Anthelmintic drugs for treating ascariasis

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To evaluate drug regimens for treating A. lumbricoides infection.

Background

Ascaris lumbricoides, also known as roundworm, is a soil-transmitted helminth that infects humans and animals. It is common throughout the world, affecting mainly tropical and subtropical areas such as sub-Saharan Africa and Southeast Asia (Bethony 2006; WHO 1981; WHO 2002; WHO 2011a). Between 2003 and 2005, an estimated 4.2 billion people were exposed to A. lumbricoides (de Silva 2003), resulting in between 807 to 1221 million people infected globally (Bethony 2006) and an annual infection incidence of approximately 10.5 million cases (Crompton 2001). Complications related to ascaris infection cause more than 60,000 deaths annually (WHO 2001; WHO 2011a). The most affected groups are children of preschool and school age of both genders (Xu 1995).

Ascariasis is transmitted through the faecal-oral route. Infection occurs when food, utensils, or hands contaminated with embryonated eggs are ingested. The eggs hatch in the small intestine, releasing the larvae that pass through the intestinal wall and migrate through the liver and heart, up to the lungs. In the lung passage, the larvae are expectorated and swallowed, passing through the gastrointestinal tract until they arrive at the small intestine, where they mature into adults worms and produce new eggs that are expelled with faeces contaminating the environment (CDC 2009; WHO 2001; WHO 2011a). Reinfection occurs only when contaminated eggs are ingested, since these parasites do not multiply in the human host (WHO 2011a). The distribution of A. lumbricoides in the community can be either aggregated or over-dispersed, with most infected people harbouring few or no worms, and a small proportion of infected people harbouring a very high number of worms (Holland 2009).

The relationship between A. lumbricoides infection and socioeconomic variables is intense, as soil-transmitted helminth infections are linked to a lack of sanitation and poverty (Stepek 2006; WHO 2011a). Others factors such as unhygienic housing conditions, precarious health care, and poor educational or financial resources result in difficulties in the management of ascariasis, especially among economically disadvantaged groups (Bethony 2006 ; WHO 2001 ; WHO 2002; WHO 2005; WHO 2011a).

Description of the condition

In general, people infected with A. lumbricoides are asymptomatic. However, the infection can manifest as abdominal discomfort, anorexia, diarrhoea and vomiting (Bethony 2006; Jardim-Botelho 2008), and is associated with both chronic and acute morbidity, particularly in growing children. Specialists consider nutritional impairment as a common presentation, mainly manifested by anaemia. A. lumbricoides infection can also result in an allergic inflammatory response to parasites and parasite antigens in infected people. A classic example is the asthma-like illness, Loeffler's syndrome, caused by the passage of A. lumbricoides larvae through the lungs. Also, exposure to A. lumbricoides can cause or increase asthma symptoms and bronchial hyperreactivity (Cooper 2009; Leonardi-Bee 2006). A. lumbricoides is a persistent parasite and may impact upon a person's immune responses and the transmission and recognition of other pathogens. The bystander chronic infection is associated with increased susceptibility to other pathogens as well as reduced vaccine efficacy (Stelekati 2012). Complications of A. lumbricoides infection are related to intestinal or biliary obstruction, or both, that lead to pancreatitis, cholecystitis, cholangitis, appendicitis, intestinal volvulus, perforation of an intestinal segment and peritonitis (Hefny 2009; Khuroo 1990; Pawlowski 1985). Notably, the same clinical features can occur in people infected with Ascaris suum, which is a similar species with characteristics that make it be very difficult to distinguish from A. lumbricoides infection (Crompton 1989). It is likely that both species co-occur especially in places where pigs and humans coexist (Kofie 1983; Maruyama 1997).

Helminth infection can cause damage to the intestinal mucosa of the infected person, resulting in malabsorption of nutrients by the person's digestive system. Also, the helminth competes for nutritional resources with its human host (Hall 2008; Stepek 2006; WHO 2011a) and can cause lactose intolerance (Hall 2008; Stephenson 2000). Poor school attendance and low cognitive performance are associated with ascariasis infection in school age children. Comparisons between infected and uninfected children have shown a lower academic performance of infected children at school, mainly when the children harboured moderate to heavy infections (Bethony 2006; De Silva 2003; Stepek 2006; Stephenson 2000; WHO 2000; WHO 2011a). Treatment of A. lumbricoides infection, either alone or in combination with treatment for other helminth infections, is associated with improvements in appetite, weight gain and physical fitness in school children (Adams 1994; Stephenson 1993). A decrease in infection incidence and an improvement in nutritional status are likely to lead to improvements in children's school performance (Nokes 1992; Stepek 2006).

Diagnosis

Peripheral eosinophilia occurs during migration of larval A. lumbricoides through the infected person's lungs, but sometimes appears at other stages of A. lumbricoides infection (Ehrhardt 2008). In heavily-infected individuals, a mass of worms may be detectable following plain X-ray of the abdomen. The worms contrast against the gas in the bowel, typically producing a 'whirlpool' effect (Reeder 1998). Ultrasound and endoscopy are useful for diagnosis of hepatobiliary and pancreatic duct involvement (Reeder 1998). Computed tomographic (CT) scanning or magnetic resonance imaging (MRI) may identify worms in the liver or bile ducts but are not usually necessary (Khuroo 1985; Khuroo 1990).

Parasitological diagnosis of ascariasis is made by examining stool specimens for the microscopic identification of eggs. Characteristic eggs may be seen on direct examination of faeces or by using concentration techniques (CDC 2009). Faecal smears and the Kato–Katz technique, also referred to as Kato thick smear exam, consist of microscopic examination of a known amount of faecal material that permits an egg count to be performed (Katz 1972; Santos 2005; WHO 2001; WHO 2011a). This method is widely used to confirm ascariasis infection and is recommended by the World Health Organization (WHO) as the standard method for evaluating prevalence and intensity of soil-transmitted helminthiasis in endemic communities. It is an easy technique to use in field situations or when a great number of specimens need to be examined. However, it requires well-trained laboratory technicians and quality control measures to ascertain accurate diagnosis of ascariasis and other helminth infections (Bergquist 2009; Montresor 1998; Pawlowski 1985; WHO 1991). Also, the stool filtration method, which has been previously described for finding S. mansoni eggs in stool samples, is an option to detect A. lumbricoides eggs (Bell 1975). Intensity of infection is measured in terms of eggs per gram (epg) of faeces and is classified as either a light-intensity infection (between 1 to 4999 epg, a moderate-intensity infection (between 5000 to 49,999 epg) or a heavy-intensity infection (≥ 50,000 epg) based on the report of WHO Expert Committee (WHO 2002). Adult worms are occasionally present in the stools. They may pass through the mouth, nose or rectum and are recognizable by their macroscopic characteristics (WHO 2011a).

Description of the intervention

Interventions against worm infection include deworming using anthelminthic drugs, improvement of water and sanitation, and health education. The WHO recommends three public health drug treatment policies (WHO 2011a):

  • Selective: individual deworming based on a diagnosis of infection.

  • Targeted: group deworming where a (risk) group is treated without prior diagnosis.

  • Universal: population deworming in which the whole community is treated irrespective of infection status.

The WHO considers the target groups for drug treatment to be pre-school-age children (aged between one and five years), school-age children (aged between six and 15 years) and women of childbearing age. The recommended frequency of treatment is once per year for low-risk communities with between 20% to 50% infection prevalence, or twice per year for high-risk communities with > 50% infection prevalence (WHO 2011a). However, the evidence to recommend deworming drugs in targeted community programmes is not clear. According to a recent systematic review (Taylor-Robinson 2012), community deworming seems to have little or no effect on haemoglobin levels of the infected person. Also, there was poor evidence on the effect of community deworming on cognition, school attendance and performance, with no obvious or consistent effect.

Anthelmintic drugs listed on the WHO Model List of Essential Medicines for deworming drugs of geo-helminths (WHO 2000) include albendazole, levamisole, mebendazole, pyrantel and ivermectin. Nitazoxanide, piperazine, tetrachlorethylene and thiabendazole are also used. Benzimidazoles (albendazole and mebendazole) are effective low cost drugs and are used to treat a variety of parasitic infestations by interfering with the parasitic worm's microtubular system (Utzinger 2004). The ease of administration,availability and accumulated scientific knowledge showing high efficacy resulted in this drug being widely used in large scale treatment and control of soil-transmitted helminthiasis and preventive chemotherapy (Bennett 2000; Keiser 2008; WHO 2002). Single-dose albendazole achieves high cure rates againstA. lumbricoides infection (Venkatesan 1998) and resulted in a 100% cure rate in one trial (Belizario 2003). Mebendazole is an equivalent alternative to albendazole and may cause the same adverse effects, such as transient gastrointestinal discomfort, headache and leukopenia. Both albendazole and mebendazole are donated to national ministries of health through the WHO and other organizations and are the drugs of choice in helminth control programmes (WHO 2012). Levamisole and pyrantel palmoate act as nicotinic acetylcholine receptor agonists (Utzinger 2004). Levamisole has been studied less intensively, and the availability of this drug is limited, but it is currently considered a safe and effective drug. In mass treatment it showed significant differences in pre- and post-treatment in the egg count value (Asaolu 1991). Pyrantel pamoate is cited in the WHO Essential Drugs Guideline as an anthelmintic drug and was reported as an effective single-dose drug for treating ascariasis in a recent systematic review and meta-analysis (Keiser 2008; WHO 2000). Ivermectin is most commonly used to treat lymphatic filariasis, onchocerciasis, loiasis and strongyloidiasis. It is also moderately effective against T. trichiura and is approved for treating human ascariasis. It causes paralysis of adult worms and seems to be effective (Wen 2008). Piperazine citrate acts paralysing the worms, which aids expulsion from the infected person's body (del Castillo 1964). However, it is now being withdrawn from the market as other drug alternatives are less toxic and more efficacious. Nitazoxanide is a new antiprotozoal drug reported as an effective choice against a broad range of parasites, including A. lumbricoides (Fox 2005; Galvan-Ramirez 2007). This drug has been listed as a potential drug candidate for human-soil transmitted helminthiasis and further research has been suggested (Diaz 2003). Anthelmintic drugs not registered for this purpose but occasionally compared with these drugs are praziquantel and diethylcarbamazine (Belizario 2003; Long 2007; WHO 2000).

How the intervention might work

Ascariasis causes a high disease burden worldwide. Health education and sanitation improvements are very important to reduce the number of people infected. However, drug treatment of infected individuals is necessary to break the cycle of transmission (Bethony 2006; WHO 2005). Infected individuals should be treated with drugs to remove adult worms from the gastrointestinal tract and reduce disease transmission (WHO 2001). The use of anthelminthic drugs focuses on the treatment of symptomatic infections, however drugs are used also to reduce morbidity in endemic communities (Bethony 2006).

Some randomized trials suggests that poor cognitive performance, malnutrition and anaemia may be potentially reversible following treatment with anthelmintic drugs (Hall 2008 ; Stepek 2006). Even when a person has concomitant infections, such as hookworm, Trichuris trichiura or Schistosoma haematobium infection, treatment may improve nutritional status (Adams 1994; Stephenson 1993). A recent systematic review suggested that selective deworming probably increases weight and may increase haemoglobin in children confirmed to have worms on the basis of screening (Taylor-Robinson 2012).

Why it is important to do this review

Ascariasis remains a neglected disease despite its distribution and the overall number of infected individuals. Also, A. lumbricoides and other helminth infections can affect the infected person's immune system and alter susceptibility to other parasitic diseases, such as malaria. Previous studies suggest that large-scale deworming programmes can have a protective effect on malaria morbidity in children (Kirwan 2010; Stelekati 2012). The main goals of deworming programmes are to reduce the number of heavily infected people; reduce environmental contamination and risk of infection for other people; reduce micronutrient loss (eg iron loss through intestinal bleeding in hookworm infection); improve nutritional status, cognitive functions and learning abilities (WHO 2011a). Although many anthelmintic drugs exist, the most effective regimen and the optimal doses to treat ascariasis are not well known.

Some authors have said that wide scale administration of anthelmintics exerts increasing drug pressure on parasite populations and favour parasite genotypes that can resist anthelmintic drugs (Vercruysse 2011). Occurrence of resistance to anthelmintics in nematode populations has been described in veterinary medicine and highlights the potential for treatments used frequently in chemotherapy programs to select drug-resistant worms (Wolstenholme 2004). For example, reduction in the efficacy of mebendazole compared with historical controls has been documented in studies in Zanzibar and Vietnam (Albonico 2003; Flohr 2007).

The WHO have highlighted the need to closely monitor anthelmintic drug efficacy (Vercruysse 2011). Currently there are few research-based studies about anthelmintic drugs, a very limited number of drugs that do not meet all needs in terms of efficacy and there are no new anthelmintic drugs in late-stage development (Geary 2010). Recently, the first well-designed systematic review and meta-analysis to assess the efficacy of albendazole, mebendazole, levamisole and pyrantel pamoate was published (Keiser 2008). It included 20 randomized trials and assessed the efficacy of single-dose oral  against A. lumbricoides, and showed consistent high cure rates and a significant reduction on the intensity of the infection. However, it confirmed that there was a paucity of high quality trials regarding anthelmintic treatment and the majority of trials were carried out more than 20 years ago, and reinforced the need for new trials and the evaluation of new anthelmintic drugs used.

Objectives

To evaluate drug regimens for treating A. lumbricoides infection.

Methods

Criteria for considering studies for this review

Types of studies

Randomized controlled clinical trials (RCTs) that randomize individual patients or clusters (eg household) will be included.

Types of participants

Adults and children with ascariasis. Eligible studies must diagnose ascariasis by microscopic identification of A. lumbricoides eggs in the stool, direct examination of faeces or by using concentration techniques.

Types of interventions

We will include drugs used for treating ascariasis listed on the WHO Model List of Essential Medicines for deworming (WHO 2011b). These include albendazole, mebendazole, levamisole, pyrantel and ivermectin. Other drugs used are nitazoxanide, piperazine, tetrachlorethylene and thiabendazole.

We will include studies examining the use of the existing drugs either as a monotherapy, or as a combined therapy, in single dose or in multiple dose regimens.

If additional interventions are used they must be allocated to all patients included in the trial. The additional interventions can include, but not limited to, education, micronutrient supplementation, malaria chemoprevention or use of other drugs.

Control: No intervention, placebo, different doses of any of the drugs, or different combination of drugs.

Types of outcome measures

Primary outcomes
  • Cure rate at end of treatment (CR). We define 'cured' as eradication of parasites from stool samples

If timepoints of follow-up results are similar across studies we will stratify them into categories.

Secondary outcomes
  • Faecal egg count at end of treatment (FEC)

We will not include effects on nutritional indicators, haemoglobin and school performance. There is a specific systematic review about this topic already published (Taylor-Robinson 2012).

Adverse outcomes
  • Any kind of complication (intestinal or biliary obstruction, pancreatitis, cholecystitis, cholangitis, appendicitis, intestinal volvulus, perforation of an intestinal segment and peritonitis, etc.)

  • Serious adverse events (hospitalization, life threatening events or death)

  • Other adverse events

Search methods for identification of studies

We will attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press and in progress).

Electronic searches

We will search the following databases: Cochrane Infectious Disease Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; and LILACS using the search terms detailed in Appendix 1. We will also search the meta Register of Controlled Trials and the WHO Clinical Trials Search Portal using 'ascariasis*"' or 'roundworm as search terms.

Searching other resources

We will also check the reference lists of all trials and relevant articles identified by the above methods.

Data collection and analysis

Selection of studies

Two authors (MG and NM) will independently screen all citations and abstracts identified by the search against the inclusion criteria. MG and NM will independently obtain and assess potentially eligible articles for inclusion in the review using a pre-designed eligibility form based on the inclusion criteria. If there are any disagreements,we will consult the third author (LOC) and we will resolve it through discussion. We will document the reasons for the exclusion of studies that do not meet the inclusion criteria.

For multiple publications from the same trial, we will consider only one data set.

Data extraction and management

Two authors (MG and NM) will extract data independently from included studies using a data extraction form, detailed in Appendix 2. A third author (LOC) will check the data extraction. Overall, we plan to extract the number of patients randomized and analysed in each treatment group of each trial. For dichotomous outcomes, we plan to extract the number of patients with the event. For continuous outcomes, we will extract means and standard errors when possible. Otherwise we will try to extract medians and ranges or other summary statistics. Where change from baseline results are presented alongside results purely based on the end value, we only will extract the change from baseline results. For trials that randomize clusters and have adjusted for clustering in the analysis, we will try to extract a measure of effect and its standard error. We will try to extract the average cluster size, intra-cluster correlation coefficient (ICC), number of clusters and cluster type (Higgins 2011a). For cluster RCTs that did not adjust for clustering, we will extract the same data as for trials that individuals randomized. MG will input the data into a database. NM and LOC will check the data entered.

Assessment of risk of bias in included studies

Two authors (MG and NM) will independently assess the risk of bias in the included trials. This will be checked by a third author (LOC). We will assess the following six components: sequence generation; allocation concealment; blinding; incomplete outcome data; selective outcome reporting and other biases. For RCTs randomized by cluster, we will assess several additional components including: recruitment bias; baseline imbalance; loss of clusters; incorrect analysis; and compatibility with RCTs randomized by individual. For each of these components, we will place a judgment of risk of bias as low, high or unclear/unknown as described in Appendix 3. We will display the results in risk of bias tables, a risk of bias summary and a risk of bias graph (Higgins 2011a). We will resolve any disagreements through discussion with the third author (LOC).

Measures of treatment effect

We will summarize continuous data (means and standard deviations) using the mean differences. We plan to use the risk ratio to compare the treatment and control groups for dichotomous outcomes. We will present all treatment effects with 95% confidence intervals (CIs).

Unit of analysis issues

Cluster-RCTs

We will consider data as having been analysed correctly if either:

  1. the analysis was conducted at the same level as the allocation (ie at the ’cluster’ level); or

  2. the analysis was conducted at the level of the individual, but appropriate statistical correction for the clustering was performed

For cluster-RCTs when the analyses had not been adjusted for clustering, we will attempt to adjust the results for clustering by estimating the design effect calculated as 1+(m-1)*ICC where m is the average cluster size and ICC is the intra-cluster correlation coefficient. To make the adjustment, we will estimate a treatment effect that did not adjust for clustering and then multiply the standard errors of the estimate by the square root of the design effect. When the true ICC is unknown, we will estimate it from other included cluster-RCTs (Higgins 2011b).

If it is not possible to approximately correct the results, we will present the measure of effect and their CIs values in the results text or in a table.

Grading the quality of evidence

We will use the principles of the GRADE system (Schünemann 2011) to assess the quality of the body of evidence associated with all main outcomes. The GRADE approach appraises the quality of a body of evidence considering within study risk of bias, the directness of the evidence, heterogeneity in the data, precision of effect estimates and risk of publication bias. We will construct a Summary of Findings (SoF) table using the GRADE profiler software (GRADEpro).

Dealing with missing data

We will assess missing outcomes data and we will report its proportion. As far as possible, we will carry out analyses on an intention-to-treat principle for all outcomes. If there are missing data, we will perform a complete case analysis based on the patients for which an outcome was measured.

Assessment of heterogeneity

We will assess heterogeneity by visual inspection of the forest plot and we will use the I2 statistic and the Chi2 test with a P value of 0.1 to quantify it. We will investigate possible causes of heterogeneity in subgroup analyses.

Assessment of reporting biases

We will use a funnel plots to assess whether the review is subject to publication bias. If we detect asymmetry, we will explore causes other than publication bias. We will construct a funnel plot if we include 10 or more RCTs in the review.

Data synthesis

We will use Review Manager (RevMan) to perform analyses. We will combine the outcome measures from the individual trials in a meta-analysis to provide a pooled effect estimate if there are enough studies and if they are sufficiently similar in terms of anthelmintic drug and doses used. We will stratify the analyses according to the comparison (as in the types of interventions section) and by timepoint of follow-up. We will pool results from trials that randomize individuals and results from cluster RCTs that adjust for clustering in meta-analysis, using the generic inverse variance method. We will present results from trials that do not adjust for clustering in the text or additional tables and will be labelled as "other results". We will perform fixed-effect meta-analysis if there is no heterogeneity and random-effects meta-analysis if the assessment results reveal heterogeneity and the heterogeneity cannot be explained by doing subgroup analysis (Higgins 2011b). We will include only a single pair-wise comparison in each meta-analysis of studies with multiple intervention groups. If we consider all intervention groups to be considered eligible for the same meta-analysis, we will be combine the groups creating a single pair-wise comparison. We will combine all relevant experimental intervention groups into a single group and all relevant control groups into a single control group.

We plan to carry out the following comparisons:

Comparison 1: Any drug for treating ascariasis versus placebo or no intervention.

Comparison 2: Any combination of two or more drugs for treating ascariasis versus placebo or no intervention.

Comparison 3: Any drug for treating ascariasis versus a different drug for treating ascariasis.

Comparison 4: Any combination of two or more drugs for treating ascariasis versus any single drug for treating ascariasis.

Comparison 5: Any combination of two or more drugs for treating ascariasis versus a different combination.

Comparison 6: Any dose of a drug for treating ascariasis versus a different dose of the same drug.

Comparison 7: Any doses of a combination of drugs for treating ascariasis versus different doses of the same combination of drugs.

Subgroup analysis and investigation of heterogeneity

If we detect heterogeneity by the assessment methods, we will conduct the following subgroup analyses: age (pre-school children, schoolchildren and adults); duration of follow-up; intensity of infection (according to WHO classification); geographical region (Asia, Africa, Mediterranean basin and South America), decade of studies' publication.

Sensitivity analysis

We will perform sensitivity analyses based on the following characteristics below if sufficient numbers of studies are identified:

  1. We will repeat the meta-analyses to assess the effect of including only cluster designs

  2. We will repeat the meta-analyses to assess the effect of including studies 'low risk of bias' overall versus those identified as having a 'high risk of bias' overall (Higgins 2011a; Appendix 3)

  3. We will exclude studies with high levels of missing data (percentage of participants lost > 30%, or where differences between the groups exceed 10%, or both)

Acknowledgements

This protocol was funded by the São Paulo Research Foundation (FAPESP). The views expressed in this protocol are not necessarily those of FAPESP.

The editorial base of the Cochrane Infectious Diseases Group is funded by UKaid from the UK Government for the benefit of developing countries. The academic editor for this protocol was Professor Paul Garner.

Appendices

Appendix 1. Search methods: detailed search strategies

Search set CIDG SR^ CENTRAL MEDLINE

 

EMBASE

 

LILACS

1Ascari*Ascariasis [MeSH]Ascariasis [MeSH]Ascariasis [Emtree]Ascari$
2albendazoleAscaris [Mesh]Ascaris [Mesh]Ascaris ti, abalbendazole
3mebendazoleAscari* ti, abAscari* ti, ab1 OR 2mebendazole
4levamisole1 OR 2 OR 31 OR 2 OR 3Albendazole [Emtree]levamisole
5ivermectinAlbendazole [MeSH]Albendazole [MeSH]Mebendazole [Emtree]ivermectin
6pyrantelMebendazole [MeSH]Mebendazole [MeSH]Levamisole [Emtree]pyrantel
7piperazineLevamisole [MeSH]Levamisole [MeSH]Ivermectin [Emtree]piperazine
8nitazoxanideIvermectin [MeSH]Ivermectin [MeSH]Pyrantel palmoate ti, abnitazoxanide
9tetrachlorethylenePyrantel palmoate [MeSH]Pyrantel palmoate [MeSH]Piperazine citrate [Emtree]Tetrachlorethylene
10thiabendazolePiperazine citrate ti, abPiperazine citrate ti, abNitazoxanide [Emtree]Thiabendazole
11tiabendazoleNitazoxanide ti, abNitazoxanide ti, abTetrachlorethylene [Emtree]2-10/OR
122-11/ORTetrachlorethylene [MeSH]Tetrachlorethylene [MeSH]Thiabendazole ti, ab1 AND 11
131 AND 12Thiabendazole [MeSH]Thiabendazole [MeSH]Tiabendazole [Emtree] 
14 Tiabendazole ti, abTiabendazole ti, ab4-13/OR 
15 5-14/OR5-14/OR3 AND 14 
16 4 AND 154 AND 15Limit 15 to Humans 
17  Limit 16 to Human  
 ^Cochrane Infectious Diseases Group Specialized Register    

Appendix 2. Data extraction form

Updated September 17, 2011

Source
Study ID  Version    Date  
Citation Review author ID ☐LOC     ☐MVFG     ☐NSM
Reference here
Eligibility

Author's explanation to confirm eligibility for review

 

Randomized Controlled Trial (RCT)

Cluster-RCT

Unclear

Reason for exclusion

 

Not a RCT   

Other

Unclear

Methods

Study design

Unclear

Not reported

RCT    

Cluster -RCT

Quasi-RCT

Cohort Study

Case control study

Cross-sectional study

Other

 

Total study duration

Unclear  Not reported

 
Participants

Total number

Unclear  Not reported

All groups:

Ascaris groups:

 

Others:

Setting/Inclusion criteria

Unclear  Not reported

 

Diagnostic criteria

Unclear  Not reported

 
Age ☐Unclear  Not reported 
Sex ☐Unclear  Not reported 
Country ☐Unclear  Not reported 
Co-morbidity ☐Unclear  Not reported  

Socio-demographics

Unclear  Not reported

 
Ethnicity  ☐Unclear  Not reported  
Date of study ☐Unclear  Not reported 
Interventions

Total number of intervention groups    

Unclear  Not reported

 
Group 1: Group 2:
Intervention  Intervention  
Participants (n)  Participants (n)  
Group 3: Group 4:
Intervention  Intervention  
Participants (n)  Participants (n)  
Outcomes
For each outcome of interest:
Outcome 1 
 ☐Collected  ☐Reported ☐Unclear  ☐Not reported

Outcome definition (with diagnostic criteria if relevant)

Unclear  Not reported

  

Include unit of measurement (if relevant)

☐Unclear  ☐Not reported

Results

Results should be collected only for the outcomes specified to be of interest in the protocol

For each outcome of interest:
Outcome 1  
Sample size ☐Unclear  Not reported  
Missing participants* ☐Unclear  Not reported  

Summary data for each intervention group

(e.g. 2×2 table for dichotomous data; means and SDs for continuous data)

Unclear  Not reported

 
Estimate of effect with confidence interval; P value ☐Unclear  Not reported 
Subgroup analyses ☐Unclear  Not reported  
Follow-up
Intervention      
Time Evaluation 1st time 2nd time 3rd time 1st time 2nd time 3rd time 1st time 2nd time 3rd time
                 
Outcome 1                  
Number of stool samples                  
Number of participants                  
Number of missing participants                  
Number of participants cured                  
% participants cured                  
Miscellaneous
Funding source 
Ethical approval 
Key conclusions of the study authors 
Miscellaneous comments from the study authors 
References to other relevant studies  
Correspondence required  
Miscellaneous comments by the review authors  
Risk of Bias table
Sequence generation
Description

 

☐Adequate                      ☐Inadequate                   ☐Unclear

Judgment☐High risk                       ☐Low risk                        ☐Unclear
Allocation concealment
Description

 

☐Adequate                      ☐Inadequate                   ☐Unclear

Judgment☐High risk                       ☐Low risk                        ☐Unclear
Blinding of participants and personnel
Description

 

☐Adequate                      ☐Inadequate                   ☐Unclear

Judgment☐High risk                       ☐Low risk                        ☐Unclear
Blinding of outcome assessment
Description

 

☐Adequate                      ☐Inadequate                   ☐Unclear

Judgment☐High risk                       ☐Low risk                        ☐Unclear
Incomplete outcome data
Description

 

☐Adequate                      ☐Inadequate                   ☐Unclear

Judgment☐High risk                       ☐Low risk                        ☐Unclear
Selective reporting
Description

 

☐Adequate                      ☐Inadequate                   ☐Unclear

Judgment☐High risk                       ☐Low risk                        ☐Unclear
Others bias
Description

 

 

☐Adequate                      ☐Inadequate                   ☐Unclear

Judgment☐High risk                       ☐Low risk                        ☐Unclear

 

Appendix 3. Authors judgment of risk of bias

Potential bias

Authors’ judgement

 

Random sequence generation (selection bias)

 

 

High - not randomized or quasi-randomized

Unclear - “randomized” stated, but method not reported

Low - describes method of randomization

 

Allocation concealment (selection bias)

High - not concealed, open label trial for individually randomized or method of concealment not adequate

Unclear - details of method not reported or insufficient details

Low - central allocation, sequentially numbered opaque sealed envelopes

 

Blinding (performance bias and detection bias)

 

High - personnel, participants or outcome assessors were not blinded

Unclear - no details reported, insufficient details reported

Low - personnel, participants and outcome assessors were blinded

Incomplete outcome data (attrition bias)

High - losses to follow-up not evenly distributed across intervention and control group, high attrition rate (20% or more for the main outcome)

Unclear - no details reported, insufficient details reported

Low - no losses to follow-up, losses below 20% and evenly distributed across groups, intention-to-treat analysis used

Note: for cluster RCTs, the loss relates to the clusters

Selective reporting (reporting bias)

High – did not fully report measured or relevant outcomes

Unclear – insufficient information reported to judge

Low – all expected outcomes were reported 

Other bias

Low – no obvious other source of bias of concern to reviewers

High – major source of bias such as unexplained differences in baseline characteristics

Contributions of authors

Lucieni Oliveira Conterno (LOC): conceived the review question, coordinated, edited and approved the protocol.

Marcos Garcia (MG): completed the first draft of the protocol, edited and approved the protocol, and is guarantor for the protocol.

Natália Mukai (NM): completed the first draft of the protocol, edited and approved the protocol.

 

Declarations of interest

LOC: None known

MG: None known

NM: None known

Sources of support

Internal sources

  • Marília Medical School - FAMEMA, Brazil.

External sources

  • Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP, Brazil.

Ancillary