Widening geographic range of Rift Valley fever disease clusters associated with climate change in East Africa.

BACKGROUND: Recent epidemiology of Rift Valley fever (RVF) disease in Africa suggests growing frequency and expanding geographic range of small disease clusters in regions that previously had not reported the disease. We investigated factors associated with the phenomenon by characterising recent RVF disease events in East Africa. METHODS: Data on 100 disease events (2008-2022) from Kenya, Uganda and Tanzania were obtained from public databases and institutions, and modelled against possible geoecological risk factors of occurrence including altitude, soil type, rainfall/precipitation, temperature, normalised difference vegetation index (NDVI), livestock production system, land-use change and long-term climatic variations. Decadal climatic variations between 1980 and 2022 were evaluated for association with the changing disease pattern. RESULTS: Of 100 events, 91% were small RVF clusters with a median of one human (IQR, 1-3) and three livestock cases (IQR, 2-7). These clusters exhibited minimal human mortality (IQR, 0-1), and occurred primarily in highlands (67%), with 35% reported in areas that had never reported RVF disease. Multivariate regression analysis of geoecological variables showed a positive correlation between occurrence and increasing temperature and rainfall. A 1°C increase in temperature and a 1-unit increase in NDVI, one months prior were associated with increased RVF incidence rate ratios of 1.20 (95% CI 1.1, 1.2) and 1.93 (95% CI 1.01, 3.71), respectively. Long-term climatic trends showed a significant decadal increase in annual mean temperature (0.12-0.3°C/decade, p<0.05), associated with decreasing rainfall in arid and semi-arid lowlands but increasing rainfall trends in highlands (p<0.05). These hotter and wetter highlands showed increasing frequency of RVF clusters, accounting for 76% and 43% in Uganda and Kenya, respectively. CONCLUSION: These findings demonstrate the changing epidemiology of RVF disease. The widening geographic range of disease is associated with climatic variations, with the likely impact of wider dispersal of virus to new areas of endemicity and future epidemics.

A qualitative assessment of influenza vaccine uptake among children in Kenya.

Background: Influenza is a significant contributor to acute respiratory infections (ARI), and children < 5 years are at increased risk of severe influenza disease. In Kenya the influenza vaccine is not included in the Kenya Expanded Programme on Immunization (KEPI). To inform roll-out of a national influenza vaccination program, we implemented an influenza vaccine demonstration project in Nakuru and Mombasa counties in Kenya from 2019 to 2021 and set out to establish factors driving influenza vaccine acceptance and hesitancy among caregivers of children aged 6-23 months. Methods: Using semi-structured questionnaires, we conducted eight focus group discussions among community members and twelve key informant interviews among healthcare workers to elicit both lay and expert opinions. Thematic analysis of the interviews was conducted using the World Health Organization's "3 Cs" model of vaccine hesitancy to determine reasons for acceptance or hesitancy of the influenza vaccine. Results: The influenza vaccine was well received among community members and healthcare workers though concerns were raised. Vaccine hesitancy was fuelled by misconceptions about reasons for introducing the vaccine (confidence), perceptions that influenza was not a serious disease (complacency) and administrative fees required at some facilities (convenience). Despite the use of various advocacy, communication and social mobilisation strategies targeted at educating the community on the influenza disease and importance of vaccination, there remained a perception of inadequate reach of the sensitization among some community members. Contextual factors such as the COVID-19 pandemic affected uptake, and parents expressed concern over the growing number of vaccines recommended for children. Conclusion: Despite lingering concerns, caregivers had their children vaccinated indicating that vaccine hesitancy exists, even among those who accepted the vaccine for their children. Efforts targeted at increasing confidence in and reducing misconceptions towards vaccines through effective communication strategies, are likely to lead to increased vaccine uptake.

Widening geographic range of Rift Valley fever disease clusters associated with climate change in East Africa.

Background: Recent epidemiology of Rift Valley fever (RVF) disease in Africa suggests growing frequency and expanding geographic range of small disease clusters in regions that previously had not reported the disease. We investigated factors associated with the phenomenon by characterizing recent RVF disease events in East Africa. Methods: Data on 100 disease events (2008 - 2022) from Kenya, Uganda, and Tanzania were obtained from public databases and institutions, and modeled against possible geo-ecological risk factors of occurrence including altitude, soil type, rainfall/precipitation, temperature, normalized difference vegetation index (NDVI), livestock production system, land-use change, and long-term climatic variations. Decadal climatic variations between 1980-2022 were evaluated for association with the changing disease pattern. Results: Of 100 events, 91% were small RVF clusters with a median of one human (IQR, 1-3) and 3 livestock cases (IQR, 2-7). These clusters exhibited minimal human mortality (IQR 0-1), and occurred primarily in highlands (67%), with 35% reported in areas that had never reported RVF disease. Multivariate regression analysis of geo-ecological variables showed a positive correlation between occurrence and increasing temperature and rainfall. A 1oC increase in temperature and 1-unit increase in NDVI, 1-3 months prior were associated with increased RVF incidence rate ratios (IRR) of 1.20 (95% CI 1.1,1.2) and 9.88 (95% CI 0.85, 119.52), respectively. Long-term climatic trends showed significant decadal increase in annual mean temperature (0.12 to 0.3oC/decade, P<0.05), associated with decreasing rainfall in arid and semi-arid lowlands but increasing rainfall trends in highlands (P<0.05). These hotter and wetter highlands showed increasing frequency of RVF clusters, accounting for 76% and 43% in Uganda and Kenya, respectively. Conclusion: These findings demonstrate the changing epidemiology of RVF disease. The widening geographic range of disease is associated with climatic variations, with the likely impact of wider dispersal of virus to new areas of endemicity and future epidemics. Key questions: What is already known on this topic?: Rift Valley fever is recognized for its association with heavy rainfall, flooding, and El Niño rains in the East African region. A growing body of recent studies has highlighted a shifting landscape of the disease, marked by an expanding geographic range and an increasing number of small RVF clusters.What this study adds: This study challenges previous beliefs about RVF, revealing that it predominantly occurs in small clusters rather than large outbreaks, and its association with El Niño is not as pronounced as previously thought. Over 65% of these clusters are concentrated in the highlands of Kenya and Uganda, with 35% occurring in previously unaffected regions, accompanied by an increase in temperature and total rainfall between 1980 and 2022, along with a rise in the annual number of rainy days. Notably, the observed rainfall increases are particularly significant during the short-rains season (October-December), aligning with a secondary peak in RVF incidence. In contrast, the lowlands of East Africa, where typical RVF epidemics occur, display smaller and more varied trends in annual rainfall.How this study might affect research, practice, or policy: The worldwide consequence of the expanding RVF cluster is the broader dispersion of the virus, leading to the establishment of new regions with virus endemicity. This escalation heightens the risk of more extensive extreme-weather-associated RVF epidemics in the future. Global public health institutions must persist in developing preparedness and response strategies for such scenarios. This involves the creation and approval of human RVF vaccines and therapeutics, coupled with a rapid distribution plan through regional banks.

Risk factors of adverse birth outcomes among a cohort of pregnant women in Coastal Kenya, 2017-2019.

INTRODUCTION: Adverse birth outcomes particularly preterm births and congenital anomalies, are the leading causes of infant mortality globally, and the burden is highest in developing countries. We set out to determine the frequency of adverse birth outcomes and the risk factors associated with such outcomes in a cohort of pregnant women in Kenya. METHODS: From October 2017 to July 2019, pregnant women < 28 weeks gestation were enrolled and followed up until delivery in three hospitals in coastal Kenya. Newborns were examined at delivery. Among women with birth outcome data, we assessed the frequency of congenital anomalies defined as gastroschisis, umbilical hernia, limb abnormalities and Trisomy 21, and adverse birth outcomes, defined as either stillbirth, miscarriage, preterm birth, small for gestational age, or microcephaly. We used log-binomial regression to identify maternal characteristics associated with the presence of at least one adverse outcome. RESULTS: Among the 2312 women enrolled, 1916 (82.9%) had birth outcome data. Overall, 402/1916 (20.9%; 95% confidence interval (CI): 19.1-22.8) pregnancies had adverse birth outcomes. Specifically, 66/1916 (3.4%; 95% CI: 2.7-4.4) were stillbirths, 34/1916 (1.8%; 95% CI: 1.2-2.4) were miscarriages and 23/1816 (1.2%; 95% CI: 0.8-1.9) had congenital anomalies. Among the participants with anthropometric measurements data, 142/1200 (11.8%; 95% CI: 10.1 - 13.8) were small for gestational age and among the participants with ultrasound records, 143/1711 (8.4%; 95% CI: 7.1-9.8) were preterm. Febrile illnesses in current pregnancy (adjusted risk ratio (aRR): 1.7; 95% CI: 1.1-2.8), a history of poor birth outcomes in prior pregnancy (aRR: 1.8; 95% CI: 1.3-2.4) and high blood pressure in pregnancy (aRR: 3.9, 95% CI: (1.7-9.2) were independently associated with adverse birth outcomes in a model that included age, education, human immunodeficiency virus status and high blood pressure at enrolment. CONCLUSION: We found similar rates of overall adverse birth outcomes, congenital anomalies, and small for gestational age but higher rates of stillbirths and lower rates of prematurity compared to the rates that have been reported in the sub-Saharan Africa region. However, the rates of adverse birth outcomes in this study were comparable to other studies conducted in Kenya. Febrile illnesses during the current pregnancy, previous history of poor birth outcomes and high blood pressure in pregnancy are predictive of an increased risk of adverse birth outcomes.

Correction: Experiences of doctoral students enrolled in a research fellowship program to support doctoral training in Africa (2014 to 2018): The Consortium for Advanced Research Training in Africa odyssey.

[This corrects the article DOI: 10.1371/journal.pone.0252863.].

Higher livestock abortion burden in arid and semi-arid lands, Kenya, 2019-2020.

Tracking livestock abortion patterns over time and across factors such as species and agroecological zones (AEZs) could inform policies to mitigate disease emergence, zoonoses risk, and reproductive losses. We conducted a year-long population-based active surveillance of livestock abortion between 2019 and 2020, in administrative areas covering 52% of Kenya's landmass and home to 50% of Kenya's livestock. Surveillance sites were randomly selected to represent all AEZs in the country. Local animal health practitioners electronically transmitted weekly abortion reports from each ward, the smallest administrative unit, to a central server, using a simple short messaging service (SMS). Data were analyzed descriptively by administrative unit, species, and AEZ to reveal spatiotemporal patterns and relationships with rainfall and temperature. Of 23,766 abortions reported in all livestock species, sheep and goats contributed 77%, with goats alone contributing 53%. Seventy-seven per cent (n = 18,280) of these abortions occurred in arid and semi-arid lands (ASALs) that primarily practice pastoralism production systems. While spatiotemporal clustering of cases was observed in May-July 2019 in the ASALs, there was a substantial seasonal fluctuation across AEZs. Kenya experiences high livestock abortion rates, most of which go unreported. We recommend further research to document the national true burden of abortions. In ASALs, studies linking pathogen, climate, and environmental surveillance are needed to assign livestock abortions to infectious or non-infectious aetiologies and conducting human acute febrile illnesses surveillance to detect any links with the abortions.

Comparing performance of year-round and campaign-mode influenza vaccination strategies among children aged 6-23 months in Kenya: 2019-2021.

INTRODUCTION: In 2016, the Kenya National Immunization Technical Advisory Group requested additional programmatic and cost effectiveness data to inform the choice of strategy for a national influenza vaccination program among children aged 6-23 months of age. In response, we conducted an influenza vaccine demonstration project to compare the performance of a year-round versus campaign-mode vaccination strategy. Findings from this demonstration project will help identify essential learning lessons for a national program. METHODS: We compared two vaccine delivery strategies: (i) a year-round vaccination strategy where influenza vaccines were administered throughout the year at health facilities. This strategy was implemented in Njoro sub-county in Nakuru (November 2019 to October 2021) and Jomvu sub-county in Mombasa (December 2019 to October 2021), (ii) a campaign-mode vaccination strategy where vaccines were available at health facilities over four months. This strategy was implemented in Nakuru North sub-county in Nakuru (June to September 2021) and Likoni sub-county in Mombasa (July to October 2021). We assessed differences in coverage, dropout rates, vaccine wastage, and operational needs. RESULTS: We observed similar performance between strategies in coverage of the first dose of influenza vaccine (year-round strategy 59.7 %, campaign strategy 63.2 %). The coverage obtained in the year-round sub-counties was similar (Njoro 57.4 %; Jomvu 63.1 %); however, more marked differences between campaign sub-counties were observed (Nakuru North 73.4 %; Likoni 55.2 %). The campaign-mode strategy exceeded the cold chain capacity of participating health facilities, requiring thrice monthly instead of once monthly deliveries, and was associated with a two-fold increase in workload compared to the year-round strategy (168 vaccines administered per day in the campaign strategy versus 83 vaccines administered per day in the year-round strategy). CONCLUSION: Although both strategies had similar coverage levels, the campaign-mode strategy was associated with considerable operational needs that could significantly impact the immunization program.

Costs of seasonal influenza vaccine delivery in a pediatric demonstration project for children aged 6-23 months - Nakuru and Mombasa Counties, Kenya, 2019-2021.

BACKGROUND: During November 2019-October 2021, a pediatric influenza vaccination demonstration project was conducted in four sub-counties in Kenya. The demonstration piloted two different delivery strategies: year-round vaccination and a four-month vaccination campaign. Our objective was to compare the costs of both delivery strategies. METHODS: Cost data were collected using standardized questionnaires and extracted from government and project accounting records. We reported total costs and costs per vaccine dose administered by delivery strategy from the Kenyan government perspective in 2021 US$. Costs were separated into financial costs (monetary expenditures) and economic costs (financial costs plus the value of existing resources). We also separated costs by administrative level (national, regional, county, sub-county, and health facility) and program activity (advocacy and social mobilization; training; distribution, storage, and waste management; service delivery; monitoring; and supervision). RESULTS: The total estimated cost of the pediatric influenza demonstration project was US$ 225,269 (financial) and US$ 326,691 (economic) for the year-round delivery strategy (30,397 vaccine doses administered), compared with US$ 214,753 (financial) and US$ 242,385 (economic) for the campaign strategy (25,404 doses administered). Vaccine purchase represented the largest proportion of costs for both strategies. Excluding vaccine purchase, the cost per dose administered was US$ 1.58 (financial) and US$ 5.84 (economic) for the year-round strategy and US$ 2.89 (financial) and US$ 4.56 (economic) for the campaign strategy. CONCLUSIONS: The financial cost per dose was 83% higher for the campaign strategy than the year-round strategy due to larger expenditures for advocacy and social mobilization, training, and hiring of surge staff for service delivery. However, the economic cost per dose was more comparable for both strategies (year-round 22% higher than campaign), balanced by higher costs of operating equipment and monitoring activities for the year-round strategy. These delivery cost data provide real-world evidence to inform pediatric influenza vaccine introduction in Kenya.

Resilience of routine childhood immunization services in two counties in Kenya in the face of the COVID-19 pandemic.

The recently emerged coronavirus disease 2019 (COVID-19) has caused considerable morbidity and mortality worldwide and disrupted health services. We describe the effect of the COVID-19 pandemic on utilization of childhood vaccination services during the pandemic. Using a mixed methods approach combining retrospective data review, a cross-sectional survey, focus group discussions among care givers and key informant interviews among nurses, we collected data between May and September 2021 in Mombasa and Nakuru counties. Overall, there was a <2 % decline in the number of vaccine doses administered during the pandemic period compared to the pre-pandemic period but this was statistically insignificant, both for the pentavalent-1 vaccine (ß = -0.013, p = 0.505) and the pentavalent-3 vaccine (ß = -0.012, p = 0.440). In government health facilities, there was 7.7 % reduction in the number of pentavalent-1 (ß = -0.08, p = 0.010) and 10.4 % reduction in the number of pentavalent-3 (ß = -0.11, p < 0.001) vaccine doses that were administered during the pandemic period. In non-government facilities, there was a 25.8 % increase in the number of pentavalent-1 (ß=0.23, p < 0.001) and 31.0 % increase in the number of pentavalent-3 (ß = -0.27, p < 0.001) vaccine doses that were administered facilities during the pandemic period. The strategies implemented to maintain immunization services during the pandemic period included providing messaging on the availability and importance of staying current with routine vaccination and conducting catch-up vaccinations and vaccination outreaches. Our findings suggest that the COVID-19 pandemic did not impact childhood vaccination services in Mombasa and Nakuru counties in Kenya. The private health facilities cushioned vaccination services against the effects of the pandemic and the strategies that were put in place by the ministry of health ensured continuation of vaccination services and encouraged uptake of the services during the pandemic period in the two counties in Kenya. These findings provide useful information to safeguard vaccination services during future pandemics.

Potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study.

BACKGROUND: Influenza is a major year-round cause of respiratory illness in Kenya, particularly in children under 5. Current influenza vaccines result in short-term, strain-specific immunity and were found in a previous study not to be cost-effective in Kenya. However, next-generation vaccines are in development that may have a greater impact and cost-effectiveness profile. METHODS: We expanded a model previously used to evaluate the cost-effectiveness of seasonal influenza vaccines in Kenya to include next-generation vaccines by allowing for enhanced vaccine characteristics and multi-annual immunity. We specifically examined vaccinating children under 5 years of age with improved vaccines, evaluating vaccines with combinations of increased vaccine effectiveness, cross-protection between strains (breadth) and duration of immunity. We evaluated cost-effectiveness using incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits (INMBs) for a range of values for the willingness-to-pay (WTP) per DALY averted. Finally, we estimated threshold per-dose vaccine prices at which vaccination becomes cost-effective. RESULTS: Next-generation vaccines can be cost-effective, dependent on the vaccine characteristics and assumed WTP thresholds. Universal vaccines (assumed to provide long-term and broad immunity) are most cost-effective in Kenya across three of four WTP thresholds evaluated, with the lowest median value of ICER per DALY averted ($263, 95% Credible Interval (CrI): $ - 1698, $1061) and the highest median INMBs. At a WTP of $623, universal vaccines are cost-effective at or below a median price of $5.16 per dose (95% CrI: $0.94, $18.57). We also show that the assumed mechanism underlying infection-derived immunity strongly impacts vaccine outcomes. CONCLUSIONS: This evaluation provides evidence for country-level decision makers about future next-generation vaccine introduction, as well as global research funders about the potential market for these vaccines. Next-generation vaccines may offer a cost-effective intervention to reduce influenza burden in low-income countries with year-round seasonality like Kenya.

Anthrax hotspot mapping in Kenya support establishing a sustainable two-phase elimination program targeting less than 6% of the country landmass.

Using data collected from previous (n = 86) and prospective (n = 132) anthrax outbreaks, we enhanced prior ecological niche models (ENM) and added kernel density estimation (KDE) approaches to identify anthrax hotspots in Kenya. Local indicators of spatial autocorrelation (LISA) identified clusters of administrative wards with a relatively high or low anthrax reporting rate to determine areas of greatest outbreak intensity. Subsequently, we modeled the impact of vaccinating livestock in the identified hotspots as a national control measure. Anthrax suitable areas included high agriculture zones concentrated in the western, southwestern and central highland regions, consisting of 1043 of 1450 administrative wards, covering 18.5% country landmass, and hosting 30% of the approximately 13 million cattle population in the country. Of these, 79 wards covering 5.5% landmass and hosting 9% of the cattle population fell in identified anthrax hotspots. The rest of the 407 administrative wards covering 81.5% of the country landmass, were classified as low anthrax risk areas and consisted of the expansive low agricultural arid and semi-arid regions of the country that hosted 70% of the cattle population, reared under the nomadic pastoralism. Modelling targeted annual vaccination of 90% cattle population in hotspot administrative wards reduced > 23,000 human exposures. These findings support an economically viable first phase of anthrax control program in low-income countries where the disease is endemic, that is focused on enhanced animal and human surveillance in burden hotspots, followed by rapid response to outbreaks anchored on public education, detection and treatment of infected humans, and ring vaccination of livestock. Subsequently, the global anthrax elimination program focused on sustained vaccination and surveillance in livestock in the remaining few hotspots for a prolonged period (> 10 years) may be implemented.

Outbreak of Middle East Respiratory Syndrome Coronavirus in Camels and Probable Spillover Infection to Humans in Kenya.

The majority of Kenya's > 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0−24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April−September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya.

Imported SARS-COV-2 Variants of Concern Drove Spread of Infections Across Kenya During the Second Year of the Pandemic.

Background: Using classical and genomic epidemiology, we tracked the COVID-19 pandemic in Kenya over 23 months to determine the impact of SARS-CoV-2 variants on its progression. Methods: SARS-CoV-2 surveillance and testing data were obtained from the Kenya Ministry of Health, collected daily from 306 health facilities. COVID-19-associated fatality data were also obtained from these health facilities and communities. Whole SARS-CoV-2 genome sequencing were carried out on 1241 specimens. Results: Over the pandemic duration (March 2020 - January 2022) Kenya experienced five waves characterized by attack rates (AR) of between 65.4 and 137.6 per 100,000 persons, and intra-wave case fatality ratios (CFR) averaging 3.5%, two-fold higher than the national average COVID-19 associated CFR. The first two waves that occurred before emergence of global variants of concerns (VoC) had lower AR (65.4 and 118.2 per 100,000). Waves 3, 4, and 5 that occurred during the second year were each dominated by multiple introductions each, of Alpha (74.9% genomes), Delta (98.7%), and Omicron (87.8%) VoCs, respectively. During this phase, government-imposed restrictions failed to alleviate pandemic progression, resulting in higher attack rates spread across the country. Conclusions: The emergence of Alpha, Delta, and Omicron variants was a turning point that resulted in widespread and higher SARS-CoV-2 infections across the country.

Near-Complete SARS-CoV-2 Seroprevalence among Rural and Urban Kenyans despite Significant Vaccine Hesitancy and Refusal.

Considering the early inequity in global COVID-19 vaccine distribution, we compared the level of population immunity to SARS-CoV-2 with vaccine uptake and refusal between rural and urban Kenya two years after the pandemic onset. A population-based seroprevalence study was conducted in the city of Nairobi (n = 781) and a rural western county (n = 810) between January and February 2022. The overall SARS-CoV-2 seroprevalence was 90.2% (95% CI, 88.6−91.2%), including 96.7% (95% CI, 95.2−97.9%) among urban and 83.6% (95% CI, 80.6−86.0%) among rural populations. A comparison of immunity profiles showed that >50% of the rural population were strongly immunoreactive compared to <20% of the urban population, suggesting more recent infections or vaccinations in the rural population. More than 45% of the vaccine-eligible (≥18 years old) persons had not taken a single dose of the vaccine (hesitancy), including 47.6% and 46.9% of urban and rural participants, respectively. Vaccine refusal was reported in 19.6% of urban and 15.6% of rural participants, attributed to concern about vaccine safety (>75%), inadequate information (26%), and concern about vaccine effectiveness (9%). Less than 2% of vaccine refusers cited religious or cultural beliefs. These findings indicate that despite vaccine inequity, hesitancy, and refusal, herd immunity had been achieved in Kenya and likely other African countries by early 2022, with natural infections likely contributing to most of this immunity. However, vaccine campaigns should be sustained due to the need for repeat boosters associated with waning of SARS-CoV-2 immunity and emergence of immune-evading virus variants.

Histopathology Is Key to Interpreting Multiplex Molecular Test Results From Postmortem Minimally Invasive Tissue Samples.

BACKGROUND: Minimally invasive tissue sampling (MITS) is an alternative to complete autopsy for determining causes of death. Multiplex molecular testing performed on MITS specimens poses challenges of interpretation, due to high sensitivity and indiscriminate detection of pathogenic, commensal, or contaminating microorganisms. METHODS: MITS was performed on 20 deceased children with respiratory illness, at 10 timepoints up to 88 hours postmortem. Samples were evaluated by multiplex molecular testing on fresh tissues by TaqMan® Array Card (TAC) and by histopathology, special stains, immunohistochemistry (IHC), and molecular testing (PCR) on formalin-fixed, paraffin-embedded (FFPE) tissues. Results were correlated to determine overall pathologic and etiologic diagnoses and to guide interpretation of TAC results. RESULTS: MITS specimens collected up to 3 days postmortem were adequate for histopathologic evaluation and testing. Seven different etiologic agents were detected by TAC in 10 cases. Three cases had etiologic agents detected by FFPE or other methods and not TAC; 2 were agents not present on TAC, and 2 were streptococci that may have been species other than those present on TAC. Result agreement was 43% for TAC and IHC or PCR, and 69% for IHC and PCR. Extraneous TAC results were common, especially when aspiration was present. CONCLUSIONS: TAC can be performed on MITS up to 3 days after death with refrigeration and provides a sensitive method for detection of pathogens but requires careful interpretation in the context of clinicoepidemiologic and histopathologic findings. Interpretation of all diagnostic tests in aggregate to establish overall case diagnoses maximizes the utility of TAC in MITS.

Effect of Time Since Death on Multipathogen Molecular Test Results of Postmortem Specimens Collected Using Minimally Invasive Tissue Sampling Techniques.

BACKGROUND: We used postmortem minimally invasive tissue sampling (MITS) to assess the effect of time since death on molecular detection of pathogens among respiratory illness-associated deaths. METHODS: Samples were collected from 20 deceased children (aged 1-59 months) hospitalized with respiratory illness from May 2018 through February 2019. Serial lung and/or liver and blood samples were collected using MITS starting soon after death and every 6 hours thereafter for up to 72 hours. Bodies were stored in the mortuary refrigerator for the duration of the study. All specimens were analyzed using customized multipathogen TaqMan® array cards (TACs). RESULTS: We identified a median of 3 pathogens in each child's lung tissue (range, 1-8; n = 20), 3 pathogens in each child's liver tissue (range, 1-4; n = 5), and 2 pathogens in each child's blood specimen (range, 0-4; n = 5). Pathogens were not consistently detected across all collection time points; there was no association between postmortem interval and the number of pathogens detected (P = .43) and no change in TAC cycle threshold value over time for pathogens detected in lung tissue. Human ribonucleoprotein values indicated that specimens collected were suitable for testing throughout the study period. CONCLUSIONS: Results suggest that lung, liver, and blood specimens can be collected using MITS procedures up to 4 days after death in adequately preserved bodies. However, inconsistent pathogen detection in samples needs careful consideration before drawing definitive conclusions on the etiologic causes of death.

Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.

BACKGROUND: How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes. METHODS: We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed. RESULTS: The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage. CONCLUSION: The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.

High seroprevalence of SARS-CoV-2 but low infection fatality ratio eight months after introduction in Nairobi, Kenya.

BACKGROUND: The lower than expected COVID-19 morbidity and mortality in Africa has been attributed to multiple factors, including weak surveillance. This study estimated the burden of SARS-CoV-2 infections eight months into the epidemic in Nairobi, Kenya. METHODS: A population-based, cross-sectional survey was conducted using multi-stage random sampling to select households within Nairobi in November 2020. Sera from consenting household members were tested for antibodies to SARS-CoV-2. Seroprevalence was estimated after adjusting for population structure and test performance. Infection fatality ratios (IFRs) were calculated by comparing study estimates with reported cases and deaths. RESULTS: Among 1,164 individuals, the adjusted seroprevalence was 34.7% (95% CI 31.8-37.6). Half of the enrolled households had at least one positive participant. Seropositivity increased in more densely populated areas (spearman's r=0.63; p=0.009). Individuals aged 20-59 years had at least two-fold higher seropositivity than those aged 0-9 years. The IFR was 40 per 100,000 infections, with individuals ≥60 years old having higher IFRs. CONCLUSION: Over one-third of Nairobi residents had been exposed to SARS-CoV-2 by November 2020, indicating extensive transmission. However, the IFR was >10-fold lower than that reported in Europe and the USA, supporting the perceived lower morbidity and mortality in sub-Saharan Africa.