Beatrice Olack

Evaluation of the optimal recall period for disease symptoms in home-based morbidity surveillance in rural and urban Kenya

Background In African settings with poor access to health care, surveillance and surveys of disease burden are often done through home visits. The optimal recall period to capture data on symptoms and health utilization is unknown. Methods We collected illness data among 53 000 people during fortnightly home visits in rural and urban Kenya. Dates of cough, fever and diarrhoea in the past 2 weeks and health-seeking behaviour were recorded. Incidence rates were modelled using Poisson regression for data collected from 1 July 2006 to 30 June 2007. Results Incidence rates were higher in days 0–6 before the home visit than in days 7–13 before the home visit for all three symptoms, for the rural and urban sites, for children and adults, for self- and proxy-reported symptoms and for severe and non-severe illness in children. Recall decay was steeper in the rural than the urban sites, and for proxy- than self-reported symptoms. The daily prevalence of symptoms fell <80% of the maximum prevalence when asking about symptoms >3 days before the home visit for children and >4 days for persons ≥5 years of age. Recall of previously documented clinic visits, and prescriptions of antimalarials and antibiotics also declined by ∼7, 15 and 23% per week, respectively, in children aged <5 years, and 6, 20 and 16%, respectively, in older persons (P < 0.0001 for each decline). Conclusions A 2-week recall period underestimates true disease rates and health-care utilization. Shorter recall periods of 3 days in children and 4 days in adults would likely yield more accurate data.

Population-based incidence of typhoid fever in an urban informal settlement and a rural area in Kenya: Implications for typhoid vaccine use in Africa

Background High rates of typhoid fever in children in urban settings in Asia have led to focus on childhood immunization in Asian cities, but not in Africa, where data, mostly from rural areas, have shown low disease incidence. We set out to compare incidence of typhoid fever in a densely populated urban slum and a rural community in Kenya, hypothesizing higher rates in the urban area, given crowding and suboptimal access to safe water, sanitation and hygiene. Methods During 2007-9, we conducted population-based surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural area in western Kenya. Participants had free access to study clinics; field workers visited their homes biweekly to collect information about acute illnesses. In clinic, blood cultures were processed from patients with fever or pneumonia. Crude and adjusted incidence rates were calculated. Results In the urban site, the overall crude incidence of Salmonella enterica serovar Typhi (S. Typhi) bacteremia was 247 cases per 100,000 person-years of observation (pyo) with highest rates in children 5–9 years old (596 per 100,000 pyo) and 2–4 years old (521 per 100,000 pyo). Crude overall incidence in Lwak was 29 cases per 100,000 pyo with low rates in children 2–4 and 5–9 years old (28 and 18 cases per 100,000 pyo, respectively). Adjusted incidence rates were highest in 2–4 year old urban children (2,243 per 100,000 pyo) which were >15-fold higher than rates in the rural site for the same age group. Nearly 75% of S. Typhi isolates were multi-drug resistant. Conclusions This systematic urban slum and rural comparison showed dramatically higher typhoid incidence among urban children <10 years old with rates similar to those from Asian urban slums. The findings have potential policy implications for use of typhoid vaccines in increasingly urban Africa.

The Burden of Common Infectious Disease Syndromes at the Clinic and Household Level from Population-Based Surveillance in Rural and Urban Kenya

Background Characterizing infectious disease burden in Africa is important for prioritizing and targeting limited resources for curative and preventive services and monitoring the impact of interventions. Methods From June 1, 2006 to May 31, 2008, we estimated rates of acute lower respiratory tract illness (ALRI), diarrhea and acute febrile illness (AFI) among >50,000 persons participating in population-based surveillance in impoverished, rural western Kenya (Asembo) and an informal settlement in Nairobi, Kenya (Kibera). Field workers visited households every two weeks, collecting recent illness information and performing limited exams. Participants could access free high-quality care in a designated referral clinic in each site. Incidence and longitudinal prevalence were calculated and compared using Poisson regression. Results Incidence rates resulting in clinic visitation were the following: ALRI — 0.36 and 0.51 episodes per year for children <5 years and 0.067 and 0.026 for persons ≥5 years in Asembo and Kibera, respectively; diarrhea — 0.40 and 0.71 episodes per year for children <5 years and 0.09 and 0.062 for persons ≥5 years in Asembo and Kibera, respectively; AFI — 0.17 and 0.09 episodes per year for children <5 years and 0.03 and 0.015 for persons ≥5 years in Asembo and Kibera, respectively. Annually, based on household visits, children <5 years in Asembo and Kibera had 60 and 27 cough days, 10 and 8 diarrhea days, and 37 and 11 fever days, respectively. Household-based rates were higher than clinic rates for diarrhea and AFI, this difference being several-fold greater in the rural than urban site. Conclusions Individuals in poor Kenyan communities still suffer from a high burden of infectious diseases, which likely hampers their development. Urban slum and rural disease incidence and clinic utilization are sufficiently disparate in Africa to warrant data from both settings for estimating burden and focusing interventions.

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, Spearmans 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.

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.

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

Summary 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.

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.

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.

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.

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 224 (23%) of 976 stool specimens. 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.