Management of acute diarrhoea in diabetic patients using oral rehydration solutions containing glucose,rice, or glycine.

OBJECTIVE--To assess the risk of hyperglycaemia with two standard oral rehydration solutions that contain carbohydrate compared with a carbohydrate free solution during rehydration of diabetic patients with acute diarrhoea. DESIGN--Prospective randomised allocation to one of three oral rehydration solutions (World Health Organisation (glucose), rice, or glycine) groups after admission to hospital with acute diarrhoea. SETTING--Dhaka hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS--45 diabetic patients aged between 15 and 60 who had had diarrhoea for fewer than three days on admission. MAIN OUTCOME MEASURES--Fluctuation of blood glucose concentrations measured three times a day, daily stool output, and time taken for recovery from diarrhoea. RESULTS--There were no significant differences in blood glucose concentrations, stool output, and duration of recovery from diarrhoea among the three groups. CONCLUSIONS--Oral rehydration solutions containing glucose, rice powder, or glycine can be safely administered to diabetic patients with acute diarrhoea and some dehydration.     

Oral rehydration formula containing alanine and glucose for treatment of diarrhoea: a controlled trial.

OBJECTIVE--To determine whether adding L-alanine to the glucose based oral rehydration solution recommended by the World Health Organisation would improve its efficacy in treating acute diarrhoea. DESIGN--Randomised double blind controlled trial of oral rehydration solution containing L-alanine and glucose. SETTING--Inpatient service of a hospital treating diarrhoea. PATIENTS--97 Male patients aged 6-59 years admitted to the hospital with acute and severe dehydration due to diarrhoea associated with Vibrio cholerae or enterotoxigenic Escherichia coli. Forty nine received the standard glucose based oral rehydration solution (control group) and 48 this solution with alanine added (study group). INTERVENTIONS--All of the patients received rapid intravenous acetate solution for the initial four hours after admission, which fully corrected the signs of dehydration. They were then admitted to the study and randomised. Immediately after the intravenous treatment oral rehydration treatment was started. All of the patients received oral tetracycline for 48 hours, starting 24 hours after start of the study. If signs of dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until they were fully corrected and then continued to take the assigned oral rehydration solution. END POINT--Passage of the last watery stool. MEASUREMENTS and MAIN RESULTS--The median stool output/kg body weight during the initial 24 hours of oral rehydration treatment and until diarrhoea stopped was reduced in the study group compared with the control group from 309 ml to 196 ml and from 393 ml to 236 ml respectively. Intake of oral rehydration solution and intravenous acetate solution was reduced from 455 ml to 308 ml and from 616 ml to 425 ml respectively. Two patients in the study group compared with 18 patients in the control group required unscheduled rapid intravenous acetate solution to correct signs of dehydration during oral rehydration treatment. CONCLUSION--Oral rehydration solution containing L-alanine was considerably better than standard oral rehydration solution at reducing the severity of symptoms and the need for fluid of male patients with diarrhoea associated with V cholerae and enterotoxigenic E coli.     

Proabsorptive effect of glycerol as a glucose substitute in oral rehydration solutions

We hypothesized that glycerol, a readily diffusable hydrophilic substance, may effectively substitute for glucose and enhance intestinal water and sodium absorption in an oral rehydration solution (ORS). This was evaluated using a low osmolality (230-240 mOsm/kg) ORS containing 75 mmol/L sodium and a combination of glucose:glycerol (in mmol/L) 75:0, 50:25; 37.5:37.5, 25:50, 10:65, or 0:75 during 3-hour long in vivo rat jejunal perfusions. Water, sodium, potassium, glucose and glycerol absorption, and unidirectional fluid movement (J(in), J(eff)) were determined. Sodium and net water absorptions were maximal at glucose:glycerol ratios between 37.5:37.5 and 10:65 mmol/L. In the absence of glucose (0:75), absorption of water and electrolytes was lower than at any other concentration. The greater net rehydration seemed to be due to a higher J(in) as glycerol was increased up to 65 mmol/L. Potassium absorption followed a similar pattern. With 50 mmol/L glycerol and 25 mmol/L glucose, there was a marked expansion of the lamina propria extracellular space and increased intercellular expansion between enterocytes. These results indicate that glycerol may be an effective partial substitute for glucose in ready-to-use ORS by producing an improved rate of water and electrolyte absorption.     

Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials.

OBJECTIVE--To define the benefit of rice oral rehydration salts solution in relation to the glucose based World Health Organisation oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhoea. DESIGN--Meta-analysis using data from 13 available randomised trials that compared these two formulations. SUBJECTS--The studies compared 1367 patients with cholera, severe cholera-like diarrhoea, or acute non-cholera diarrhoea. 668 received the standard WHO solution and 699 the rice based solution. INTERVENTION--Each trial report was reviewed to determine patient eligibility, the number of patients who were randomised and the number of these excluded from analysis, details of the randomisation procedure, and the precise timing of the outcome measurements. MAIN OUTCOME MEASURES--Stool output during the first 24 hours; weighted estimates of the difference in mean stool output between treatments. RESULTS--The rice solution significantly reduced the rate of stool output during the first 24 hours by 36% (95% confidence interval 28 to 44%) in adults with cholera and by 32% (19 to 45%) in children with cholera. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only 18% (6 to 30%). CONCLUSIONS--The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in such patients. The benefit is considerably smaller for children with acute, noncholera diarrhoea and should be more precisely defined before its practical value can be judged.     

Randomised double blind trial of single dose doxycycline for treating cholera in adults.

OBJECTIVE--To compare the efficacy of a single dose of doxycycline (200 or 300 mg) with the standard multiple doses of tetracycline in patients with cholera. DESIGN--Randomised double blind controlled trial. Patients were given a single 200 mg dose of doxycycline, a single 300 mg dose of doxycycline, or multiple doses of tetracycline (500 mg, six hourly intervals). SETTING--Hospital in Bangladesh treating diarrhoea. PATIENTS--261 Patients aged over 15 admitted to the hospital with severe dehydration due to acute watery diarrhoea associated with Vibrio cholerae. All vibrios isolated from the stools and rectal swabs of patients, including those patients with prolonged excretion of vibrios, were sensitive to tetracycline. The stools of all patients at admission were negative for shigella and salmonella. INTERVENTIONS--All patients received rapid intravenous acetate solution for the first four hours after admission to hospital. They were then entered in the study and randomised. Oral rehydration was started immediately after the intravenous treatment. If signs of severe dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until dehydration was fully corrected. MAIN OUTCOME MEASURES--Stool output in first 24 hours and till diarrhoea stopped, total intake of oral rehydration fluid, duration of diarrhoea, and excretion of vibrio after receiving antibiotic treatment. RESULTS--The median stool outputs during the first 24 hours (275 ml/kg body weight) and till diarrhoea stopped (296 ml/kg body weight) were significantly higher in patients receiving 200 mg doxycycline as a single dose than in patients receiving either standard tetracycline (242 ml/kg body weight and 254 ml/kg body weight) or 300 mg doxycycline (226 ml/kg body weight and 255 ml/kg body weight). Similarly, median consumption of oral rehydration solution (18.45 l) was significantly higher in patients receiving 200 mg doxycycline than in patients receiving either 300 mg doxycycline (16.10 l) or standard tetracycline (14.80 l). Almost equal numbers of patients in each group required unscheduled intravenous acetate solution to correct dehydration during antibiotic treatment. Patients treated with doxycycline (low or high dose), however, had more prolonged excretion of bacteria. CONCLUSIONS--A single 300 mg dose of doxycycline is as effective as the standard multiple dose tetracycline treatment for cholera in terms of stool output, duration of diarrhoea, vomiting, and requirement for oral rehydration solution.     

Intravenous rehydration for diarrheal dehydration of eutrophic children: survey of protocols provided at Colombian medical schools

Introduction. In all cases of severe dehydration from diarrhea, WHO recommends rapid rehydration. If oral rehydration in children is contraindicated, intravenous rehydration is recommended for immediate administration. However, methods of intravenous rehydration appear to be inadequately addressed in the medical schools of Colombia. Objective. Current approaches to oral rehydration were summarized, and instructors were informed concerning current WHO recommendations. Materials and methods. A survey was designed for pediatric instructors in Colombian medical schools. Direct questions about rehydration methods were included as well as presentation of theoretical clinical situations with dehydrated children. The survey also asked for the conditions necessary for intravenous rehydration and method of administration (volume, solution, concentration and speed of infusion). Results. Forty-one surveys were included (82% of medical schools in Colombia). Inadequate contraindications for oral rehydration therapy were made in 41%. Rapid and slow intravenous rehydration was recommended in 71% and 29%, respectively; 57% recommended fluid bolus to rehydrate. Adequate volumes were recommended by less than half of the respondents and adequate sodium concentration was recommended by 85%. In 56% of medical schools, glucose was not included in solutions and 66% use Ringer lactate. Normal saline solution, dextrose solution with electrolytes and polyelectrolytes solutions are also used. Conclusions. Misconceptions are common concerning the contraindications to oral rehydration therapy. One-third of medical schools promote a slow therapy despite the superiority of the rapid therapy. Uniformity for rapid therapy schemes is lacking. Bolus rehydration is commonly advocated despite the fact that this method is unsupported by the literature. Concepts about rehydration must be updated in medical schools and a national guide for intravenous rehydration is recommended.     

Control of diarrhoeal disease in Tonga 1978-83.

Tonga, like many developing countries, suffers from a shortage of medical staff and a high morbidity and mortality from paediatric diarrhoeal disease. In 1980 a programme was started to train medical assistants and village administrators in the correct use of oral rehydration salt solution for rehydration. The effect on morbidity, mortality, and admission to hospital over the six years 1978-83 was assessed. After the introduction of the scheme the number of deaths due to diarrhoea fell considerably and the state of hydration in children admitted to hospital with diarrhoea greatly improved. It is recommended that similar programmes be adopted where clinical problems of diarrhoea with dehydration persist. Instruction in the use of oral rehydration fluid was most effectively given by non-medical staff to groups of mothers, rather than by paediatricians in their inevitably brief, although important, explanation given in hospital.     

Effect on clinical outcome of breast feeding during acute diarrhoea.

The effects of oral rehydration fluid alone and of oral rehydration fluid plus breast feeding on the course and outcome of acute diarrhoea were assessed in two groups of 26 children aged under 2 years. Children who continued to be breast fed during treatment with oral rehydration solutions passed significantly fewer diarrhoeal stools. They also passed, on average, a smaller volume of diarrhoeal stools and recovered from diarrhoea sooner after the start of treatment. Their requirement for oral rehydration fluid was significantly reduced. Breast feeding exerts a beneficial effect on the course and outcome of acute diarrhoea by reducing the number and volume of diarrhoeal stools.     

Loperamide in acute diarrhoea in childhood: results of a double blind,placebo controlled multicentre clinical trial. Diarrhoeal Diseases Study Group (UK).

A total of 315 young children with acute diarrhoea were included in a double blind, hospital based multicentre trial of loperamide at two dose levels (0.8 mg and 0.4 mg/kg/24 h), given with standard oral rehydration therapy versus placebo plus oral rehydration therapy. The overall recovery rate was slowest in the placebo group and fastest in the group given loperamide 0.8 mg. Comparisons between weights on admission and weights by day 3 showed that a larger proportion of children in the loperamide groups gained weight than in the placebo group. No serious side effects of loperamide were observed, but the drug was withdrawn in one infant because of mild abdominal distention. The results indicate that loperamide, in the doses employed, is safe and may in selected cases be a useful adjunct to oral rehydration in the management of acute diarrhoea in well nourished children.     

口服补液减轻40%血容量失血大鼠肠组织缺血性损伤

目的：研究口服葡萄糖-电解质液（GES）对大鼠40%血容量失血时肠组织缺血性损伤的影响。方法：雄性SD大鼠,用氯胺酮-速眠新Ⅱ肌注复合麻醉后,行右颈动脉插管。随机分为3组（n=24）：GES对照组（GES）,失血性休克组（HS）和失血性休克＋口服GES液组（HS＋GES）。GES组：不放血,手术后口服GES;HS和HS＋GES组按全身血容量的40%分两次间隔15min放血制作失血性休克模型。HS＋GES组于失血后0.5h、1h和6h分3次给予3倍失血量的GES灌胃。用激光多谱勒血流仪测定失血后2h、4h和24h肠组织血流量（IBF）后,处死动物后取肠组织检测二胺氧化酶（DAO）和Na^＋-K^＋-ATP酶活性,测定肠组织含水率（WG）,并做病理学检查。结果：HS＋GES组IBF和Na-K-ATP酶活性均显著高于HS组（P〈0.05）,但显著低于GES组（P〈0.05）;失血各组肠WG显著高于GES组（P〈0.05）,24h时HS＋GES组WG显著低于HS组（P〈0.05）;HS＋GES组24hDAO活性均显著高于HS组（P〈0.05）,但显著低于GES组（P〈0.05）;失血后24h病理检查HS＋GES组肠组织水肿和充血改变比HS组明显减轻。结论：口服GES液能显著增加大鼠失血性休克早期IBF,提高Na^＋-K^＋-ATP酶和DAO活性,减轻肠组织水肿和缺血性损伤。     

The Molecular Basis for Control of ETEC Enterotoxin Expression in Response to Environment and Host

Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhoea in humans and neonatal farm animals. Annually, 380,000 human deaths, and multi-million dollar losses in the farming industry, can be attributed to ETEC infections. Illness results from the action of enterotoxins, which disrupt signalling pathways that manage water and electrolyte homeostasis in the mammalian gut. The resulting fluid loss is treated by oral rehydration. Hence, aqueous solutions of glucose and salt are ingested by the patient. Given the central role of enterotoxins in disease, we have characterised the regulatory trigger that controls toxin production. We show that, at the molecular level, the trigger is comprised of two gene regulatory proteins, CRP and H-NS. Strikingly, this renders toxin expression sensitive to both conditions encountered on host cell attachment and the components of oral rehydration therapy. For example, enterotoxin expression is induced by salt in an H-NS dependent manner. Furthermore, depending on the toxin gene, expression is activated or repressed by glucose. The precise sensitivity of the regulatory trigger to glucose differs because of variations in the regulatory setup for each toxin encoding gene.     

再水合溶液能有效改善急性脱水女举重运动员的运动表现

本研究旨在探讨女子举重运动员急性脱水后口服4种不同组成的溶液,对液体存留率、胃肠道舒适度、血液值和无氧动力的影响。本研究以12位大学生女子举重运动员为对象,采交叉、平衡次序设计;研究参与者于脱水2%体重后分别补充相当于1.5倍脱水量的低渗透压电解质液(HES)、等渗透压电解质液(IES)、运动饮料(SB)或纯水(W),补充时间为脱水后立即、再水合期的30 min、60 min及90 min。再水合期间记录胃肠舒适分数、测量体重(计算液体存留率),并采集静脉血以测量血液渗透压、葡萄糖及钠、钾与氯离子,于脱水前与再水合期120 min时进行Wingate无氧动力测验。研究结果显示:补充HES、IES及运动饮料(SB)于再水合期90 min时的胃肠道舒适分数显著低于补充纯水(W)、而补充3种溶液于再水合期60 min时的血糖值则显著高于补充纯水(W),补充HES于再水合期120 min时的血钾值显著高于补充运动饮料(SB)及纯水(W);但补充4种溶液后的无氧动力与液体存留率并无显著差异。本研究证实举重运动员急性脱水后补充4种不同口服再水合溶液并不会影响再水合后的无氧动力,但补充含有糖类及电解质的溶液能有较佳的胃肠道舒适度,并血糖与血液电解质有维持的效果。     

Acute diarrhoeal disease in rabbit: bacteriological diagnosis and efficacy of oral rehydration in combination with loperamide hydrochloride

Acute outbreaks of diarrhoea with high mortality rates are frequently observed in rabbits. Amongst various aetiological factors Escherichia coli or its toxins have been found to be commonly incriminated. Sulphonamides or antibiotics are used to treat rabbits with bacterial diarrhoea. The result of the antibiotic treatment is moderately successful. We had good results using oral rehydration treatment in combination with loperamide hydrochloride (Immodium) in a colony of rabbits with E. coli diarrhoea.     

The freeze-dried preservation of liposome encapsulated hemoglobin: a potential blood substitute

In this report, the ability of carbohydrates (trehalose, sucrose, and glucose) to preserve the blood substitute liposome-encapsulated hemoglobin (LEH) in the freeze-dried state is examined. The water-free stabilization of individual components of this blood substitute and LEH is reported. Lyophilization of hemoglobin solutions in the absence of carbohydrates results in significant oxidative degradation of Hb as measured by a large increase (approximately 60%) in methemoglobin. Hb samples lyophilized in increasing carbohydrate concentrations show reduced levels of methemoglobin, and at 0.5 M trehalose, sucrose, or glucose, these levels are reduced to nearly the same levels as unlyophilized controls. Storage of lyophilized Hb samples following rehydration at 4 degrees C shows the same rate of methemoglobin formation regardless of whether carbohydrates are present. This suggests that carbohydrates prevent Hb oxidation in the dry state but are less effective at retarding oxidative damage to Hb in solution. The addition of 0.25 M trehalose or sucrose to LEH results in the maintenance of liposomal size following lyophilization. In these experiments, glucose was least effective at inhibiting dehydration-induced LEH fusion. Lyophilization of LEH in 0.25 M trehalose or sucrose also results in significantly greater retention of the encapsulated hemoglobin following lyophilization and rehydration. These results suggest that the long-term stabilization of LEH in the dry state is a realizable goal.     

Randomised controlled trial comparing oral and intravenous rehydration therapy in children with diarrhoea.

OBJECTIVE--To determine the effectiveness of oral rehydration in children with moderate dehydration caused by gastroenteritis, and to compare the complications of oral and intravenous treatment. DESIGN--Randomised controlled trial. SETTING--Emergency department and infectious diseases ward in a large urban teaching hospital. PATIENTS--111 children aged 3-36 months who had been previously healthy, had had diarrhoea for seven days or less, had clinical signs of dehydration, and were not in shock. Six children were withdrawn because the diagnosis was incorrect (four in oral group, two in intravenous group) and one (oral group) was withdrawn at her parents'' request. INTERVENTIONS--Oral rehydration fluid was given by mouth or nasogastric tube, or both to 52 children. The remaining 52 received intravenous rehydration fluids but were allowed to drink. MAIN OUTCOME MEASURES--Success or failure of rehydration. Number of times child vomited or passed stool after starting treatment. Time taken to rehydrate. RESULTS--Oral treatment failed in two children (failure rate 3.8%, upper 95% confidence limit 11.6%) and intravenous treatment in none. Vomiting was more common in the oral group (p less than 0.01): 26 of 50 children (52%) in the oral group and 11 of 50 (22%) in the intravenous group vomited during rehydration. There was no significant difference between the two treatment groups in the number of stools passed during rehydration (p = 0.09). None of the children had serious complications of treatment. CONCLUSION--Rehydration by mouth or nasogastric tube is a safe and effective treatment for moderately dehydrated children with gastroenteritis.     

Clinical trial of berberine in acute watery diarrhoea.

Four hundred adults presenting with acute watery diarrhoea were entered into a randomised, placebo controlled, double blind clinical trial of berberine, tetracycline, and tetracycline and berberine to study the antisecretory and vibriostatic effects of berberine. Of 185 patients with cholera, those given tetracycline or tetracycline and berberine had considerably reduced volume and frequency of diarrhoeal stools, duration of diarrhoea, and volumes of required intravenous and oral rehydration fluid. Berberine did not produce an antisecretory effect. Analysis by factorial design equations, however, showed a reduction in diarrhoeal stools by one litre and a reduction in cyclic adenosine monophosphate concentrations in stools by 77% in the groups given berberine. Considerably fewer patients given tetracycline or tetracycline and berberine excreted vibrios in stools after 24 hours than those given berberine alone. Neither tetracycline nor berberine had any benefit over placebo in 215 patients with non-cholera diarrhoea.     

Glucose- but Not Rice-Based Oral Rehydration Therapy Enhances the Production of Virulence Determinants in the Human Pathogen Vibrio cholerae

Despite major attempts to prevent cholera transmission, millions of people worldwide still must address this devastating disease. Cholera research has so far mainly focused on the causative agent, the bacterium Vibrio cholerae, or on disease treatment, but rarely were results from both fields interconnected. Indeed, the treatment of this severe diarrheal disease is mostly accomplished by oral rehydration therapy (ORT), whereby water and electrolytes are replenished. Commonly distributed oral rehydration salts also contain glucose. Here, we analyzed the effects of glucose and alternative carbon sources on the production of virulence determinants in the causative agent of cholera, the bacterium Vibrio cholerae during in vitro experimentation. We demonstrate that virulence gene expression and the production of cholera toxin are enhanced in the presence of glucose or similarly transported sugars in a ToxR-, TcpP- and ToxT-dependent manner. The virulence genes were significantly less expressed if alternative non-PTS carbon sources, including rice-based starch, were utilized. Notably, even though glucose-based ORT is commonly used, field studies indicated that rice-based ORT performs better. We therefore used a spatially explicit epidemiological model to demonstrate that the better performing rice-based ORT could have a significant impact on epidemic progression based on the recent outbreak of cholera in Haiti. Our results strongly support a change of carbon source for the treatment of cholera, especially in epidemic settings.     

A case of cholera in Kingston,Ont.

A case of cholera occurred in Kingston, Ont. in 1974 in a traveller from South Africa. Treatment, based on an understanding of the pathophysiology of cholera diarrhea and the mechanism of action of the Vibrio cholerae enterotoxin on gastrointestinal fluid loss, consisted of correcting the severe loss of fluid and electrolytes and the metabolic acidosis, as soon as the patient could tolerate taking fluids orally, further fluid replacement consisted increasingly of oral administration of glucose and saline. Tetracycline therapy was given only to shorten the duration of the acute illness.     

Impact of NGO Training and Support Intervention on Diarrhoea Management Practices in a Rural Community of Bangladesh: An Uncontrolled,Single-Arm Trial

Purpose/Objective

The evolving Non-Governmental Organization (NGO) sector in Bangladesh provides health services directly, however some NGOs indirectly provide services by working with unlicensed providers. The primary objective of this study was to examine the impact of NGO training of unlicensed providers on diarrhoea management and the scale up of zinc treatment in rural populations.

Methods

An uncontrolled, single-arm trial for a training and support intervention on diarrhoea outcomes was employed in a rural sub-district of Bangladesh during 2008. Two local NGOs and their catchment populations were chosen for the study. The intervention included training of unlicensed health care providers in the management of acute childhood diarrhoea, particularly emphasizing zinc treatment. In addition, community-based promotion of zinc treatment was carried out. Baseline and endline ecologic surveys were carried out in intervention and control villages to document changes in treatments received for diarrhoea in under-five children.

Results

Among surveyed household with an active or recent acute childhood diarrhoea episode, 69% sought help from a health provider. Among these, 62.8% visited an unlicensed private provider. At baseline, 23.9% vs. 22% of control and intervention group children with diarrhoea had received zinc of any type. At endline (6 months later) this had changed to 15.3% vs. 30.2%, respectively. The change in zinc coverage was significantly higher in the intervention villages (p<0.01). Adherence with giving zinc for 10 days or more was significantly higher in the intervention households (9.2% vs. 2.5%; p<0.01). Child''s age, duration of diarrhoea, type of diarrhoea, parental year of schooling as well as oral rehydration solution (ORS) and antibiotic usage were significant predictors of zinc usage.

Conclusion

Training of unlicensed healthcare providers through NGOs increased zinc coverage in the diarrhoea management of under-five children in rural Bangladesh households.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02143921","term_id":"NCT02143921"}}NCT02143921     

The Recognition of and Care Seeking Behaviour for Childhood Illness in Developing Countries: A Systematic Review

Background

Pneumonia, diarrhoea, and malaria are among the leading causes of death in children. These deaths are largely preventable if appropriate care is sought early. This review aimed to determine the percentage of caregivers in low- and middle-income countries (LMICs) with a child less than 5 years who were able to recognise illness in their child and subsequently sought care from different types of healthcare providers.

Methods and Findings

We conducted a systematic literature review of studies that reported recognition of, and/or care seeking for episodes of diarrhoea, pneumonia or malaria in LMICs. The review is registered with PROSPERO (registration number: CRD42011001654). Ninety-one studies met the inclusion criteria. Eighteen studies reported data on caregiver recognition of disease and seventy-seven studies on care seeking. The median sensitivity of recognition of diarrhoea, malaria and pneumonia was low (36.0%, 37.4%, and 45.8%, respectively). A median of 73.0% of caregivers sought care outside the home. Care seeking from community health workers (median: 5.4% for diarrhoea, 4.2% for pneumonia, and 1.3% for malaria) and the use of oral rehydration therapy (median: 34%) was low.

Conclusions

Given the importance of this topic to child survival programmes there are few published studies. Recognition of diarrhoea, malaria and pneumonia by caregivers is generally poor and represents a key factor to address in attempts to improve health care utilisation. In addition, considering that oral rehydration therapy has been widely recommended for over forty years, its use remains disappointingly low. Similarly, the reported levels of care seeking from community health workers in the included studies are low even though global action plans to address these illnesses promote community case management. Giving greater priority to research on care seeking could provide crucial evidence to inform child mortality programmes.