Search

BackgroundUnderstanding dietary patterns in a population is critical for decision making. This study aimed to identify the prevailing dietary patterns and their associated individual and school environment factors among school going adolescents in Lusaka, Zambia.MethodA cross-sectional study involving 404 Grade 10 pupils from 10 secondary schools in Lusaka district was conducted. A 108-item unquantified Food Frequency Questionnaire (FFQ) was used to assess the learner's food intake practices. Principal component analysis (PCA) was used to derive dietary patterns from the 108 food items. In addition, a mapping of food vendors and types of food sold was conducted in the same 10 schools using a semi-structured observation checklist. Bivariate and multivariate multilevel regression was used to analyse the individual and school level determinants of the adolescent dietary patterns.ResultsThe average age of learners was 16.1 years (SD 1.4 years); 234 (58%) were female while 170 (42%) male. “Snacking,” “vegetarian,” “health conscious,” and “traditional” dietary patterns accounting for 54.5% of variability in learner's diets were identified using PCA. At individual level, having weekly pocket money was significantly associated with snacking (p ≤ 0.0001). Self-identified poverty was associated with snacking (p ≤ 0.0001), vegetarian (p = 0.009) and traditional (p = 0.009) dietary patterns. School level factors like a school tuckshop (similar to canteen) that sells fast foods or a kantemba (semi-permanent makeshift store) within the school vicinity (p = 0.023) were significantly associated with a snacking dietary pattern. School tuckshop selling nshima (a thick maize based porridge) was significantly associated with vegetarian (p = 0.007), health conscious (p = 0.02) and traditional dietary patterns (p=0.01) while a tuckshop with fruit significantly predicted traditional (p ≤ 0.0001), vegetarian (p = 0.041), and snacking (p = 0.002), dietary patterns. Having a supermarket or fast food restaurants in the school vicinity did not significantly influence any dietary pattern.ConclusionBoth individual behavioral and school environment level factors were found to be significant determinants of the four dietary patterns identified in this study.

Efforts to eliminate malaria transmission need evidence-based strategies. However, accurately assessing end-game malaria elimination strategies is challenging due to the low level of transmission and the rarity of infections. We hypothesised that presumptively treating individuals during reactive case detection (RCD) would reduce transmission and that serology would more sensitively detect this change over standard approaches. We conducted a cluster randomised control trial (NCT02654912) of presumptive reactive focal drug administration (RFDA-intervention) compared to the standard of care, reactive focal test and treat (RFTAT-control) in Southern Province, Zambia-an area of low seasonal transmission (overall incidence of ~3 per 1,000). We measured routine malaria incidence from health facilities as well as PCR parasite prevalence / antimalarial seroprevalence in an endline cross-sectional population survey. No significant difference was identified from routine incidence data and endline prevalence by polymerase chain reaction (PCR) had insufficient numbers of malaria infections (i.e., 16 infections among 6,276 children) to assess the intervention. Comparing long-term serological markers, we found a 19% (95% CI = 4-32%) reduction in seropositivity for the RFDA intervention using a difference in differences approach incorporating serological positivity and age. We also found a 37% (95% CI = 2-59%) reduction in seropositivity to short-term serological markers in a post-only comparison. These serological analyses provide compelling evidence that RFDA both has an impact on malaria transmission and is an appropriate end-game malaria elimination strategy. Furthermore, serology provides a more sensitive approach to measure changes in transmission that other approaches miss, particularly in very low transmission settings. Trial Registration: Registered at www.clinicaltrials.gov (NCT02654912, 13/1/2016).

Abstract Background Zambia has set itself the ambitious target of eliminating malaria by 2021. To continue tracking transmission to zero, new interventions, tools and approaches are required. Methods Urban reactive case detection (RCD) was performed in Lusaka city from 2011 to 2015 to better understand the location and drivers of malaria transmission. Briefly, index cases were followed to their home and all consenting individuals living in the index house and nine proximal houses were tested with a malaria rapid diagnostic test and treated if positive. A brief survey was performed and for certain responses, a dried blood spot sample collected for genetic analysis. Aggregate health facility data, individual RCD response data and genetic results were analysed spatially and against environmental correlates. Results Total number of malaria cases remained relatively constant, while the average age of incident cases and the proportion of incident cases reporting recent travel both increased. The estimated R0 in Lusaka was

Background: Despite the burden of HIV being highest in sub-Saharan Africa (SSA), research expertise and capacity to address scientific questions regarding complications of HIV and ART, especially chronic non-communicable conditions, is limited in the region. The comorbidities prevalent in persons with HIV are mediated through diverse mechanisms, many of which can be context or region-specific and are yet to be elucidated. The phenotype, risk factors, and effective interventions for these conditions may differ between populations and settings, and therefore there is an urgent need for research to help understand these processes and how to best address them in SSA. Here, we report the research capacity building activities in SSA conducted by the University of Zambia (UNZA)-Vanderbilt Training Partnership for HIV-Nutrition-Metabolic Research (UVP), drawing lessons and challenges for a wide global health audience. Methods: We reviewed program data and conducted interviews with program leaders and participants to understand and document the progress and outcomes of the partnership. We report the program’s early achievements, highlighting drivers and challenges. Results: Between 2015 and 2019, UVP made substantial progress on its goals of training new UNZA PhD scientists to investigate complex nutritional and metabolic factors related to long-term HIV complications and comorbidities. The program has supported 11 UNZA PhD students with dual UNZA-Vanderbilt mentorship; three have graduated, and other candidates are progressing in their PhD studies. The project also supported institutional capacity through UNZA faculty participation in Vanderbilt grant writing workshops, with strong success in obtaining grants among those who participated. UVP also supported development of greater structure to UNZA’s PhD program and a mentorship curriculum, both now adopted by UNZA. The major drivers for success included UVP’s alignment of goals between UNZA and Vanderbilt, and local institutional ownership. The longstanding history of collaborations between the two institutions contributed substantially to alignment and mutual support of UVP’s goals. Several challenges were noted, including limits on direct research funding for students and a relatively small pool of funded investigators at UNZA. Conclusions: Despite some challenges, UVP has achieved positive outcomes over its first four years. Longstanding partnerships and local institutional ownership were the main drivers. We expect the challenges to mitigated as the project continues and produces more UNZA researchers and teams and more funded projects, collectively building the local research community. With continued resources and clear focus, we expect that UNZA’s investigators and partners will attract research funding and generate high-impact research outputs across a broad range of studies in HIV as well as newer threats from non-communicable conditions experienced by long-term survivors of HIV and by the general population.

Summary: Background: Radical measures are required to identify and reduce blindness due to diabetes to achieve the Sustainable Development Goals by 2030. Therefore, we evaluated the accuracy of an artificial intelligence (AI) model using deep learning in a population-based diabetic retinopathy screening programme in Zambia, a lower-middle-income country. Methods: We adopted an ensemble AI model consisting of a combination of two convolutional neural networks (an adapted VGGNet architecture and a residual neural network architecture) for classifying retinal colour fundus images. We trained our model on 76 370 retinal fundus images from 13 099 patients with diabetes who had participated in the Singapore Integrated Diabetic Retinopathy Program, between 2010 and 2013, which has been published previously. In this clinical validation study, we included all patients with a diagnosis of diabetes that attended a mobile screening unit in five urban centres in the Copperbelt province of Zambia from Feb 1 to June 31, 2012. In our model, referable diabetic retinopathy was defined as moderate non-proliferative diabetic retinopathy or worse, diabetic macular oedema, and ungradable images. Vision-threatening diabetic retinopathy comprised severe non-proliferative and proliferative diabetic retinopathy. We calculated the area under the curve (AUC), sensitivity, and specificity for referable diabetic retinopathy, and sensitivities of vision-threatening diabetic retinopathy and diabetic macular oedema compared with the grading by retinal specialists. We did a multivariate analysis for systemic risk factors and referable diabetic retinopathy between AI and human graders. Findings: A total of 4504 retinal fundus images from 3093 eyes of 1574 Zambians with diabetes were prospectively recruited. Referable diabetic retinopathy was found in 697 (22·5%) eyes, vision-threatening diabetic retinopathy in 171 (5·5%) eyes, and diabetic macular oedema in 249 (8·1%) eyes. The AUC of the AI system for referable diabetic retinopathy was 0·973 (95% CI 0·969–0·978), with corresponding sensitivity of 92·25% (90·10–94·12) and specificity of 89·04% (87·85–90·28). Vision-threatening diabetic retinopathy sensitivity was 99·42% (99·15–99·68) and diabetic macular oedema sensitivity was 97·19% (96·61–97·77). The AI model and human graders showed similar outcomes in referable diabetic retinopathy prevalence detection and systemic risk factors associations. Both the AI model and human graders identified longer duration of diabetes, higher level of glycated haemoglobin, and increased systolic blood pressure as risk factors associated with referable diabetic retinopathy. Interpretation: An AI system shows clinically acceptable performance in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, and diabetic macular oedema in population-based diabetic retinopathy screening. This shows the potential application and adoption of such AI technology in an under-resourced African population to reduce the incidence of preventable blindness, even when the model is trained in a different population. Funding: National Medical Research Council Health Service Research Grant, Large Collaborative Grant, Ministry of Health, Singapore; the SingHealth Foundation; and the Tanoto Foundation.

Arthropod vectors transmit organisms that cause many emerging and reemerging diseases, and their control is reliant mainly on the use of chemical insecticides. Only a few classes of insecticides are available for public health use, and the increased spread of insecticide resistance is a major threat to sustainable disease control. The primary strategy for mitigating the detrimental effects of insecticide resistance is the development of an insecticide resistance management plan. However, few examples exist to show how to implement such plans programmatically. We describe the formulation and implementation of a resistance management plan for mosquito vectors of human disease in Zambia. We also discuss challenges, steps taken to address the challenges, and directions for the future.

INTRODUCTION:Sub-Saharan Africa is experiencing an epidemiological transition as the burden of NCDs overtake communicable diseases. However, it is unknown what capacity and gaps exist at primary care level to address the growing burden of NCDs. This study aimed to assess the Zambian health system's capacity to address in NCDs, using an adapted WHO Essential Non Communicable Disease Interventions (WHO PEN) tool. METHODOLOGY:This was a cross-sectional facility survey in the three districts conducted from September 2017 to October 2017. We defined facility readiness along five domains: basic equipment, essential services, diagnostic capacity, counseling services, and essential medicines. For each domain, we calculated an index as the mean score of items expressed as percentage. These indices were compared to an agreed cutoff at 70%, meaning that a facility index or district index below 70% off was considered as 'not ready' to manage NCDs at that level. All analysis were performed using Stata 15 MP. RESULTS:There appeared to be wide heterogeneity between facilities in respect of readiness to manage NCDs. Only 6 (including the three 1st level hospitals) out of the 46 facilities were deemed ready to manage NCDs. Only the first level hospitals scored a mean index higher than the 70% cut off; With regard to medications needed to manage NCDs, urban and rural health facilities were comparably equipped. However, there was evidence that calcium channel blockers (p = 0.013) and insulin (p = 0.022) were more likely to be available in urban and semi-urban health facilities compared to rural facilities. CONCLUSION:Our study revealed gaps in primary health care capacity to manage NCDs in Zambia, with almost all health facilities failing to reach the minimum threshold. These results could be generalized to other similar districts in Zambia and the sub-region, where health systems remain focused on infectious rather than non-communicable Disease. These results should attract policy attention and potentially form the basis to review current approach to NCD care at the primary care level in Zambia and Sub-Saharan Africa.

BACKGROUND:There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia's programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions. METHODOLOGY/PRINCIPAL FINDINGS:A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids, DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s. CONCLUSIONS/SIGNIFICANCE:Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management plan.

To determine whether HIV-1 infection and HIV-1-related immunosuppression were risk factors for severe malaria in adults with some immunity to malaria, we conducted a case-control study in Luanshya, Zambia, during December 2005-March 2007. For each case-patient with severe malaria, we selected 2 matched controls (an adult with uncomplicated malaria and an adult without signs of disease). HIV-1 infection was present in 93% of case-patients, in 52% of controls with uncomplicated malaria, and in 45% of asymptomatic controls. HIV-1 infection was a highly significant risk factor for adults with severe malaria compared with controls with uncomplicated malaria (odds ratio [OR] 12.6, 95% confidence interval [CI] 2.0-78.8, p = 0.0005) and asymptomatic controls (OR 16.6, 95% CI 2.5-111.5, p = 0.0005). Persons with severe malaria were more likely to have a CD4 count <350/microL than were asymptomatic controls (OR 23.0, 95% CI 3.35-158.00, p<0.0001). [ABSTRACT FROM AUTHOR]

Abstract Background Malaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL) that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum. Objective The study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP) had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated P. falciparum malaria in Ndola, Zambia. Methods Between 2005 and 2006, 304 children (6-59 months old) with uncomplicated P. falciparum were enrolled, randomized to AL (101) or DHA/PQP (203) and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF), late clinical failure (LCF, late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR). Recurrent infections were genotyped to distinguish between recrudescence and new infection. Results No ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p < 0.001). Most failure were new infections and PCR-corrected ACPR was similar in the two study arms (OR: 0.69; 95%CI: 0.22-2.26; p = 0.33). Similar results were observed for day 42, i.e. higher PCR-uncorrected ACPR for DHA/PQP, mainly due to the difference observed up to day 28, while the PCR-corrected ACPR was similar: DHA/PQP: 93% (179/192), AL: 93% (84/90), (OR: 0.92; 95%CI: 0.30-2.64; p = 0.85). Except for cough, more frequent in the DHA/PQP arm (p = 0.04), there were no differences between treatment arms in the occurrence of adverse events. Two serious adverse events were probably associated to AL treatment. Conclusion DHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia. Trial Registration ISRCTN16263443, at http://www.controlled-trials.com/isrctn

Abstract Background HIV-1 infection affects malaria humeral immunity during pregnancy, but data for non-pregnant adults are lacking. This study reports the impact of HIV-1 infection and other variables on the level of malaria humeral immunity in adults with clinical malaria and whether humeral immune suppression was a risk factor for treatment failure. Methods Sera of 224 HIV-1 infected and 115 uninfected adults were compared for IgG to merozoite antigens AMA-1 and MSP2 (3D7 and FC27 types) determined by ELISA, and for IgG to the Variant Surface Antigens (VSA) of three different parasite line E8B, A4 and HCD6 determined by flow cytometry. Results Compared to HIV-1 uninfected adults, AMA-1 IgG was lower in HIV-1 infected (P = 0.02) and associated with low CD4 count AMA-1 IgG (P = 0.003). Low IgG to all three merozoite antigens was associated with less anemia (P = 0.03). High parasite load was associated with low MSP2 IgG 3D7 and FC27 types (P = 0.02 and P = 0.08). Antibody levels to VSA did not differ between HIV-1 infected and uninfected adults. However, low VSA IgGs were associated with high parasite load (P ≤ 0.002 for each parasite line) and with treatment failure (P ≤ 0.04 for each parasite line). Conclusion HIV-1 affects humeral responses to AMA-1, but seems to marginally or not affect humeral responses to other merozoite antigens and VSAs. The latter were important for controlling parasite density and predict treatment outcome.

Abstract Background In Zambia, unacceptably high resistance to commonly used antimalarial drugs prompted the choice of artemether-lumefantrine (AL) as first line treatment for uncomplicated Plasmodium falciparum malaria. Although the safety and efficacy of AL have been extensively documented, no clinical trials had been carried out in Zambia. Methods Nine hundred seventy one adult patients with uncomplicated malaria were randomized to either sulfadoxine-pyrimethamine (SP)(486) or AL (485) and followed up for 45 days. Outcome of treatment was defined according to the standard WHO classification. Recurrent parasitaemia were genotyped to distinguish between recrudescence and new infection. Results Fever at day 3 was significantly lower (AL: 0.9%; 4/455; SP: 3,5%; 15/433; p = 0.007) and the mean haemoglobin at day 45 significantly higher (AL: 134 g/l; SP 130 g/l; p = 0.02) in the AL group. Almost all clinical symptoms cleared faster with AL. Early treatment failure was significantly higher in the SP (25/464) than in the AL (2/463) (OR: 13.1 95% CI: 3.08–55.50; P < 0.001). The rate of new infections was similar in both groups (18 with SP and 19 with AL). Late clinical failure (OR: 2.55; 95% CI: 1.34–4.84; P = 0.004) and late parasitological failure (OR:3.18; 95% CI: 1.25–8.09; P = 0.02) were significantly higher in the SP group. Total treatment failure was significantly higher in the SP group (96/393; 19.3%) as compared to the AL (22/403; 5.4%) group (OR: 4.15; 95% CI: 2.52–6.83; P < 0.001). Conclusion In Zambia, the new first line regimen AL is far more efficacious than SP in treating uncomplicated P. falciparum malaria in adults. Data on safety and efficacy of AL in pregnant women are urgently needed.

Artemisinin-based combination therapy (ACT) is the first-line recommended treatment for uncomplicated malaria. Pharmacokinetic (PK) properties in pregnant women are often based on small studies and need to be confirmed and validated in larger pregnant patient populations. This study aimed to evaluate the PK properties of amodiaquine and its active metabolite, desethylamodiaquine, and piperaquine in women in their second and third trimester of pregnancy with uncomplicated P. falciparum infections. Eligible pregnant women received either artesunate-amodiaquine (200/540 mg daily, n = 771) or dihydroartemisinin-piperaquine (40/960 mg daily, n = 755) for 3 days (NCT00852423). Population PK properties were evaluated using nonlinear mixed-effects modeling, and effect of gestational age and trimester was evaluated as covariates. 1071 amodiaquine and 1087 desethylamodiaquine plasma concentrations, and 976 piperaquine plasma concentrations, were included in the population PK analysis. Amodiaquine concentrations were described accurately with a one-compartment disposition model followed by a two-compartment disposition model of desethylamodiaquine. The relative bioavailability of amodiaquine increased with gestational age (1.25% per week). The predicted exposure to desethylamodiaquine was 2.8%-32.2% higher in pregnant women than that reported in non-pregnant women, while day 7 concentrations were comparable. Piperaquine concentrations were adequately described by a three-compartment disposition model. Neither gestational age nor trimester had significant impact on the PK of piperaquine. The predicted exposure and day 7 concentrations of piperaquine were similar to that reported in non-pregnant women. In conclusion, the exposure to desethylamodiaquine and piperaquine was similar to that in non-pregnant women. Dose adjustment is not warranted for women in their second and their trimester of pregnancy., (© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Attractive targeted sugar bait (ATSB) stations are a novel tool with potential to complement current approaches to malaria vector control. To assess the public health value of ATSB station deployment in areas of high coverage with standard vector control, a two-arm cluster-randomized controlled trial (cRCT) of Sarabi ATSB® stations (Westham Ltd., Hod-Hasharon, Israel) was conducted in Western Province, Zambia, a high-burden location were Anopheles funestus is the dominant vector. The trial included 70 clusters and was designed to measure the effect of ATSBs on case incidence and infection prevalence over two 7-month deployments. Reported here are results of the vector surveillance component of the study, conducted in a subset of 20 clusters and designed to provide entomological context to guide overall interpretation of trial findings., Methods: Each month, 200 paired indoor-outdoor human landing catch (HLC) and 200 paired light trap (LT) collections were conducted to monitor An. funestus parity, abundance, biting rates, sporozoite prevalence, and entomological inoculation rates (EIR)., Results: During the study 20,337 female An. funestus were collected, 11,229 from control and 9,108 from intervention clusters. A subset of 3,131 HLC specimens were assessed for parity: The mean non-parous proportion was 23.0% (95% CI 18.2-28.7%, total n = 1477) in the control and 21.2% (95% CI 18.8-23.9%, total n = 1654) in the intervention arm, an OR = 1.05 (95% CI 0.82-1.34; p = 0.688). A non-significant reduction in LT abundance (RR = 0.65 [95% CI 0.30-1.40, p = 0.267]) was associated with ATSB deployment. HLC rates were highly variable, but model results indicate a similar non-significant trend with a RR = 0.68 (95%CI 0.22-2.00; p = 0.479). There were no effects on sporozoite prevalence or EIR., Conclusions: Anopheles funestus parity did not differ across study arms, but ATSB deployment was associated with a non-significant 35% reduction in vector LT density, results that are consistent with the epidemiological impact reported elsewhere. Additional research is needed to better understand how to maximize the potential impact of ATSB approaches in Zambia and other contexts., Trial Registration Number: This trial was registered with Clinicaltrials.gov (NCT04800055, 16 March 2021)., (© 2024. The Author(s).)

Background: The neurological, airway, respiratory, cardiovascular and other, with a subscore of surgical severity (NARCO-SS) is a scoring system which assesses the presence of systemic disease and the risk the operation poses to the patient. A number of patients that undergo major abdominal surgery suffer adverse events. The aim of the study was to determine the reliability of NARCO-SS in predicting peri-operative adverse events and to determine the risk factors for peri-operative adverse events in paediatric patients undergoing elective abdominal surgery., Materials and Methods: Prospective cohort study. Consecutively sampled patients from December 2019 to December 2020 were used. Patients scheduled for elective abdominal surgery were scored pre-operatively and end points were; when an adverse event occurred or up to day 30. Analysis of the reliability of the tool, bivariate and multivariate logistics regression was done., Results: One hundred and nineteen patients were enrolled and 49% of them had adverse events. Both bivariate and multivariate analyses showed no significant association between the NARCO-SS score and the occurrence of adverse events. The area under the receiver operating characteristics curve (area under the curve) of the NARCO-SS for adverse events was 0.518; there was a significant correlation between high scores and mortality. Longer duration of surgery and complex surgery were the risk factors for adverse events., Conclusions: The NARCO-SS score was found to be a poor predictor of adverse events with a fair inter-rater reliability as a scoring tool. Future research could evaluate a modification of neurological and airway categories., (Copyright © 2024 Copyright: © 2024 African Journal of Paediatric Surgery.)

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma worldwide, accounting for up to 40% of new non-Hodgkin Lymphoma (NHL) globally. People living with HIV are up to 17 times more likely to develop NHL, and as such, DLBCL is the leading cause of cancer death in this high-risk population. While histologically indistinguishable, HIV-associated (HIV+) and HIV-negative (HIV-) DLBCL are molecularly distinct, and biological differences may have implications for the development of future therapeutic interventions. Further, the impact of immunologic differences in people with HIV, including preceding ART, remains largely unknown. Here, we investigate the impact of HIV infection and ART exposure on the clinical features of DLBCL and T-cell immune response by performing imaging mass cytometry on our unique patient cohort in Malawi. In this cohort, HIV infection is positively prognostic, and HIV+/ART-naïve patients have the best outcomes. No established biomarkers other than Ki67 are associated with HIV or ART status, and the only tumour-intrinsic biomarkers that remain prognostic are MYC and MYC/BCL2 protein co-expression. Finally, TCR clonality is associated with distinct tumour-T cell interactions by HIV/ART status, indicating differential anti-tumour immune responses. We demonstrate previously undescribed HIV and ART-related differences in the DLBCL tumour microenvironment., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Soft actuators are one of the most promising technological advancements with potential solutions to diverse fields' day-to-day challenges. Soft actuators derived from hydrogel materials possess unique features such as flexibility, responsiveness to stimuli, and intricate deformations, making them ideal for soft robotics, artificial muscles, and biomedical applications. This review provides an overview of material composition and design techniques for hydrogel actuators, exploring 3D printing, photopolymerization, cross-linking, and microfabrication methods for improved actuation. It examines applications of hydrogel actuators in biomedical, soft robotics, bioinspired systems, microfluidics, lab-on-a-chip devices, and environmental, and energy systems. Finally, it discusses challenges, opportunities, advancements, and regulatory aspects related to hydrogel actuators., (© 2024 Wiley‐VCH GmbH.)

Enteric infections due to viral pathogens are a major public health concern. Detecting the risk areas requires a strong surveillance system for pathogenic viruses in sources such as wastewater. Towards building an environmental surveillance system in Zambia, we aimed to identify group A rotavirus (RVA) and human adenovirus (HAdV) in wastewater. Convenient sampling was conducted at four study sites every Tuesday for five consecutive weeks. The research team focused on three different methods of viral concentration to determine the suitability in terms of cost and applicability for a regular surveillance system: the bag-mediated filtration system (BMFS), polyethylene glycol-based (PEG) precipitation, and skimmed milk (SM) flocculation. We screened 20 wastewater samples for HAdV and RVA using quantitative polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR). Of the 20 samples tested using qPCR, 18/20 (90%) tested positive for HAdV and 14/20 (70%) tested positive for RVA. For the genetic sequencing, qPCR positives were subjected to cPCR, of which 12 positives were successfully amplified. The human adenovirus was identified with a nucleotide identity range of 98.48% to 99.53% compared with the reference genome from GenBank. The BMFS and SM flocculation were the most consistent viral concentration methods for HAdV and RVA, respectively. A statistical analysis of the positives showed that viral positivity differed by site ( p < 0.001). SM and PEG may be the most appropriate options in resource-limited settings such as Zambia due to the lower costs associated with these concentration methods. The demonstration of HAdV and RVA detection in wastewater suggests the presence of the pathogens in the communities under study and the need to establish a routine wastewater surveillance system for the identification of pathogens.

This review elucidated the recent advances in integrating microalgal communities in monitoring metal pollution in aquatic ecosystems of sub-Saharan Africa (SSA). It also highlighted the potential of incorporating microalgae as bioindicators in emerging technologies, identified research gaps, and suggested directions for further research in biomonitoring of metal pollution. Reputable online scholarly databases were used to identify research articles published between January 2000 and June 2023 for synthesis. Results indicated that microalgae were integrated either individually or combined with other bioindicators, mainly macroinvertebrates, macrophytes, and fish, alongside physicochemical monitoring. There was a significantly low level of integration (< 1%) of microalgae for biomonitoring aquatic metal pollution in SSA compared to other geographical regions. Microalgal communities were employed to assess compliance (76%), in diagnosis (38%), and as early-warning systems (38%) of aquatic ecological health status. About 14% of biomonitoring studies integrated microalgal eDNA, while other technologies, such as remote sensing, artificial intelligence, and biosensors, are yet to be significantly incorporated. Nevertheless, there is potential for the aforementioned emerging technologies for monitoring aquatic metal pollution in SSA. Future monitoring in the region should also consider the standardisation and synchronisation of integrative biomonitoring and embrace the "Citizen Science" concept at national and regional scales., (© 2024. The Author(s).)

The most common subtype of lymphoma globally, diffuse large B cell lymphoma (DLBCL), is a leading cause of cancer death in people with HIV. The restructuring of the T cell compartment because of HIV infection and antiretroviral therapy (ART) may have implications for modern treatment selection, but current understanding of these dynamic interactions is limited. Here, we investigated the T cell response to DLBCL by sequencing the T cell receptor (TCR) repertoire in a cohort of HIV-negative (HIV-), HIV+/ART-experienced, and HIV+/ART-naive patients with DLBCL. HIV+/ART-naive tumor TCR repertoires were more clonal and more distinct from each other than HIV- and HIV+/ART-experienced ones. Further, increased overlap between tumor and blood TCR repertoires was associated with improved survival and HIV/ART status. Our study describes TCR repertoire characteristics for the first time to our knowledge in an African DLBCL cohort and demonstrates contributions of HIV infection and ART exposure to the DLBCL TCR repertoire.

The present zwitterionic hydrogel-based wearable sensor exhibits various limitations, such as limited degradation capacity, unavoidable toxicity resulting from initiators, and poor mechanical properties that cannot satisfy practical demands. Herein, we present an initiator and crosslinker-free approach to prepare polyethylene glycol (PEG)@poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl) (PSBMA) interpenetrating polymer network (IPN) hydrogels that are self-polymerized via sunlight-induced and non-covalent crosslinking through electrostatic interaction and hydrogen bonding among polymer chains. The PEG@PSBMA IPN hydrogel possesses tissue-like softness, superior stretchability (∼2344.6% elongation), enhanced fracture strength (∼39.5 kPa), excellent biocompatibility, antibacterial property, reliable adhesion, and ionic conductivity. Furthermore, the sensor based on the IPN hydrogel demonstrates good sensitivity and cyclic stability, enabling effective real-time monitoring of human body activities. Moreover, it is worth noting that the excellent degradability in the saline solution within 8 h makes the prepared hydrogel-based wearable sensor free from the electronic device contamination. We believe that the proposed strategy for preparing physical zwitterionic hydrogels will pave the way for fabricating eco-friendly wearable devices.

Genomic surveillance of Plasmodium falciparum malaria can provide policy-relevant information about antimalarial drug resistance, diagnostic test failure, and the evolution of vaccine targets. Yet the large and low complexity genome of P. falciparum complicates the development of genomic methods, while resource constraints in malaria endemic regions can limit their deployment. Here, we demonstrate an approach for targeted nanopore sequencing of P. falciparum from dried blood spots (DBS) that enables cost-effective genomic surveillance of malaria in low-resource settings. We release software that facilitates flexible design of amplicon sequencing panels and use this software to design two target panels for P. falciparum. The panels generate 3-4 kbp reads for eight and sixteen targets respectively, covering key drug-resistance associated genes, diagnostic test antigens, polymorphic markers and the vaccine target csp. We validate our approach on mock and field samples, demonstrating robust sequencing coverage, accurate variant calls within coding sequences, the ability to explore P. falciparum within-sample diversity and to detect deletions underlying rapid diagnostic test failure., (© 2024. The Author(s).)

The pathology laboratory at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi was established in 2011. We published our initial experiences in laboratory development and telepathology in 2013 and 2016, respectively. The purpose of this paper is to provide an update on our work by highlighting the positive role laboratory development has played in improving regional cancer care and research. In addition, we provide a summary of the adult pathology data from specimens received between July 1, 2011, and May 31, 2019, with an emphasis on malignant diagnoses. We compare these summaries to estimates of cancer incidence in this region to identify gaps and future needs., 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 © 2024 Brownlee, Dewey, Chagomerana, Tomoka, Mulenga, Khan, Kampani, Chimzimu, Gastier-Foster, Westmoreland, Ozuah, Krysiak, Malamba-Banda, Painschab, Gopal and Fedoriw.)

Introduction: Coronavirus disease-19 led to a significant reduction in surgery worldwide. Studies, however, of the effect on surgical volume for pediatric patients in low-income and middle-income countries (LMICs) are limited., Methods: A survey was developed to estimate waitlists in LMICs for priority surgical conditions in children. The survey was piloted and revised before it was deployed over email to 19 surgeons. Pediatric surgeons at 15 different sites in eight countries in sub-Saharan Africa and Ecuador completed the survey from February 2021 to June 2021. The survey included the total number of children awaiting surgery and estimates for specific conditions. Respondents were also able to add additional procedures., Results: Public hospitals had longer wait times than private facilities. The median waitlist was 90 patients, and the median wait time was 2 mo for elective surgeries., Conclusions: Lengthy surgical wait times affect surgical access in LMICs. Coronavirus disease-19 had been associated with surgical delays around the world, exacerbating existing surgical backlogs. Our results revealed significant delays for elective, urgent, and emergent cases across sub-Saharan Africa. Stakeholders should consider approaches to scale the limited surgical and perioperative resources in LMICs, create mitigation strategies for future pandemics, and establish ways to monitor waitlists on an ongoing basis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Zambia's National Malaria Elimination Program transitioned to Fludora Fusion in 2019 for annual indoor residual spraying (IRS) in Nchelenge District, an area with holoendemic malaria transmission. Previously, IRS was associated with reductions in parasite prevalence during the rainy season only, presumably because of insufficient residual insecticide longevity. This study assessed the impact of transitioning from Actellic 300CS to long-acting Fludora Fusion using active surveillance data from 2014 through 2021. A difference-in-differences analysis estimated changes in rainy season parasite prevalence associated with living in a sprayed house, comparing insecticides. The change in the 2020 to 2021 dry season parasite prevalence associated with living in a house sprayed with Fludora Fusion was also estimated. Indoor residual spraying with Fludora Fusion was not associated with decreased rainy season parasite prevalence compared with IRS with Actellic 300CS (ratio of prevalence ratios [PRs], 1.09; 95% CI, 0.89-1.33). Moreover, living in a house sprayed with either insecticide was not associated with decreased malaria risk (Actellic 300CS: PR, 0.97; 95% CI, 0.86-1.10; Fludora Fusion: rainy season PR, 1.06; 95% CI, 0.89-1.25; dry season PR, 1.21; 95% CI, 0.99-1.48). In contrast, each 10% increase in community IRS coverage was associated with a 4% to 5% reduction in parasite prevalence (rainy season: PR, 0.95; 95% CI, 0.92-0.97; dry season: PR, 0.96; 95% CI, 0.94-0.99), suggesting a community-level protective effect, and corroborating the importance of high-intervention coverage.

Objective: Zambia has embarked on improving the diagnostic capacity by setting up high throughput and accurate machines in the testing process and introduction of dried blood spot (DBS) as a sample type. This was a cross sectional study to verify dried blood spot as a sample type for HIV viral load and early infant diagnosis (EID) on Hologic Panther platform and Evaluate the analytical performance (precision, linearity and measurement of uncertainty) of the Hologic Panther., Results: The specificity and sensitivity of EID performance of Aptima Quant Dx assay on Hologic panther machine against the gold standard machine COBAS Taqman (CAP/CTM) was 100% with an overall agreement of 100%. The quantitative HIV Viral Load (VL) accuracy had a positive correlation of (0.96) obtained against the gold standard (plasma samples) run on COBAS4800 platform. Analytical performance of the Hologic panther machine was evaluated; Precision low positive repeatability 3.50154 and within lab 2.268915 at mean 2.88 concentration and precision high positive repeatability 1.116955 and within lab 2.010677 at mean 5.09 concentration were obtained confirming manufacturers claims. Uncertainty of measurement for this study was found to be ± 71 copies/ml. Linearity studies were determined and all points were within acceptable limits. We therefore recommend DBS as a sample type alternative to plasma for the estimation of HIV-1 viral load and EID diagnosis on the Hologic panther machine., (© 2023. The Author(s).)

Introduction: Wilms tumor therapy in low- and middle-income countries (LMICs) relies on treatment protocols adapted to resource limitations, but these protocols have rarely been evaluated in real-world settings. Such evaluations are necessary to identify high-impact research priorities for clinical and implementation trials in LMICs. The purpose of this study was to identify highest priority targets for future clinical and implementation trials in sub-Saharan Africa by assessing outcomes of a resource-adapted treatment protocol in Malawi., Methods: We conducted a retrospective cohort study of children treated for Wilms tumor with an adapted SIOP-backbone protocol in Lilongwe, Malawi between 2016 and 2021. Survival analysis assessed variables associated with poor outcome with high potential for future research and intervention., Results: We identified 136 patients, most commonly with stage III (n = 35; 25.7%) or IV disease (n = 35; 25.7%). Two-year event-free survival (EFS) was 54% for stage I/II, 51% for stage III, and 13% for stage IV. A single patient with stage V disease survived to 1 year. Treatment abandonment occurred in 36 (26.5%) patients. Radiotherapy was indicated for 55 (40.4%), among whom three received it. Of these 55 patients, 2-year EFS was 31%. Of 14 patients with persistent metastatic pulmonary disease at the time of nephrectomy, none survived to 2 years. Notable variables independently associated with survival were severe acute malnutrition (hazard ratio [HR]: 1.9), increasing tumor stage (HR: 1.5), and vena cava involvement (HR: 3.1)., Conclusion: High-impact targets for clinical and implementation trials in low-resource settings include treatment abandonment, late presentation, and approaches optimized for healthcare systems with persistently unavailable radiotherapy., (© 2023 Wiley Periodicals LLC.)

An uninterrupted supply of vaccines at different supply chain levels is a basic component of a functional immunization programme and care service. There can be no progress toward achieving universal health coverage and sustainable development without continuous availability of essential medicines and vaccines in healthcare facilities. Shortages of vaccines, particularly at health facility level is an issue of grave concern that requires urgent attention in South Africa. The causes of vaccine stock-outs are multifactorial and may be linked to a broader systems issue. These factors include challenges at higher levels such as delays in the delivery of stock from the pharmaceutical depot; health facility level factors, which include a lack of commitment from healthcare workers and managers; human resource factors, such as, staff shortages, and lack of skilled personnel. Therefore, there is a compelling need to address the factors associated with shortages of vaccines in health facilities. This paper highlights the challenges of vaccine availability in South Africa, the associated factors, the available interventions, and recommended interventions for the expanded programme on immunization in South Africa. We propose a system redesign approach as a potentially useful intervention.

Objectives: To determine the prevalence of COVID-19 postmortem setting in Lusaka, Zambia., Design: A systematic, postmortem prevalence study., Setting: A busy, inner-city morgue in Lusaka., Participants: We sampled a random subset of all decedents who transited the University Teaching Hospital morgue. We sampled the posterior nasopharynx of decedents using quantitative PCR. Prevalence was weighted to account for age-specific enrolment strategies., Interventions: Not applicable-this was an observational study., Primary Outcomes: Prevalence of COVID-19 detections by PCR. Results were stratified by setting (facility vs community deaths), age, demographics and geography and time., Secondary Outcomes: Shifts in viral variants; causal inferences based on cycle threshold values and other features; antemortem testing rates., Results: From 1118 decedents enrolled between January and June 2021, COVID-19 was detected among 32.0% (358/1116). Roughly four COVID-19+ community deaths occurred for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only ~10% of COVID-19+ deaths were identified in life. During peak transmission periods, COVID-19 was detected in ~90% of all deaths. We observed three waves of transmission that peaked in July 2020, January 2021 and ~June 2021: the AE.1 lineage and the Beta and Delta variants, respectively. PCR signals were strongest among those whose deaths were deemed 'probably due to COVID-19', and weakest among children, with an age-dependent increase in PCR signal intensity., Conclusions: COVID-19 was common among deceased individuals in Lusaka. Antemortem testing was rarely done, and almost never for community deaths. Suspicion that COVID-19 was the cause of deaths was highest for those with a respiratory syndrome and lowest for individuals <19 years., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Efforts to eliminate malaria transmission need evidence-based strategies. However, accurately assessing end-game malaria elimination strategies is challenging due to the low level of transmission and the rarity of infections. We hypothesised that presumptively treating individuals during reactive case detection (RCD) would reduce transmission and that serology would more sensitively detect this change over standard approaches. We conducted a cluster randomised control trial (NCT02654912) of presumptive reactive focal drug administration (RFDA-intervention) compared to the standard of care, reactive focal test and treat (RFTAT-control) in Southern Province, Zambia-an area of low seasonal transmission (overall incidence of ~3 per 1,000). We measured routine malaria incidence from health facilities as well as PCR parasite prevalence / antimalarial seroprevalence in an endline cross-sectional population survey. No significant difference was identified from routine incidence data and endline prevalence by polymerase chain reaction (PCR) had insufficient numbers of malaria infections (i.e., 16 infections among 6,276 children) to assess the intervention. Comparing long-term serological markers, we found a 19% (95% CI = 4-32%) reduction in seropositivity for the RFDA intervention using a difference in differences approach incorporating serological positivity and age. We also found a 37% (95% CI = 2-59%) reduction in seropositivity to short-term serological markers in a post-only comparison. These serological analyses provide compelling evidence that RFDA both has an impact on malaria transmission and is an appropriate end-game malaria elimination strategy. Furthermore, serology provides a more sensitive approach to measure changes in transmission that other approaches miss, particularly in very low transmission settings. Trial Registration: Registered at www.clinicaltrials.gov (NCT02654912, 13/1/2016)., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2022 Bridges 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.)

Background: Severe malaria resulting from Plasmodium falciparum infection is the leading parasitic cause of death in children worldwide, and severe malarial anemia (SMA) is the most common clinical presentation. The evidence in support of current blood transfusion guidelines for patients with SMA is limited., Methods: We conducted a retrospective cohort study of 911 hospitalized children with SMA in a holoendemic region of Zambia to examine the association of whole blood transfusion with in-hospital survival. Data were analyzed in adjusted logistic regression models using multiple imputation for missing data., Results: The median age of patients was 24 months (interquartile range, 16-30) and overall case fatality was 16%. Blood transfusion was associated with 35% reduced odds of death in children with SMA (odds ratio, 0.65; 95% confidence interval, .52-.81; P = .0002) corresponding to a number-needed-to-treat (NNT) of 14 patients. Children with SMA complicated by thrombocytopenia were more likely to benefit from transfusion than those without thrombocytopenia (NNT = 5). Longer storage time of whole blood was negatively associated with survival and with the posttransfusion rise in the platelet count but was not associated with the posttransfusion change in hemoglobin concentration., Conclusions: Whole blood given to pediatric patients with SMA was associated with improved survival, mainly among those with thrombocytopenia who received whole blood stored for <4 weeks. These findings point to a potential use for incorporating thrombocytopenia into clinical decision making and management of severe malaria, which can be further assessed in prospective studies, and underline the importance of maintaining reliable blood donation networks in areas of high malaria transmission., Competing Interests: Potential conflicts of interest . W. J. M. reports grants or contracts outside the scope of this work, all paid to Johns Hopkins University, from the National Institutes of Health, Bill & Melinda Gates Foundation, and Gavi, the Vaccine Alliance. T. A. L. reports book royalties from Taylor and Francis; consulting fees from the University of Massachusetts (payment to author for educational program review), the University of Minnesota (payment to author for educational program advisory board), and Annual Reviews (payment to author for editorial board); payment for expert testimony on Urban League et al. v Ross et al. (2020 Census issues) from the NYU Brennan Center; and participation on the NIDDK DSMB. T. A. S. reports grants or contracts outside the scope of this work from the National Institutes of Health and Unitaid, both paid to the institution, and Johns Hopkins Malaria Research Institute, paid within institution; multiple United States and international patents for antimalarial drug development (inventions and therapies unrelated to this manuscript); and stock or stock options (multiple in retirement accounts, managed stocks; none directly in pharmaceuticals and none in any way related to work in this manuscript). J. B. K. reports support for attending meetings and travel from the Science of Malaria Eradication in Barcelona. All other authors report no potential conflicts. 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 the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Zambia experienced a major cholera outbreak in 2017-2018, with more than 5905 cases reported countrywide, predominantly from the peri-urban slums of Lusaka city. The WHO recommends the use of oral cholera vaccines (OCVs) together with traditional control measures, including health promotion, provision of safe water and improving sanitation, in cholera endemic areas and during cholera outbreaks. In response to this outbreak, the Zambian government implemented the OVC campaign and administered the Euvichol-plus vaccine in the high-risk subdistricts of Lusaka. Although OCVs have been shown to be effective in preventing cholera infection in cholera endemic and outbreak settings, the effectiveness of the Euvichol-plus vaccine has not yet been evaluated in Zambia. This study aimed to determine the effectiveness of two doses of OCV administered during the 2017/2018 vaccination campaign., Methods: We conducted a matched case-control study involving 79 cases and 316 controls following the mass vaccination campaign in the four subdistricts of Lusaka (Chawama, Chipata, Kanyama and Matero). Matching of controls was based on the place of residence, age and sex. Conditional logistic regression was used for analysis. Adjusted OR (AOR), 95% CI and vaccine effectiveness (1-AOR) for two doses of Euvichol-plus vaccine and any dose were estimated (p < 0.05)., Results: The AOR vaccine effectiveness for two doses of Euvichol-plus OCV was 81.0% (95% CI 66.0% to 78.0%; p<0.01). Secondary analysis showed that vaccine effectiveness for any dose was 74.0% (95% CI 50.0% to 86.0%; p<0.01)., Conclusion: These findings show that two doses of Euvichol-plus OCV are effective in a cholera outbreak setting in Lusaka, Zambia. The findings also indicate that two doses are more effective than a single dose and thus support the use of two doses of the vaccine as part of an integrated intervention to cholera control during outbreaks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)