Effect of Maternally Derived Anti-protein and Anticapsular IgG Antibodies on the Rate of Acquisition of Nasopharyngeal Carriage of Pneumococcus in Newborns

BACKGROUND: In developing countries, introduction of pneumococcal conjugate vaccine has not eliminated circulation of vaccine serotypes. Vaccinating pregnant mothers to increase antibody concentrations in their newborn infants may reduce the acquisition of pneumococcal carriage and subsequent risk of disease. We explored the efficacy of passive immunity, attributable to anti-protein and anticapsular pneumococcal antibodies, against acquisition of carriage. METHODS: We examined the rate of nasopharyngeal acquisition of pneumococci in the first 90 days of life associated with varying anticapsular and anti-protein antibody concentrations in infant cord/maternal venous blood in Kilifi, Kenya. We used multivariable Cox proportional hazard models to estimate continuous functions relating acquisition of nasopharyngeal carriage to the concentration of maternally derived antibody. RESULTS: Cord blood or maternal venous samples were collected from 976 mother-infant pairs. Pneumococci were acquired 561 times during 33,905 person-days of follow-up. Increasing concentrations of anti-protein antibodies were associated with either a reduction (PhtD1, PspAFam2, Spr0096, StkP) or, paradoxically, an increase (CbpA, LytC, PcpA, PiaA, PspAFam1, RrgBT4) in acquisition rate. We observed a nonsignificant reduction in the incidence of homologous carriage acquisition with high concentrations of maternally derived anticapsular antibodies to 5 serotypes (6A, 6B, 14, 19F, and 23F). CONCLUSION: The protective efficacy of several anti-protein antibodies supports the strategy of maternal vaccination to protect young infants from carriage and invasive disease. We were not able to demonstrate that passive anticapsular antibodies were protective against carriage acquisition at naturally occurring concentrations though it remains possible they may do so at the higher concentrations elicited by vaccination

Effect of Maternally Derived Anti-protein and Anticapsular IgG Antibodies on the Rate of Acquisition of Nasopharyngeal Carriage of Pneumococcus in Newborns.

Background: In developing countries, introduction of pneumococcal conjugate vaccine has not eliminated circulation of vaccine serotypes. Vaccinating pregnant mothers to increase antibody concentrations in their newborn infants may reduce the acquisition of pneumococcal carriage and subsequent risk of disease. We explored the efficacy of passive immunity, attributable to anti-protein and anticapsular pneumococcal antibodies, against acquisition of carriage. Methods: We examined the rate of nasopharyngeal acquisition of pneumococci in the first 90 days of life associated with varying anticapsular and anti-protein antibody concentrations in infant cord/maternal venous blood in Kilifi, Kenya. We used multivariable Cox proportional hazard models to estimate continuous functions relating acquisition of nasopharyngeal carriage to the concentration of maternally derived antibody. Results: Cord blood or maternal venous samples were collected from 976 mother-infant pairs. Pneumococci were acquired 561 times during 33,905 person-days of follow-up. Increasing concentrations of anti-protein antibodies were associated with either a reduction (PhtD1, PspAFam2, Spr0096, StkP) or, paradoxically, an increase (CbpA, LytC, PcpA, PiaA, PspAFam1, RrgBT4) in acquisition rate. We observed a nonsignificant reduction in the incidence of homologous carriage acquisition with high concentrations of maternally derived anticapsular antibodies to 5 serotypes (6A, 6B, 14, 19F, and 23F). Conclusion: The protective efficacy of several anti-protein antibodies supports the strategy of maternal vaccination to protect young infants from carriage and invasive disease. We were not able to demonstrate that passive anticapsular antibodies were protective against carriage acquisition at naturally occurring concentrations though it remains possible they may do so at the higher concentrations elicited by vaccination

Whole genome phylogenetic investigation of a West Nile virus strain isolated from a tick sampled from livestock in north eastern Kenya

BACKGROUND:West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neurological disease in humans and horses. Mosquitoes are the traditional vectors for WNV; however, the virus has also been isolated from tick species in North Africa and Europe which could be a means of introduction and spread of the virus over long distances through migratory birds. Although WNV has been isolated in mosquitoes in Kenya, paucity of genetic and pathogenicity data exists. We previously reported the isolation of WNV from ticks collected from livestock and wildlife in Ijara District of Kenya, a hotspot for arbovirus activity. Here we report the full genome sequence and phylogenetic investigation of their origin and relation to strains from other regions. METHODS: A total of 10,488 ticks were sampled from animal hosts, classified to species and processed in pools of up to eight ticks per pool. Virus screening was performed by cell culture, RT-PCR and sequencing. Phylogenetic analysis was carried out to determine the evolutionary relationships of our isolate. RESULTS: Among other viruses, WNV was isolated from a pool of Rhipicephalus pulchellus sampled from cattle, sequenced and submitted to GenBank (Accession number: KC243146). Comparative analysis with 27 different strains revealed that our isolate belongs to lineage 1 and clustered relatively closely to isolates from North Africa and Europe, Russia and the United States. Overall, Bayesian analysis based on nucleotide sequences showed that lineage 1 strains including the Kenyan strain had diverged 200years ago from lineage 2 strains of southern Africa. Ijara strain collected from a tick sampled on livestock was closest to another Kenyan strain and had diverged 20years ago from strains detected in Morocco and Europe and 30years ago from strains identified in the USA. CONCLUSION: To our knowledge, this is the first characterized WNV strain isolated from R. pulchellus. The epidemiological role of this tick in WNV transmission and dissemination remains equivocal but presents tick verses mosquito virus transmission has been neglected. Genetic data of this strain suggest that lineage 1 strains from Africa could be dispersed through tick vectors by wild migratory birds to Europe and beyond

Rates of acquisition of pneumococcal colonization and transmission probabilities, by serotype, among newborn infants in Kilifi District, Kenya.

BACKGROUND: Herd protection and serotype replacement disease following introduction of pneumococcal conjugate vaccine (PCV) are attributable to the vaccine's impact on colonization. Prior to vaccine introduction in Kenya, we did an epidemiological study to estimate the rate of pneumococcal acquisition, by serotype, in an uncolonized population. METHODS: Nasopharyngeal swab specimens were taken from newborns aged ≤ 7 days and weekly thereafter for 13 weeks. Parents, and siblings aged <10 years, were swabbed at monthly intervals. Swabs were transported in skim milk-tryptone-glucose-glycerin and cultured on gentamicin blood agar. Pneumococci were serotyped by the Quellung reaction. We used survival analysis and Cox regression analysis to examine serotype-specific acquisition rates and risk factors and calculated transmission probabilities from the pattern of acquisitions within the family. RESULTS: Of 1404 infants recruited, 887 were colonized by 3 months of age, with the earliest acquisition detected on the first day of life. The median time to acquisition was 38.5 days. The pneumococcal acquisition rate was 0.0189 acquisitions/day (95% confidence interval, .0177-.0202 acquisitions/day). Serotype-specific acquisition rates varied from 0.00002-0.0025 acquisitions/day among 49 different serotypes. Season, coryza, and exposure to cigarettes, cooking fumes, and other children in the home were each significant risk factors for acquisition. The transmission probability per 30-day duration of contact with a carrier was 0.23 (95% CI, .20-.26). CONCLUSIONS: Newborn infants in Kilifi have high rates of nasopharyngeal acquisition of pneumococci. Half of these acquisitions involve serotypes not included in any current vaccine. Several risk factors are modifiable through intervention. Newborns represent a consistent population of pneumococcus-naive individuals in which to estimate the impact of PCV on transmission

Rates of acquisition and clearance of pneumococcal serotypes in the nasopharynges of children in Kilifi District, Kenya.

BACKGROUND: To understand and model the impact of pneumococcal conjugate vaccines at the population level, we need to know the transmission dynamics of individual pneumococcal serotypes. We estimated serotype-specific clearance and acquisition rates of nasopharyngeal colonization among Kenyan children. METHODS: Children aged 3-59 months who were identified as carriers in a cross-sectional survey were followed-up approximately 1, 2, 4, 8, 16, and 32 days later and monthly thereafter until culture of 2 consecutive swabs yielded an alternative serotype or no pneumococcus. Serotype-specific clearance rates were estimated by exponential regression of interval-censored carriage durations. Duration was estimated as the reciprocal of the clearance rate, and acquisition rates were estimated on the basis of prevalence and duration, assuming an equilibrium state. RESULTS: Of 2840 children sampled between October 2006 and December 2008, 1868 were carriers. The clearance rate was 0.032 episodes/day (95% confidence interval [CI], .030-.034), for a carriage duration of 31.3 days, and the rate varied by serotype (P< .0005). Carriage durations for the 28 serotypes with ≥ 10 carriers ranged from 6.7 to 50 days. Clearance rates increased with year of age, adjusted for serotype (hazard ratio, 1.21; 95% CI, 1.15-1.27). The acquisition rate was 0.061 episodes/day (95% CI, .055-.067), which did not vary with age. Serotype-specific acquisition rates varied from 0.0002 to 0.0022 episodes/day. Serotype-specific acquisition rates correlated with prevalence (r=0.91; P< .00005) and with acquisition rates measured in a separate study involving 1404 newborns in Kilifi (r=0.87; P< .00005). CONCLUSIONS: The large sample size and short swabbing intervals provide a precise description of the prevalence, duration, and acquisition of carriage of 28 pneumococcal serotypes. In Kilifi, young children experience approximately 8 episodes of carriage per year. The declining prevalence with age is attributable to increasing clearance rates

Childhood acute illness and nutrition (CHAIN) network: A protocol for a multi-site prospective cohort study to identify modifiable risk factors for mortality among acutely ill children in Africa and Asia

Introduction: Children admitted to hospitals in resource-poor settings remain at risk of both inpatient and post-discharge mortality. While known risk factors such as young age and nutritional status can identify children at risk, they do not provide clear mechanistic targets for intervention. The Childhood Acute Illness and Nutrition (CHAIN) cohort study aims to characterise the biomedical and social risk factors for mortality in acutely ill children in hospitals and after discharge to identify targeted interventions to reduce mortality.Methods and analysis: The CHAIN network is currently undertaking a multi-site, prospective, observational cohort study, enrolling children aged 1 week to 2 years at admission to hospitals at nine sites located in four African and two South Asian countries. The CHAIN Network supports the sites to provide care according to national and international guidelines. Enrolment is stratified by anthropometric status and children are followed throughout hospitalisation and for 6 months after discharge. Detailed clinical, demographic, anthropometric, laboratory and social exposures are assessed. Scheduled visits are conducted at 45, 90 and 180 days after discharge. Blood, stool and rectal swabs are collected at enrolment, hospital discharge and follow-up. The primary outcome is inpatient or post-discharge death. Secondary outcomes include readmission to hospital and nutritional status after discharge. Cohort analysis will identify modifiable risks, children with distinct phenotypes, relationships between factors and mechanisms underlying poor outcomes that may be targets for intervention. A nested case-control study examining infectious, immunological, metabolic, nutritional and other biological factors will be undertaken.Ethics and dissemination: This study protocol was reviewed and approved primarily by the Oxford Tropical Research Ethics Committee, and the institutional review boards of all partner sites. The study is being externally monitored. Results will be published in open access peer-reviewed scientific journals and presented to academic and policy stakeholders

Serological evidence of Flavivirus circulation in human populations in Northern Kenya : an assessment of disease risk 2016-2017

BACKGROUND: Yellow fever, Dengue, West Nile and Zika viruses are re-emerging mosquito-borne Flaviviruses of public health concern. However, the extent of human exposure to these viruses and associated disease burden in Kenya and Africa at large remains unknown. We assessed the seroprevalence of Yellow fever and other Flaviviruses in human populations in West Pokot and Turkana Counties of Kenya. These areas border Uganda, South Sudan and Ethiopia where recent outbreaks of Yellow fever and Dengue have been reported, with possibility of spillover to Kenya. METHODOLOGY: Human serum samples collected through a cross-sectional survey in West Pokot and Turkana Counties were screened for neutralizing antibodies to Yellow fever, Dengue-2, West Nile and Zika virus using the Plaque Reduction Neutralization Test (PRNT). Seroprevalence was compared by county, site and important human demographic characteristics. Adjusted odds ratios (aOR) were estimated using Firth logistic regression model. RESULTS: Of 877 samples tested, 127 neutralized with at least one of the four flaviviruses (14.5, 95% CI 12.3–17.0%), with a higher proportion in Turkana (21.1%, n = 87/413) than in West Pokot (8.6%, n = 40/464). Zika virus seroprevalence was significantly higher in West Pokot (7.11%) than in Turkana County (0.24%; χ 2 P < 0.0001). A significantly higher Yellow fever virus seroprevalence was also observed in Turkana (10.7%) compared to West Pokot (1.29%; χ 2 P < 0.0001). A high prevalence of West Nile virus was detected in Turkana County only (10.2%) while Dengue was only detected in one sample, from West Pokot. The odds of infection with West Nile virus was significantly higher in males than in females (aOR = 2.55, 95% CI 1.22–5.34). Similarly, the risk of Zika virus infection in West Pokot was twice higher in males than females (aOR = 2.01, 95% CI 0.91–4.41). CONCLUSION: Evidence of neutralizing antibodies to West Nile and Zika viruses indicates that they have been circulating undetected in human populations in these areas. While the observed Yellow Fever prevalence in Turkana and West Pokot Counties may imply virus activity, we speculate that this could also be as a result of vaccination following the Yellow Fever outbreak in the Omo river valley, South Sudan and Uganda across the borderNational Institutes of Health (NIH), UK Aid from the UK Government, Swedish International Development Cooperation Agency (Sida), Swiss Agency for Development and Cooperation (SDC) and the Kenyan Government.http://www.virologyj.compm2020Medical Virolog

Seroprevalence of Crimean Congo hemorrhagic fever virus in Ijara District, Kenya

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease mainly affecting pastoralists who come in contact with animals infested with Hyalomma ticks, which are the key vectors of CCHF virus (CCHFV). CCHFV has been detected among these ticks in parts of North Eastern Kenya. This study aimed to identify acute cases of CCHF, and to determine the extent of previous exposure to CCHFV in an outpatient population attending Sangailu and Ijara health centers, Ijara District, North Eastern Kenya, presenting with acute febrile illnesses. A total of 517 human serum samples were collected from these patients. The samples were screened for the presence of IgM and IgG antibodies to CCHF using CCCHF-IgG and IgM ELISA test kits. A multivariable logistic regression model was used to investigate the risk factors associated with evidence of exposure to CCHFV. A single patient tested positive for anti-CCHF IgM, while 96 were positive for anti-CCHF IgG. The seroprevalence of CCHFV was 23% in Sangailu and 14% in Ijara. Most exposed persons were aged 40–49 years. The likelihood of exposure was highest among farmers (29%). Age, location, and contact with donkeys were significantly associated with exposure to CCHFV. Acute CCHFV infections could be occurring without being detected in this population. This study confirms human exposure to CCHF virus in Ijara District, Kenya, and identifies several significant risk factors associated with exposure to CCHFV.Google.org, the philanthropic arm of Google.http://www.liebertpub.com/publication.aspx?pub_id=6

Plant resting site preferences and parity rates among the vectors of Rift Valley Fever in northeastern Kenya

Background Mosquito lifespan can influence the circulation of disease causing pathogens because it affects the time available for infection and transmission. The life-cycle of mosquitoes is determined by intrinsic and environmental factors, which can include the availability of hosts and suitable resting environments that shelter mosquitoes from extreme temperature and desiccating conditions. This study determined the parity rates (an indirect measure of survival) and plant resting preference of vectors of Rift Valley fever (RVF) in northeastern Kenya. Methods Resting mosquitoes were trapped during the rainy and the dry season using a Prokopack aspirator from vegetation, whereas general adult populations were trapped using CDC light traps. At each site, sampling was conducted within a 1 km2 area, subdivided into 500 × 500 m quadrants and four 250 × 250 m sub-quadrants from which two were randomly selected as sampling units. In each sampling unit, plants were randomly selected for aspiration of mosquitoes. Only Aedes mcintoshi and Ae. ochraceus were dissected to determine parity rates while all mosquito species were used to assess plant resting preference. Results Overall, 1124 (79 %, 95 % CI = 76.8–81.1 %) mosquitoes were parous. There was no significant difference in the number of parous Ae. mcintoshi and Ae. ochraceus. Parity was higher in the rainy season than in the dry season. Daily survival rate was estimated to be 0.93 and 0.92 among Ae. ochraceus and Ae. mcintoshi, respectively. Duosperma kilimandscharicum was the most preferred plant species with the highest average capture of primary (3.64) and secondary (5.83) vectors per plant, while Gisekia africana was least preferred. Conclusion Survival rate of each of the two primary vectors of RVF reported in this study may provide an indication that these mosquitoes can potentially play important roles in the circulation of diseases in northern Kenya. Resting preference of the mosquitoes in vegetation may influence their physiology and enhance longevity. Thus, areas with such vegetation may be associated with an increased risk of transmission of arboviruses to livestock and humans