The Relationship between Anti-merozoite Antibodies and Incidence of Plasmodium falciparum Malaria: A Systematic Review and Meta-analysis

A systematic review and meta-analysis examining the association between anti-merozoite antibody responses and incidence of Plasmodium falciparum malaria by Freya Fowkes and colleagues aids identification of antigens that confer protection from malaria

Associated factors and global adherence of cervical cancer screening in 2019:a systematic analysis and modelling study

BACKGROUND: Cervical cancer screening is vital for its prevention. Adherence is a crucial indicator that implies the individual willingness to take cervical cancer screening. We aimed to estimate the global and regional adherence rates of cervical cancer screening in 2019 and identify its associated factors among general women. METHOD: We searched studies in PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, ProQuest theses database and Google Web, without a lower time limit and until 23 June, 2021. Survey studies were considered eligible if they investigated cervical cancer screening adherence among general women, with data on sample size, the number of adherent subjects, and/or adherence rate. Random-effects were used to pool the odds ratios (ORs) of associated factors of adherence. Using modelling analysis, we estimated 2019 overall and age-specific adherence rates at the global and regional levels in women aged 20–69 years. RESULTS: Eight thousand two hundred ninety records were identified, and 153 articles were included. Being married (vs not married: OR, 1.34; 95% confidence interval [CI]: 1.23–1.46), higher educational attainment (higher than high school vs less than high school: OR, 1.44; 95% CI: 1.35–1.53), having healthcare (OR, 1.64; 95% CI: 1.43–1.88), former smoking (OR, 1.20; 95% CI: 1.07–1.34), physical activity (OR, 1.19; 95% CI: 1.05–1.36), parity (OR, 1.07; 95% CI: 1.01–1.12), and chronic disease (OR, 1.17; 95% CI: 1.04–1.32) were associated with better adherence, whereas obesity (vs normal: OR, 0.85; 95% CI: 0.74–0.97) and current smoking (vs former/never: OR, 0.64; 95% CI: 0.54–0.76) were associated with worse adherence. In 2019, the adherence was at 33.66% (95% CI: 23.34–39.30%) worldwide, and was higher in high-income countries (HICs) (75.66, 95% CI: 66.74–82.81%) than in low and middle-income countries (LMICs) (24.91, 95% CI: 14.30–30.24%). It varied across regions, the highest in the European region (65.36, 95% CI: 55.40–74.19%), but the lowest in the African region (5.28, 95% CI: 3.43–8.03%). CONCLUSIONS: Cervical cancer screening adherence remained low globally, exhibiting geographical discrepancy with HICs higher than LMICs. Further implementations of screening programs should comprehensively consider the local economy, social benefits, and demographic structure to adapt delivery for vulnerable or underserved women to boost screening adherence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12992-022-00890-w

The Global Epidemiological Transition in Cardiovascular Diseases:Unrecognised Impact of Endemic Infections on Peripheral Artery Disease

An epidemiological transition in the prevalence of peripheral artery disease (PAD) is taking place especially in low- and middle-income countries (LMICs) where an ageing population and adoption of western lifestyles are associated with an increase in PAD. We discuss the limited evidence which suggests that infection, potentially mediated by inflammation, may be a risk factor for PAD, and show by means of an ecological analysis that country-level prevalence of the major endemic infections of HIV, tuberculosis and malaria are associated with the prevalence of PAD. While further research is required, we propose that scientists and health authorities pay more attention to the interplay between communicable and non-communicable diseases, and we suggest that limiting the occurrence of endemic infections might have some effect on slowing the epidemiological transition in PAD

Einfluß der Substrate Sauerstoff (O2) und L-Arginin der Stickstoffmonoxid(NO)-Synthase auf die endogene NO-Bildung und die Atemluftkonzentration von NO

Zielsetzungen: Beeinflussung der endogenen NO-Bildung durch die Substrate der NOS und durch NO selbst. Entwicklung von NO-Atemkurven und von Meßmethoden für die eNO-Bestimmung in der Atemluft, um die Etablierung der NO-Messung in Diagnostik und Therapieüberwachung weiterzuentwickeln. Weiterentwicklung der NO-Meßtechnik, so daß Atemluftkurven online abgeleitet werden können und damit eine bessere örtliche Zuordnung ermöglicht wird. Probanden: An Gruppe 1 wurden Untersuchungen zum Meßgasvolumenstrom durchgeführt. An Gruppe 2 machten wir Nasenmessungen. Vergleichsmessungen zwischen eNO-Reservoir und eNO-Atemluftkurve wurden an Gruppe 3 durchgeführt. Mit Gruppe 4 wurden Messungen zur Stabilität von eNO durchgeführt. Der Einfluß der Umgebungsluft auf eNO wurden an Gruppe 5 untersucht. In Gruppe 6 wurde der Effekt von Sauerstoff untersucht, ebenso in Gruppe 7. Die Argininbelastungsmessungen erfolgten an Gruppe 8. An den Gruppen 9 und 10 erfolgten Untersuchungen an intubierten Probanden. Ergebnisse: Die Untersuchung zum Meßgasvolumenstrom an Gruppe 1 zeigten Werteabweichungen zwischen 9±4 ppb und 11±4 ppb bei Meßgasvolumenströmen zwischen 1000 ml/min und 500 ml/min. Die Nasenmessungen an Gruppe 2 zeigten Nasen-NO-Mittelwerte von 147±92 ppb. An Gruppe 3 wurden die Vergleichsmessungen von eNO-Reservoir und eNO-Atemluftkurve durchgeführt. Die MW der Atemluftkurve lagen um 4 ppb höher als die MW der Reservoirmessungen. Bei einer Korrelation von r2=0,83 zeigten die Werte nach Bland-Altman keine Übereinstimmung. Die Messungen zur Stabilität von eNO wurden an Gruppe 4 durchgeführt. An fünf aufeinanderfolgenden Tagen zeigten die Mittelwerte der Probanden VK zwischen 0,13-0,57 bei 21% FiO2, bei 50% FiO2 lagen die VK zwischen 0,14-0,65. Es fanden sich große Schwankungen bei diesen Werten. Bei den fünf aufeinanderfolgenden Messungen an einem Tag zeigten die Probanden bei 21% FiO2 VK von 0-0,13. Bei 50% FiO2 lagen die VK zwischen 0,05-0,2. Die Abweichungen dieser Werte waren sehr gering, eNO war relativ stabil. An Gruppe 5 wurden die Messungen zum Einfluß der Umgebungsluft auf eNO durchgeführt. Bei den Messungen mit Umgebungs-NO > 0 lag der MW mit 13±4 ppb höher, als bei den Messungen mit Umgebungs-NO = 0 (MW = 9±5 ppb). Die Werteabweichungen der Probanden erfolgten in alle Richtungen. An Gruppe 6 wurden Messungen zum Einfluß von O2 mit fünf unterschiedlichen FiO2-Konzentrationen durchgeführt. Es ergab sich ein Anstieg von 3±2 ppb bei 10% FiO2 auf 7±2 ppb bei 21% FiO2. Bei einer Erhöhung auf 50% FiO2 stieg eNO auf 12±5 ppb an. Die NOS scheint durch O2 stimulierbar zu sein, eNO steigt signifikant an, oberhalb von 50 % FiO2 kommt es zur Sättigung. Bei Hypoxie fällt eNO ab. An Gruppe 7 wurden Messungen zum Einfluß von O2 mit zwei FiO2-Werten durchgeführt. Hier wurde ein Werteanstieg von 5±4 ppb bei 21% FiO2 auf 8±5 ppb bei 50% FiO2 gemessen. Bei einem Breathholding-Manöver konnte ebenfalls ein eNO-Anstieg erreicht werden. Die Argininbelastungsmessungen erfolgten mit Gruppe 8. Es kam zu einem eNO-Anstieg von 3±2 ppb vor Arginingabe auf 10±5 ppb 30 Minuten nach Arginininfusion. Es folgte ein Werteplateau mit einem leichten Abfall von eNO auf 9±5 ppb nach 120 Minuten. An den Gruppen 9 und 10 wurden eNO-Messungen an intubierten Probanden durchgeführt. Mit eNO-MW zwischen 1±1 ppb und 3±1 ppb lagen sie niedriger als die Werte bei nichtintubierten Probanden. Schlußfolgerungen: Es wurde gezeigt, daß NO in der Atemluft meßbar ist und daß die Werte eines Atemzyklus als Kurve aufgezeigt werden können. Messungen mit einem empfindlicheren Meßgerät könnten die Kurven und ihre Aussagekraft weiter verbessern. Die Untersuchungen haben bestätigt, daß die Bildung und Freisetzung von NO stimulierbar ist. Dadurch scheint es möglich, Aussagen über die Anwesenheit von NOS zu machen. Die eNO-Messung könnte eine neue Möglichkeit in der Diagnostik und Therapieüberwachung von Krankheiten bieten, die mit veränderter NOS-Aktivität einhergehen. Der NO-Analysator konnte verbessert werden. Für die Fortführung der Untersuchungen sollte ein Gerät mit einer höheren Empfindlichkeit verwendet werden, um niedrige eNO-Werte besser erfassen zu können

The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria

Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity

Estimating Gestational Age in Late Presenters to Antenatal Care in a Resource-Limited Setting on the Thai-Myanmar Border

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Antibody responses to Plasmodium falciparum and Plasmodium vivax blood-stage and sporozoite antigens in the postpartum period

During pregnancy a variety of immunological changes occur to accommodate the fetus. It is unknown whether these changes continue to affect humoral immunity postpartum or how quickly they resolve. IgG levels were measured to P. falciparum and P. vivax antigens in 201 postpartum and 201 controls over 12 weeks. Linear mixed-effects models assessed antibody maintenance over time and the effect of microscopically confirmed Plasmodium spp. infection on antibody levels, and whether this was different in postpartum women compared with control women. Postpartum women had reduced Plasmodium spp. antibody levels compared to controls at baseline. Over 12 weeks, mean antibody levels in postpartum women increased to levels observed in control women. Microscopically confirmed P. falciparum and P. vivax infections during follow-up were associated with an increase in species-specific antibodies with similar magnitudes of boosting observed in postpartum and control women. Antibodies specific for pregnancy-associated, VAR2CSA-expressing parasites did not rapidly decline postpartum and did not boost in response to infection in either postpartum or control women. After pregnancy, levels of malaria-specific antibodies were reduced, but recovered to levels seen in control women. There was no evidence of an impaired ability to mount a boosting response in postpartum women

Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure

Background: Leading malaria vaccine, RTS,S, is based on the circumsporozoite protein (CSP) of sporozoites. RTS,S confers partial protection against malaria in children, but efficacy wanes relatively quickly after primary immunization. Vaccine efficacy has some association with anti-CSP IgG; however, it is unclear how these antibodies function, and how functional antibodies are induced and maintained over time. Recent studies identified antibodycomplement interactions as a potentially important immune mechanism against sporozoites. Here, we investigated whether RTS,S vaccine-induced antibodies could function by interacting with complement. Methods: Serum samples were selected from children in a phase IIb trial of RTS,S/AS02A conducted at two study sites of high and low malaria transmission intensity in Manhiça, Mozambique. Samples following primary immunization and 5-year post-immunization follow-up time points were included. Vaccine-induced antibodies were characterized by isotype, subclass, and epitope specificity, and tested for the ability to fix and activate complement. We additionally developed statistical methods to model the decay and determinants of functional antibodies after vaccination. Results: RTS,S vaccination induced anti-CSP antibodies that were mostly IgG1, with some IgG3, IgG2, and IgM. Complement-fixing antibodies were effectively induced by vaccination, and targeted the central repeat and Cterminal regions of CSP. Higher levels of complement-fixing antibodies were associated with IgG that equally recognized both the central repeat and C-terminal regions of CSP. Older age and higher malaria exposure were significantly associated with a poorer induction of functional antibodies. There was a marked decay in functional complement-fixing antibodies within months after vaccination, as well as decays in IgG subclasses and IgM. Statistical modeling suggested the decay in complement-fixing antibodies was mostly attributed to the waning of anti-CSP IgG1, and to a lesser extent IgG3. Conclusions: We demonstrate for the first time that RTS,S can induce complement-fixing antibodies in young malaria-exposed children. The short-lived nature of functional responses mirrors the declining vaccine efficacy of RTS,S over time. The negative influence of age and malaria exposure on functional antibodies has implications for understanding vaccine efficacy in different settings. These findings provide insights into the mechanisms and longevity of vaccine-induced immunity that will help inform the future development of highly efficacious and longlasting malaria vaccines