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Background: Over the last two decades, global stakeholders and the Nigerian government have invested approximately $2 billion in malaria control, reducing parasite prevalence to 23% from 42% in 2010. However, there is a risk that the modest gains will be reversed due to unmet resource gaps. Backward integration is presented in this paper as a viable option for sustainable funding of malaria intervention commodities in Nigeria. Methods: Following a critical appraisal of the resource profile and malaria expenditure, a conceptual framework on backward integration as a means of ensuring long-term supply of malaria intervention commodities was developed. The study analyzed secondary annual data from the National Malaria Elimination Programme to estimate commodity needs for the period 2018-2020, as well as total resources committed and the financial gap. Findings: The funds needed to implement national malaria interventions from 2018 to 2020 totaled US$ 1,122,332,318, of which US$ 531,228,984 (47.3%) were funded. The Nigerian government contributed 2.5%, the Global Fund (26.7%), the President's Malaria Initiative [PMI] (16.5%), and the Department for International Development [DFID] (6.2%). The funding shortfall was $591,103,335, or 52.7% of the needs. Various funding scenarios were evaluated for their relative merits and limitations, including advocacy for more external funding, bank borrowing, increased domestic resources, and backward integration. Interpretation: The study concluded that backward integration should be used, based on a government-led public-private partnership that will increase local production of malaria intervention commodities that are accessible and affordable through market-based demand and supply arrangements.

Background The collateral damages from measures adopted to mitigate the coronavirus disease 2019 (COVID-19) pandemic have been projected to negatively impact malaria in sub-Saharan Africa. Herein, we compare the prevalence and outcomes of childhood severe malaria during the pre-COVID-19 and COVID-19 periods at a tertiary health facility in Nigeria. Methods This was a retrospective review of cases of severe malaria admitted from 1st January to 31st December 2019 (pre-COVID-19 period) and 1st January to 31st December 2020 (COVID-19 period). We extracted relevant information, including demographics, the duration of symptoms before presentation, forms of severe malaria, and outcomes of hospitalization (discharged or death). Results In the pre-COVID-19 period, there were a total of 2312 admissions to the EPU and 1685 in the COVID-19 period, representing a decline of 27%. In contrast, there were 263 and 292 severe malaria admissions in the pre-COVID-19 and COVID-19 periods, respectively, representing an 11% increase in the absolute number of cases. The prevalence rates were 11.4% in the pre-COVID-19 period and 17.3% in the COVID-19 period, representing an increase of 52% in the percentage differences. The mortality rate in the COVID-19 period was higher than the pre-COVID-19 period ([10.3%; 30/292 vs. 2.3%; 6/263], p 0.001). The death rate increased by 350% during the COVID-19 period. The odds ratio (OR) of a child dying from severe malaria in the COVID-19 era was 4.9 [95% confidence interval (CI): 2.008 to 11.982]. In the COVID-19 era, presentation at a health facility was also delayed (p = 0.029), as were the odds of multiple features of severe malaria manifestations (OR-1.9, 95% CI, 1.107 to 3.269; p = 0.020). Conclusion This study shows that the prevalence of severe childhood malaria increased by as much as 11.0%, with a disproportionate increase in mortality compared to the pre-pandemic level. Most children with severe malaria presented late with multiple features of severe malaria, probably contributing to the poor hospitalization outcomes (death) observed in this study.

Background Acute kidney injury (AKI) is an underrecognized complication of severe malaria and an independent risk factor for mortality among children. Objective To determine the incidence and factors predictive of AKI as defined by the pediatric risk, injury, failure, loss, and end-stage (pRIFLE) criteria in children with severe malaria and to assess in-hospital mortality rates in malarial AKI (MAKI). Methods This was a prospective cohort study in 170 children aged 0.5 to 14 years with confirmed Plasmodium falciparum on peripheral blood smears and clinical and/or laboratory features of severe malaria. Serum creatinine was determined using the Jaffe method and glomerular filtration rate (eGFR) was estimated using the Schwartz equation. The primary outcome was the incidence of AKI as defined by the pRIFLE criteria. Secondary outcomes included in-hospital mortality comparison between AKI and non-AKI groups, as well as factors predictive of AKI. Results The incidence of MAKI was 61.2% (104/170) and was comparable between males (66.7%) and females (70.6%). Mean eGFR was lower among children with AKI than those without [42.00 (SD 22) vs. 98.7 (SD 3.9) mL/min/1.73m2, respectively; P=0.005]. Children with MAKI were categorized as having risk (47/104; 45.2%), injury (33/104; 31.7%), or failure (24/104; 23.1%). Mortality rates in AKI and non-AKI subjects were comparable (4.8% vs. 4.6%; P=0.888). Predictors of MAKI were hemoglobinuria [adjusted OR (aOR) 3.948; 95%CI 1.138 to 8.030], deep acidotic breathing (aOR 2.991; 95%CI 3.549 to 66.898), and longer hospital stay (aOR 2.042; 95%CI 3.617 to 12.156). Children with MAKI were more likely to have a longer hospital stay by a mean of 2.5 days. Conclusion AKI is a common complication in children with severe malaria. MAKI has a low mortality rate comparable to those with severe malaria but without AKI. Hemoglobinuria, deep acidotic breathing, and longer hospital stay were predictive of MAKI.

Introduction: Recent reports of artemisinin partial resistance from Rwanda and Uganda are worrisome and suggest a future policy change to adopt new antimalarials. We conducted a case study on the evolution, adoption, and implementation of new antimalarial treatment policies in Nigeria. The main objective is providing perspectives to enhance the future uptake of new antimalarials, with an emphasis on stakeholder engagement strategies. Methods This case study is based on an analysis of policy documents and stakeholders’ perspectives drawn from an empirical study conducted in Nigeria, 2019–2020. A mixed methods approach was adopted, including historical accounts, review of programme and policy documents, and qualitative in-depth interviews and focus group discussions. Themes for the framework were developed and applied to the case study. Results Based on policy documents reviewed, the adoption of artemisinin-based combination therapies (ACTs) in Nigeria was swift due to political will, funding and support from global developmental partners. However, implementation of ACTs was met with resistance from suppliers, distributors, prescribers, and end-users, attributed to market dynamics, costs and inadequate stakeholder engagement. Deployment of ACTs in Nigeria witnessed more developmental partner support, robust data generation, ACT case-management strengthening and evidence on antimalarial use in severe malaria and antenatal care management. We propose a framework for effective stakeholder engagement for future adoption of new antimalarials or antimalarial treatment strategies. The framework covers the pathway from generating evidence to making treatment accessible and affordable to end-users. It addresses who to engage with, the content of engagement and what strategies would support effective engagement with key stakeholders at different levels of the transition process. Conclusion Early and staged engagement of stakeholders from global bodies through regulatory authorities to end-users at the community level is critical to the successful adoption and uptake of new antimalarial treatment policies. A framework for these engagements has been proposed as a unique contribution to enhancing this process.

Background The collateral damages from measures adopted to mitigate the COVID-19 pandemic have been projected to impact negatively on malaria in sub-Saharan Africa. Herein, we compared the prevalence and outcomes of childhood severe malaria during pre-COVID-19 and COVID-19 periods at a tertiary health facility in Nigeria. Methods This was a retrospective review of cases of severe malaria admitted from 1st January to 31st December 2019 (pre-COVID-19 period) and 1st January to 31st December 2020 (COVID-19 period). We extracted relevant information including demographics, duration of symptoms before presentation, forms of severe malaria, and outcomes of hospitalization (discharged or death). Results In the pre-Covid period, there were a total of 2312 admissions to the EPU and 1685 in the covid period representing a decline of 27%. In contrast, there were 263 and 292 severe malaria admissions in the pre-COVID-19 and COVID-19 periods, respectively, representing an 11% increase in the absolute number of cases. The prevalence rates were 11.4% in the pre-COVID-19 period and 17.3% in the COVID-19 period representing an increase of 52% in the percentage differences. The mortality rate in COVID-19 period was higher than the pre-COVID-19 period ([10.3%;30/292 vs 2.3% 6/263], p

Background Artemisinin-based combination therapies (ACTs) are the recommended treatment for uncomplicated Plasmodium falciparum malaria in all malaria endemic countries. Artemisinin resistance, partner drug resistance, and subsequent ACT failure are widespread in Southeast Asia. The more recent independent emergence of artemisinin resistance in Africa is alarming. In response, triple artemisinin-based combination therapies (TACTs) are being developed to mitigate the risks associated with increasing drug resistance. Since ACTs are still effective in Africa, where malaria is mainly a paediatric disease, the potential deployment of TACTs raises important ethical questions. This paper presents an analysis of stakeholders’ perspectives regarding key ethical considerations to be considered in the deployment of TACTs in Africa provided they are found to be safe, well-tolerated and effective for the treatment of uncomplicated malaria. Methods We conducted a qualitative study in Burkina Faso and Nigeria assessing stakeholders’ (policy makers, suppliers and end-users) perspectives on ethical issues regarding the potential future deployment of TACTs through 68 in-depth interviews and 11 focus group discussions. Findings Some respondents suggested that there should be evidence of local artemisinin resistance before they consider deploying TACTs, while others suggested that TACTs should be deployed to protect the efficacy of current ACTs. Respondents suggested that additional side effects of TACTs compared to ACTs should be minimal and the cost of TACTs to end-users should not be higher than the cost of current ACTs. There was some disagreement among respondents regarding whether patients should have a choice of treatment options between ACTs and TACTs or only have TACTs available, while ACTs are still effective. The study also suggests that community, public and stakeholder engagement activities are essential to support the introduction and effective uptake of TACTs. Conclusion Addressing ethical issues regarding TACTs and engaging early with stakeholders will be important for their potential deployment in Africa.

IntroductionDespite the relatively higher neonatal morbidity and mortality in developing countries, there are limited data on the detailed analysis of the burden in Nigeria. With a database of over 14,000 admissions, this study presents a compelling picture of the current trends disaggregated by their gestational age groups. It provides unique opportunities for better-targeted interventions for further reducing newborn mortality in line with SDG 3, Target 3.2.MethodsThis prospective observational study involved newborn babies admitted to the Neonatal Intensive Care Unit of the University of Ilorin Teaching Hospital, Kwara State, Nigeria, between January 2007 and December 2018. The outcome was the neonatal mortality rates. The exposure variables included birth weight, gestational age (preterm versus term), and clinical diagnosis. Frequencies were generated on tables and charts, and the trends or associations were determined.ResultsOf the 14,760 neonates admitted, 9,030 (61.2%) were term babies, 4,847 (32.8%) were preterm babies, and in 792 (5%) of the admissions, the gestational ages could not be determined. Males constituted a higher proportion with 55.9%, and the total number of deaths in the study period was 14.7%. The mortality ratio was highest among babies with a birth weight of less than 1,000 g (38.0%) and gestational age of less than 28 weeks (65.5%). The trend analysis showed that the mortality rate decreased from 17.8 to 13% over the 12 years, p-value < 0.0001. For term babies, mortality decreased by 45%, from 15.7% in 2007 to 8.7% in 2018, while the decline in mortality for preterm babies was 28.4%, from 25.7% in 2007 to 18.4% in 2018. For both categories, p-values were < 0.001. Regarding morbidity in term babies, asphyxia occurred in (1:3), jaundice (1:5), sepsis (1:6), and respiratory disorders (1:6) of admissions. For mortality, asphyxia occurred in (1:2), sepsis (1:5), jaundice (1:8), and respiratory disorders (1:10) of deaths. The leading causes of morbidity among preterm babies were asphyxia (1:4), sepsis (1:5), respiratory disorders (1:9), and jaundice (1.10). For mortality, their contributions were asphyxia (≈1:2); sepsis (1:5); respiratory disorders (1:9), and jaundice (1:10).ConclusionThere was a marked improvement in neonatal mortality trends. However, severe perinatal asphyxia, sepsis, hyperbilirubinemia, and respiratory disorders were the leading conditions contributing to 75% of the morbidities and mortalities. Measures to further accelerate the reduction in neonatal morbidity and mortality are discussed.

PURPOSE: Routine eye examination in early life is not the practice in most resource-limited countries. Delay in the presentation for eye problems is typical. Community health officers are often consulted by caregivers for all health problems during routine immunization and well-baby clinics in primary healthcare for children aged 0–2 years. This study evaluated the value and limitation of interview, Bruckner red reflex test, and instrument vision screener by noneye care middle-level staff of rural and urban well-baby immunization clinics, in early detection and referral for childhood eye disorders. MATERIALS AND METHODS: This was a cross-sectional study. Middle-level community health workers (CHWs) working at well-baby/ immunization clinics were trained to perform vision screening using interview of caregivers, red reflex eye examination with ophthalmoscope, and instrument vision screener (Welch Allyn SPOT™ Vision Screener) without mydriatic drugs during routine immunization of children aged 0–2 years. IRB approval was obtained. RESULTS: Over a 6-month period in 2017, the CHWs screened 5609 children. Overall, 628 (11.2%) patients were referred to the tertiary child eye care unit. Referred cases included cataract, glaucoma, congenital nasolacrimal duct obstruction, ophthalmia neonatorum, retinoblastoma, and significant refractive errors. Referral from the interview of mothers was enhanced if specific questions to elicit visual function were asked. Bruckner red reflex test was more effective than instrument vision screener in the detection of cataract and life-threatening diseases such as retinoblastoma. Instrument vision screener was preferred by parents and better at detecting amblyopic risk factors. CONCLUSION: Preschool vision screening during routine immunization by primary healthcare workers in resource-limited settings was effective. Whenever instrument vision screener does not give any recommendation during screening, consider vision- or life-threatening pathology and refer.

There is a paucity of information regarding the epidemiology and outcome of COVID-19 from low/middle-income countries, including from Nigeria. This single-center study described the clinical features, laboratory findings, and predictors of in-hospital mortality of COVID-19 patients. Patients admitted between April 10, 2020 and June 10, 2020 were included. Forty-five patients with a mean age of 43 (16) years, predominantly male (87%), presented with fever (38%), cough (29%), or dyspnea (24%). In-hospital mortality was 16%. The independent predictors of mortality were hypoxemia (adjusted odds ratio [aOR]: 2.5; 95% CI: 1.3–5.1) and creatinine > 1.5 mg/dL (aOR: 4.3; 95% CI: 1.9–9.8).

Introduction Triple artemisinin-based combination therapies (TACTs) are being developed as a response to artemisinin and partner drug resistance in the treatment of falciparum malaria in Southeast Asia. In African countries, where current artemisinin-based combination therapies (ACTs) are still effective, TACTs have the potential to benefit the larger community and future patients by mitigating the risk of drug resistance. This study explores the extent to which the antimalarial drug markets in African countries are ready for a transition to TACTs. Methods A qualitative study was conducted in Nigeria and Burkina Faso and comprised in-depth interviews (n = 68) and focus group discussions (n = 11) with key actor groups in the innovation system of antimalarial therapies. Results Evidence of ACT failure in African countries and explicit support for TACTs by the World Health Organization (WHO) and international funders were perceived important determinants for the market prospects of TACTs in Nigeria and Burkina Faso. At the country level, slow regulatory and implementation procedures were identified as potential barriers towards rapid TACTs deployment. Integrating TACTs in public sector distribution channels was considered relatively straightforward. More challenges were expected for integrating TACTs in private sector distribution channels, which are characterized by patient demand and profit motives. Finally, several affordability and acceptability issues were raised for which ACTs were suggested as a benchmark. Conclusion The market prospects of TACTs in Nigeria and Burkina Faso will depend on the demonstration of the added value of TACTs over ACTs, their advocacy by the WHO, the inclusion of TACTs in financial and regulatory arrangements, and their alignment with current distribution and deployment practices. Further clinical, health-economic and feasibility studies are required to inform decision makers about the broader implications of a transition to TACTs in African counties. The recent reporting of artemisinin resistance and ACT failure in Africa might change important determinants of the market readiness for TACTs.

ObjectivesRetinopathy of prematurity (ROP) will become a major cause of blindness in Nigerian children unless screening and treatment services expand. This article aims to describe the collaborative activities undertaken to improve services for ROP between 2017 and 2020 as well as the outcome of these activities in Nigeria.DesignDescriptive case study.SettingNeonatal intensive care units in Nigeria.ParticipantsStaff providing services for ROP, and 723 preterm infants screened for ROP who fulfilled screening criteria (gestational age Methods and analysisA WhatsApp group was initiated for Nigerian ophthalmologists and neonatologists in 2018. Members participated in a range of capacity-building, national and international collaborative activities between 2017 and 2018. A national protocol for ROP was developed for Nigeria and adopted in 2018; 1 year screening outcome data were collected and analysed. In 2019, an esurvey was used to collect service data from WhatsApp group members for 2017–2018 and to assess challenges in service provision.ResultsIn 2017 only six of the 84 public neonatal units in Nigeria provided ROP services; this number had increased to 20 by 2018. Of the 723 babies screened in 10 units over a year, 127 (17.6%) developed any ROP; and 29 (22.8%) developed type 1 ROP. Only 13 (44.8%) babies were treated, most by intravitreal bevacizumab. The screening criteria were revised in 2020. Challenges included lack of equipment to regulate oxygen and to document and treat ROP, and lack of data systems.ConclusionROP screening coverage and quality improved after national and international collaborative efforts. To scale up and improve services, equipment for neonatal care and ROP treatment is urgently needed, as well as systems to monitor data. Ongoing advocacy is also essential.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Background Malaria remains a public health burden especially in Nigeria. To develop new malaria control and elimination strategies or refine existing ones, understanding parasite population diversity and transmission patterns is crucial. Methods In this study, characterization of the parasite diversity and structure of Plasmodium falciparum isolates from 633 dried blood spot samples in Nigeria was carried out using 12 microsatellite loci of P. falciparum. These microsatellite loci were amplified via semi-nested polymerase chain reaction (PCR) and fragments were analysed using population genetic tools. Results Estimates of parasite genetic diversity, such as mean number of different alleles (13.52), effective alleles (7.13), allelic richness (11.15) and expected heterozygosity (0.804), were high. Overall linkage disequilibrium was weak (0.006, P Conclusion The high level of parasite genetic diversity and low population structuring in this study suggests that parasite populations circulating in Nigeria are homogenous. However, higher resolution methods, such as the 24 SNP barcode and whole genome sequencing, may capture more specific parasite genetic signatures circulating in the country. The results obtained can be used as a baseline for parasite genetic diversity and structure, aiding in the formulation of appropriate therapeutic and control strategies in Nigeria.

Introduction: According to the World Malaria Report 2019, Africa accounts for 94% of the global malaria deaths. While malaria prevalence and mortality have declined over the years, recent reports suggest that these gains may stand the risk of being reversed if resistance to Artemisinin Combination Therapies (ACTs) spreads from Southeast Asia to Africa. Efforts are being made to develop new treatments that will address the looming threat of ACT resistance, including the development of triple artemisinin combination therapies (TACTs). The proposed study seeks to explore the views of stakeholders on the key ethical, regulatory and market-related issues that should be considered in the potential introduction of triple artemisinin combination therapies (TACTs) in Africa. Methods: The study employed qualitative research methods involving in-depth interviews and focus group discussions (FGDs) with stakeholders, who will be directly affected by the potential deployment of triple artemisinin combination treatments, as regulators, suppliers and end-users. Participants will be purposively selected and will include national regulatory authorities, national malaria control programs, clinicians, distributors and retailers as well as community members in selected districts in Burkina Faso and Nigeria. Discussion: The proposed study is unique in being one of the first studies that seeks to understand the ethical, social, regulatory and market position issues prior to the development of a prospective antimalarial medicine.

Background The development and spread of artemisinin-resistant Plasmodium falciparum malaria in Greater Mekong Subregion has created impetus for continuing global monitoring of efficacy of artemisinin-based combination therapies (ACTs). This post analyses is aimed to evaluate changes in early treatment response markers 10 years after the adoption of ACTs as first-line treatments of uncomplicated falciparum malaria in Nigeria. Methods At 14 sentinel sites in six geographical areas of Nigeria, we evaluated treatment responses in 1341 children under 5 years and in additional 360 children under 16 years with uncomplicated malaria enrolled in randomized trials of artemether-lumefantrine versus artesunate-amodiaquine at 5-year interval in 2009–2010 and 2014–2015 and at 2-year interval in 2009–2010 and 2012–2015, respectively after deployment in 2005. Results Asexual parasite positivity 1 day after treatment initiation (APPD1) rose from 54 to 62% and 2 days after treatment initiation from 5 to 26% in 2009–2010 to 2014–2015 (P = 0.002 and P 75 000 μl− 1, haematocrit > 27% 1 day post-treatment initiation, treatment with artemether-lumefantrine and enrolment in 2014–2015 independently predicted APPD1. In parallel, Kaplan-Meier estimated risk of recurrent infections by day 28 rose from 8 to 14% (P = 0.005) and from 9 to 15% (P = 0.02) with artemether-lumefantrine and artesunate-amodiaquine, respectively. Mean asexual parasitaemia half-life increased significantly from 1.1 h to 1.3 h within 2 years (P

Background: In Nigeria, neonatal jaundice is commonly treated by overhead phototherapy with neonates lying supine, often with effective exposure of less than one half of the body surface. Total body exposure in phototherapy has been in use for less than 2 years in Nigeria, but is available in only five neonatal centres.Aim: To compare the effectiveness of total body exposure (TBPE) with the conventional partial exposure (COPT) for treatment of hyperbilirubinaemia.Methods: Eleven datasets from 10 neonatal units across Nigeria were retrieved. They included neonates with severe hyperbilirubinaemia treated with TBPE using the Firefly® device (MTTS Asia) as a test group. The remainder of the patients, the controls, were treated with COPT. Any requirement for exchange blood transfusion (EBT) in either group was documented. Total serum bilirubin (TSB) >213.8 μmol/L (12.5 mg/dL) was treated as severe hyperbilirubinaemia. The efficiency of the intervention was determined according to the time taken for a severe case to be downgraded to mild at ≤213.8 μmol/L.Results: A total of 486 patients were studied, 343 controls and 143 cases. Mean (SD) postnatal age was 6 days (0.7) for cases and 5 (0.9) for controls, for gestational age (GA) in completed weeks was 36 (0.5) for cases and 37 (0.7) for controls and for birthweight was 2.7 kg (0.25) for cases and 2.7 (0.22) for controls. Mean (SD) pre-intervention TSB was 299.3 (35.7) μmol/L for cases and 327.3 (13.9) for controls. Severity downgrade day was Day 2 (0.4) for cases and Day 5 (1.1) for controls. Overall relative EBT rate was 6% for cases and 55% for controls (p= 0.0001), and early preterm relative EBT rate was 0% for cases and 68% for controls (p < 0.01).Conclusion: TBPE was quicker and safer for reduction of hyperbilirubinaemia and patients rarely required EBT. TBPE is recommended for rapid reduction of serum bilirubin levels and the reduction of treatment costs, morbidity and mortality in low- and middle-income countries.Abbreviations: EBT, exchange blood transfusion; TBPE, total body exposure technique; COPT, conventional partial exposure; TSB, total serum bilirubin; SB, serum bilirubin; NNJ, neonatal jaundice; SCNU, special care neonatal unit; LMIC, low- and middle-income countries; HIC, high-income countries; LED, light-emitting diode.

Background: The value of Cystatin C as a biomarker of Glomerular filtration rate (GFR) among African newborns is unknown, due to paucity of studies, restricting the measurement of GFR in this popul...

Additional file 1. Shows the Number of different and effective alleles in parasite populations according to study location.

Introduction: According to the World Malaria Report 2019, Africa accounts for 94% of the global malaria deaths. While malaria prevalence and mortality have declined over the years, recent reports suggest that these gains may stand the risk of being reversed if resistance to Artemisinin Combination Therapies (ACTs) spreads from Southeast Asia to Africa. Efforts are being made to develop new treatments that will address the looming threat of ACT resistance, including the development of triple artemisinin combination therapies (TACTs). The proposed study seeks to explore the views of stakeholders on the key ethical, regulatory and market-related issues that should be considered in the potential introduction of triple artemisinin combination therapies (TACTs) in Africa. Methods: The study employed qualitative research methods involving in-depth interviews and focus group discussions (FGDs) with stakeholders, who will be directly affected by the potential deployment of triple artemisinin combination treatments, as regulators, suppliers and end-users. Participants will be purposively selected and will include national regulatory authorities, national malaria control programs, clinicians, distributors and retailers as well as community members in selected districts in Burkina Faso and Nigeria. Discussion: The proposed study is unique in being one of the first studies that seeks to understand the ethical, social, regulatory and market position issues prior to the development of a prospective antimalarial medicine.

Additional file 3. Shows expected heterozygosity (He) values of microsatellite loci from parasite populations in the nine States.

Additional file 2. Shows the allelic richness values in parasite populations per microsatellite loci.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Background The coverage of long lasting insecticidal nets (LLIN) and intermittent preventive treatment of malaria in pregnancy (IPTp) uptake for the prevention of malaria commonly vary by geography. Many sub-Saharan Africa (SSA) countries, including Nigeria are adopting the use of LLIN and IPTp to fight malaria. Albeit, the coverage of these interventions to prevent malaria across geographical divisions have been understudied in many countries. In this study, we aimed to explore the differentials in LLIN and IPTp uptake across Nigerian geopolitical zones. Methods We analyzed data from Nigeria Multiple Indicator Cluster Survey (MICS) 2016–17. The outcome variables were IPTp and LLIN uptake among women of childbearing age (15–49 years). A total sample of 24,344 women who had given birth were examined for IPTp use and 36,176 women for LLIN use. Percentages, Chi-square test and multivariable logit models plots were used to examine the geopolitical zones differentials in IPTp and LLIN utilization. Data was analyzed at 5% level of significance. Results The overall prevalence of IPTp was 76.0% in Nigeria. Moreover, there were differences across geopolitical zones: North Central (71.3%), North East (76.9%), North West (78.2%), South East (76.1%), South South (79.7%) and South West (72.4%) respectively. Furthermore, the prevalence of LLIN was 87.7%% in Nigeria. Also, there were differences across geopolitical zones: North Central (89.1%), North East (91.8%), North West (90.0%), South East (77.3%), South South (81.1%) and South West (69.8%) respectively. Women who have access to media use, married, educated and non-poor were more likely to uptake IPTp. On the other hand, rural dwellers and those with media use were more likely to use LLIN. Conversely, married, educated, non-poor and women aged 25–34 and 35+ were less likely to use LLIN. Conclusion Though the utilization of IPTp and LLIN was relatively high, full coverage are yet to be achieved. There was geopolitical zones differentials in the prevalence of IPTp and LLIN in Nigeria. Promoting the utilization of IPTp and LLINs across the six geopolitical zones through intensive health education and widespread mass media campaigns will help to achieve the full scale IPTp and LLIN utilization.

Objectives: Serum creatinine levels are often used to diagnose acute kidney injury (AKI), but may not necessarily accurately reflect changes in glomerular filtration rate (GFR). This study aimed to compare the prevalence of AKI in children with severe malaria using diagnostic criteria based on creatinine values in contrast to cystatin C. Methods: This prospective cross-sectional study was performed between June 2016 and May 2017 at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. A total of 170 children aged 0.5–14 years old with severe malaria were included. Serum cystatin C levels were determined using a particle-enhanced immunoturbidmetric assay method, while creatinine levels were measured using the Jaffe reaction. Renal function assessed using cystatin C-derived estimated GFR (eGFR) was compared to that measured using three sets of criteria based on creatinine values including the Kidney Disease: Improved Global Outcomes (KDIGO) and World Health Organization (WHO) criteria as well as an absolute creatinine cut-off value of >1.5 mg/dL. Results: Mean serum cystatin C and creatinine levels were 1.77 ± 1.37 mg/L and 1.23 ± 1.80 mg/dL, respectively (P = 0.002). According to the KDIGO, WHO and absolute creatinine criteria, the frequency of AKI was 32.4%, 7.6% and 16.5%, respectively. In contrast, the incidence of AKI based on cystatin C-derived eGFR was 51.8%. Overall, the rate of detection of AKI was significantly higher using cystatin C compared to the KDIGO, WHO and absolute creatinine criteria (P = 0.003

Heiner syndrome (HS) is a rare hypersensitivity reaction of an infant or young child to cow milk proteins. It is a disease characterised by failure to thrive, respiratory symptoms like cough, dyspnoea, wheeze and rhinitis with accompanying chest infiltrates on chest radiograph; gastrointestinal symptoms like vomiting, diarrhoea; and anaemia. The non-specific nature of the disease can result in delayed diagnosis and treatment and central to the condition is hypersensitivity to cow milk proteins.Several cases have been reported worldwide but there has been no report of this condition in Africa.We highlight the case of a sixteen week old child seen in our facility with features typical of Heiner syndrome. Clinicians should have a high index of suspicion for this condition especially in children predominantly on infant formula

Background: In Okelele, Ilorin, Kwara State, Nigeria, malaria remains an important public health concern with a little information about its prevalence. Objective: To determine the prevalence of malaria infection at Okelele Health Centre, Okelele, Ilorin. Methodology: A cross-sectional descriptive study in which patients were diagnosed clinically with severe or uncomplicated malaria at the study site was conducted. Rapid diagnostic testing (RDT) for malaria and microscopy using Giemsa staining by thick and thin blood smears were done for study patients. Results: In this study, 200 malaria patients attending Okelele Health Centre, Okelele, Ilorin, were tested for malaria infection, with females having the highest prevalence rates and parasitemia density. The highest positivity rates were found in children

In non-anaemic children with malaria, early-appearing anaemia (EAA) is common following artemisinin-based combination treatments (ACTs) and it may become persistent (PEAA). The factors contributing to and kinetics of resolution of the deficit in haematocrit from baseline (DIHFB) characteristic of ACTs-related PEAA were evaluated in 540 consecutive children with malaria treated with artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine. Asymptomatic PEAA occurred in 62 children. In a multiple logistic regression model, a duration of illness ≤3 days before presentation, haematocrit Trial registration: Pan Africa Clinical Trial Registration PACTR201709002064150, 1 March 2017 http://www.pactr.org

Background Nigeria commenced a phased programmatic deployment of rapid diagnostic tests (RDT) at the primary health care (PHC) facility levels since 2011. Despite various efforts, the national testing rate for malaria is still very low. The uptake of RDT has been variable. This study was undertaken to determine the provider and patient perceptions to RDT use at the PHC level in Nigeria with their implications for improving uptake and compliance. Methods A cross-sectional survey was conducted in 120 randomly selected PHCs across six states, across the six-geopolitical zones of Nigeria in January 2013. Health facility staff interviews were conducted to assess health workers (HW) perception, prescription practices and determinants of RDT use. Patient exit interviews were conducted to assess patient perception of RDT from ten patients/caregivers who met the eligibility criterion and were consecutively selected in each PHC, and to determine HW’s compliance with RDT test results indirectly. Community members, each selected by their ward development committees in each Local Government Area were recruited for focus group discussion on their perceptions to RDT use. Results Health workers would use RDT results because of confidence in RDT results (95.4%) and its reduction in irrational use of artemisinin-based combination therapy (ACT) (87.2%). However, in Enugu state, RDT was not used by health workers because of the pervasive notion RDT that results were inaccurate. Among the 1207 exit interviews conducted, 549 (45.5%) had received RDT test. Compliance rate (administering ACT to positive patients and withholding ACT from negative patients) from patient exit interviews was 90.2%. Among caregivers/patients who had RDT done, over 95% knew that RDT tested for malaria, felt it was necessary and liked the test. Age of patients less than 5 years (p = 0.04) and “high” educational status (p = 0.0006) were factors influencing HW’s prescription of ACT to RDT negative patients. Conclusion The study demonstrated positive perception to RDT use by HW and among community members with good compliance rate among health workers at the PHC level. This positive perception should be explored in improving the current low level of malaria testing in Nigeria while addressing the influence of age on HW administration of ACT to RDT negative cases.

Background In acute falciparum malaria, asexual parasite reduction ratio two days post-treatment initiation (PRRD2) ≥ 10 000 per cycle has been used as a measure of the rapid clearance of parasitaemia and efficacy of artemisinin derivatives. However, there is little evaluation of alternative measures; for example, parasite reduction ratio one day after treatment initiation (PRRD1) and its relationship with parasite clearance time (PCT) or PRRD2. This study evaluated the use of PRRD1 as a measure of responsiveness to antimalarial drugs. Methods In acutely malarious children treated with artesunate-amodiaquine (AA), artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHP), the relationships between PRRD1 or PRRD2 and PCT, and between PRRD1 and PRRD2 were evaluated using linear regression. Agreement between estimates of PCT using PRRD1 and PRRD2 linear regression equations was evaluated using the Bland-Altman analysis. Predictors of PRRD1 > 5000 per half cycle and PRRD2 ≥ 10 000 per cycle were evaluated using stepwise multiple logistic regression models. Using the linear regression equation of the relationship between PRRD1 and PCT previously generated in half of the DHP-treated children during the early study phase, PCT estimates were compared in a prospective blinded manner with PCTs determined by microscopy during the later study phase in the remaining half. Results In 919 malarious children, PRRD1 was significantly higher in DHP- and AA-treated compared with AL-treated children (P 15 months, parasitaemia > 10 000/μl and DHP treatment independently predicted PRRD1 > 5000 per half cycle, while age > 30 months, haematocrit ≥31%, body temperature > 37.4 °C, parasitaemia > 100 000/μl, PRRD1 value > 1000 and no gametocytaemia independently predicted PRRD2 ≥ 10 000 per cycle. Using the linear regression equation generated during the early phase in 166 DHP-treated children, PCT estimates and PCTs determined by microscopy in the 155 children in the later phase were similar in the same patients. Conclusions PRRD1 and estimates of PCT using PRRD1 linear regression equation of PRRD1 and PCT can be used in therapeutic efficacy studies. Trial registration Pan African Clinical Trial Registration PACTR201709002064150, 1 March 2017, http://www.pactr.org

Background Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children. Methods Malarious 4% were evaluated by stepwise multiple logistic regression models. Survival analysis and kinetics of DAFH were evaluated by Kaplan-Meier estimator and non-compartment model, respectively. Results Pre-treatment, 355 of 959 children were anaemic. Duration of illness >2 days and parasitaemia ≤10,000 μL−1 were independent predictors of anaemia pre-treatment. EAA occurred in 301 of 604 children. Predictors of EAA were age ≤ 15 months, history of fever pre-treatment and enrolment haematocrit ≤35%. The probabilities of progression from normal haematocrit to EAA were similar for all treatments. MAFH >4% occurred in 446 of 694 children; its predictors were anaemia pre-treatment, enrolment parasitaemia ≤50,000 μL−1, parasitaemia one day post-treatment initiation and gametocytaemia. DAFH >4% occurred in 334 of 719 children; its predictors were history of fever pre-and fever 1 day post-treatment initiation, haematocrit ≥37%, and parasitaemia >100,000 μL−1. In 432 children, declines in DAFH deficits were monoexponential with overall estimated half-time of 2.2d (95% CI 1.9–2.6). Area under curve of deficits in DAFH versus time and estimated half-time were significantly higher in non-anaemic children indicating greater loss of haematocrit in these children. Conclusion After ten years of adoption of ACTs, anaemia is common pre-and early post-treatment, falls in haematocrit attributable to a single infection is high, and DAFH >4% is common and significantly lower in anaemic compared to non-anaemic Nigerian children. Trial registration Pan African Clinical Trial Registry (PACTR) [ PACTR201709002064150, 1 March 2017 ].

Successful control of malaria depends upon the detailed knowledge of its epidemiology, including the knowledge of environmental, behavioral, socio-economic and socio-demographic factors that influence its prevalence, and on the knowledge and use of preventive measures. We carried out a cross-sectional study to assess the risk factors for malaria in children presenting with fever in rural Gambia. Three hundred and seventy-six children aged 5 months to 10 years presenting to Farafenni health centre, the Gambia with fever or history of fever were enrolled. The socio-demographic characteristics, clinical findings, and knowledge and use of preventive measures in malaria were documented. Finger-prick blood sampling for malaria was obtained and two sets of smears (thick and thin) were prepared and stained with Giemsa stain. One hundred and eighty two children (48.4%) had malaria. The significant risk factors associated with malaria were non-use of insecticide treated bed nets [χ2 = 8.82, P = 0.01, (95% confidence interval 0.10–0.67)] and age [χ2 = 9.18, P = 0.004, (95% confidence interval 0.31–0.78)]. There were no significant associations identified between the development of malaria and parental education, occupation, knowledge of the cause of malaria, type of roof or wall in the home, or whether the parents reared livestock.

Since congenital malaria had previously been thought to be rare, blood film examination for malaria parasites is still sometimes not routinely performed in ill neonates in malaria-endemic regions. Because of increasing published reports of congenital malaria in Nigeria, there is a need to characterize the clinical and laboratory manifestations associated with malaria parasitemia within the first few hours of life. In a 12-month (April 2003-March 2004), multicenter study in Nigeria, thin and thick blood smears made from maternal (finger prick), placental aspirates, cord blood and neonate (heel prick taken within 4 hours of life) were Giemsa-stained and examined by light microscopy for asexual stages of Plasmodium. Parasitemic neonates were closely monitored for clinical and laboratory features of symptomatic malaria. Plasmodium falciparum was found in 5.1% (95/1875) of neonatal heel pricks; mean parasite density was low (mean = 48/μL, range 8–200/μL). Antepartum maternal and placental parasitemia were the most important risk factors for congenital parasitemia ( P P P 37.5°;) within the first 24 hours of life (100%) and refusal to suck (10.8%). Anemia at birth (hematocrit P = 0.03, OR = 1.84). The mean hematocrit of parasitemic neonates within 4 hours of life was 49.5 ± 6.4 as compared to 52.6 ± 8.2 in non-parasitemic babies ( P = 0.001). Furthermore, the mean hematocrit was 44.0 ± 5.5% in the symptomatic parasitemic babies. All symptomatic babies were treated with oral chloroquine with a cure rate of 89.1%. Treatment failures subsequently received oral sulfadoxine-pyrimethamine with good outcome. The febrile newborn should be evaluated for malaria especially if there is a history of prolonged labor or in the presence of maternal malaria infection. Efforts should be intensified to reduce the burden of maternal, placental malaria and therefore congenital malaria.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.).

Background : Plasmodium falciparum, the most dangerous malaria parasite species to humans remains an important public health concern in Okelele, a rural community in Ilorin, Kwara State, Nigeria. There is however little information about the genetic diversity of Plasmodium falciparum in Nigeria. Objective : To determine the population genomic diversity of Plasmodium falciparum in malaria patients attending Okelele Community Healthcare Centre, Okelele, Ilorin, Kwara State. Methods : In this study, 50 Plasmodium falciparum strains Merozoite Surface Protein 1, Merozoite Surface Protein 2 and Glutamate Rich Protein were analysed from Okelele Health Centre, Okelele, Ilorin, Nigeria. Genetic diversity of P. falciparum isolates were analysed from nested polymerase chain reactions (PCR) of the MSP-1 (K1, MAD 20 and RO33), MSP-2 (FC27 and 3D7) and Glutamate Rich Protein allelic families respectively. Results : Polyclonal infections were more in majority of the patients for MSP-1 allelic families while monoclonal infections were more for MSP-2 allelic families. Multiplicity of infection for MSP-1, MSP-2 and GLURP were 1.7, 1.8 and 2.05 respectively Conclusion : There is high genetic diversity in MSP – 2 and GLURP allelic families of Plasmodium falciparum isolates from Okelele Health Centre, Ilorin, Nigeria. Keywords : Plasmodium falciparum, Merozoite Surface Protein, genetic diversity.

The effect of meteorologically-induced high room temperature on neonates and incubators in a tropical climate was studied. Two rooms were designated for the study. The main nursery hall served as the ‘control-room' where environmental conditions remained unaltered. A sun-shading and wall-lagging method was applied to the ‘test-room' to reduce the warming effect of high sunlight intensity. A weather monitoring station was installed to separately record meteorological changes outside the nursery and both study rooms. Incubator set-points and process temperatures were recorded hourly using digital thermometer from 8:00 h to 21:00 h daily. All set ups were allowed to continue through the harmattan and dry season months. On the cumulative average, 80% of Incubators malfunctioned in the control-room, and 9% in the test-room. Minimisation of meteorological heat transmission into nursery wards is an essential factor to consider for designing and setting up a neonatal centre in a tropical climate.

OBJECTIVE: To explore the cost-effectiveness of parenteral artesunate for the treatment of severe malaria in children and its potential impact on hospital budgets. METHODS: The costs of inpatient care of children with severe malaria were assessed in four of the 11 sites included in the African Quinine Artesunate Malaria Treatment trial, conducted with over 5400 children. The drugs, laboratory tests and intravenous fluids provided to 2300 patients from admission to discharge were recorded, as was the length of inpatient stay, to calculate the cost of inpatient care. The data were matched with pooled clinical outcomes and entered into a decision model to calculate the cost per disability-adjusted life year (DALY) averted and the cost per death averted. FINDINGS: The mean cost of treating severe malaria patients was similar in the two study groups: 63.5 United States dollars (US$) (95% confidence interval, CI: 61.7-65.2) in the quinine arm and US$ 66.5 (95% CI: 63.7-69.2) in the artesunate arm. Children treated with artesunate had 22.5% lower mortality than those treated with quinine and the same rate of neurological sequelae: (artesunate arm: 2.3 DALYs per patient; quinine arm: 3.0 DALYs per patient). Compared with quinine as a baseline, artesunate showed an incremental cost per DALY averted and an incremental cost per death averted of US$ 3.8 and US$ 123, respectively. CONCLUSION: Artesunate is a highly cost-effective and affordable alternative to quinine for treating children with severe malaria. The budgetary implications of adopting artesunate for routine use in hospital-based care are negligible.