Publications by authors named "Catherine Falade"

61 Publications

Serum cytokine profile of pregnant women with malaria, intestinal helminths and HIV infections in Ibadan, Nigeria.

Parasitol Res 2022 May 6. Epub 2022 May 6.

Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.

Malaria, helminthiasis and HIV are widespread in developing countries taking a heavy toll on pregnant women. Due to similar environmental and human factors of transmission, they co-exist. The epidemiology and pathology of these diseases have been extensively studied but data on serum cytokine profile changes which is crucial in pregnancy is limited. The aim of this study was to evaluate the co-infections and their impact on peripheral blood cytokines. Blood and stool samples were collected from recruited 18-45-year-old pregnant women in different trimesters who were apparently healthy with no obvious complications in pregnancy. Pretested questionnaires were administered for personal and socio-demographic details. Malaria parasitemia in Giemsa-stained thick blood films was examined microscopically. Stool samples were screened for helminths using Kato-Katz method. Cytokine levels of TNF-α, IFN-γ, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and IL-17 in 121 serum samples were determined using ELISA. Data were analysed using descriptive statistics and Mann-Whitney U test at α Relative to the single infections, there were significant reductions in IFN-γ and IL-13 in second and third trimesters respectively in those with Plasmodium and helminth co-infection. IFN-γ and IL-17 were elevated while IL-1α and IL-12p70 were reduced in co-infection of helminths and HIV. Co-infection of Plasmodium and HIV in second and third trimesters showed significant elevations in IL-1α, IL-10 and IL-17 while TNF-α, IL-4 and IL-12p70 were significantly reduced. HIV in pregnancy and its co-infection with Plasmodium resulted in significant distortions in the cytokine profile. However, helminth and its co-infection with Plasmodium or HIV produced less changes in the cytokine profile.
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http://dx.doi.org/10.1007/s00436-022-07531-6DOI Listing
May 2022

Malaria parasite density and plasma apolipoprotein A1 in symptomatic and asymptomatic infections in Nigerian children.

J Vector Borne Dis 2021 Oct-Dec;58(4):311-316

Department of Pharmacology & Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria.

Background & Objectives: Alterations in plasma apolipoproteins in individuals with malaria infection and their potential roles in the pathogenesis are known but the link between the malaria parasite density and apolipoprotein A1 (apo-A1) level is insufficiently understood. This study was conducted to determine whether the plasma apo-A1 level is influenced by the degree of parasitaemia in malaria infections.

Methods: In a case-control study, a convenient sample of children aged 2-10 years with uncomplicated malaria cases (UMC), asymptomatic parasitaemia cases (APC) and healthy children without parasitaemia (HCP) was recruited. The cases consisted of 61 UMC and 21 APC, while the controls consisted of 24 HCP. Levels of apo-A1 was determined using immunoturbidimetric assay and compared among the different degrees of parasite density.

Results: Of the 82 participants with parasitaemia, density was ≤1000/μL in 12, 1001-10000/μL in 21 and >10000/μL in 49 children. There was significant difference among the mean values of apolipoprotein A1 of the three groups, viz: UMC [91.4 (95% CI: 81.3, 101.5) mg/dL], APC [67.0 (95% CI: 48.9, 84.9) mg/dL] and HCP [99.0 (95% CI: 76.6, 121.3) mg/dL], p=0.029. Post-hoc analysis revealed that the mean plasma level of apo-A1 in HCP was significantly higher than APC by 32.0±12.4 mg/dL and UMC by 7.5±4.2 mg/dL. However, there were no differences in the mean apolipoprotein A1 levels among the three groups of parasite density.

Interpretation & Conclusion: The presence of parasitaemia causes a remarkable reduction in apolipoprotein A1 level that was not influenced by the degree of parasitaemia.
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http://dx.doi.org/10.4103/0972-9062.318309DOI Listing
April 2022

The CircumVent Project: a CPAP/O helmet solution for non-invasive ventilation using an implementation research framework.

Implement Sci Commun 2021 Aug 26;2(1):93. Epub 2021 Aug 26.

Nigerian Institute of Medical Research, Lagos, Nigeria.

Background: Acute respiratory failure, a major cause of death in COVID-19, is managed with high-flow oxygen therapy via invasive mechanical ventilation. In resource-limited settings like Nigeria, the shortage of ventilators and oxygen supply makes this option challenging. Evidence-based non-invasive alternatives to mechanical ventilation such as the use of continuous positive airway pressure (CPAP) devices exist, but there have been concerns that non-invasive ventilation may expose healthcare workers to infection from aerosolized dispersion of SARS-CoV-2. We propose to evaluate the feasibility, adaptability and acceptability of a CPAP/O helmet solution for non-invasive ventilation among patients with COVID-19 and health workers in eight COVID-19 treatment and isolation centers in Nigeria.

Methods: The study will occur in 4 stages: (1) convene a Steering Committee of key stakeholders and recruit implementation sites; (2) use the integrated Promoting Action on Research Implementation in Health Services (i-PARiHS) framework to guide a needs assessment of treatment centers' capacity to use high-flow oxygen therapy to treat COVID-19 patients and utilize the findings to develop an implementation strategy for the use of a CPAP/O helmet solution; (3) build infrastructure to support training and data monitoring processes and to develop implementation protocols to evaluate the adaptability of the strategy for the use of the CPAP/O helmet; and (4) train health workers, distribute a CPAP/O helmet solution for non-invasive ventilation, pilot test the implementation strategy, and assess feasibility of its use and acceptability that includes monitoring altered risk of SARS-CoV-2 infection among healthcare workers.

Discussion: The CPAP/O helmet solution for non-invasive ventilation in Nigeria can serve as a scalable model for resource-poor countries, and beyond the COVID-19 pandemic, has the potential to be deployed for the treatment of pneumonia and other respiratory diseases.

Trial Registration: NCT04929691. Registered June 18, 2021-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04929691.
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http://dx.doi.org/10.1186/s43058-021-00193-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390034PMC
August 2021

Surveillance of Pretreatment Drug Resistance Among HIV-Infected Children in Ibadan, Nigeria.

AIDS Res Hum Retroviruses 2021 12 11;37(12):922-929. Epub 2021 Aug 11.

Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria.

There are about 2.1 million children infected with HIV globally and about 120,000 deaths annually. Nigeria has one of the highest rates of pediatric HIV infection globally. Pretreatment HIV drug resistance data inform the choice of first- and second-line antiretroviral therapy (ART) regimens. This study investigated the prevalence of HIV drug-resistant strains among ART-naive children in Ibadan, Nigeria. A total of 20 children aged <15 years were enrolled. Demographic, clinical, and laboratory data were documented. Total nucleic acid was extracted from blood samples after which amplification of HIV-1 pol gene was done using polymerase chain reaction. Amplified gene was sequenced using big dye sequencing method. The sequenced HIV-1 pol gene was typed and analyzed for identification of mutations indicative of drug resistance across the different classes of ART. HIV-1 RNA pol gene was successfully amplified in 12/20 (60%) children. All were identified as HIV-1 and the subtypes were G and CRF 02AG, recombinant of 02_AG/G and recombinant of 02_AG/A1. Drug-resistant mutations (DRMs) were identified in 4/12 (33%). Three out of the four mutations were identified as non-nucleoside reverse transcriptase inhibitors DRM (K103N), whereas the fourth had nucleoside reverse transcriptase inhibitors DRM (M184V). Results from this preliminary study show that drug resistance among ART-naive children is a problem in Ibadan. Pretreatment drug resistance testing is desirable in children before initiation of ART to guide effective treatment.
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http://dx.doi.org/10.1089/AID.2020.0272DOI Listing
December 2021

Malaria, Helminth Infections and Clinical Status Among HIV-Infected Pregnant Women.

Int J MCH AIDS 2021 19;10(1):81-87. Epub 2020 Feb 19.

Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.

Background Or Objectives: Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is widespread in sub-Saharan Africa with similarity in geographical distribution of major pathogens of public health interest. The aim of this study was to assess the effect of malaria and helminths on CD4 count, hematocrit values and viral load among HIV-infected pregnant women.

Methods: One hundred and ninety-seven HIV-infected pregnant women aged 18-45 years were recruited from a registered HIV clinic and questionnaires were administered for socio-demographic details. Screening for malaria parasites in blood was through microscopy while helminths were identified in stool using Kato-Katz method. Hematocrit levels were determined through centrifugation of blood collected in capillary tubes. At the time of recruitment, most recent CD4 count and viral load was obtained from the patients' case notes.

Results: About three-quarters (73.6%) of the women had above primary school level of education while more than half (60.2%) were petty traders. The prevalence of malaria parasites in the blood samples was 24.9%, while 3% were infected with helminths. There was only a single case of malaria, helminths and HIV co-infection in the study group. Prevalence of anemia was 75.6% with eight cases (4.1%) of severe anemia. About 86.6% of the women with anemia had low CD4 count (χ= 8.801, p=0.032). The mean CD4 count was significantly lower among those with co-infection of malaria and HIV.

Conclusion And Global Health Implications: Malaria or helminth infection among HIV-infected women lowers the CD4 count and increases the viral load with little changes in hematocrit values. Routine screening of HIV-infected women for probable multiple infections will aid in improving their overall health and well-being.
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http://dx.doi.org/10.21106/ijma.352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905432PMC
February 2020

Ethical issues in the COVID-19 pandemic control preparedness in a developing economy.

Pan Afr Med J 2020 29;35(Suppl 2):95. Epub 2020 Jun 29.

Ethics Sub-committee of the Coronavirus Pandemic Response Committee, University of Ibadan, Ibadan, Nigeria.

Adequate preparation for highly pathogenic infectious disease pandemic can reduce the incidence, prevalence and burden of diseases like COVID-19 pandemic. An antidote to the spread of the disease is adequate preparation for its control since there is no proven curative measure yet. Effective management of identified cases, social distancing, contact tracing and provision of basic infrastructure to facilitate compliance with preventive measures, testing are proven management strategies. Although these measures seem to be the best options presently, it is important to pay attention to ethical issues arising from the implementation process to ensure best practice. While disease epidemic is not alien to human societies, lessons from previous outbreaks are vital for addressing future outbreaks. For effective control of this pandemic, there should be a clear definition of social distancing in terms of distance and space in line with the WHO definition, adequate provision of basic amenities, screening and testing with specific criteria for selecting those to be screened. Also, there should be a free testing procedure, access to treatment opportunities for those who test positive, ethical free contact tracing practice, respect for the autonomy of those to be tested, and global best practice of open science, open data and data sharing practices. In conclusion, a framework/guideline for epidemic/pandemic ethics guidance should be developed while an ethical sensitive communication manual should be prepared for public engagement on epidemic and pandemic.
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http://dx.doi.org/10.11604/pamj.supp.2020.35.23121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875799PMC
March 2021

The need for social group interventions to increase malaria rapid diagnostic test uptake in Nigeria.

Lancet Glob Health 2021 03;9(3):e231-e232

Department of Paediatrics and Child Health, University of Ilorin, Ilorin, Nigeria; National Malaria Elimination Programme, Federal Ministry of Health, Abuja, Nigeria.

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http://dx.doi.org/10.1016/S2214-109X(21)00032-2DOI Listing
March 2021

Contributions of malaria, helminths, HIV and iron deficiency to anaemia in pregnant women attending ante-natal clinic in SouthWest Nigeria.

Afr Health Sci 2020 Sep;20(3):1035-1044

Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.

Background: Iron deficiency is a dominant source of anaemia in many settings. To evaluate the key cause of anaemia in the study area, the prevalence of anaemia due to major public health diseases was compared with anaemia due to iron deficiency.

Methods: Pregnant women were recruited from ante-natal (n=490) and HIV clinics (n=217) with their personal data documented using a questionnaire. Microscopy of Giemsa-stained thick smears was used for detection of malaria parasites while helminths in stools were detected using direct smear method. Haematocrit values were determined by capillary method. Serum ferritin levels were determined using enzyme-linked immunosorbent assay. Data was analysed using SPSS version 22.0.

Results: The mean age of the recruited women was 28.6±5.4 years old. There were 68.1% cases of anaemia of which 35.5% was due to infections only predominantly HIV and malaria, 14.9% from unknown sources while anaemia due to iron deficiency only was 7.1%.

Conclusion: It can safely be inferred that malaria and HIV predispose to anaemia than iron deficiency in the study area. Although pregnant women are dewormed and given IPTp for helminths and malaria treatment respectively, there should be complementary routine malaria screening at ANC visits for those with HCT values <33% and those infected with HIV.
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http://dx.doi.org/10.4314/ahs.v20i3.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751510PMC
September 2020

Malaria and COVID-19: commonalities, intersections and implications for sustaining malaria control.

Pan Afr Med J 2020 1;37(Suppl 1). Epub 2020 Sep 1.

Department of Pharmacology & Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria.

The devastating impact of infectious disease outbreaks and pandemics on health systems could be overwhelming especially when there is an overlap in clinical presentations with other disease conditions. A case in point is the disruptive effect of the Ebola Virus Disease outbreak on health service delivery and its consequences for malaria management in the affected West and Central African countries between 2014 and 2016. This could be the case with the current infectious disease pandemic (COVID-19) the world is experiencing as malaria illness shares many symptoms with COVID-19 illness. Caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is reported to have originated from Wuhan city, China in December 2019. COVID-19 was declared a Public Health Emergency of International Concern on 30 January 2020 and declared a pandemic on March 11, 2020 by the World Health Organization (WHO). Practically, all community infrastructure has been activated in affected countries in response to COVID-19. However, the deployment of huge resources in combating COVID-19 pandemic should not be a missed opportunity for the advancement of infectious diseases control including malaria. This calls for conscious and heightened effort to sustain the gains in malaria control. The WHO has emphasized that the response to the COVID-19 pandemic must utilize and strengthen existing infrastructure for addressing malaria and other infectious diseases globally. Leveraging these to maintain malaria control activities in endemic countries could boost and help to sustain the gains in malaria control in accordance with the 2016-2030 Global technical strategy for malaria (GTS) milestones. In addition, it will help to keep the "High burden to high impact" (HBHI) and other initiatives on track. This article highlights the commonalities of the two diseases, discusses implications and recommendations to support decision making strategies to keep malaria control on track in the COVID-19 pandemic era.
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http://dx.doi.org/10.11604/pamj.supp.2020.37.1.25738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704348PMC
January 2021

The fidelity of implementation of recommended care for children with malaria by community health workers in Nigeria.

Implement Sci 2020 03 4;15(1):13. Epub 2020 Mar 4.

Epidemiology and Biostatistics Research Unit, Institute of Advanced Medical Research and Training (IMARAT), College of Medicine, University of Ibadan, Ibadan, Nigeria.

Background: In the context of task shifting, a promoted approach to healthcare delivery in resource-poor settings, trained community health workers (CHWs) have been shown to be effective in delivering quality care of malaria for febrile under-5 children. While their effectiveness has been documented, the fidelity of implementation (FOI) has not been adequately studied. By understanding and measuring whether an intervention has been performed with fidelity, researchers and practitioners gain a better understanding of how and why an intervention works, and the extent to which outcomes can be improved. The objective of this study was to assess the FOI of a recommended protocol for malaria care by CHWs in a resource-poor setting in Nigeria.

Methods: Thirty-five female CHWs who participated in a 3-day training on home management of malaria among under-5 children were studied. They managed 1,646 children over the implementation period and then underwent evaluation via a one-time hospital-based observation by the trainers. During the evaluation, a pre-tested standard checklist was used to compute performance scores for CHWs; doctors and nurses were selected to serve as the gold standard for comparison. Performance scores (PS) recorded during the evaluation were used to assess adherence and compliance with the recommended treatment protocol.

Results: Of the 4 skill domains assessed, adherence was greatest for compliance with malaria treatment recommendations (94%) and lowest for post-treatment initiation counseling of home-based caregivers (69%). The average overall adherence of 83% was comparable to adherence by gold standard comparators. Mean PS was not found to be significantly associated with CHW demographics. Scores for clinical evaluation among those whose occupation was not healthcare-related were significantly lowered by 0.52 [95% CI (1.05-0.01), p = 0.05]. Compliance with the treatment protocol increased by 23% for every unit increase in total PS (p = 0.07) and doubled for every unit increase in scores for post-treatment initiation counseling of caregivers (p = 0.002).

Conclusions: Studying intervention fidelity stands to identify the shortcomings of implementation and specific areas to target for improvement in future adoption or implementation. This study concludes that future trainings should emphasize clinical evaluation and post-treatment counseling of caregivers by CHWs to ensure the best outcome for children.
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http://dx.doi.org/10.1186/s13012-020-0968-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057616PMC
March 2020

Evaluation of a capacity building intervention on malaria treatment for under-fives in rural health facilities in Niger State, Nigeria.

Malar J 2020 Feb 24;19(1):90. Epub 2020 Feb 24.

Disease Control Department, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

Background: Despite the uptake of parasitological testing into policy and practice, appropriate prescription of anti-malarials and artemisinin-based combination therapy (ACT) in accordance with test results is variable. This study describes a National Malaria Control Programme-led capacity building intervention which was implemented in 10 States of Nigeria. Using the experience of Niger State, this study assessed the effect on malaria diagnosis and prescription practices among febrile under-fives in rural health facilities.

Methods: The multicomponent capacity building intervention consisted of revised case management manuals; cascade training from national to state level carried out at the local government area (LGA) level; and on the job capacity development through supportive supervision. The evaluation was conducted in 28, principally government-owned, health facilities in two rural LGAs of Niger State, one in which the intervention case management of malaria was implemented and the other acted as a comparison area with no implementation of the intervention. Three outcomes were considered in the context of rapid diagnostic testing (RDT) for malaria which were: the prevalence of RDT testing in febrile children; appropriate treatment of RDT-positive children; and appropriate treatment of RDT-negative children. Outcomes were compared post-intervention between intervention and comparison areas using multivariate logistic regression.

Results: The intervention did not improve appropriate management of under-fives in intervention facilities above that seen for under-fives in comparison facilities. Appropriate treatment with artemisinin-based combinations of RDT-positive and RDT-negative under-fives was equally high in both areas. However, appropriate treatment of RDT-negative children, when defined as receipt of no ACT or any other anti-malarials, was better in comparison areas. In both areas, a small number of RDT-positives were not given ACT, but prescribed an alternative anti-malarial, including artesunate monotherapy. Among RDT-negatives, no under-fives were prescribed artesunate as monotherapy.

Conclusion: In a context of significant stock-outs of both ACT medicines and RDTs, under-fives were not more appropriately managed in intervention than comparison areas. The malaria case management intervention implemented through cascade training reached only approximately half of health workers managing febrile under-fives in this setting. Implementation studies on models of cascade training are needed to define what works in what context.
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http://dx.doi.org/10.1186/s12936-020-03167-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041190PMC
February 2020

and Not or Polymorphism Mediates Clinical Malaria and Parasitemia among Children from Nigeria.

Microorganisms 2020 Jan 23;8(2). Epub 2020 Jan 23.

Department of Biomedical Sciences, College of Health Sciences and Technology, Rochester Institute of Technology, Rochester, NY 14623, USA.

Malaria remains a significant disease, causing epic health problems and challenges all over the world, especially in sub-Saharan Africa. CD209 and CD28 genes act as co-stimulators and regulators of the immune system, while the STAT6 gene has been reported to mediate cytokine-induced responses. Single nucleotide polymorphisms of these genes might lead to differential disease susceptibility among populations at risk for malaria, due to alterations in the immune response. We aim to identify key drivers of the immune response to malaria infection among the three SNPs: CD209 (rs4804803), CD28 (rs35593994) and STAT6 (rs3024974). After approval and informed consent, we genotyped blood samples from a total of 531 children recruited from Nigeria using the Taqman SNP genotyping assay and performed comparative analysis of clinical covariates among malaria-infected children. Our results reveal the CD209 (rs4804803) polymorphism as a susceptibility factor for malaria infection, significantly increasing the risk of disease among children, but not CD28 (rs35593994) or STAT6 (rs3024974) polymorphisms. Specifically, individuals with the homozygous mutant allele (rs4804803G/G) for the CD209 gene have a significantly greater susceptibility to malaria, and presented with higher mean parasitemia. This observation may be due to a defective antigen presentation and priming, leading to an ineffective downstream adaptive immune response needed to combat infection, as well as the resultant higher parasitemia and disease manifestation. We conclude that the gene is a critical driver of the immune response during malaria infection, and can serve as a predictor of disease susceptibility or a biomarker for disease diagnosis.
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http://dx.doi.org/10.3390/microorganisms8020158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074881PMC
January 2020

Consequences of restricting antimalarial drugs to rapid diagnostic test-positive febrile children in south-west Nigeria.

Trop Med Int Health 2019 11 3;24(11):1291-1300. Epub 2019 Oct 3.

London School of Tropical Medicine and Hygiene, London, UK.

Objectives: To investigate the consequence of restricting antimalarial treatment to febrile children that test positive to a malaria rapid diagnostic test (MRDT) only in an area of intense malaria transmission.

Methods: Febrile children aged 3-59 months were screened with an MRDT at health facilities in south-west Nigeria. MRDT-positive children received artesunate-amodiaquine (ASAQ), while MRDT-negative children were treated based on the clinical diagnosis of non-malaria febrile illness. The primary endpoint was the risk of developing microscopy-positive malaria within 28 days post-treatment.

Results: 309 (60.5%) of 511 children were MRDT-positive while 202 (39.5%) were MRDT-negative at enrolment. 18.5% (50/275) of MRDT-positive children and 7.6% (14/184) of MRDT-negative children developed microscopy-positive malaria by day 28 post-treatment (ρ = 0.001). The risk of developing clinical malaria by day 28 post-treatment was higher among the MRDT-positive group than the MRDT-negative group (adjusted OR 2.74; 95% CI, 1.4, 5.4). A higher proportion of children who were MRDT-positive at enrolment were anaemic on day 28 compared with the MRDT-negative group (12.6% vs. 3.1%; ρ = 0.001). Children in the MRDT-negative group made more unscheduled visits because of febrile illness than those in MRDT-positive group (23.2% vs. 12.0%; ρ = 0.001).

Conclusion: Restricting ACT treatment to MRDT-positive febrile children only did not result in significant adverse outcomes. However, the risk of re-infection within 28 days was significantly higher among MRDT-positive children despite ASAQ treatment. A longer-acting ACT may be needed as the first-line drug of choice for treating uncomplicated malaria in high-transmission settings to prevent frequent re-infections.
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http://dx.doi.org/10.1111/tmi.13304DOI Listing
November 2019

Molecular surveillance of pfhrp2 and pfhrp3 genes deletion in Plasmodium falciparum isolates and the implications for rapid diagnostic tests in Nigeria.

Acta Trop 2019 Aug 16;196:121-125. Epub 2019 May 16.

Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Osogbo, Nigeria. Electronic address:

Prompt diagnosis and appropriate treatment of malaria remain the hallmark for reducing malaria-related mortality in high transmission areas. Plasmodium falciparum histidine-rich protein2 (PfHRP2) based rapid diagnostic tests (RDT) play a vital role in prompt and accurate malaria diagnosis. However, pfhrp2 gene deletion threatens the RDT test sensitivity. This study reports the presence of pfhrp2 and pfhrp3 genes deletion among parasite isolates in Nigeria. Febrile children were screened using histidine-rich protein (HRP2) specific RDT (SD-Bioline RDT) and microscopy for P. falciparum infections. All RDT negative samples were re-evaluated by polymerase chain reaction (PCR). The presence of parasite in RDT false negative cases and randomly selected RDT positive cases were validated using PCRs targeting glutamate-rich protein (glurp) and merozoite surface proteins (msp-1 and msp-2). Thereafter, exon 2 of pfhrp2 and pfhrp3 were amplified, and Sanger sequenced. A total of 511 febrile children were enrolled out of which 309 (61%) were positive by RDT. The presence of pfhrp2 and pfhrp3 genes were analyzed in 66 PCR positive samples comprising of 31 RDT false negative and 35 RDT true positive randomly selected samples. The pfhrp2 and pfhrp3 genes failed to amplify in 17% (11/66) and 6% (4/66) samples, respectively. Seven of the eleven samples had only pfhrp2 deletion while four had both pfhrp2 and pfhrp3 deletions. The absence of the pfhrp2 gene may be responsible for the seven RDT false negative cases observed. Three RDT positive cases lacked pfhrp2 whereas pfhrp3 was absent in only four RDT false negative cases. The pfhrp2 and pfhrp3 amino acid repeat sequences were highly diverse. The P. falciparum isolates lacking pfhrp2 and pfhrp3 genes may be circulating and contributing to RDT false negativity in Nigeria. More studies in larger population and seasonally defined cases will be needed to determine the extent of pfhrp2/3 genes deletion in different geographical areas of Nigeria.
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http://dx.doi.org/10.1016/j.actatropica.2019.05.016DOI Listing
August 2019

High prevalence of dihydrofolate reductase gene mutations in Plasmodium falciparum parasites among pregnant women in Nigeria after reported use of sulfadoxine-pyrimethamine.

Pathog Glob Health 2018 03 10;112(2):86-92. Epub 2018 Jan 10.

b Institute of Tropical Medicine , Eberhard Karls University of Tübingen , Tübingen , Germany.

This study assesses the prevalence of asymptomatic Plasmodium falciparum parasitemia positivity and P. falciparum dihydrofolate reductase (pfdhfr) mutations in parasite isolates among pregnant women in Southwest Nigeria. Plasmodium falciparum parasitemia was confirmed by microscopy and nested PCR in 200 pregnant women attending antenatal care. The prevalence of pfdhfr polymorphisms was determined by direct sequencing of the gene fragments containing the C50R, N51I, C59R, S108N, and I164L mutations. Information on the use of antimalarial drugs and methods applied to prevent malaria were obtained by a questionnaire. The prevalence of asymptomatic P. falciparum infection was 30% (60/200). The frequency of the pfdhfr triple-mutant alleles (N51I, C59R, and S108N) was 63% (38/60); none of the isolates carried the I164L mutation. Among the investigated pregnant women, 40% used un-prescribed antimalarials such as dihydroartemisinin (18%), chloroquine (14%) or pyrimethamine (9%), while only 20.5% used sulfadoxine-pyrimethamine for prevention and 39.5% did not use any drug. The prevalence of P. falciparum parasitemia (37%) was higher among pregnant women who had not taken any antimalarial drugs. A significant difference in the prevalence of the pfdhfr triple-mutant alleles was observed among women who took SP (90%) compared to those who did not take any drug (82%) and women who took dihydroartemisinin (67%) p = 0.007). Poor adherence to the World Health Organisation (WHO) strategies for malaria prevention among pregnant women was observed in addition to high prevalence of pfdhfr mutations. These findings underline the need to improve control of malaria among pregnant women in the study area.
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http://dx.doi.org/10.1080/20477724.2017.1422615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056817PMC
March 2018

Extensive diversity in the allelic frequency of Plasmodium falciparum merozoite surface proteins and glutamate-rich protein in rural and urban settings of southwestern Nigeria.

Malar J 2018 01 2;17(1). Epub 2018 Jan 2.

Tropical Disease Research Laboratory, College of Health Sciences, Ladoke Akintola University of Technology, Osogbo, Nigeria.

Background: Nigeria carries a high burden of malaria which makes continuous surveillance for current information on genetic diversity imperative. In this study, the merozoite surface proteins (msp-1, msp-2) and glutamate-rich protein (glurp) of Plasmodium falciparum collected from two communities representing rural and urban settings in Ibadan, southwestern Nigeria were analysed.

Methods: A total of 511 febrile children, aged 3-59 months, whose parents/guardians provided informed consent, were recruited into the study. Capillary blood was obtained for malaria rapid diagnostic test, thick blood smears for parasite count and blood spots on filter paper for molecular analysis.

Results: Three-hundred and nine samples were successfully genotyped for msp-1, msp-2 and glurp genes. The allelic distribution of the three genes was not significantly different in the rural and urban communities. R033 and 3D7 were the most prevalent alleles in both rural and urban communities for msp-1 and msp-2, respectively. Eleven of glurp RII region genotypes, coded I-XII, with sizes ranging from 500 to 1100 base pairs were detected in the rural setting. Genotype XI (1000-1050 bp) had the highest prevalence of 41.5 and 38.5% in rural and urban settings, respectively. Overall, 82.1 and 70.0% of samples had multiclonal infection with msp-1 gene resulting in a mean multiplicity of infection (MOI) of 2.8 and 2.6 for rural and urban samples, respectively. Msp-1 and msp-2 genes displayed higher levels of diversity and higher MOI rates than the glurp gene.

Conclusion: Significant genetic diversity was observed between rural and urban parasite populations in Ibadan, southwestern Nigeria. The results of this study show that malaria transmission intensity in these regions is still high. No significant difference was observed between rural and urban settings, except for a completely different msp-1 allele, compared to previous reports, thereby confirming the changing face of malaria transmission in these communities. This study provides important baseline information required for monitoring the impact of malaria elimination efforts in this region and data points useful in revising current protocols.
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http://dx.doi.org/10.1186/s12936-017-2149-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749027PMC
January 2018

Genetic Diversity of CD14 Promoter Gene Polymorphism () is Associated With Regulation of Malaria Parasitemia and Susceptibility to Infection.

Infect Dis (Auckl) 2017 17;10:1178633617726781. Epub 2017 Aug 17.

Department of Biomedical Sciences, College of Health Sciences and Technology, Rochester Institute of Technology, Rochester, NY, USA.

CD14 is a multifunctional receptor expressed on many cell types and has been shown to mediate immune response resulting in the activation of an inflammatory cascade, with polymorphism of its promoter (rs2569190) found to be associated with susceptibility to several diseases. In malaria infection, the CD14 gene demonstrated a pathogenic profile in regulating experimental cerebral malaria, with reports of elevated levels of soluble CD14 in serum of patients but no definitive conclusion. We present a detailed analysis of genetic diversity of CD14 promoter gene (snp -159 C/T; rs2519190) polymorphism between a malaria-infected group and uninfected controls and its association with clinical parameters of disease. Genomic DNA samples obtained from 106 malaria-infected patients and 277 uninfected controls were elucidated with a polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Our results show a significant diversity ( = 3.32E-06) in the genotypic frequency (3.8% versus 22.4%) of the rs2569190 mutant variant between the malaria-infected group and controls, respectively. The mutant allele had the lowest frequency among the malaria-infected group demonstrating its necessity for infection. Mean parasitemia (parasites/μL of blood) was significantly regulated based on CD14 polymorphic profile (19 855 versus 37 041 versus 49 396 for homozygote mutants, heterozygotes, and homozygote wild type, respectively). Interestingly, we found no association between CD14 genetic variants with fever, age of patients, or anemia. How this affects disease severity between subregional and continental groups deserves further clarification, including extending these studies in a larger group and among severe and asymptomatic patients with malaria.
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http://dx.doi.org/10.1177/1178633617726781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624288PMC
August 2017

Genetic variants of tumor necrosis factor-α -308G/A (rs1800629) but not Toll-interacting proteins or vitamin D receptor genes enhances susceptibility and severity of malaria infection.

Immunogenetics 2018 02 30;70(2):135-140. Epub 2017 Sep 30.

Department of Biomedical Sciences, College of Health Sciences and Technology, Rochester Institute of Technology, 153 Lomb Memorial Drive, Rochester, NY, 14623, USA.

Susceptibility to malaria infection has been associated with host genetic polymorphisms that differs between groups. We hypothesize that Toll-interacting proteins (TOLLIP), vitamin D receptor (VDR) and tumor necrosis factor-α (TNF) genes are significant contributors to susceptibility and disease severity in Plasmodium falciparum (Pf) infection. Our aim is to explore the genomic diversity and haplotype frequency of these genes, as well as extrapolate possible association with markers of severity, between malaria-infected and healthy controls. Genomic DNA samples extracted from the blood of 107 malaria-infected patients and 190 uninfected controls were analyzed, with no difference in genotypic or allelic frequencies of TOLLIP and VDR polymorphisms. However, a significant difference in the genotypic (p = 2.20E-16) and allelic frequencies (p = 2.20E-16) of the TNF-α (snp rs1800629) polymorphism was found. The preponderance of the mutant variant among the malaria-infected show a possible impaired capacity to mount an effective immune response, potentially confirmed by our association results. This result calls for analysis of clearly delineated uncomplicated versus severe disease groups, including serum assays, providing a basis to conclude that susceptibility to malaria infection and potential contribution to disease severity is significantly associated with polymorphisms of the tumor necrosis factor-α but not TOLLIP or VDR genes.
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http://dx.doi.org/10.1007/s00251-017-1032-4DOI Listing
February 2018

Assessing Acceptability of a Diagnostic and Malaria Treatment Package Delivered by Community Health Workers in Malaria-Endemic Settings of Burkina Faso, Nigeria, and Uganda.

Clin Infect Dis 2016 Dec;63(suppl 5):S306-S311

Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Nigeria.

Background:  The efficacy of artemisinin-based combination therapy (ACT) and rectal artesunate for severe malaria in children is proven. However, acceptability of a package of interventions that included use of malaria rapid diagnostic tests (RDTs), ACTs, and rectal artesunate when provided by community health workers (CHWs) is uncertain. This study assessed acceptability of use of CHWs for case management of malaria using RDTs, ACTs, and rectal artesunate.

Methods:  The study was carried out in Burkina Faso, Nigeria, and Uganda in 2015 toward the end of an intervention using CHWs to provide diagnosis and treatment. Focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with parents of sick children, community leaders, and health workers to understand whether they accepted the package for case management of malaria using CHWs. Transcripts from FGDs and KII recordings were analyzed using content analysis. The findings were described, interpreted, and reported in the form of narratives.

Results:  Treatment of malaria using the CHWs was acceptable to caregivers and communities. The CHWs were perceived to be accessible, diligent, and effective. There were no physical, social, or cultural barriers to accessing the CHWs' services. Respondents were extremely positive about the intervention and were concerned that CHWs had limited financial and nonfinancial incentives that would reduce their motivation and willingness to continue.

Conclusions:  Treatment of malaria using CHWs was fully accepted. CHWs should be compensated, trained, and well supervised.

Clinical Trials Registration:  ISRCTN13858170.
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http://dx.doi.org/10.1093/cid/ciw630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146702PMC
December 2016

Malaria Rapid Diagnostic Tests and Malaria Microscopy for Guiding Malaria Treatment of Uncomplicated Fevers in Nigeria and Prereferral Cases in 3 African Countries.

Clin Infect Dis 2016 Dec;63(suppl 5):S290-S297

UNICEF/UNDP/World Bank/WHO/Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.

Background:  The World Health Organization recommends that malaria treatment be based on demonstration of the infecting Plasmodium parasite specie. Malaria rapid diagnostic tests (RDTs) are recommended at community points of care because they are accurate and rapid. We report on parasitological results in a malaria study in selected rural communities in 3 African countries.

Methods:  In Nigeria, community health workers (CHWs) performed RDTs (SD-Bioline) and thick blood smears on all children suspected to have malaria. Malaria RDT-positive children able to swallow received artemisinin-based combination therapy (Coartem). In all countries, children unable to take oral drugs received prereferral rectal artesunate irrespective of RDT result and were referred to the nearest health facility. Thick blood smears and RDTs were usually taken at hospital admission. In Nigeria and Burkina Faso, RDT cassettes and blood smears were re-read by an experienced investigator at study end.

Results:  Trained CHWs enrolled 2148 children in Nigeria. Complete parasitological data of 1860 (86.6%) enrollees were analyzed. The mean age of enrollees was 30.4 ± 15.7 months. The prevalence of malaria parasitemia in the study population was 77.8% (1447/1860), 77.6% (1439/1855), and 54.1% (862/1593) by RDT performed by CHWs vs an expert clinical research assistant vs microscopy (gold standard), respectively. Geometric mean parasite density was 6946/µL (range, 40-436 450/µL). There were 49 cases of RDT false-negative results with a parasite density range of 40-54 059/µL. False-negative RDT results with high parasitemia could be due to non-falciparum infection or result from a prozone effect. Sensitivity and specificity of SD-Bioline RDT results as read by CHWs were 94.3% and 41.6%, respectively, while the negative and positive predictive values were 86.1% and 65.6%, respectively. The level of agreement in RDT reading by the CHWs and experienced research staff was 86.04% and κ statistic of 0.60. The malaria parasite positivity rate by RDT and microscopy among children with danger signs in the 3 countries was 67.9% and 41.8%, respectively.

Conclusions:  RDTs are useful in guiding malaria management and were successfully used for diagnosis by trained CHWs. However, false-negative RDT results were identified and can undermine confidence in results and control efforts.
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http://dx.doi.org/10.1093/cid/ciw628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146700PMC
December 2016

Compliance With Referral Advice After Treatment With Prereferral Rectal Artesunate: A Study in 3 Sub-Saharan African Countries.

Clin Infect Dis 2016 Dec;63(suppl 5):S283-S289

UNICEF/UNDP/World Bank/WHO/Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.

Background:  Children aged <5 years were enrolled in a large study in 3 countries of sub-Saharan Africa because they had danger signs preventing them from being able to take oral medications. We examined compliance and factors associated with compliance with referral advice for those who were treated with rectal artesunate.

Methods:  Patient demographic data, speed of accessing treatment after danger signs were recognized, clinical symptoms, malaria microscopy, treatment-seeking behavior, and compliance with referral advice were obtained from case record forms of 179 children treated with prereferral rectal artesunate in a multicountry study. We held focus group discussions and key informant interviews with parents, community health workers (CHWs), and facility staff to understand the factors that deterred or facilitated compliance with referral advice.

Results:  There was a very high level of compliance (90%) among patients treated with prereferral rectal artesunate. Age, symptoms at baseline (prostration, impaired consciousness, convulsions, coma), and malaria status were not related to referral compliance in the analysis.

Conclusions:  Teaching CHWs to diagnose and treat young children with prereferral rectal artesunate is feasible in remote communities of Africa, and high compliance with referral advice can be achieved.
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http://dx.doi.org/10.1093/cid/ciw627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146699PMC
December 2016

Compliance With Malaria Rapid Diagnostic Testing by Community Health Workers in 3 Malaria-Endemic Countries of Sub-Saharan Africa: An Observational Study.

Clin Infect Dis 2016 Dec;63(suppl 5):S276-S282

UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.

Background:  The World Health Organization recommends that all malaria management be based on parasitological identification. We monitored performance of trained community health workers (CHWs) in adhering to this recommendation to restrict artemisinin-based combination therapies (ACTs) to positive rapid diagnostic test (RDT)-confirmed cases in children in 3 malaria-endemic sub-Saharan African countries.

Methods:  In 33 villages in Burkina Faso, 45 villages in Nigeria, and 84 villages in Uganda, 265 CHWs were trained over a minimum of 3 days to diagnose malaria using RDTs (prepare, read, record results, and inform the patient about results) and treat RDT-confirmed uncomplicated malaria cases with ACTs. In Nigeria, CHWs were also taught to obtain a thick blood smear. Spent RDT kits and prepared blood slides were collected and interpreted independently in Burkina Faso and Nigeria to confirm CHWs' diagnoses. Interviews were held with 12 of 17 CHWs who prescribed ACTs for patients with RDT-negative test results, and with 16 of 29 caregivers to determine factors related to noncompliance.

Results:  Of 12 656 patients treated with ACTs in the participating countries (5365 in Burkina Faso, 1648 in Nigeria, and 5643 in Uganda), 29 patients (8 from Burkina Faso, 17 from Nigeria, 4 from Uganda) were RDT negative. The small number of RDT-negative ACT-treated cases limits statistical analysis. Only a few CHWs were involved, and they were more likely to be traders rather than farmers (odds ratio [OR], 6.15; 95% confidence interval [CI], 2.09-18.07; P = .0004). RDT-negative children who were treated with ACTs had a significantly higher probability of residing in a village other than that of the CHW (OR, 3.85; 95% CI, 1.59-9.30; P = .0018). Parental pressure was identified in interviews with parents.

Conclusions:  Noncompliance with results of RDT tests is relatively rare when CHWs are trained and well supervised.

Clinical Trials Registration:  ISRCTN13858170.
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http://dx.doi.org/10.1093/cid/ciw626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146698PMC
December 2016

Motivation of Community Health Workers in Diagnosing, Treating, and Referring Sick Young Children in a Multicountry Study.

Clin Infect Dis 2016 Dec;63(suppl 5):S270-S275

UNICEF/UNDP/World Bank/WHO/Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.

Background:  Community health workers (CHWs) are an important element of care provision for a wide range of conditions, but their turnover rate is high. Many studies have been conducted on health workers' motivation, focusing on formal sector staff but not CHWs. Although CHWs are easy to recruit, motivating and retaining them for service delivery is difficult. This article investigates factors influencing CHW motivation and retention in health service delivery.

Methods:  Quantitative and qualitative data were collected to identify the key factors favoring motivation and retention of CHWs as well as those deterring them. We interviewed 47, 25, and 134 CHWs in Burkina Faso, Nigeria, and Uganda, respectively, using a structured questionnaire. Focus group discussions (FGDs) were also conducted with CHWs, community participants, and facility health workers.

Results:  Except for Burkina Faso, most CHWs were female. Average age was between 38 and 41 years, and most came from agricultural communities. The majority (52%-80%) judged they had a high to very high level of satisfaction, but most CHWs (approximately 75%) in Burkina Faso and Uganda indicated that they would be prepared to leave the job, citing income as a major reason. Community recognition and opportunities for training and supervision were major incentives in all countries, but the volume of unremunerated work, at a time when both malaria-positive cases and farming needs were at their peak, was challenging.

Conclusions:  Most CHWs understood the volunteer nature of their position but desired community recognition and modest financial remuneration.

Clinical Trials Registration:  ISRCTN13858170.
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http://dx.doi.org/10.1093/cid/ciw625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146697PMC
December 2016

Training Community Health Workers to Manage Uncomplicated and Severe Malaria: Experience From 3 Rural Malaria-Endemic Areas in Sub-Saharan Africa.

Clin Infect Dis 2016 Dec;63(suppl 5):S264-S269

UNICEF/UNDP/World Bank/WHO/Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.

Background:  Use of community health workers (CHWs) to increase access to diagnosis and treatment of malaria is recommended by the World Health Organization. The present article reports on training and performance of CHWs in applying these recommendations.

Methods:  Two hundred seventy-nine CHWs were trained for 3-5 days in Burkina Faso, Nigeria, and Uganda, and 19 were certified to diagnose and treat only uncomplicated malaria and 235 to diagnose and treat both uncomplicated and severe malaria. Almost 1 year after training, 220 CHWs were assessed using standard checklists using facility staff responses as the reference standard.

Results:  Training models were slightly different in the 3 countries, but the same topics were covered. The main challenges noticed were the low level of education in rural areas and the involvement of health staff in the supervision process. Overall performance was 98% (with 99% in taking history, 95% in measuring temperature, 85% for measuring respiratory rates, 98% for diagnosis, 98% for classification, and 99% for prescribing treatment). Young, single, new CHWs performed better than their older, married, more experienced counterparts.

Conclusions:  Training CHWs for community-based diagnosis and treatment of uncomplicated and severe malaria is possible with basic and refresher training and close supervision of CHWs' performance.

Clinical Trials Registration:  ISRCTRS13858170.
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http://dx.doi.org/10.1093/cid/ciw624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146696PMC
December 2016

Impact of Improving Community-Based Access to Malaria Diagnosis and Treatment on Household Costs.

Clin Infect Dis 2016 Dec;63(suppl 5):S256-S263

UNICEF/UNDP/World Bank/WHO/Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.

Background:  Community health workers (CHWs) were trained in Burkina Faso, Nigeria, and Uganda to diagnose febrile children using malaria rapid diagnostic tests, and treat positive malaria cases with artemisinin-based combination therapy (ACT) and those who could not take oral medicines with rectal artesunate. We quantified the impact of this intervention on private household costs for childhood febrile illness.

Methods:  Households with recent febrile illness in a young child in previous 2 weeks were selected randomly before and during the intervention and data obtained on household costs for the illness episode. Household costs included consultation fees, registration costs, user fees, diagnosis, bed, drugs, food, and transport costs. Private household costs per episode before and during the intervention were compared. The intervention's impact on household costs per episode was calculated and projected to districtwide impacts on household costs.

Results:  Use of CHWs increased from 35% of illness episodes before the intervention to 50% during the intervention (P < .0001), and total household costs per episode decreased significantly in each country: from US Dollars (USD) $4.36 to USD $1.54 in Burkina Faso, from USD $3.90 to USD $2.04 in Nigeria, and from USD $4.46 to USD $1.42 in Uganda (all P < .0001). There was no difference in the time used by the child's caregiver to care for a sick child (59% before intervention vs 51% during intervention spent ≤2 days). Using the most recent population figures for each study district, we estimate that the intervention could save households a total of USD $29 965, USD $254 268, and USD $303 467, respectively, in the study districts in Burkina Faso, Nigeria, and Uganda.

Conclusions:  Improving access to malaria diagnostics and treatments in malaria-endemic areas substantially reduces private household costs. The key challenge is to develop and strengthen community human resources to deliver the intervention, and ensure adequate supplies of commodities and supervision. We demonstrate feasibility and benefit to populations living in difficult circumstances.

Clinical Trials Registration:  ISRCTN13858170.
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http://dx.doi.org/10.1093/cid/ciw623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146695PMC
December 2016

Feasibility of Malaria Diagnosis and Management in Burkina Faso, Nigeria, and Uganda: A Community-Based Observational Study.

Clin Infect Dis 2016 Dec;63(suppl 5):S245-S255

UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases, World Health Organization, Geneva, Switzerland.

Background:  Malaria-endemic countries are encouraged to increase, expedite, and standardize care based on parasite diagnosis and treat confirmed malaria using oral artemisinin-based combination therapy (ACT) or rectal artesunate plus referral when patients are unable to take oral medication.

Methods:  In 172 villages in 3 African countries, trained community health workers (CHWs) assessed and diagnosed children aged between 6 months and 6 years using rapid histidine-rich protein 2 (HRP2)-based diagnostic tests (RDTs). Patients coming for care who could take oral medication were treated with ACTs, and those who could not were treated with rectal artesunate and referred to hospital. The full combined intervention package lasted 12 months. Changes in access and speed of care and clinical course were determined through 1746 random household interviews before and 3199 during the intervention.

Results:  A total of 15 932 children were assessed: 6394 in Burkina Faso, 2148 in Nigeria, and 7390 in Uganda. Most children assessed (97.3% [15 495/15 932]) were febrile and most febrile cases (82.1% [12 725/15 495]) tested were RDT positive. Almost half of afebrile episodes (47.6% [204/429]) were RDT positive. Children eligible for rectal artesunate contributed 1.1% of episodes. The odds of using CHWs as the first point of care doubled (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.9-2.4; P < .0001). RDT use changed from 3.2% to 72.9% (OR, 80.8; 95% CI, 51.2-127.3; P < .0001). The mean duration of uncomplicated episodes reduced from 3.69 ± 2.06 days to 3.47 ± 1.61 days, Degrees of freedom (df) = 2960, Student's t (t) = 3.2 (P = .0014), and mean duration of severe episodes reduced from 4.24 ± 2.26 days to 3.7 ± 1.57 days, df = 749, t = 3.8, P = .0001. There was a reduction in children with danger signs from 24.7% before to 18.1% during the intervention (OR, 0.68; 95% CI, .59-.78; P < .0001).

Conclusions:  Provision of diagnosis and treatment via trained CHWs increases access to diagnosis and treatment, shortens clinical episode duration, and reduces the number of severe cases. This approach, recommended by the World Health Organization, improves malaria case management.

Clinical Trials Registration:  ISRCTN13858170.
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http://dx.doi.org/10.1093/cid/ciw622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146694PMC
December 2016

Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V.

Int J Parasitol Drugs Drug Resist 2016 12 29;6(3):220-229. Epub 2016 Sep 29.

Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north. Genomic DNA was extracted from filter paper blood spots and placental impressions. Point mutations at codons 16, 50, 51, 59, 108, 140 and 164 of the dhfr gene and codons 431, 436, 437, 540, 581 and 613 of the dhps gene were evaluated by nested PCR amplification followed by direct sequencing. The distribution of the dhps-431V mutation was widespread throughout Nigeria with the highest prevalence in Enugu (46%). In Ibadan where we had sequential sampling, its prevalence increased from 0% to 6.5% between 2003 and 2008. Although there were various combinations of dhps mutations with 431V, the combination 431V + 436A + 437G+581G+613S was the most common. All these observations support the view that dhps-431V is on the increase. In addition, P. falciparum DHPS crystal structure modelling shows that the change from Isoleucine to Valine (dhps-431V) could alter the effects of both S436A/F and A437G, which closely follow the 2nd β-strand. Consequently, it is now a research priority to assess the implications of dhps-VAGKGS mutant haplotype on continuing use of SP in seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy (IPTp). Our data also provides surveillance data for SP resistance markers in Nigeria between 2003 and 2015.
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http://dx.doi.org/10.1016/j.ijpddr.2016.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094156PMC
December 2016

Medication errors among health professionals in Nigeria: A national survey.

Int J Risk Saf Med 2016 Aug;28(2):77-91

Federal Medical Centre, Jalingo, Nigeria.

Background: Medication errors are preventable causes of patient harm with significant contributions to adverse drug events but they remain understudied in Nigeria.

Objectives: To estimate the prevalence of self-reported medication errors among health professionals and examine their knowledge of medication errors with the hope of identifying appropriate measures to promote medication safety.

Methods: A cross sectional survey among doctors, pharmacists and nurses in 10 tertiary hospitals. Information was obtained using a self-administered structured questionnaire. Correct responses evaluating the knowledge of prescription, dispensing and administration errors were scored one mark each and the composite scores computed. Appropriate statistics were applied to summarize and establish the relationship between variables at 5% level of significance using SPSS 17.0.

Results: A total of 2,386 professionals participated in the study (46.3% nurses, 44.9% doctors, 8.8% pharmacists).The prevalence of self-reported medication errors was 47%.The professional groups differ in their knowledge of all the aspects of medication errors with professional cadres influencing knowledge.Overwork was the most reason for being error prone (59.2%) and only 35.5% had ever reported medication error. 33.4% did not think reporting was necessary.

Conclusions: The prevalence of medication errors is high among health care professionals in Nigeria. Knowledge gaps and practice deficiencies were identified requiring interventions.
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http://dx.doi.org/10.3233/JRS-160721DOI Listing
August 2016

Social context surrounding HIV diagnosis and construction of masculinity: a qualitative study of stigma experiences of heterosexual HIV positive men in southwest Nigeria.

BMC Public Health 2016 06 13;16:507. Epub 2016 Jun 13.

Department of Marketing Communication, Emerson College, 120 Boylston Street, P.O. Box 0234, Boston, MA, 02116-4624, USA.

Background: Though research has documented experiences of stigma and its effects on the lives of women living with HIV/AIDS, there is limited research on heterosexual positive HIV men experience of stigma in Nigeria. This study explored how social context surrounding HIV diagnosis impacts stigma experiences of heterosexual HIV positive men and their construction of masculinity in southwest Nigeria.

Methods: Using purposive sampling, 17 heterosexual HIV positive men were recruited through community based organization to participate in two hours focus group discussions or 45 min in-depth interviews that were audio-recorded. Without using the word stigma, discussions and interviews were guided by four questions that explored participants' experiences of living with HIV/AIDS. Interviews and discussions were conducted in three languages: English, Yoruba and Pidgin English. Thematic data analysis approach was in coding transcribed data, while social constructivist thinking guided data analysis.

Results: Participants ranged in age from 30 to 57 years old, and all were receiving antiretroviral therapy. Findings indicated that participants' experiences of stigma might be moderated by the social context surrounding their HIV diagnosis, and whether they have met the socio-cultural construction of masculinity. Participants whose diagnosis were preceded by immediate family members' diagnosis were less likely to report experiencing HIV stigma and more likely to report "not feeling less than a man" and educating others about HIV/AIDS. Contrarily, participants whose diagnosis was preceded by their own sickness were more likely to report isolation, sigma and feeling of being less than a man. All participants reported limiting their sexual intimacy, and those with children reported adjusting how they performed their role as fathers.

Conclusions: Social context surrounding HIV diagnosis impact how heterosexual HIV positive men experience HIV related stigma and how they perceive themselves as men, which may influence their care seeking behaviors. These findings have implications for HIV programs geared towards African heterosexual men in general and HIV positive men in particular.
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http://dx.doi.org/10.1186/s12889-016-3165-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906588PMC
June 2016

Potential antimalarial activity of Methyl Jasmonate and its effect on lipid profiles in Plasmodium Berghei infected mice.

Afr Health Sci 2015 Sep;15(3):841-50

University of Ibadan, Institute for Advanced Medical Research and Training (IAMRAT), College of Medicine.

Background: The antimalarial activity and lipid profiles of Methyl Jasmonate (MJ) were investigated against established malaria infection in vivo using BALB/c mice.

Methods: Arteether (AE) and chloroquine (CQ) were used as reference drugs while ethanol was used as the vehicle for drug delivery for MJ.

Results: Mice treated with 10 and 25 mg/kg MJ showed a remarkable reduction in percentage parasitemia by 68.3% and 78.2% on day 10(post treatment) respectively while 45.4% and 87.2% reduction in percentage parasitemia were observed in the group treated with 50 mg/kg on day 3 and 10 (post treatment) respectively. The highest mean survival time was observed in CQ followed by AE and MJ in dose-dependent manner. A progressive decrease in packed cell volume (PCV) was observed in infected untreated mice which led to the death of all the mice by day 9 (post treatment). Infected mice treated with MJ showed reduced level of HDL and LDL compared with infected untreated group. As the dose of MJ increased in infected mice cholesterol levels increased while there was reduction in triglyceride.

Conclusion: Overall there was marked decrease in parasitemia in Plasmodium berghei infected mice treated with graded doses of MJ but appears to have reduced antimalarial activity compared with CQ and AE.
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http://dx.doi.org/10.4314/ahs.v15i3.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765454PMC
September 2015
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