Sérgio Cimerman

Giardiasis: a pharmacotherapy review

Giardia lamblia, the cause of human giardiasis, is among the most common intestinal protozoa worldwide. Human infection may range from asymptomatic shedding of giardial cysts to symptomatic giardiasis, being responsible for abdominal cramps, nausea, acute or chronic diarrhoea, with malabsorption and failure of children to thrive. At present, treatment options include the nitroimidazoles derivatives; especially metronidazole, which has been the mainstay of treatment for decades and is still widely used. The increasing number of reports of refractory cases with this group of drugs and other antigiardial agents, has raised concern and led to a search for other compounds, some of which have arisen due to the introduction of drugs initially addressed to other diseases. The present article examines some of the most important points of antigiardial pharmacotherapy available at present and the future prospects of development of new agents.

Giardiasis: The Ever-Present Threat of a Neglected Disease

Although giardiasis has been a threat to mankind for thousands of years, this protozoan infection was, until recently, relatively neglected. Giardia duodenalis is recognised as a major cause of parasite-induced diarrhoea in humans and animals, and is currently an important public health problem, placing a heavy burden on both diagnostic and treatment services at health care institutions, mostly in developing countries, but also in highly developed countries. Steady progress in recent years, using a combination of molecular, immunological, and clinical approaches, has substantially increased our understanding of Giardia and important aspects of the clinical manifestations that it causes. The purpose of this review is to provide an overview of the extent of Giardia infection, the implications of water and food in Giardia transmission, new aspects regarding clinical diagnosis and environmental detection, treatment, and some approaches towards prevention and control. A number of future research priorities are also presented.

Treatment of intestinal protozoan infections in children

Intestinal protozoan infections are a worldwide problem in both industrialised and unindustrialised countries; in the latter they may be the cause of significant morbidity and mortality. Children, in particular, are more likely to experience considerable morbidity. Most intestinal protozoan infections can cause acute or chronic diarrhoea in healthy individuals and may result in intractable, life-threatening illness in patients with immunosuppressive diseases such as AIDS. Adequate identification and treatment of these infections may provide significant benefit for individual patients and public health. This article presents an update on the pharmacotherapy currently available for amoebiasis, giardiasis and other intestinal protozoan infections.

Sexual transmission of giardiasis: A neglected route of spread?

Sexually transmitted infections (STIs) are often discussed in the context of syphilis, gonorrhea, herpes, chlamydiasis and AIDS. However, since the past 30 years of the last century, epidemiology and natural history studies have led to improved understanding of giardiasis as a STI, as a result of oral-anal sexual contact. Studies suggest that Giardia is an increasingly recognized infection that may be underdiagnosed under the STI context. Health care providers should maintain a high index of suspicion for Giardia, obtain suitable diagnostic tests to identify and screen those at high risk for this infection, institute appropriate therapy, counsel patients regarding treatment compliance, follow-up, encourage partner notification and teach strategies for preventing the transmission of this disease, including the discussion of the risk of enteric infections after oral-anal sexual contact. We summarize some data concerning the research and clinical literature on Giardia infection as a STI and identify the specific recommendations for control of giardiasis as STI that available evidence indicates can reduce its transmission.

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.

Mebendazole Compared with Secnidazole in the Treatment of Adult Giardiasis: A Randomised, No-Inferiority, Open Clinical Trial

To compare the efficacy and safety of mebendazole and secnidazole in the treatment of giardiasis in adult patients, a single-centre, parallel group, open-label, randomized non-inferiority trial was carried out. One-hundred and 26 participants who had symptomatic Giardia mono-infection took part in the study. Direct wet mount and/or Ritchie concentration techniques and physical examinations were conducted at the time of enrolment and at the follow-up visit. The primary outcome measure was parasitological cure, performed at 3, 5, 10 days post-treatment. Negative faecal specimens for Giardia were ensured by the same parasitological techniques. At follow up (day 10) the parasitological cure rate for the per protocol populations was 88.7% (55/62) for MBZ and 91.8% (56/61) for SNZ. For the intention to treat populations the cure rate at the end of treatment was 85.9% (55/64) for MBZ and 90.3% (56/62) for SNZ. Both analyzes showed there was not significant statistical difference between MBZ and SNZ treatment efficacy. Both drugs were well tolerated, only mild, transient and self-limited side effects were reported and did not require discontinuation of treatment. A 3-day course of mebendazole seems to be as efficacious and safe for treatment of giardiasis as a single dose of secnidazole in adults.

Variaciones en las manifestaciones clínicas de la giardiosis en pacientes pediátricos hospitalizados, según grupos de edades

INTRODUCTION It has been suggested that the clinical features of giardiasis might vary in patients of different age groups. OBJECTIVE To compare clinical presentation of giardiasis in children less than 5 years of age and older children. METHODS A retrospective study of patients hospitalized with giardiasis during 2007 was performed. The clinical features of the two age groups were compared. Additionally, length of stay was analyzed. RESULTS In total, 170 patients were included. In children ≥ 5 years of age, abdominal pain and urticaria were significantly more frequent (OR=9.46; 95%CI: 4.35-20.52,P5=0.000+ and OR=11.0; 95%CI: 1.205-101.11, P=0.023, respectively). Diarrhoea was more frequently found in children younger than 5 years (OR=6.45; IC 95%: 3. 12-13.37, P=0.000+). The frequencies of other symptoms were similar. Length of stay was significantly higher in children under 5 years of age. DISCUSSION AND CONCLUSIONS Clinical presentations differed in some aspects among the examined age group of our paediatric patients. Our finding might be of importance for an early recognition of giardiasis, which is essential for an accurate diagnosis and a prompt treatment.

An Old Drug Against Giardiasis: Mebendazole as a Treatment Option

Lalle recently reviewed Giardiasis in the Post Genomic Era: Treatment, Drug Resistance and Novel Therapeutic Perspectives [1], and did not include mebendazole (MBZ) as an effective drug against giardiasis. Certainly, even when MBZ was found to be ineffective by Gascon et al. [2], and di Martino et al. [3], its use has been proposed for some authors as a potential candidate for this parasitic disease since it has evident effects in vitro and in vivo. Various drug regimens have been assayed against giardiasis, mainly in children, to find out the best option in this relatively novel indication (see Table 1). According to the results obtained, MBZ appears to be also an important option for the treatment of G. lamblia infections, at least, in children. It should be noticed that the use of this drug, additinally, has some advantages including the lower incidence of mild and selflimited adverse events -maybe due to its poor absorption from the gastrointestinal tract-, the lack of interference with the normal flora and the possibility of clear or reduce the parasitic burden of some of the common intestinal helminths with may co-occur, reducing – indirectly, at the same timethe environment contamination with eggs of other sensitive organisms, e.g., intestinal nematodes, which are especially frequent in tropical climates throughout the world. We may state, as a conclusion, that MBZ seems to have its role in the treatment of children with giardiasis and might be considered as an alternative, especially when first-line drugs have failed, were not tolerated or are not available. Also, MBZ could be possible taken as adjunctive therapy in combination with other available antigiardial drugs in order to obtain higher cure rates.

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.