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Background: Selective mass chemotherapy is known to be very effective in reducing and controlling the prevalence of urinary schistosomiasis. However, re-infection and resurgence of Schistosoma (S) haematobium infection after effective mass chemotherapy is also common in the absence of other control programmes. Objective: To determine the prevalence of S. haematobium infection among primary school children in a rural community, ten years after effective mass chemotherapy in the same school. Subjects and Methods: The prevalence and intensity of S. haematobium infection were determined in a rural primary school by the nytel milipore filter method in 2003. The results were compared with those of a similar study carried out in the same primary school ten years earlier, before and after effective mass chemotherapy. Results: In the current study, two hundred and twenty six of the 443 children studied had urinary schistosomiasis giving a prevalence of 51.0 percent. One hundred and seventy five (77.4 percent) of those infected had infection of mild intensity (

Introduction: Continued endemicity of intestinal nematodes infestation in children in our environment despite availability of potent and safe anthelmintic drugs is of public health interest. Objective: This study assessed the comparative efficacy of selected anthelmintic drugs namely Mebendazole, pyrantel pamoate and levamisole-against common intestinal nematodes namely Ascaris lumbricoides, Hookworm (Ancylostoma duodenale and Necator amer icanus) and Trichuris trichuria in children in Calabar Municipality, South- South Nigeria Method: One hundred and thirty eight pupils from four primary schools in Ikot Ishie/Ikot Ansa communities of Calabar with worm infestation (Ascaris, hookworm and Trichuris including mixed infestation) were randomized by simple balloting to one of the following anthelmintic drugs (Mebendazole 500mg, Pyrantel 10mg/kg or Levamisole 2.5mg/ kg). The efficacy of the drugs was determined by the level of clearance of worm egg/ova from fresh stool samples of the pupils on post-treatment examination. Result: The study showed the three anthelmintic drugs displaying one hundred percent (100%) efficacy in respect of Ascaris and trichuris worms, but less so for hookworm. Mebendazole displayed 90.48%, Pyrantel 45.16%) and Levamisole (17.86%) efficacy level against hookworm. Conclusion: The overall result indicates that Mebendazole was the most efficacious agent against the three common intestinal worms.

Background: Malaria, earlier considered rare in neonates, has been reported with increasing frequency in the last decade. Neonatal malaria diagnosis is challenging because the clinical features are non-specific, variable and also overlap with bacterial infection. Aim: To determine the prevalence of neonatal malaria and the associated clinical features in newborn babies with fever. Patients and methods: One hundred and fifty neonates with fever admitted into the Newborn unit of the University of Calabar Teaching Hospital, over a six month period, were recruited consecutively. Symptoms and signs for each neonate were documented. Blood film for malaria parasites and investigation for sepsis workup were done before commencement of drugs. Results: One hundred and fifty babies were recruited. Most (85.3%) of the babies were aged ≤7 days. One hundred and thirty six (90.7%) of the mothers were booked for antenatal care (ANC). Most of the babies were from primiparous women (54.7%). Six babies (4%) had malaria parasitaemia with four (2.7%) being congenital malaria and two (1.3%) acquired malaria. Plasmodium falciparum was the only species identified. All six with malaria were from the 136 booked mothers. Four of the affected six neonates also had septicaemia. The clinical features in babies with malaria only were, fever, fast breathing and jaundice while those with malaria and bacterial co-infection had, in addition, poor suck. Conclusion: Malaria infection and septicemia can coexist in some Nigerian newborns and since the clinical presentation of each of these condition are closely similar, it is recommend that malaria parasite investigation be included as part of the investigation in the newborns with fever. This approach can help to avoid a delay in applying the appropriate therapeutic intervention

Background: The Bacille Calmette-Guérin (BCG) vaccine, given as a single dose, offers variable protection against Tuberculosis (TB). It is plausible that repeat doses could improve the effectiveness of the BCG vaccine in settings where the population remain at risk of the disease. Objective: To assess the effectiveness of BCG revaccination as a booster dose in preventing TB in Low- and Middle- Income Countries (LMICs). Methods: We searched the electronic databases without language or publication restrictions and followed the procedures for preparing systematic reviews, including assessing the risk of bias as outlined in the Cochrane handbook. We included randomised controlled trials (RCTs) conducted in LMICs involving children and adults receiving one or more BCG vaccine doses after the primary BCG vaccination. The incidence of severe forms of TB, active TB and adverse events were the primary outcomes. Results: Five RCTs were included in this systematic review. Revaccination with BCG probably makes little or no difference to the risk of active TB measured after five years (Relative risk (RR) 1.16, 95% CI 0.88 to 1.51; 348,083 participants; one study, moderate certainty evidence) or nine years post-revaccination (RR 0.96, 95% CI 0.82 to 1.12; 348,083 participants; one study, moderate certainty evidence). In populations with HIV co-infection, revaccination probably increases the risk of pulmonary tuberculosis compared to placebo (RR 1.74, 95% CI 1.00 to 3.01; 46,764 participants; one study, moderate certainty evidence). Conclusion: The available evidence suggests that BCG revaccination probably makes little or no difference in preventing tuberculosis disease in LMICs.

Introduction: Insecticide treated net (ITN) is pivotal to malaria control but reports show a relatively low ITN utilization when compared to household ownership. It is important to explore the determinants of ITN utilization in order to bridge this gap. Objectives: To determine the factors associated with ITN utilization among under-fives. Method: A cross sectional study was conducted from February to April 2015 among under-fives in Afaha Ikot Obio Nkan in Akwa Ibom State, Nigeria. A systematic random sampling technique was used to select 494 households from which 413 under-fives were recruited. Information on ITN utilization was obtained using a WHO validated tool. The independent predictors of ITN utilization were determined. Result: ITN was mainly used to prevent mosquito bites (48.3%) and malaria (29.2%). Non-utilization was mainly attributed to heat (38.5%), ‘no reason’ (11.5%) and low mosquito activity (11.1%). Household head of 30-39 years, the presence of two under-fives in a household and the number of ITNs observed hanging over bed spaces were the independent of predictors utilization. Conclusion: Caregivers aged 30 – 39 years, presence of two under-five children in a household and the number of ITNs observed hanging over bed spaces were the predictors of ITN utilization.

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., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

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., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Lassa fever is a viral haemorrhagic fever endemic in Nigeria. Improved surveillance and testing capacity have revealed in an increased number of reported cases and apparent geographic spread of Lassa fever in Nigeria. We described the recent four-year trend of Lassa fever in Nigeria to improve understanding of its epidemiology and inform the design of appropriate interventions., Methods: We analysed the national surveillance data on Lassa fever maintained by the Nigeria Centre for Diseases Control (NCDC) and described trends, sociodemographic, geographic distribution, and clinical outcomes. We compared cases, positivity, and clinical outcomes in the period January 2018 to December 2021., Results: We found Lassa fever to be reported throughout the year with more than half the cases reported within the first quarter of the year, a recent increase in numbers and geographic spread of the virus, and male and adult (>18 years) preponderance. Case fatality rates were worse in males, the under-five and elderly, during off-peak periods, and among low reporting states., Conclusion: Lassa fever is endemic in Nigeria with a recent increase in numbers and geographical distribution. Sustaining improved surveillance, enhanced laboratory diagnosis and improved case management capacity during off-peak periods should remain a priority. Attention should be paid to the very young and elderly during outbreaks. Further research efforts should identify and address specific factors that determine poor clinical outcomes., Competing Interests: The authors declared no competing interests., (Copyright: © 2022 Dalhat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Plasmodium falciparum immune escape mechanisms affect antigens being prioritized for vaccine design. As a result of the multiple surface antigens the parasite exhibits at different life cycle stages, designing a vaccine that would efficiently boost the immune system in clearing infections has been challenging. The P. falciparum cell-traversal protein for ookinetes and sporozoite (Pfceltos) is instrumental for ookinete traversal of the mosquito midgut and sporozoites invasion of the human liver cells. Pfceltos elicits both humoral and cellular immune response but has been reported with multiple single nucleotide polymorphisms in global isolates. A cross-sectional survey, conducted in southern Nigeria, between January-March 2021 recruited 283 individuals. Of this, 166 demonstrated P. falciparum infections (86 from Cross River and 80 from Edo), 48 (55.8%) while only 36 (45%) were amplified for Pfceltos gene from both sites respectively. Fifty amplified samples were sequenced and analysed for their diversity, polymorphisms and population structure of the gene. The number of segregating sites in Edo State was higher (34) than that of Cross River State. Though nucleotide diversity was higher for Edo compared to Cross River State (θw = 0.02505; π = 0.03993 versus θw = 0.00930; π = 0.01033 respectively), the reverse was the case for haplotype diversity (0.757 versus 0.890 for Edo and Cross River respectively). Of the twelve haplotypes observed from both states, only two (KASLPVEK and NAFLSFEK) were shared, with haplotype prevalence higher in Edo (16% and 36%) than Cross River (8% and 4%). The Tajima's D test was positive for both states, with Fst value showing a strong genetic differentiation (Fst = 0.25599), indicating the occurrence of balancing selection favoring haplotype circulation at a low frequency. The shared haplotypes, low Hst and Fst values presents a challenge to predict the extent of gene flow. High LD values present a grim public health consequence should a Pfceltos-conjugated vaccine be considered for prophylaxis in Nigeria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s).)

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., (Copyright © 2021 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

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., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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., (Copyright © 2020 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Importance: To prepare for future coronavirus disease 2019 (COVID-19) waves, Nigerian policy makers need insights into community spread of COVID-19 and changes in rates of infection associated with government-mandated closures and restrictions., Objectives: To measure the association of closures and restrictions with aggregate mobility and the association of mobility with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and to characterize community spread of COVID-19., Design, Setting, and Participants: This cross-sectional study used aggregated anonymized mobility data from smartphone users in Nigeria who opted to provide location history (from a pool of up to 40 million individuals) collected between February 27 and July 21, 2020. The analyzed data included daily counts of confirmed SARS-CoV-2 infections and daily changes in aggregate mobility across 6 categories: retail and recreation, grocery and pharmacy, parks, transit stations, workplaces, and residential. Closures and restrictions were initiated on March 30, 2020, and partially eased on May 4, 2020., Main Outcomes and Measures: Interrupted time series were used to measure associations of closures and restrictions with aggregate mobility. Negative binomial regression was used to evaluate associations between confirmed SARS-CoV-2 infections and mobility categories. Averted infections were estimated by subtracting cumulative confirmed infections from estimated infections assuming no closures and restrictions., Results: Closures and restrictions had negative associations with mean change in daily aggregate mobility in retail and recreation (-46.87 [95% CI, -55.98 to -37.76] percentage points; P < .001), grocery and pharmacy (-28.95 [95% CI, -40.12 to -17.77] percentage points; P < .001), parks (-43.59 [95% CI, -49.89 to -37.30] percentage points; P < .001), transit stations (-47.44 [95% CI, -56.70 to -38.19] percentage points; P < .001), and workplaces (-53.07 [95% CI, -67.75 to -38.39] percentage points; P < .001) and a positive association with mobility in residential areas (24.10 [95% CI, 19.14 to 29.05] percentage points; P < .001). Most of these changes reversed after closures and restrictions were partially eased (retail and recreation: 14.63 [95% CI, 10.95 to 18.30] percentage points; P < .001; grocery and pharmacy: 15.29 [95% CI, 10.90 to 19.67] percentage points; P < .001; parks: 6.48 [95% CI, 3.98 to 8.99] percentage points; P < .001; transit stations: 17.93 [95% CI, 14.03 to 21.83] percentage points; P < .001; residential: -5.59 [95% CI, -9.08 to -2.09] percentage points; P = .002). Additionally, every percentage point increase in aggregate mobility was associated with higher incidences of SARS-CoV-2 infection in residential areas (incidence rate ratio [IRR], 1.03 [95% CI, 1.00 to 1.07]; P = .04), transit stations (IRR, 1.02 [95% CI, 1.00 to 1.03]; P = .008), and workplaces (IRR, 1.01 [95% CI, 1.00 to 1.02]; P = .04). Lastly, closures and restrictions may have been associated with averting up to 5.8 million SARS-CoV-2 infections over the study period., Conclusions and Relevance: In this cross-sectional study, closures and restrictions had significant associations with aggregate mobility and were associated with decreased SARS-CoV-2 infections. These findings suggest that future anticontagion measures need better infection control and contact tracing in residential areas, transit stations, and workplaces.

Although Plasmodium falciparum continues to be the main target for malaria elimination, other Plasmodium species persist in Africa. Their clinical diagnosis is uncommon, whereas rapid diagnostic tests (RDTs), the most widely used malaria diagnostic tools, are only able to distinguish between P. falciparum and non- falciparum species, the latter as "pan-species." Blood samples from health facilities were collected in southern Nigeria (Lagos and Calabar) in 2017 (October-December) and Calabar only in 2018 (October-November), and analyzed by several methods, namely, microscopy, quantitative real-time PCR (qPCR), and peptide serology targeting candidate antigens ( Plasmodium malariae apical membrane antigen, P . malariae lactose dehydrogenase, and P . malariae circumsporozoite surface protein). Both microscopy and qPCR diagnostic approaches detected comparable proportions (∼80%) of all RDT-positive samples infected with the dominant P. falciparum malaria parasite. However, higher proportions of non- falciparum species were detected by qPCR than microscopy, 10% against 3% infections for P. malariae and 3% against 0% for Plasmodium ovale , respectively. No Plasmodium vivax infection was detected. Infection rates for P. malariae varied between age-groups, with the highest rates in individuals aged > 5 years. Plasmodium malariae -specific seroprevalence rates fluctuated in those aged < 10 years but generally reached the peak around 20 years of age for all peptides. The heterogeneity and rates of these non-falciparum species call for increased specific diagnosis and targeting by elimination strategies.

The study was carried out to determine relative abundance, species diversity, of Anopheles species (Diptera: Culicidae) in selected forested areas in Cross River State, Nigeria and the prevalence of malaria infection in the specimens. Mosquitoes were collected using pyrethrum spray catch and Centre for Disease Control light traps modified with yeast and sugar to generate carbon dioxide (CO2) and identified using morphological identification keys. We used a multiplex polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) to simultaneously distinguish sibling species of the An. gambiae s.l, including separation of An. gambiae s.s. and An. coluzzii (Diptera: Culicidae). The samples were also screened for Plasmodium infection using the enzyme-linked immunosorbent assay. One hundred and four Anopheles specimens were collected during the study of which 97% was An. gambiae complex and 3% was An. rufipes (Diptera: Culicidae). Only 77% of the An. gambiae s.l. was identify to species level. The result shows that 41.6% was An. gambiae s.s. and 34.6% was An. coluzzii. No sporozoite of Plasmodium was detected in the Anopheles species. The study also found a hybrid form of An. gambiae s.s. and An. coluzzii. These findings suggest the first documented evidence of hybrid forms of An. gambiae s.s./An. coluzzii in South Eastern Nigeria although its epidemiological implication is still not clear., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background In children with sickle cell anaemia (SCA), ischaemic electrocardiogram (ECG) changes occur during both vaso-occlusive crises (VOC) and the steady state. Myocardial ischaemia evidenced by an ischaemic pattern on ECG may lead to myocardial injury which is evidenced by elevated serum cardiac troponin T (cTnT). Occasionally, the myocardial injury is fatal. Aim To determine the relationship between raised serum cTnT levels and an ischaemic ECG pattern in children with SCA. Methods This was a dual study design comprising a prospective cohort study of a group of children with SCA observed during VOC and 6 weeks later during follow-up steady state, and a case-control study of SCA children and apparently healthy children. The subjects were 34 SCA children aged 5-17 years and 34 age- and sex-matched apparently healthy controls with haemoglobin genotype AA attending University of Calabar Teaching Hospital. VOC was diagnosed by clinical examination and a history of bone pain. During VOC and follow-up steady state, an ECG was performed and blood taken for serum cTnT estimation. In the apparently healthy children, only serum cTnT was estimated. Serum cTnT was analysed by electrochemiluminescence immune-assay. Ischaemic ECG was assessed using the World Heart Federation criteria. Results Twenty-eight (82.4%) SCA children had elevated serum cTnT during VOC and it was elevated in only six (17.6%) of them during the steady state. An ischaemic ECG was observed in 25 (73.5%) and 20 (58.8%) of them during VOC and the steady state, respectively. Ischaemic ECG identified SCA children with elevated cTnT during VOC (sensitivity 75%, specificity 33.3%) and the follow-up steady state (sensitivity 50%, specificity 39.3%). Measures of agreement between ECG and cTnT in detecting myocardial injury were poor during VOC (κ 0.07, p = 0.68) and the follow-up steady state (κ - 0.06, p = 0.63). Conclusions Most SCA children have an ischaemic ECG with elevated serum cTnT, especially during VOC, which suggests ischaemic-induced cardiac injury. However, elevated serum cTnT can occur without an ischaemic ECG and vice versa . Performing only electrocardiography or cTnT to detect ischaemia-induced cardiac injury may be misleading. Therefore, when there is a high index of suspicion, both tests should be undertaken, especially during VOC, to ensure prompt, effective treatment. Abbreviations AHC, apparently healthy children; AUC, area under the ROC curve; BMI, body mass index; cTnT, cardiac troponin T; ECG, electrocardiogram; EDTA, ethylene diamine tetra-acetic acid; GFR, glomerular filtration rate; HbS, haemoglobin S; HLA, human leucocyte antigen; LVH, left ventricular hypertrophy; ROC, receiver operating characteristic; SCA, sickle cell anaemia; UCTH, University of Calabar Teaching Hospital; URL, upper reference limit; USFDA, United States Food and Drug Administration; USNIH, United States National Institutes of Health; VOC, vaso-occlusive painful crisis; WHF, World Heart Federation.

Introduction: fever is the primary symptom of most childhood illnesses and a cause of concern to their caregivers. The antipyretics commonly used to treat fever are ibuprofen and paracetamol. Most studies on the effectiveness of ibuprofen and paracetamol in treating fever in under-fives were conducted in Europe and North America with very few in African children. This study was aimed at assessing the effectiveness and safety of a single dose therapy of ibuprofen versus paracetamol for treating childhood fever in Nigeria., Methods: a randomized, controlled clinical trial was conducted in the University of Calabar Teaching Hospital, in Nigeria. A total of 140 eligible children aged 6-59 months with tympanic temperature of 38°C-40°C were enrolled, and 70 of them were assigned to one arm that received a single dose of ibuprofen (10mg/kg) and 70 had paracetamol (15mg/kg). After drug administration, the children were admitted and observed in the hospital for six hours during which period a half-hourly temperature measurement and monitoring for adverse events were done., Results: the overall result showed that ibuprofen had a better fever reducing effect compared to paracetamol. The proportion of afebrile children in the ibuprofen versus paracetamol group at 1.5-2.5 hours of administration of the drugs was statistically significant (p = 0.04). The adverse events of both drugs were mild and quite comparable with vomiting being the commonest., Conclusion: ibuprofen is more effective in the treating fever in under-fives compared to paracetamol. The adverse events of both drugs were mild and comparable., Competing Interests: The authors declare no competing interests., (Copyright: Ekaete Olajide Alaje et al.)

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)., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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., (Copyright © 2019 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

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.

Background: Understanding socioeconomic disparities in all-cause and cause-specific mortality can help inform prevention and treatment strategies., Objectives: To quantify cause-specific mortality rates by socioeconomic status across seven health and demographic surveillance systems (HDSS) in five countries (Ethiopia, Kenya, Malawi, Mozambique, and Nigeria) in the INDEPTH Network in sub-Saharan Africa., Methods: We linked demographic residence data with household survey data containing living standards and education information we used to create a poverty index. Person-years lived and deaths between 2003 and 2016 (periods varied by HDSS) were stratified in each HDSS by age, sex, year, and number of deprivations on the poverty index (0-8). Causes of death were assigned to each death using the InterVA-4 model based on responses to verbal autopsy questionnaires. We estimated rate ratios between socioeconomic groups (2-4 and 5-8 deprivations on our poverty index compared to 0-2 deprivations) for specific causes of death and calculated life expectancy for the deprivation groups., Results: Our pooled data contained almost 3.5 million person-years of observation and 25,038 deaths. All-cause mortality rates were higher among people in households with 5-8 deprivations on our poverty index compared to 0-2 deprivations, controlling for age, sex, and year (rate ratios ranged 1.42 to 2.06 across HDSS sites). The poorest group had consistently higher death rates in communicable, maternal, neonatal, and nutritional conditions (rate ratios ranged 1.34-4.05) and for non-communicable diseases in several sites (1.14-1.93). The disparities in mortality between 5-8 deprivation groups and 0-2 deprivation groups led to lower life expectancy in the higher-deprivation groups by six years in all sites and more than 10 years in five sites., Conclusions: We show large disparities in mortality on the basis of socioeconomic status across seven HDSS in sub-Saharan Africa due to disparities in communicable disease mortality and from non-communicable diseases in some sites. Life expectancy gaps between socioeconomic groups within sites were similar to the gaps between high-income and lower-middle-income countries. Prevention and treatment efforts can benefit from understanding subpopulations facing higher mortality from specific conditions.

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.

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.

Background: Supportive psychotherapy, in individual or group settings, may help improve surgical outcomes for women and girls living with female genital mutilation (FGM)., Objectives: To assess whether supportive psychotherapy given alongside surgical procedures to correct complications of FGM improves clinical outcomes., Search Strategy: We searched major databases including CENTRAL, Medline, African Index Medicus, SCOPUS, PsycINFO, and others. There were no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies., Selection Criteria: We included studies of girls and women living with any type of FGM who received supportive psychotherapy or client education sessions alongside any surgical procedure to correct health complications from FGM., Data Collection and Analysis: Two team members independently screened studies for eligibility., Main Results: There were no eligible studies identified., Conclusions: There is no direct evidence for the benefits or harms of supportive psychotherapy alongside surgical procedures for women and girls living with FGM. Research evidence is urgently needed to guide clinical practice., Prospero Registration: 42015024639., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Deinfibulation is a surgical procedure carried out to re-open the vaginal introitus of women living with type III female genital mutilation (FGM)., Objectives: To assess the impact of deinfibulation on gynecologic or obstetric outcomes by comparing women who were deinfibulated with women with type III FGM or women without FGM., Search Strategy: Major databases including CENTRAL, MEDLINE, and Scopus were searched until August 2015., Selection Criteria: We included nonrandomized studies that compared obstetric outcomes of women with deinfibulation, type III FGM (not deinfibulated during labor), and no FGM., Data Collection and Analysis: Quality of evidence was determined following the GRADE methodology. Summary measures were calculated using odds ratios at 95% confidence intervals., Results: We found no randomized controlled trials. We included four case-control studies. The quality of evidence was very low. Compared with women with type III FGM at delivery, deinfibulated women had a significant reduction in the risk of having a cesarean delivery or postpartum hemorrhage. Compared with women without FGM, deinfibulated women had a similar risk of episiotomy, cesarean delivery, vaginal lacerations, postpartum hemorrhage, and blood loss at vaginal delivery. The length of second stage of labor, mean maternal hospital stay, and Apgar scores less than 7 were also comparable., Conclusions: Low-quality evidence suggests deinfibulation improves birth outcomes for women with type III FGM., Prospero Registration: CRD42015024466., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: There remains no consensus on the best timing of deinfibulation in women with type III female genital mutilation (FGM)., Objectives: To conduct a systematic review of the effects of antepartum or intrapartum deinfibulation on childbirth outcomes in women with type III FGM., Search Strategy: The following major databases were searched: Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov, from inception until August 2015 without any language restrictions., Selection Criteria: Studies of pregnant women or girls with type III FGM who were deinfibulated antepartum or intrapartum were included., Data Collection and Analysis: Two team members independently screened and collected data. Quality of evidence was assessed using GRADE. Summary odds ratios and proportions were calculated when possible., Results: There is no evidence of a significant difference between antepartum and intrapartum deinfibulation for obstetric outcomes such as duration of labor, perineal lacerations, episiotomies, postpartum hemorrhage, and cesarean deliveries. Outcomes in women living with type III FGM and those who have undergone deinfibulation were not statistically different; however, trends show a benefit for deinfibulation. All studies were underpowered to detect statistical differences., Conclusion: Larger studies are required to have full confidence in these findings., Prospero Registration: CRD42015024464., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Female genital mutilation (FGM) is associated with psychological consequences such as post-traumatic stress disorder (PSTD), depression, and anxiety disorders. Cognitive behavioral therapy (CBT), an empirically supported form of psychotherapy, may be an effective treatment for these psychological sequelae of FGM., Objectives: To assess the effectiveness of CBT among individuals living with any type of FGM and diagnosed to have PTSD, depression, or anxiety disorders., Search Strategies: CENTRAL, Medline, African Index Medicus, SCOPUS, PILOTS, POPLINE, PsycINFO, WHOLIS, LILACS, ERIC, NYAM Library, CINAHL, Web of Science were searched from inception up to August 10, 2015., Selection Criteria: Both randomized and nonrandomized studies comparing the efficacy of CBT to other forms of interventions for PTSD, depression, or anxiety disorders in individuals with FGM, were systematically reviewed., Data Collection and Analysis: We did not identify any studies with eligible design that addressed the objective of the review., Main Results: There are no included studies., Conclusion: Future studies need to look beyond establishing the prevalence and correlates of FGM to conducting well-designed, randomized controlled studies or well-designed interventional observational studies for the management of the psychological consequences of women and girls living with FGM., Prospero Registration: CRD42015024458., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Female sexual dysfunction is the persistent or recurring decrease in sexual desire or arousal, the difficulty or inability to achieve an orgasm, and/or the feeling of pain during sexual intercourse. Impaired sexual function can occur with all types of female genital mutilation (FGM) owing to the structural changes, pain, or traumatic memories associated with the procedure., Objectives: To conduct a systematic review of randomized and nonrandomized studies into the effects of sexual counseling with or without genital lubricants on the sexual function of women living with FGM., Search Strategy: Cochrane Central Register of Controlled Trials, MEDLINE, African Index Medicus, SCOPUS, LILACS, CINAHL, ClinicalTrials.gov, Pan African Clinical Trials Registry, and other databases were searched to August 2015. The reference lists of retrieved studies were checked for reports of additional studies, and lead authors contacted for additional data., Selection Criteria: Studies of girls and women living with any type of FGM who received counselling interventions for sexual dysfunction were included., Data Collection and Analysis: No relevant studies that addressed the objective of the review were identified., Conclusions: Despite a comprehensive search, the authors could not find evidence of the effects of sexual counseling on the sexual function of women living with FGM. Studies assessing this intervention are needed., Prospero Registration: CRD42015024593., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Women and girls who have undergone type III female genital mutilation (FGM) may suffer urologic complications such as recurrent urinary tract infections, obstruction, stones, and incontinence., Objective: To assess the effectiveness of deinfibulation for preventing and treating urologic complications in women and girls living with FGM., Search Strategy: The following major databases were searched from inception to August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, SCOPUS, Web of Science, and ClinicalTrials.gov without language restrictions., Selection Criteria: Randomized controlled studies (RCTs) or observational studies with controls were considered., Data Collection and Analysis: We screened the results of the search independently for potentially relevant studies and applied inclusion and exclusion criteria for the full texts of the relevant studies., Results: No RCTs were found. We found three case reports and a retrospective case review, all of which were excluded., Conclusion: There is no evidence on the use of deinfibulation to improve urologic complications among women with type III FGM. Current clinical practice may be informed by anecdotal evidence from case reports. Appropriate RCTs and observational studies with comparison groups in countries where FGM is common are needed. PROSPERO registration: CRD42015024901., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Counselling is a routine practice done before deinfibulation in women with type III female genital mutilation (FGM). However, cultural and social pressures, in addition to maladaptation to the changes in the body post deinfibulation, cause some women to choose to be reinfibulated after being deinfibulated., Objective: To conduct a systematic review of the impact of counselling prior to deinfibulation on patient satisfaction, marital satisfaction, and rate of requests for reinfibulation among women living with type III FGM. The secondary aim was to assess the impact of male partner involvement in counselling on patient satisfaction, marital satisfaction, and rate of requests for reinfibulation., Search Strategy: Major databases including Cochrane Central Register of Controlled Trials, Medline, SCOPUS, and ClinicalTrials.gov were searched until August 2015., Selection Criteria: Studies comparing women with type III FGM who received counselling before deinfibulation versus no counselling were included., Data Collection and Analysis: Two team members independently screened and collected data., Results: No eligible studies were identified., Conclusion: There is no evidence to conclude that counselling before deinfibulation influences patients' satisfaction with overall quality of care or rates of request for reinfibulation., Prospero Registration: CRD42015024675., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: The persistence of female genital mutilation (FGM) in some countries, despite an overall decline in the prevalence of the practice, calls for improvement in the capacity of healthcare workers and institutions to provide optimal care for this population., Objectives: To determine the impact of providing information on FGM and its consequences to healthcare providers on their attitudes toward FGM, and quality of care and patient satisfaction., Search Strategy: The following major databases were searched from inception to August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, SCOPUS, Web of Science, and ClinicalTrials.gov, without language restrictions., Selection Criteria: Controlled studies were included based on use of objective measures., Data Collection and Analysis: Two team members independently screened and collected data. Relative risks and proportions were calculated and evidence assessed using the GRADE (Grade of Recommendation, Assessment, Development and Evaluation) approach., Results: One study was identified. Based on this study there was no evidence to suggest change in healthcare provider outcomes after the intervention., Conclusions: Despite a comprehensive search, only one study of low methodological quality was included. This precludes a definitive conclusion regarding the impact of providing information on FGM to healthcare providers. More research is needed., Prospero Registration: CRD42015024570., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Vulvar and clitoral pain are known complications of female genital mutilation (FGM). Several interventions have been used to treat these conditions. This review focuses on surgical and nonsurgical interventions to improve vulvar and clitoral pain in women living with FGM., Objective: To evaluate the impact of nonsurgical and surgical interventions for alleviating vulvar and clitoral pain in women living with any type of FGM and to assess the associated adverse events., Search Strategy: The search included the following major databases: Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov. These were searched from inception until August 10, 2015 without any language restrictions., Selection Criteria: Study designs included randomized controlled trials, cluster randomized trials, nonrandomized trials, cohort studies, case-control studies, controlled before-and-after studies, historical control studies, and interrupted time series with reported data comparing outcomes among women with FGM who were treated for clitoral or vulvar pain with either surgical or nonsurgical interventions., Data Collection and Analysis: Two team members independently screened studies for eligibility., Results: No studies were included., Conclusion: Limited information exists on management of vulvar and clitoral pain in women living with FGM. This constitutes an important area for further research., Prospero Registration: CRD42015024521., (© 2017 International Federation of Gynecology and Obstetrics.The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Female genital mutilation (FGM) has become recognized worldwide as an extreme form of violation of the human rights of girls and women. Strategies have been employed to curb the practice., Objective: To conduct a systematic review of randomized and nonrandomized studies of the effects of providing educational interventions on the body image and care-seeking behavior of girls and women living with FGM with the view to ending the practice., Search Strategy: CENTRAL, MEDLINE, and other databases were searched up to August 10, 2015 without any language restrictions., Selection Criteria: Studies that provided education to women and/or girls living with any type of FGM or residing in countries where FGM is predominantly practiced were included., Data Collection and Analysis: Two authors independently screened and collected data. We summarized dichotomous outcomes using odds ratios and evidence was assessed using the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation)., Results: Educational interventions resulted in fewer women recommending FGM for their daughters and also reduced the incidence of FGM cases among daughters of women who received the educational interventions., Conclusion: These findings need to be validated with large randomized trials., Prospero Registration: 42015024637., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)