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1.  Preface 
PMCID: PMC3748495  PMID: 23629933
2.  Health Care-Seeking Behavior During Childhood Diarrheal Illness: Results of Health Care Utilization and Attitudes Surveys of Caretakers in Western Kenya, 2007–2010 
We interviewed caretakers of 1,043 children < 5 years old in a baseline cross-sectional survey (April to May 2007) and > 20,000 children on five separate subsequent occasions (May of 2009 to December 31, 2010) to assess healthcare seeking patterns for diarrhea. Diarrhea prevalence during the preceding 2 weeks ranged from 26% at baseline to 4–11% during 2009–2010. Caretakers were less likely to seek healthcare outside the home for infants (versus older children) with diarrhea (adjusted odds ratio [aOR] = 0.33, confidence interval [CI] = 0.12–0.87). Caretakers of children with reduced food intake (aOR = 3.42, CI = 1.37–8.53) and sunken eyes during their diarrheal episode were more likely to seek care outside home (aOR = 4.76, CI = 1.13–8.89). Caretakers with formal education were more likely to provide oral rehydration solution (aOR = 3.01, CI = 1.41–6.42) and visit a healthcare facility (aOR = 3.32, CI = 1.56–7.07). Studies calculating diarrheal incidence and healthcare seeking should account for seasonal trends. Improving caretakers' knowledge of home management could prevent severe diarrhea.
PMCID: PMC3748498  PMID: 23629929
3.  High Prevalence of Rickettsia africae Variants in Amblyomma variegatum Ticks from Domestic Mammals in Rural Western Kenya: Implications for Human Health 
Vector Borne and Zoonotic Diseases  2014;14(10):693-702.
Tick-borne spotted fever group (SFG) rickettsioses are emerging human diseases caused by obligate intracellular Gram-negative bacteria of the genus Rickettsia. Despite being important causes of systemic febrile illnesses in travelers returning from sub-Saharan Africa, little is known about the reservoir hosts of these pathogens. We conducted surveys for rickettsiae in domestic animals and ticks in a rural setting in western Kenya. Of the 100 serum specimens tested from each species of domestic ruminant 43% of goats, 23% of sheep, and 1% of cattle had immunoglobulin G (IgG) antibodies to the SFG rickettsiae. None of these sera were positive for IgG against typhus group rickettsiae. We detected Rickettsia africae–genotype DNA in 92.6% of adult Amblyomma variegatum ticks collected from domestic ruminants, but found no evidence of the pathogen in blood specimens from cattle, goats, or sheep. Sequencing of a subset of 21 rickettsia-positive ticks revealed R. africae variants in 95.2% (20/21) of ticks tested. Our findings show a high prevalence of R. africae variants in A. variegatum ticks in western Kenya, which may represent a low disease risk for humans. This may provide a possible explanation for the lack of African tick-bite fever cases among febrile patients in Kenya.
PMCID: PMC4208559  PMID: 25325312
Ambylomma variegatum; Rickettsia africae; Tick-borne spotted fever group; African tick-bite fever
4.  Access to Waterless Hand Sanitizer Improves Student Hand Hygiene Behavior in Primary Schools in Nairobi, Kenya 
Handwashing is difficult in settings with limited resources and water access. In primary schools within urban Kibera, Kenya, we investigated the impact of providing waterless hand sanitizer on student hand hygiene behavior. Two schools received a waterless hand sanitizer intervention, two schools received a handwashing with soap intervention, and two schools received no intervention. Hand cleaning behavior after toilet use was monitored for 2 months using structured observation. Hand cleaning after toileting was 82% at sanitizer schools (N = 2,507 toileting events), 38% at soap schools (N = 3,429), and 37% at control schools (N = 2,797). Students at sanitizer schools were 23% less likely to have observed rhinorrhea than control students (P = 0.02); reductions in student-reported gastrointestinal and respiratory illness symptoms were not statistically significant. Providing waterless hand sanitizer markedly increased student hand cleaning after toilet use, whereas the soap intervention did not. Waterless hand sanitizer may be a promising option to improve student hand cleansing behavior, particularly in schools with limited water access.
PMCID: PMC3771275  PMID: 23836575
5.  Antibody persistence in mothers one year after pneumococcal immunization in pregnancy 
Vaccine  2012;30(34):5063-5066.
Pneumococcal infections are a significant cause of morbidity and mortality, and young infants are particularly vulnerable to infection. Maternal immunization can protect infants, but there are limited data on the duration of pneumococcal vaccine antibody in pregnant women. We report on maternal antibody concentrations one year after immunization with 23-valent pneumococcal polysaccharide (23vPPS) vaccine.
The Mother's Gift study randomly assigned 340 pregnant Bangladeshi mothers between ages 18 and 36 to receive either inactivated influenza vaccine (Fluarix®) or the 23vPPS vaccine (Pneumovax®) during the third trimester. Sera were collected before immunization, at delivery, and at one year post-delivery. We determined anti-capsular IgG antibody to 9 pneumococcal serotypes by a multiplex Luminex ELISA. We report antibody geometric mean concentrations (GMCs) for 9 serotypes, 12 month/delivery geometric mean ratios (GMRs) and proportions seroprotected (>0.35 mcg/mL) in 23vPPS vaccine recipients and controls at delivery and at 12 months.
Among pneumococcal vaccinees, GMCs remained stable, with an overall 12 month/delivery GMR of 0.83 (95% CI, 0.75–0.92). In the control group, GMCs increased with a mean ratio of 1.98 (95% CI, 1.81–2.17; P < 0.0001). GMCs in these vaccinees did not decline significantly in the 12 months after antenatal immunization.
GMCs in these adult vaccinees and controls did not decline significantly in the 12 months after antenatal immunization. Interestingly, mothers who did not receive 23vPPS in pregnancy show a substantial increase of GMC for most serotypes in the first year after immunization. Further studies are needed to determine the need for repeat doses of 23vPPS vaccine in subsequent pregnancies more than a year later.
PMCID: PMC4133759  PMID: 22709949
Pneumococcal vaccine; Maternal immunization; Antibody titers
6.  Molecular Detection of Adenoviruses, Rhabdoviruses, and Paramyxoviruses in Bats from Kenya 
We screened 217 bats of at least 20 species from 17 locations in Kenya during July and August of 2006 for the presence of adenovirus, rhabdovirus, and paramyxovirus nucleic acids using generic reverse transcription polymerase chain reaction (RT-PCR) and PCR assays. Of 217 bat fecal swabs examined, 4 bats were adenovirus DNA-positive, 11 bats were paramyxovirus RNA-positive, and 2 bats were rhabdovirus RNA-positive. Three bats were coinfected by two different viruses. By sequence comparison and phylogenetic analysis, the Kenya bat paramyxoviruses and rhabdoviruses from this study may represent novel viral lineages within their respective families; the Kenya bat adenoviruses could not be confirmed as novel, because the same region sequences from other known bat adenovirus genomes for comparison were lacking. Our study adds to previous evidence that bats carry diverse, potentially zoonotic viruses and may be coinfected with more than one virus.
PMCID: PMC4125246  PMID: 24865685
7.  Molecular detection of Rickettsia felis and Candidatus Rickettsia Asemboensis in Fleas from Human Habitats, Asembo, Kenya 
The flea-borne rickettsioses murine typhus (Rickettsia typhi) and flea-borne spotted fever (FBSF) (Rickettsia felis) are febrile diseases distributed among humans worldwide. Murine typhus has been known to be endemic to Kenya since the 1950s, but FBSF was only recently documented in northeastern (2010) and western (2012) Kenya. To characterize the potential exposure of humans in Kenya to flea-borne rickettsioses, a total of 330 fleas (134 pools) including 5 species (Xenopsylla cheopis, Ctenocephalides felis, Ctenocephalides canis, Pulex irritans, and Echidnophaga gallinacea) were collected from domestic and peridomestic animals and from human dwellings within Asembo, western Kenya. DNA was extracted from the 134 pooled flea samples and 89 (66.4%) pools tested positively for rickettsial DNA by 2 genus-specific quantitative real-time PCR (qPCR) assays based upon the citrate synthase (gltA) and 17-kD antigen genes and the Rfelis qPCR assay. Sequences from the 17-kD antigen gene, the outer membrane protein (omp)B, and 2 R. felis plasmid genes (pRF and pRFd) of 12 selected rickettsia-positive samples revealed a unique Rickettsia sp. (n=11) and R. felis (n=1). Depiction of the new rickettsia by multilocus sequence typing (MLST) targeting the 16S rRNA (rrs), 17-kD antigen gene, gltA, ompA, ompB, and surface cell antigen 4 (sca4), shows that it is most closely related to R. felis but genetically dissimilar enough to be considered a separate species provisionally named Candidatus Rickettsia asemboensis. Subsequently, 81 of the 134 (60.4%) flea pools tested positively for Candidatus Rickettsia asemboensis by a newly developed agent-specific qPCR assay, Rasemb. R. felis was identified in 9 of the 134 (6.7%) flea pools, and R. typhi the causative agent of murine typhus was not detected in any of 78 rickettsia-positive pools assessed using a species-specific qPCR assay, Rtyph. Two pools were found to contain both R. felis and Candidatus Rickettsia asemboensis DNA and 1 pool contained an agent, which is potentially new.
PMCID: PMC3741420  PMID: 23675818
Rickettsia; Fleas; PCR; Multilocus sequence typing; Surveillance
8.  The impact of home-based HIV counseling and testing on care-seeking and incidence of common infectious disease syndromes in rural western Kenya 
BMC Infectious Diseases  2014;14:376.
In much of Africa, most individuals living with HIV do not know their status. Home-based counseling and testing (HBCT) leads to more HIV-infected people learning their HIV status. However, there is little data on whether knowing one’s HIV-positive status necessarily leads to uptake of HIV care, which could in turn, lead to a reduction in the prevalence of common infectious disease syndromes.
In 2008, Kenya Medical Research Institute (KEMRI) in collaboration with the Centers for Disease Control and Prevention (CDC) offered HBCT to individuals (aged ≥13 years) under active surveillance for infectious disease syndromes in Lwak in rural western Kenya. HIV test results were linked to morbidity and healthcare-seeking data collected by field workers through bi-weekly home visits. We analyzed changes in healthcare seeking behaviors using proportions, and incidence (expressed as episodes per person-year) of acute respiratory illness (ARI), severe acute respiratory illness (SARI), acute febrile illness (AFI) and diarrhea among first-time HIV testers in the year before and after HBCT, stratified by their test result and if HIV-positive, whether they sought care at HIV Patient Support Centers (PSCs).
Of 9,613 individuals offered HBCT, 6,366 (66%) were first-time testers, 698 (11%) of whom were HIV-infected. One year after HBCT, 50% of HIV-infected persons had enrolled at PSCs – 92% of whom had started cotrimoxazole and 37% of those eligible for antiretroviral treatment had initiated therapy. Among HIV-infected persons enrolled in PSCs, AFI and diarrhea incidence decreased in the year after HBCT (rate ratio [RR] 0.84; 95% confidence interval [CI] 0.77 – 0.91 and RR 0.84, 95% CI 0.73 – 0.98, respectively). Among HIV-infected persons not attending PSCs and among HIV-uninfected persons, decreases in incidence were significantly lower. While decreases also occurred in rates of respiratory illnesses among HIV-positive persons in care, there were similar decreases in the other two groups.
Large scale HBCT enabled a large number of newly diagnosed HIV-infected persons to know their HIV status, leading to a change in care seeking behavior and ultimately a decrease in incidence of common infectious disease syndromes through appropriate treatment and care.
PMCID: PMC4107953  PMID: 25005353
Home based HIV counseling and testing; Infectious disease incidence; Healthcare seeking
9.  Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition 
Genome Biology  2014;15(6):R76.
Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease.
We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age.
Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.
PMCID: PMC4072981  PMID: 24995464
10.  Results From the First Six Years of National Sentinel Surveillance for Influenza in Kenya, July 2007–June 2013 
PLoS ONE  2014;9(6):e98615.
Recent studies have shown that influenza is associated with significant disease burden in many countries in the tropics, but until recently national surveillance for influenza was not conducted in most countries in Africa.
In 2007, the Kenyan Ministry of Health with technical support from the CDC-Kenya established a national sentinel surveillance system for influenza. At 11 hospitals, for every hospitalized patient with severe acute respiratory illness (SARI), and for the first three outpatients with influenza-like illness (ILI) per day, we collected both nasopharyngeal and oropharyngeal swabs. Beginning in 2008, we conducted in-hospital follow-up for SARI patients to determine outcome. Specimens were tested by real time RT-PCR for influenza A and B. Influenza A-positive specimens were subtyped for H1, H3, H5, and (beginning in May 2009) A(H1N1)pdm09.
From July 1, 2007 through June 30, 2013, we collected specimens from 24,762 SARI and 14,013 ILI patients. For SARI and ILI case-patients, the median ages were 12 months and 16 months, respectively, and 44% and 47% were female. In all, 2,378 (9.6%) SARI cases and 2,041 (14.6%) ILI cases were positive for influenza viruses. Most influenza-associated SARI cases (58.6%) were in children <2 years old. Of all influenza-positive specimens, 78% were influenza A, 21% were influenza B, and 1% were influenza A/B coinfections. Influenza circulated in every month. In four of the six years influenza activity peaked during July–November. Of 9,419 SARI patients, 2.7% died; the median length of hospitalization was 4 days.
During six years of surveillance in Kenya, influenza was associated with nearly 10 percent of hospitalized SARI cases and one-sixth of outpatient ILI cases. Most influenza-associated SARI and ILI cases were in children <2 years old; interventions to reduce the burden of influenza, such as vaccine, could consider young children as a priority group.
PMCID: PMC4067481  PMID: 24955962
11.  Shigella Isolates From the Global Enteric Multicenter Study Inform Vaccine Development 
Shigella case isolates from the Global Enteric Multicenter Study were serotyped to guide vaccine development. A quadrivalent vaccine that includes O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 should provide broad protection.
Background. Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged <60 months and matched controls without diarrhea during 3 years at 4 sites in Africa and 3 in Asia. Shigella was 1 of the 4 most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development.
Methods. Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control.
Results. Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b.
Conclusions. A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens.
PMCID: PMC4166982  PMID: 24958238
serotyping; Shigella; shigellosis; vaccines
12.  Village-Randomized Clinical Trial of Home Distribution of Zinc for Treatment of Childhood Diarrhea in Rural Western Kenya 
PLoS ONE  2014;9(5):e94436.
Zinc treatment shortens diarrhea episodes and can prevent future episodes. In rural Africa, most children with diarrhea are not brought to health facilities. In a village-randomized trial in rural Kenya, we assessed if zinc treatment might have a community-level preventive effect on diarrhea incidence if available at home versus only at health facilities.
We randomized 16 Kenyan villages (1,903 eligible children) to receive a 10-day course of zinc and two oral rehydration solution (ORS) sachets every two months at home and 17 villages (2,241 eligible children) to receive ORS at home, but zinc at the health–facility only. Children’s caretakers were educated in zinc/ORS use by village workers, both unblinded to intervention arm. We evaluated whether incidence of diarrhea and acute lower respiratory illness (ALRI) reported at biweekly home visits and presenting to clinic were lower in zinc villages, using poisson regression adjusting for baseline disease rates, distance to clinic, and children’s age.
There were no differences between village groups in diarrhea incidence either reported at the home or presenting to clinic. In zinc villages (1,440 children analyzed), 61.2% of diarrheal episodes were treated with zinc, compared to 5.4% in comparison villages (1,584 children analyzed, p<0.0001). There were no differences in ORS use between zinc (59.6%) and comparison villages (58.8%). Among children with fever or cough without diarrhea, zinc use was low (<0.5%). There was a lower incidence of reported ALRI in zinc villages (adjusted RR 0.68, 95% CI 0.46–0.99), but not presenting at clinic.
In this study, home zinc use to treat diarrhea did not decrease disease rates in the community. However, with proper training, availability of zinc at home could lead to more episodes of pediatric diarrhea being treated with zinc in parts of rural Africa where healthcare utilization is low.
Trial Registration NCT00530829
PMCID: PMC4023937  PMID: 24835009
13.  Health care utilization for acute illnesses in an urban setting with a refugee population in Nairobi, Kenya: a cross-sectional survey 
Estimates place the number of refugees in Nairobi over 100,000. The constant movement of refugees between countries of origin, refugee camps, and Nairobi poses risk of introduction and transmission of communicable diseases into Kenya. We assessed the care-seeking behavior of residents of Eastleigh, a neighborhood in Nairobi with urban refugees.
During July and August 2010, we conducted a Health Utilization Survey in Section II of Eastleigh. We used a multistage random cluster sampling design to identify households for interview. A standard questionnaire on the household demographics, water and sanitation was administered to household caretakers. Separate questionnaires were administered to household members who had one or more of the illnesses of interest.
Of 785 households targeted for interview, data were obtained from 673 (85.7%) households with 3,005 residents. Of the surveyed respondents, 290 (9.7%) individuals reported acute respiratory illness (ARI) in the previous 12 months, 222 (7.4%) reported fever in the preceding 2 weeks, and 54 (1.8%) reported having diarrhea in the 30 days prior to the survey. Children <5 years old had the highest frequency of all the illnesses surveyed: 17.1% (95% CI 12.2-21.9) reported ARI, 10.0% (95% CI 6.2-13.8) reported fever, and 6.9% (3.8-10.0) reported diarrhea during the time periods specified for each syndrome. Twenty-nine [7.5% (95% CI 4.3-10.7)] hospitalizations were reported among all age groups of those who sought care. Among participants who reported ≥1 illness, 330 (77.0%) sought some form of health care; most (174 [59.8%]) sought health care services from private health care providers. Fifty-five (18.9%) participants seeking healthcare services visited a pharmacy. Few residents of Eastleigh (38 [13.1%]) sought care at government-run facilities, and 24 (8.2%) sought care from a relative, a religious leader, or a health volunteer. Of those who did not seek any health care services (99 [23.0%]), the primary reason was cost (44.8%), followed by belief that the person was not sick enough (34.6%).
Health care utilization in Eastleigh is high; however, a large proportion of residents opt to seek care at private clinics or pharmacies, despite the availability of accessible government-provided health care services in this area.
PMCID: PMC4021024  PMID: 24885336
Health care utilization; Urban refugees; Eastleigh; Kenya
14.  Survey of Culture, GoldenGate Assay, Universal Biosensor Assay, and 16S rRNA Gene Sequencing as Alternative Methods of Bacterial Pathogen Detection 
Journal of Clinical Microbiology  2013;51(10):3263-3269.
Cultivation-based assays combined with PCR or enzyme-linked immunosorbent assay (ELISA)-based methods for finding virulence factors are standard methods for detecting bacterial pathogens in stools; however, with emerging molecular technologies, new methods have become available. The aim of this study was to compare four distinct detection technologies for the identification of pathogens in stools from children under 5 years of age in The Gambia, Mali, Kenya, and Bangladesh. The children were identified, using currently accepted clinical protocols, as either controls or cases with moderate to severe diarrhea. A total of 3,610 stool samples were tested by established clinical culture techniques: 3,179 DNA samples by the Universal Biosensor assay (Ibis Biosciences, Inc.), 1,466 DNA samples by the GoldenGate assay (Illumina), and 1,006 DNA samples by sequencing of 16S rRNA genes. Each method detected different proportions of samples testing positive for each of seven enteric pathogens, enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), Shigella spp., Campylobacter jejuni, Salmonella enterica, and Aeromonas spp. The comparisons among detection methods included the frequency of positive stool samples and kappa values for making pairwise comparisons. Overall, the standard culture methods detected Shigella spp., EPEC, ETEC, and EAEC in smaller proportions of the samples than either of the methods based on detection of the virulence genes from DNA in whole stools. The GoldenGate method revealed the greatest agreement with the other methods. The agreement among methods was higher in cases than in controls. The new molecular technologies have a high potential for highly sensitive identification of bacterial diarrheal pathogens.
PMCID: PMC3811648  PMID: 23884998
15.  Examining strain diversity and phylogeography in relation to an unusual epidemic pattern of respiratory syncytial virus (RSV) in a long-term refugee camp in Kenya 
BMC Infectious Diseases  2014;14:178.
A recent longitudinal study in the Dadaab refugee camp near the Kenya-Somalia border identified unusual biannual respiratory syncytial virus (RSV) epidemics. We characterized the genetic variability of the associated RSV strains to determine if viral diversity contributed to this unusual epidemic pattern.
For 336 RSV positive specimens identified from 2007 through 2011 through facility-based surveillance of respiratory illnesses in the camp, 324 (96.4%) were sub-typed by PCR methods, into 201 (62.0%) group A, 118 (36.4%) group B and 5 (1.5%) group A-B co-infections. Partial sequencing of the G gene (coding for the attachment protein) was completed for 290 (89.5%) specimens. These specimens were phylogenetically analyzed together with 1154 contemporaneous strains from 22 countries.
Of the 6 epidemic peaks recorded in the camp over the period, the first and last were predominantly made up of group B strains, while the 4 in between were largely composed of group A strains in a consecutive series of minor followed by major epidemics. The Dadaab group A strains belonged to either genotype GA2 (180, 98.9%) or GA5 (2, < 1%) while all group B strains (108, 100%) belonged to BA genotype. In sequential epidemics, strains within these genotypes appeared to be of two types: those continuing from the preceding epidemics and those newly introduced. Genotype diversity was similar in minor and major epidemics.
RSV strain diversity in Dadaab was similar to contemporaneous diversity worldwide, suggested both between-epidemic persistence and new introductions, and was unrelated to the unusual epidemic pattern.
PMCID: PMC4021307  PMID: 24690157
Attachment (G) protein; Displaced population; Epidemics; Genetic diversity; Genotype; Refugee; RSV
16.  Risk Factors for Severe Rift Valley Fever Infection in Kenya, 2007 
A large Rift Valley fever (RVF) outbreak occurred in Kenya from December 2006 to March 2007. We conducted a study to define risk factors associated with infection and severe disease. A total of 861 individuals from 424 households were enrolled. Two hundred and two participants (23%) had serologic evidence of acute RVF infection. Of these, 52 (26%) had severe RVF disease characterized by hemorrhagic manifestations or death. Independent risk factors for acute RVF infection were consuming or handling products from sick animals (odds ratio [OR] = 2.53, 95% confidence interval [CI] = 1.78–3.61, population attributable risk percentage [PAR%] = 19%) and being a herdsperson (OR 1.77, 95% CI = 1.20–2.63, PAR% = 11%). Touching an aborted animal fetus was associated with severe RVF disease (OR = 3.83, 95% CI = 1.68–9.07, PAR% = 14%). Consuming or handling products from sick animals was associated with death (OR = 3.67, 95% CI = 1.07–12.64, PAR% = 47%). Exposures related to animal contact were associated with acute RVF infection, whereas exposures to mosquitoes were not independent risk factors.
PMCID: PMC2913492  PMID: 20682901
18.  An Investigation of a Major Outbreak of Rift Valley Fever in Kenya: 2006–2007 
An outbreak of Rift Valley fever (RVF) occurred in Kenya during November 2006 through March 2007. We characterized the magnitude of the outbreak through disease surveillance and serosurveys, and investigated contributing factors to enhance strategies for forecasting to prevent or minimize the impact of future outbreaks. Of 700 suspected cases, 392 met probable or confirmed case definitions; demographic data were available for 340 (87%), including 90 (26.4%) deaths. Male cases were more likely to die than females, Case Fatality Rate Ratio 1.8 (95% Confidence Interval [CI] 1.3–3.8). Serosurveys suggested an attack rate up to 13% of residents in heavily affected areas. Genetic sequencing showed high homology among viruses from this and earlier RVF outbreaks. Case areas were more likely than non-case areas to have soil types that retain surface moisture. The outbreak had a devastatingly high case-fatality rate for hospitalized patients. However, there were up to 180,000 infected mildly ill or asymptomatic people within highly affected areas. Soil type data may add specificity to climate-based forecasting models for RVF.
PMCID: PMC2913496  PMID: 20682900
19.  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
20.  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
21.  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
22.  Mortality Trends Observed in Population-Based Surveillance of an Urban Slum Settlement, Kibera, Kenya, 2007–2010 
PLoS ONE  2014;9(1):e85913.
We used population based infectious disease surveillance to characterize mortality rates in residents of an urban slum in Kenya.
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.
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.
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.
PMCID: PMC3904840  PMID: 24489678
23.  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
24.  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
25.  IgA and Neutralizing Antibodies to Influenza A Virus in Human Milk: A Randomized Trial of Antenatal Influenza Immunization 
PLoS ONE  2013;8(8):e70867.
Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. ( identifier NCT00142389;
Methods and Findings
The Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154).
The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the cellular and immunologic mechanisms of breast milk-mediated protection after antepartum immunization.
Trial Registration NCT00142389
PMCID: PMC3743877  PMID: 23967126

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