Godfrey Bigogo

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.

Non-pneumococcal mitis-group streptococci confound detection of pneumococcal capsular serotype-specific loci in upper respiratory tract

We performed culture-based and PCR-based tests for pneumococcal identification and serotyping from carriage specimens collected in rural and urban Kenya. Nasopharyngeal specimens from 237 healthy children <5 years old (C-NPs) and combined nasopharyngeal/oropharyngeal specimens from 158 adults (A-NP/OPs, 118 HIV-positive) were assessed using pneumococcal isolation (following broth culture enrichment) with Quellung-based serotyping, real-time lytA-PCR, and conventional multiplexed PCR-serotyping (cmPCR). Culture-based testing from C-NPs, HIV-positive A-NP/OPs, and HIV-negative A-NP/OPs revealed 85.2%, 40.7%, and 12.5% pneumococcal carriage, respectively. In contrast, cmPCR serotypes were found in 93.2%, 98.3%, and 95.0% of these sets, respectively. Two of 16 lytA-negative C-NPs and 26 of 28 lytA-negative A-NP/OPs were cmPCR-positive for 1–10 serotypes (sts) or serogroups (sgs). A-NP/OPs averaged 5.5 cmPCR serotypes/serogroups (5.2 in HIV-positive, 7.1 in HIV-negative) and C-NPs averaged 1.5 cmPCR serotypes/serogroups. cmPCR serotypes/serogroups from lytA-negative A-NP/OPs included st2, st4, sg7F/7A, sg9N/9L, st10A, sg10F/10C/33C, st13, st17F, sg18C/18A/18B/18F, sg22F/22A, and st39. Nine strains of three non-pneumococcal species (S. oralis, S. mitis, and S. parasanguinis) (7 from A-OP, 1 from both A-NP and A-OP, and 1 from C-NP) were each cmPCR-positive for one of 7 serotypes/serogroups (st5, st13, sg15A/15F, sg10F/10C/33C, sg33F/33A/37, sg18C/18A/18B/18F, sg12F/12A/12B/ 44/46) with amplicons revealing 83.6–99.7% sequence identity to pneumococcal references. In total, 150 cmPCR amplicons from carriage specimens were sequenced, including 25 from lytA-negative specimens. Amplicon sequences derived from specimens yielding a pneumococcal isolate with the corresponding serotype were identical or highly conserved (>98.7%) with the reference cmPCR amplicon for the st, while cmPCR amplicons from lytA-negative specimens were generally more divergent. Separate testing of 56 A-OPs and 56 A-NPs revealed that ∼94% of the positive cmPCR results from A-NP/OPs were from OP microbiota. In contrast, A-NPs yielded >2-fold more pneumococcal isolates than A-OPs. Verified and suspected non-pneumococcal cmPCR serotypes/serogroups appeared to be relatively rare in C-NPs and A-NPs compared to A-OPs. Our findings indicate that non-pneumococcal species can confound serotype-specific PCR and other sequence-based assays due to evolutionarily conserved genes most likely involved in biosynthesis of surface polysaccharide structures.

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.

Etiology and Incidence of Viral and Bacterial Acute Respiratory Illness among Older Children and Adults in Rural Western Kenya, 2007–2010

Background Few comprehensive data exist on disease incidence for specific etiologies of acute respiratory illness (ARI) in older children and adults in Africa. Methodology/Principal Findings From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0°C or oxygen saturation <90% or hospitalization). We also collected swabs from asymptomatic controls, from which we calculated pathogen-attributable fractions, adjusting for age, season, and HIV-status, in logistic regression. We calculated incidence by pathogen, adjusting for health-seeking for ARI and pathogen-attributable fractions. Among 3,406 ARI patients >5 years old (adjusted annual incidence 12.0 per 100 person-years), influenza A virus was the most common virus (22% overall; 11% inpatients, 27% outpatients) and Streptococcus pneumoniae was the most common bacteria (16% overall; 23% inpatients, 14% outpatients), yielding annual incidences of 2.6 and 1.7 episodes per 100 person-years, respectively. Influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human metapneumovirus were more prevalent in swabs among cases (22%, 6%, 8% and 5%, respectively) than controls. Adenovirus, parainfluenza viruses, rhinovirus/enterovirus, parechovirus, and Mycoplasma pneumoniae were not more prevalent among cases than controls. Pneumococcus and non-typhi Salmonella were more prevalent among HIV-infected adults, but prevalence of viruses was similar among HIV-infected and HIV-negative individuals. ARI incidence was highest during peak malaria season. Conclusions/Signficance Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings.

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.

Viral and bacterial causes of severe acute respiratory illness among children aged less than 5 years in a high malaria prevalence area of western Kenya, 2007-2010.

Background: Few comprehensive data exist on the etiology of severe acute respiratory illness (SARI) among African children. Methods: From March 1, 2007 to February 28, 2010, we collected blood for culture and nasopharyngeal and oropharyngeal swabs for real-time quantitative polymerase chain reaction for 10 viruses and 3 atypical bacteria among children aged <5 years with SARI, defined as World Health Organization–classified severe or very severe pneumonia or oxygen saturation <90%, who visited a clinic in rural western Kenya. We collected swabs from controls without febrile or respiratory symptoms. We calculated odds ratios for infection among cases, adjusting for age and season in logistic regression. We calculated SARI incidence, adjusting for healthcare seeking for SARI in the community. Results: Two thousand nine hundred seventy-three SARI cases were identified (54% inpatient, 46% outpatient), yielding an adjusted incidence of 56 cases per 100 person-years. A pathogen was detected in 3.3% of noncontaminated blood cultures; non-typhi Salmonella (1.9%) and Streptococcus pneumoniae (0.7%) predominated. A pathogen was detected in 84% of nasopharyngeal/oropharyngeal specimens, the most common being rhino/enterovirus (50%), respiratory syncytial virus (RSV, 22%), adenovirus (16%) and influenza viruses (8%). Only RSV and influenza viruses were found more commonly among cases than controls (odds ratio 2.9, 95% confidence interval: 1.3–6.7 and odds ratio 4.8, 95% confidence interval: 1.1–21, respectively). Incidence of RSV, influenza viruses and S. pneumoniae were 7.1, 5.8 and 0.04 cases per 100 person-years, respectively. Conclusions: Among Kenyan children with SARI, RSV and influenza virus are the most likely viral causes and pneumococcus the most likely bacterial cause. Contemporaneous controls are important for interpreting upper respiratory tract specimens.

Respiratory Syncytial Virus Circulation in Seven Countries With Global Disease Detection Regional Centers

BACKGROUND Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children globally, with the highest burden in low- and middle-income countries where the association between RSV activity and climate remains unclear. METHODS Monthly laboratory-confirmed RSV cases and associations with climate data were assessed for respiratory surveillance sites in tropical and subtropical areas (Bangladesh, China, Egypt, Guatemala, Kenya, South Africa, and Thailand) during 2004-2012. Average monthly minimum and maximum temperatures, relative humidity, and precipitation were calculated using daily local weather data from the US National Climatic Data Center. RESULTS RSV circulated with 1-2 epidemic periods each year in site areas. RSV seasonal timing and duration were generally consistent within country from year to year. Associations between RSV and weather varied across years and geographic locations. RSV usually peaked in climates with high annual precipitation (Bangladesh, Guatemala, and Thailand) during wet months, whereas RSV peaked during cooler months in moderately hot (China) and arid (Egypt) regions. In South Africa, RSV peaked in autumn, whereas no associations with seasonal weather trends were observed in Kenya. CONCLUSIONS Further understanding of RSV seasonality in developing countries and various climate regions will be important to better understand the epidemiology of RSV and for timing the use of future RSV vaccines and immunoprophylaxis in low- and middle-income countries.

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.

High rate of pneumococcal bacteremia in a prospective cohort of older children and adults in an area of high HIV prevalence in rural western Kenya

BackgroundAlthough causing substantial morbidity, the burden of pneumococcal disease among older children and adults in Africa, particularly in rural settings, is not well-characterized. We evaluated pneumococcal bacteremia among 21,000 persons ≥5 years old in a prospective cohort as part of population-based infectious disease surveillance in rural western Kenya from October 2006-September 2008.MethodsBlood cultures were done on patients meeting pre-defined criteria - severe acute respiratory illness (SARI), fever, and admission for any reason at a referral health facility within 5 kilometers of all 33 villages where surveillance took place. Serotyping of Streptococcus pneumoniae was done by latex agglutination and quellung reaction and antibiotic susceptibility testing was done using broth microdilution. We extrapolated incidence rates based on persons with compatible illnesses in the surveillance population who were not cultured. We estimated rates among HIV-infected persons based on community HIV prevalence. We projected the national burden of pneumococcal bacteremia cases based on these rates.ResultsAmong 1,301 blood cultures among persons ≥5 years, 52 (4%) yielded pneumococcus, which was the most common bacteria isolated. The yield was higher among those ≥18 years than 5-17 years (6.9% versus 1.6%, p < 0.001). The highest yield was for inpatients with SARI (10%), compared with SARI outpatients (3%) and acute febrile outpatients (1%). Serotype 1 pneumococcus was most common (42% isolates) and 71% were serotypes included in the 10-valent pneumococcal conjugate vaccine (PCV10). Non-susceptibility to beta-lactam antibiotics was low (<5%), but to trimethoprim-sulfamethoxazole was high (>95%). The crude rate of pneumococcal bacteremia was 129/100,000 person-years, and the adjusted rate was 419/100,000 person-years. Nineteen (61%) of 31 patients with HIV results were HIV-positive. The adjusted rate among HIV-infected persons was 2,399/100,000 person-years (Rate ratio versus HIV-negative adults, 19.7, 95% CI 12.4-31.1). We project 58,483 cases of pneumococcal bacteremia will occur in Kenyan adults in 2010.ConclusionsPneumococcal bacteremia rates were high among persons ≥5 years old, particularly among HIV-infected persons. Ongoing surveillance will document if expanded use of highly-active antiretroviral treatment for HIV and introduction of PCV10 for Kenyan children (anticipated in late 2010) result in substantial secondary benefits by reducing pneumococcal disease in adults.