Adapting Longstanding Public Health Collaborations between Government of Kenya and CDC Kenya in Response to the COVID-19 Pandemic, 2020-2021.

Kenya's Ministry of Health (MOH) and the US Centers for Disease Control and Prevention in Kenya (CDC Kenya) have maintained a 40-year partnership during which measures were implemented to prevent, detect, and respond to disease threats. During the COVID-19 pandemic, the MOH and CDC Kenya rapidly responded to mitigate disease impact on Kenya's 52 million residents. We describe activities undertaken jointly by the MOH and CDC Kenya that lessened the effects of COVID-19 during 5 epidemic waves from March through December 2021. Activities included establishing national and county-level emergency operations centers and implementing workforce development and deployment, infection prevention and control training, laboratory diagnostic advancement, enhanced surveillance, and information management. The COVID-19 pandemic provided fresh impetus for the government of Kenya to establish a national public health institute, launched in January 2022, to consolidate its public health activities and counter COVID-19 and future infectious, vaccine-preventable, and emerging zoonotic diseases.

Building laboratory capacity to detect and characterize pathogens of public and global health security concern in Kenya.

Since 1979, multiple CDC Kenya programs have supported the development of diagnostic expertise and laboratory capacity in Kenya. In 2004, CDC's Global Disease Detection (GDD) program within the Division of Global Health Protection in Kenya (DGHP-Kenya) initiated close collaboration with Kenya Medical Research Institute (KEMRI) and developed a laboratory partnership called the Diagnostic and Laboratory Systems Program (DLSP). DLSP built onto previous efforts by malaria, human immunodeficiency virus (HIV) and tuberculosis (TB) programs and supported the expansion of the diagnostic expertise and capacity in KEMRI and the Ministry of Health. First, DLSP developed laboratory capacity for surveillance of diarrheal, respiratory, zoonotic and febrile illnesses to understand the etiology burden of these common illnesses and support evidenced-based decisions on vaccine introductions and recommendations in Kenya. Second, we have evaluated and implemented new diagnostic technologies such as TaqMan Array Cards (TAC) to detect emerging or reemerging pathogens and have recently added a next generation sequencer (NGS). Third, DLSP provided rapid laboratory diagnostic support for outbreak investigation to Kenya and regional countries. Fourth, DLSP has been assisting the Kenya National Public Health laboratory-National Influenza Center and microbiology reference laboratory to obtain World Health Organization (WHO) certification and ISO15189 accreditation respectively. Fifth, we have supported biosafety and biosecurity curriculum development to help Kenyan laboratories safely and appropriately manage infectious pathogens. These achievements, highlight how in collaboration with existing CDC programs working on HIV, tuberculosis and malaria, the Global Health Security Agenda can have significantly improve public health in Kenya and the region. Moreover, Kenya provides an example as to how laboratory science can help countries detect and control of infectious disease outbreaks and other public health threats more rapidly, thus enhancing global health security.

Cholera Outbreak in Dadaab Refugee Camp, Kenya - November 2015-June 2016.

Dadaab Refugee camp in Garissa County, Kenya, hosts nearly 340,000 refugees in five subcamps (Dagahaley, Hagadera, Ifo, Ifo2, and Kambioos) (1). On November 18 and 19, 2015, during an ongoing national cholera outbreak (2), two camp residents were evaluated for acute watery diarrhea (three or more stools in ≤24 hours); Vibrio cholerae serogroup O1 serotype Ogawa was isolated from stool specimens collected from both patients. Within 1 week of the report of index cases, an additional 45 cases of acute watery diarrhea were reported. The United Nations High Commissioner for Refugees and their health-sector partners coordinated the cholera response, community outreach and water, sanitation, and hygiene (WASH) activities; Médecins Sans Frontiéres and the International Rescue Committee were involved in management of cholera treatment centers; CDC performed laboratory confirmation of cases and undertook GIS mapping and postoutbreak response assessment; and the Garissa County Government and the Kenya Ministry of Health conducted a case-control study. To prevent future cholera outbreaks, improvements to WASH and enhanced disease surveillance systems in Dadaab camp and the surrounding area are needed.

The contribution of respiratory pathogens to fatal and non-fatal respiratory hospitalizations: a pilot study of Taqman Array Cards (TAC) in Kenya.

BACKGROUND: Respiratory diseases cause substantial morbidity and mortality worldwide, with sub-Saharan Africa bearing the greatest burden. Identifying etiologies of respiratory disease is important to inform cost effective treatment, prevention and control strategies. Testing for all of the different pathogens that are potentially associated with respiratory illnesses is challenging. We piloted the use of a multi-pathogen respiratory Taqman Array Cards (TAC) to identify pathogens in respiratory samples collected from non-fatal and fatal cases and their matched asymptomatic controls. METHODS: This is a case control study comparing viral and bacterial pathogens detected among non-fatal and fatal cases to those detected among age and time matched asymptomatic controls. We used McNemar's test to compare proportions of pathogens detected among cases (non-fatal and fatal) to their matched asymptomatic controls. We used Mann-Whitney test to compare the distribution of median Cycle threshold (Ct) values among non-fatal and fatal cases to their corresponding asymptomatic controls. RESULTS: There were 72 fatal and 72 non-fatal cases matched to 72 controls. We identified at least one pathogen in 109/144 (76%) cases and 59/72 (82%) controls. For most pathogens, the median Ct values were lower among cases (fatal and non-fatal) compared to asymptomatic controls. CONCLUSIONS: Similar rates of pathogen detection among cases and controls make interpretation of results challenging. Ct-values might be helpful in interpreting clinical relevance of detected pathogens using multi-pathogen diagnostic tools.

Ebola Laboratory Response at the Eternal Love Winning Africa Campus, Monrovia, Liberia, 2014-2015.

West Africa experienced the first epidemic of Ebola virus infection, with by far the greatest number of cases in Guinea, Sierra Leone, and Liberia. The unprecedented epidemic triggered an unparalleled response, including the deployment of multiple Ebola treatment units and mobile/field diagnostic laboratories. The National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention deployed a joint laboratory to Monrovia, Liberia, in August 2014 to support the newly founded Ebola treatment unit at the Eternal Love Winning Africa (ELWA) campus. The laboratory operated initially out of a tent structure but quickly moved into a fixed-wall building owing to severe weather conditions, the need for increased security, and the high sample volume. Until May 2015, when the laboratory closed, the site handled close to 6000 clinical specimens for Ebola virus diagnosis and supported the medical staff in case patient management. Laboratory operation and safety, as well as Ebola virus diagnostic assays, are described and discussed; in addition, lessons learned for future deployments are reviewed.

Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus-Infected Patients.

BACKGROUND: The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. METHODS: All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. RESULTS: The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. CONCLUSIONS: Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.

The Merits of Malaria Diagnostics during an Ebola Virus Disease Outbreak.

Malaria is a major public health concern in the countries affected by the Ebola virus disease epidemic in West Africa. We determined the feasibility of using molecular malaria diagnostics during an Ebola virus disease outbreak and report the incidence of Plasmodium spp. parasitemia in persons with suspected Ebola virus infection.

Development of a TaqMan Array Card for Acute-Febrile-Illness Outbreak Investigation and Surveillance of Emerging Pathogens, Including Ebola Virus.

Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. Convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR-based TaqMan array card (TAC) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 AFI-associated organisms, including 15 viruses (chikungunya, Crimean-Congo hemorrhagic fever [CCHF] virus, dengue, Ebola virus, Bundibugyo virus, Sudan virus, hantaviruses [Hantaan and Seoul], hepatitis E, Marburg, Nipah virus, o'nyong-nyong virus, Rift Valley fever virus, West Nile virus, and yellow fever virus), 8 bacteria (Bartonella spp., Brucella spp., Coxiella burnetii, Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, and Yersinia pestis), and 3 protozoa (Leishmania spp., Plasmodium spp., and Trypanosoma brucei). Two extrinsic controls (phocine herpesvirus 1 and bacteriophage MS2) were included to ensure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, interassay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and the TAC exhibited an overall 88% (278/315; 95% confidence interval [CI], 84% to 92%) sensitivity and a 99% (5,261/5,326, 98% to 99%) specificity. This TaqMan array card can be used in field settings as a rapid screen for outbreak investigation or for the surveillance of pathogens, including Ebola virus.

Burden of Invasive Nontyphoidal Salmonella Disease in a Rural and Urban Site in Kenya, 2009-2014.

BACKGROUND: Invasive infections with nontyphoidal Salmonella (NTS) lead to bacteremia in children and adults and are an important cause of illness in Africa; however, few data on the burden of NTS bacteremia are available. We sought to determine the burden of invasive NTS disease in a rural and urban setting in Kenya. METHODS: We conducted the study in a population-based surveillance platform in a rural setting in western Kenya (Lwak), and an informal urban settlement in Nairobi (Kibera) from 2009 to 2014. We obtained blood culture specimens from participants presenting with acute lower respiratory tract illness or acute febrile illness to a designated outpatient facility in each site, or any hospital admission for a potentially infectious cause (rural site only). Incidence was calculated using a defined catchment population and adjusting for specimen collection and healthcare-seeking practices. RESULTS: A total of 12 683 and 9524 blood cultures were analyzed from Lwak and Kibera, respectively. Of these, 428 (3.4%) and 533 (5.6%) grew a pathogen; among those, 208 (48.6%) and 70 (13.1%) were positive for NTS in Lwak and Kibera, respectively. Overall, the adjusted incidence of invasive NTS disease was higher in Lwak (839.4 per 100,000 person-years of observation [PYO]) than in Kibera (202.5 per 100,000 PYO). The highest adjusted incidences were observed in children <5 years of age (Lwak 3914.3 per 100,000 PYO and Kibera 997.9 per 100,000 PYO). The highest adjusted annual incidence was 1927.3 per 100,000 PYO (in 2010) in Lwak and 220.5 per 100,000 PYO (in 2011) in Kibera; the lowest incidences were 303.3 and 62.5 per 100,000 PYO, respectively (in 2012). In both sites, invasive NTS disease incidence generally declined over the study period. CONCLUSIONS: We observed an extremely high burden of invasive NTS disease in a rural area of Kenya and a lesser, but still substantial, burden in an urban slum. Although the incidences in both sites declined during the study period, invasive NTS infections remain an important cause of morbidity in these settings, particularly among children <5 years old.

Use of Sentinel Surveillance Platforms for Monitoring SARS-CoV-2 Activity: Evidence From Analysis of Kenya Influenza Sentinel Surveillance Data.

BACKGROUND: Little is known about the cocirculation of influenza and SARS-CoV-2 viruses during the COVID-19 pandemic and the use of respiratory disease sentinel surveillance platforms for monitoring SARS-CoV-2 activity in sub-Saharan Africa. OBJECTIVE: We aimed to describe influenza and SARS-CoV-2 cocirculation in Kenya and how the SARS-CoV-2 data from influenza sentinel surveillance correlated with that of universal national surveillance. METHODS: From April 2020 to March 2022, we enrolled 7349 patients with severe acute respiratory illness or influenza-like illness at 8 sentinel influenza surveillance sites in Kenya and collected demographic, clinical, underlying medical condition, vaccination, and exposure information, as well as respiratory specimens, from them. Respiratory specimens were tested for influenza and SARS-CoV-2 by real-time reverse transcription polymerase chain reaction. The universal national-level SARS-CoV-2 data were also obtained from the Kenya Ministry of Health. The universal national-level SARS-CoV-2 data were collected from all health facilities nationally, border entry points, and contact tracing in Kenya. Epidemic curves and Pearson r were used to describe the correlation between SARS-CoV-2 positivity in data from the 8 influenza sentinel sites in Kenya and that of the universal national SARS-CoV-2 surveillance data. A logistic regression model was used to assess the association between influenza and SARS-CoV-2 coinfection with severe clinical illness. We defined severe clinical illness as any of oxygen saturation <90%, in-hospital death, admission to intensive care unit or high dependence unit, mechanical ventilation, or a report of any danger sign (ie, inability to drink or eat, severe vomiting, grunting, stridor, or unconsciousness in children younger than 5 years) among patients with severe acute respiratory illness. RESULTS: Of the 7349 patients from the influenza sentinel surveillance sites, 76.3% (n=5606) were younger than 5 years. We detected any influenza (A or B) in 8.7% (629/7224), SARS-CoV-2 in 10.7% (768/7199), and coinfection in 0.9% (63/7165) of samples tested. Although the number of samples tested for SARS-CoV-2 from the sentinel surveillance was only 0.2% (60 per week vs 36,000 per week) of the number tested in the universal national surveillance, SARS-CoV-2 positivity in the sentinel surveillance data significantly correlated with that of the universal national surveillance (Pearson r=0.58; P<.001). The adjusted odds ratios (aOR) of clinical severe illness among participants with coinfection were similar to those of patients with influenza only (aOR 0.91, 95% CI 0.47-1.79) and SARS-CoV-2 only (aOR 0.92, 95% CI 0.47-1.82). CONCLUSIONS: Influenza substantially cocirculated with SARS-CoV-2 in Kenya. We found a significant correlation of SARS-CoV-2 positivity in the data from 8 influenza sentinel surveillance sites with that of the universal national SARS-CoV-2 surveillance data. Our findings indicate that the influenza sentinel surveillance system can be used as a sustainable platform for monitoring respiratory pathogens of pandemic potential or public health importance.

Diagnostic accuracy of the Panbio COVID-19 antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation.

BACKGROUND: Accurate and timely diagnosis is essential in limiting the spread of SARS-CoV-2 infection. The reference standard, rRT-PCR, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen RDTs provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%. METHODS: This evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention's (CDC) rRT-PCR test. RESULTS: We evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms <5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those with onset of symptoms >7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30. CONCLUSION: The overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool only for symptomatic patients in high-risk settings with limited access to rRT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.

Dynamic Incidence of Typhoid Fever over a 10-Year Period (2010-2019) in Kibera, an Urban Informal Settlement in Nairobi, Kenya.

Typhoid fever burden can vary over time. Long-term data can inform prevention strategies; however, such data are lacking in many African settings. We reexamined typhoid fever incidence and antimicrobial resistance (AMR) over a 10-year period in Kibera, a densely populated urban informal settlement where a high burden has been previously described. We used data from the Population Based Infectious Diseases Surveillance platform to estimate crude and adjusted incidence rates and prevalence of AMR in nearly 26,000 individuals of all ages. Demographic and healthcare-seeking information was collected through household visits. Blood cultures were processed for patients with acute fever or lower respiratory infection. Between 2010 and 2019, 16,437 participants were eligible for blood culture and 11,848 (72.1%) had a culture performed. Among 11,417 noncontaminated cultures (96.4%), 237 grew Salmonella enterica serovar Typhi (2.1%). Overall crude and adjusted incidences were 95 and 188 cases per 100,000 person-years of observation (pyo), respectively. Annual crude incidence varied from 144 to 233 between 2010 and 2012 and from 9 to 55 between 2013 and 2018 and reached 130 per 100,000 pyo in 2019. Children 5-9 years old had the highest overall incidence (crude, 208; adjusted, 359 per 100,000 pyo). Among isolates tested, 156 of 217 were multidrug resistant (resistant to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole [71.9%]) and 6 of 223 were resistant to ciprofloxacin (2.7%). Typhoid fever incidence resurged in 2019 after a prolonged period of low rates, with the highest incidence among children. Typhoid fever control measures, including vaccines, could reduce morbidity in this setting.

Heterogenous transmission and seroprevalence of SARS-CoV-2 in two demographically diverse populations with low vaccination uptake in Kenya, March and June 2021.

Background: SARS-CoV-2 has extensively spread in cities and rural communities, and studies are needed to quantify exposure in the population. We report seroprevalence of SARS-CoV-2 in two well-characterized populations in Kenya at two time points. These data inform the design and delivery of public health mitigation measures. Methods: Leveraging on existing population based infectious disease surveillance (PBIDS) in two demographically diverse settings, a rural site in western Kenya in Asembo, Siaya County, and an urban informal settlement in Kibera, Nairobi County, we set up a longitudinal cohort of randomly selected households with serial sampling of all consenting household members in March and June/July 2021. Both sites included 1,794 and 1,638 participants in the March and June/July 2021, respectively. Individual seroprevalence of SARS-CoV-2 antibodies was expressed as a percentage of the seropositive among the individuals tested, accounting for household clustering and weighted by the PBIDS age and sex distribution. Results: Overall weighted individual seroprevalence increased from 56.2% (95%CI: 52.1, 60.2%) in March 2021 to 63.9% (95%CI: 59.5, 68.0%) in June 2021 in Kibera. For Asembo, the seroprevalence almost doubled from 26.0% (95%CI: 22.4, 30.0%) in March 2021 to 48.7% (95%CI: 44.3, 53.2%) in July 2021. Seroprevalence was highly heterogeneous by age and geography in these populations-higher seroprevalence was observed in the urban informal settlement (compared to the rural setting), and children aged <10 years had the lowest seroprevalence in both sites. Only 1.2% and 1.6% of the study participants reported receipt of at least one dose of the COVID-19 vaccine by the second round of serosurvey-none by the first round. Conclusions: In these two populations, SARS-CoV-2 seroprevalence increased in the first 16 months of the COVID-19 pandemic in Kenya. It is important to prioritize additional mitigation measures, such as vaccine distribution, in crowded and low socioeconomic settings.

Genome Sequence of Escherichia coli Isolated from an Adult in Kibera, an Urban Informal Settlement in Nairobi, Kenya.

An Escherichia coli strain (sequence type 636) was isolated from an adult residing in an urban informal settlement in Nairobi, Kenya, and was sequenced using the Illumina MiSeq platform. The draft genome was 5,075,726 bp, with a Col(BS512) plasmid plus aph(6)-Id, blaTEM-1B, and dfrA7 genes, which encode kanamycin, ampicillin, and trimethoprim resistance proteins, respectively.

Severe acute respiratory illness surveillance for influenza in Kenya: Patient characteristics and lessons learnt.

BACKGROUND: We describe the epidemiology and clinical features of Kenyan patients hospitalized with laboratory-confirmed influenza compared with those testing negative and discuss the potential contribution of severe acute respiratory illness (SARI) surveillance in monitoring a broader range of respiratory pathogens. METHODS: We described demographic and clinical characteristics of SARI cases among children (<18 years) and adults, separately. We compared disease severity (clinical features and treatment) of hospitalized influenza positive versus negative cases and explored independent predictors of death among SARI cases using a multivariable logistic regression model. RESULTS: From January 2014 to December 2018, 11,166 persons were hospitalized with SARI and overall positivity for influenza was ~10%. There were 10,742 (96%) children (<18 years)-median age of 1 year, interquartile range (IQR = 6 months, 2 years). Only 424 (4%) of the SARI cases were adults (≥18 years), with median age of 38 years (IQR 28 years, 52 years). There was no difference in disease severity comparing influenza positive and negative cases among children. Children hospitalized with SARI who had an underlying illness had greater odds of in-hospital death compared with those without (adjusted odds ratio 2.11 95% CI 1.09-4.07). No further analysis was done among adults due to the small sample size. CONCLUSION: Kenya's sentinel surveillance for SARI mainly captures data on younger children. Hospital-based platforms designed to monitor influenza viruses and associated disease burden may be adapted and expanded to other respiratory viruses to inform public health interventions. Efforts should be made to capture adults as part of routine respiratory surveillance.

Molecular characterization of circulating Salmonella Typhi strains in an urban informal settlement in Kenya.

A high burden of Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) bacteremia has been reported from urban informal settlements in sub-Saharan Africa, yet little is known about the introduction of these strains to the region. Understanding regional differences in the predominant strains of S. Typhi can provide insight into the genomic epidemiology. We genetically characterized 310 S. Typhi isolates from typhoid fever surveillance conducted over a 12-year period (2007-2019) in Kibera, an urban informal settlement in Nairobi, Kenya, to assess the circulating strains, their antimicrobial resistance attributes, and how they relate to global S. Typhi isolates. Whole genome multi-locus sequence typing (wgMLST) identified 4 clades, with up to 303 pairwise allelic differences. The identified genotypes correlated with wgMLST clades. The predominant clade contained 290 (93.5%) isolates with a median of 14 allele differences (range 0-52) and consisted entirely of genotypes 4.3.1.1 and 4.3.1.2. Resistance determinants were identified exclusively in the predominant clade. Determinants associated with resistance to aminoglycosides were observed in 245 isolates (79.0%), sulphonamide in 243 isolates (78.4%), trimethoprim in 247 isolates (79.7%), tetracycline in 224 isolates (72.3%), chloramphenicol in 247 isolates (79.6%), ß-lactams in 239 isolates (77.1%) and quinolones in 62 isolates (20.0%). Multidrug resistance (MDR) determinants (defined as determinants conferring resistance to ampicillin, chloramphenicol and cotrimoxazole) were found in 235 (75.8%) isolates. The prevalence of MDR associated genes was similar throughout the study period (2007-2012: 203, 76.3% vs 2013-2019: 32, 72.7%; Fisher's Exact Test: P = 0.5478, while the proportion of isolates harboring quinolone resistance determinants increased (2007-2012: 42, 15.8% and 2013-2019: 20, 45.5%; Fisher's Exact Test: P<0.0001) following a decline in S. Typhi in Kibera. Some isolates (49, 15.8%) harbored both MDR and quinolone resistance determinants. There were no determinants associated with resistance to cephalosporins or azithromycin detected among the isolates sequenced in this study. Plasmid markers were only identified in the main clade including IncHI1A and IncHI1B(R27) in 226 (72.9%) isolates, and IncQ1 in 238 (76.8%) isolates. Molecular clock analysis of global typhoid isolates and isolates from Kibera suggests that genotype 4.3.1 has been introduced multiple times in Kibera. Several genomes from Kibera formed a clade with genomes from Kenya, Malawi, South Africa, and Tanzania. The most recent common ancestor (MRCA) for these isolates was from around 1997. Another isolate from Kibera grouped with several isolates from Uganda, sharing a common ancestor from around 2009. In summary, S. Typhi in Kibera belong to four wgMLST clades one of which is frequently associated with MDR genes and this poses a challenge in treatment and control.

Carriage of antimicrobial-resistant bacteria in a high-density informal settlement in Kenya is associated with environmental risk-factors.

BACKGROUND: The relationship between antibiotic use and antimicrobial resistance varies with cultural, socio-economic, and environmental factors. We examined these relationships in Kibera, an informal settlement in Nairobi-Kenya, characterized by high population density, high burden of respiratory disease and diarrhea. METHODS: Two-hundred households were enrolled in a 5-month longitudinal study. One adult (≥ 18 years) and one child (≤ 5 years) participated per household. Biweekly interviews (n = 1516) that included questions on water, sanitation, hygiene, and antibiotic use in the previous two weeks were conducted, and 2341 stool, 2843 hand swabs and 1490 drinking water samples collected. Presumptive E. coli (n = 34,042) were isolated and tested for susceptibility to nine antibiotics. RESULTS: Eighty percent of presumptive E. coli were resistant to ≥ 3 antibiotic classes. Stool isolates were resistant to trimethoprim (mean: 81%), sulfamethoxazole (80%), ampicillin (68%), streptomycin (60%) and tetracycline (55%). Ninety-seven households reported using an antibiotic in at least one visit over the study period for a total of 144 episodes and 190 antibiotic doses. Enrolled children had five times the number of episodes reported by enrolled adults (96 vs. 19). Multivariable linear mixed-effects models indicated that children eating soil from the household yard and the presence of informal hand-washing stations were associated with increased numbers of antimicrobial-resistant bacteria (counts increasing by 0·27-0·80 log10 and 0·22-0·51 log10 respectively, depending on the antibiotic tested). Rainy conditions were associated with reduced carriage of antimicrobial-resistant bacteria (1·19 to 3·26 log10 depending on the antibiotic tested). CONCLUSIONS: Antibiotic use provided little explanatory power for the prevalence of antimicrobial resistance. Transmission of resistant bacteria in this setting through unsanitary living conditions likely overwhelms incremental changes in antibiotic use. Under such circumstances, sanitation, hygiene, and disease transmission are the limiting factors for reducing the prevalence of resistant bacteria.

Seroprevalence and risk factors of SARS-CoV-2 infection in an urban informal settlement in Nairobi, Kenya, December 2020.

Introduction: Urban informal settlements may be disproportionately affected by the COVID-19 pandemic due to overcrowding and other socioeconomic challenges that make adoption and implementation of public health mitigation measures difficult. We conducted a seroprevalence survey in the Kibera informal settlement, Nairobi, Kenya, to determine the extent of SARS-CoV-2 infection. Methods: Members of randomly selected households from an existing population-based infectious disease surveillance (PBIDS) provided blood specimens between 27 th November and 5 th December 2020. The specimens were tested for antibodies to the SARS-CoV-2 spike protein. Seroprevalence estimates were weighted by age and sex distribution of the PBIDS population and accounted for household clustering. Multivariable logistic regression was used to identify risk factors for individual seropositivity.   Results: Consent was obtained from 523 individuals in 175 households, yielding 511 serum specimens that were tested. The overall weighted seroprevalence was 43.3% (95% CI, 37.4 - 49.5%) and did not vary by sex. Of the sampled households, 122(69.7%) had at least one seropositive individual. The individual seroprevalence increased by age from 7.6% (95% CI, 2.4 - 21.3%) among children (<5 years), 32.7% (95% CI, 22.9 - 44.4%) among children 5 - 9 years, 41.8% (95% CI, 33.0 - 51.1%) for those 10-19 years, and 54.9%(46.2 - 63.3%) for adults (≥20 years). Relative to those from medium-sized households (3 and 4 individuals), participants from large (≥5 persons) households had significantly increased odds of being seropositive, aOR, 1.98(95% CI, 1.17 - 1.58), while those from small-sized households (≤2 individuals) had increased odds but not statistically significant, aOR, 2.31 (95% CI, 0.93 - 5.74).  Conclusion: In densely populated urban settings, close to half of the individuals had an infection to SARS-CoV-2 after eight months of the COVID-19 pandemic in Kenya. This highlights the importance to prioritize mitigation measures, including COVID-19 vaccine distribution, in the crowded, low socioeconomic settings.

Serologic Evidence of the Geographic Distribution of Bacterial Zoonotic Agents in Kenya, 2007.

Diseases of zoonotic origin contribute to the burden of febrile illnesses in developing countries. We evaluated serologic evidence of exposure to Bacillus anthracis, Brucella spp., spotted fever group rickettsioses (SFGR), and typhus group rickettsioses (TGR) from samples of persons aged 15-64 years collected during a nationwide human immunodeficiency virus (HIV) serosurvey conducted in 2007 in Kenya. The seropositivity observed for pathogens was B. anthracis 11.3%, Brucella spp. 3.0%, SFGR 23.3%, and TGR 0.6%. On univariate analysis, seropositivity for each pathogen was significantly associated with the following risk factors: B. anthracis with province of residence; Brucella spp. with sex, education level, and wealth; SFGR with age, education level, wealth, and province of residence; and TGR with province of residence. On multivariate analysis, seropositivity remained significantly associated with wealth and province for B. anthracis; with sex and age for Brucella spp; and with sex, education level, and province of residence for SFGR whereas TGR had no significance. High IgG seropositivity to these zoonotic pathogens (especially, B. anthracis and SFGR) suggests substantial exposure. These pathogens should be considered in the differential diagnosis of febrile illness in Kenya.

Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007.

Arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in Kenya and East Africa. In this study, we used 1,091 HIV-negative blood specimens from the 2007 Kenya AIDS Indicator Survey (KAIS 2007) to test for the presence of IgG antibodies to dengue virus (DENV), chikungunya virus (CHIKV) and Rift Valley fever virus (RVFV).The KAIS 2007 was a national population-based survey conducted by the Government of Kenya to provide comprehensive information needed to address the HIV/AIDS epidemic. Antibody testing for arboviruses was performed on stored blood specimens from KAIS 2007 through a two-step sandwich IgG ELISA using either commercially available kits or CDC-developed assays. Out of the 1,091 samples tested, 210 (19.2%) were positive for IgG antibodies against at least one of the three arboviruses. DENV was the most common of the three viruses tested (12.5% positive), followed by RVFV and CHIKV (4.5% and 0.97%, respectively). For DENV and RVFV, the participant's province of residence was significantly associated (P≤.01) with seropositivity. Seroprevalence of DENV and RVFV increased with age, while there was no correlation between province of residence/age and seropositivity for CHIKV. Females had twelve times higher odds of exposure to CHIK as opposed to DENV and RVFV where both males and females had the same odds of exposure. Lack of education was significantly associated with a higher odds of previous infection with either DENV or RVFV (p <0.01). These data show that a number of people are at risk of arbovirus infections depending on their geographic location in Kenya and transmission of these pathogens is greater than previously appreciated. This poses a public health risk, especially for DENV.