Profile: The Kenya Multi-Site Serosurveillance (KEMIS) collaboration

The Kenya Multi Site Serosurveillance (KEMIS) collaboration set out to implement an integrated, nationally representative, population-based program of serological surveillance for past infection for a number of important infectious diseases in Kenya. The project started in December 2021 and built on a portfolio of SARS-CoV-2 research conducted in 2020 and 2021. In this profile paper, we describe the background of the KEMIS collaboration, its aim and objectives, the Health and Demographic Surveillance System sites that were involved in data collection, and the key activities undertaken. We also explain how we established governance and management of the KEMIS collaboration, and reflect on opportunities, challenges, lessons learned, and future directions.</ns4:p

A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania

<div><p>Introduction</p><p>In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics. The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment.</p><p>Methods</p><p>We conducted a year-long exploratory study of fever syndrome among patients ≥ 1 year if age, presenting to clinical settings with an axillary temperature of ≥37.5°C and symptomatic onset of ≤5 days. Blood and naso-pharyngeal/oral-pharyngeal (NP/OP) specimens were collected and analyzed, respectively, using AFI and respiratory TaqMan Array Cards (TAC) for multi-pathogen detection of 57 potential causative agents. Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection.</p><p>Results</p><p>From 15 September 2014–13 September 2015, 1007 febrile patients were enrolled, and 997 contributed an epidemiologic survey, including: 14% (n = 139) 1<5yrs, 19% (n = 186) 5-14yrs, and 67% (n = 672) ≥15yrs. AFI TAC and respiratory TAC were performed on 842 whole blood specimens and 385 NP/OP specimens, respectively. Of the 57 agents surveyed, <i>Plasmodium</i> was the most common agent detected. AFI TAC detected nucleic acid for one or more of seven microbial agents in 49% of AFI blood samples, including: <i>Plasmodium</i> (47%), <i>Leptospira</i> (3%), <i>Bartonella</i> (1%), <i>Salmonella enterica</i> (1%), <i>Coxiella burnetii</i> (1%), <i>Rickettsia</i> (1%), and West Nile virus (1%). Respiratory TAC detected nucleic acid for 24 different microbial agents, including 12 viruses and 12 bacteria. The most common agents detected among our surveyed population were: <i>Haemophilus influenzae</i> (67%), <i>Streptococcus pneumoniae</i> (55%), <i>Moraxella catarrhalis</i> (39%), <i>Staphylococcus aureus</i> (37%), <i>Pseudomonas aeruginosa</i> (36%), Human Rhinovirus (25%), influenza A (24%), <i>Klebsiella pneumoniae</i> (14%), Enterovirus (15%) and group A <i>Streptococcus</i> (12%). Our epidemiologic investigation demonstrated both age and symptomatic presentation to be associated with a number of detected agents, including, but not limited to, influenza A and <i>Plasmodium</i>. Linear regression of fully-adjusted mean cycle threshold (C_t) values for <i>Plasmodium</i> also identified statistically significant lower mean C_t values for older children (20.8), patients presenting with severe fever (21.1) and headache (21.5), as well as patients admitted for in-patient care and treatment (22.4).</p><p>Conclusions</p><p>This study is the first to employ two syndromic TaqMan Array Cards for the simultaneous survey of 57 different organisms to better characterize the type and prevalence of detected agents among febrile patients. Additionally, we provide an analysis of the association between adjusted mean C_t values for <i>Plasmodium</i> and key clinical and demographic variables, which may further inform clinical decision-making based upon intensity of infection, as observed across endemic settings of sub-Saharan Africa.</p></div

Box plots of parasite load (C_t) by level of parasite intensity.

<p>Box plots of parasite load (C_t) by level of parasite intensity.</p

Clinical characteristics of enrolled febrile pediatric and adult patients.

<p>Clinical characteristics of enrolled febrile pediatric and adult patients.</p

Statistically significant findings from domain-specific and combined multivariate regression model of prevalent agents detected.

<p>Statistically significant findings from domain-specific and combined multivariate regression model of prevalent agents detected.</p

Frequency of detection of single and multiple organisms by the AFI TAC assay.

<p>Frequency of detection of single and multiple organisms by the AFI TAC assay.</p

Demographic and socio-economic characteristics of enrolled febrile patients.

<p>Demographic and socio-economic characteristics of enrolled febrile patients.</p

High seroprevalence of Immunoglobulin G (IgG) and IgM antibodies to SARS-CoV-2 in asymptomatic and symptomatic individuals amidst vaccination roll-out in western Kenya.

The population's antibody response is a key factor in comprehending SARS-CoV-2 epidemiology. This is especially important in African settings where COVID-19 impact, and vaccination rates are relatively low. This study aimed at characterizing the Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in both SARS-CoV-2 asymptomatic and symptomatic individuals in Kisumu and Siaya counties in western Kenya using enzyme linked immunosorbent assays. The IgG and IgM overall seroprevalence in 98 symptomatic and asymptomatic individuals in western Kenya between December 2021-March 2022 was 76.5% (95% CI = 66.9-84.5) and 29.6% (95% CI = 20.8-39.7) respectively. In terms of gender, males had slightly higher IgG positivity 87.5% (35/40) than females 68.9% (40/58). Amidst the ongoing vaccination roll-out during the study period, over half of the study participants (55.1%, 95% CI = 44.7-65.2) had not received any vaccine. About one third, (31.6%, 95% CI = 22.6-41.8) of the study participants had been fully vaccinated, with close to a quarter (13.3% 95% CI = 7.26-21.6) partially vaccinated. When considering the vaccination status and seroprevalence, out of the 31 fully vaccinated individuals, IgG seropositivity was 81.1% (95% CI = 70.2-96.3) and IgM seropositivity was 35.5% (95% CI = 19.22-54.6). Out of the participants that had not been vaccinated at all, IgG seroprevalence was 70.4% (95% CI 56.4-82.0) with 20.4% (95% CI 10.6-33.5) seropositivity for IgM antibodies. On PCR testing, 33.7% were positive, with 66.3% negative. The 32 positive individuals included 12(37.5%) fully vaccinated, 8(25%) partially vaccinated and 12(37.5%) unvaccinated. SARs-CoV-2 PCR positivity did not significantly predict IgG (p = 0.469 [95% CI 0.514-4.230]) and IgM (p = 0.964 [95% CI 0.380-2.516]) positivity. These data indicate a high seroprevalence of antibodies to SARS-CoV-2 in western Kenya. This suggests that a larger fraction of the population was infected with SARS-CoV-2 within the defined period than what PCR testing could cover

Fully adjusted mean cycle threshold (C_t) values associated with demographic and clinical factors as determined by multivariate linear regression.

<p>Dependent Variable: <i>Plasmodium</i> Cycle Threshold (C_t); (Tested: 842; Positive: 399).</p

Detections of viral, bacterial and parasitic agents by acute febrile illness (AFI) and respiratory TAC.

<p>Detections of viral, bacterial and parasitic agents by acute febrile illness (AFI) and respiratory TAC.</p