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RTS,S/AS01E has been tested in a phase 3 malaria vaccine study with partial efficacy in African children and infants. In a cohort of 1028 subjects from one low (Bagomoyo) and two high (Nanoro, Kintampo) malaria transmission sites, we analysed IgG plasma/serum concentration and avidity to CSP (NANP-repeat and C-terminal domains) after a 3-dose vaccination against time to clinical malaria events during 12-months. Here we report that RTS,S/AS01E induces substantial increases in IgG levels from pre- to post-vaccination ( p  < 0.001), higher in NANP than C-terminus (2855 vs 1297 proportional change between means), and higher concentrations and avidities in children than infants ( p  < 0.001). Baseline CSP IgG levels are elevated in malaria cases than controls ( p  < 0.001). Both, IgG magnitude to NANP (hazard ratio [95% confidence interval] 0.61 [0.48–0.76]) and avidity to C-terminus (0.07 [0.05–0.90]) post-vaccination are significantly associated with vaccine efficacy. IgG avidity to the C-terminus emerges as a significant contributor to RTS,S/AS01E-mediated protection. RTS,S/AS01E has been tested in a phase 3 malaria vaccine trial and has shown partial efficacy in children and infants. Here, the authors analyze IgG concentration and avidity to CSP in ~1000 participants and show that IgG avidity to the C-terminus of CSP is significantly associated with vaccine-mediated protection.

The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naïve adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5–12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 × 10 5 , 9.0 × 10 5 or 1.8 × 10 6 PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 × 10 5 dose group = −6.5%, P  = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% ( P  = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vδ2 + Vγ9 + T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vδ2 + Vγ9 + T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group. The PfSPZ Vaccine does not protect infants from infection with Plasmodium falciparum , the major cause of malaria.

Breast cancer is one of the most significant causes of death for women around the world. Breast thermography supported by deep convolutional neural networks is expected to contribute significantly to early detection and facilitate treatment at an early stage. The goal of this study is to investigate the behavior of different recent deep learning methods for identifying breast disorders. To evaluate our proposal, we built classifiers based on deep convolutional neural networks modelling inception V3, inception V4, and a modified version of the latter called inception MV4. MV4 was introduced to maintain the computational cost across all layers by making the resultant number of features and the number of pixel positions equal. DMR database was used for these deep learning models in classifying thermal images of healthy and sick patients. A set of epochs 3–30 were used in conjunction with learning rates 1 × 10 –3 , 1 × 10 –4 and 1 × 10 –5 , Minibatch 10 and different optimization methods. The training results showed that inception V4 and MV4 with color images, a learning rate of 1 × 10 –4 , and SGDM optimization method, reached very high accuracy, verified through several experimental repetitions. With grayscale images, inception V3 outperforms V4 and MV4 by a considerable accuracy margin, for any optimization methods. In fact, the inception V3 (grayscale) performance is almost comparable to inception V4 and MV4 (color) performance but only after 20–30 epochs. inception MV4 achieved 7% faster classification response time compared to V4. The use of MV4 model is found to contribute to saving energy consumed and fluidity in arithmetic operations for the graphic processor. The results also indicate that increasing the number of layers may not necessarily be useful in improving the performance.

A field experiment was conducted during the 2022-2023 agricultural season in two locations, the first in Salah al-Din province/Shirqat District (the discount area), which is about 130 km from the center of the Mosul District, and the second location is the village of al-Hamra in the Nimrud District, which is 50 km from the center of the Mosul District, with the aim of knowing effect of five Types of fertilizers on the growth and yield of four cultivars of durum wheat. A factorial experiment was conducted with two factors and a completely randomized block design (RCBD), with a split-plot system and three replicates. Each replicate contained five main plots that represented the levels of the first factor (fertilizer treatments), and then the levels of the second factor were randomly distributed within them Cultivars (which were four secondary experimental units, and the fertilizers used in the experiment were (mineral fertilizer, organic fertilizer, nanofertilizer, biofertiliser, humic fertilizer). As for the cultivars, they were four cultivars of durum wheat (Sekandrioz, Dor 85, Sardar and Parasiful). Study of the following traits: number of days to flowering, plant height, number of tillers, flag leaf area, spike number, spike length, number of grains per spike, weight of 1000 grains, grain yield, and biological yield. The results obtained from this study were as follows: The mineral fertilizer treatment was excelled in trait of grain yield for Al-Shirqat location, plant height, flag leaf area, and spike length for the Nimrud location, number of tillers, number of spike, and biological yield for the two locations, with values reaching (7934.7 kg.ha -1 , 91.64 cm, 46.74 cm 2 , 8, 64 cm, 410.92 tillers m -2 , 375.00 shore m-2, 365.50 spike m-2, 321.58 spike m -2 , 16539 kg.ha -1 and 16724 kg.ha -1 ) respectively. The nanofertilizer treatment was excelled in trait of the number of grains per spike for Al-Sharqat location, with an average of (51.55 grains. spike -1 ). The biofertilizer treatment was excelled in trait of the number of days to flowering at Al-Nimrud location, with an average of (137.83 days). The humic fertilizer treatment was excelled in plant height at Al-Sharqat location, with an average of (92.41 cm). The Dor 85 cultivar achieved significantly excelled in the two traits of flag leaf area and weight of 1000 grain for both locations, with averages reaching (33.64 cm2, 46.51 cm2, 54.73 g, 50.37 g) respectively. Al-Sardar cultivar gave a significantly excelled in the number of days to flowering, with an average of (118.66 days) for Al-Sharqat location. The Parasiful cultivar was superior in spike length for both locations, with an average of (9.59 cm, 9.25 cm). In the interaction of the two factors, the Parasiful cultivar and the mineral fertilizer treatment gave the highest averages for the number of tillers and the number of spike for both locations, amounting to (444.33 and 415.33 tillers.m -2 ), respectively. The interaction of the Sardar cultivar with organic fertilizer treatment recorded the highest grain yield at the Nimrud location, with an average of (8752 kg.ha -1 )

Pre-vaccination monocyte-to-lymphocyte ratio was previously suggested as a marker for malaria vaccine effectiveness. We investigated the potential of this cell ratio as a marker for malaria vaccine efficacy and effectiveness. Effectiveness was investigated by using clinical malaria endpoint, and efficacy was investigated by using surrogate endpoints of Plasmodium falciparum prepatent period, parasite density, and multiplication rates in a controlled human malaria infection trial (CHMI). We evaluated the correlation between monocyte-to-lymphocyte ratio and RTS,S vaccine effectiveness using Cox regression modeling with clinical malaria as the primary endpoint. Of the 1704 participants in the RTS,S field trial, data on monocyte-to-lymphocyte ratio was available for 842 participants, of whom our analyses were restricted. We further used Spearman Correlations and Cox regression modeling to evaluate the correlation between monocyte-to-lymphocyte ratio and Whole Sporozoite malaria vaccine efficacy using the surrogate endpoints. Of the 97 participants in the controlled human malaria infection vaccine trials, hematology and parasitology information were available for 82 participants, of whom our analyses were restricted. The unadjusted efficacy of RTS,S malaria vaccine was 54% (95% CI: 37%-66%, p <0.001). No correlation was observed between monocyte-to-lymphocyte ratio and RTS,S vaccine efficacy (Hazard Rate (HR):0.90, 95%CI:0.45-1.80; p = 0.77). The unadjusted efficacy of Whole Sporozoite malaria vaccine in the appended dataset was 17.6% (95%CI:10%-28.5%, p<0.001). No association between monocyte-to-lymphocyte ratio and the Whole Sporozoite malaria vaccine was found against either the prepatent period (HR = 1.16; 95%CI:0.51-2.62, p = 0.72), parasite density (rho = 0.004, p = 0.97) or multiplication rates (rho = 0.031, p = 0.80). Monocyte-to-lymphocyte ratio alone may not be an adequate marker for malaria vaccine efficacy. Further investigations on immune correlates and underlying mechanisms of immune protection against malaria could provide a clearer explanation of the differences between those protected in comparison with those not protected against malaria by vaccination.

In sub-Saharan Africa (SSA), epidemiological data for chronic kidney disease (CKD) are scarce. We conducted a prospective cross-sectional study including 952 patients in an outpatient clinic in Tanzania to explore CKD prevalence estimates and the association with cardiovascular and infectious disorders. According to KDIGO, we measured albumin-to-creatinine ratio and calculated eGFR using CKD-EPI formula. Factors associated with CKD were calculated by logistic regression. Venn diagrams were modelled to visualize interaction between associated factors and CKD. Overall, the estimated CKD prevalence was 13.6% (95% CI 11-16%). Ninety-eight patients (11.2%) (95% CI 9-14%) were categorized as moderate, 12 (1.4%) (95% CI 0-4%) as high, and 9 (1%) (95% CI 0-3%) as very high risk according to KDIGO. History of tuberculosis (OR 3.75, 95% CI 1.66-8.18; p = 0.001) and schistosomiasis (OR 2.49, 95% CI 1.13-5.18; p = 0.02) were associated with CKD. A trend was seen for increasing systolic blood pressure (OR 1.02 per 1 mmHg, 95% CI 1.00-1.03; p = 0.01). Increasing BMI (OR 0.92 per 1kg/m2, 95% CI 0.88-0.96; p = <0.001) and haemoglobin (OR 0.82 per 1g/dL, 95% CI 0.72-0.94; p = 0.004) were associated with risk reduction. Diabetes was associated with albuminuria (OR 2.81, 95% CI 1.26-6.00; p = 0.009). In 85% of all CKD cases at least one of the four most common factors (hypertension, diabetes, anaemia, and history of tuberculosis or schistosomiasis) was associated with CKD. A singular associated factor was found in 61%, two in 14%, and ≥3 in 10% of all CKD cases. We observed a high prevalence estimate for CKD and found that both classical cardiovascular and neglected infectious diseases might be associated with CKD in a semi-rural population of SSA. Our finding provides further evidence for the hypothesis that the \"double burden\" of non-communicable and endemic infectious diseases might affect kidney health in SSA.

The use of malaria rapid diagnostic tests (RDTs) as a source for nucleic acids that can be analyzed via nucleic acid amplification techniques has several advantages, including minimal amounts of blood, sample collection, simplified storage and shipping conditions at room temperature. We have systematically developed and extensively evaluated a procedure to extract total nucleic acids from used malaria RDTs. The co-extraction of DNA and RNA molecules from small volumes of dried blood retained on the RDTs allows detection and quantification of P. falciparum parasites from asymptomatic patients with parasite densities as low as 1 Pf/µL blood using reverse transcription quantitative PCR. Based on the extraction protocol we have developed the ENAR (Extraction of Nucleic Acids from RDTs) approach; a complete workflow for large-scale molecular malaria surveillance. Using RDTs collected during a malaria indicator survey we demonstrated that ENAR provides a powerful tool to analyze nucleic acids from thousands of RDTs in a standardized and high-throughput manner. We found several, known and new, non-synonymous single nucleotide polymorphisms in the propeller region of the kelch 13 gene among isolates circulating on Bioko Island, Equatorial Guinea.

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis . A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies. The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis . A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.

Pre-vaccination monocyte-to-lymphocyte ratio was previously suggested as a marker for malaria vaccine effectiveness. We investigated the potential of this cell ratio as a marker for malaria vaccine efficacy and effectiveness. Effectiveness was investigated by using clinical malaria endpoint, and efficacy was investigated by using surrogate endpoints of Plasmodium falciparum prepatent period, parasite density, and multiplication rates in a controlled human malaria infection trial (CHMI). We evaluated the correlation between monocyte-to-lymphocyte ratio and RTS,S vaccine effectiveness using Cox regression modeling with clinical malaria as the primary endpoint. Of the 1704 participants in the RTS,S field trial, data on monocyte-to-lymphocyte ratio was available for 842 participants, of whom our analyses were restricted. We further used Spearman Correlations and Cox regression modeling to evaluate the correlation between monocyte-to-lymphocyte ratio and Whole Sporozoite malaria vaccine efficacy using the surrogate endpoints. Of the 97 participants in the controlled human malaria infection vaccine trials, hematology and parasitology information were available for 82 participants, of whom our analyses were restricted. The unadjusted efficacy of RTS,S malaria vaccine was 54% (95% CI: 37%-66%, p <0.001). No correlation was observed between monocyte-to-lymphocyte ratio and RTS,S vaccine efficacy (Hazard Rate (HR):0.90, 95%CI:0.45-1.80; p = 0.77). The unadjusted efficacy of Whole Sporozoite malaria vaccine in the appended dataset was 17.6% (95%CI:10%-28.5%, p<0.001). No association between monocyte-to-lymphocyte ratio and the Whole Sporozoite malaria vaccine was found against either the prepatent period (HR = 1.16; 95%CI:0.51-2.62, p = 0.72), parasite density (rho = 0.004, p = 0.97) or multiplication rates (rho = 0.031, p = 0.80). Monocyte-to-lymphocyte ratio alone may not be an adequate marker for malaria vaccine efficacy. Further investigations on immune correlates and underlying mechanisms of immune protection against malaria could provide a clearer explanation of the differences between those protected in comparison with those not protected against malaria by vaccination.

Parasitic infectious agents rarely occur in isolation. Epidemiological evidence is mostly lacking, and little is known on how the two common parasites Plasmodium and soil transmitted helminths (STH) interact. There are contradictory findings in different studies. Synergism, antagonism and neutral effect have been documented between Plasmodium and STH. This study investigated the impact of STH on clinical malaria presentation and treatment outcome. A matched case control study with a semi longitudinal follow up according to World Health Organization (WHO) antimalarial surveillance guideline was done among children aged 2 months to 9 years inclusively living in western rural areas of Bagamoyo, coastal region of Tanzania. Cases were children with uncomplicated and severe malaria enrolled from the health facilities while controls were children with asymptomatic Plasmodium parasitemia enrolled from the same community. In simple conditional regression analysis there was a tendency for a protective effect of STH on the development of clinical malaria [OR = 0.6, 95% CI of 0.3-1.3] which was more marked for Enterobius vermicularis species [OR = 0.2, 95% CI of 0.0-0.9]. On the contrary, hookworm species tended to be associated with increased risk of clinical malaria [OR = 3.0, 95% CI of 0.9-9.5]. In multiple conditional regression analysis, the overall protective effect was lower for all helminth infection [OR = 0.8, 95% CI of 0.3-1.9] but remained significantly protective for E. vermicularis species [OR = 0.1, 95% CI of 0.0-1.0] and borderline significant for hookworm species [OR = 3.6, 95% CI of 0.9-14.3]. Using ordinal logistic regression which better reflects the progression of asymptomatic Plasmodium parasitemia to severe malaria, there was a 50% significant protective effect with overall helminths [OR = 0.5, 95% CI of 0.3-0.9]. On the contrary, hookworm species was highly predictive of uncomplicated and severe malaria [OR = 7.8, 95% (CI of 1.8-33.9) and 49.7 (95% CI of 1.9-1298.9) respectively]. Generally, children infected with STH had higher geometric mean time to first clearance of parasitemia. The findings of a protective effect of E. vermicularis and an enhancing effect of hookworms may explain the contradictory results found in the literature about impact of helminths on clinical malaria. More insight should be gained on possible mechanisms for these opposite effects. These results should not deter at this stage deworming programs but rather foster implementation of integrated control program for these two common parasites.