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1.  Tuberculin Skin Tests versus Interferon-Gamma Release Assays in Tuberculosis Screening among Immigrant Visa Applicants 
Objective. Use of tuberculin skin tests (TSTs) and interferon gamma release assays (IGRAs) as part of tuberculosis (TB) screening among immigrants from high TB-burden countries has not been fully evaluated. Methods. Prevalence of Mycobacterium tuberculosis infection (MTBI) based on TST, or the QuantiFERON-TB Gold test (QFT-G), was determined among immigrant applicants in Vietnam bound for the United States (US); factors associated with test results and discordance were assessed; predictive values of TST and QFT-G for identifying chest radiographs (CXRs) consistent with TB were calculated. Results. Of 1,246 immigrant visa applicants studied, 57.9% were TST positive, 28.3% were QFT-G positive, and test agreement was 59.4%. Increasing age was associated with positive TST results, positive QFT-G results, TST-positive but QFT-G-negative discordance, and abnormal CXRs consistent with TB. Positive predictive values of TST and QFT-G for an abnormal CXR were 25.9% and 25.6%, respectively. Conclusion. The estimated prevalence of MTBI among US-bound visa applicants in Vietnam based on TST was twice that based on QFT-G, and 14 times higher than a TST-based estimate of MTBI prevalence reported for the general US population in 2000. QFT-G was not better than TST at predicting abnormal CXRs consistent with TB.
doi:10.1155/2014/217969
PMCID: PMC3967820  PMID: 24738031
2.  A sham case-control study of effectiveness of DTP-Hib-hepatitis B vaccine against rotavirus acute gastroenteritis in Kenya 
Background
In many GAVI-eligible countries, effectiveness of new vaccines will be evaluated by case-control methodology. To inform the design and assess selection bias of a future case-control study of rotavirus vaccine effectiveness (VE) in western Kenya, we performed a sham case-control study evaluating VE of pentavalent vaccine (DTP-Hib-HepB) against rotavirus acute gastroenteritis (AGE).
Methods
From ongoing rotavirus surveillance, we defined cases as children 12 weeks to 23 months old with EIA-confirmed rotavirus AGE. We enrolled one community-based and two hospital-based control groups. We collected vaccination status from cards at enrollment, or later in homes, and evaluated VE by logistic regression.
Results
We enrolled 91 cases (64 inpatient, 27 outpatient), 252 non-rotavirus AGE facility-based controls (unmatched), 203 non-AGE facility-based controls (age-matched) and 271 community controls (age-matched). Documented receipt of 3 pentavalent doses was 77% among cases and ranged from 81-86% among controls. One percent of cases and 0-2% of controls had no pentavalent doses. The adjusted odds ratio of three versus zero doses for being a case was 3.27 (95% CI 0.01-1010) for community controls and 0.69 (95% CI 0.06-7.75) for non-rotavirus hospital-based AGE controls, translating to VE of -227% and 31%, respectively, with wide confidence intervals. (No facility-based non-AGE controls were unvaccinated.) Similar results were found for ≥2 pentavalent doses and for severe rotavirus AGE.
Conclusions
The study showed that it is feasible to carry out a real case control in the study area, but this needs to be done as soon as the vaccine is introduced to capture the real impact. Sham case-control or pilot studies before vaccine introduction can be useful in designing case-control VE studies.
doi:10.1186/1471-2334-14-77
PMCID: PMC3926679  PMID: 24517198
Rotavirus; Case-control; Vaccine effectiveness
3.  ‘We Keep It Secret So No One Should Know’ – A Qualitative Study to Explore Young Schoolgirls Attitudes and Experiences with Menstruation in Rural Western Kenya 
PLoS ONE  2013;8(11):e79132.
Background
Keeping girls in school offers them protection against early marriage, teen pregnancy, and sexual harms, and enhances social and economic equity. Studies report menstruation exacerbates school-drop out and poor attendance, although evidence is sparse. This study qualitatively examines the menstrual experiences of young adolescent schoolgirls.
Methods and Findings
The study was conducted in Siaya County in rural western Kenya. A sample of 120 girls aged 14–16 years took part in 11 focus group discussions, which were analysed thematically. The data gathered were supplemented by information from six FGDs with parents and community members. Emergent themes were: lack of preparation for menarche; maturation and sexual vulnerability; menstruation as an illness; secrecy, fear and shame of leaking; coping with inadequate alternatives; paying for pads with sex; and problems with menstrual hygiene. Girls were unprepared and demonstrated poor reproductive knowledge, but devised practical methods to cope with menstrual difficulties, often alone. Parental and school support of menstrual needs is limited, and information sparse or inaccurate. Girls’ physical changes prompt boys and adults to target and brand girls as ripe for sexual activity including coercion and marriage. Girls admitted ‘others’ rather than themselves were absent from school during menstruation, due to physical symptoms or inadequate sanitary protection. They described difficulties engaging in class, due to fear of smelling and leakage, and subsequent teasing. Sanitary pads were valued but resource and time constraints result in prolonged use causing chafing. Improvised alternatives, including rags and grass, were prone to leak, caused soreness, and were perceived as harmful. Girls reported ‘other girls’ but not themselves participated in transactional sex to buy pads, and received pads from boyfriends.
Conclusions
In the absence of parental and school support, girls cope, sometimes alone, with menarche in practical and sometimes hazardous ways. Emotional and physical support mechanisms need to be included within a package of measures to enable adolescent girls to reach their potential.
doi:10.1371/journal.pone.0079132
PMCID: PMC3828248  PMID: 24244435
4.  Exploring Risk Perception and Attitudes to Miscarriage and Congenital Anomaly in Rural Western Kenya 
PLoS ONE  2013;8(11):e80551.
Background
Understanding the socio-cultural context and perceptions of adverse pregnancy outcomes is important for informing the best approaches for public health programs. This article describes the perceptions, beliefs and health-seeking behaviours of women from rural western Kenya regarding congenital anomalies and miscarriages.
Methods
Ten focus group discussions (FGDs) were undertaken in a rural district in western Kenya in September 2010. The FGDs included separate groups consisting of adult women of childbearing age, adolescent girls, recently pregnant women, traditional birth attendants and mothers of children with a birth defect. Participants were selected purposively. A deductive thematic framework approach using the questions from the FGD guides was used to analyse the transcripts.
Results
There was substantial overlap between perceived causes of miscarriages and congenital anomalies and these were broadly categorized into two groups: biomedical and cultural. The biomedical causes included medications, illnesses, physical and emotional stresses, as well as hereditary causes. Cultural beliefs mostly related to the breaking of a taboo or not following cultural norms. Mothers were often stigmatised and blamed following miscarriage, or the birth of a child with a congenital anomaly. Often, women did not seek care following miscarriage unless there was a complication. Most reported that children with a congenital anomaly were neglected either because of lack of knowledge of where care could be sought or because these children brought shame to the family and were hidden from society.
Conclusion
The local explanatory model of miscarriage and congenital anomalies covered many perceived causes within biomedical and cultural beliefs. Some of these fuelled stigmatisation and blame of the mother. Understanding of these beliefs, improving access to information about the possible causes of adverse outcomes, and greater collaboration between traditional healers and healthcare providers may help to reduce stigma and increase access to formal healthcare providers.
doi:10.1371/journal.pone.0080551
PMCID: PMC3827434  PMID: 24236185
5.  Trauma-Related Mortality among Adults in Rural Western Kenya: Characterising Deaths Using Data from a Health and Demographic Surveillance System 
PLoS ONE  2013;8(11):e79840.
Background
Information on trauma-related deaths in low and middle income countries is limited but needed to target public health interventions. Data from a health and demographic surveillance system (HDSS) were examined to characterise such deaths in rural western Kenya.
Methods And Findings
Verbal autopsy data were analysed. Of 11,147 adult deaths between 2003 and 2008, 447 (4%) were attributed to trauma; 71% of these were in males. Trauma contributed 17% of all deaths in males 15 to 24 years; on a population basis mortality rates were greatest in persons over 65 years. Intentional causes accounted for a higher proportion of male than female deaths (RR 2.04, 1.37-3.04) and a higher proportion of deaths of those aged 15 to 65 than older people. Main causes in males were assaults (n=79, 25%) and road traffic injuries (n=47, 15%); and falls for females (n=17, 13%). A significantly greater proportion of deaths from poisoning (RR 5.0, 2.7-9.4) and assault (RR 1.8, 1.2-2.6) occurred among regular consumers of alcohol than among non-regular drinkers. In multivariate analysis, males had a 4-fold higher risk of death from trauma than females (Adjusted Relative Risk; ARR 4.0; 95% CI 1.7-9.4); risk of a trauma death rose with age, with the elderly at 7-fold higher risk (ARR 7.3, 1.1-49.2). Absence of care was the strongest predictor of trauma death (ARR 12.2, 9.4-15.8). Trauma-related deaths were higher among regular alcohol drinkers (ARR 1.5, 1.1-1.9) compared with non-regular drinkers.
Conclusions
While trauma accounts for a small proportion of deaths in this rural area with a high prevalence of HIV, TB and malaria, preventive interventions such as improved road safety, home safety strategies for the elderly, and curbing harmful use of alcohol, are available and could help diminish this burden. Improvements in systems to record underlying causes of death from trauma are required.
doi:10.1371/journal.pone.0079840
PMCID: PMC3820584  PMID: 24244569
6.  Field Evaluation of a Broadly Sensitive HIV-1 In-House Genotyping Assay for Use with both Plasma and Dried Blood Spot Specimens in a Resource-Limited Country 
Journal of Clinical Microbiology  2013;51(2):529-539.
HIV-1 drug resistance (HIVDR) assays are important tools in clinical management of HIV-infected patients on antiretroviral therapy (ART) and surveillance of drug-resistant variants at population levels. The high cost associated with commercial assays hinders their use in resource-limited settings. We adopted and validated a low-cost in-house assay using 68 matched plasma and dried blood spot (DBS) samples with a median viral load (VL) of 58,187 copies/ml, ranging from 253 to 3,264,850 against the commercial assay ViroSeq. Results indicated that the in-house assay not only had a higher plasma genotyping rate than did ViroSeq (94% versus 78%) but also was able to genotype 89.5% (51/57) of the matched DBS samples with VLs of ≥1,000 copies/ml. The sensitivity in detecting DR mutations by the in-house assay was 98.29% (95% confidence interval [CI], 97.86 to 98.72) on plasma and 96.54 (95% CI, 95.93 to 97.15) on DBS, and the specificity was 99.97% (95% CI, 99.91 to 100.00) for both sample types compared to ViroSeq. The minor DR mutation differences detected by the in-house assay against ViroSeq did not result in clinical significance. In addition, cost analysis showed that the in-house assay could reduce the genotyping cost by about 60% for both plasma and DBS compared to ViroSeq. This field condition evaluation highlights the potential utility of a cost-effective, subtype-independent, in-house genotyping assay using both plasma and DBS specimens for HIVDR clinical monitoring and population-based surveillance in resource-limited settings.
doi:10.1128/JCM.02347-12
PMCID: PMC3553877  PMID: 23224100
7.  An Analysis of Pregnancy-Related Mortality in the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya 
PLoS ONE  2013;8(7):e68733.
Background
Pregnancy-related (PR) deaths are often a result of direct obstetric complications occurring at childbirth.
Methods and Findings
To estimate the burden of and characterize risk factors for PR mortality, we evaluated deaths that occurred between 2003 and 2008 among women of childbearing age (15 to 49 years) using Health and Demographic Surveillance System data in rural western Kenya. WHO ICD definition of PR mortality was used: “the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death”. In addition, symptoms and events at the time of death were examined using the WHO verbal autopsy methodology. Deaths were categorized as either (i) directly PR: main cause of death was ascribed as obstetric, or (ii) indirectly PR: main cause of death was non-obstetric. Of 3,223 deaths in women 15 to 49 years, 249 (7.7%) were PR. One-third (34%) of these were due to direct obstetric causes, predominantly postpartum hemorrhage, abortion complications and puerperal sepsis. Two-thirds were indirect; three-quarters were attributable to human immunodeficiency virus (HIV/AIDS), malaria and tuberculosis. Significantly more women who died in lower socio-economic groups sought care from traditional birth attendants (p = 0.034), while less impoverished women were more likely to seek hospital care (p = 0.001). The PR mortality ratio over the six years was 740 (95% CI 651–838) per 100,000 live births, with no evidence of reduction over time (χ2 linear trend = 1.07; p = 0.3).
Conclusions
These data supplement current scanty information on the relationship between infectious diseases and poor maternal outcomes in Africa. They indicate low uptake of maternal health interventions in women dying during pregnancy and postpartum, suggesting improved access to and increased uptake of skilled obstetric care, as well as preventive measures against HIV/AIDS, malaria and tuberculosis among all women of childbearing age may help to reduce pregnancy-related mortality.
doi:10.1371/journal.pone.0068733
PMCID: PMC3712942  PMID: 23874741
8.  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.
doi:10.4269/ajtmh.12-0755
PMCID: PMC3748498  PMID: 23629929
9.  Perspectives of men on antenatal and delivery care service utilisation in rural western Kenya: a qualitative study 
Background
Poor utilisation of facility-based antenatal and delivery care services in Kenya hampers reduction of maternal mortality. Studies suggest that the participation of men in antenatal and delivery care is associated with better health care seeking behaviour, yet many reproductive health programs do not facilitate their involvement. This qualitative study conducted in rural Western Kenya, explored men’s perceptions of antenatal and delivery care services and identified factors that facilitated or constrained their involvement.
Methods
Eight focus group discussions were conducted with 68 married men between 20-65 years of age in May 2011. Participants were of the Luo ethnic group residing in Asembo, western Kenya. The area has a high HIV-prevalence and polygamy is common. A topic guide was used to guide the discussions and a thematic framework approach for data analysis.
Results
Overall, men were positive in their views of antenatal and delivery care, as decision makers they often encouraged, some even ‘forced’, their wives to attend for antenatal or delivery care. Many reasons why it was beneficial to accompany their wives were provided, yet few did this in practice unless there was a clinical complication. The three main barriers relating to cultural norms identified were: 1) pregnancy support was considered a female role; and the male role that of provider; 2) negative health care worker attitudes towards men’s participation, and 3) couple unfriendly antenatal and delivery unit infrastructure.
Conclusion
Although men reported to facilitate their wives’ utilisation of antenatal and delivery care services, this does not translate to practice as adherence to antenatal-care schedules and facility based delivery is generally poor. Equally, reasons proffered why they should accompany their wives are not carried through into practice, with barriers outweighing facilitators. Recommendations to improve men involvement and potentially increase services utilisation include awareness campaigns targeting men, exploring promotion of joint HIV testing and counselling, staff training, and design of couple friendly antenatal and delivery units.
doi:10.1186/1471-2393-13-134
PMCID: PMC3691751  PMID: 23800139
Pregnancy; Antenatal care; Delivery care; Decision making; Male involvement
10.  The impact of hotspot-targeted interventions on malaria transmission: study protocol for a cluster-randomized controlled trial 
Trials  2013;14:36.
Background
Malaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community.
Methods/design
Hotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations.
Discussion
This study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection.
Trial registration
NCT01575613. The protocol was registered online on 20 March 2012; the first community was randomized on 26 March 2012.
doi:10.1186/1745-6215-14-36
PMCID: PMC3576332  PMID: 23374910
Anopheles; elimination; epidemiology; eradication; falciparum; heterogeneity; immunology; malaria; molecular; transmission
11.  Prevalence of HIV and Other Sexually Transmitted Infections among Female Sex Workers in Kisumu, Western Kenya, 1997 and 2008 
PLoS ONE  2013;8(1):e54953.
Background
In 1997, a survey in Kisumu found a prevalence of HIV infection among female sex workers (FSW) of 75%. Only 50% reported using a condom with the last client. In 2008, we conducted another survey to collect data to inform an intervention targeting FSW in Kisumu.
Methods
In 2008 FSW were recruited by respondent-driven sampling. Women completed a questionnaire and were tested for HIV and other sexually transmitted infections (STIs). Multiple logistic regression analysis was done to explore factors associated with HIV-infection, and with condom use. Prevalence of HIV infection was compared in the two surveys from 1997 and 2008. Multivariate analysis was used to assess whether a change in HIV prevalence between the two surveys could be explained by changes in socio-demographic characteristics and/or behavioral factors.
Results
481 FSW participated in the 2008 study. HIV prevalence was 56.5% (95% CI 52.0–61.6). Factors independently associated with HIV were age older than 29 years; being a widow; STI treatment in the past year; herpes simplex virus Type-2 infection; bacterial vaginosis; and trichomoniasis. Condom use with last client was reported by 75.0% (95% CI 70.9–78.9). Predictors of condom use with the last client were age older than 29 years; higher price paid by last client; ever having been tested for HIV. Predictors of unprotected sex were being drunk during last sex act; usually having sex during menses; and STI treatment in the past year. The odds ratio of HIV infection associated with year of survey was 0.49 (95% CI 0.33–0.75) after adjusting for socio-demographic and behavioral factors.
Conclusions
The prevalence of HIV among FSW in Kisumu was found to be lower in 2008 than in 1997, while reported condom use was higher. However, access to HIV/STI prevention and care services needs to improve to further decrease HIV transmission between FSW and their clients.
doi:10.1371/journal.pone.0054953
PMCID: PMC3553007  PMID: 23372801
12.  The Combination of Indoor Residual Spraying and Insecticide-Treated Nets Provides Added Protection against Malaria Compared with Insecticide-Treated Nets Alone 
Both insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS) reduce malaria in high malaria transmission areas.1–3 The combined effect of these interventions is unknown. We conducted a non-randomized prospective cohort study to determine protective efficacy of IRS with ITNs (ITN + IRS) compared with ITNs alone (ITN only) in preventing Plasmodium falciparum parasitemia. At baseline, participants provided blood samples for malaria smears, were presumptively treated for malaria, and received ITNs. Blood smears were made monthly and at sick visits. In total, 1,804 participants were enrolled. Incidence of P. falciparum parasitemia in the ITN + IRS and ITN only groups was 18 and 44 infections per 100 persons-years at risk, respectively (unadjusted rate ratio = 0.41; 95% confidence interval [CI] = 0.31–0.56). Adjusted protective efficacy of ITN + IRS compared with ITN only was 62% (95% CI = 0.50–0.72). The combination of IRS and ITN might be a feasible strategy to further reduce malaria transmission in areas of persistent perennial malaria transmission.
doi:10.4269/ajtmh.2011.10-0684
PMCID: PMC3225156  PMID: 22144448
13.  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.
doi:10.4269/ajtmh.2011.11-0178
PMCID: PMC3225166  PMID: 22144458
14.  Mortality Trends from 2003 to 2009 among Adolescents and Young Adults in Rural Western Kenya Using a Health and Demographic Surveillance System 
PLoS ONE  2012;7(11):e47017.
Background
Targeted global efforts to improve survival of young adults need information on mortality trends; contributions from health and demographic surveillance system (HDSS) are required.
Methods and Findings
This study aimed to explore changing trends in deaths among adolescents (15–19 years) and young adults (20–24 years), using census and verbal autopsy data in rural western Kenya using a HDSS. Mid-year population estimates were used to generate all-cause mortality rates per 100,000 population by age and gender, by communicable (CD) and non-communicable disease (NCD) causes. Linear trends from 2003 to 2009 were examined. In 2003, all-cause mortality rates of adolescents and young adults were 403 and 1,613 per 100,000 population, respectively, among females; and 217 and 716 per 100,000, respectively, among males. CD mortality rates among females and males 15–24 years were 500 and 191 per 100,000 (relative risk [RR] 2.6; 95% confidence intervals [CI] 1.7–4.0; p<0.001). NCD mortality rates in same aged females and males were similar (141 and 128 per 100,000, respectively; p = 0.76). By 2009, young adult female all-cause mortality rates fell 53% (χ2 for linear trend 30.4; p<0.001) and 61.5% among adolescent females (χ2 for linear trend 11.9; p<0.001). No significant CD mortality reductions occurred among males or for NCD mortality in either gender. By 2009, all-cause, CD, and NCD mortality rates were not significantly different between males and females, and among males, injuries equalled HIV as the top cause of death.
Conclusions
This study found significant reductions in adolescent and young adult female mortality rates, evidencing the effects of targeted public health programmes, however, all-cause and CD mortality rates among females remain alarmingly high. These data underscore the need to strengthen programmes and target strategies to reach both males and females, and to promote NCD as well as CD initiatives to reduce the mortality burden amongst both gender.
doi:10.1371/journal.pone.0047017
PMCID: PMC3489847  PMID: 23144796
15.  A Reversal in Reductions of Child Mortality in Western Kenya, 2003–2009 
We report and explore changes in child mortality in a rural area of Kenya during 2003–2009, when major public health interventions were scaled-up. Mortality ratios and rates were calculated by using the Kenya Medical Research Institute/Centers for Disease Control and Prevention Demographic Surveillance System. Inpatient and outpatient morbidity and mortality, and verbal autopsy data were analyzed. Mortality ratios for children less than five years of age decreased from 241 to 137 deaths/1,000 live-births in 2003 and 2007 respectively. In 2008, they increased to 212 deaths/1,000 live-births. Mortality remained elevated during the first 8 months of 2009 compared with 2006 and 2007. Malaria and/or anemia accounted for the greatest increases in child mortality. Stock-outs of essential antimalarial drugs during a time of increased malaria transmission and disruption of services during civil unrest may have contributed to increased mortality in 2008–2009. To maintain gains in child survival, implementation of good policies and effective interventions must be complemented by reliable supply and access to clinical services and essential drugs.
doi:10.4269/ajtmh.2011.10-0678
PMCID: PMC3183762  PMID: 21976557
16.  Integrated community-directed intervention for schistosomiasis and soil transmitted helminths in western Kenya – a pilot study 
Parasites & Vectors  2012;5:182.
Background
Schistosome and soil-transmitted helminth (STH) infections are recognized as major global public health problems, causing severe and subtle morbidity, including significant educational and nutritional effects in children. Although effective and safe drugs are available, ensuring access to these drugs by all those at risk of schistosomiasis and STHs is still a challenge. Community-directed intervention (CDI) has been used successfully for mass distribution of drugs for other diseases such as onchocerciasis and lymphatic filariasis. A national control programme is yet to be instituted in Kenya and evidence for cost-effective strategies for reaching most affected communities is needed. This study evaluated the effectiveness and feasibility of the CDI strategy in the control of schistosomiasis and STHs, in East Uyoma location, Rarieda district, a community of western Kenya that is highly endemic for both infections.
Results
Pre-treatment prevalence of S. mansoni averaged 17.4% (range 5-43%) in the entire location. Treatment coverage in different villages ranged from 54.19 to 96.6% by community drug distributor (CDD) records. Assessment from a household survey showed coverage of 52.3 -91.9% while the proportion of homesteads (home compounds) covered ranged from 54.9-98.5%. Six months after one round of drug distribution, the prevalence levels of S. mansoni, hookworm and Trichuris trichura infections were reduced by 33.2%, 69.4% and 42.6% respectively.
Conclusions
This study shows that CDI is an accepted and effective strategy in the mass treatment of schistosomiasis and STH infections in resource constrained communities in Kenya and may be useful in similar communities elsewhere. A controlled trial comparing CDI and school based mass drug administration to demonstarte their relative advantages is ongoing.
doi:10.1186/1756-3305-5-182
PMCID: PMC3447651  PMID: 22937890
17.  Screening Strategies for Tuberculosis Prevalence Surveys: The Value of Chest Radiography and Symptoms 
PLoS ONE  2012;7(7):e38691.
Background
We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding.
Methods
All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR) and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture.
Results
Presence of any abnormality on CXR had 94% (95%CI 88–98) sensitivity (92% in HIV-infected and 100% in HIV-uninfected) and 73% (95%CI 68–77) specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for ‘any TB symptom’ which had 90% (95%CI 84–95) sensitivity (96% in HIV-infected and 82% in HIV-uninfected) and 32% (95%CI 30–34) specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97–100) sensitivity. Specificity was 65% (95%CI 61–68). Sequential application of first a symptom screen for ‘any symptom’, followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%.
Conclusion
CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not feasible.
doi:10.1371/journal.pone.0038691
PMCID: PMC3391193  PMID: 22792158
18.  Risk Factors for Death among Children Less than 5 Years Old Hospitalized with Diarrhea in Rural Western Kenya, 2005–2007: A Cohort Study 
PLoS Medicine  2012;9(7):e1001256.
A hospital-based surveillance study conducted by Ciara O'Reilly and colleagues describes the risk factors for death amongst children who have been hospitalized with diarrhea in rural Kenya.
Background
Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya.
Methods and Findings
We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal Salmonella were identified in 10% (118), Campylobacter in 5% (57), and Shigella in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal Salmonella were detected in 22%, Shigella in 11%, rotavirus in 9%, Campylobacter in 5%, and S. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal Salmonella (adjusted odds ratio [aOR] = 6·8; 95% CI 3·1–14·9), and children <5 years to have Shigella (aOR = 5·5; 95% CI 2·2–14·0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0·4; 95% CI 0·2–0·8). Further risk factors for death included being malnourished (aOR = 4·2; 95% CI 2·1–8·7); having oral thrush on physical exam (aOR = 2·3; 95% CI 1·4–3·8); having previously sought care at a hospital for the illness (aOR = 2·2; 95% CI 1·2–3·8); and being dehydrated as diagnosed at discharge/death (aOR = 2·5; 95% CI 1·5–4·1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home.
Conclusion
Nontyphoidal Salmonella and Shigella are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Diarrhea—passing three or more loose or liquid stools per day—kills about 1.5 million young children every year, mainly in low- and middle-income countries. Globally, it is the second leading cause of death in under-5-year olds, causing nearly one in five child deaths. Diarrhea, which can lead to life-threatening dehydration, is a common symptom of gastrointestinal infections. The pathogens (viruses, bacteria, and parasites) that cause diarrhea spread through contaminated food or drinking water, and from person to person through poor hygiene and inadequate sanitation (unsafe disposal of human excreta). Interventions that prevent diarrhea include improvements in water supplies, sanitation and hygiene, the promotion of breast feeding, and vaccination against rotavirus (a major viral cause of diarrhea). Treatments for diarrhea include oral rehydration salts, which prevent and treat dehydration, zinc supplementation, which decreases the severity and duration of diarrhea, and the use of appropriate antibiotics when indicated for severe bacterial diarrhea.
Why Was This Study Done?
Nearly half of deaths from diarrhea among young children occur in Africa where diarrhea is the single largest cause of death among under 5-year-olds and a major cause of childhood illness. Unfortunately, although some of the risk factors for death from diarrhea in children in sub-Saharan Africa have been identified (for example, having other illnesses, poor nutrition, and not being breastfed), little is known about the relative contributions of different diarrhea-causing pathogens to diarrheal deaths. Clinicians need to know which of these pathogens are most likely to cause death in children so that they can manage their patients appropriately. In this cohort study, the researchers characterize the causes and risk factors associated with death among young children hospitalized for diarrhea in Nyanza Province, western Kenya, an area where most households have no access to safe drinking water and a quarter lack latrines. In a cohort study, a group of people with a specific condition is observed to identify which factors lead to different outcomes.
What Did the Researchers Do and Find?
The researchers enrolled all the children under 5 years old who were hospitalized over a two-year period for diarrhea at two district hospitals in Nyanza Province, tested their stool samples for diarrhea-causing viral and bacterial pathogens, and recorded which patients died in-hospital. They then used multivariable regression analysis (a statistical method) to determine which risk factors and diarrheal pathogens were associated with death among the children. During the study, 1,146 children were hospitalized, 107 of whom died in the hospital. 10% of all the stool samples contained nontyphoidal Salmonella, 4% contained Shigella (two types of diarrhea-causing bacteria), and 19% contained rotavirus. By contrast, 22% of the samples taken from children who died contained nontyphoidal Salmonella, 11% contained Shigella, 9% contained rotavirus, and 5% contained Campylobacter (another bacterial pathogen that causes diarrhea). Compared to survivors, infants (children under 1 year of age) who died were nearly seven times more likely to have nontyphoidal Salmonella in their stools and children under 5 years old who died were five and half times more likely to have Shigella in their stools but less likely to have rotavirus in their stools. Other factors associated with death included being malnourished, having oral thrush (a fungal infection of the mouth), having previously sought hospital care for diarrhea, and being dehydrated.
What Do These Findings Mean?
These findings indicate that, among young children admitted to the hospital in western Kenya with diarrhea, infections with nontyphoidal Salmonella and with Shigella (but not with rotavirus) were associated with an increased risk of death. Because this study only captured deaths in hospital and most diarrheal deaths in developing countries occur at home, these results may not accurately reflect the pathogens associated with overall childhood diarrheal deaths. In addition, they may not be generalizable to other geographical regions. Nevertheless, given that that there are currently no vaccines available for most bacterial diarrheal diseases, these findings highlight the importance of Kenya and other developing countries implementing effective strategies for the prevention and management of diarrheal diseases in children such as increasing access to improved water, sanitation, and hygiene, and community-level promotion of the use of oral rehydration solution and zinc supplements. They also suggest that enhanced surveillance and simplified laboratory diagnostics for diarrheal pathogens could help clinicians identify those children presenting to hospital with diarrhea who are at high risk of death and prioritize their treatment.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001256.
The World Health Organization provides information on diarrhea (in several languages); its 2009 report with UNICEF Diarrhea: why children are still dying and what can be done, which includes the WHO/UNICEF recommendations for the treatment and prevention of diarrhea in children, can be downloaded from the Internet
The children's charity UNICEF, which protects the rights of children and young people around the world, provides information on diarrhea (in several languages)
doi:10.1371/journal.pmed.1001256
PMCID: PMC3389023  PMID: 22802736
19.  Spatial and temporal dynamics of malaria transmission in rural Western Kenya 
Parasites & Vectors  2012;5:86.
Background
Understanding the relationship between Plasmodium falciparum malaria transmission and health outcomes requires accurate estimates of exposure to infectious mosquitoes. However, measures of exposure such as mosquito density and entomological inoculation rate (EIR) are generally aggregated over large areas and time periods, biasing the outcome-exposure relationship. There are few studies examining the extent and drivers of local variation in malaria exposure in endemic areas.
Methods
We describe the spatio-temporal dynamics of malaria transmission intensity measured by mosquito density and EIR in the KEMRI/CDC health and demographic surveillance system using entomological data collected during 2002–2004. Geostatistical zero inflated binomial and negative binomial models were applied to obtain location specific (house) estimates of sporozoite rates and mosquito densities respectively. Model-based predictions were multiplied to estimate the spatial pattern of annual entomological inoculation rate, a measure of the number of infective bites a person receive per unit of time. The models included environmental and climatic predictors extracted from satellite data, harmonic seasonal trends and parameters describing space-time correlation.
Results
Anopheles gambiae s.l was the main vector species accounting for 86 % (n = 2309) of the total mosquitoes collected with the remainder being Anopheles funestus. Sixty eight percent (757/1110) of the surveyed houses had no mosquitoes. Distance to water bodies, vegetation and day temperature were strongly associated with mosquito density. Overall annual point estimates of EIR were 6.7, 9.3 and 9.6 infectious bites per annum for 2002, 2003 and 2004 respectively. Monthly mosquito density and EIR varied over the study period peaking in May during the wet season each year. The predicted and observed densities of mosquitoes and EIR showed a strong seasonal and spatial pattern over the study area.
Conclusions
Spatio-temporal maps of malaria transmission intensity obtained in this study are not only useful in understanding variability in malaria epidemiology over small areas but also provide a high resolution exposure surface that can be used to analyse the impact of transmission on malaria related and all-cause morbidity and mortality.
doi:10.1186/1756-3305-5-86
PMCID: PMC3464956  PMID: 22541138
20.  Population-Based Biochemistry, Immunologic and Hematological Reference Values for Adolescents and Young Adults in a Rural Population in Western Kenya 
PLoS ONE  2011;6(6):e21040.
Background
There is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in sub-Saharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management.
Methods and Findings
A panel of 298, HIV-seronegative individuals aged 13–34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (<18 years)-to-adults (≥18 years) ratio and the male-to-female ratio was 1∶1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.S-derived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1–4) which would exclude them from participating in clinical trials.
Conclusion
Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya.
doi:10.1371/journal.pone.0021040
PMCID: PMC3119664  PMID: 21713038
21.  Bed net ownership in Kenya: the impact of 3.4 million free bed nets 
Malaria Journal  2010;9:183.
Background
In July and September 2006, 3.4 million long-lasting insecticide-treated bed nets (LLINs) were distributed free in a campaign targeting children 0-59 months old (CU5s) in the 46 districts with malaria in Kenya. A survey was conducted one month after the distribution to evaluate who received campaign LLINs, who owned insecticide-treated bed nets and other bed nets received through other channels, and how these nets were being used. The feasibility of a distribution strategy aimed at a high-risk target group to meet bed net ownership and usage targets is evaluated.
Methods
A stratified, two-stage cluster survey sampled districts and enumeration areas with probability proportional to size. Handheld computers (PDAs) with attached global positioning systems (GPS) were used to develop the sampling frame, guide interviewers back to chosen households, and collect survey data.
Results
In targeted areas, 67.5% (95% CI: 64.6, 70.3%) of all households with CU5s received campaign LLINs. Including previously owned nets, 74.4% (95% CI: 71.8, 77.0%) of all households with CU5s had an ITN. Over half of CU5s (51.7%, 95% CI: 48.8, 54.7%) slept under an ITN during the previous evening. Nearly forty percent (39.1%) of all households received a campaign net, elevating overall household ownership of ITNs to 50.7% (95% CI: 48.4, 52.9%).
Conclusions
The campaign was successful in reaching the target population, families with CU5s, the risk group most vulnerable to malaria. Targeted distribution strategies will help Kenya approach indicator targets, but will need to be combined with other strategies to achieve desired population coverage levels.
doi:10.1186/1475-2875-9-183
PMCID: PMC2912322  PMID: 20576145
22.  Impact of Antiretroviral Therapy on the Incidence of Tuberculosis: The Brazilian Experience, 1995–2001 
PLoS ONE  2007;2(9):e826.
Background
The human immunodeficiency virus (HIV) fuels tuberculosis (TB) epidemics. In controlled clinical trials, antiretroviral therapy (ART) reduces TB incidence in HIV-infected patients. In this study we determine if, under programmatic conditions, Brazil's policy of universal ART access has impacted TB incidence among HIV-infected patients.
Methods
We abstracted clinical information from records of HIV-infected patients managed in the public sector in 11 Brazilian states between 1/1/1995 and 12/31/2001. Case ascertainment (TB and HIV) utilized guidelines (with added stringency) published by Brazil's Ministry of Health. We determined TB incidence and hazards ratio (HR) for ART-naïve and ART-treated [including highly active ART (HAART)] patients employing Cox proportional hazards analysis.
Results
Information from 463 HIV-infected patients met study criteria. The median age of the study population was 34 years, 70% were male, and mean follow-up to primary endpoints—TB, death, and last clinic visit—was 330, 1059, and 1125 days, respectively. Of the 463 patients, 76 (16%) remained ART-naïve. Of the patients who never received HAART (n = 157) 81 were treated with ART non-HAART. Of the patients who received any ART (n = 387), 306 were treated with HAART (includes those patients who later switched from ART non-HAART to HAART). Tuberculosis developed in 39/463 (8%) patients. Compared to HAART- and ART non-HAART-treated patient groups, TB incidence was 10- (p<0.001) and 2.5-fold (p = 0.03) higher in ART-naïve patients, respectively. The median baseline absolute CD4+ T-lymphocyte count for patients who developed TB was not significantly different from that of patients who remained TB free. In multivariate analysis, the incidence of TB was statistically significantly lower in HAART-treated [HR 0.2; 95% (CI 0.1, 0.6); p<0.01] compared to ART naïve patients. A baseline CD4+ T-lymphocyte count <200 cells/mm3 [HR 2.5; (95% CI 1.2, 5.4); p<0.01], prior hospitalization [HR 4.2; (95% CI 2.0, 8.8); p<0.001], prior incarceration [HR 4.1; 95% CI 1.6, 10.3); p<0.01], and a positive tuberculin skin test [HR 3.1; (95% CI 1.1, 9.0); p = 0.04] were independently and positively associated with incident TB.
Conclusion
In this population-based study we demonstrate an 80% reduction in incident TB, under programmatic conditions, in HAART-treated HIV-infected patients compared to ART-naïve patients.
doi:10.1371/journal.pone.0000826
PMCID: PMC1952142  PMID: 17786198
23.  HIV-Associated TB in An Giang Province, Vietnam, 2001–2004: Epidemiology and TB Treatment Outcomes 
PLoS ONE  2007;2(6):e507.
Background
Mortality is high in HIV-infected TB patients, but few studies from Southeast Asia have documented the benefits of interventions, such as co-trimoxazole (CTX), in reducing mortality during TB treatment. To help guide policy in Vietnam, we studied the epidemiology of HIV-associated TB in one province and examined factors associated with outcomes, including the impact of CTX use.
Methodology/Principal Findings
We retrospectively abstracted data for all HIV-infected persons diagnosed with TB from 2001–2004 in An Giang, a province in southern Vietnam in which TB patients receive HIV counseling and testing. We used standard WHO definitions to classify TB treatment outcomes. We conducted multivariate analysis to identify risk factors for the composite outcome of death, default, or treatment failure during TB treatment. From 2001–2004, 637 HIV-infected TB patients were diagnosed in An Giang. Of these, 501 (79%) were male, 321 (50%) were aged 25–34 years, and the most common self-reported HIV risk factor was sex with a commercial sex worker in 221 (35%). TB was classified as smear-positive in 531 (83%). During TB treatment, 167 (26%) patients died, 9 (1%) defaulted, and 6 (1%) failed treatment. Of 454 patients who took CTX, 116 (26%) had an unsuccessful outcome compared with 33 (70%) of 47 patients who did not take CTX (relative risk, 0.4; 95% confidence interval [CI], 0.3–0.5). Adjusting for male sex, rural residence, TB smear status and disease location, and the occurrence of adverse events during TB treatment in multivariate analysis, the benefit of CTX persisted (adjusted odds ratio for unsuccessful outcome 0.1; CI, 0.1–0.3).
Conclusions/Significance
In An Giang, Vietnam, HIV-associated TB was associated with poor TB treatment outcomes. Outcomes were significantly better in those taking CTX. This finding suggests that Vietnam should consider applying WHO recommendations to prescribe CTX to all HIV-infected TB patients.
doi:10.1371/journal.pone.0000507
PMCID: PMC1876817  PMID: 17551587
24.  Worldwide Emergence of Extensively Drug-resistant Tuberculosis 
Emerging Infectious Diseases  2007;13(3):380-387.
Mycobacterium tuberculosis strains are becoming resistant to not only the most powerful first-line drugs but also many second-line drugs.
Mycobacterium tuberculosis strains that are resistant to an increasing number of second-line drugs used to treat multidrug-resistant tuberculosis (MDR-TB) are becoming a threat to public health worldwide. We surveyed the Network of Supranational Reference Laboratories for M. tuberculosis isolates that were resistant to second-line anti-TB drugs during 2000–2004. We defined extensively drug-resistant TB (XDR-TB) as MDR-TB with further resistance to ≥3 of the 6 classes of second-line drugs. Of 23 eligible laboratories, 14 (61%) contributed data on 17,690 isolates, which reflected drug susceptibility results from 48 countries. Of 3,520 (19.9%) MDR-TB isolates, 347 (9.9%) met criteria for XDR-TB. Further investigation of population-based trends and expanded efforts to prevent drug resistance and effectively treat patients with MDR-TB are crucial for protection of public health and control of TB.
doi:10.3201/eid1303.061400
PMCID: PMC2725916  PMID: 17552090
Mycobacterium tuberculosis; tuberculosis; multidrug-resistant; infectious diseases; emerging; second-line drugs; research
25.  Adherence to Antimicrobial Inhalational Anthrax Prophylaxis among Postal Workers, Washington, D.C., 2001 
Emerging Infectious Diseases  2002;8(10):1138-1144.
In October 2001, two envelopes containing Bacillus anthracis spores were processed at the Washington, D.C., Processing and Distribution Center of the U.S. Postal Service; inhalational anthrax developed in four workers at this facility. More than 2,000 workers were advised to complete 60 days of postexposure prophylaxis to prevent inhalational anthrax. Interventions to promote adherence were carried out to support workers, and qualitative information was collected to evaluate our interventions. A quantitative survey was administered to a convenience sample of workers to assess factors influencing adherence. No anthrax infections developed in any workers involved in the interventions or interviews. Of 245 workers, 98 (40%) reported full adherence to prophylaxis, and 45 (18%) had completely discontinued it. Experiencing adverse effects to prophylaxis, anxiety, and being <45 years old were risk factors for discontinuing prophylaxis. Interventions, especially frequent visits by public health staff, proved effective in supporting adherence.
doi:10.3201/eid0810.020331
PMCID: PMC2730315  PMID: 12396929
adherence; Bacillus anthracis; bioterrorism; antimicrobial prophylaxis; compliance

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