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

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

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

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

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

Distribution and abundance of key vectors of Rift Valley fever and other arboviruses in two ecologically distinct counties in Kenya

Background Rift Valley fever (RVF) is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences. Humans become infected through mosquito bites and contact with infected livestock. The virus is maintained between outbreaks through vertically infected eggs of the primary vectors of Aedes species which emerge following rains with extensive flooding. Infected female mosquitoes initiate transmission among nearby animals, which amplifies virus, thereby infecting more mosquitoes and moving the virus beyond the initial point of emergence. With each successive outbreak, RVF has been found to expand its geographic distribution to new areas, possibly driven by available vectors. The aim of the present study was to determine if RVF virus (RVFV) transmission risk in two different ecological zones in Kenya could be assessed by looking at the species composition, abundance and distribution of key primary and secondary vector species and the level of virus activity. Methodology Mosquitoes were trapped during short and long rainy seasons in 2014 and 2015 using CO2 baited CDC light traps in two counties which differ in RVF epidemic risk levels(high risk Tana-River and low risk Isiolo),cryo-preserved in liquid nitrogen, transported to the laboratory, and identified to species. Mosquito pools were analyzed for virus infection using cell culture screening and molecular analysis. Findings Over 69,000 mosquitoes were sampled and identified as 40 different species belonging to 6 genera (Aedes, Anopheles, Mansonia, Culex, Aedeomyia, Coquillettidia). The presence and abundance of Aedes mcintoshi and Aedes ochraceus, the primary mosquito vectors associated with RVFV transmission in outbreaks, varied significantly between Tana-River and Isiolo. Ae. mcintoshi was abundant in Tana-River and Isiolo but notably, Aedes ochraceus found in relatively high numbers in Tana-River (n = 1,290), was totally absent in all Isiolo sites. Fourteen virus isolates including Sindbis, Bunyamwera, and West Nile fever viruses were isolated mostly from Ae. mcintoshi sampled in Tana-River. RVFV was not detected in any of the mosquitoes. Conclusion This study presents the geographic distribution and abundance of arbovirus vectors in two Kenyan counties, which may assist with risk assessment for mosquito borne diseases

Detection of rift valley Fever virus interepidemic activity in some hotspot areas of kenya by sentinel animal surveillance, 2009-2012

Rift Valley fever virus causes an important zoonotic disease of humans and small ruminants in Eastern Africa and is spread primarily by a mosquito vector. In this region, it occurs as epizootics that typically occur at 5–15-year intervals associated with unusual rainfall events. It has hitherto been known that the virus is maintained between outbreaks in dormant eggs of the mosquito vector and this has formed the basis of understanding of the epidemiology and control strategies of the disease. We show here that seroconversion and sporadic acute disease do occur during the interepidemic periods (IEPs) in the absence of reported cases in livestock or humans. The finding indicates that previously undetected low-level virus transmission during the IEPs does occur and that epizootics may also be due to periodic expansion of mosquito vectors in the presence of both circulating virus and naïve animals

The Prevalence and Risk Factors for Pneumococcal Colonization of the Nasopharynx among Children in Kilifi District, Kenya

BACKGROUND: Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine-serotype pneumococci but increase in the carriage of non-vaccine serotypes. We studied the epidemiology of carriage among children 3-59 months old before vaccine introduction in Kilifi, Kenya. METHODS: In a rolling cross-sectional study from October 2006 to December 2008 we approached 3570 healthy children selected at random from the population register of the Kilifi Health and Demographic Surveillance System and 134 HIV-infected children registered at a specialist clinic. A single nasopharyngeal swab was transported in STGG and cultured on gentamicin blood agar. A single colony of pneumococcus was serotyped by Quellung reaction. RESULTS: Families of 2840 children in the population-based sample and 99 in the HIV-infected sample consented to participate; carriage prevalence was 65.8% (95% CI, 64.0-67.5%) and 76% (95% CI, 66-84%) in the two samples, respectively. Carriage prevalence declined progressively with age from 79% at 6-11 months to 51% at 54-59 months (p<0.0005). Carriage was positively associated with coryza (Odds ratio 2.63, 95%CI 2.12-3.25) and cough (1.55, 95%CI 1.26-1.91) and negatively associated with recent antibiotic use (0.53 95%CI 0.34-0.81). 53 different serotypes were identified and 42% of isolates were of serotypes contained in the 10-valent PCV. Common serotypes declined in prevalence with age while less common serotypes did not. CONCLUSION: Carriage prevalence in children was high, serotypes were diverse, and the majority of strains were of serotypes not represented in the 10-valent PCV. Vaccine introduction in Kenya will provide a natural test of virulence for the many circulating non-vaccine serotypes