Newborn and child health national and provincial clinical practice guidelines in South Africa, Nigeria and Malawi: a scoping review.

BACKGROUND: Low and middle-income countries remain disproportionately affected by high rates of child mortality. Clinical practice guidelines are essential clinical tools supporting implementation of effective, safe, and cost-effective healthcare. High-quality evidence-based guidelines play a key role in improving clinical management to impact child mortality. We aimed to identify and assess the quality of guidelines for newborn and child health published in South Africa, Nigeria and Malawi in the last 5 years (2017-2022). METHODS: We searched relevant websites (June-July 2022), for publicly available national and subnational de novo or adapted guidelines, addressing newborn and child health in the three countries. Pairs of reviewers independently extracted information from eligible guidelines (scope, topic, target population and users, responsible developers, stakeholder consultation process, adaptation description, assessment of evidence certainty). We appraised guideline quality using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument. RESULTS: We identified 40-guidelines from the three countries. Of these, 8/40 reported being adopted from a parent guideline. More guidelines (n = 19) provided guidance on communicable diseases than on non-communicable diseases (n = 8). Guidelines were most often developed by national health ministries (n = 30) and professional societies (n = 14). Eighteen guidelines reported on stakeholder consultation; with Nigeria (10/11) and Malawi (3/6) faring better than South Africa (5/23) in reporting this activity. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used in 1/7 guidelines that reported assessing certainty of evidence. Overall guidelines scored well on two AGREE II domains: scope and purpose median (IQR) score 68% (IQR 47-83), and clarity of presentation 81% (67-94). Domains critical for ensuring credible guidance scored below 20%: rigour of development 11% (4-32) and editorial independence 6% (0-27). CONCLUSION: National ministries and professional societies drive guideline activities in Malawi, Nigeria and South Arica. However, the methods and reporting do not adhere to global standards. We found low AGREE II scores for rigour of guideline development and editorial independence and limited use of GRADE or adaptation methods. This undermines the credibility of available guidelines to support evidence-informed care. Our findings highlight the importance of ongoing efforts to strengthen partnerships, capacity, and support for guideline development.

Hand hygiene for the prevention of infections in neonates.

BACKGROUND: Annually, infections contribute to approximately 25% of the 2.8 million neonatal deaths worldwide. Over 95% of sepsis-related neonatal deaths occur in low- and middle-income countries. Hand hygiene is an inexpensive and cost-effective method of preventing infection in neonates, making it an affordable and practicable intervention in low- and middle-income country settings. Therefore, hand hygiene practices may hold strong prospects for reducing the occurrence of infection and infection-related neonatal death. OBJECTIVES: To determine the effectiveness of different hand hygiene agents for preventing neonatal infection in both community and health facility settings. SEARCH METHODS: Searches were conducted without date or language limits in December 2022 in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Cumulated Index to Nursing and Allied Health Literature (CINAHL), clinicaltrials.gov and International Clinical Trials Registry Platform (ICTRP) trial registries. The reference lists of retrieved studies or related systematic reviews were screened for studies not identified by the searches.   SELECTION CRITERIA: We included randomized controlled trials (RCTs), cross-over trials, and cluster trials that included pregnant women, mothers, other caregivers, and healthcare workers who received interventions within either the community setting or in health facility settings, and the neonates  in the neonatal care units or community settings. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and the GRADE approach to assess the certainty of evidence. Primary outcomes were incidence of suspected infection (author-defined in study) within the first 28 days of life, bacteriologically confirmed infection within the first 28 days of life, all-cause mortality within the first seven days of life (early neonatal death), and all-cause mortality from the 8th to the 28th day of life (late neonatal death). MAIN RESULTS: Our review included six studies: two RCTs, one cluster-RCT, and three cross-over trials. Three studies involved 3281 neonates; the remaining three did not specify the actual number of neonates included in their study. Three studies involved 279 nurses working in neonatal intensive care units (NICUs). The number of nurses included was not specified by one study. A cluster-RCT included 103 pregnant women of over 34 weeks gestation from 10 villages in a community setting (sources of data: 103 mother-neonate pairs) and another community-based study included 258 married pregnant women at 32 to 34 weeks of gestation (the trial reported adverse events on 258 mothers and 246 neonates). Studies examined the effectiveness of different hand hygiene practices for the incidence of suspected infection (author-defined in study) within the first 28 days of life. Three studies were rated as having low risk for allocation bias,  two studies were rated as unclear risk, and one was rated as having high risk. One study was rated as having a low risk of bias for allocation concealment,  one study was rated as unclear risk, and four werw rated as having high risk. Two studies were rated as having low risk for performance bias and two were rated as having low risk for attrition bias.  One class of agent versus another class of agent: 2% chlorhexidine gluconate (CHG) compared to alcohol hand sanitiser (61% alcohol and emollients) For this comparison, no study assessed the effect of the intervention on the incidence of suspected infection within the first 28 days of life. Two percent chlorhexidine gluconate (CHG) probably reduces the risk of all infection in neonates compared to 61% alcohol hand sanitiser in regard to the incidence of all bacteriologically confirmed infection within the first 28 days of life (RR 0.79, 95% confidence interval (CI) 0.66 to 0.93; 2932 participants, 1 study; moderate-certainty evidence), number needed to treat for an additional beneficial outcome (NNTB): 385. The adverse outcome was reported as mean self-reported skin change and mean observer-reported skin change. There may be little to no difference between the effects of 2% CHG on nurses' skin compared to alcohol hand sanitiser, based on very low-certainty evidence for mean self-reported skin change (mean difference (MD) -0.80, 95% CI -1.59 to 0.01; 119 participants, 1 study) and on mean observer reported skin change (MD -0.19, CI -0.35 to -0.03; 119 participants, 1 study), respectively. We identified no study that reported on all-cause mortality and other outcomes for this comparison. None of the included studies assessed all-cause mortality within the first seven days of life nor the duration of hospital stay. One class of agent versus two or more other classes of agent: CHG compared to plain liquid soap + hand sanitiser We identified no studies that reported on our primary and secondary outcomes for this comparison except for author-defined adverse events. We are very uncertain whether plain soap plus hand sanitiser is better than CHG for nurses' skin based on very low-certainty evidence (MD -1.87, 95% CI -3.74 to -0.00; 16 participants, 1 study; very low-certainty evidence).  One agent versus standard care: alcohol-based handrub (hand sanitiser) versus usual care The evidence is very uncertain whether alcohol-based handrub is better than 'usual care' in the prevention of suspected infections, as reported by mothers (RR 0.98, CI 0.69 to 1.39; 103 participants, 1 study, very low-certainty evidence). We are uncertain whether alcohol-based hand sanitiser is better than 'usual care' in reducing the occurrence of early and late neonatal mortality (RR 0.29, 95% CI 0.01 to 7.00; 103 participants, 1 study; very low-certainty evidence) and (RR 0.29, CI 0.01 to 7.00; 103 participants, 1 study; very low-certainty evidence), respectively. We identified no studies that reported on other outcomes for this comparison. AUTHORS' CONCLUSIONS: We found a paucity of data that would allow us to reach meaningful conclusions pertaining to the superiority of one form of antiseptic hand hygiene agent over another for the prevention of neonatal infection. Also, the sparse available data were of moderate- to very low-certainty. We are uncertain as to the superiority of one hand hygiene agent over another because this review included very few studies with very serious study limitations.

Interventions for improving coverage of childhood immunisation in low- and middle-income countries.

BACKGROUND: Immunisation plays a major role in reducing childhood morbidity and mortality. Getting children immunised against potentially fatal and debilitating vaccine-preventable diseases remains a challenge despite the availability of efficacious vaccines, particularly in low- and middle-income countries. With the introduction of new vaccines, this becomes increasingly difficult. There is therefore a current need to synthesise the available evidence on the strategies used to bridge this gap. This is a second update of the Cochrane Review first published in 2011 and updated in 2016, and it focuses on interventions for improving childhood immunisation coverage in low- and middle-income countries. OBJECTIVES: To evaluate the effectiveness of intervention strategies to boost demand and supply of childhood vaccines, and sustain high childhood immunisation coverage in low- and middle-income countries. SEARCH METHODS: We searched CENTRAL, MEDLINE, CINAHL, and Global Index Medicus (11 July 2022). We searched Embase, LILACS, and Sociological Abstracts (2 September 2014). We searched WHO ICTRP and ClinicalTrials.gov (11 July 2022). In addition, we screened reference lists of relevant systematic reviews for potentially eligible studies, and carried out a citation search for 14 of the included studies (19 February 2020). SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs), non-randomised RCTs (nRCTs), controlled before-after studies, and interrupted time series conducted in low- and middle-income countries involving children that were under five years of age, caregivers, and healthcare providers. DATA COLLECTION AND ANALYSIS: We independently screened the search output, reviewed full texts of potentially eligible articles, assessed the risk of bias, and extracted data in duplicate, resolving discrepancies by consensus. We conducted random-effects meta-analyses and used GRADE to assess the certainty of the evidence. MAIN RESULTS: Forty-one studies involving 100,747 participants are included in the review. Twenty studies were cluster-randomised and 15 studies were individually randomised controlled trials. Six studies were quasi-randomised. The studies were conducted in four upper-middle-income countries (China, Georgia, Mexico, Guatemala), 11 lower-middle-income countries (Côte d'Ivoire, Ghana, Honduras, India, Indonesia, Kenya, Nigeria, Nepal, Nicaragua, Pakistan, Zimbabwe), and three lower-income countries (Afghanistan, Mali, Rwanda). The interventions evaluated in the studies were health education (seven studies), patient reminders (13 studies), digital register (two studies), household incentives (three studies), regular immunisation outreach sessions (two studies), home visits (one study), supportive supervision (two studies), integration of immunisation services with intermittent preventive treatment of malaria (one study), payment for performance (two studies), engagement of community leaders (one study), training on interpersonal communication skills (one study), and logistic support to health facilities (one study). We judged nine of the included studies to have low risk of bias; the risk of bias in eight studies was unclear and 24 studies had high risk of bias. We found low-certainty evidence that health education (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.15 to 1.62; 6 studies, 4375 participants) and home-based records (RR 1.36, 95% CI 1.06 to 1.75; 3 studies, 4019 participants) may improve coverage with DTP3/Penta 3 vaccine. Phone calls/short messages may have little or no effect on DTP3/Penta 3 vaccine uptake (RR 1.12, 95% CI 1.00 to 1.25; 6 studies, 3869 participants; low-certainty evidence); wearable reminders probably have little or no effect on DTP3/Penta 3 uptake (RR 1.02, 95% CI 0.97 to 1.07; 2 studies, 1567 participants; moderate-certainty evidence). Use of community leaders in combination with provider intervention probably increases the uptake of DTP3/Penta 3 vaccine (RR 1.37, 95% CI 1.11 to 1.69; 1 study, 2020 participants; moderate-certainty evidence). We are uncertain about the effect of immunisation outreach on DTP3/Penta 3 vaccine uptake in children under two years of age (RR 1.32, 95% CI 1.11 to 1.56; 1 study, 541 participants; very low-certainty evidence). We are also uncertain about the following interventions improving full vaccination of children under two years of age: training of health providers on interpersonal communication skills (RR 5.65, 95% CI 3.62 to 8.83; 1 study, 420 participants; very low-certainty evidence), and home visits (RR 1.29, 95% CI 1.15 to 1.45; 1 study, 419 participants; very low-certainty evidence). The same applies to the effect of training of health providers on interpersonal communication skills on the uptake of DTP3/Penta 3 by one year of age (very low-certainty evidence). The integration of immunisation with other services may, however, improve full vaccination (RR 1.29, 95% CI 1.16 to 1.44; 1 study, 1700 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Health education, home-based records, a combination of involvement of community leaders with health provider intervention, and integration of immunisation services may improve vaccine uptake. The certainty of the evidence for the included interventions ranged from moderate to very low. Low certainty of the evidence implies that the true effect of the interventions might be markedly different from the estimated effect. Further, more rigorous RCTs are, therefore, required to generate high-certainty evidence to inform policy and practice.

What makes knowledge translation work in practice? Lessons from a demand-driven and locally led project in Cameroon, Jordan and Nigeria.

BACKGROUND: Over the years, the knowledge translation (KT) field has moved from promoting linearized models to embracing the importance of interaction and learning. Likewise, there is now increased attention on the transfer of KT approaches to new environments. Some scholars, however, have warned that ideas about transferability still hinge on linear thinking and doing. In the current study, we therefore sought to use a more reflexive approach to KT and to study how actors align KT approaches with their local environments. METHODS: Our (auto) ethnographic study took place in a wider KT project. This project intended to combine three components: (1) co-organizing demand-driven, locally led and embedded KT cycles in Cameroon, Jordan, and Nigeria, (2) building upon established KT methods and (3) equipping and empowering local teams. We conducted 63 semi-structured interviews with key KT actors, observed 472 h of KT practices, and collected a paper trail of documents. At the same time, we also compiled project exchanges, such as project documents, plans, protocols, field notes, meeting notes and an archive of (email) correspondence between project members. We analysed all data abductively. RESULTS: We show that there were numerous moments where the design of our project indeed enabled us to align with local practices and needs. Yet this often did not suffice, and the project design sometimes conflicted with other logics and values. By analysing these tensions, we want to show that doing KT work which acts upon different values and knowledges and is sensitive towards the different effects that it produces demands both structuring projects in a specific way and requires significant alignment work of KT actors in practice. CONCLUSIONS: We show that practising KT more reflexively relies on two important conditions. First, KT projects have to be structured with sufficient discretionary space. Second, even though the structure of a project is important, there will be continuous need for alignment work. It is important to facilitate such alignment work and to further support it. In the discussion of this paper, we therefore articulate three design principles and three sensitivities. These elements can be used to make future KT projects more reflexive and sensitive to (social) complexity.

PATIENT-RELATED FACTORS AND CLINICAL MANAGEMENT OUTCOMES OF RETINOBLASTOMA IN CALABAR, NIGERIA.

Background: Retinoblastoma is curable in industrialized countries. However, it is associated with mortality in resource-poor nations due to disparities and poor access to eye care. Aim was to determine the relationships between patient-related factors and clinical outcomes of Retinoblastoma management in a tertiary hospital in Nigeria. Materials and methods: This was a retrospective study of all children who were diagnosed and treated for Retinoblastoma from January 2017 through December 2022. Information obtained from their records included biosocioeconomic data, symptoms, lag time from initial symptoms, staging, treatment and outcome (dead or alive). Results: Fifty-three patients, aged 6 to 88 months on first hospital presentation were recruited. There were 29(54.7%) females and 20(37.7%) patients died. Parental low socioeconomic class, rural residence and poor nutrition occurred more in those that survived, though not significantly (p>0.05). Median(interquartile) age at diagnosis [24(18-36) months, p=0.005] and lag time [13(6-20) months, p=0.274] were low in the survived group. Bilateral Retinoblastoma (20.8%,p=0.002), brain metastasis (22.6%,p<0.001), IRSS IV (18.9%,p=0.01) and relapse (34%,p<0.001) occurred more among the patients that died. The overall survival (OS) was 22(11.77-32.23) months with 1-year OS of 63%. Treatment with only chemotherapy [HR 4.76(95%CI:1.726-13.128)], incomplete chemotherapy [HR 5.61(95%CI:1.271-24.741)], relapse [HR 5.98(95%CI:1.376-25.983)] and eye surgery after 3 chemotherapy cycles [HR 8.22(95%CI:1.087-62.239)] were predictors of mortality. Conclusion: Early presentation of retinoblastoma especially of advanced and bilateral disease may lead to improved survival if chemotherapy and eye surgery are appropriately performed. Routine screening and immediate referral of retinoblastoma particularly in rural areas are recommended.

Multiple Plasmodium falciparum drug resistance polymorphisms identified in a pregnant woman with severe malaria and a concomitant spontaneous abortion in Cross River, Nigeria, West Africa.

BACKGROUND: The development of resistance by Plasmodium falciparum to anti-malarial drugs impedes any benefits of the drug. In addition, absence or delayed availability of current anti-malarial drugs in remote areas has the potential to results to parasite escape and continuous transmission. CASE PRESENTATION: The case of a 29-year old pregnant woman from Biase Local Government Area in Cross River State Nigeria presenting with febrile illness and high body temperature of 38.7 °C was reported. She looked pale and vomited twice on arrival at the health facility. Her blood smear on the first day of hospitalization was positive for P. falciparum by RDT, microscopy (21,960 parasite/µl) and real-time PCR, with a PCV of 18%. She was treated with 600 mg intravenous quinine in 500 ml of 5% Dextrose/0.9% Saline 8-hourly for 24 h. On the second day of hospitalization, she complained of weakness, persistent high-grade fever and vaginal bleeding. A bulging amnion from an extended cervix was observed. Following venous blood collection for laboratory investigations, 600 µg of misoprostol was inserted into the posterior fornix of her vagina as part of her obstetric care. Parenteral quinine was discontinued, and she was given full therapeutic regimen of artemether-lumefantrine 80/480 mg tablets to be taken for 3 days beginning from the second day. Her blood samples on the second and third day of hospitalization remained positive for P. falciparum by all three diagnostic methods. Single nucleotide polymorphism (SNP) assay on all three P. falciparum isolates revealed the presence of variants associated with multiple drug resistant markers. DISCUSSION: Infecting P. falciparum isolates may have been resistant to initial quinine treatment resulting from parasite cross-resistance with other quinoline associated resistant markers such as 86Y and 184 F. CONCLUSIONS: Therefore, the likely transmission of similarly resistant parasites in the study area calls for reinforcement of interventions and adherence to current World Health Organization guidelines in administering only approved drugs to individuals in order to mitigate parasite escape and eventual transmission to other susceptible individuals.

Comparison of standardised milk-based, standardised non-milk based and hospital-based formulations on the anthropometric indices of under-fives with moderate acute malnutrition: A randomised clinical trial.

BACKGROUND: Moderate acute malnutrition (MAM) causes impaired anthropometry, which can be reversed by supplementary feeding. The present study aimed to compare the effect of a standardised milk-based formulation (SMBF), standardised non-milk based formulation (SNMBF) and hospital-based formulation (HBF) on anthropometric indices of children aged <5 years with MAM. METHODS: This was a randomised clinical trial during which eligible children aged 6-59 months with MAM received SMBF, SNMBF or HBF over 4 months. They were followed up on a biweekly basis during which their weight, mid upper arm circumference (MUAC) and length/height were measured. The effect of the formulations was determined at the end of the period by the change in their anthropometric indices using 'per protocol' analysis. p < 0.05 was considered statistically significant. RESULTS: There were 157 evaluable participants of whom 54 received the SMBF, 57 received the SNMBF and 46 received the HBF. The overall result showed a significant improvement in the mean weight and MUAC of the children. Subgroup analysis showed a significant improvement in mean weight and MUAC among children aged 6-23 months (p = 0.013) and improvement in MUAC only among those aged 24-59 months (p = 0.03). CONCLUSIONS: The formulations significantly improved the mean weight and MUAC of children with MAM.

Intermittent preventive treatment for malaria in infants.

BACKGROUND: Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited. OBJECTIVES: To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria-endemic areas. SEARCH METHODS: We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta-analyses and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 12 trials that enrolled 19,098 infants; all were conducted in sub-Saharan Africa. Three trials were cluster-RCTs. IPTi with sulfadoxine-pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin-piperaquine (1 trial, 147 participants; year 2013), amodiaquine-artesunate (1 study, 684 participants; year 2008), and SP-artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin-based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 30% reduction (rate ratio 0.70, 0.62 to 0.80; 10 studies, 10,602 participants). The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention. IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.78, 0.69 to 0.88; 8 trials, 8774 participants, moderate-certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate-certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate-certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate-certainty evidence). IPTi with SP probably made little or no difference to all-cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate-certainty evidence). Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia. A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate-certainty evidence) and parasitaemia (moderate-certainty evidence). AUTHORS' CONCLUSIONS: In areas of sub-Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission. Evidence from SP studies over a 19-year period shows declining efficacy, which may be due to increasing drug resistance. Combinations with ACTs appear promising as suitable alternatives for IPTi.

Hand hygiene for the prevention of infections in neonates.

BACKGROUND: Annually, infections contribute to approximately 25% of the 2.8 million neonatal deaths worldwide. Over 95% of sepsis-related neonatal deaths occur in low- and middle-income countries. Hand hygiene is an inexpensive and cost-effective method of preventing infection in neonates, making it an affordable and practicable intervention in low- and middle-income settings. Therefore, hand hygiene practices may hold strong prospects for reducing the occurrence of infection and infection-related neonatal death. OBJECTIVES: To determine the effectiveness of different hand hygiene agents for preventing neonatal infection in community and health facility settings. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5), in the Cochrane Library; MEDLINE via PubMed (1966 to 10 May 2019); Embase (1980 to 10 May 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 10 May 2019). We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. Searches were updated 1 June 2020. SELECTION CRITERIA: We included RCTs, cross-over trials, and quasi-RCTs that included pregnant women, mothers, other caregivers, and healthcare workers who received interventions within the community or in health facility settings DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and the GRADE approach to assess the certainty of evidence. Primary outcomes were incidence of (study author-defined) suspected infection within the first 28 days of life, bacteriologically confirmed infection within the first 28 days of life, all-cause mortality within the first seven days of life (early neonatal death), and all-cause mortality from the 8th to the 28th day of life (late neonatal death). MAIN RESULTS: Our review included five studies: one RCT, one quasi-RCT, and three cross-over trials with a total of more than 5450 neonates (two studies included all neonates but did not report the actual number of neonates involved). Four studies involved 279 nurses working in neonatal intensive care units and all neonates on admission. The fifth study did not clearly state how many nurses were included in the study. Studies examined the effectiveness of different hand hygiene practices for the incidence of (study author-defined) suspected infection within the first 28 days of life. Two studies were rated as low risk for selection bias, another two were rated as high risk, and one study was rated as unclear risk. One study was rated as low risk for allocation bias, and four were rated as high risk. Only one of the five studies was rated as low risk for performance bias. 4% chlorhexidine gluconate (CHG) compared to plain liquid soap We are uncertain whether plain soap is better than 4% chlorhexidine gluconate (CHG) for nurses' skin based on very low-certainty evidence (mean difference (MD) -1.75, 95% confidence interval (CI) -3.31 to -0.19; 16 participants, 1 study; very low-certainty evidence). We identified no studies that reported on other outcomes for this comparison. 4% chlorhexidine gluconate compared to triclosan 1% One study compared 1% w/v triclosan with 4% chlorhexidine gluconate and suggests that 1% w/v triclosan may reduce the incidence of suspected infection (risk ratio (RR) 1.04, 95% CI 0.19 to 5.60; 1916 participants, 1 study; very low-certainty evidence). There may be fewer cases of infection in the 1% w/v triclosan group compared to the 4% chlorhexidine gluconate group (RR 6.01, 95% CI 3.56 to 10.14; 1916 participants, 1 study; very low-certainty evidence); however, we are uncertain of the available evidence. We identified no study that reported on all-cause mortality, duration of hospital stay, and adverse events for this comparison. 2% CHG compared to alcohol hand sanitiser (61% alcohol and emollients) We are uncertain whether 2% chlorhexidine gluconate reduces the risk of all infection in neonates compared to 61% alcohol hand sanitiser with regards to the incidence of all bacteriologically confirmed infection within the first 28 days of life (RR 2.19, 95% CI 1.79 to 2.69; 2932 participants, 1 study; very low-certainty evidence) in the 2% chlorhexidine gluconate group, but the evidence is very uncertain.   The adverse outcome was reported as mean visual scoring on the skin. There may be little to no difference between the effects of 2% CHG on nurses' skin compared to alcohol hand sanitiser based on very low-certainty evidence (MD 0.80, 95% CI 0.01 to 1.59; 118 participants, 1 study; very low-certainty evidence). We identified no study that reported on all-cause mortality and other outcomes for this comparison. None of the included studies assessed all-cause mortality within the first seven days of life nor duration of hospital stay.  AUTHORS' CONCLUSIONS: We are uncertain as to the superiority of one hand hygiene agent over another because this review included very few studies with very serious study limitations.

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 CENTRAL, MEDLINE, Embase, nine other databases, the World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), and metaRegister of Controlled Trials (mRCT) on 8 January 2020, together with reference checking, citation searching and contact with study authors to identify additional studies. 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 risks of bias. We stratified the analyses for child day-care centres or schools, community, and hospital-based settings. Where appropriate, we pooled incidence rate ratios (IRRs) using the generic inverse variance method and a random-effects model with a 95% confidence interval (CI). We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 29 RCTs: 13 trials from child day-care centres or schools in mainly high-income countries (54,471 participants), 15 community-based trials in LMICs (29,347 participants), and one hospital-based trial among people with AIDS in a high-income country (148 participants). All the trials and follow-up assessments were of short-term duration. Hand-washing promotion (education activities, sometimes with provision of soap) at child day-care facilities or schools prevent around one-third of diarrhoea episodes in high-income countries (incidence rate ratio (IRR) 0.70, 95% CI 0.58 to 0.85; 9 trials, 4664 participants, high-certainty evidence) and may prevent a similar proportion in LMICs, but only two trials from urban Egypt and Kenya have evaluated this (IRR 0.66, 95% CI 0.43 to 0.99; 2 trials, 45,380 participants; low-certainty evidence). Only four 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; 3 trials, 1845 participants; low-certainty evidence). Hand-washing promotion among communities in LMICs probably prevents around one-quarter of diarrhoea episodes (IRR 0.71, 95% CI 0.62 to 0.81; 9 trials, 15,950 participants; moderate-certainty evidence). However, six of these nine trials were from Asian settings, with only one trial from South America and two trials from sub-Saharan Africa. In seven 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: RR 0.66, 95% CI 0.58 to 0.75; 7 trials, 12,646 participants; education only: RR 0.84, 95% CI 0.67 to 1.05; 2 trials, 3304 participants). There was increased hand washing at major prompts (before eating or cooking, after visiting the toilet, or cleaning the baby's bottom) and increased compliance with hand-hygiene procedure (behavioural outcome) in the intervention groups compared with the control in community trials (data not pooled: 4 trials, 3591 participants; high-certainty evidence). Hand-washing promotion for the one trial conducted in a hospital among a 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; 1 trial, 148 participants; moderate-certainty evidence). Hand-washing frequency increased to seven times a day in the intervention group versus three times a day in the control arm in this hospital trial (1 trial, 148 participants; moderate-certainty evidence). We found no trials evaluating the effects of hand-washing promotions on diarrhoea-related deaths or cost effectiveness. 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%. The included trials do not provide evidence about the long-term impact of the interventions.

ANTECEDENTES: La diarrea es responsable de 1 800 000 muertes de niños en los países de ingresos bajos y medios (PIBM). Una de las estrategias identificadas para prevenir la diarrea es el lavado de manos. OBJETIVOS: Evaluar los efectos de las intervenciones de promoción del lavado de manos sobre los episodios de diarrea en niños y adultos. MÉTODOS DE BÚSQUEDA: El 8 de enero de 2020 se realizaron búsquedas en CENTRAL, MEDLINE, Embase, en otras nueve bases de datos, la Plataforma de registros internacionales de ensayos clínicos (ICTRP) de la Organización Mundial de la Salud (OMS) y el metaRegister of Controlled Trials (mRCT), además de comprobación de referencias, búsqueda de citas y contacto con los autores de los estudios para identificar estudios adicionales. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) individuales y por conglomerados que compararon los efectos de las intervenciones de lavado de manos sobre los episodios de diarrea en niños y adultos, con ninguna intervención. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron la elegibilidad de los ensayos, extrajeron los datos y evaluaron los riesgos de sesgo. Los análisis se estratificaron por guarderías infantiles o escuelas, comunidad y contextos hospitalarios. Cuando fue conveniente, se agruparon los cocientes de la tasa de incidencia (CTI) según el método de la varianza inversa genérica y un modelo de efectos aleatorios con un intervalo de confianza (IC) del 95%. Se utilizaron los criterios GRADE para evaluar la certeza de la evidencia. RESULTADOS PRINCIPALES: Se incluyeron 29 ECA: 13 ensayos de guarderías infantiles o escuelas en países principalmente de ingresos altos (54 471 participantes), 15 ensayos comunitarios en PIMB (29 347 participantes) y un ensayo hospitalario en pacientes con sida en países de ingresos altos (148 participantes). Todos los ensayos y evaluaciones de seguimiento fueron a corto plazo. La promoción del lavado de manos (actividades educativas, a veces con la provisión de jabón) en las guarderías infantiles o las escuelas previene alrededor de un tercio de los episodios de diarrea en los países de ingresos altos (cociente de tasa de incidencia [CTI] 0,70; IC del 95%: 0,58 a 0,85; nueve ensayos, 4664 participantes, evidencia de certeza alta), y podría prevenir una proporción similar en los PIMB, pero solo dos ensayos en zonas urbanas de Egipto y Kenya lo han evaluado (CTI 0,66; IC del 95%: 0,43 a 0,99; dos ensayos, 45 380 participantes, evidencia de certeza baja). Solo cuatro ensayos informaron sobre medidas de cambio en el comportamiento y los métodos de recopilación de datos fueron susceptibles de sesgo. En un ensayo de los EE.UU. se informó de que el comportamiento de lavado de manos mejoró; y en el ensayo de Kenya que proporcionó jabón gratuito, el lavado de manos no aumentó, pero sí el uso de jabón (datos no agrupados; tres ensayos, 1845 participantes, evidencia de certeza baja). La promoción del lavado de manos entre las comunidades en los PIMB probablemente previene alrededor de una cuarta parte de los episodios de diarrea (CTI 0,71; IC del 95%: 0,62 a 0,81; nueve ensayos, 15 950 participantes, evidencia de calidad moderada). Sin embargo, seis de estos nueve ensayos procedían de entornos asiáticos, y solo hubo un ensayo en América del Sur y dos en el África subsahariana. En siete ensayos, el jabón se suministró gratuitamente junto con la educación para el lavado de manos, y el tamaño del efecto medio general fue mayor que en los dos ensayos que no suministraron jabón (jabón suministrado: RR 0,66; IC del 95%: 0,58 a 0,75; siete ensayos, 12 646 participantes; solo educación: RR 0,84; IC del 95%: 0,67 a 1,05; dos ensayos, 3304 participantes). Hubo un aumento del lavado de manos en los momentos más importantes (antes de comer o cocinar, después de ir al baño o de limpiar el trasero del niño), y un aumento en el cumplimiento del procedimiento de higiene de las manos (resultado conductual) en los grupos de intervención, en comparación el control, en los ensayos comunitarios (datos no agrupados: cuatro ensayos, 3591 participantes; evidencia de certeza alta). La promoción del lavado de manos en el único ensayo realizado en un hospital en una población de alto riesgo mostró una reducción significativa de los episodios medios de diarrea (1,68 menos) en el grupo de intervención (diferencia de medias ­1,68; IC del 95%: ­1,93 a ­1,43; un ensayo, 148 participantes, evidencia de certeza moderada). En este ensayo hospitalario la frecuencia del lavado de manos aumentó hasta siete veces al día en el grupo de intervención versus tres veces al día en el grupo control (un ensayo, 148 participantes, evidencia de certeza moderada). No se encontraron ensayos que evaluaran los efectos de la promoción del lavado de manos sobre las muertes relacionadas con la diarrea ni el coste­efectividad. CONCLUSIONES DE LOS AUTORES: La promoción del lavado de manos probablemente reduce los episodios de diarrea en las guarderías infantiles de los países de altos ingresos y en las comunidades que viven en los PIMB, en aproximadamente el 30%. Los ensayos incluidos no aportan evidencia sobre el efecto a largo plazo de esta intervención.

Hand hygiene for the prevention of infections in neonates.

This Cochrane Review has been withdrawn from publication. Errors were identified in the data extraction process and in the reporting of results, and as such the findings of the review may not be reliable. The authors and the Cochrane Neonatal Co-ordinating Editor agreed to withdraw the review, following an internal investigation. The authors are undertaking a full revision of this Cochrane Review, with the intention of publishing a new version.

Vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children.

BACKGROUND: Nutritional rickets is a disease which affects children, especially in low- and middle-income countries. It causes problems such as skeletal deformities and impaired growth. The most common cause of nutritional rickets is vitamin D deficiency. Vitamin D administered with or without calcium is commonly regarded as the mainstay of treatment. In some sunny countries, however, where children are believed to have adequate vitamin D production from exposure to ultraviolet light, but who are deficient in calcium due to low dietary intake, calcium alone has also been used in the treatment of nutritional rickets. Therefore, it is important to compare the effects of vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children living in different settings. OBJECTIVES: To assess the effects of vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, LILACS, WHO ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 25 July 2019. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCT) involving children aged 0 to 18 years with nutritional rickets which compared treatment with vitamin D, calcium or a combination of vitamin D and calcium. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the title and abstracts of all studies, extracted data and assessed the risk of bias of included studies. We resolved any disagreements by consensus or recourse to a third review author. We conducted meta-analyses for the outcomes reported by study authors. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI) and, for continuous outcomes, we calculated mean differences (MD) with 95% CIs. We assessed the certainty of the evidence of the included studies using GRADE. MAIN RESULTS: We identified 4562 studies; of these, we included four RCTs with 286 participants. The studies compared two or more of the following: vitamin D, calcium or vitamin D plus calcium. The number of participants randomised to receive vitamin D was 64, calcium was 102 and vitamin D plus calcium was 120. Two studies were conducted in India and two were conducted in Nigeria. None of the included studies had a low risk of bias in all domains. Three studies had a high risk of bias in at least one domain. The age of the participants ranged between six months and 14 years. The duration of follow-up ranged between 12 weeks and 24 weeks. Two studies compared vitamin D to calcium. There is low-certainty evidence that, at 24 weeks' follow-up, calcium alone improved the healing of rickets compared to vitamin D alone (RR 3.26, 95% CI 1.59 to 6.69; P = 0.001; 1 study, 71 participants). Comparing vitamin D to calcium showed no firm evidence of an advantage or disadvantage in reducing morbidity (fractures) (RR 0.27, 95% CI 0.03 to 2.32; P = 0.23; 1 study, 71 participants; very low-certainty evidence). Adverse events were not reported. Two studies compared vitamin D plus calcium to vitamin D at 12 or 24 weeks. Vitamin D plus calcium improved healing of rickets compared to vitamin D alone at 24 weeks' follow-up (RR 3.06, 95% CI 1.49 to 6.29; P = 0.002; 1 study, 75 participants; low-certainty evidence). There is no conclusive evidence in favour of either intervention for reducing morbidity (fractures) (RR 0.24, 95% CI 0.03 to 2.08; P = 0.20; 1 study, 71 participants; very low-certainty evidence) or adverse events (RR 4.76, 95% CI 0.24 to 93.19; P = 0.30; 1 study, 39 participants; very low-certainty evidence). All four included studies compared vitamin D plus calcium to calcium at different follow-up times. There is no conclusive evidence on whether vitamin D plus calcium in comparison to calcium alone improved healing of rickets at 24 weeks' follow-up (RR 1.17, 95% CI 0.72 to 1.90; P = 0.53; 2 studies, 140 participants; very low-certainty evidence). Evidence is also inconclusive for morbidity (fractures) (RR 0.89, 95% CI 0.06 to 13.76; P = 0.94; 1 study, 72 participants; very low-certainty evidence) and adverse events (RR 4.29, 0.22 to 83.57; P = 0.34; 1 study, 37 participants; very low-certainty evidence). Most of the evidence in the review is low or very low certainty due to risk of bias, imprecision or both. None of the included studies assessed all-cause mortality, health-related quality of life or socioeconomic effects. One study assessed growth pattern but this was not measured at the time-point stipulated in the protocol of our review (one or more years after commencement of therapy). AUTHORS' CONCLUSIONS: This review provides low-certainty evidence that vitamin D plus calcium or calcium alone improve healing in children with nutritional rickets compared to vitamin D alone. We are unable to make conclusions on the effects of the interventions on adverse events or morbidity (fractures).

Intermittent preventive treatment for malaria in infants.

BACKGROUND: Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub-Saharan Africa. The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited. OBJECTIVES: To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria-endemic areas. SEARCH METHODS: We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria-endemic areas. DATA COLLECTION AND ANALYSIS: The primary outcome was clinical malaria (fever plus asexual parasitaemia). Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data. We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs). We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI. Where appropriate, we combined data in meta-analyses and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 12 trials that enrolled 19,098 infants; all were conducted in sub-Saharan Africa. Three trials were cluster-RCTs. IPTi with sulfadoxine-pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256). Trials evaluating ACTs included dihydroartemisinin-piperaquine (1 trial, 147 participants; year 2013), amodiaquine-artesunate (1 study, 684 participants; year 2008), and SP-artesunate (1 trial, 676 participants; year 2008). The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009). One trial evaluated IPTi with amodiaquine in Tanzania (2000). Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin-based combination therapy (ACT). Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 27% reduction (rate ratio 0.73, 0.65 to 0.82; 10 studies, 10,602 participants). The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention. IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.79, 0.74 to 0.85; 8 trials, 8774 participants, moderate-certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate-certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate-certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate-certainty evidence). IPTi with SP probably made little or no difference to all-cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate-certainty evidence). Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia. A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate-certainty evidence) and parasitaemia (moderate-certainty evidence). AUTHORS' CONCLUSIONS: In areas of sub-Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission. Evidence from SP studies over a 19-year period shows declining efficacy, which may be due to increasing drug resistance. Combinations with ACTs appear promising as suitable alternatives for IPTi. 2 December 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (3 Dec, 2018) were included.

Artemether for severe malaria.

BACKGROUND: In 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to this recommendation many countries, particularly in Africa, had begun to use artemether, an alternative artemisinin derivative. This Cochrane Review evaluates intramuscular artemether compared with both quinine and artesunate. OBJECTIVES: To assess the efficacy and safety of intramuscular artemether versus any other parenteral medication in the treatment of severe malaria in adults and children. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, and LILACS, ISI Web of Science, conference proceedings, and reference lists of articles. We also searched the WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing trials up to 7 September 2018. We checked the reference lists of all studies identified by the search. We examined references listed in review articles and previously compiled bibliographies to look for eligible studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing intramuscular artemether with intravenous/intramuscular quinine or artesunate for treating severe malaria. DATA COLLECTION AND ANALYSIS: The primary outcome was all-cause death. Two review authors independently screened each article by title and abstract, and examined potentially relevant studies for inclusion using an eligibility form. Two review authors independently extracted data and assessed risk of bias of included studies. We summarized dichotomous outcomes using risk ratios (RRs) and continuous outcomes using mean differences (MDs), and have presented both measures with 95% confidence intervals (CIs). Where appropriate, we combined data in meta-analyses and used the GRADE approach to summarize the certainty of the evidence. MAIN RESULTS: We included 19 RCTs, enrolling 2874 adults and children with severe malaria, carried out in Africa (12 trials) and in Asia (7 trials).Artemether versus quinineFor children, there is probably little or no difference in the risk of death between intramuscular artemether and quinine (RR 0.97, 95% CI 0.77 to 1.21; 13 trials, 1659 participants, moderate-certainty evidence). Coma resolution time may be about five hours shorter with artemether (MD -5.45, 95% CI -7.90 to -3.00; six trials, 358 participants, low-certainty evidence). Artemether may make little difference to neurological sequelae (RR 0.84, 95% CI 0.66 to 1.07; seven trials, 968 participants, low-certainty evidence). Compared to quinine, artemether probably shortens the parasite clearance time by about nine hours (MD -9.03, 95% CI -11.43 to -6.63; seven trials, 420 participants, moderate-certainty evidence), and may shorten the fever clearance time by about three hours (MD -3.73, 95% CI -6.55 to -0.92; eight trials, 457 participants, low-certainty evidence).For adults, treatment with intramuscular artemether probably results in fewer deaths than treatment with quinine (RR 0.59, 95% CI 0.42 to 0.83; four trials, 716 participants, moderate-certainty evidence).Artemether versus artesunateArtemether and artesunate have not been directly compared in randomized trials in children.For adults, mortality is probably higher with intramuscular artemether (RR 1.80, 95% CI 1.09 to 2.97; two trials, 494 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Artemether appears to be more effective than quinine in children and adults. Artemether compared to artesunate has not been extensively studied, but in adults it appears inferior. These findings are consistent with the WHO recommendations that artesunate is the drug of choice, but artemether is acceptable when artesunate is not available.

Intermittent screening and treatment with artemether-lumefantrine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in pregnancy: a facility-based, open-label, non-inferiority trial in Nigeria.

BACKGROUND: The spread of SP resistance may compromise the effectiveness of intermittent preventive treatment of malaria in pregnancy (MiP) with sulfadoxine-pyrimethamine (IPTp-SP) across Africa. However, there is no recommended alternative medicine for IPTp or alternative strategy for prevention of MiP. This poses problems for the prevention of MiP. This study investigated, whether screening with a rapid diagnostic test for malaria at routine antenatal clinic attendances and treatment of only those who are positive (intermittent screening and treatment) with artemether-lumefantrine is as effective and safe as IPTp-SP in pregnant women. METHODS: During antenatal clinic sessions at the General Hospital Calabar, Nigeria, held between October 2013 and November 2014, 459 pregnant women were randomized into either the current standard IPTp-SP or intermittent screening and treatment with artemether-lumefantrine (ISTp-AL). All women received a long-lasting insecticide-treated net at enrolment. Study women had a maximum of four scheduled visits following enrolment. Haemoglobin concentration and peripheral parasitaemia were assessed in the third trimester (36-40 weeks of gestation). Birth weight was documented at delivery or within a week for babies delivered at home. RESULTS: In the third trimester, the overall prevalence of severe anaemia (Hb < 8 g/dl) and moderate (8-10.9 g/dl) anaemia was 0.8 and 27.7%, respectively, and was similar in both treatment groups (p = 0.204). The risk of third-trimester severe anaemia did not differ significantly between both treatment arms (risk difference - 1.75% [95% CI - 4.16 to 0.66]) although the sample was underpowered for this outcome due to several participants being unavailable to give a blood sample. The risk of third-trimester maternal parasitaemia was significantly lower in the ISTp-AL arm (RD - 3.96% [95% CI - 7.76 to - 0.16]). The risk of low birthweight was significantly lower in the ISTp-AL arm after controlling for maternal age, gravidity and baseline parasitaemia (risk difference - 1.53% [95% CI - 1.54 to - 1.15]). Women in the ISTp-AL arm complained of fever more frequently compared to women in the IPTp-SP arm (p = 0.022). CONCLUSIONS: The trial results suggest that in an area of high malaria transmission with moderate sulfadoxine-pyrimethamine resistance, ISTp with artemether-lumefantrine may be an effective strategy for controlling malaria in pregnancy. Trial registration PACTR, PACTR201308000543272. Registered 29 April 2013, http://www.pactr.org/ATMWeb/appmanager/atm/atmregistry?dar=true&tNo=PACTR201308000543272.

Honey for acute cough in children.

BACKGROUND: Cough causes concern for parents and is a major cause of outpatient visits. Cough can impact quality of life, cause anxiety, and affect sleep in children and their parents. Honey has been used to alleviate cough symptoms. This is an update of reviews previously published in 2014, 2012, and 2010. OBJECTIVES: To evaluate the effectiveness of honey for acute cough in children in ambulatory settings. SEARCH METHODS: We searched CENTRAL (2018, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (2014 to 8 February 2018), Embase (2014 to 8 February 2018), CINAHL (2014 to 8 February 2018), EBSCO (2014 to 8 February 2018), Web of Science (2014 to 8 February 2018), and LILACS (2014 to 8 February 2018). We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) on 12 February 2018. The 2014 review included searches of AMED and CAB Abstracts, but these were not searched for this update due to lack of institutional access. SELECTION CRITERIA: Randomised controlled trials comparing honey alone, or in combination with antibiotics, versus no treatment, placebo, honey-based cough syrup, or other over-the-counter cough medications for children aged 12 months to 18 years for acute cough in ambulatory settings. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six randomised controlled trials involving 899 children; we added three studies (331 children) in this update.We assessed two studies as at high risk of performance and detection bias; three studies as at unclear risk of attrition bias; and three studies as at unclear risk of other bias.Studies compared honey with dextromethorphan, diphenhydramine, salbutamol, bromelin (an enzyme from the Bromeliaceae (pineapple) family), no treatment, and placebo. Five studies used 7-point Likert scales to measure symptomatic relief of cough; one used an unclear 5-point scale. In all studies, low score indicated better cough symptom relief.Using a 7-point Likert scale, honey probably reduces cough frequency better than no treatment or placebo (no treatment: mean difference (MD) -1.05, 95% confidence interval (CI) -1.48 to -0.62; I² = 0%; 2 studies; 154 children; moderate-certainty evidence; placebo: MD -1.62, 95% CI -3.02 to -0.22; I² = 0%; 2 studies; 402 children; moderate-certainty evidence). Honey may have a similar effect as dextromethorphan in reducing cough frequency (MD -0.07, 95% CI -1.07 to 0.94; I² = 87%; 2 studies; 149 children; low-certainty evidence). Honey may be better than diphenhydramine in reducing cough frequency (MD -0.57, 95% CI -0.90 to -0.24; 1 study; 80 children; low-certainty evidence).Giving honey for up to three days is probably more effective in relieving cough symptoms compared with placebo or salbutamol. Beyond three days honey probably had no advantage over salbutamol or placebo in reducing cough severity, bothersome cough, and impact of cough on sleep for parents and children (moderate-certainty evidence). With a 5-point cough scale, there was probably little or no difference between the effects of honey and bromelin mixed with honey in reducing cough frequency and severity.Adverse events included nervousness, insomnia, and hyperactivity, experienced by seven children (9.3%) treated with honey and two children (2.7%) treated with dextromethorphan (risk ratio (RR) 2.94, 95% Cl 0.74 to 11.71; I² = 0%; 2 studies; 149 children; low-certainty evidence). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14, 95% Cl 0.01 to 2.68; 1 study; 80 children; low-certainty evidence). When honey was compared with placebo, 34 children (12%) in the honey group and 13 (11%) in the placebo group complained of gastrointestinal symptoms (RR 1.91, 95% CI 1.12 to 3.24; I² = 0%; 2 studies; 402 children; moderate-certainty evidence). Four children who received salbutamol had rashes compared to one child in the honey group (RR 0.19, 95% CI 0.02 to 1.63; 1 study; 100 children; moderate-certainty evidence). No adverse events were reported in the no-treatment group. AUTHORS' CONCLUSIONS: Honey probably relieves cough symptoms to a greater extent than no treatment, diphenhydramine, and placebo, but may make little or no difference compared to dextromethorphan. Honey probably reduces cough duration better than placebo and salbutamol. There was no strong evidence for or against using honey. Most of the children received treatment for one night, which is a limitation to the results of this review. There was no difference in occurrence of adverse events between the honey and control arms.

Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women in Southeast Nigeria.

Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent preventive treatment of malaria in pregnancy in most of sub-Saharan Africa. Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium falciparum. This study determined the prevalence of Pfdhfr and Pfdhps polymorphisms found in asymptomatic pregnant women attending antenatal care in Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women attending antenatal care clinics were enrolled after obtaining informed consent. Malaria diagnosis testing was done using thick and thin smears. Dried blood spot filter papers were collected. Parasite DNA was extracted from the filter papers using a chelex extraction. Extraction was followed by nested PCR and restriction enzyme digestion. P. falciparum infection was detected by microscopy in 7% (32/459) participants. Twenty-eight P. falciparum isolates were successfully genotyped. In the Pfdhfr gene, the triple mutation was almost fixed; S108N mutation was (100%), N51I (93%) and C59R mutations (93%), whereas the I164L mutation was absent. The prevalence of Pfdhps S436A, A437G, A581G and A613S mutations was 82.1% (23/28), 96.4% (27/28), 71.4% (20/28) and 71.4% (20/28) respectively. The K540E mutation was absent. The prevalence of the Pfdhfr triple mutation IRNI was 92.9% (26/28). The efficacy of SP as IPTp in Southeast Nigeria may be severely threatened. The continuous monitoring of SP molecular markers of resistance is required to assess thresholds. The evaluation of alternative preventive treatment strategies and drug options for preventing malaria in pregnancy may be necessary.

Fluid replacement therapy for acute episodes of pain in people with sickle cell disease.

BACKGROUND: Treating vaso-occlusive painful crises in people with sickle cell disease is complex and requires multiple interventions. Extra fluids are routinely given as adjunct treatment, regardless of the individual's state of hydration with the aim of slowing or stopping the sickling process and thereby alleviating pain. This is an update of a previously published Cochrane Review. OBJECTIVES: To determine the optimal route, quantity and type of fluid replacement for people with sickle cell disease with acute painful crises. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We also conducted searches of Embase (November 2007), LILACS, www.ClinicalTrials.gov (05 January 2010), and the WHO ICTRP (30 June 2017).Date of most recent search of the Group's Haemoglobinopathies Trials Register: 16 February 2017. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared the administration of supplemental fluids adjunctive to analgesics by any route in people with any type of sickle cell disease during an acute painful episode, under medical supervision (inpatient, day care or community). DATA COLLECTION AND ANALYSIS: No relevant trials have yet been identified. MAIN RESULTS: Sixteen trials were identified by the searches, all of which were not eligible for inclusion in the review. AUTHORS' CONCLUSIONS: Treating vaso-occlusive crises is complex and requires multiple interventions. Extra fluids, generally oral or intravenous, are routinely administered during acute painful episodes to people with sickle cell disease regardless of the individual's state of hydration. Reports of their use during these acute painful episodes do not state the efficacy of any single route, type or quantity of fluid compared to another. However, there are no randomised controlled trials that have assessed the safety and efficacy of different routes, types or quantities of fluid. This systematic review identifies the need for a multicentre randomised controlled trial assessing the efficacy and possible adverse effects of different routes, types and quantities of fluid administered to people with sickle cell disease during acute painful episodes.

Anaemia following Artemisinin-Based Combination Treatments of Uncomplicated Plasmodium falciparum Malaria in Children: Temporal Patterns of Haematocrit and the Use of Uncomplicated Hyperparasitaemia as a Model for Evaluating Late-Appearing Anaemia.

BACKGROUND: In severe malaria, intravenous artesunate may cause delayed haemolytic anaemia but there has been little evaluation of the propensity of oral artemisinin-based combination treatments (ACTs) to cause late-appearing anaemia. METHODS: The frequency of anaemia (haematocrit <30%), and temporal changes in haematocrit were evaluated in 1,191 malarious children following ACTs. "Haematocrit conservation" was evaluated by using the fall in haematocrit/1,000 asexual parasites cleared from the peripheral blood (FIH/1,000 asexual parasites cpb), and the ratio of the average haematocrit (on the first 3 days of starting treatment):total parasitaemia cleared. RESULTS: The frequency of anaemia decreased significantly following treatment. FIH/1,000 asexual parasites cpb, average haematocrit:total parasitaemia cleared, and mean haematocrit 5 weeks after treatment began were significantly lower in hyperparasitaemic children than in children without hyperparasitaemia, suggesting haematocrit conservation during treatment followed later by a loss of haematocrit. Asymptomatic late-appearing anaemia occurred in 6% of the children. CONCLUSION: Artesunate-amodiaquine and artemether-lumefantrine contribute to haematocrit conservation at high parasitaemias but may cause late-appearing anaemia.

Abdominal Pain-predominant Functional Gastrointestinal Disorders in Adolescent Nigerians.

OBJECTIVES: To determine the prevalence, pattern, and predisposing factors of abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) in adolescent Nigerians. METHODS: A cross-sectional study was conducted in 2 states in the southern part of Nigeria in June 2014. Adolescents of age 10 to 18 years were recruited from 11 secondary schools using a stratified random sampling technique. A validated self-administered questionnaire on Rome III criteria for diagnosing AP-FGIDs and its determinants were filled by the participants in a classroom setting. RESULTS: A total of 874 participants filled the questionnaire. Of this, 818 (93.4%) filled it properly and were included in the final analysis. The mean age of the participants was 14.6 ±â€Š2.0 years with 409 (50.0%) being boys. AP-FGIDs were present in 81 (9.9%) participants. Forty six (5.6%) of the study participants had irritable bowel syndrome (IBS), 21 (2.6%) functional abdominal pain, 15 (1.8%) abdominal migraine while 3 (0.4%) had functional dyspepsia. The difference in AP-FGIDs between adolescents residing in rural and urban areas was not statistically significant (P = 0.22). Intestinal and extra-intestinal symptoms occurred more frequently in those with AP-FGIDs. Nausea was the only symptom independently associated with AP-FGIDs (p = 0.015). Multiple regression analysis showed no significant association between stressful life events and AP-FGIDs. CONCLUSIONS: AP-FGIDs are a significant health problem in Nigerian adolescents. In addition to the intestinal symptoms, most of the affected children and others also had extraintestinal symptoms. None of the stressful life events evaluated was significantly associated with FGIDs.