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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.  Subsidising artemisinin-based combination therapy in the private retail sector 
Background
Malaria causes ill health and death in Africa. Treating illness promptly with artemisinin-based combination therapy (ACT) is likely to cure people and avoid the disease progressing to more severe forms and death. In many countries, ACT use remains low. Part of the problem is that most people seek treatment from the retail sector where ACTs are expensive; this expense is a barrier to their use.
The Global Fund and other international organisations are subsidising the cost of ACTs for private retail providers to improve access to ACTs. The subsidy was initially organised through a stand-alone initiative, called the Affordable Medicines Facility-malaria (AMFm), but has since been integrated into the Global Fund core grant management and financial processes.
Objectives
To assess the effect of programmes that include ACT price subsidies for private retailers on ACT use, availability, price and market share.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1, The Cochrane Library, including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EbscoHost), EconLit (ProQuest), Global Health (OvidSP), Regional Indexes (Global Health Library, WHO), LILACS (Global Health Library, WHO), Science Citation Index and Social Sciences Citation Index (ISI Web of Science) and Health Management (ProQuest). All databases were searched February 2015, except for Health Management which was searched November 2013, without any date, language or publication status restrictions. We also searched the International Clinical Trials Registry Platform (ICTRP; WHO), ClinicalTrials.gov (NIH) and various grey literature sources. We also conducted a cited reference search for all included studies in ISI Web of Knowledge, checked references of identified articles and contacted authors to identify additional studies.
Selection criteria
Randomised trials, non-randomised trials, controlled before-after studies and interrupted-time-series studies that compared the effects of ACT price subsidies for private retailers to no subsidies or alternative ACT financing mechanisms were eligible for inclusion. Two authors independently screened and selected studies for inclusion.
Data collection and analysis
Two review authors independently extracted data, assessed study risk of bias and confidence in effect estimates (certainty of evidence) using Grading of Recommendations, Assessment, Development and Evaluation (GRADE).
Main results
We included four trials (two cluster-randomised trials reported in three articles and two non-randomised cluster trials). Three trials assessed retail sector ACT subsidies combined with supportive interventions (retail outlet provider training, community awareness and mass media campaigns). One trial assessed vouchers provided to households to purchase subsidised ACTs. Price subsidies ranged from 80% to 95%. One trial enrolled children under five years of age; the other three trials studied people of all age groups. The studies were done in rural districts in East Africa (Kenya, Uganda and Tanzania).
In this East Africa setting, these ACT subsidy programmes increased the percentage of children under five years of age receiving ACTs on the day, or following day, of fever onset by 25 percentage points (95% confidence interval (CI) 14.1 to 35.9 percentage points; 1 study, high certainty evidence). This suggests that in practice, among febrile children under five years of age with an ACT usage rate of 5% without a subsidy, subsidy programmes would increase usage by between 19% and 41% over a one year period.
The ACT subsidy programmes increased the percentage of retail outlets stocking ACTs for children under five years of age by 31.9 percentage points (95% CI 26.3 to 37.5 percentage points; 1 study, high certainty evidence). Effects on ACT stocking for patients of any age is unknown because the certainty of evidence was very low.
The ACT subsidy programmes decreased the median cost of ACTs for children under five years of age by US$ 0.84 (median cost per ACT course without subsidy: US$ 1.08 versus with subsidy: US$ 0.24; 1 study, high certainty evidence).
The ACT subsidy programmes increased the market share of ACTs for children under five years of age by between 23.6 and 63.0 percentage points (1 study, high certainty evidence).
The ACT subsidy programmes decreased the use of older antimalarial drugs (such as amodiaquine and sulphadoxine-pyrimethamine) among children under five years of age by 10.4 percentage points (95% CI 3.9 to 16.9 percentage points; 1 study, high certainty evidence).
None of the three studies of ACT subsidies reported the number of patients treated who had confirmed malaria.
Vouchers increased the likelihood that an illness is treated with an ACT by 16 to 23 percentage points; however, vouchers were associated with a high rate of over-treatment of malaria (only 56% of patients taking ACTs from the drug shop tested positive for malaria under the 92% subsidy; 1 study, high certainty evidence).
Authors' conclusions
Programmes that include substantive subsidies for private sector retailers combined with training of providers and social marketing improved use and availability of ACTs for children under five years of age with suspected malaria in research studies from three countries in East Africa. These programmes also reduced prices of ACTs, improved market share of ACTs and reduced the use of older antimalarial drugs among febrile children under five years of age. The research evaluates drug delivery but does not assess whether the patients had confirmed (parasite-diagnosed) malaria. None of the included studies assessed patient outcomes; it is therefore not known whether the effects seen in the studies would translate to an impact on health.
PLAIN LANGUAGE SUMMARY
Subsidising artemisinin-based combination therapy in drug shops and pharmacies
We conducted a review of the effect of subsidising artemisinin-based combination therapy (ACT) drugs for malaria. We searched for all relevant studies up to February 2015 and identified four. Our findings are summarised below.
Background
Malaria causes ill health and death in Africa, particularly in children under five years of age and poor rural populations. The World Health Organization recommends that people use ACT to treat malaria. ACT drugs are available at shops and pharmacies, but these drugs are expensive and people often choose cheaper, older, less effective drugs instead. The Global Fund and other international organisations have therefore decided to subsidise the cost of ACT drugs so that people can buy them from shops and pharmacies at prices similar to, or lower than, those of the older, less effective drugs.
What is the effect of delivery programmes that subsidise ACT prices?
We included four studies. One study looked at the effect of subsidising ACT drugs for children under five years of age and three studies looked at subsidising ACT drugs for people of all ages. All studies were from rural districts in East Africa (Kenya, Uganda and Tanzania). ACT price subsidies were accompanied with activities (such as staff training at shops and pharmacies, community awareness and mass media campaigns) to promote appropriate use of antimalarial drugs in all except one study. In all four studies, the effect of subsidising the drugs was compared to not subsidising the drugs. Price subsidies ranged from 80% to 95% of the actual price; vouchers to households were used in one study.
The findings from these studies indicate that ACT subsidy programmes:
lead to a substantial increase in the number of children under five years of age who used ACTs when they had a fever (high certainty evidence);
lead to a substantial increase in the number of shops that stocked ACTs for children under five years of age (high certainty evidence); we could not draw any conclusion on the effect on the number of shops that stocked ACTs for patients of any age because the quality of evidence was very low;
lead to a substantial decrease in the price of ACTs for children under five years of age (high certainty evidence);
lead to a substantial increase in the market share of ACTs for children under five years of age (high certainty evidence); and
lead to a decrease in the use of older, less effective antimalarials among children under five years of age (high certainty evidence).
None of the studies measured whether the subsidy programmes led to any harmful effects (such as the inappropriate use of ACTs, in other words people who receive ACTs but do not actually have malaria).
The review findings also showed that subsidising ACT prices using vouchers lead to an increase in the likelihood that an illness was treated with an ACT among people seeking treatment for fever or suspected malaria. However, vouchers also lead to an increase in inappropriate use of ACTs (high certainty evidence).
doi:10.1002/14651858.CD009926.pub2
PMCID: PMC4916935  PMID: 26954551
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.  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
6.  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
7.  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
8.  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
9.  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
10.  Integrated management of childhood illness (IMCI) strategy for children under five 
Background
More than 7.5 million children younger than age five living in low- and middle-income countries die every year. The World Health Organization (WHO) developed the integrated management of childhood illness (IMCI) strategy to reduce mortality and morbidity and to improve quality of care by improving the delivery of a variety of curative and preventive medical and behavioral interventions at health facilities, at home, and in the community.
Objectives
To evaluate the effects of programs that implement the IMCI strategy in terms of death, nutritional status, quality of care, coverage with IMCI deliverables, and satisfaction of beneficiaries.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; MEDLINE; EMBASE, Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EbscoHost; the Latin American Caribbean Health Sciences Literature (LILACS), Virtual Health Library (VHL); the WHO Library & Information Networks for Knowledge Database (WHOLIS); the Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Science; Population Information Online (POPLINE); the WHO International Clinical Trials Registry Platform (WHO ICTRP); and the Global Health, Ovid and Health Management, ProQuest database. We performed searches until 30 June 2015 and supplemented these by searching revised bibliographies and by contacting experts to identify ongoing and unpublished studies.
Selection criteria
We sought to include randomised controlled trials (RCTs) and controlled before-after (CBA) studies with at least two intervention and two control sites evaluating the generic IMCI strategy or its adaptation in children younger than age five, and including at minimum efforts to improve health care worker skills for case management. We excluded studies in which IMCI was accompanied by other interventions including conditional cash transfers, food supplementation, and employment. The comparison group received usual health services without provision of IMCI.
Data collection and analysis
Two review authors independently screened searches, selected trials, and extracted, analysed and tabulated data. We used inverse variance for cluster trials and an intracluster co-efficient of 0.01 when adjustment had not been made in the primary study. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) approach to assess the certainty of evidence.
Main results
Two cluster-randomised trials (India and Bangladesh) and two controlled before-after studies (Tanzania and India) met our inclusion criteria. Strategies included training of health care staff, management strengthening of health care systems (all four studies), and home visiting (two studies). The two studies from India included care packages targeting the neonatal period.
One trial in Bangladesh estimated that child mortality may be 13% lower with IMCI, but the confidence interval (CI) included no effect (risk ratio (RR) 0.87, 95% CI 0.68 to 1.10; 5090 participants; low-certainty evidence). One CBA study in Tanzania gave almost identical estimates (RR 0.87, 95% CI 0.72 to 1.05; 1932 participants).
One trial in India examined infant and neonatal mortality by implementing the integrated management of neonatal and childhood illness (IMNCI) strategy including post-natal home visits. Neonatal and infant mortality may be lower in the IMNCI group compared with the control group (infant mortality hazard ratio (HR) 0.85, 95% CI 0.77 to 0.94; neonatal mortality HR 0.91, 95% CI 0.80 to 1.03; one trial, 60,480 participants; low-certainty evidence).
We estimated the effect of IMCI on any mortality measured by combining infant and child mortality in the one IMCI and the one IMNCI trial. Mortality may be reduced by IMCI (RR 0.85, 95% CI 0.78 to 0.93; two trials, 65,570 participants; low-certainty evidence).
Two trials (India, Bangladesh) evaluated nutritional status and noted that there may be little or no effect on stunting (RR 0.94, 95% CI 0.84 to 1.06; 5242 participants, two trials; low-certainty evidence) and there is probably little or no effect on wasting (RR 1.04, 95% CI 0.87 to 1.25; two trials, 4288 participants; moderate-certainty evidence).The Tanzania CBA study showed similar results.
Investigators measured quality of care by observing prescribing for common illnesses at health facilities (727 observations, two studies; very low-certainty evidence) and by observing prescribing by lay health care workers (1051 observations, three studies; very low-certainty evidence). We could not confirm a consistent effect on prescribing at health facilities or by lay health care workers, as certainty of the evidence was very low.
For coverage of IMCI deliverables, we examined vaccine and vitamin A coverage, appropriate care seeking, and exclusive breast feeding. Two trials (India, Bangladesh) estimated vaccine coverage for measles and reported that there is probably little or no effect on measles vaccine coverage (RR 0.92, 95% CI 0.80 to 1.05; two trials, 4895 participants; moderate-certainty evidence), with similar effects seen in the Tanzania CBA study. Two studies measured the third dose of diphtheria, pertussis, and tetanus vaccine; and two measured vitamin A coverage, all providing little or no evidence of increased coverage with IMCI.
Four studies (2 from India, and 1 each from Tanzania and Bangladesh) reported appropriate care seeking and derived information from careful questioning of mothers about recent illness. Some studies on effects of IMCI may report better care seeking behavior, but others do not report this.
All four studies recorded maternal responses on exclusive breast feeding. They provided mixed results and very low-certainty evidence. Therefore, we do not know whether IMCI impacts exclusive breast feeding.
No studies reported on the satisfaction of mothers and service users.
Authors' conclusions
The mix of interventions examined in research studies evaluating the IMCI strategy varies, and some studies include specific inputs to improve neonatal health. Most studies were conducted in South Asia. Implementing the integrated management of childhood illness strategy may reduce child mortality, and packages that include interventions for the neonatal period may reduce infant mortality. IMCI may have little or no effect on nutritional status and probably has little or no effect on vaccine coverage. Maternal care seeking behavior may be more appropriate with IMCI, but study results have been mixed, providing evidence of very low certainty about whether IMCI has effects on adherence to exclusive breast feeding.
PLAIN LANGUAGE SUMMARY
Integrated management of childhood illness (IMCI) strategy for children younger than five years of age
What is the aim of this review?
The aim of this Cochrane review is to assess the effects of programs that use the World Health Organization integrated management of childhood illness (IMCI) strategy. Cochrane researchers searched for all potentially relevant studies and found four studies that met review criteria.
Key messages
This review shows that use of the World Health Organization IMCI strategy may led to fewer deaths among children from birth to five years of age. Effects of IMCI on other issues, such as illness or quality of care, were mixed, and some evidence of this was of very low certainty. In the future, researchers should explore how the IMCI strategy can best be delivered.
What was studied in the review?
More than 7.5 million children globally die each year before reaching the age of five. Most are from poor communities and live in the poorest countries. These children are more likely than others to suffer from malnutrition and from infections such as neonatal sepsis, measles, diarrhoea, malaria, and pneumonia.
Effective strategies to prevent and treat sick children are available but do not reach them. One reason for this is that health care services are often too far away or too expensive. Health facilities in these settings often lack supplies and well-trained health care workers. In addition, ill children may have several health problems at the same time, and this can make diagnosis and treatment difficult for health care workers.
In the 1990s, the World Health Organization (WHO) developed a strategy called integrated management of childhood illness (IMCI) to address these problems. This strategy aims to prevent death and disease while improving the quality of care for ill children up to the age of five. It consists of three parts.
• Improving the skills of health care workers by providing training and guidelines.
• Improving how health care systems are organized and managed, including access to supplies.
• Visiting homes and communities to promote good child rearing practices and good nutrition, while encouraging parents to bring their children to a clinic when the children are ill.
The WHO encourages countries to adapt the IMCI strategy to their own national settings. Types of childhood illnesses prioritised and ways in which services are delivered may vary from country to country.
What are the main results of the review?
This Cochrane review included four studies assessing the effectiveness of the IMCI strategy. These studies were conducted in Tanzania, Bangladesh, and India. The IMCI strategy was used very differently across studies. For instance, the study from Tanzania implemented health care worker training and improved drug supply but did not include home visits or community activities; the study from Bangladesh added new health care workers while training existing health care workers; and the two Indian studies specifically targeted newborns as well as older children.
This review showed that use of IMCI:
• may lead to fewer deaths among children from birth to five years of age (low-certainty evidence);
• may have little or no effect on the number of children suffering from stunting (low-certainty evidence);
• probably has little or no effect on the number of children suffering from wasting (moderate-certainty evidence);
• probably has little or no effect on the number of children who receive measles vaccines; and
• may lead to mixed results on the number of parents seeking care for their child when he or she is ill.
We do not know whether IMCI has any effect on the way health care workers treat common illnesses because certainty of the evidence was assessed as very low.
We do not know whether IMCI has any effect on the number of mothers who exclusively breast feed their child, because certainty of the evidence was assessed as very low.
None of the included studies assessed the satisfaction of mothers and service users by using an IMCI strategy.
How up-to-date is this review?
Review authors searched for studies that had been published up to 30 June 2015.
doi:10.1002/14651858.CD010123.pub2
PMCID: PMC4943011  PMID: 27378094
11.  Monitoring iCCM referral systems: Bugoye Integrated Community Case Management Initiative (BIMI) in Uganda 
Malaria Journal  2016;15:247.
Background
In Uganda, over half of under-five child mortality is attributed to three infectious diseases: malaria, pneumonia and diarrhoea. Integrated community case management (iCCM) trains village health workers (VHWs) to provide in-home diagnosis and treatment of these common childhood illnesses. For severely ill children, iCCM relies on a functioning referral system to ensure timely treatment at a health facility. However, referral completion rates vary widely among iCCM programmes and are difficult to monitor. The Bugoye Integrated Community Case Management Initiative (BIMI) is an iCCM programme operating in Bugoye sub-county, Uganda. This case study describes BIMI’s experience with monitoring referral completion at Bugoye Health Centre III (BHC), and outlines improvements to be made within iCCM referral systems.
Methods
This study triangulated multiple data sources to evaluate the strengths and gaps in the BIMI referral system. Three quantitative data sources were reviewed: (1) VHW report of referred patients, (2) referral forms found at BHC, and (3) BHC patient records. These data sources were collated and triangulated from January–December 2014. The goal was to determine if patients were completing their referrals and if referrals were adequately documented using routine data sources.
Results
From January–December 2014, there were 268 patients referred to BHC, as documented by VHWs. However, only 52 of these patients had referral forms stored at BHC. Of the 52 referral forms found, 22 of these patients were also found in BHC register books recorded by clinic staff. Thus, the study found a mismatch between VHW reports of patient referrals and the referral visits documented at BHC. This discrepancy may indicate several gaps: (1) referred patients may not be completing their referral, (2) referral forms may be getting lost at BHC, and, (3) referred patients may be going to other health facilities or drug shops, rather than BHC, for their referral.
Conclusions
This study demonstrates the challenges of effectively monitoring iCCM referral completion, given identified limitations such as discordant data sources, incomplete record keeping and lack of unique identifiers. There is a need to innovate and improve the ways by which referral compliance is monitored using routine data, in order to improve the percentage of referrals completed. Through research and field experience, this study proposes programmatic and technological solutions to rectify these gaps within iCCM programmes facing similar challenges. With improved monitoring, VHWs will be empowered to increase referral completion, allowing critically ill children to access needed health services.
Electronic supplementary material
The online version of this article (doi:10.1186/s12936-016-1300-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12936-016-1300-z
PMCID: PMC4850682  PMID: 27129920
Africa; Child mortality; Case management; Referral; Paediatric malaria
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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
18.  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
19.  Health workers’ perspectives, knowledge and skills regarding community case management of childhood diarrhoea and pneumonia: a qualitative inquiry for an implementation research project “Nigraan” in District Badin, Sindh, Pakistan 
Background
Pakistan’s Lady Health Worker Programme aims to provide care to children sick with pneumonia and diarrhoea, which continues to cause 27 % under-five mortality in Pakistan. The quality of supervision received by Lady Health Workers (LHWs) in the programme influence their knowledge and skills, in turn impacting their ability to provide care.
Methods
This study is part of an implementation research project titled “Nigraan” (an Urdu word meaning supervisor), and explores LHW and Lady Health Supervisor (LHS) perspectives regarding the role of supervision in improving LHWs performance and motivation in district Badin, Sindh, Pakistan. Their knowledge and skills regarding integrated community case management (iCCM) of diarrhoea and pneumonia were also assessed. Fourteen focus group discussions and 20 in-depth interviews were conducted as part of this qualitative inquiry. Analysis was done using QSR NVivo version 10.
Results
Most LHWs and LHSs identified pneumonia and diarrhoea as two major causes of death among children under-five. Poverty, illiteracy, poor hygiene and lack of clean drinking water were mentioned as underlying causes of high mortality due to diarrhoea and pneumonia. LHWs and LHSs gaps in knowledge included classification of dehydration, correctly preparing ORS and prescribing correct antibiotics in pneumonia. Lack of training, delayed salaries and insufficient medicines and other supplies were identified as major factors impeding appropriate knowledge and skill development for iCCM of childhood diarrhoea and pneumonia. LHWs considered adequate supervision and the presence of LHSs during household visits as a factor facilitating their performance. LHWs did not have a preference for written or verbal feedback, but LHSs considered written individual feedback to LHWs to be more useful than group and verbal feedback.
Conclusion
LHWs have knowledge and skill gaps that prevent them from providing effective care for diarrhoea and pneumonia. Enhanced supportive feedback from LHSs could improve LHWs skills and performance.
doi:10.1186/s12913-016-1699-5
PMCID: PMC5009648  PMID: 27585826
Implementation research; Community health workers; Integrated community case management; Childhood diarrhoea and pneumonia; Qualitative inquiry; Pakistan
20.  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
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.  Hand washing promotion for preventing diarrhoea 
Background
Diarrhoea accounts for 1.8 million deaths in children in low- and middle-income countries (LMICs). One of the identified strategies to prevent diarrhoea is hand washing.
Objectives
To assess the effects of hand washing promotion interventions on diarrhoeal episodes in children and adults.
Search methods
We searched the Cochrane Infectious Diseases Group Specialized Register (27 May 2015); CENTRAL (published in the Cochrane Library 2015, Issue 5); MEDLINE (1966 to 27 May 2015); EMBASE (1974 to 27 May 2015); LILACS (1982 to 27 May 2015); PsycINFO (1967 to 27 May 2015); Science Citation Index and Social Science Citation Index (1981 to 27 May 2015); ERIC (1966 to 27 May 2015); SPECTR (2000 to 27 May 2015); Bibliomap (1990 to 27 May 2015); RoRe, The Grey Literature (2002 to 27 May 2015); World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), metaRegister of Controlled Trials (mRCT), and reference lists of articles up to 27 May 2015. We also contacted researchers and organizations in the field.
Selection criteria
Individually randomized controlled trials (RCTs) and cluster-RCTs that compared the effects of hand washing interventions on diarrhoea episodes in children and adults with no intervention.
Data collection and analysis
Three review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. We stratified the analyses for child day-care centres or schools, community, and hospital-based settings. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CIs). We used the GRADE approach to assess the quality of evidence.
Main results
We included 22 RCTs: 12 trials from child day-care centres or schools in mainly high-income countries (54,006 participants), nine community-based trials in LMICs (15,303 participants), and one hospital-based trial among people with acquired immune deficiency syndrome (AIDS) (148 participants).
Hand washing promotion (education activities, sometimes with provision of soap) at child day-care facilities or schools prevents around one-third of diarrhoea episodes in high income countries (rate ratio 0.70; 95% CI 0.58 to 0.85; nine trials, 4664 participants, high quality evidence), and may prevent a similar proportion in LMICs but only two trials from urban Egypt and Kenya have evaluated this (rate ratio 0.66, 95% CI 0.43 to 0.99; two trials, 45,380 participants, low quality evidence). Only three trials reported measures of behaviour change and the methods of data collection were susceptible to bias. In one trial from the USA hand washing behaviour was reported to improve; and in the trial from Kenya that provided free soap, hand washing did not increase, but soap use did (data not pooled; three trials, 1845 participants, low quality evidence).
Hand washing promotion among communities in LMICs probably prevents around one-quarter of diarrhoea episodes (rate ratio 0.72, 95% CI 0.62 to 0.83; eight trials, 14,726 participants, moderate quality evidence). However, six of these eight trials were from Asian settings, with only single trials from South America and sub-Saharan Africa. In six trials, soap was provided free alongside hand washing education, and the overall average effect size was larger than in the two trials which did not provide soap (soap provided: rate ratio 0.66, 95% CI 0.56 to 0.78; six trials, 11,422 participants; education only: rate ratio: 0.84, 95% CI 0.67 to 1.05; two trials, 3304 participants). There was increased hand washing at major prompts (before eating/cooking, after visiting the toilet or cleaning the baby's bottom), and increased compliance to hand hygiene procedure (behavioural outcome) in the intervention groups than the control in community trials (data not pooled: three trials, 3490 participants, high quality evidence).
Hand washing promotion for the one trial conducted in a hospital among high-risk population showed significant reduction in mean episodes of diarrhoea (1.68 fewer) in the intervention group (Mean difference 1.68, 95% CI 1.93 to 1.43; one trial, 148 participants, moderate quality evidence). There was increase in hand washing frequency, seven times per day in the intervention group versus three times in the control in this hospital trial (one trial, 148 participants, moderate quality evidence).
We found no trials evaluating or reporting the effects of hand washing promotions on diarrhoea-related deaths, all-cause-under five mortality, or costs.
Authors' conclusions
Hand washing promotion probably reduces diarrhoea episodes in both child day-care centres in high-income countries and among communities living in LMICs by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term.
PLAIN LANGUAGE SUMMARY
Hand washing promotion for preventing diarrhoea
Review question
This Cochrane Review summarises trials evaluating the effects of promoting hand washing on the incidence of diarrhoea among children and adults in day-care centres, schools, communities, or hospitals. After searching for relevant trials up to 27 May 2015, we included 22 randomized controlled trials conducted in both high-income countries (HICs) and low- and middle-income countries (LMICs). These trials enrolled 69,309 children and 148 adults.
How does hand washing prevent diarrhoea and how might hand washing be promoted
Diarrhoea causes many deaths in children below five years of age, mostly in LMICs. The organisms causing diarrhoea are transmitted from person to person through food and water contaminated with faeces, or through person-to-person contact. Hand washing after defecation, or after cleaning a baby's bottom, and before preparing and eating food, can therefore reduce the risk of diarrhoea. Hand washing can be promoted through group or individual training on hygiene education, germ-health awareness, use of posters, leaflets, comic books, songs, and drama.
What this review says
Hand washing promotion at child day-care facilities or schools in HICs probably prevents around 30% of diarrhoea episodes (high quality evidence), and may prevent a similar proportion in schools in LMICs (low quality evidence). Among communities in LMICs hand washing promotion prevents around 28% of diarrhoea episodes (moderate quality evidence). In the only hospital-based trial included in this review, hand washing promotion also had important reduction in the mean episodes of diarrhoea (moderate quality evidence). This is based on only a single trial with few participants and thus there is need for more trials to confirm this. Effects of hand washing promotion on related hand hygiene behaviour changes improved more in the intervention groups than in the control in all the settings (low to high quality evidence). None of the included trials assessed the effect of handwashing promotion on diarrhoeal-related deaths, all-cause under-five mortality, or the cost-effectiveness of hand washing promotions.
Conclusion
Hand washing promotion in HICs and LMICs settings may reduce incidence of diarrhoea by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term.
doi:10.1002/14651858.CD004265.pub3
PMCID: PMC4563982  PMID: 26346329
23.  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
24.  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
25.  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

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