The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries.

BACKGROUND: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent. METHODS: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010-2014) and a fever study in Ghana (2007-2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site. RESULTS: Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S. Enteritidis and S. Typhimurium in Ghana; an ST313 isolate carrying blaCTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries. CONCLUSIONS: We identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.

Causes of preterm and low birth weight neonatal mortality in a rural community in Kenya: evidence from verbal and social autopsy.

BACKGROUND: Under-five mortality in Kenya has declined over the past two decades. However, the reduction in the neonatal mortality rate has remained stagnant. In a country with weak civil registration and vital statistics systems, there is an evident gap in documentation of mortality and its causes among low birth weight (LBW) and preterm neonates. We aimed to establish causes of neonatal LBW and preterm mortality in Migori County, among participants of the PTBI-K (Preterm Birth Initiative-Kenya) study. METHODS: Verbal and social autopsy (VASA) interviews were conducted with caregivers of deceased LBW and preterm neonates delivered within selected 17 health facilities in Migori County, Kenya. The probable cause of death was assigned using the WHO International Classification of Diseases (ICD-10). RESULTS: Between January 2017 to December 2018, 3175 babies were born preterm or LBW, and 164 (5.1%) died in the first 28 days of life. VASA was conducted among 88 (53.7%) of the neonatal deaths. Almost half (38, 43.2%) of the deaths occurred within the first 24 h of life. Birth asphyxia (45.5%), neonatal sepsis (26.1%), respiratory distress syndrome (12.5%) and hypothermia (11.0%) were the leading causes of death. In the early neonatal period, majority (54.3%) of the neonates succumbed to asphyxia while in the late neonatal period majority (66.7%) succumbed to sepsis. Delay in seeking medical care was reported for 4 (5.8%) of the neonatal deaths. CONCLUSION: Deaths among LBW and preterm neonates occur early in life due to preventable causes. This calls for enhanced implementation of existing facility-based intrapartum and immediate postpartum care interventions, targeting asphyxia, sepsis, respiratory distress syndrome and hypothermia.

Environmental, Metabolic, and Inflammatory Factors Converge in the Pathogenesis of Moderate Acute Malnutrition in Children: An Observational Cohort Study.

Acute malnutrition affects more than 50 million children worldwide. These children are at an increased risk of morbidity and mortality from infectious disease. However, the pathogenesis of acute malnutrition and mechanisms underlying the increased risk and poor outcomes from infection are not well understood. Our objective was to identify differences in inflammation and inflammatory responses between children with moderate acute malnutrition (MAM) and healthy controls (HCs), and search for environmental, pathophysiological, and metabolic factors that may influence this response. Sixteen children with MAM and 16 HCs aged 18-36 months were studied in Nairobi, Kenya. None of the children had symptoms of an infectious disease (fever, diarrhea, or cough) in the 2 weeks before enrollment and sample collection. Demographic and health data were provided by their primary caregivers. Blood samples were collected to measure various biomarkers and the response to an inflammatory stimulus. Children with MAM were more frequently from households with contaminated water, crowding, and unstable income sources. They also had increases in basal inflammation, circulating bacterial lipopolysaccharide (LPS), markers of intestinal damage, and an exaggerated whole blood inflammatory response to LPS. Metabolic changes in children with MAM led to increased plasma levels of long-chain fatty acids, which were found to contribute to the pro-inflammatory state. These exploratory findings suggest convergence of multiple factors to promote dysregulated inflammatory responses and prompt several mechanistic hypotheses that can be pursued to better understand the pathogenesis of MAM.

The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa.

There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.

Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study.

BACKGROUND: Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents. METHODS: We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment. FINDINGS: Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0-0) in Sudan to 383 (274-535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178-316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau. INTERPRETATION: Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study. FUNDING: Bill & Melinda Gates Foundation.

The Relationship Between Invasive Nontyphoidal Salmonella Disease, Other Bacterial Bloodstream Infections, and Malaria in Sub-Saharan Africa.

BACKGROUND: Country-specific studies in Africa have indicated that Plasmodium falciparum is associated with invasive nontyphoidal Salmonella (iNTS) disease. We conducted a multicenter study in 13 sites in Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania to investigate the relationship between the occurrence of iNTS disease, other systemic bacterial infections, and malaria. METHODS: Febrile patients received a blood culture and a malaria test. Isolated bacteria underwent antimicrobial susceptibility testing, and the association between iNTS disease and malaria was assessed. RESULTS: A positive correlation between frequency proportions of malaria and iNTS was observed (P = .01; r = 0.70). Areas with higher burden of malaria exhibited higher odds of iNTS disease compared to other bacterial infections (odds ratio [OR], 4.89; 95% CI, 1.61-14.90; P = .005) than areas with lower malaria burden. Malaria parasite positivity was associated with iNTS disease (OR, 2.44; P = .031) and gram-positive bacteremias, particularly Staphylococcus aureus, exhibited a high proportion of coinfection with Plasmodium malaria. Salmonella Typhimurium and Salmonella Enteritidis were the predominant NTS serovars (53/73; 73%). Both moderate (OR, 6.05; P = .0001) and severe (OR, 14.62; P < .0001) anemia were associated with iNTS disease. CONCLUSIONS: A positive correlation between iNTS disease and malaria endemicity, and the association between Plasmodium parasite positivity and iNTS disease across sub-Saharan Africa, indicates the necessity to consider iNTS as a major cause of febrile illness in malaria-holoendemic areas. Prevention of iNTS disease through iNTS vaccines for areas of high malaria endemicity, targeting high-risk groups for Plasmodium parasitic infection, should be considered.

A Multicountry Molecular Analysis of Salmonella enterica Serovar Typhi With Reduced Susceptibility to Ciprofloxacin in Sub-Saharan Africa.

BACKGROUND: Salmonella enterica serovar Typhi is a predominant cause of bloodstream infections in sub-Saharan Africa (SSA). Increasing numbers of S. Typhi with resistance to ciprofloxacin have been reported from different parts of the world. However, data from SSA are limited. In this study, we aimed to measure the ciprofloxacin susceptibility of S. Typhi isolated from patients with febrile illness in SSA. METHODS: Febrile patients from 9 sites within 6 countries in SSA with a body temperature of ≥38.0°C were enrolled in this study. Blood samples were obtained for bacterial culture, and Salmonella isolates were identified biochemically and confirmed by multiplex polymerase chain reaction (PCR). Antimicrobial susceptibility of all Salmonella isolates was performed by disk diffusion test, and minimum inhibitory concentrations (MICs) against ciprofloxacin were measured by Etest. All Salmonella isolates with reduced susceptibility to ciprofloxacin (MIC > 0.06 µg/mL) were screened for mutations in quinolone resistance-determining regions in target genes, and the presence of plasmid-mediated quinolone resistance (PMQR) genes was assessed by PCR. RESULTS: A total of 8161 blood cultures were performed, and 100 (1.2%) S. Typhi, 2 (<0.1%) Salmonella enterica serovar Paratyphi A, and 27 (0.3%) nontyphoid Salmonella (NTS) were isolated. Multidrug-resistant S. Typhi were isolated in Kenya (79% [n = 38]) and Tanzania (89% [n = 8]) only. Reduced ciprofloxacin-susceptible (22% [n = 11]) S. Typhi were isolated only in Kenya. Among those 11 isolates, all had a Glu133Gly mutation in the gyrA gene combined with either a gyrA (Ser83Phe) or gyrB mutation (Ser464Phe). One Salmonella Paratyphi A isolate with reduced susceptibility to ciprofloxacin was found in Senegal, with 1 mutation in gyrA (Ser83Phe) and a second mutation in parC (Ser57Phe). Mutations in the parE gene and PMQR genes were not detected in any isolate. CONCLUSIONS: Salmonella Typhi with reduced susceptibility to ciprofloxacin was not distributed homogenously throughout SSA. Its prevalence was very high in Kenya, and was not observed in other study countries. Continuous monitoring of antimicrobial susceptibility is required to follow the potential spread of antimicrobial-resistant isolates throughout SSA.

The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies.

BACKGROUND: New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. METHODS: Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. RESULTS: Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. CONCLUSIONS: By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs.

Risk factors of hypertension among adults aged 35-64 years living in an urban slum Nairobi, Kenya.

BACKGROUND: Hypertension is an emerging public health problem in Sub Saharan Africa (SSA) and urbanization is considered to favor its emergence. Given a paucity of information on hypertension and associated risk factors among urban slum dwellers in SSA, we aimed to characterize the distribution of risk factors for hypertension and investigate their association with hypertension in an urban slum in Kenya. METHODS: We conducted a community based cross-sectional survey among adults 35 years and older living in Kibera slum Nairobi, Kenya. Trained interviewers collected data on socio demographic characteristics and self reported health behaviours using modified World Health Organization stepwise surveillance questionnaire for chronic disease risk factors. Anthropometric and blood pressure measurements were performed following standard procedures. Multiple logistic regression was used for analysis and odds ratios with 95 % confidence intervals were calculated to identify risk factors associated with hypertension. RESULT: A total of 1528 adults were surveyed with a mean age of 46.7 years. The age-standardized prevalence of hypertension was 29.4 % (95 % CI 27.0-31.7). Among the 418 participants classified as hypertensive, over one third (39.0 %) were unaware they had hypertension. Prevalence of current smoking and alcohol consumption was 8.5 and 13.1 % respectively. Over one quarter 26.2 % participants were classified as overweight (Body Mass Index [BMI] ≥25 to ≤29.9 kg/m(2)), and 17 % classified as obese (BMI ≥30 kg/m(2)). Overweight, obesity, current smoking, some level of education, highest wealth index, moderate physical activity, older age and being widowed were each independently associated with hypertension. When fit in a multivariable logistic regression model, being a widow [AOR = 1.7; (95 % CI, 1.1-2.6)], belonging to the highest wealth index [AOR = 1.6; (95 % CI, 1.1-2.5)], obesity [AOR = 1.8; 95 % CI, 1.1-3.1)] and moderate physical activity [AOR = 1.9; (95 % CI, 1.2-3.0)], all remained significantly associated with hypertension. CONCLUSION: Hypertension in the slum is a public health problem affecting at least one in three adults aged 35-64 years. Age, marital status, wealth index, physical inactivity and body mass index are important risk factors associated with hypertension. Prevention measures targeting the modifiable risk factors associated with hypertension are warranted to curb hypertension and its progressive effects.

Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya.

There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37-4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12-8.56) and 0.27 (95% CI 0.14-0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study.

Bloodstream Infections and Frequency of Pretreatment Associated With Age and Hospitalization Status in Sub-Saharan Africa.

BACKGROUND: The clinical diagnosis of bacterial bloodstream infections (BSIs) in sub-Saharan Africa is routinely confused with malaria due to overlapping symptoms. The Typhoid Surveillance in Africa Program (TSAP) recruited febrile inpatients and outpatients of all ages using identical study procedures and enrollment criteria, thus providing an opportunity to assess disease etiology and pretreatment patterns among children and adults. METHODS: Inpatients and outpatients of all ages with tympanic or axillary temperatures of ≥38.0 or ≥37.5°C, respectively, and inpatients only reporting fever within the previous 72 hours were eligible for recruitment. All recruited patients had one blood sample drawn and cultured for microorganisms. Data from 11 TSAP surveillance sites in nine different countries were used in the analysis. Bivariate analysis was used to compare frequencies of pretreatment and BSIs in febrile children (<15 years old) and adults (≥15 years old) in each country. Pooled Cochran Mantel-Haenszel odds ratios (ORs) were calculated for overall trends. RESULTS: There was no significant difference in the odds of a culture-proven BSI between children and adults among inpatients or outpatients. Among both inpatients and outpatients, children had significantly higher odds of having a contaminated blood culture compared with adults. Using country-pooled data, child outpatients had 66% higher odds of having Salmonella Typhi in their bloodstream than adults (OR, 1.66; 95% confidence interval [CI], 1.01-2.73). Overall, inpatient children had 59% higher odds of pretreatment with analgesics in comparison to inpatient adults (OR, 1.59; 95% CI, 1.28-1.97). CONCLUSIONS: The proportion of patients with culture-proven BSIs in children compared with adults was similar across the TSAP study population; however, outpatient children were more likely to have Salmonella Typhi infections than outpatient adults. This finding points to the importance of including outpatient facilities in surveillance efforts, particularly for the surveillance of typhoid fever. Strategies to reduce contamination among pediatric blood cultures are needed across the continent to prevent the misdiagnosis of BSI cases in children.

Severe acute respiratory infection in children in a densely populated urban slum in Kenya, 2007-2011.

BACKGROUND: Reducing acute respiratory infection burden in children in Africa remains a major priority and challenge. We analyzed data from population-based infectious disease surveillance for severe acute respiratory illness (SARI) among children <5 years of age in Kibera, a densely populated urban slum in Nairobi, Kenya. METHODS: Surveillance was conducted among a monthly mean of 5,874 (range = 5,778-6,411) children <5 years old in two contiguous villages in Kibera. Participants had free access to the study clinic and their health events and utilization were noted during biweekly home visits. Patients meeting criteria for SARI (WHO-defined severe or very severe pneumonia, or oxygen saturation <90%) from March 1, 2007-February 28, 2011 had blood cultures processed for bacteria, and naso- and oro- pharyngeal swabs collected for quantitative real-time reverse transcription polymerase chain reaction testing for influenza viruses, parainfluenza viruses (PIV), respiratory syncytial virus (RSV), adenovirus, and human metapneumovirus (hMPV). Swabs collected during January 1, 2009 - February 28, 2010 were also tested for rhinoviruses, enterovirus, parechovirus, Mycoplasma pneumoniae, and Legionella species. Swabs were collected for simultaneous testing from a selected group of control-children visiting the clinic without recent respiratory or diarrheal illnesses. RESULTS: SARI overall incidence was 12.4 cases/100 person-years of observation (PYO) and 30.4 cases/100 PYO in infants. When comparing detection frequency in swabs from 815 SARI cases and 115 healthy controls, only RSV and influenza A virus were significantly more frequently detected in cases, although similar trends neared statistical significance for PIV, adenovirus and hMPV. The incidence for RSV was 2.8 cases/100 PYO and for influenza A was 1.0 cases/100 PYO. When considering all PIV, the rate was 1.1 case/100 PYO and the rate per 100 PYO for SARI-associated disease was 1.5 for adenovirus and 0.9 for hMPV. RSV and influenza A and B viruses were estimated to account for 16.2% and 6.7% of SARI cases, respectively; when taken together, PIV, adenovirus, and hMPV may account for >20% additional cases. CONCLUSIONS: Influenza viruses and RSV (and possibly PIV, hMPV and adenoviruses) are important pathogens to consider when developing technologies and formulating strategies to treat and prevent SARI in children.

Increased Rates of Respiratory and Diarrheal Illnesses in HIV-Negative Persons Living With HIV-Infected Individuals in a Densely Populated Urban Slum in Kenya.

BACKGROUND: Prolonged pathogen shedding and increased duration of illness associated with infections in immunosuppressed individuals put close human immunodeficiency virus (HIV)-negative contacts of HIV-infected persons at increased risk of exposure to infectious pathogens. METHODS: We calculated incidence and longitudinal prevalence (number of days per year) of influenzalike illness (ILI), diarrhea, and nonspecific febrile illness during 2008 from a population-based surveillance program in the urban slum of Kibera (Kenya) that included 1830 HIV-negative household contacts of HIV-infected individuals and 13 677 individuals living in exclusively HIV-negative households. RESULTS: For individuals ≥5 years old, incidence was significantly increased for ILI (risk ratio [RR], 1.47; P < .05) and diarrhea (RR, 1.41; P < .05) in HIV-negative household contacts of HIV-infected individuals compared with exclusively HIV-negative households. The risk of illness among HIV-negative persons was directly proportional to the number of HIV-infected persons living in the home for ILI (RR, 1.39; P < .05) and diarrhea (RR, 1.36; P < .01). We found no increased rates of illness in children <5 years old who lived with HIV-infected individuals. CONCLUSIONS: Living with HIV-infected individuals is associated with modestly increased rates of respiratory and diarrheal infections in HIV-negative individuals >5 years old. Targeted interventions are needed, including ensuring that HIV-infected persons are receiving appropriate care and treatment.

Mortality trends observed in population-based surveillance of an urban slum settlement, Kibera, Kenya, 2007-2010.

BACKGROUND: We used population based infectious disease surveillance to characterize mortality rates in residents of an urban slum in Kenya. METHODS: We analyzed biweekly household visit data collected two weeks before death for 749 cases who died during January 1, 2007 to December 31, 2010. We also selected controls matched by age, gender and having a biweekly household visit within two weeks before death of the corresponding case and compared the symptoms reported. RESULTS: The overall mortality rate was 6.3 per 1,000 person years of observation (PYO) (females: 5.7; males: 6.8). Infant mortality rate was 50.2 per 1000 PYOs, and it was 15.1 per 1,000 PYOs for children <5 years old. Poisson regression indicates a significant decrease over time in overall mortality from (6.0 in 2007 to 4.0 in 2010 per 1000 PYOs; p<0.05) in persons ≥ 5 years old. This decrease was predominant in females (7.8 to 5.7 per 1000 PYOs; p<0.05). Two weeks before death, significantly higher prevalence for cough (OR = 4.7 [95% CI: 3.7-5.9]), fever (OR = 8.1 [95% CI: 6.1-10.7]), and diarrhea (OR = 9.1 [95% CI: 6.4-13.2]) were reported among participants who died (cases) when compared to participants who did not die (controls). Diarrhea followed by fever were independently associated with deaths (OR = 14.4 [95% CI: 7.1-29.2]), and (OR = 11.4 [95% CI: 6.7-19.4]) respectively. CONCLUSIONS: Despite accessible health care, mortality rates are high among people living in this urban slum; infectious disease syndromes appear to be linked to a substantial proportion of deaths. Rapid urbanization poses an increasing challenge in national efforts to improve health outcomes, including reducing childhood mortality rates. Targeting impoverished people in urban slums with effective interventions such as water and sanitation interventions are needed to achieve national objectives for health.

Use of population-based surveillance to determine the incidence of rotavirus gastroenteritis in an urban slum and a rural setting in Kenya.

BACKGROUND: Rotavirus gastroenteritis is a major cause of mortality among children <2 years of age. Disease burden data are important for introducing and sustaining new rotavirus vaccines in immunization programs. METHODS: We analyzed population-based infectious disease surveillance data from 2007 to 2010 from Kenyan sites in rural and urban slum areas. Stool specimens were collected from patients of all ages presenting to study clinics with diarrheal disease and tested for rotavirus by enzyme immunoassay. Incidence rates were adjusted using data on healthcare utilization (from biweekly home visits) and proportion of stools collected at study clinics from patients meeting case definitions. RESULTS: Rotavirus was detected in 285 (9.0%) of 3174 stools tested, including 122 (11.9%) from children <5 years of age and 162 (7.6%) from participants ≥5 years of age. Adjusted incidence rates for infants were 13,419 and 12,135 per 100,000 person-years of observation in rural and urban areas, respectively. Adjusted incidence rates were high in adults across age ranges. The rates suggest that annually, among children <5 years of age, there are >54,500 cases of rotavirus-associated gastroenteritis in rural Nyanza Province and >16,750 cases in Nairobi urban slums. CONCLUSIONS: Community-based surveillance in urban and rural Kenya suggests that rotavirus plays an important role as a cause of acute gastroenteritis in adults, as well as in children. In addition to substantially preventing illness and complications from diarrheal disease in children, rotavirus infant immunization has the potential of indirectly preventing diarrheal disease in older children and adults, assuming children are the predominant sources of transmission.

Epidemiology of respiratory syncytial virus infection in rural and urban Kenya.

BACKGROUND: Information on the epidemiology of respiratory syncytial virus (RSV) infection in Africa is limited for crowded urban areas and for rural areas where the prevalence of malaria is high. METHODS: At referral facilities in rural western Kenya and a Nairobi slum, we collected nasopharyngeal/oropharyngeal (NP/OP) swab specimens from patients with influenza-like illness (ILI) or severe acute respiratory illness (SARI) and from asymptomatic controls. Polymerase chain reaction assays were used for detection of viral pathogens. We calculated age-specific ratios of the odds of RSV detection among patients versus the odds among controls. Incidence was expressed as the number of episodes per 1000 person-years of observation. RESULTS: Between March 2007 and February 2011, RSV was detected in 501 of 4012 NP/OP swab specimens (12.5%) from children and adults in the rural site and in 321 of 2744 NP/OP swab specimens (11.7%) from those in the urban site. Among children aged <5 years, RSV was detected more commonly among rural children with SARI (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.3), urban children with SARI (OR, 8.5; 95% CI, 3.1-23.6), and urban children with ILI (OR, 3.4; 95% CI, 1.2-9.6), compared with controls. The incidence of RSV disease was highest among infants with SARI aged <1 year (86.9 and 62.8 episodes per 1000 person-years of observation in rural and urban sites, respectively). CONCLUSIONS: An effective RSV vaccine would likely substantially reduce the burden of respiratory illness among children in rural and urban areas in Africa.

Urban leptospirosis in Africa: a cross-sectional survey of Leptospira infection in rodents in the Kibera urban settlement, Nairobi, Kenya.

Leptospirosis is a widespread but under-reported cause of morbidity and mortality. Global re-emergence of leptospirosis has been associated with the growth of informal urban settlements in which rodents are thought to be important reservoir hosts. Understanding the multi-host epidemiology of leptospirosis is essential to control and prevent disease. A cross-sectional survey of rodents in the Kibera settlement in Nairobi, Kenya was conducted in September-October 2008 to demonstrate the presence of pathogenic leptospires. A real-time quantitative polymerase chain reaction showed that 41 (18.3%) of 224 rodents carried pathogenic leptospires in their kidneys, and sequence data identified Leptospira interrogans and L. kirschneri in this population. Rodents of the genus Mus (37 of 185) were significantly more likely to be positive than those of the genus Rattus (4 of 39; odds ratio = 15.03). Questionnaire data showed frequent contact between humans and rodents in Kibera. This study emphasizes the need to quantify the public health impacts of this neglected disease at this and other urban sites in Africa.

Use of population-based surveillance to define the high incidence of shigellosis in an urban slum in Nairobi, Kenya.

BACKGROUND: Worldwide, Shigella causes an estimated 160 million infections and >1 million deaths annually. However, limited incidence data are available from African urban slums. We investigated the epidemiology of shigellosis and drug susceptibility patterns within a densely populated urban settlement in Nairobi, Kenya through population-based surveillance. METHODS: Surveillance participants were interviewed in their homes every 2 weeks by community interviewers. Participants also had free access to a designated study clinic in the surveillance area where stool specimens were collected from patients with diarrhea (≥3 loose stools within 24 hours) or dysentery (≥1 stool with visible blood during previous 24 hours). We adjusted crude incidence rates for participants meeting stool collection criteria at household visits who reported visiting another clinic. RESULTS: Shigella species were isolated from 262 (24%) of 1,096 stool specimens [corrected]. The overall adjusted incidence rate was 408/100,000 person years of observation (PYO) with highest rates among adults 34-49 years old (1,575/100,000 PYO). Isolates were: Shigella flexneri (64%), S. dysenteriae (11%), S. sonnei (9%), and S. boydii (5%). Over 90% of all Shigella isolates were resistant to trimethoprim-sulfamethoxazole and sulfisoxazole. Additional resistance included nalidixic acid (3%), ciprofloxacin (1%) and ceftriaxone (1%). CONCLUSION: More than 1 of every 200 persons experience shigellosis each year in this Kenyan urban slum, yielding rates similar to those in some Asian countries. Provision of safe drinking water, improved sanitation, and hygiene in urban slums are needed to reduce disease burden, in addition to development of effective Shigella vaccines.

Epidemiology, seasonality, and burden of influenza and influenza-like illness in urban and rural Kenya, 2007-2010.

BACKGROUND: The epidemiology and burden of influenza remain poorly defined in sub-Saharan Africa. Since 2005, the Kenya Medical Research Institute and Centers for Disease Control and Prevention-Kenya have conducted population-based infectious disease surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural community in western Kenya. METHODS: Nasopharyngeal and oropharyngeal swab specimens were obtained from patients who attended the study clinic and had acute lower respiratory tract (LRT) illness. Specimens were tested for influenza virus by real-time reverse-transcription polymerase chain reaction. We adjusted the incidence of influenza-associated acute LRT illness to account for patients with acute LRT illness who attended the clinic but were not sampled. RESULTS: From March 2007 through February 2010, 4140 cases of acute LRT illness were evaluated in Kibera, and specimens were collected from 1197 (27%); 319 (27%) were positive for influenza virus. In Lwak, there were 6733 cases of acute LRT illness, and specimens were collected from 1641 (24%); 359 (22%) were positive for influenza virus. The crude and adjusted rates of medically attended influenza-associated acute LRT illness were 6.9 and 13.6 cases per 1000 person-years, respectively, in Kibera, and 5.6 and 23.0 cases per 1000 person-years, respectively, in Lwak. In both sites, rates of influenza-associated acute LRT illness were highest among children <2 years old and lowest among adults ≥50 years old. CONCLUSION: In Kenya, the incidence of influenza-associated acute LRT illness was high in both rural and urban settings, particularly among the most vulnerable age groups.

Differing burden and epidemiology of non-Typhi Salmonella bacteremia in rural and urban Kenya, 2006-2009.

BACKGROUND: The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change. METHODS: As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006-2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0°C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured. RESULTS: NTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman's correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy. CONCLUSIONS: NTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa.