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1.  Prescription for antibiotics at drug shops and strategies to improve quality of care and patient safety: a cross-sectional survey in the private sector in Uganda 
BMJ Open  2016;6(3):e010632.
Objectives
The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety in the private health sector in Uganda.
Methods
A survey was conducted within 57 parishes from August to October 2014 in Mukono District, Uganda. Data was captured on the following variables: drug shop characteristics, training of staff in management of pneumonia, availability of guidelines and basic equipment, available antibiotics, knowledge on treatment of pneumonia in children aged <5 years. The main study outcome was the proportion of private health facilities prescribing an antibiotic.
Results
A total of 170 registered drug shops were surveyed between August and October 2014. The majority of drug shops, 93.5% were prescribing antibiotics, especially amoxicillin and trimethoprim-sulfamethoxazole (septrin). The professional qualification of a provider was significantly associated with this practice, p=0.04; where lower cadre staff (nursing assistants and enrolled nurses) overprescribed antibiotics. A third, 29.4% of drug shop providers reported that antibiotics were the first-line treatment for children with diarrhoea; yet the standard guideline is to give oral rehydration salts and zinc tablets. Only few providers, 8.2%, had training on antibiotics, with 10.6% on pneumonia case management. Further to this, 7.1% drug shops had WHO-Integrated Management of Childhood Illness guidelines, and a negligible proportion (<1%) had respiratory timers and baby weighing scales. Although the majority of providers, 82.4%, knew severe signs and symptoms of pneumonia, few, 17.6%, knew that amoxicillin was the first-line drug for treatment of pneumonia in children according to the guidelines.
Conclusions
There is urgent need to regulate drug shop practices of prescribing and selling antibiotics, for the safety of patients seeking care at these outlets.
doi:10.1136/bmjopen-2015-010632
PMCID: PMC4800164  PMID: 26980439
2.  Adherence to treatment guidelines for acute diarrhoea in children up to 12 years in Ujjain, India - a cross-sectional prescription analysis 
Background
Diarrhoea accounts for 20% of all paediatric deaths in India. Despite WHO recommendations and IAP (Indian Academy of Paediatrics) and Government of India treatment guidelines, few children suffering from acute diarrhoea in India receive low osmolarity oral rehydration solution (ORS) and zinc from health care providers. The aim of this study was to analyse practitioners' prescriptions for acute diarrhoea for adherence to treatment guidelines and further to determine the factors affecting prescribing for diarrhoea in Ujjain, India.
Methods
This cross-sectional study was conducted in pharmacies and major hospitals of Ujjain, India. We included prescriptions from all practitioners, including those from modern medicine, Ayurveda, Homeopathy as well as informal health-care providers (IHPs). The data collection instrument was designed to include all the possible medications that are given for an episode of acute diarrhoea to children up to 12 years of age. Pharmacy assistants and resident medical officers transferred the information regarding the current diarrhoeal episode and the treatment given from the prescriptions and inpatient case sheets, respectively, to the data collection instrument.
Results
Information was collected from 843 diarrhoea prescriptions. We found only 6 prescriptions having the recommended treatment that is ORS along with Zinc, with no additional probiotics, antibiotics, racecadotril or antiemetics (except Domperidone for vomiting). ORS alone was prescribed in 58% of the prescriptions; while ORS with zinc was prescribed in 22% of prescriptions, however these also contained other drugs not included in the guidelines. Antibiotics were prescribed in 71% of prescriptions. Broad-spectrum antibiotics were prescribed and often in illogical fixed-dose combinations. One such illogical combination, ofloxacin with ornidazole, was the most frequent oral antibiotic prescribed (22% of antibiotics prescribed). Practitioners from alternate system of medicine and IHPs are significantly less likely (OR 0.13, 95% CI 0.04-0.46, P = 0.003) to prescribe ORS and zinc than pediatricians. Practitioners from 'free' hospitals are more likely to prescribe ORS and zinc (OR 4.94, 95% CI 2.45-9.96, P < 0.001) and less likely to prescribe antibiotics (OR 0.01, 95% CI 0.01-0-04, P < 0.001) compared to practitioners from 'charitable' hospitals. Accompanying symptoms like the presence of fever, pain, blood in the stool and vomiting significantly increased antibiotic prescribing.
Conclusion
This study demonstrated low adherence to standard treatment guidelines for management of acute diarrhoea in children under 12 years in Ujjain, India. Key public health concerns were the low use of zinc and the high use of antibiotics, found in prescriptions from both specialist paediatricians as well as practitioners from alternate systems of medicine and informal health-care providers. To improve case management of acute diarrhoea, continuing professional development programme targeting the practitioners of all systems of medicine is necessary.
doi:10.1186/1471-2334-11-32
PMCID: PMC3045317  PMID: 21276243
3.  Diarrhoea in adults (acute) 
BMJ Clinical Evidence  2011;2011:0901.
Introduction
An estimated 4.6 billion cases of diarrhoea occurred worldwide in 2004, resulting in 2.2 million deaths.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 72 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution), vitamin A supplementation, and zinc supplementation.
Key Points
Diarrhoea is an alteration in normal bowel movement, characterised by increased frequency, volume, and water content of stools, often defined clinically as an increase in stool frequency to three or more liquid or semi-formed motions in 24 hours. An estimated 4.6 billion cases of diarrhoeal illness occurred worldwide in 2004, causing 2.2 million deaths, 1.5 million of which were in children.
This review examines the effects of treatments in adults.
In people from resource-poor countries, antisecretory agents, such as racecadotril, seem to be as effective at improving symptoms of diarrhoea as antimotility agents, such as loperamide, but with fewer adverse effects. Empirical treatment with antibiotics also seems to reduce the duration of diarrhoea and improve symptoms in this population, although it can produce adverse effects such as rash, myalgia, and nausea.Instructing people to refrain from taking any solid food for 24 hours does not seem to be a useful treatment, although the evidence for this is sparse.We don't know how effective oral rehydration solutions or antibiotics plus antimotility agents are in this population, as we did not find any RCTs.
Antisecretory agents, antibiotics, and antimotility agents also seem to be effective in treating people from resource-rich countries who are travelling to resource-poor countries. Antibiotics plus antimotility agents may be more effective than antibiotics alone at reducing the duration of diarrhoea in people with travellers' diarrhoea. Bismuth subsalicylate is effective in treating travellers' diarrhoea, but less so than loperamide, and with more adverse effects (primarily black tongue and black stools).We don't know the effectiveness of oral rehydration solutions or restricting diet in reducing symptoms of diarrhoea in people travelling to resource-poor countries.
For people from resource-poor countries with mild or moderate diarrhoea, antisecretory agents seem to be as beneficial as antimotility agents, and cause fewer adverse effects (particularly rebound constipation). We didn't find sufficient evidence to allow us to judge the efficacy of antibiotics, antibiotics plus antimotility agents, or oral rehydration solutions in this population.
Oral rehydration solutions are considered to be beneficial in people from resource-poor countries who have severe diarrhoea. Studies have shown that amino acid-based and rice-based oral rehydration solutions are beneficial, but the evidence is less clear about the efficacy of bicarbonate or reduced osmolarity solutions.Rice-based oral rehydration solutions seem more beneficial compared with glucose-based oral rehydration solutions in reducing the duration of severe diarrhoea in resource-poor countries.
We don't know whether intravenous rehydration is more beneficial than oral rehydration or enteral rehydration through a nasogastric tube. We don't know whether antimotility agents, antisecretory agents, antibiotics, or antibiotics plus antimotility agents are effective for treating people with severe diarrhoea in resource-poor countries.We found no evidence on the use of zinc or vitamin A supplementation in adults in a resource-poor setting.
PMCID: PMC3217748  PMID: 21718555
4.  Drug seller adherence to clinical protocols with integrated management of malaria, pneumonia and diarrhoea at drug shops in Uganda 
Malaria Journal  2015;14:277.
Background
Drug shops are usually the first source of care for febrile children in Uganda although the quality of care they provide is known to be poor. Within a larger quasi-experimental study introducing the WHO/UNICEF recommended integrated community case management (iCCM) of malaria, pneumonia and diarrhoea intervention for community health workers in registered drug shops, the level of adherence to clinical protocols by drug sellers was determined.
Methods
All drug shops (N = 44) in the intervention area were included and all child visits (N = 7,667) from October 2011–June 2012 to the participating drug shops were analysed. Drug shops maintained a standard iCCM register where they recorded the children seen, their symptoms, diagnostic test performed, treatments given and actions taken. The proportion of children correctly assessed and treated was determined from the registers.
Results
Malaria management: 6,140 of 7,667 (80.1%) total visits to drug shops were of children with fever. 5986 (97.5%) children with fever received a malaria rapid diagnostic test (RDT) and the RDT positivity rate was 78% (95% CI 77–79). 4,961/5,307 (93.4%) children with a positive RDT received artemisinin combination therapy. Pneumonia management: after respiratory rate assessment of children with cough and fast/difficult breathing, 3,437 (44.8%) were categorized as “pneumonia”, 3,126 (91.0%) of whom received the recommended drug—amoxicillin. Diarrhoea management: 2,335 (30.5%) child visits were for diarrhoea with 2,068 (88.6%) correctly treated with oral rehydration salts and zinc sulphate. Dual/Triple classification: 2,387 (31.1%) children had both malaria and pneumonia and 664 (8.7%) were classified as having three illnesses. Over 90% of the children with dual or triple classification were treated appropriately. Meanwhile, 381 children were categorized as severely sick (with a danger sign) with 309 (81.1%) of them referred for appropriate management.
Conclusion
With the introduction of the iCCM intervention at drug shops in Eastern Uganda, it was possible to achieve high adherence to the treatment protocols, which is likely compatible with increased quality of care.
Electronic supplementary material
The online version of this article (doi:10.1186/s12936-015-0798-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12936-015-0798-9
PMCID: PMC4502601  PMID: 26178532
5.  A protocol for engaging unlicensed private drug shops in Rural Eastern Uganda for Integrated Community Case Management (ICCM) of malaria, pneumonia and diarrhoea in children under 5 years of age 
BMJ Open  2015;5(10):e009133.
Introduction
Malaria, pneumonia and diarrhoea are leading causes of death in young children in Uganda. In 2010, Integrated Community Case Management (ICCM) was adopted in Uganda for community level diagnosis and treatment of these diseases through community health workers. However, 50–60% of sick children will receive treatment from the private sector, especially drug shops. Only about half of drug shops are licensed and the quality of care is poor. There is an urgent need to improve quality of care and regulation of drug shops in Uganda.
Methods
This is a pre–post cross-sectional study with before and after measurement in an intervention area in Kamujli district. A snowball mapping exercise, exit interviews, focus group discussions and interviews will be used. 25 randomly selected drug shops will be selected for an intervention that will assist drug shops to become licensed, and provide five days of ICCM training, subsidised prepackaged medicines (artemisinin-based combination therapies for malaria, amoxicillin for pneumonia, Oral Rehydration Salts/zinc for diarrhoea) and free diagnostic tools (rapid diagnostic tests, respiratory timers, thermometers, algorithms). We anticipate a sample size of 1200 (600 at baseline and 600 at the end of the study).
Analysis
Quantitative data will be analysed using SPSS for proportions and CIs. Bivariate and multiple logistic regression analysis with adjustment for clustering of data will be performed to adjust for confounding and determine intervention effect. Qualitative data will be entered into NVivo 10 and analysed using content analysis.
Ethics and Dissemination
Research ethics approval is received from the University of Calgary (REB 14–0269), and Makerere University (IRB00011353). Findings from this study will be disseminated through journal articles and conference presentations, and will illustrate the feasibility of introducing ICCM for drug shops.
doi:10.1136/bmjopen-2015-009133
PMCID: PMC4606439  PMID: 26446166
6.  Management of paediatric illnesses by patent and proprietary medicine vendors in Nigeria 
Malaria Journal  2015;14:232.
Background
In Nigeria and elsewhere, informal drug sellers, or patent and proprietary medicine vendors (PPMVs), are a common source of care for children with malaria, diarrhoea, and pneumonia. However, their knowledge and stocking of recommended treatments for these common childhood illnesses are not well understood.
Methods
A census of PPMV shops was conducted in Kogi and Kwara states. A shop survey was conducted on a subset of 250 shops. Multivariate regression analysis was used to assess associations between shop worker characteristics and (1) knowledge of optimal treatments for malaria, diarrhoea, and pneumonia, and (2) stocking of essential medicines to treat these illnesses.
Results
From the census, 89.9 % of shops stocked oral rehydration solution (ORS), while 61.1 % of shops stocked artemisinin-based combination therapies and 72.2 % of shops stocked amoxicillin. Stocking patterns varied by state, urban/rural location, and according to whether or not the shop was headed by someone with formal health training (e.g. having a professional health education degree). In multivariate analyses, selling drugs wholesale and participating in any training in the past year was associated with a higher likelihood of naming the correct treatment for malaria, and having formal health training was associated with stocking ORS. However, few other PPMV characteristics were predictive of correct knowledge of optimal treatments and stocking behaviour.
Conclusion
Many PPMVs lack the knowledge and tools to properly treat common childhood illnesses. PPMV knowledge and selling of essential medicines for these illnesses should be strengthened to improve child health in Nigeria.
doi:10.1186/s12936-015-0747-7
PMCID: PMC4465720  PMID: 26041654
Malaria; Pneumonia; Diarrhoea; Nigeria; Private sector; Drug vendors; Integrated management of childhood illnesses; Community case management
7.  Household Management of Childhood Diarrhoea: A Population-based Study in Nicaragua 
Diarrhoea remains an important cause of mortality and morbidity among children in Nicaragua. As the majority of diarrhoeal cases are treated at home and appropriate household management can lessen severity of diarrhoea, the objective of this study was to examine household management of childhood diarrhoea. A simple random sample of households was selected from the Health and Demographic Surveillance Site-León. Parents or caretakers of children below five years of age, who developed diarrhoea (n=232), were surveyed about household diarrhoea management practices in 2011. Fifty-seven percent of children received oral rehydration therapy (ORT) in the home prior to visiting any health facility. We encountered certain practices in contradiction with WHO recommendations for the management of diarrhoea in communities: 41% of children were offered protein-rich foods less frequently during diarrhoeal episodes, 20% of children were nursed less frequently or not at all during diarrhoeal episodes, and zinc supplementation was recommended at only 39% of visits with healthcare providers. Our findings provide insights for efforts to improve the household management of childhood diarrhoea in Nicaragua.
PMCID: PMC4089083  PMID: 24847604
Child; Diarrhoea; Household management; Nicaragua
8.  Increased Access to Care and Appropriateness of Treatment at Private Sector Drug Shops with Integrated Management of Malaria, Pneumonia and Diarrhoea: A Quasi-Experimental Study in Uganda 
PLoS ONE  2014;9(12):e115440.
Introduction
Drug shops are a major source of care for children in low income countries but they provide sub-standard care. We assessed the feasibility and effect on quality of care of introducing diagnostics and pre-packaged paediatric-dosage drugs for malaria, pneumonia and diarrhoea at drug shops in Uganda.
Methods
We adopted and implemented the integrated community case management (iCCM) intervention within registered drug shops. Attendants were trained to perform malaria rapid diagnostic tests (RDTs) in each fever case and count respiratory rate in each case of cough with fast/difficult breathing, before dispensing recommended treatment. Using a quasi-experimental design in one intervention and one non-intervention district, we conducted before and after exit interviews for drug seller practices and household surveys for treatment-seeking practices in May–June 2011 and May–June 2012. Survey adjusted generalized linear models and difference-in-difference analysis was used.
Results
3759 (1604 before/2155 after) household interviews and 943 (163 before/780 after) exit interviews were conducted with caretakers of children under-5. At baseline, no child at a drug shop received any diagnostic testing before treatment in both districts. After the intervention, while no child in the non-intervention district received a diagnostic test, 87.7% (95% CI 79.0–96.4) of children with fever at the intervention district drug shops had a parasitological diagnosis of malaria, prior to treatment. The prevalence ratios of the effect of the intervention on treatment of cough and fast breathing with amoxicillin and diarrhoea with ORS/zinc at the drug shop were 2.8 (2.0–3.9), and 12.8 (4.2–38.6) respectively. From the household survey, the prevalence ratio of the intervention effect on use of RDTs was 3.2 (1.9–5.4); Artemisinin Combination Therapy for malaria was 0.74 (0.65–0.84), and ORS/zinc for diarrhoea was 2.3 (1.2–4.7).
Conclusion
iCCM can be utilized to improve access and appropriateness of care for children at drug shops.
doi:10.1371/journal.pone.0115440
PMCID: PMC4277343  PMID: 25541703
9.  Childhood diarrhoeal deaths in seven low- and middle-income countries 
Abstract
Objective
To investigate the clinical characteristics of children who died from diarrhoea in low- and middle-income countries, such as the duration of diarrhoea, comorbid conditions, care-seeking behaviour and oral rehydration therapy use.
Methods
The study included verbal autopsy data on children who died from diarrhoea between 2000 and 2012 at seven sites in Bangladesh, Ethiopia, Ghana, India, Pakistan, Uganda and the United Republic of Tanzania, respectively. Data came from demographic surveillance sites, randomized trials and an extended Demographic and Health Survey. The type of diarrhoea was classified as acute watery, acute bloody or persistent and risk factors were identified. Deaths in children aged 1 to 11 months and 1 to 4 years were analysed separately.
Findings
The proportion of childhood deaths due to diarrhoea varied considerably across the seven sites from less than 3% to 30%. Among children aged 1–4 years, acute watery diarrhoea accounted for 31–69% of diarrhoeal deaths, acute bloody diarrhoea for 12–28%, and persistent diarrhoea for 12–56%. Among infants aged 1–11 months, persistent diarrhoea accounted for over 30% of diarrhoeal deaths in Ethiopia, India, Pakistan, Uganda and the United Republic of Tanzania. At most sites, more than 40% of children who died from persistent diarrhoea were malnourished.
Conclusion
Persistent diarrhoea remains an important cause of diarrhoeal death in young children in low- and middle-income countries. Research is needed on the public health burden of persistent diarrhoea and current treatment practices to understand why children are still dying from the condition.
doi:10.2471/BLT.13.134809
PMCID: PMC4208570  PMID: 25378757
10.  Incidence and Clinical Characteristics of Group A Rotavirus Infections among Children Admitted to Hospital in Kilifi, Kenya  
PLoS Medicine  2008;5(7):e153.
Background
Rotavirus, predominantly of group A, is a major cause of severe diarrhoea worldwide, with the greatest burden falling on young children living in less-developed countries. Vaccines directed against this virus have shown promise in recent trials, and are undergoing effectiveness evaluation in sub-Saharan Africa. In this region limited childhood data are available on the incidence and clinical characteristics of severe group A rotavirus disease. Advocacy for vaccine intervention and interpretation of effectiveness following implementation will benefit from accurate base-line estimates of the incidence and severity of rotavirus paediatric admissions in relevant populations. The study objective was to accurately define the incidence and severity of group A rotavirus disease in a resource-poor setting necessary to make informed decisions on the need for vaccine prevention.
Methods and Findings
Between 2002 and 2004 we conducted prospective surveillance for group A rotavirus infection at Kilifi District Hospital in coastal Kenya. Children < 13 y of age were eligible as “cases” if admitted with diarrhoea, and “controls” if admitted without diarrhoea. We calculated the incidence of hospital admission with group A rotavirus using data from a demographic surveillance study of 220,000 people in Kilifi District. Of 15,347 childhood admissions 3,296 (22%) had diarrhoea, 2,039 were tested for group A rotavirus antigen and, of these, 588 (29%) were positive. 372 (63%) rotavirus-positive cases were infants. Of 620 controls 19 (3.1%, 95% confidence interval [CI] 1.9–4.7) were rotavirus positive. The annual incidence (per 100,000 children) of rotavirus-positive admissions was 1,431 (95% CI 1,275–1,600) in infants and 478 (437–521) in under-5-y-olds, and highest proximal to the hospital. Compared to children with rotavirus-negative diarrhoea, rotavirus-positive cases were less likely to have coexisting illnesses and more likely to have acidosis (46% versus 17%) and severe electrolyte imbalance except hyponatraemia. In-hospital case fatality was 2% among rotavirus-positive and 9% among rotavirus-negative children.
Conclusions
In Kilifi > 2% of children are admitted to hospital with group A rotavirus diarrhoea in the first 5 y of life. This translates into over 28,000 vaccine-preventable hospitalisations per year across Kenya, and is likely to be a considerable underestimate. Group A rotavirus diarrhoea is associated with acute life-threatening metabolic derangement in otherwise healthy children. Although mortality is low in this clinical research setting this may not be generally true in African hospitals lacking rapid and appropriate management.
Combining prospective hospital-based surveillance with demographic data in Kilifi, Kenya, James Nokes and colleagues assess the burden of rotavirus diarrhea in young children.
Editors' Summary
Background.
Rotavirus is a leading global cause of diarrhea in babies and young children. Indeed, most children become infected at least once with this virus before their fifth birthday. Rotavirus is usually spread by children or their caregivers failing to wash their hands properly after going to the toilet and then contaminating food or drink. The symptoms of rotavirus infection—diarrhea, vomiting, and fever—are usually mild, but if the diarrhea is severe it can quickly lead to dehydration. Mild to moderate dehydration can be treated at home by providing the patient with plenty of fluids or with a special rehydration drink that replaces lost water and salts. However, for infants or toddlers who become severely dehydrated, rehydration with intravenous fluids (fluids injected directly into a vein) in hospital may be essential. Unfortunately, in developing countries in sub-Saharan Africa and elsewhere, this treatment is not widely available and every year more than half a million young children die from rotavirus infections.
Why Was This Study Done?
Two rotavirus vaccines that could reduce this burden of disease are currently undergoing clinical trials to determine their effectiveness in sub-Saharan Africa. However, very little is known about the incidence of severe rotavirus infections among children living in this region (that is, how many children develop severe disease every year) or about the clinical characteristics of the disease here. Public-health officials need this baseline information before they can make informed decisions about the mass introduction of rotavirus vaccination and to help them judge whether the intervention has been successful if it is introduced. In this study, the researchers examine the incidence and clinical characteristics of rotavirus infections (specifically, group A rotavirus [GARV] infections; there are several different rotaviruses but GARV causes most human infections) among children admitted to the district hospital in Kilifi, Kenya.
What Did the Researchers Do and Find?
During the 3-year study, more than 15,000 children under the age of 13 years were admitted to Kilifi District Hospital, a little under a quarter of whom had severe diarrhea. Nearly a third of the patients admitted with diarrhea who were tested had a GARV-specific protein in their stools (faeces); by contrast, only three in 100 children admitted without diarrhea showed any evidence of GARV infection. Two-thirds of the GARV-positive children were infants (under 1 year old). Using these figures and health surveillance data (records of births, deaths, and causes of death) collected in the area around the hospital, the researchers calculated that the annual incidence (per 100,000 children) of GARV-positive hospital admissions in the region was 1,431 for infants and 478 for children under age 5 years. Children with GARV-positive diarrhea were less likely to have other illnesses (for example, malnutrition) than those admitted with GARV-negative diarrhea, the researchers report, but were more likely to have life-threatening complications such as severe dehydration and salt imbalances in their blood. However, despite being more ill on admission, only 1 in 50 children with GARV-positive diarrhea died, compared to nearly 1 in 10 of the children with GARV-negative diarrhea; the GARV-positive children also left hospital quicker than those who were GARV-negative.
What Do These Findings Mean?
These findings indicate that severe GARV-positive diarrhea is a major cause of hospital admission among otherwise healthy young children in the Kilifi region of Kenya. By the time they are 5 years old, the researchers estimate that 1 in 50 of the children living in this region will have been admitted to hospital with severe GARV-positive diarrhea. Because rotavirus vaccines prevent virtually all severe rotavirus-associated disease (at least in developed countries where their effectiveness has been extensively tested), the researchers estimate that vaccination might prevent more than 28,000 hospitalizations annually across Kenya; however, this prediction assumes that it is valid to extrapolate from the data obtained from this one district hospital to the entire country.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050153.
The US Centers for Disease Control and Prevention provides information about rotavirus infections, surveillance, and vaccination (in English and Spanish)
The UK National Health Service Direct health encyclopedia provides information on rotavirus infections
MedlinePlus also provides links to information on rotavirus (in English and Spanish)
The African Rotavirus Surveillance Network is working to improve knowledge about rotavirus infections in Africa
The Rotavirus Vaccine Program aims to reduce child illness and death from diarrhea by increasing the availability of rotavirus vaccines in developing countries (in English and Spanish)
PATH, a nonprofit international organization that aims to create sustainable, culturally relevant solutions to global health problems, also provides detailed information on rotavirus surveillance and disease burden
doi:10.1371/journal.pmed.0050153
PMCID: PMC2488191  PMID: 18651787
11.  Application of basic pharmacology and dispensing practice of antibiotics in accredited drug-dispensing outlets in Tanzania 
Background
Provision of pharmaceutical services in accredited drug-dispensing outlets (ADDOs) in Tanzania has not been reported. This study compared the antibiotics dispensing practice between ADDOs and part II shops, or duka la dawa baridi (DLDBs), in Tanzania.
Methodology
This was a cross-sectional study that was conducted in ADDOs and DLDBs. A simulated client method for data collection was used, and a total of 85 ADDOs, located in Mvomero, Kilombero, and Morogoro rural districts, were compared with 60 DLDBs located in Kibaha district. The research assistants posed as simulated clients and requested to buy antibiotics from ADDOs and DLDBs after presenting a case scenario or disease condition. Among the diseases presented were those requiring antibiotics and those usually managed only by oral rehydration salt or analgesics. The simulated clients wanted to know the antibiotics that were available at the shop. The posed questions set a convincing ground to the dispenser either to dispense the antibiotic directly, request a prescription, or refer the patient to a health facility. Proportions were used to summarize categorical variables between ADDOs and DLDBs, and the chi-square test was used to test for statistical difference between the two drug-outlet types in terms of antibiotic-dispensing practice.
Results
As many as 40% of trained ADDO dispensers no longer worked at the ADDO shops, so some of the shops employed untrained staff. A larger proportion of ADDOs than DLDBs dispensed antibiotics without prescriptions (P = 0.004). The overall results indicate that there was no difference between the two types of shops in terms of adhering to regulations for dispensing antibiotics. However, in some circumstances, eg, antibiotic sale without prescription and no referral made, for complicated cases, ADDOs performed worse than DLDBs. As many as 30% of DLDBs and 35% of ADDOs dispensed incomplete doses of antibiotics. In both ADDOs and DLDBs, fortified procaine penicillin powder was dispensed as topical application for injuries.
Conclusion
There was no statistical difference between ADDOs and DLDBs in the violation of dispensing practice and both ADDOs and DLDBs expressed poor knowledge of the basic pharmacology of antibiotics.
doi:10.2147/DHPS.S36409
PMCID: PMC3565572  PMID: 23403610
antibiotic-dispensing practice; duka la dawa baridi; accredited drug-dispensing outlets
12.  Diarrhoea in adults (acute) 
BMJ Clinical Evidence  2008;2008:0901.
Introduction
An estimated 4000 million cases of diarrhoea occurred worldwide in 1996, resulting in 2.5 million deaths.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries traveling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, and oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution).
Key Points
Diarrhoea is watery or liquid stools, usually with an increase in stool weight above 200 g daily and an increase in daily stool frequency. An estimated 4000 million cases of diarrhoea occurred worldwide in 1996, resulting in 2.5 million deaths.
In people from resource-poor countries, antisecretory agents, such as racecadotril, seem to be as effective at improving symptoms of diarrhoea as antimotility agents, such as loperamide, but with fewer adverse effects. Empirical treatment with antibiotics also seems to reduce the duration of diarrhoea and improve symptoms in this population, although it can produce adverse effects such as rash, myalgia, and nausea.Instructing people to refrain from taking any solid food for 24 hours does not appear to be a useful treatment, although the evidence for this is sparse.We don't know how effective oral rehydration solutions or antibiotics plus antimotility agents are in this population, as we did not find any RCTs.
Antisecretory agents, antibiotics, and antimotility agents also appear to be effective in treating people from resource-rich countries who are travelling to resource-poor countries. We don't know whether antibiotics plus antimotility agents are more effective than either treatment alone or placebo. Bismuth subsalicylate is effective in treating travellers' diarrhoea, but less so than loperamide, and with more adverse effects (primarily black tongue and black stools).We don't know the effectiveness of oral rehydration solutions or restricting diet in reducing symptoms of diarrhoea in people travelling to resource-poor countires.
For people from resource-poor countires with mild or moderate diarrhoea, antisecretory agents seem to be as beneficial as antimotility agents, and cause fewer adverse effects (particularly rebound constipation). We didn't find sufficient evidence to allow us to judge the efficacy of antibiotics, antibiotics plus antimotility agents, or oral rehydration solutions in this population.
Oral rehydration solutions are considered to be beneficial in people from resource-poor countries who have severe diarrhoea. Studies have shown that amino acid-based and rice-based oral rehydration solutions are beneficial, but the evidence is less clear about the efficacy of bicarbonate or reduced osmolarity solutions.
We don't know whether intravenous rehydration is more beneficial than oral rehydration or enteral rehydration through a nasogastric tube. We don't know whether antimotility agents, antisecretory agents, antibiotics, or antiobiotics plus antimotility agents are effective for treating people with severe diarrhoea in resource-poor countries.
PMCID: PMC2907942  PMID: 19450323
13.  Operational Issues and Trends Associated with the Pilot Introduction of Zinc for Childhood Diarrhoea in Bougouni District, Mali 
Zinc for the treatment of childhood diarrhoea was introduced in a pilot area in southern Mali to prepare for a cluster-randomized effectiveness study and to inform policies on how to best introduce and promote zinc at the community level. Dispersible zinc tablets in 14-tablet blister packs were provided through community health centres and drug kits managed by community health workers (CHWs) in two health zones in Bougouni district, Mali. Village meetings and individual counselling provided by CHWs and head nurses at health centres were the principal channels of communication. A combination of methods were employed to (a) detect problems in communication about the benefits of zinc and its mode of administration; (b) identify and resolve obstacles to implementation of zinc through existing health services; and (c) describe household-level constraints to the adoption of appropriate home-management practices for diarrhoea, including administration of both zinc and oral rehydration solution (ORS). Population-based household surveys with caretakers of children sick in the previous two weeks were carried out before and four months after the introduction of zinc supplementation. Household follow-up visits with children receiving zinc from the health centres and CHWs were conducted on day 3 and 14 after treatment for a subsample of children. A qualitative process evaluation also was conducted to investigate operational issues. Preliminary evidence from this study suggests that the introduction of zinc does not reduce the use of ORS and may reduce inappropriate antibiotic use for childhood diarrhoea. Financial access to treatments, management of concurrent diarrhoea and fever, and high use of unauthorized drug vendors were identified as factors affecting the effectiveness of the intervention in this setting. The introduction of zinc, if not appropriately integrated with other disease-control strategies, has the potential to decrease the appropriate presumptive treatment of childhood malaria in children with diarrhoea and fever in malaria-endemic areas.
PMCID: PMC2740667  PMID: 18686549
Antibiotic use; Diarrhoea; Child health; Oral rehydration solutions; Oral rehydration therapy; Zinc; Zinc therapy; Mali
14.  Treatment of Diarrhoea in Rural African Communities: An Overview of Measures to Maximise the Medicinal Potentials of Indigenous Plants 
Diarrhoea is a major cause of morbidity and mortality in rural communities in Africa, particularly in children under the age of five. This calls for the development of cost effective alternative strategies such as the use of herbal drugs in the treatment of diarrhoea in these communities. Expenses associated with the use of orthodox medicines have generated renewed interest and reliance on indigenous medicinal plants in the treatment and management of diarrhoeal infections in rural communities. The properties of many phenolic constituents of medicinal plants such as their ability to inhibit enteropooling and delay gastrointestinal transit are very useful in the control of diarrhoea, but problems such as scarcity of valuable medicinal plants, lack of standardization of methods of preparation, poor storage conditions and incertitude in some traditional health practitioners are issues that affect the efficacy and the practice of traditional medicine in rural African communities. This review appraises the current strategies used in the treatment of diarrhoea according to the Western orthodox and indigenous African health-care systems and points out major areas that could be targeted by health-promotion efforts as a means to improve management and alleviate suffering associated with diarrhoea in rural areas of the developing world. Community education and research with indigenous knowledge holders on ways to maximise the medicinal potentials in indigenous plants could improve diarrhoea management in African rural communities.
doi:10.3390/ijerph9113911
PMCID: PMC3524604  PMID: 23202823
diarrhea; gastrointestinal transit; indigenous medicinal plants; health-promotion efforts; rural Africa
15.  Effect of Household-Based Drinking Water Chlorination on Diarrhoea among Children under Five in Orissa, India: A Double-Blind Randomised Placebo-Controlled Trial 
PLoS Medicine  2013;10(8):e1001497.
Sophie Boisson and colleagues conducted a double-blind, randomized placebo-controlled trial in Orissa, a state in southeast India, to evaluate the effect of household water treatment in preventing diarrheal illnesses in children aged under five years of age.
Please see later in the article for the Editors' Summary
Background
Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five.
Methods and Findings
We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC) tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence) among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC), an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating equations to account for clustering at the household level. The impact of the intervention on weight-for-age z scores (WAZ) was analysed using random effect linear regression.
Over the follow-up period, 84,391 child-days of observations were recorded, representing 88% of total possible child-days of observation. The longitudinal prevalence of diarrhoea among intervention children was 1.69% compared to 1.74% among controls. After adjusting for clustering within household, the prevalence ratio of the intervention to control was 0.95 (95% CI 0.79–1.13). The mean WAZ was similar among children of the intervention and control groups (−1.586 versus −1.589, respectively). Among intervention households, 51% reported their child's drinking water to be treated with the tablets at the time of visit, though only 32% of water samples tested positive for residual chlorine. Faecal contamination of drinking water was lower among intervention households than controls (geometric mean TTC count of 50 [95% CI 44–57] per 100 ml compared to 122 [95% CI 107–139] per 100 ml among controls [p<0.001] [n = 4,546]).
Conclusions
Our study was designed to overcome the shortcomings of previous double-blinded trials of household water treatment in low-income settings. The sample size was larger, the follow-up period longer, both urban and rural populations were included, and adherence and water quality were monitored extensively over time. These results provide no evidence that the intervention was protective against diarrhoea. Low compliance and modest reduction in water contamination may have contributed to the lack of effect. However, our findings are consistent with other blinded studies of similar interventions and raise additional questions about the actual health impact of household water treatment under these conditions.
Trial Registration
ClinicalTrials.gov NCT01202383
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Millennium Development Goal 7 calls for halving the proportion of the global population without sustainable access to safe drinking water between 1990 and 2015. Although this target was met in 2010, according to latest figures, 768 million people world-wide still rely on unimproved drinking water sources. Access to clean drinking water is integral to good health and a key strategy in reducing diarrhoeal illness: Currently, 1.3 million children aged less than five years die of diarrhoeal illnesses every year with a sixth of such deaths occurring in one country—India. Although India has recently made substantial progress in improving water supplies throughout the country, currently almost 90% of the rural population does not have a water connection to their house and drinking water supplies throughout the country are extensively contaminated with human waste. A strategy internationally referred to as Household Water Treatment and Safe Storage (HWTS), which involves people boiling, chlorinating, and filtering water at home, has been recommended by the World Health Organization and UNICEF to improve water quality at the point of delivery.
Why Was This Study Done?
The WHO and UNICEF strategy to promote HWTS is based on previous studies from low-income settings that found that such interventions could reduce diarrhoeal illnesses by between 30%–40%. However, these studies had several limitations including reporting bias, short follow up periods, and small sample sizes; and importantly, in blinded studies (in which both the study participants and researchers are unaware of which participants are receiving the intervention or the control) have found no evidence that HWTS is protective against diarrhoeal illnesses. So the researchers conducted a blinded study (a double-blind, randomized placebo-controlled trial) in Orissa, a state in southeast India, to address those shortcomings and evaluate the effect of household water treatment in preventing diarrhoeal illnesses in children under five years of age.
What Did the Researchers Do and Find?
The researchers conducted their study in 11 informal settlements (where the inhabitants do not benefit from public water or sewers) in the state's capital city and also in 20 rural villages. 2,163 households were randomized to receive the intervention—the promotion and free distribution of sodium dichloroisocyanurate (chlorine) disinfection tablets with instruction on how to use them—or placebo tablets that were similar in appearance and had the same effervescent base as the chlorine tablets. Trained field workers visited households every month for 12 months (between December 2010 and December 2011) to record whether any child had experienced diarrhoea in the previous three days (as reported by the primary care giver). The researchers tested compliance with the intervention by asking participants if they had treated the water and also by testing for chlorine in the water.
Using these methods, the researchers found that over the 12-month follow-up period, the longitudinal prevalence of diarrhoea among children in the intervention group was 1.69% compared to 1.74% in the control group, a non-significant finding (a finding that could have happened by chance). There was also no difference in diarrhoea prevalence among other household members in the two groups and no difference in weight for age z scores (a measurement of growth) between children in the two groups. The researchers also found that although just over half (51%) of households in the intervention group reported treating their water, on testing, only 32% of water samples tested positive for chlorine. Finally, the researchers found that water quality (as measured by thermotolerant coliforms, TTCs) was better in the intervention group than the control group.
What Do These Findings Mean?
These findings suggest that treating water with chlorine tablets has no effect in reducing the prevalence of diarrhoea in both children aged under five years and in other household members in Orissa, India. However, poor compliance was a major issue with only a third of households in the intervention group confirmed as treating their water with chlorine tablets. Furthermore, these findings are limited in that the prevalence of diarrhoea was lower than expected, which may have also reduced the power of detecting a potential effect of the intervention. Nevertheless, this study raises questions about the health impact of household water treatment and highlights the key challenge of poor compliance with public health interventions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001497.
The website of the World Health Organization has a section dedicated to household water treatment and safe storage, including a network to promote the use of HWTS and a toolkit to measure HWTS
The Water Institute hosts the communications portal for the International Network on Household Water Treatment and Safe Storage
doi:10.1371/journal.pmed.1001497
PMCID: PMC3747993  PMID: 23976883
16.  Private Sector Drug Shops in Integrated Community Case Management of Malaria, Pneumonia, and Diarrhea in Children in Uganda 
We conducted a survey involving 1,604 households to determine community care-seeking patterns and 163 exit interviews to determine appropriateness of treatment of common childhood illnesses at private sector drug shops in two rural districts of Uganda. Of children sick within the last 2 weeks, 496 (53.1%) children first sought treatment in the private sector versus 154 (16.5%) children first sought treatment in a government health facility. Only 15 (10.3%) febrile children treated at drug shops received appropriate treatment for malaria. Five (15.6%) children with both cough and fast breathing received amoxicillin, although no children received treatment for 5–7 days. Similarly, only 8 (14.3%) children with diarrhea received oral rehydration salts, but none received zinc tablets. Management of common childhood illness at private sector drug shops in rural Uganda is largely inappropriate. There is urgent need to improve the standard of care at drug shops for common childhood illness through public–private partnerships.
doi:10.4269/ajtmh.2012.11-0791
PMCID: PMC3748528  PMID: 23136283
17.  Getting closer to people: family planning provision by drug shops in Uganda 
Private drug shops can effectively provide contraceptive methods, especially injectables, complementing government services. Most drug shop clients in 4 peri-urban areas of Uganda were continuing users of DMPA; had switched from other providers, mainly government clinics, because the drug shops had fewer stock-outs and were more convenient (closer location, shorter waiting time, more flexible hours); and were satisfied with the quality of services. The drug shops provided a substantial part of the total market share for family planning services in their areas.
Private drug shops can effectively provide contraceptive methods, especially injectables, complementing government services. Most drug shop clients in 4 peri-urban areas of Uganda were continuing users of DMPA; had switched from other providers, mainly government clinics, because the drug shops had fewer stock-outs and were more convenient (closer location, shorter waiting time, more flexible hours); and were satisfied with the quality of services. The drug shops provided a substantial part of the total market share for family planning services in their areas.
ABSTRACT
Background:
Private-sector drug shops are often the first point of health care in sub-Saharan Africa. Training and supporting drug shop and pharmacy staff to provide a wide range of contraceptive methods and information is a promising high-impact practice for which more information is needed to fully document implementation experience and impact.
Methods:
Between September 2010 and March 2011, we trained 139 drug shop operators (DSOs) in 4 districts of Uganda to safely administer intramuscular DMPA (depot medroxyprogesterone acetate) contraceptive injections. In 2012, we approached 54 of these DSOs and interviewed a convenience sample of 585 of their family planning clients to assess clients' contraceptive use and perspectives on the quality of care and satisfaction with services. Finally, we compared service statistics from April to June 2011 from drug shops, community health workers (CHWs), and government clinics in 3 districts to determine the drug shop market share of family planning services.
Results:
Most drug shop family planning clients interviewed were women with low socioeconomic status. The large majority (89%) were continuing family planning users. DMPA was the preferred contraceptive. Almost half of the drug shop clients had switched from other providers, primarily from government health clinics, mostly as a result of more convenient locations, shorter waiting times, and fewer stock-outs in drug shops. All clients reported that the DSOs treated them respectfully, and 93% trusted the drug shop operator to maintain privacy. Three-quarters felt that drug shops offered affordable family planning services. Most of the DMPA clients (74%) were very satisfied with receiving their method from the drug shop and 98% intended to get the next injection from the drug shop. Between April and June 2011, clinics, CHWs, and drug shops in 3 districts delivered equivalent proportions of couple-years of protection, with drug shops leading marginally at 36%, followed by clinics (33%) and CHWs (31%).
Conclusion:
Drug shops can be a viable and convenient source of short-acting contraceptive methods, including DMPA, serving as a complement to government services. Family planning programs in Uganda and elsewhere should consider including drug shops in the network of community-based family planning providers.
doi:10.9745/GHSP-D-14-00085
PMCID: PMC4307862  PMID: 25611480
18.  Antimicrobial drugs for treating cholera 
Background
Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs.
Objectives
To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules.
Search methods
We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014.
Selection criteria
Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial.
Data collection and analysis
Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach.
Main results
Thirty-nine trials were included in this review with 4623 participants.
Antimicrobials versus placebo or no treatment
Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43.51 to -30.03, 19 trials, 1013 participants, moderate quality evidence). Antimicrobial therapy also reduced the total stool volume by 50% (ROM 0.5, 95% CI 0.45 to 0.56, 18 trials, 1042 participants, moderate quality evidence) and reduced the amount of rehydration fluids required by 40% (ROM 0.60, 95% CI 0.53 to 0.68, 11 trials, 1201 participants, moderate quality evidence). The mean duration of fecal excretion of vibrios was reduced by almost three days (MD 2.74 days, 95% CI -3.07 to -2.40, 12 trials, 740 participants, moderate quality evidence).
There was substantial heterogeneity in the size of these benefits, probably due to differences in the antibiotic used, the trial methods (particularly effective randomization), and the timing of outcome assessment. The benefits of antibiotics were seen both in trials recruiting only patients with severe dehydration and in those recruiting patients with mixed levels of dehydration.
Comparisons of antimicrobials
In head-to-head comparisons, there were no differences detected in diarrhoea duration or stool volume for tetracycline compared to doxycycline (three trials, 230 participants, very low quality evidence); or tetracycline compared to ciprofloxacin or norfloxacin (three trials, 259 participants, moderate quality evidence). In indirect comparisons with substantially more trials, tetracycline appeared to have larger benefits than doxycycline, norfloxacin and trimethoprim-sulfamethoxazole for the primary review outcomes.
Single dose azithromycin shortened the duration of diarrhoea by over a day compared to ciprofloxacin (MD -32.43, 95% CI -62.90 to -1.95, two trials, 375 participants, moderate quality evidence) and by half a day compared to erythromycin (MD -12.05, 95% CI -22.02 to -2.08, two trials, 179 participants, moderate quality evidence). It was not compared with tetracycline.
Authors' conclusions
In treating cholera, antimicrobials result in substantial improvements in clinical and microbiological outcomes, with similar effects observed in severely and non-severely ill patients. Azithromycin and tetracycline may have some advantages over other antibiotics.
PLAIN LANGUAGE SUMMARY
Antibiotics for treating cholera
Cochrane Collaboration researchers conducted a review of the effects of antibiotics for treating people with cholera. After searching for relevant trials, they included 39 randomized controlled trials enrolling 4623 people with cholera.
What is cholera and how might antibiotics work
Cholera is a form of severe watery diarrhoea, which spreads from person to person through food and water contaminated with the bacterium Vibrio cholerae. Cholera is common in places with poor water and sanitation, and sometimes causes large epidemics with thousands of people falling ill.
Cholera can cause severe dehydration and death, so the main treatment is to give fluids and salt either orally as oral rehydration salts, or by injection. By clearing the bacteria earlier than the patients own immune system, antibiotics could reduce the duration and severity of the illness, and reduce onward transmission to other people.
What the research says
Antibiotic treatment shortened the duration of diarrhoea by about one and a half days (the normal duration is between three and four days), and reduced the total amount of diarrhoea fluid by half. Consequently, the need for rehydration fluids was also reduced by almost half.
Antibiotic treatment also shortened the period of time where the patient remains contagious by reducing the duration of excretion of Vibrio cholerae in the diarrhoea.
The benefits of antibiotics were seen in trials recruiting only people with severe dehydration, and in those recruiting people with mixed levels of dehydration.
Tetracycline or azithromycin appear more effective than some of the other antibiotics tested, but the choice of which antibiotic to use will depend on local drug resistance.
doi:10.1002/14651858.CD008625.pub2
PMCID: PMC4468928  PMID: 24944120
19.  Knowledge and Use of Zinc Supplementation in the Management of Childhood Diarrhoea among Health Care Workers in Public Primary Health Facilities in Benin-City, Nigeria 
Zinc supplementation reduces the severity, duration and recurrence of childhood acute diarrhoea. These beneficial effects of zinc in the treatment of diarrhoea led to the inclusion of a 10-14 days treatment regimen by the WHO/UNICEF. This study assessed the level of knowledge and use of zinc supplementation in the management of childhood diarrhoea among health care workers in public primary health facilities in Benin-City, Nigeria.
Methodology:
This cross-sectional study was carried out among the total population of health care providers in public primary health facilities in Benin-City. Data collection was done using a pre-tested, structured, self-administered questionnaire and data was analyzed using SPSS version 15.0.
Results:
A total of 168 health care workers participated in the study. Two-thirds of them were aware of zinc supplementation but specific knowledge of zinc supplementation in the management of childhood acute diarrhoea was poor. Thirty-five percent of them prescribed zinc when managing childhood diarrhoea and only 10% of these do so for every case of childhood diarrhoea. About 84.6% of them prescribed the correct dose of zinc while less than half of them prescribe it for the correct duration. All but one of them prescribed zinc in addition to ORS in line with the WHO guideline.
Discussion:
The study revealed a gap in the knowledge and practice of use of zinc supplementation in the management of childhood diarrhoea. It is recommended that nationwide campaigns should be embarked on to promote the use of zinc supplementation in the clinical management of childhood diarrhoea.
doi:10.5539/gjhs.v4n2p68
PMCID: PMC4777055  PMID: 22980153
Zinc supplementation; Childhood diarrhoea; Health care providers
20.  Impact Monitoring of the National Scale Up of Zinc Treatment for Childhood Diarrhea in Bangladesh: Repeat Ecologic Surveys 
PLoS Medicine  2009;6(11):e1000175.
Charles Larson and colleagues find that 23 months into a national campaign to scale up zinc treatment for diarrhea in children under age 5 years, only 10% of children with diarrhea in rural areas and 20%–25% in urban/municipal areas were getting the treatment.
Background
Zinc treatment of childhood diarrhea has the potential to save 400,000 under-five lives per year in lesser developed countries. In 2004 the World Health Organization (WHO)/UNICEF revised their clinical management of childhood diarrhea guidelines to include zinc. The aim of this study was to monitor the impact of the first national campaign to scale up zinc treatment of childhood diarrhea in Bangladesh.
Methods/Findings
Between September 2006 to October 2008 seven repeated ecologic surveys were carried out in four representative population strata: mega-city urban slum and urban nonslum, municipal, and rural. Households of approximately 3,200 children with an active or recent case of diarrhea were enrolled in each survey round. Caretaker awareness of zinc as a treatment for childhood diarrhea by 10 mo following the mass media launch was attained in 90%, 74%, 66%, and 50% of urban nonslum, municipal, urban slum, and rural populations, respectively. By 23 mo into the campaign, approximately 25% of urban nonslum, 20% of municipal and urban slum, and 10% of rural under-five children were receiving zinc for the treatment of diarrhea. The scale-up campaign had no adverse effect on the use of oral rehydration salt (ORS).
Conclusions
Long-term monitoring of scale-up programs identifies important gaps in coverage and provides the information necessary to document that intended outcomes are being attained and unintended consequences avoided. The scale-up of zinc treatment of childhood diarrhea rapidly attained widespread awareness, but actual use has lagged behind. Disparities in zinc coverage favoring higher income, urban households were identified, but these were gradually diminished over the two years of follow-up monitoring. The scale up campaign has not had any adverse effect on the use of ORS.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Diarrheal disease is a significant global health problem with approximately 4 billion cases and 2.5 million deaths annually. The overwhelming majority of cases are in developing countries where there is a particularly high death rate among children under five years of age. Diarrhea is caused by bacterial, parasitic, or viral pathogens, which often spread in contaminated water. Poor hygiene and sanitation, malnutrition, and lack of medical care all contribute to the burden of this disease. Replacing lost fluids and salts is a cheap and effective method to rehydrate people following dehydration caused by diarrhea. Clinical trials show that zinc, as part of a treatment for childhood diarrhea, not only helps to reduce the severity and duration of diarrhea but also reduces the likelihood of a repeat episode in the future. Zinc is now included in the guidelines by the World Health Organization (WHO)/UNICEF for treatment of childhood diarrhea.
Why Was This Study Done?
Zinc treatment together with traditional oral rehydration salts therapy following episodes of diarrhea could potentially benefit millions of children in areas where diarrheal disease is prevalent. The “Scaling Up of Zinc for Young Children” (SUZY) project was established in 2003 to provide zinc treatment for diarrhea in all children under five years of age in Bangladesh. The project was supported by a partnership of public, private, nongovernmental organization, and multinational sector agencies during its scale up to a national campaign across Bangladesh. The partners helped to develop the scale-up campaign, produce and distribute zinc tablets, train health professionals to provide zinc treatment, and create media campaigns (such as advertisements in TV, radio, and newspapers) to raise awareness and promote the use of zinc for diarrhea. The researchers wanted to monitor how effective and successful the national campaign was at promoting zinc treatment for childhood diarrhea. Also, they wanted to highlight any potential problems during the implementation of health care initiatives in areas with deprived health systems.
What Did the Researchers Do and Find?
The researchers set up survey sites to monitor results from the first two years of the SUZY campaign. Four areas, each representing different segments of the population across Bangladesh were surveyed; urban slums, urban nonslums, municipal (small city), and rural. There are approximately 1.5 million children under the age of five across these sites. Households in each survey site were selected at random, and seven surveys were conducted at each site between September 2006 and October 2008—about 3,200 children with diarrhea for each survey. Over 90% of parents used private sector providers of drug treatment so the campaign focused on distribution of zinc tablets in the private sector. They were also available free of charge in the public health sector. TV and radio campaigns for zinc treatment rapidly raised awareness across Bangladesh. Awareness was less than 10% in all communities prelaunch and peaked 10 months later at 90%, 74%, 66%, and 50% in urban nonslum, municipal, urban slum, and rural sites, respectively. However, after 23 months only 25% of urban nonslum, 20% of municipal and urban slum, and 10% of rural children under five years of age were actually using zinc for childhood diarrhea. Use of zinc was shown to be safe, with few side-effects, and did not affect the use of traditional treatments for diarrhea. Researchers also found that many children were not given the correct ten-day course of treatment; 50% of parents were sold seven or fewer zinc tablets.
What Do These Findings Mean?
These findings show that the first national campaign promoting zinc treatment for childhood diarrhea in Bangladesh has had some success. Addition of zinc tablets for diarrhea treatment did not interfere with existing therapies. Mass media campaigns, using TV and radio, were useful for promoting health care initiatives nationwide alongside the education of health care providers and care-givers. The study also identified areas where more work is needed. Surveys in more remote, hard to reach sites in Bangladesh would provide better representation of the country as a whole. High awareness of zinc did not translate into high use. Repeated surveying in the same subdistricts may have overestimated actual awareness levels. Furthermore, mass media messages must link with messages from health care providers to help to reinforce and promote understanding of the use of zinc. A change in focus of media messages from awareness to promoting household decision-making may aid the adoption of zinc treatment for childhood diarrhea and improve adherence.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000175
The International Centre for Diarrhoeal Disease Research, Bangladesh Web site has information about the study
The World Health Organisation provides information on diarrhea
The study was sponsored by the Bill & Melinda Gates Foundation
doi:10.1371/journal.pmed.1000175
PMCID: PMC2765636  PMID: 19888335
21.  Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda 
Malaria Journal  2013;12:131.
Background
Since drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation of the cluster randomized trial.
Methods
A survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district, central Uganda. A cluster was defined as a parish representing a cluster of drug shops. Data was collected using two structured questionnaires: a provider questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received.
Results
Among febrile patients seen at drug shops, 35% had a positive RDT result and 27% had a positive blood slide. Many patients (55%) had previously sought care from another drug shop prior to this consultation. Three quarters (73%) of all febrile patients seen at drug shops received an anti-malarial, of whom 39% received an ACT and 33% received quinine. The rest received another non-artemisinin monotherapy. Only one third (32%) of patients with a positive blood slide had received treatment with Coartem® while 34% of those with a negative blood slide had not received an anti-malarial. Overall appropriate treatment was 34 (95% CI: 28 – 40) with substantial between-cluster variation, ranging from 1% to 55%.
Conclusion
In this setting, the proportion of malaria patients receiving appropriate ACT treatment at drug shops was low. This was due to the practice of presumptive treatment, inadequate training on malaria management and lack of knowledge that Coartem® was the recommended first-line treatment for malaria. There is urgent need for interventions to improve treatment of malaria at these outlets.
doi:10.1186/1475-2875-12-131
PMCID: PMC3637132  PMID: 23587179
22.  Improving community case management of diarrhoea and pneumonia in district Badin, Pakistan through a cluster randomised study—the NIGRAAN trial protocol 
Background
Diarrhoea and pneumonia contribute 30% of deaths in children under 5 in Pakistan. Pakistan’s Lady Health Workers Programme (LHW-P) covers about 60% of the population but has had little impact in reducing morbidity and mortality related to these major childhood killers. An external evaluation of the LHW-P suggests that lack of supportive supervision of LHWs by lady health supervisors (LHSs) is a key determinant of this problem. Project NIGRAAN aims to improve knowledge and skills of LHWs and community caregivers through supervisory strategies employed by LHSs. Ultimately, community case management (CCM) of childhood pneumonia and diarrhoea will improve.
Methods/Design
NIGRAAN is a cluster-randomised trial in District Badin, Pakistan. There are approximately 1100 LHWs supervised by 36 LHSs in Badin. For this study, each LHS serves as a cluster. All LHSs working permanently in Badin who regularly conduct and report field visits are eligible. Thirty-four LHSs have been allocated to either intervention or control arms in a ratio of 1:1 through computer-generated simple randomisation technique. Five LHWs from each LHSs are also randomly picked. All 34 LHSs and 170 LHWs will be actively monitored. The intervention consists of training to build LHS knowledge and skills, clinical mentorship and written feedback to LHWs. Pre- and post-intervention assessments of LHSs, LHWs and community caregivers will be conducted via focus group discussions, in-depth interviews, knowledge assessment questionnaires, skill assessment scorecards and household surveys.
Primary outcome is improvement in CCM practices of childhood diarrhoea and pneumonia and will be assessed at the cluster level.
Discussion
NIGRAAN takes a novel approach to implementation research and explores whether training of LHSs in supervisory skills results in improving the CCM practices of childhood diarrhoea and pneumonia. No significant harm to participants is anticipated. The enablers and barriers towards improved CCM would provide recommendations to policymakers for scale up of this intervention nationally and regionally.
Trial registration
NIGRAAN is registered with the ‘Australian New Zealand Clinical Trials Registry’. Registration Number: ACTRN12613001261707
doi:10.1186/s13012-014-0186-9
PMCID: PMC4297376  PMID: 25490971
Community case management; Pneumonia and diarrhoea; LHW programme; Supervision; Implementation research; Pakistan
23.  Cost-effectiveness of live oral attenuated human rotavirus vaccine in Tanzania 
Background
Globally, diarrhoea is the second leading cause of morbidity and mortality, responsible for the annual loss of about 10% of the total global childhood disease burden. In Tanzania, Rotavirus infection is the major cause of severe diarrhoea and diarrhoeal mortality in children under five years. Immunisation can reduce the burden, and Tanzania added rotavirus vaccine to its national immunisation programme in January 2013. This study explores the cost effectiveness of introducing rotavirus vaccine within the Tanzania Expanded Programme on Immunisation (EPI).
Methods
We quantified all health system implementation costs, including programme costs, to calculate the cost effectiveness of adding rotavirus immunisation to EPI and the existing provision of diarrhoea treatment (oral rehydration salts and intravenous fluids) to children. We used ingredients and step down costing methods. Cost and coverage data were collected in 2012 at one urban and one rural district hospital and a health centre in Tanzania. We used Disability Adjusted Life Years (DALYs) as the outcome measure and estimated incremental costs and health outcomes using a Markov transition model with weekly cycles up to a five-year time horizon.
Results
The average unit cost per vaccine dose at 93% coverage is US$ 8.4, with marked difference between the urban facility US$ 5.2; and the rural facility US$ 9.8. RV1 vaccine added to current diarrhoea treatment is highly cost effective compared to diarrhoea treatment given alone, with incremental cost effectiveness ratio of US$ 112 per DALY averted, varying from US$ 80–218 in sensitivity analysis. The intervention approaches a 100% probability of being cost effective at a much lower level of willingness-to-pay than the US$609 per capita Tanzania gross domestic product (GDP).
Conclusions
The combination of rotavirus immunisation with diarrhoea treatment is likely to be cost effective when willingness to pay for health is higher than USD 112 per DALY. Universal coverage of the vaccine will accelerate progress towards achievement of the child health Millennium Development Goals.
doi:10.1186/s12962-015-0033-0
PMCID: PMC4422135  PMID: 25949216
Cost; Cost-effectiveness; Rotavirus; Vaccine
24.  Evaluation of Integrated Community Case Management in Eight Districts of Central Uganda 
PLoS ONE  2015;10(8):e0134767.
Objective
Evidence is limited on whether Integrated Community Case Management (iCCM) improves treatment coverage of the top causes of childhood mortality (acute respiratory illnesses (ARI), diarrhoea and malaria). The coverage impact of iCCM in Central Uganda was evaluated.
Methods
Between July 2010 and December 2012 a pre-post quasi-experimental study in eight districts with iCCM was conducted; 3 districts without iCCM served as controls. A two-stage household cluster survey at baseline (n = 1036 and 1042) and end line (n = 3890 and 3844) was done in the intervention and comparison groups respectively. Changes in treatment coverage and timeliness were assessed using difference in differences analysis (DID). Mortality impact was modelled using the Lives Saved Tool.
Findings
5,586 Village Health Team members delivered 1,907,746 treatments to children under age five. Use of oral rehydration solution (ORS) and zinc treatment of diarrhoea increased in the intervention area, while there was a decrease in the comparison area (DID = 22.9, p = 0.001). Due to national stock-outs of amoxicillin, there was a decrease in antibiotic treatment for ARI in both areas; however, the decrease was significantly greater in the comparison area (DID = 5.18; p<0.001). There was a greater increase in Artemisinin Combination Therapy treatment for fever in the intervention areas than in the comparison area but this was not significant (DID = 1.57, p = 0.105). In the intervention area, timeliness of treatments for fever and ARI increased significantly higher in the intervention area than in the comparison area (DID = 2.12, p = 0.029 and 7.95, p<0.001, respectively). An estimated 106 lives were saved in the intervention area while 611 lives were lost in the comparison area.
Conclusion
iCCM significantly increased treatment coverage for diarrhoea and fever, mitigated the effect of national stock outs of amoxicillin on ARI treatment, improved timeliness of treatments for fever and ARI and saved lives.
doi:10.1371/journal.pone.0134767
PMCID: PMC4534192  PMID: 26267141
25.  Role of Antidiarrhoeal Drugs as Adjunctive Therapies for Acute Diarrhoea in Children 
Acute diarrhoea is a leading cause of child mortality in developing countries. Principal pathogens include Escherichia coli, rotaviruses, and noroviruses. 90% of diarrhoeal deaths are attributable to inadequate sanitation. Acute diarrhoea is the second leading cause of overall childhood mortality and accounts for 18% of deaths among children under five. In 2004 an estimated 1.5 million children died from diarrhoea, with 80% of deaths occurring before the age of two. Treatment goals are to prevent dehydration and nutritional damage and to reduce duration and severity of diarrhoeal episodes. The recommended therapeutic regimen is to provide oral rehydration solutions (ORS) and to continue feeding. Although ORS effectively mitigates dehydration, it has no effect on the duration, severity, or frequency of diarrhoeal episodes. Adjuvant therapy with micronutrients, probiotics, or antidiarrhoeal agents may thus be useful. The WHO recommends the use of zinc tablets in association with ORS. The ESPGHAN/ESPID treatment guidelines consider the use of racecadotril, diosmectite, or probiotics as possible adjunctive therapy to ORS. Only racecadotril and diosmectite reduce stool output, but no treatment has yet been shown to reduce hospitalisation rate or mortality. Appropriate management with validated treatments may help reduce the health and economic burden of acute diarrhoea in children worldwide.
doi:10.1155/2013/612403
PMCID: PMC3603675  PMID: 23533446

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