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1.  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.
PMCID: PMC3854886  PMID: 24080637
2.  Caretakers’ Perception towards Using Zinc to Treat Childhood Diarrhoea in Rural Western Kenya 
Zinc treatment for diarrhoea can shorten the course and prevent future episodes among children worldwide. However, knowledge and acceptability of zinc among African mothers is unknown. We identified children aged 3 to 59 months, who had diarrhoea within the last three months and participated in a home-based zinc treatment study in rural Kenya. Caretakers of these children were enrolled in two groups; zinc-users and non-users. A structured questionnaire was administered to all caretakers, inquiring about knowledge and appropriate use of zinc. Questions on how much the caretakers were willing to pay for zinc were asked. Proportions were compared using Mantel-Haenszel test, and medians were compared using Wilcoxon Rank Sum test. Among 109 enrolled caretakers, 73 (67%) used zinc, and 36 (33%) did not. Sixty-four (88%) caretakers in zinc-user group reported satisfaction with zinc treatment. Caretakers in the zinc-user group more often correctly identified appropriate zinc treatment (98%-100%) than did those in the non-user group (64−72%, p<0.001). Caretakers in the zinc-user group answered more questions about zinc correctly or favourably (median 10 of 11) compared to those in the non-user group (median 6.3 of 11, p<0.001). Caretakers in the zinc-user group were willing to pay more for a course of zinc in the future than those in the non-user group (median US$ 0.26, p<0.001). Caretakers of children given zinc recently had favourable impressions on the therapy and were willing to pay for it in the future. Active promotion of zinc treatment in clinics and communities in Africa could lead to greater knowledge, acceptance, and demand for zinc.
PMCID: PMC3805881  PMID: 24288945
Acceptability; Community treatment; Diarrhoeal disease; Zinc; Kenya
3.  Preface 
PMCID: PMC3748495  PMID: 23629933
4.  Health care seeking for Childhood Diarrhea in Developing Countries: Evidence from Seven Sites in Africa and Asia 
We performed serial Health Care Utilization and Attitudes Surveys (HUASs) among caretakers of children ages 0–59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case-control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0–11 months of age), from 0.4% to 4.7% for toddlers (12–23 months of age), and from 0.3% to 2.4% for preschoolers (24–59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15–56%, 17–64%, and 7–33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial HUASs as a tool for optimizing operational and methodological issues related to the performance of a large case-control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings.
PMCID: PMC3748499  PMID: 23629939
5.  Additional Diagnostic Yield of Adding Serology to PCR in Diagnosing Viral Acute Respiratory Infections in Kenyan Patients 5 Years of Age and Older 
The role of serology in the setting of PCR-based diagnosis of acute respiratory infections (ARIs) is unclear. We found that acute- and convalescent-phase paired-sample serologic testing increased the diagnostic yield of naso/oropharyngeal swabs for influenza virus, respiratory syncytial virus (RSV), human metapneumovirus, adenovirus, and parainfluenza viruses beyond PCR by 0.4% to 10.7%. Although still limited for clinical use, serology, along with PCR, can maximize etiologic diagnosis in epidemiologic studies.
PMCID: PMC3535781  PMID: 23114699
6.  Non-pneumococcal mitis-group streptococci confound detection of pneumococcal capsular serotype-specific loci in upper respiratory tract 
PeerJ  2013;1:e97.
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.
PMCID: PMC3698467  PMID: 23825797
Pneumococcal serotype-specific loci; Mitis group streptococci; Oropharyngeal and nasopharyngeal flora; PCR for serotype deduction
7.  Healthcare-use for Major Infectious Disease Syndromes in an Informal Settlement in Nairobi, Kenya 
A healthcare-use survey was conducted in the Kibera informal settlement in Nairobi, Kenya, in July 2005 to inform subsequent surveillance in the site for infectious diseases. Sets of standardized questionnaires were administered to 1,542 caretakers and heads of households with one or more child(ren) aged less than five years. The average household-size was 5.1 (range 1-15) persons. Most (90%) resided in a single room with monthly rents of US$ 4.50-7.00. Within the previous two weeks, 49% of children (n=1,378) aged less than five years (under-five children) and 18% of persons (n=1,139) aged ≥5 years experienced febrile, diarrhoeal or respiratory illnesses. The large majority (>75%) of illnesses were associated with healthcare-seeking. While licensed clinics were the most-frequently visited settings, kiosks, unlicensed care providers, and traditional healers were also frequently visited. Expense was cited most often (50%) as the reason for not seeking healthcare. Of those who sought healthcare, 34-44% of the first and/or the only visits were made with non-licensed care providers, potentially delaying opportunities for early optimal intervention. The proportions of patients accessing healthcare facilities were higher with diarrhoeal disease and fever (but not for respiratory diseases in under-five children) than those reported from a contemporaneous study conducted in a rural area in Kenya. The findings support community-based rather than facility-based surveillance in this setting to achieve objectives for comprehensive assessment of the burden of disease.
PMCID: PMC3126984  PMID: 21608421
Acute respiratory infection; Diarrhoeal diseases; Febrile illness; Healthcare-seeking; Healthcare-use; Informal settlements; Pneumonia; Slums; Urbanization; Kenya
8.  Coxiella burnetii in Humans, Domestic Ruminants, and Ticks in Rural Western Kenya 
We conducted serological surveys for Coxiella burnetii in archived sera from patients that visited a rural clinic in western Kenya from 2007 to 2008 and in cattle, sheep, and goats from the same area in 2009. We also conducted serological and polymerase chain reaction-based surveillance for the pathogen in 2009–2010, in human patients with acute lower respiratory illness, in ruminants following parturition, and in ticks collected from ruminants and domestic dogs. Antibodies against C. burnetii were detected in 30.9% (N = 246) of archived patient sera and in 28.3% (N = 463) of cattle, 32.0% (N = 378) of goats, and 18.2% (N = 159) of sheep surveyed. Four of 135 (3%) patients with acute lower respiratory illness showed seroconversion to C. burnetii. The pathogen was detected by polymerase chain reaction in specimens collected from three of six small ruminants that gave birth within the preceding 24 hours, and in five of 10 pools (50%) of Haemaphysalis leachi ticks collected from domestic dogs.
PMCID: PMC3592534  PMID: 23382156
9.  The Global Enteric Multicenter Study (GEMS) of Diarrheal Disease in Infants and Young Children in Developing Countries: Epidemiologic and Clinical Methods of the Case/Control Study 
Background. Diarrhea is a leading cause of illness and death among children aged <5 years in developing countries. This paper describes the clinical and epidemiological methods used to conduct the Global Enteric Multicenter Study (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the population-based burden, microbiologic etiology, and adverse clinical consequences of acute moderate-to-severe diarrhea (MSD) among a censused population of children aged 0–59 months seeking care at health centers in sub-Saharan Africa and South Asia.
Methods. GEMS was conducted at 7 field sites, each serving a population whose demography and healthcare utilization practices for childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year from selected health centers serving each site in each of 3 age strata (0–11, 12–23, and 24–59 months), along with 1–3 matched community controls. Cases and controls supplied clinical, epidemiologic, and anthropometric data at enrollment and again approximately 60 days later, and provided enrollment stool specimens for identification and characterization of potential diarrheal pathogens. Verbal autopsy was performed if a child died. Analytic strategies will calculate the fraction of MSD attributable to each pathogen and the incidence, financial costs, nutritional consequences, and case fatality overall and by pathogen.
Conclusions. When completed, GEMS will provide estimates of the incidence, etiology, and outcomes of MSD among infants and young children in sub-Saharan Africa and South Asia. This information can guide development and implementation of public health interventions to diminish morbidity and mortality from diarrheal diseases.
PMCID: PMC3502307  PMID: 23169936
10.  Exploring Household Economic Impacts of Childhood Diarrheal Illnesses in 3 African Settings 
Beyond the morbidity and mortality burden of childhood diarrhea in sub-Saharan African are significant economic costs to affected households. Using survey data from 3 of the 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali) participating in the Global Enteric Multicenter Study (GEMS), we estimated the direct medical, direct nonmedical, and indirect (productivity losses) costs borne by households due to diarrhea in young children. Mean cost per episode was $2.63 in Gambia, $6.24 in Kenya, and $4.11 in Mali. Direct medical costs accounted for less than half of these costs. Mean costs understate the distribution of costs, with 10% of cases exceeding $6.50, $11.05, and $13.84 in Gambia, Kenya, and Mali. In all countries there was a trend toward lower costs among poorer households and in 2 of the countries for diarrheal illness affecting girls. For poor children and girls, this may reflect reduced household investment in care, which may result in increased risks of mortality.
PMCID: PMC3502313  PMID: 23169944
11.  Examining the Use of Oral Rehydration Salts and Other Oral Rehydration Therapy for Childhood Diarrhea in Kenya 
Reductions in the use of oral rehydration therapy (ORT) in sub-Saharan Africa highlight the need to examine caregiver perceptions of ORT during diarrheal episodes. Qualitative research involving group discussions with childcare providers and in-depth interviews with 45 caregivers of children < 5 years of age who had experienced diarrhea was conducted in one rural and urban site in Kenya during July–December 2007. Diarrhea was considered a dangerous condition that can kill young children. Caregivers preferred to treat diarrhea with Western drugs believed to be more effective in stopping diarrhea than ORT. Inconsistent recommendations from health workers regarding use of oral rehydration solution (ORS) caused confusion about when ORS is appropriate and whether it requires a medical prescription. In the rural community, causal explanations about diarrhea, beliefs in herbal remedies, cost, and distance to health facilities presented additional barriers to ORS use. Health communication is needed to clarify the function of ORT in preventing dehydration.
PMCID: PMC3225165  PMID: 22144457
12.  Community Case Management of Childhood Diarrhea in a Setting with Declining Use of Oral Rehydration Therapy: Findings from Cross-Sectional Studies among Primary Household Caregivers, Kenya, 2007 
We sought to determine factors associated with appropriate diarrhea case management in Kenya. We conducted a cross-sectional survey of caregivers of children < 5 years of age with diarrhea in rural Asembo and urban Kibera. In Asembo, 61% of respondents provided oral rehydration therapy (ORT), 45% oral rehydration solution (ORS), and 64% continued feeding. In Kibera, 75% provided ORT, 43% ORS, and 46% continued feeding. Seeking care at a health facility, risk perception regarding death from diarrhea, and treating a child with oral medications were associated with ORT and ORS use. Availability of oral medication was negatively associated. A minority of caregivers reported that ORS is available in nearby shops. In Kenya, household case management of diarrhea remains inadequate for a substantial proportion of children. Health workers have a critical role in empowering caregivers regarding early treatment with ORT and continued feeding. Increasing community ORS availability is essential to improving diarrhea management.
PMCID: PMC3225166  PMID: 22144458
13.  Challenges of Establishing the Correct Diagnosis of Outbreaks of Acute Febrile Illnesses in Africa: The Case of a Likely Brucella Outbreak among Nomadic Pastoralists, Northeast Kenya, March–July 2005 
An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed.
PMCID: PMC3205640  PMID: 22049048
14.  Video Surveillance Captures Student Hand Hygiene Behavior, Reactivity to Observation, and Peer Influence in Kenyan Primary Schools 
PLoS ONE  2014;9(3):e92571.
In-person structured observation is considered the best approach for measuring hand hygiene behavior, yet is expensive, time consuming, and may alter behavior. Video surveillance could be a useful tool for objectively monitoring hand hygiene behavior if validated against current methods.
Student hand cleaning behavior was monitored with video surveillance and in-person structured observation, both simultaneously and separately, at four primary schools in urban Kenya over a study period of 8 weeks.
Video surveillance and in-person observation captured similar rates of hand cleaning (absolute difference <5%, p = 0.74). Video surveillance documented higher hand cleaning rates (71%) when at least one other person was present at the hand cleaning station, compared to when a student was alone (48%; rate ratio  = 1.14 [95% CI 1.01–1.28]). Students increased hand cleaning rates during simultaneous video and in-person monitoring as compared to single-method monitoring, suggesting reactivity to each method of monitoring. This trend was documented at schools receiving a handwashing with soap intervention, but not at schools receiving a sanitizer intervention.
Video surveillance of hand hygiene behavior yields results comparable to in-person observation among schools in a resource-constrained setting. Video surveillance also has certain advantages over in-person observation, including rapid data processing and the capability to capture new behavioral insights. Peer influence can significantly improve student hand cleaning behavior and, when possible, should be exploited in the design and implementation of school hand hygiene programs.
PMCID: PMC3968003  PMID: 24676389
15.  Predicting Mortality among Hospitalized Children with Respiratory Illness in Western Kenya, 2009–2012 
PLoS ONE  2014;9(3):e92968.
Pediatric respiratory disease is a major cause of morbidity and mortality in the developing world. We evaluated a modified respiratory index of severity in children (mRISC) scoring system as a standard tool to identify children at greater risk of death from respiratory illness in Kenya.
Materials and Methods
We analyzed data from children <5 years old who were hospitalized with respiratory illness at Siaya District Hospital from 2009–2012. We used a multivariable logistic regression model to identify patient characteristics predictive for in-hospital mortality. Model discrimination was evaluated using the concordance statistic. Using bootstrap samples, we re-estimated the coefficients and the optimism of the model. The mRISC score for each child was developed by adding up the points assigned to each factor associated with mortality based on the coefficients in the multivariable model.
We analyzed data from 3,581 children hospitalized with respiratory illness; including 218 (6%) who died. Low weight-for-age [adjusted odds ratio (aOR) = 2.1; 95% CI 1.3–3.2], very low weight-for-age (aOR = 3.8; 95% CI 2.7–5.4), caretaker-reported history of unconsciousness (aOR = 2.3; 95% CI 1.6–3.4), inability to drink or breastfeed (aOR = 1.8; 95% CI 1.2–2.8), chest wall in-drawing (aOR = 2.2; 95% CI 1.5–3.1), and being not fully conscious on physical exam (aOR = 8.0; 95% CI 5.1–12.6) were independently associated with mortality. The positive predictive value for mortality increased with increasing mRISC scores.
A modified RISC scoring system based on a set of easily measurable clinical features at admission was able to identify children at greater risk of death from respiratory illness in Kenya.
PMCID: PMC3965502  PMID: 24667695
16.  Preparedness for Highly Pathogenic Avian Influenza Pandemic in Africa 
Emerging Infectious Diseases  2007;13(10):1453-1458.
Africa’s strategies for pandemic influenza must also strengthen overall public health capacity.
Global concerns about an impending influenza pandemic escalated when highly pathogenic influenza A subtype H5N1 appeared in Nigeria in January 2006. The potential devastation from emergence of a pandemic strain in Africa has led to a sudden shift of public health focus to pandemic preparedness. Preparedness and control activities must work within the already strained capacity of health infrastructure in Africa to respond to immense existing public health problems. Massive attention and resources directed toward influenza could distort priorities and damage critical public health programs. Responses to concerns about pandemic influenza should strengthen human and veterinary surveillance and laboratory capacity to help address a variety of health threats. Experiences in Asia should provide bases for reassessing strategies for Africa and elsewhere. Fowl depopulation strategies will need to be adapted for Africa. Additionally, the role of avian vaccines should be comprehensively evaluated and clearly defined.
PMCID: PMC2851538  PMID: 18257986
Influenza; avian; Africa; H5N1; capacity; Nigeria; surveillance; pandemic; IDSR; health priorities; research
17.  Secondary Household Transmission of 2009 Pandemic Influenza A (H1N1) Virus among an Urban and Rural Population in Kenya, 2009–2010 
PLoS ONE  2012;7(6):e38166.
In Kenya, >1,200 laboratory-confirmed 2009 pandemic influenza A (H1N1) (pH1N1) cases occurred since June 2009. We used population-based infectious disease surveillance (PBIDS) data to assess household transmission of pH1N1 in urban Nairobi (Kibera) and rural Lwak.
We defined a pH1N1 patient as laboratory-confirmed pH1N1 infection among PBIDS participants during August 1, 2009–February 5, 2010, in Kibera, or August 1, 2009–January 20, 2010, in Lwak, and a case household as a household with a laboratory-confirmed pH1N1 patient. Community interviewers visited PBIDS-participating households to inquire about illnesses among household members. We randomly selected 4 comparison households per case household matched by number of children aged <5. Comparison households had a household visit 10 days before or after the matched patient symptom onset date. We defined influenza-like illnesses (ILI) as self-reported cough or sore throat, and a self-reported fever ≤8 days after the pH1N1 patient's symptom onset in case households and ≤8 days before selected household visit in comparison households. We used the Cochran-Mantel-Haenszel test to compare proportions of ILIs among case and comparison households, and log binomial-model to compare that of Kibera and Lwak.
Among household contacts of patients with confirmed pH1N1 in Kibera, 4.6% had ILI compared with 8.2% in Lwak (risk ratio [RR], 0.5; 95% confidence interval [CI], 0.3–0.9). Household contacts of patients were more likely to have ILIs than comparison-household members in both Kibera (RR, 1.8; 95% CI, 1.1–2.8) and Lwak (RR, 2.6; 95% CI, 1.6–4.3). Overall, ILI was not associated with patient age. However, ILI rates among household contacts were higher among children aged <5 years than persons aged ≥5 years in Lwak, but not Kibera.
Substantial pH1N1 household transmission occurred in urban and rural Kenya. Household transmission rates were higher in the rural area.
PMCID: PMC3372521  PMID: 22701610
18.  Molecular Epidemiology of Geographically Dispersed Vibrio cholerae, Kenya, January 2009–May 2010 
Emerging Infectious Diseases  2012;18(6):925-931.
Isolates represent multiple genetic lineages, a finding consistent with multiple emergences from endemic reservoirs.
Numerous outbreaks of cholera have occurred in Kenya since 1971. To more fully understand the epidemiology of cholera in Kenya, we analyzed the genetic relationships among 170 Vibrio cholerae O1 isolates at 5 loci containing variable tandem repeats. The isolates were collected during January 2009–May 2010 from various geographic areas throughout the country. The isolates grouped genetically into 5 clonal complexes, each comprising a series of genotypes that differed by an allelic change at a single locus. No obvious correlation between the geographic locations of the isolates and their genotypes was observed. Nevertheless, geographic differentiation of the clonal complexes occurred. Our analyses showed that multiple genetic lineages of V. cholerae were simultaneously infecting persons in Kenya. This finding is consistent with the simultaneous emergence of multiple distinct genetic lineages of V. cholerae from endemic environmental reservoirs rather than recent introduction and spread by travelers.
PMCID: PMC3358164  PMID: 22607971
phenotypes; genotypes; Vibrio cholerae; cholera; characterization; molecular epidemiology; outbreaks; bacteria; Kenya
19.  Neonatal outcomes after influenza immunization during pregnancy: a randomized controlled trial 
There are limited data about the effect of maternal influenza infection on fetuses and newborns. We performed a secondary analysis of data from the Mother’s Gift project, a randomized study designed to test the effectiveness of inactivated influenza and pneumococcal vaccines during pregnancy.
In the Mother’s Gift project, 340 pregnant women in Bangladesh received either inactivated influenza vaccine or 23-valent pneumococcal polysaccharide vaccine (control). This study was performed from August 2004 through December 2005. We performed a secondary analysis of outcomes following maternal influenza immunization during two periods: when influenza virus was not circulating (September 2004 through January 2005) and when influenza virus was circulating (February through October 2005). We assessed gestational age, mean birth weight and the proportion of infants who were small for gestational age.
During the period with no circulating influenza virus, there were no differences in the incidence of respiratory illness with fever per 100 person-months among mothers and infants in the two groups (influenza vaccine: 3.9; control: 4.0; p > 0.9). The proportion of infants who were small for gestational age and the mean birth weight were similar between groups (small for gestational age: influenza vaccine 29.1%, control 34.3%; mean birth weight: influenza vaccine 3083 g, control 3053 g). During the period with circulating influenza virus, there was a substantial reduction in the incidence per 100 person-months of respiratory illness with fever among the mothers and infants who had received the influenza vaccine (influenza vaccine: 3.7; control: 7.2; p = 0.0003). During this period, the proportion of infants who were small for gestational age was lower in the influenza vaccine group than in the control group (25.9% v. 44.8%; p = 0.03). The mean birth weight was higher among infants whose mothers received the influenza vaccine than among those who received the control vaccine during this period (3178 g v. 2978 g; p = 0.02).
During the period with circulating influenza virus, maternal immunization during pregnancy was associated with a lower proportion of infants who were small for gestational age and an increase in mean birth weight. These data need confirmation but suggest that prevention of influenza infection in pregnancy can influence intrauterine growth.
Trial Registration: NCT 00142389
PMCID: PMC3314035  PMID: 22353593
20.  Sequential Rift Valley Fever Outbreaks in Eastern Africa Caused by Multiple Lineages of the Virus 
The Journal of Infectious Diseases  2010;203(5):655-665.
Background. During the Rift Valley fever (RVF) epidemic of 2006–2007 in eastern Africa, spatial mapping of the outbreaks across Kenya, Somalia, and Tanzania was performed and the RVF viruses were isolated and genetically characterized.
Methods. Following confirmation of the RVF epidemic in Kenya on 19 December 2006 and in Tanzania on 2 February 2007, teams were sent to the field for case finding. Human, livestock, and mosquito specimens were collected and viruses isolated. The World Health Organization response team in Kenya worked with the WHO’s polio surveillance team inside Somalia to collect information and specimens from Somalia.
Results. Seven geographical foci that reported hundreds of livestock and >25 cases in humans between December 2006 and June 2007 were identified. The onset of RVF cases in each epidemic focus was preceded by heavy rainfall and flooding for at least 10 days. Full-length genome analysis of 16 RVF virus isolates recovered from humans, livestock, and mosquitoes in 5 of the 7 outbreak foci revealed 3 distinct lineages of the viruses within and across outbreak foci.
Conclusion. The findings indicate that the sequential RVF epidemics in the region were caused by multiple lineages of the RVF virus, sometimes independently activated or introduced in distinct outbreak foci.
PMCID: PMC3071275  PMID: 21282193
21.  Role of China in the Quest to Define and Control Severe Acute Respiratory Syndrome 
Emerging Infectious Diseases  2003;9(9):1037-1041.
China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may then be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome. There must be support for systematically addressing these fundamental questions in China and rapidly disseminating results.
PMCID: PMC3016762  PMID: 14519236
SARS; Severe acute respiratory syndrome; China; wildlife; animals; genetic; sequence; incidence; Seroprevalence; transmission; super-spreader; evolution; emergence; outcome
22.  Differing Burden and Epidemiology of Non-Typhi Salmonella Bacteremia in Rural and Urban Kenya, 2006–2009 
PLoS ONE  2012;7(2):e31237.
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.
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.
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.
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.
PMCID: PMC3283637  PMID: 22363591
23.  Relationship of Climate, Geography, and Geology to the Incidence of Rift Valley Fever in Kenya during the 2006–2007 Outbreak 
We estimated Rift Valley fever (RVF) incidence as a function of geological, geographical, and climatological factors during the 2006–2007 RVF epidemic in Kenya. Location information was obtained for 214 of 340 (63%) confirmed and probable RVF cases that occurred during an outbreak from November 1, 2006 to February 28, 2007. Locations with subtypes of solonetz, calcisols, solonchaks, and planosols soil types were highly associated with RVF occurrence during the outbreak period. Increased rainfall and higher greenness measures before the outbreak were associated with increased risk. RVF was more likely to occur on plains, in densely bushed areas, at lower elevations, and in the Somalia acacia ecological zone. Cases occurred in three spatial temporal clusters that differed by the date of associated rainfall, soil type, and land usage.
PMCID: PMC3269292  PMID: 22302875
24.  Rickettsia felis Infection in Febrile Patients, Western Kenya, 2007–2010 
Emerging Infectious Diseases  2012;18(2):328-331.
To determine previous exposure and incidence of rickettsial infections in western Kenya during 2007–2010, we conducted hospital-based surveillance. Antibodies against rickettsiae were detected in 57.4% of previously collected serum samples. In a 2008–2010 prospective study, Rickettsia felis DNA was 2.2× more likely to be detected in febrile than in afebrile persons.
PMCID: PMC3310467  PMID: 22304807
rickettsial infections; Rickettsia felis; rickettsia; Kenya; fever of unknown origin
25.  Population-Based Incidence of Typhoid Fever in an Urban Informal Settlement and a Rural Area in Kenya: Implications for Typhoid Vaccine Use in Africa 
PLoS ONE  2012;7(1):e29119.
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.
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.
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.
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.
PMCID: PMC3261857  PMID: 22276105

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