Search

Vitamin A deficiency is a global health challenge, particularly in the developing world. Diet based approaches, using locally available foods, are recommended for providing long term, sustainable solutions. The ProFarmer project, initiated in Malawi, encouraged local farmers to re-adopt landrace crop varieties. Orange maize was used as a case study. Over time, reintroducing this carotenoid-rich crop is predicted to increase provitamin A content in the Malawian diet. Furthermore, it is considered a relatively simple, cost-effective approach that has the potential to reduce dependence on food fortification. This study was aimed at evaluating the impact of the reintroduction of landrace orange maize on nutrition knowledge, attitudes and behaviours (KAB) in women of farming families that currently cultivate the crop. Women were selected, as they are largely responsible for food preparation and providing healthy foods for their families. Additionally, the overall diet adequacy in women living in rural Malawi was assessed. A total of 336 females took part in the cross-sectional study. Before the study, the participating farming families underwent a training program run by local Agriculture Extension workers prior to receiving seeds for cultivation. The training included an explanation of the rationale behind reintroducing landrace maize and nutrition education regarding the health aspects of providing provitamin A through locally grown foods. Families that had recently joined the project and families that had already harvested the crop in previous years were included in the study sample. A semi-structured questionnaire was used to determine KAB regarding orange maize. Diet quality was also assessed using the FAO Minimum Dietary Diversity questionnaire (MDD-W) designed for women. Independent t-tests and Chi-square tests were performed where appropriate. Positive attitudes towards growing and consuming landrace orange maize were recorded. However, only 32% of the women understood the nutritional benefits. Dietary Diversity scores, a proxy for nutrient adequacy, were low with only 34% of women consuming a sufficiently diverse diet. Despite low levels of nutritional knowledge, landrace orange maize was well accepted by families in rural Malawi and presents an affordable, sustainable option for increasing dietary sources of provitamin A. Nutrition education emphasizing the advantages of eating orange maize and expanding diet diversity is recommended in Malawi. [ABSTRACT FROM AUTHOR]

Importance: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae., Objective: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher., Design, Setting, and Participants: This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023., Intervention: The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher., Main Outcomes and Measures: The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance., Results: Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07)., Conclusions and Relevance: This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia., Trial Registration: ClinicalTrials.gov Identifier: NCT03399318.

Introduction: coronavirus disease 2019 (COVID-19) transmission dynamics in the communities of low- and middle-income countries, particularly sub-Saharan African countries, are still not fully understood. This study aimed to determine the characteristics of COVID-19 secondary transmission during the first wave of the epidemic (March-October 2020) in Lusaka, Zambia., Methods: we conducted an observational study on COVID-19 secondary transmission among residents in Lusaka City, between March 18 and October 30, 2020. We compared the secondary attack rate (SAR) among different environmental settings of contacts and characteristics of primary cases (e.g, demographics, medical conditions) by logistic regression analysis., Results: out of 1862 confirmed cases of COVID-19, 272 primary cases generated 422 secondary cases through 216 secondary transmission events. More contacts and secondary transmissions were reported in planned residential areas than in unplanned residential areas. Households were the most common environmental settings of secondary transmission, representing 76.4% (165/216) of secondary transmission events. The SAR in households was higher than the overall events. None of the environmental settings or host factors of primary cases showed a statistically significant relationship with SAR., Conclusion: of the settings considered, households had the highest incidence of secondary transmission during the first wave in Lusaka, Zambia. The smaller proportion of contacts and secondary transmission in unplanned residential areas might have been due to underreporting of cases, given that those areas are reported to be vulnerable to infectious disease outbreaks. Continuous efforts are warranted to establish measures to suppress COVID-19 transmission in those high-risk environments., Competing Interests: The authors declare no competing interests., (Copyright: Millica Phiri et al.)

Globally, several children die shortly after birth and many more of them within the first 28 days of life. Sub-Sharan Africa accounts for almost half (43%) of the global neonatal death with slow progress in reduction. These neonatal deaths are associated with lack of quality care at or immediately after birth and in the first 28 days of life. This study aimed to determine the trends and risk factors of facility-based neonatal mortality in a major referral hospital in Lusaka, Zambia. We conducted retrospective analysis involving all neonates admitted in the University Teaching Hospital Neonatal Intensive Care Unit (UTH-NICU) in Lusaka from January 2018 to December 2019 (N = 2340). We determined the trends and assessed the factors associated with facility-based neonatal mortality using Generalized Linear Models (GLM) with a Poisson distribution and log link function. Overall, the facility-based neonatal mortality was 40.2% (95% CI 38.0-42.0) per 1000 live births for the 2-year period with a slight decline in mortality rate from 42.9% (95% CI 40.0-46.0) in 2018 to 37.3% (95% CI 35.0-40.0) in 2019. In a final multivariable model, home delivery (ARR: 1.70, 95% CI 1.46-1.96), preterm birth (ARR: 1.59, 95% CI 1.36-1.85), congenital anomalies (ARR: 1.59, 95% CI 1.34-1.88), low birthweight (ARR: 1.57, 95% CI 1.37-1.79), and health centre delivery (ARR: 1.48, 95% CI 1.25-1.75) were independently associated with increase in facility-based neonatal mortality. Conversely, hypothermia (ARR: 0.36, 95% CI 0.22-0.60), antenatal attendance (ARR: 0.76, 95% CI 0.68-0.85), and 1-day increase in neonatal age (ARR: 0.96, 95% CI 0.95-0.97) were independently associated with reduction in facility-based neonatal mortality. In this hospital-based study, neonatal mortality was high compared to the national and global targets. The improvement in neonatal survival observed in this study may be due to interventions including Kangaroo mother care already being implemented. Early identification and interventions to reduce the impact of risks factors of neonatal mortality in Zambia are important., (© 2024. The Author(s).)

Background: The resurgence of poliovirus infection in previously polio free regions and countries calls for renewed commitment to the global polio eradication efforts including strengthening of Acute Flaccid Paralysis (AFP) surveillance systems. Zambia is one of the countries substantially at risk for the importation of poliovirus infection from neighbouring countries including Malawi, Mozambique, and Democratic Republic of the Congo (DRC). This study describes a seven-year AFP surveillance, assesses the surveillance indicators, and highlights areas for improvement., Methods: We conducted retrospective analysis of the routinely collected AFP surveillance data from January 2015 to December 2022. The AFP surveillance indicators performance was assessed using the World Health Organisation's recommended minimum AFP surveillance indicators performance., Results: Cumulatively, a total of 1715 AFP cases were reported over the study period. More than half, 891 (52%) of reported cases were aged < 5 years with 917 (53.5%) of males. More than half, 1186 (69.2%) had fever at onset, 718 (41.9%) had asymmetric paralysis and 1164 (67.9%) had their paralysis progressed within 3 days of onset. The non-polio AFP rate ranges from 3.4 to 6.4 per 100,000 children < 15 years old and stool adequacy ranging from 70.9% to 90.2% indicating sensitive surveillance with late detection of cases. The percentage of cases with early stool collection, timely transportation was above the World Health Organisation (WHO) minimum of 80% but with declining proportion of stools arriving in the laboratory in optimal condition. Completeness of 60-days follow-up evaluation was suboptimal ranging from 0.9% to 28.2%., Conclusion: The AFP surveillance system in Zambia is doing well. However, additional efforts are needed to improve early detection of cases; stool sample collection, transportation and monitoring to ensure arrival in good condition in the laboratory; and improve 60-days follow-up evaluation for evidenced-based classification of inadequate AFP cases and proper care., (© 2023. The Author(s).)

Background: Although pro-inflammatory cytokines are involved in the clearance of Plasmodium falciparum during the early stages of the infection, increased levels of these cytokines have been implicated in the pathogenesis of severe malaria. Amongst various parasite-derived inducers of inflammation, the malarial pigment haemozoin (Hz), which accumulates in monocytes, macrophages and other immune cells during infection, has been shown to significantly contribute to dysregulation of the normal inflammatory cascades., Methods: The direct effect of Hz-loading on cytokine production by monocytes and the indirect effect of Hz on cytokine production by myeloid cells was investigated during acute malaria and convalescence using archived plasma samples from studies investigating P. falciparum malaria pathogenesis in Malawian subjects. Further, the possible inhibitory effect of IL-10 on Hz-loaded cells was examined, and the proportion of cytokine-producing T-cells and monocytes during acute malaria and in convalescence was characterized., Results: Hz contributed towards an increase in the production of inflammatory cytokines, such as Interferon Gamma (IFN-γ), Tumor Necrosis Factor (TNF) and Interleukin 2 (IL-2) by various cells. In contrast, the cytokine IL-10 was observed to have a dose-dependent suppressive effect on the production of TNF among other cytokines. Cerebral malaria (CM) was characterized by impaired monocyte functions, which normalized in convalescence. CM was also characterized by reduced levels of IFN-γ-producing T cell subsets, and reduced expression of immune recognition receptors HLA-DR and CD 86, which also normalized in convalescence. However, CM and other clinical malaria groups were characterized by significantly higher plasma levels of pro-inflammatory cytokines than healthy controls, implicating anti-inflammatory cytokines in balancing the immune response., Conclusions: Acute CM was characterized by elevated plasma levels of pro-inflammatory cytokines and chemokines but lower proportions of cytokine-producing T-cells and monocytes that normalize during convalescence. IL-10 is also shown to have the potential to indirectly prevent excessive inflammation. Cytokine production dysregulated by the accumulation of Hz appears to impair the balance of the immune response to malaria and exacerbates pathology., (© 2023. The Author(s).)

In this study, electric field and magnetic flux density pollution levels were measured in southern Africa, a case of Blantyre City in Malawi, between 2020 and 2021. Sixty short-term measurements were performed using Trifield Electro Magnetic Frequency meter model TF2 in 30 different locations. Five high-population-dense sampling points were selected from school campuses, hospitals, industrial areas, markets, residential areas, and within the commercial and business center (CBC) of Blantyre. Electric field and magnetic flux density pollution monitoring was conducted between 10:00-12:00 h and 17:00-19:00 h for short-range analysis. Short-range results show that the maximum measured electric field pollution were 249.24 mV/m and 207.85 mV/m between 10:00-12:00 and 17:00-19:00 respectively, which are below the public limits of 4200.00 mV/m for public exposure. Similarly, maximum short-range results for magnetic flux density were 0.073 G and 0.057 G between 10:00-12:00 and 17:00-19:00 respectively which are below the public limits of 2 G for public exposure. Both measured electric and magnetic flux density were compared with the International Commission on Non-Ionizing Radiation Protection (ICNIRP), World health organization (WHO), and Institute of electrical and electronics engineers (IEEE). It was determined that all measured values for both electric and magnetic flux density were smaller than set limits for non-ionizing radiation for both public and occupation health. More importantly, these background measurements establish a baseline for future changes to be compared against public safety.

Violence in the community can impact access to health care. This scoping review examines the impact of urban violence upon youth (aged 15-24) access to sexual and reproductive health and trauma care in Low and Middle Income Countries (LMICs). We searched key electronic health and other databases for primary peer-reviewed studies from 2010 through June 2020. Thirty five of 6712 studies extracted met criteria for inclusion. They were diverse in terms of study objective and design but clear themes emerged. First, youth experience the environment and interpersonal relationships to be violent which impacts their access to health care. Second, sexual assault care is often inadequate, and stigma and abuse are sometimes reported in treatment settings. Third is the low rate of health seeking among youth living in a violent environment. Fourth is the paucity of literature focusing on interventions to address these issues. The scoping review suggests urban violence is a structural and systemic issue that, particularly in low-income areas in LMICs, contributes to framing the conditions for accessing health care. There is a gap in evidence about interventions that will support youth to access good quality health care in complex scenarios where violence is endemic.

Background: Recent research has established that acute kidney injury (AKI) is a common problem in severe paediatric malaria. Limited access to kidney diagnostic studies in the low resources settings where malaria is common has constrained research on this important problem., Methods: Enrolment data from an ongoing clinical trial of antipyretics in children with central nervous system (CNS) malaria, CNS malaria being malaria with seizures or coma, was used to identify risk factors for AKI at presentation. Children 2-11 years old with CNS malaria underwent screening and enrollment assessments which included demographic and anthropomorphic data, clinical details regarding the acute illness, and laboratory studies including creatinine (Cr), quantitative parasite count (qPC), quantitative histidine rich protein 2 (HRP2), lactate, and bilirubin levels. Children with a screening Cr > 106 µmol/l were excluded from the study due to the potential nephrotoxic effects of the study drug. To identify risk factors for AKI at the time of admission, children who were enrolled in the study were categorized as having AKI using estimates of their baseline (i.e. before this acute illness) kidney function and creatinine at enrollment applying the Kidney Disease: Improving Global Outcome (KDIGO) 2012 guidelines. Logistic regressions and a multivariate model were used to identify clinical and demographic risk factors for AKI at presentation among those children enrolled in the study., Results: 465 children were screened, 377 were age-appropriate with CNS malaria, 22 (5.8%) were excluded due to Cr > 106 µmol/l, and 209 were enrolled. Among the 209, AKI using KDIGO criteria was observed in 134 (64.1%). One child required dialysis during recovery. Risk factors for AKI in both the logistic regression and multivariate models included: hyperpyrexia (OR 3.36; 95% CI 1.39-8.12) and age with older children being less likely to have AKI (OR 0.72; 95% CI 0.62-0.84)., Conclusion: AKI is extremely common among children presenting with CNS malaria. Hyperpyrexia with associated dehydration may contribute to the AKI or may simply be a marker for a more inflammatory systemic response that is also affecting the kidney. Appropriate fluid management in children with CNS malaria and AKI may be challenging since generous hydration to support kidney recovery could worsen malaria-induced cerebral oedema in this critically ill population. Trial registration https://clinicaltrials.gov/ct2/show/NCT03399318., (© 2022. The Author(s).)

Background: Human immunodeficiency virus-exposed uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated whether human immunodeficiency virus (HIV)-exposure dysregulates HEU immunity, vaccine-antibody production, and human herpes virus amplify this effect., Methods: Thirty-four HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort and observed up to 6 weeks of age; and then a subsequent 43 HIV-infected and 61 HIV-uninfected mother-infant pairs were recruited into a longitudinal infant cohort at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HIV-unexposed uninfected (HU) infants., Results: We demonstrate (1) altered monocyte phagosomal function and B-cell subset homeostasis and (2) lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-tetanus toxoid immunoglobulin G titers in HEU compared with HU infants. Human herpes virus infection was similar between HEU and HU infants., Conclusions: In the era of antiretroviral therapy-mediated viral suppression, HIV exposure may dysregulate monocyte and B-cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants., Competing Interests: Potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

As COVID-19 vaccines are becoming more available, there is also a growing need to understand the population receiving the doses, existing inequalities and the intention to getting the second vaccine dose among the populations that receive the vaccines. We evaluated gender inequalities and intention to uptake of the second dose of COVID-19 AstraZeneca vaccine among adult populations in selected urban facilities of Lusaka, Zambia. A cross-sectional study design was conducted between May and June 2021 among adults who received AstraZeneca vaccine from three selected urban facilities of Lusaka, Zambia. Phone-based interviews were conducted 6 weeks after the first dose of the vaccine. Descriptive analysis and mixed-effect logistic regression were done using STATA version 16.2. Of the 1321 adults who had received AstraZeneca vaccine, 868 respondents completed the questionnaire. About, 47% (408/868) were females and 53% (460/868) were males. Median age in the study was 40 years. Majority of males were educated (54%) and employed (57%). Furthermore, majority of females that got the first dose of AstraZeneca reported experiencing side effects (76.98%) compared to males (64.24%). Among study participants, 93.7% intended to receive the AstraZeneca vaccine, of whom 46.7% (380/814) were females and 52.9% (434/814) were males. Majority of participants that did not intend to get a second dose were not married (55.56%). Only age (AOR, 1.05; 95% CI, 1.02-1.08) predicted intention to getting a second dose of AstraZeneca vaccine. We found important gender-dependent differences in the side effects reported by females that received the first dose of Astra Zeneca. Finding that intention to get the second dose of the vaccine increased with age suggests a need for enhancing COVID-19 vaccination programmes targeting young people and a need for further research to identify specific adverse effects of COVID-19 Astra Zeneca vaccines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Jacobs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: coronavirus disease (COVID-19) is primarily spread through respiratory secretions of infected persons, and face mask use has shown to decrease transmission. In Zambia, anecdotal evidence indicates low face mask use among the general population. We objectively assessed face masks use among Lusaka and Mansa residents in December 2020., Methods: we conducted a cross sectional study of face mask usage in Lusaka and Mansa Districts from 16-23 December 2020. A standardized tool was used to visually observe face mask usage and correct face mask usage at various outdoor locations in Lusaka and Mansa. Logistic regression was used to determine association of face mask use and correct face mask use with selected demographic variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported., Results: in total, 4070 persons were observed in Lusaka and 1166 Mansa Districts. Face masks usage was 24% in Lusaka and 27% in Mansa. Among the persons wearing face masks, 621 (48%) wore them correctly (52% in Lusaka and 35% in Mansa; p < 0.01 for difference). Being at a health facility (OR: 10.11 [95% CI: 7.99 - 12.81]), shopping mall (OR: 6.38 [95% CI: 5.07 - 8.03]), and school (OR: 2.39 [95% CI: 1.85 - 3.10]) were associated with wearing face masks compared to being at a bus station., Conclusion: face masks usage in public spaces was low in the two districts in Zambia, which might reduce efforts to control COVID-19. Investigating reasons for poor face masks adherence may help formulate effective strategies to increase face masks utilization in Zambia., Competing Interests: The authors declare no competing interests., (Copyright: Oluomachi Charity Nnachi et al.)

The public and patients can be powerful sensors for shaping and powering healthcare research. They are joining research teams as investigators and collaborators to co-produce evidence for the practical use of interventions in clinical practice. While clinicians and researchers are encouraged by funders and policymakers to involve the public and patients as partners in research, knowledge on what involvement consists of is limited, and the continuum between consultation, collaboration and co-production are not clearly defined. In this article, we explore Patient and Public Involvement (PPI) and introduce greater involvement through research co-production. Co-production describes ways that research partnership can work through public and patient involvement and we outline the similarities of co-production to "The Commons", a strategy utilized by economists to increase effective use of resources. We share examples of how public and patient involvement have used co-production, to demonstrate financial and health benefits. We then outline practical challenges at system, social and cultural levels and consider how others have worked to resolve them., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Community and public engagement (CPE) is increasingly becoming a key component in global health research. The National Institute for Health Research (NIHR) is one of the leading funders in the UK of global health research and requires a robust CPE element in the research it funds, along with CPE monitoring and evaluation. But what does "good" CPE look like? And what factors facilitate or inhibit good CPE? Addressing these questions would help ensure clarity of expectations of award holders, and inform effective monitoring frameworks and the development of guidance. The work reported upon here builds on existing guidance and is a first step in trying to identify the key components of what "good" CPE looks like, which can be used for all approaches to global health research and in a range of different settings and contexts. This article draws on data collected as part of an evaluation of CPE by 53 NIHR-funded award holders to provide insights on CPE practice in global health research. This data was then debated, developed and refined by a group of researchers, CPE specialists and public contributors to explore what "good" CPE looks like, and the barriers and facilitators to good CPE. A key finding was the importance, for some research, of investing in and developing long term relationships with communities, perhaps beyond the life cycle of a project; this was regarded as crucial to the development of trust, addressing power differentials and ensuring the legacy of the research was of benefit to the community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hickey, Porter, Tembo, Rennard, Tholanah, Beresford, Chandler, Chimbari, Coldham, Dikomitis, Dziro, Ekiikina, Khattak, Montenegro, Mumba, Musesengwa, Nelson, Nhunzvi, Ramirez and Staniszewska.)

Background: In Malawi, cancer is one of the leading causes of morbidity and mortality. This has led to increased use of herbal medicines for cancer management., Objective: This study aimed at identifying medicinal plants that are used for the management of cancer in the southern area of Karonga district, Northern Malawi., Methods: Semi-structured individual questionnaire interviews were used to collect ethnobotanical data from traditional herbal practitioners in the study area., Results: A total of twenty six (26) plant species from seventeen (17) botanical families were reported by Traditional Herbal Practitioners to be effective in the management of cancer. The botanical families with representation of more than one plant species were Fabaceae with five species, followed by Combretaceae and the Anacardiaceae with three species each, and Meliaceaewith with two species. The relative frequency of citation (RFC) showed that Senna singueana (RFC = 0.833), Lannea discolour (RFC = 0.833), Melia azedarach (RFC = 0.667), and Moringa oleifera (RFC = 0.667) were the medicinal plant species which were frequently mentioned and used in the study. The recipes could be a mixture of plant species or plant parts such as the leaves, barks, roots, rhizomes, seeds, flowers, and fruits., Conclusion: The study showed that a potential cancer management drug could be developed from the medicinal plant species found in the area. The results of this study could provide baseline information on medicinal plant species for further phytochemical studies and other studies to validate their use., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Plasmodium falciparum malaria still remains a major global public health challenge with over 220 million new cases and well over 400,000 deaths annually. Most of the deaths occur in sub-Saharan Africa which bears 90 % of the malaria cases. Such high P. falciparum malaria-related morbidity and mortality rates pose a huge burden on the health and economic wellbeing of the countries affected. Lately, substantial gains have been made in reducing malaria morbidity and mortality through intense malaria control initiatives such as use of effective antimalarials, intensive distribution and use of insecticide-treated nets (ITNs), and implementation of massive indoor residual spraying (IRS) campaigns. However, these gains are being threatened by widespread resistance of the parasite to antimalarials, and the vector to insecticides. Over the years the use of vaccines has proven to be the most reliable, cost-effective and efficient method for controlling the burden and spread of many infectious diseases, especially in resource poor settings with limited public health infrastructure. Nonetheless, this had not been the case with malaria until the most promising malaria vaccine candidate, RTS,S/AS01, was approved for pilot implementation programme in three African countries in 2015. This was regarded as the most important breakthrough in the fight against malaria. However, RTS,S/AS01 has been found to have some limitations, the main ones being low efficacy in certain age groups, poor immunogenicity and need for almost three boosters to attain a reasonable efficacy. Thus, the search for a more robust and effective malaria vaccine still continues and a better understanding of naturally acquired immune responses to the various stages, including the transmissible stages of the parasite, could be crucial in rational vaccine design. This review therefore compiles what is currently known about the basic biology of P. falciparum and the natural malaria immune response against malaria and progress made towards vaccine development., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Measures to limit the spread of infection during the COVID-19 global pandemic have made engaging and involving members of the community in global health research more challenging. This research aimed to explore how global health researchers adapted to the imposed pandemic measures in low and middle income countries (LMICs) and how they overcame challenges to effective community engagement and involvement (CEI)., Design: A qualitative two-stage mixed-methods study involving an online survey and a virtual round table., Setting: The survey and round table were completed online., Participants: Of 53 participants, 43 were LMIC-based or UK-based global health researchers and/or CEI professionals, and 10 worked for the National Institute for Health Research or UK Government's Department of Health and Social Care., Outcome Measures: This study aimed to capture data on: the number of CEI activities halted and adapted because of the COVID-19 pandemic; where CEI is possible; how it has been adapted; what the challenges and successes were; and the potential impact of adapted or halted CEI on global health research., Results: Pandemic control measures forced the majority of researchers to stop or amend their planned CEI activities. Most face-to-face CEI activities were replaced with remote methods, such as online communication. Virtual engagement enabled researchers to maintain already established relationships with community members, but was less effective when developing new relationships or addressing challenges around the inclusion of marginalised community groups., Conclusions: COVID-19 has highlighted the need for contingency planning and flexibility in CEI. The redesigning and adopting of remote methods has come with both advantages and disadvantages, and required new skills, access to technology, funding, reliable services and enthusiasm from stakeholders. The methods suggested have the potential to augment or substitute previously preferred CEI activities. The effectiveness and impact of these remote CEI activities need to be assessed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered an international pandemic that has led to significant public health problems. To date, limited evidence exists to suggest that drugs are effective against the disease. As possible treatments are being investigated, herbal medicines have shown potential for producing novel antiviral agents for the COVID-19 disease., Aim: This review explored the potential of Malawi's traditional medicinal plants for the management of COVID-19., Methods: The authors searched on PubMed and Google scholar for medicinal plants that are used in Malawi and published in openly available peer reviewed journals. Plants linked with antiviral treatment, anti-COVID-19 activity or COVID-19 symptoms management were targeted. These included activity against pneumonia, inflammation, cough, difficulty in breathing, pain/aches, fever, diarrhoea, rheumatism, fatigue, asthma, immunocompromised and cardiovascular diseases., Results: 11 studies were found with 306 plant species. 127 plant species had at least one COVID-19 related pharmacological activity. Of these plant species, the number of herbal entities used for each indication was: pain/aches (87), fever (2), pneumonia (9), breathing/asthma problems (5), coughing (11), diarrhoea (1), immunosuppression (8), blood issues (10), fatigue (2), heart problems (11), inflammation (8), rheumatism (10) and viral diseases (12). Thirty (30) species were used for more than one disease and Azedarachta indica topped the list (6 of the 13 COVID-19 related diseases). The majority of the species had phytochemicals known to have antiviral activity or mechanisms of actions linked to COVID-19 and consequent diseases' treatment pathways., Conclusion: Medicinal plants are a promising source of compounds that can be used for drug development of COVID-19 related diseases. This review highlights potential targets for the World Health Organization and other research entities to explore in order to assist in controlling the pandemic., (© 2021 The College of Medicine and the Medical Association of Malawi.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare: SS sits on the editorial board of this series of articles on co-production of knowledge in health research. She is part funded by NIHR Applied Research Collaboration, West Midlands; NIHR Health Protection Research Unit in gastrointestinal infections; and NIHR Health Protection Research Unit in genomics and enabling data. SS will not be involved in the editorial processes for this paper. This article is part of a series produced in conjunction with WHO and the Alliance for Health Policy Systems and Research with funding from the Doris Duke Charitable Foundation. The BMJ peer reviewed, edited, and made the decision to publish.

Introduction: Infection with Human Immunodeficiency Virus (HIV) is highly prevalent worldwide, especially in Sub-Saharan Africa, where anaemia is also widespread. HIV infection is known to be associated with anaemia and various other haematologic alterations, but little data on correlation with immunological and virologic conditions in treatment-naïve patients and impact on mortality are available. Our study aims to investigate hematologic features in HIV-infected individuals in Malawi and Mozambique and assesses possible correlations with early morality., Material and Methods: We conducted a retrospective analysis of baseline data (general details, nutritional status, full blood count and HIV infection progress data) and 12 months follow-up status for HIV+ adult patients in 22 health facilities in Malawi (11 sites) and Mozambique (11 sites) run by DREAM program. Anagraphic details, anthropometric characteristics, full blood count, CD4+ count and Viral Load data were collected from electronical medical records (EMR) for all the HIV-positive, treatment-naïve patients starting care in the sites in the period January 2007 -December 2016. Follow-up status after one year since enrolment in care was also considered. All the data extracted from the EMR were included in a dataset and then analysed. Univariate and multivariate analysis were conducted through logistical regression to investigate associations, and survival analysis analysed in a Cox regression model., Results: On the whole, 22.657 patients were included; severe and moderate anaemia were observed in 1.174 (8,2%) and 4.703 (21,9%) patients respectively. Gender, nutritional status, CD4+ count, and viral load (VL) were associated with anaemia, leukopenia, and thrombocytopenia. Among 21.166 fully evaluable patients, 8.494 (40,1%) had at least one cytopenia. Any cytopenia was present in 1/3 of patients with normal nutritional status and less advanced HIV infection, and it wouldn't be diagnosed in a basic HIV care setting. During the first year of treatment, 1.725 subjects (7,6% of the entire sample) died. Anaemia, lower Red blood cells and platelets counts correlated with mortality in the first year of care, independently by body mass index, haemoglobin, CD4+ count and VL., Conclusions: Notwithstanding anaemia is known to be associated with HIV infection at diagnosis, full blood count is not routinely performed in many African countries. Our results emphasize that including the study of a broader set of parameters in the routine HIV care services in Sub-Saharan Africa would provide significant clinical information able to predict other alterations and poor outcomes., Competing Interests: The authors have declared that no competing interests exist.

Influenza viruses often pose a serious threat to animals and human health. In an attempt to explore the potential of herbal medicine as a treatment for influenza virus infection, eleutheroside B1, a coumarin compound extracted from herba sarcandrae, was identified, which exhibited antiviral and anti‑inflammatory activities against influenza A virus. In this study, high‑throughput RNA sequencing and isobaric tags for relative and absolute quantification (iTRAQ) assays were performed to determine alterations in the non‑coding RNA (ncRNA) transcriptome and proteomics. Bioinformatics and target prediction analyses were used to decipher the potential roles of altered ncRNAs in the function of eleutheroside B1. Furthermore, long ncRNA (lncRNA) and mRNA co‑expressing networks were constructed to analyze the biological functions by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The analysis of RNA sequencing data revealed that 5 differentially expressed ncRNAs were upregulated and 3 ncRNAs were downregulated in the A549 cells infected with A/PR8/34/H1N1, with or without eleutheroside B1 treatment (PR8+eleu and PR8, respectively). Nuclear paraspeckle assembly transcript 1 (NEAT1) was differentially expressed between the PR8 and A549 cell groups. GO and KEGG pathway analyses indicated that eleutheroside B1 took advantage of the host cell biological processes and molecular function for its antiviral and anti‑inflammatory activities, as well as for regulating cytokine‑cytokine receptor interaction in the immune system, consistent with previous findings. The results of the iTRAQ assays indicated that L antigen family member 3 (LAGE3) protein, essential for tRNA processing, tRNA metabolic processes and ncRNA processing, was downregulated in the PR8+eleu compared with the PR8 group. In the present study, these comprehensive, large‑scale data analysis enhanced the understanding of multiple aspects of the transcriptome and proteomics that are involved in the antiviral and anti‑inflammatory activities of eleutheroside B1. These findings demonstrate the potential of eleutheroside B1 for use in the prevention and treatment of influenza A virus‑mediated infections.

Background/aims: Clinical trial oversight is central to the safety of participants and production of robust data. The United Kingdom Medical Research Council originally set out an oversight structure comprising three committees in 1998. The first committee, led by the trial team, is hands-on with trial conduct/operations ('Trial Management Group') and essential. The second committee (Data Monitoring Committee), usually completely independent of the trial, reviews accumulating trial evidence and is used by most later phase trials. The Independent Data Monitoring Committee makes recommendations to the third oversight committee. The third committee, ('Trial Steering Committee'), facilitates in-depth interactions of independent and non-independent trial members and gives broader oversight (blinded to comparative analysis). We investigated the roles and functioning of the third oversight committee with multiple research methods. We reflect upon these findings to standardise the committee's remit and operation and to potentially increase its usage., Methods: We utilised findings from our recent published suite of research on the third oversight committee to inform guideline revision. In brief, we conducted a survey of 38 United Kingdom-registered Clinical Trials Units, reviewed a cohort of 264 published trials, observed 8 third oversight committee meetings and interviewed 52 trialists. We convened an expert panel to discuss third oversight committees. Subsequently, we interviewed nine patient/lay third committee members and eight committee Chairs., Results: In the survey, most Clinical Trials Units required a third committee for all their trials (27/38, 71%) with independent members (ranging from 1 to 6). In the survey and interviews, the independence of the third committee was valued to make unbiased consideration of Independent Data Monitoring Committee recommendations and to advise on trial progress, protocol changes and recruitment issues in conjunction with the trial leadership. The third committee also advised funders and sponsors about trial continuation and represented patients and the public by including lay members. Of the cohort of 264 published trials, 144 reported a 'steering' committee (55%), but the independence of these members was not described so these may have been internal Trial Management Groups. Around two thirds of papers (60%) reported having an Independent Data Monitoring Committee and 26.9% neither a steering nor an Independent Data Monitoring Committee. However, before revising the third committee charter (Terms of Reference), greater standardisation is needed around defining member independence, composition, primacy of decision-making, interactions with other committees and the lifespan., Conclusion: A third oversight committee has benefits for trial oversight and conduct, and a revised charter will facilitate greater standardisation and wider adoption.

Background: Children born to HIV-positive mothers are particularly susceptible to malnutrition. Currently, monitoring programs rely on punctual anthropometric measurements to assess child growth. Growth velocities could be an additional tool in identifying critical time windows for prevention and implementation of early intervention for malnutrition., Methods: A retrospective analysis was conducted using data from 817 HIV exposed but uninfected children extracted from DREAM program database. By using the WHO reference for growth standards, patterns of weight velocity for different intervals of assessment from one to 18 months of age were explored. Odds ratios and multinomial logistic regressions between selected weight velocity Z-scores thresholds and successive malnutrition indices (at 6, 12, 18 months of age) were calculated., Results: Weight velocity was above the standard mean in the first 3 months, then progressively declined over time. In children with normal nutritional status, significant risks of becoming malnourished (mild malnutrition - underweight [OR 10.8; 95% CI: 4.5-26], chronic malnutrition - stunting [OR 8.3; 95% CI: 2-34.9] and acute malnutrition - wasting [OR 11.7; 95% CI: 1.5-90.5]) started when weight velocity Z-scores <0, at all interval ages. Multinomial regression showed that in the first 6 months, the weight velocity decrements strongly impacted on underweight (OR 17.9; 95% CI: 4-80.7), while the risk of Stunting occurred later at 18 months (OR 8.7; 95% CI: 4.3-17.6), with highest impact at the lowest thresholds., Conclusions: The assessment of weight velocity Z-scores, coupled with the already validated malnutrition indices, can support frontline health workers in early prediction of child malnutrition and performing nutritional counselling in the context of HIV/AIDS and food insecurity.

Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 β [IL-1β], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1β, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1β compared with the other subgroups. IL-1β best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.

Aims: To understand the impact of urban violence and crime on HIV care delivery., Background: Urban violence and crime can put pressure on the healthcare system and on nursing staff. Whilst there is research about the impact this has at the individual level, there is less research that places this in the context of the overall social eco-system., Design: A qualitative design using inductive thematic analysis., Methods: Between July 2016 - February 2017, we conducted in-depth interviews with 10 nurses working in two neighbourhoods with high levels of violence in Cape Town, South Africa., Results: The effects of crime and violence were evident at multiple levels resulting in participants feeling "safe and unsafe" in a context where people view crime as endemic. Resilience emerged as a key concept in the findings. Resilience was apparent at individual, community, and organizational levels and enabled continued delivery of HIV care., Conclusion: The findings demonstrate the potential role of resilience in the social eco-health system required to sustain delivery of HIV care in the midst of urban violence and gangsterism., Impact: This study examined the impact of and response to urban violence on HIV care delivery. The findings indicate that resilience manifests at all levels of the social eco-system. Understanding the mechanisms employed to cope with endemic violence helps to address these challenges in the study setting, but also has a much wider application to other areas with endemic urban violence and crime., (© 2019 John Wiley & Sons Ltd.)

Background and Rationale: Internationally, the idea of "co-production' has become more popular in health research because of the promise of partnership between researchers and patients to create research that focuses on patients' needs. Patient and public involvement (PPI) at an early stage in deciding what research should be funded, can improve the quality and impact of research. However, professional power over the process places limits on the public practising their participatory rights for involvement in commissioning research that affects them and can leave members of the public feeling unheard or excluded, particularly within the context of early phase applied health research. Aim: This article explores whether and how the public can be involved in the co-production of research commissioning early on in the process, with a focus on the power relations that pervade basic and early phase translational applied health research. Methods: An exploratory literature review of international peer-reviewed and gray health research literature using structured searches of electronic databases and key search terms. Results: There is very little literature that critically evaluates how PPI is embedded into the early phases of the commissioning process. The field of basic or early translational applied research appear to be particularly challenging. Four themes which emerged from the review are: reasons for PPI in research commissioning; benefits of PPI at strategic levels of research commissioning; contributions of patients and members of the public; improving PPI in research commissioning. Conclusion: Although the public are being consulted at some stages of the research commissioning process, it is evident that the process of determining research priorities and agendas is far from being widely co-produced. Moving PPI from a consultative paternalistic model to a collaborative partnership model should be a priority for commissioners. Significant changes to communication, practices, systems, structures, or cultures that exclude patients and the public from contributing in meaningful ways, are needed to fulfill the potential of co-produced models of research commissioning., (Copyright © 2019 Tembo, Morrow, Worswick and Lennard.)

[This corrects the article DOI: 10.1186/s40900-017-0064-0.].

Plain English Summary: There is a need for the authors of research reports to be able to communicate their work clearly and effectively to readers who are not familiar with the research area. The National Institute for Health Research (NIHR), along with a number of other funding bodies and journals, require researchers to write short lay summaries, often termed plain English summaries (PESs), to make research accessible to the general public. Because many researchers write using technical, specialised language, particularly in scientific reports, writing PESs can be challenging. In this study we looked at how to improve the quality of PESs. We took PESs which had been submitted to the NIHR Journals Library and asked authors to rewrite them using new guidance. We also asked an independent medical writer to edit the summaries. We measured the quality of these three versions (original summary, rewritten summary and edited summary) in two ways. First, we asked a group of people who were not specialists in the subject area to read and rate how easy the summaries were to understand. Secondly, we used a well-known measure called the Flesch reading ease score to assess how easy the PESs were to read. We found that there was no difference in how easy people found the summaries to understand across the three versions. However, the PESs that were rewritten by the authors and that were edited by the independent medical writer were both easier to read than the originals. This shows that PESs can be improved and for organisations who feel that employing an independent writer to edit summaries, providing clear, practical guidance to authors may be a cost-effective alternative., Background: Plain English summaries (PES) or lay summaries are often included as part of research reports and journal articles. These summaries are vital to ensure that research findings are accessible and available to non-specialist audiences, for example patients and members of the public. Writing a PES requires the adoption of a different style than is generally used in a traditional scientific report, and researchers can find this challenging. This study explored two possible ways to improve the quality of PESs in the NIHR Journals Library: 1) Providing enhanced guidance to authors and asking them to rewrite the PES and 2) Employing an independent medical writer to edit the PES., Methods: We compared the three versions of the PES (original, author rewritten and independent writer edited) to assess 1) how easy they were to understand and 2) how easy they were to read. In order to establish how easy PESs were to understand, a group of 60 public reviewers read a set of summaries and rated them on a four point scale from "Did not understand" to "Understood all". The Flesch reading ease score was used to measure how easy the summaries were to read., Results: Results indicated no significant difference across the three versions of the PES in terms of ease of understanding. However, both the author rewritten and independent writer edited versions were significantly easier to read than the original. There was no significant difference in ease of reading between these two versions., Conclusion: These findings suggest that employing independent medical writers to edit PESs and providing clear, practical guidance to authors are two ways in which the readability of PESs could be improved. Results have implications for journal editors and publishers seeking to enhance accessibility and availability of research findings.

The accurate assessment of immune competence through ex vivo analysis is paramount to our understanding of those immune mechanisms that lead to protection or susceptibility against a broad range of human pathogens. We have developed a flow cytometry-based, whole blood phagocyte functional assay that utilizes the inflammatory inducer zymosan, coupled to OxyBURST-SE, a fluorescent reporter of phagosomal oxidase activity. The assay measures both phagocytic uptake and the superoxide burst in the phagocyte populations in whole blood. We utilized this assay to demonstrate impaired superoxide burst activity in the phagocytes of hospitalized HIV-positive patients with laboratory-confirmed tuberculosis. These data validate the use of the assay to assess the immune competence of patients in a clinical setting. The method is highly reproducible with minimal intraindividual variation and opens opportunities for the rapid assessment of cellular immune competence in peripheral blood in a disease setting.

Objective: HIV and malnutrition are the two major causes of infant mortality in Sub-Saharan Africa. The study describes the impact of malnutrition on motor milestone development in HIV-exposed children., Design: Randomized community intervention trial (SMAC, Safe Milk for African Children)., Setting and Participants: Growth, motor development, and malnutrition were assessed in a sample of 76 HIV-exposed children, aged 0-24 months, at the Blantyre Dream Centre in Malawi., Main Outcome Measures: We assessed growth and selected motor milestone achievement in agreement with WHO/UNICEF criteria. Odds ratios and 95%confidence intervals were calculated according to motor milestones and malnutrition indices. Multivariable logistic regression was performed with 18 months data., Results: High rates of malnutrition were observed. Underweight increased by 6.7/9.2 and 3.2/5.5 the odds of not standing alone and not walking alone at 15 and 18 months. Stunting increased by 9.7 the odds of not standing alone at 11 months and by 6.1 the odds of not walking alone at 18 months. Wasting increased by 5.5/10.3 the odds for not walking with assistance at 12 and 18 months. Low weight for age was associated with delay in walking at 18 months (HR=2.9)., Conclusion: Malnutrition in HIV-exposed children decreases the likelihood of adequate development.

Infant malnutrition in sub-Saharan Africa is a public health priority and a challenge in high HIV prevalence areas. The Drug Resources Enhancement Against AIDS and Malnutrition program, with multiple medical centers in Sub-Saharan Africa, developed an innovative intervention for the surveillance and control of malnutrition. In a pilot initiative, 36 HIV-exposed children were evaluated at baseline upon presentation for malnutrition and at six months post- treatment. Parameters included HIV-free survival, nutritional status and change in diet. Food diary data was entered and processed using the Nutrisurvey (WHO) software. At 6 months post-intervention, a significant improvement in anthropometric parameters was noted. Slowing of linear growth was observed in patients with malaria with a mean gain in centimetres of 4.4 ± 1.7 as compared to 5.6 ± 1.7 in children with no malaria, p < 0.048 (CL 95%: -2.32, -0.01). Dietary diversity scores increased from 5.3 ± 1.9 to 6.5 ± 1.3, p < 0.01 at 6 months. A significant increase (+25%, p < 0.02) in the number of children eating fish meals was noted. Our pilot data describes positive outcomes from a rehabilitative nutritional approach based on use of local foods, peer education, anthropometric and clinical monitoring in areas of high food insecurity. The relationship between malaria and linear growth retardation requires further investigation.

Plasmodium falciparum is responsible for most of the morbidity and mortality associated with malaria and is unique in its ability to sequester in organ postcapillary venules. Specific host-parasite interactions mediate this phenomenon and the P. falciparum erythrocyte membrane protein 1 is the predominant ligand responsible for adhering to host endothelial receptors. This review focuses on the current knowledge regarding this protein family, evidence for its role in various pathogenic mechanisms and on insights that have been gained in this area from field studies.