The natural history of respiratory syncytial virus in a birth cohort: the influence of age and previous infection on reinfection and disease.

This study aimed to quantify the effect of age, time since last infection, and infection history on the rate of respiratory syncytial virus infection and the effect of age and infection history on the risk of respiratory syncytial virus disease. A birth cohort of 635 children in Kilifi, Kenya, was monitored for respiratory syncytial virus infections from January 31, 2002, to April 22, 2005. Predictors of infection were examined by Cox regression and disease risk by binomial regression. A total of 598 respiratory syncytial virus infections were identified (411 primary, 187 repeat), with 409 determined by antigen assay and 189 by antibody alone (using a "most pragmatic" serologic definition). The incidence decreased by 70% following a primary infection (adjusted hazard ratio = 0.30, 95% confidence interval: 0.21, 0.42; P < 0.001) and by 59% following a secondary infection (hazard ratio = 0.41, 95% confidence interval: 0.22, 0.73; P = 0.003), for a period lasting 6 months. Relative to the age group <6 months, all ages exhibited a higher incidence of infection. A lower risk of severe disease following infection was independently associated with increasing age (P < 0.001) but not reinfection. In conclusion, observed respiratory syncytial virus incidence was lowest in the first 6 months of life, immunity to reinfection was partial and short lived, and disease risk was age related

The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rare variant mutations.

BACKGROUND: The invasion of the red blood cells by Plasmodium falciparum merozoites involves the interplay of several proteins that are also targets for vaccine development. The proteins PfRh5-PfRipr-PfCyRPA-Pfp113 assemble into a complex at the apical end of the merozoite and are together essential for erythrocyte invasion. They have also been shown to induce neutralizing antibodies and appear to be less polymorphic than other invasion-associated proteins, making them high priority blood-stage vaccine candidates. Using available whole genome sequencing data (WGS) and new capillary sequencing data (CS), this study describes the genetic polymorphism in the Rh5 complex in P. falciparum isolates obtained from Kilifi, Kenya. METHODS: 162 samples collected in 2013 and 2014 were genotyped by capillary sequencing (CS) and re-analysed WGS from 68 culture-adapted P. falciparum samples obtained from a drug trial conducted from 2005 to 2007. The frequency of polymorphisms in the merozoite invasion proteins, PfRh5, PfRipr, PfCyRPA and PfP113 were examined and where possible polymorphisms co-occurring in the same isolates. RESULTS: From a total 70 variants, including 2 indels, 19 SNPs [27.1%] were identified by both CS and WGS, while an additional 15 [21.4%] and 36 [51.4%] SNPs were identified only by either CS or WGS, respectively. All the SNPs identified by CS were non-synonymous, whereas WGS identified 8 synonymous and 47 non-synonymous SNPs. CS identified indels in repeat regions in the p113 gene in codons 275 and 859 that were not identified in the WGS data. The minor allele frequencies of the SNPs ranged between 0.7 and 34.9% for WGS and 1.1-29.6% for CS. Collectively, 12 high frequency SNPs (> 5%) were identified: four in Rh5 codon 147, 148, 203 and 429, two in p113 at codons 7 and 267 and six in Ripr codons 190, 259, 524, 985, 1003 and 1039. CONCLUSION: This study reveals that the majority of the polymorphisms are rare variants and confirms a low level of genetic polymorphisms in all proteins within the Rh5 complex

Extracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum

© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Plasmodium falciparum secretes extracellular vesicles (PfEVs) that contain parasite-derived RNA. However, the significance of the secreted RNA remains unexplored. Here, we compare secreted and intracellular RNA from asexual cultures of six P. falciparum lines. We find that secretion of RNA via extracellular vesicles is not only periodic throughout the asexual intraerythrocytic developmental cycle but is also highly conserved across P. falciparum isolates. We further demonstrate that the phases of RNA secreted via extracellular vesicles are discernibly shifted compared to those of the intracellular RNA within the secreting whole parasite. Finally, transcripts of genes with no known function during the asexual intraerythrocytic developmental cycle are enriched in PfEVs compared to the whole parasite. We conclude that the secretion of extracellular vesicles could be a putative posttranscriptional RNA regulation mechanism that is part of or synergise the classic RNA decay processes to maintain intracellular RNA levels in P. falciparum.Peer reviewe

Community-based rehabilitation program for cerebral PALSY (CP) children in North Uganda

Background: CP is a common neurologic disease in children, with a worldwide estimated prevalence of 93 million. Data on the African context are limited. Purpose: This study was aimed at evaluating the efficacy of a mixed outpatient/home physiotherapy program in children with CP admitted to St. Mary's Lacor Hospital (Gulu), the reference center of north Uganda. Methods: This is an observational, uncontrolled, prospective study. All children with CP (aged from 0.5 to 12 years) admitted in the Physiotherapy Unit from January to December 2017 were enrolled. A written consent form (English or Acholi language) was obtained from the mother/ caregiver. Each patient was evaluated at baseline and every two weeks for three months. CP sub-types were defined according to Surveillance of Cerebral Palsy in Europe classification. The child\ub4s abilities were staged through the Gross Motor Function Classification System Expanded and Revised (GMFCS-E&amp;R; scale from I to V, the higher the worse). Changes in motor function were measured through the 66-item version (GMFM-66; scores ranging from 0 to 100, the higher the better). At baseline and subsequent visits, Bobath treatment was applied for 30 minutes by an experienced physiotherapist, who trained the caregiver on customized home exercises following a diary prescription. The functional status reported by the caregiver and the overall compliance were assessed. Changes in GMFCS-E&amp;R and GMFM-66 at 6 and 12 weeks were recorded. The normality of score distributions was tested (Shapiro-Wilks). If confirmed, repeated ANOVA modeling was applied to scores across time points. Results: Fifty-two consecutive children were enrolled (mean age 2.2 years, range 0.5-9.9). Spastic bilateral (19 patients, 36%) and dystonic (16, 31%) were the most common CP sub-types. The main cause of CP were asphyxia during the delivery (26 cases, 50%) and cerebral malaria (10, 19%). Thirty-three/52 cases (67%) presented level V GMFCS-E&amp;R. GMFM-66 mean score at baseline was 19.86 range: 0-52.9. Seventeen/52 (33%) children were assessed at 6 and/or 12 weeks, while 35 (67%) missed at least three study visits (reasons: 28 transportation cost, 2 remote home, 4 other). In 16/17 (94%) patients home exercises were performed correctly. The GMFM-66 mean score increased from 14.8 at baseline to 20.4 and to 24.9 at 6 weeks (p=0.02) and 12 weeks (p=0.00), respectively. The improvement was observed irrespectively from CP sub-type or cause of disability. Conclusion(s): Although on a small number of patients, this study suggests that a mixed outpatient/home physiotherapy program can improve CP disability in compliant children treated in a developing country, like north Uganda. The high drop-out rate and its causes point towards the need for implementing local community programs and/or transport facilities. Implications: These results suggest that a mixed outpatient/home physiotherapy program can benefit children with CP living in developing countries and strengthen the need of a policy aimed at improving the access to the physiotherapy service. In addition, they confirm that neurological damage during the assisted delivery is the major cause of CP in this conte

Spatial Congruence or Mismatch Between Phylogenetic and Functional Structure of Seed Plants Along a Tropical Elevational Gradient: Different Traits Have Different Patterns

Compared to species richness, few studies have investigated the patterns and relationship of phylogenetic and functional structures along elevational gradients. Here, we used the general additive models to determine the trends of taxonomic diversity (species richness, SR), phylogenetic and functional diversity (PD and FD), phylogenetic structure net relatedness index (NRI), and functional structure net functional relatedness index (NFRI) of seed plants along the elevational gradient in Mount Kenya, a tropical mountain in Africa. We measured growth form, fruit type, maximum height, and maximum leaf size of each species, calculated the phylogenetic signal of each trait, and tested the Pearson correlation coefficients between NRI and NFRI of each trait. Our results showed that SR, PD, and FD decreased gradually along the elevational gradient. NRI exhibited a fluctuating pattern along the elevational gradient, while NFRI of the four functional traits showed noticeably different patterns. We concluded that the relationship between the phylogenetic and functional structures in different functional traits could be congruent or mismatched along the elevational gradient. Compared with relatively conservative categorical traits (e.g., growth form and fruit type), continuous traits (e.g., height and leaf size) have a random or convergent evolutionary pattern. Therefore, they could be more easily affected by the environment and possibly have higher phenotypic plasticity

Cyst nematode bio-communication with plants: implications for novel management approaches

Bio‐communication occurs when living organisms interact with each other, facilitated by the exchange of signals including visual, auditory, tactile and chemical. The most common form of bio‐communication between organisms is mediated by chemical signals, commonly referred to as ‘semiochemicals’, and it involves an emitter releasing the chemical signal that is detected by a receiver leading to a phenotypic response in the latter organism. The quality and quantity of the chemical signal released may be influenced by abiotic and biotic factors. Bio‐communication has been reported to occur in both above‐ and below‐ground interactions and it can be exploited for the management of pests, such as cyst nematodes, which are pervasive soil‐borne pests that cause significant crop production losses worldwide. Cyst nematode hatching and successful infection of hosts are biological processes that are largely influenced by semiochemicals including hatching stimulators, hatching inhibitors, attractants and repellents. These semiochemicals can be used to disrupt interactions between host plants and cyst nematodes. Advances in RNAi techniques such as host‐induced gene silencing to interfere with cyst nematode hatching and host location can also be exploited for development of synthetic resistant host cultivars. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

Non-O ABO blood group genotypes differ in their associations with Plasmodium falciparum rosetting and severe malaria

Blood group O is associated with protection against severe malaria and reduced size and stability of P. falciparum-host red blood cell (RBC) rosettes compared to non-O blood groups. Whether the non-O blood groups encoded by the specific ABO genotypes AO, BO, AA, BB and AB differ in their associations with severe malaria and rosetting is unknown. The A and B antigens are host RBC receptors for rosetting, hence we hypothesized that the higher levels of A and/or B antigen on RBCs from AA, BB and AB genotypes compared to AO/BO genotypes could lead to larger rosettes, increased microvascular obstruction and higher risk of malaria pathology. We used a case-control study of Kenyan children and in vitro adhesion assays to test the hypothesis that “double dose” non-O genotypes (AA, BB, AB) are associated with increased risk of severe malaria and larger rosettes than “single dose” heterozygotes (AO, BO). In the case-control study, compared to OO, the double dose genotypes consistently had higher odds ratios (OR) for severe malaria than single dose genotypes, with AB (OR 1.93) and AO (OR 1.27) showing most marked difference (p = 0.02, Wald test). In vitro experiments with blood group A-preferring P. falciparum parasites showed that significantly larger rosettes were formed with AA and AB host RBCs compared to OO, whereas AO and BO genotypes rosettes were indistinguishable from OO. Overall, the data show that ABO genotype influences P. falciparum rosetting and support the hypothesis that double dose non-O genotypes confer a greater risk of severe malaria than AO/BO heterozygosity

The mRNA content of plasma extracellular vesicles provides a window into molecular processes in the brain during cerebral malaria

The impact of cerebral malaria on the transcriptional profiles of cerebral tissues is difficult to study using noninvasive approaches. We isolated plasma extracellular vesicles (EVs) from patients with cerebral malaria and community controls and sequenced their mRNA content. Deconvolution analysis revealed that EVs from cerebral malaria are enriched in transcripts of brain origin. We ordered the patients with cerebral malaria based on their EV-transcriptional profiles from cross-sectionally collected samples and inferred disease trajectory while using healthy community controls as a starting point. We found that neuronal transcripts in plasma EVs decreased with disease trajectory, whereas transcripts from glial, endothelial, and immune cells increased. Disease trajectory correlated positively with severity indicators like death and was associated with increased VEGFA-VEGFR and glutamatergic signaling, as well as platelet and neutrophil activation. These data suggest that brain tissue responses in cerebral malaria can be studied noninvasively using EVs circulating in peripheral blood

Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis

BACKGROUND: Pneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes, but the burden of pneumococcal disease in low-income and middle-income countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the effect of 10-valent PCV on the incidence of pneumonia in Kenya. METHODS: We linked prospective hospital surveillance for clinically-defined WHO severe or very severe pneumonia at Kilifi County Hospital, Kenya, from 2002 to 2015, to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45 000 children younger than 5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January, 2011. In Kilifi, there was a three-dose catch-up campaign for infants (aged <1 year) and a two-dose catch-up campaign for children aged 1-4 years, between January and March, 2011. We estimated the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia through interrupted time-series analysis, accounting for seasonal and temporal trends. FINDINGS: Between May 1, 2002 and March 31, 2015, 44 771 children aged 2-143 months were admitted to Kilifi County Hospital. We excluded 810 admissions between January and March, 2011, and 182 admissions during nurses' strikes. In 2002-03, the incidence of admission with clinically-defined pneumonia was 2170 per 100 000 in children aged 2-59 months. By the end of the catch-up campaign in 2011, 4997 (61·1%) of 8181 children aged 2-11 months had received at least two doses of PCV10 and 23 298 (62·3%) of 37 416 children aged 12-59 months had received at least one dose. Across the 13 years of surveillance, the incidence of clinically-defined pneumonia declined by 0·5% per month, independent of vaccine introduction. There was no secular trend in the incidence of radiologically-confirmed pneumonia over 8 years of study. After adjustment for secular trend and season, incidence rate ratios for admission with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated temporally with PCV10 introduction and the catch-up campaign, were 0·52 (95% CI 0·32-0·86), 0·73 (0·54-0·97), and 0·63 (0·31-1·26), respectively. Immediately before PCV10 was introduced, the annual incidence of clinically-defined pneumonia was 1220 per 100 000; this value was reduced by 329 per 100 000 at the point of PCV10 introduction. INTERPRETATION: Over 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10. FUNDING: Gavi, The Vaccine Alliance and Wellcome Trust

Factors influencing implementation of the Ministry of Health-led private medicine retailer programmes on malaria in Kenya

<p>Abstract</p> <p>Background</p> <p>Kenya has experienced a number of retail sector initiatives aimed at improving access to antimalarial medicines. This study explored stakeholders' perceptions of the role of private medicine retailers (PMRs), the value and feasibility of programme goals, perceived programme impact, factors influencing implementation and recommendations in three districts of Kenya.</p> <p>Methods</p> <p>This study was part of a larger evaluation of PMR programmes, including quantitative and qualitative components. The qualitative research was conducted to assess implementation processes and actors' experiences in the programmes, through focus group discussions with trained PMRs and mothers of children under five years, and in-depth interviews with programme managers, trainers and co-trainers.</p> <p>Results</p> <p>PMRs were perceived to provide rapid cheap treatment for non-serious conditions and used as a deliberate and continuously evaluated choice between different treatment sources. All stakeholders supported programme goals and most PMRs described increased customer satisfaction, more rational purchasing of medicine stock and increased medicine sales after participation. Factors undermining programme implementation included a lack of MoH resources to train and monitor large numbers of PMRs, the relative instability of outlets, medicines stocked and retail personnel, the large number of proprietary brands and financial challenges to retailers in stocking antimalarial medicines, and their customers in buying them. Unambiguous national support and a broad range of strategies are important to strengthen the feasibility of change in OTC antimalarial use.</p> <p>Conclusions</p> <p>Understanding the context and implementation processes of PMR programmes and the perspectives of key actors are critical to identifying measures to support their effective implementation. Financial barriers underlie many described challenges, with important implications for policies on subsidies in this sector. In spite of barriers to implementation, increased exposure to programme activities promoted trust and improved relationships between PMRs and their clients and trainers, strengthening feasibility of such interventions. Public information can strengthen PMR training programmes by engaging local communities and may facilitate performance monitoring of PMRs by their clients.</p