessed online between April and December 2011. Data for the period 1971-2010 were obtained and information was downloaded using the EndNote program developed by Thomson Reuters. RESULTS: During the study period, a total of 6,964 references (articles, reviews, editorials, letter to the editor, etc.) covering different aspects of Giardia and giardiasis were located in the PubMed database after applying the search strategy reported above. Most papers were original articles and published in English. CONCLUSIONS: In this first effort to explore the development and research productivity on giardiasis over time (no previously published bibliometric studies on giardiasis exist), two interesting characteristics of the Giardia and giardiasis literature were discovered: the concentration of papers over journals disseminating the research results, and that research in this field is growing and will likely continue to grow in the coming years.

Potential impact of macroclimatic variability on the epidemiology of giardiasis in three provinces of Cuba, 2010-2012.

Climate change and variability are common phenomena affecting various infectious diseases. Many studies have been performed on vector-borne diseases; however, few studies have addressed such influences on intestinal parasitic diseases (e.g., giardiasis). In this study, using nonlinear Poisson regression models, we assessed the potential associations between macroclimatic variation and giardiasis cases in children and school workers from three provinces of Cuba in the context of large sampling and parasitological assessment. Between 2010 and 2012, 293,019 subjects were assessed, resulting in 6357 positive for Giardia (216.95 cases/10,000 pop.; 95%CI 211.7-222.2). The variation in time for those giardiasis rates ranged from 35.8 to 525.8 cases/10,000 pop. Nonlinear Poisson regression models between the ONI index and the giardiasis incidence indicated a significant association (p<0.01). With lower values of ONI, lower incidence of giardiasis was observed at Havana (pseudo r(2)=0.0576; p<0.001) and Guantánamo (pseudo r(2)=0.0376; p<0.001). Although these results are preliminary and the magnitude of association is not higher, the results were of statistical significance. This result indicates the need to assess in detail in further studies the impact of additional macroclimatic and microclimatic variables on the epidemiology of this still important intestinal parasitic disease, not only in Cuba but also in other countries of the Caribbean and Latin American region.

Chloroquine: an old drug with new perspective against giardiasis

The occurrence of treatment failures to first-line treatment for giardiasis, one of the most widespread although neglected parasitic disease, has long been recognised. Nowadays, it starts to represent a great challenge to clinicians, especially in endemic countries. This requires the introduction of new drug interventions, but the development of novel drugs is a time and money consuming effort with most of the compounds never reaching the market. Consequently, alternative strategies are needed, especially for the treatment of giardiasis. Chloroquine (CQ), a synthetic drug developed as antimalarial agent, has been shown to also exert antigiardial activity. Here, we present a mini-research summarizing results on the treatment of human clinical cases with CQ, going through in vitro research, case report, and case series to human clinical trials, highlighting the benefits and mentioning possible adverse effects

Care-seeking behaviour and diagnostic processes for symptomatic giardiasis in children attending an academic paediatric hospital.

Giardiasis is one of the commonest intestinal parasitic infections in Cuba. In order to determine care-seeking behaviour and diagnostic processes in paediatric in-patients with giardiasis, structured questionnaires were administered by interview mothers of children with giardiasis during January to December 2010. During the study period, 97 children were diagnosed with giardiasis, of whom 86 (88·6%) caregivers were interviewed. The median number of days from symptoms onset to the first presentation in a health unit was 2 days (range: 0-15 days). The pattern of care-seeking behaviour was variable; 41 (47·7%) of children initially visited the emergency unit in a paediatric hospital. Sixty-six children had, at least, one further contact for help before diagnosis of giardiasis was made (range: 1-5 contacts) and of the 128 contact visits, 94 (73·4%) were also targeted more to hospitals. There was a median time of 6 days between the first presentation to a health unit until diagnosis, which was mainly made by microscopic examination of duodenal aspiration. Among factors investigated in mothers, only knowing other person with giardiasis had significant association with their ability to suspect giardiasis [odds ratio (OR): 29·8, 95% confidence interval (CI): 3·71-239·4, P = 0·001]. Requesting a faecal specimen or ordering duodenal aspiration for microscopic examination during the first visit appeared associated with correct diagnosis (OR: 3·84, 95% CI: 1·57-9·40, P = 0·003). Efforts should be made to increase doctors' awareness of- and diagnostic skills for childhood giardiasis. At the same time, it is necessary to improve caregivers' awareness about giardiasis.

Management of chronic Giardia infection.

Advances in our understanding of chronic giardiasis (CG) may improve our care of patients in this stage of the disease. This review proposes a new concept of CG and highlights the recent advances in our understanding and management of this condition. According to this review, management requires, initially, an accurate diagnosis, which may exclude several conditions that can mimic CG. Optimal treatment requires a tailored approach which includes the recognition of the known modifiable causes of this health condition, assessment of symptoms and potential complications, their treatment utilizing, if necessary, a multidisciplinary team, and an ongoing monitoring for the effect of therapy - weighing the efficacy of individual drugs - all of these together may lead to a successful treatment of CG.