5. Suggestions for a trial of antibiotic for Shigella dysentery.

Methods	Participants	Interventions	Outcomes	Notes
Allocation: Centralized sequence generation with table of random numbers or computer generated lists Stratified by severity of illness Sequence concealed until interventions are assigned Blinding: Those recruiting and assigning participants, those administering the intervention, and those assessing the outcomes, must all be blind to the allocated group; the administered drugs have to be identical or a double dummy technique has to be used. Liquid medications have to be in similar looking bottles, identical in shape and weight; the medications must themselves be similar in colour and flavour. Duration: Minimum of 4 weeks after completion of therapy to assess relapse	Entry criteria can be clinical dysentery, i.e. acute onset frequent loose stools with blood or mucus or both lasting for less than 72 hours and at least 3 stools per day. Other features, such as fever and tenesmus at presentation, have to be recorded but need not be necessary for inclusion into study. If it is possible to presumptively or decisively detect Shigella in stool before inclusion into study, it should be done. Real‐time PCR is a rapid but expensive method to diagnose Shigella early (Legros 2004). Sample size: (See Table 14). Age group: trials should be separately done for adults and children (less than 15 years of age) or at least presented separately if they are in the same trial. In children, infants must be a separate group. Setting: in‐ or out‐patients. The number of participants, if hospitalized for standardization of administration of the interventions, have to be reported separately from those hospitalized due to complications. Sex: men and women. Special groups (those who have higher risk of complications: Malnourished children HIV positive individuals Adults more than 50 years of age Infants Exclusion criteria: Allergy to the drug studied; history of antibiotic use for this episode of illness in the previous 48 hours; pregnant and lactating women; clinical presence of another infection needing antimicrobials	Any antibiotic studied for efficacy and safety Any other antibiotic that is the standard for the treatment of Shigella dysentery at that period of time in that country Others: placebos or probiotics to be studied only on those with no risk of complications and those who have mild illness	Primary outcomes: Number of patients with diarrhoea on follow up. Clinical relapse Adverse effects of antibiotics Life threatening adverse effects of the drug Those that require discontinuation of the drug MIld adverse events that need extra therapy but not discontinuation of the drug Duration of fever Duration of blood in stools Secondary outcomes: Removed from study due to clinical worsening Fever on follow up Abdominal pain on follow up Bacteriological cure Bacteriological relapse Duration of diarrhoea Duration of abdominal pain Number of days of hospitalisation	Once patients are randomized into the treatment groups, they should not be removed until final analysis. The trial author(s) must publish the outcome findings of the whole group first and then present data for those positive for Shigella by stool or rectal swab culture or PCR and those negative for Shigella. The data have to be presented according to the severity of illness the patients presented with. Antibiotic sensitivity patterns have to be reported for all antibiotics studied and in all groups Response to treatment stratified by in vitro antibiotic sensitivity also needs to be reported Drop‐outs: The patients who drop out after randomization due to loss of follow up, withdrawal from protocol or consent withdrawal etc have to be reported and accounted in the final analysis (intention‐to‐treat analysis).