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.

Epidemiological trends of Lassa fever in Nigeria, 2018-2021.

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.

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.

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.

Malariometric Indices among Nigerian Children in a Rural Setting.

Malaria contributes to high childhood morbidity and mortality in Nigeria. To determine its endemicity in a rural farming community in the south-south of Nigeria, the following malariometric indices, namely, malaria parasitaemia, spleen rates, and anaemia were evaluated in children aged 2-10 years. This was a descriptive cross-sectional survey among school-age children residing in a rubber plantation settlement. The children were selected from six primary schools using a multistaged stratified cluster sampling technique. They were all examined for pallor, enlarged spleen, or liver among other clinical parameters and had blood films for malaria parasites. Of the 461 children recruited, 329 (71.4%) had malaria parasites. The prevalence of malaria parasitaemia was slightly higher in the under fives than that of those ≥5 years, 76.2% and 70.3%, respectively. Splenic enlargement was present in 133 children (28.9%). The overall prevalence of anaemia was 35.7%. Anaemia was more common in the under-fives (48.8%) than in those ≥5 years (32.8%). The odds of anaemia in the under fives were significantly higher than the odds of those ≥5 years (OR = 1.95 [1.19-3.18]). Malaria is highly endemic in this farming community and calls for intensification of control interventions in the area with special attention to school-age children.

Open-label trial of three dosage regimens of fixed-dose combination of artemisinin and naphthoquine for treating uncomplicated falciparum malaria in Calabar, Nigeria.

BACKGROUND: The use of anti-malarial drug combinations with artemisinin, or with one of its derivatives, is now widely recommended to overcome drug resistance in falciparum malaria. Fixed-dose combination of artemisinin and naphthoquine is a new generation artemisinin combination therapy (ACT) offered as a single dose therapy. The aim of the study was to assess the therapeutic efficacy, safety and tolerability of three dosage schedules of fixed-dose combination of artemisinin (125 mg) and naphthoquine (50 mg) for treating uncomplicated Plasmodium falciparum malaria among adolescents and adults in Calabar, South-east Nigeria. METHOD: A total of 121 patients aged ≥15 years with uncomplicated P. falciparum malaria were enrolled and randomly assigned to three dosage schedules: (A) 700 mg (four tablets) single dose; (B) 700 mg 12-hourly x two doses; and (C) 1,400 mg (eight tablets) single dose. Patients were observed for 28 days, with clinical, parasitological, and haematological assessments. RESULTS: A total of 108 patients completed the study. The overall 28-day cure rate was 88.9%. Day 28-cure rates of the three dosage schedules were 85.3%, 93.1% and 88.9% for Group A, B and C respectively. Adverse events were few and mild, the commonest being weakness and headache; there was no serious adverse event. CONCLUSION: Concerns for emergence of parasite resistance due to the use of artemisinin-naphthoquine as single dose regimen is likely to compromise the usefulness of this potentially important combination treatment. A robust multi-centre trial is recommended to evaluate a three-day regimen with potentials to achieve high cure rates while minimizing the risk of emergence of resistant parasite strains.