Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-30 (of 32 Records) |
Query Trace: Odero C [original query] |
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Xpert MTB/RIF Ultra versus mycobacterial growth indicator tube liquid culture for detection of Mycobacterium tuberculosis in symptomatic adults: a diagnostic accuracy study
Xie YL , Eichberg C , Hapeela N , Nakabugo E , Anyango I , Arora K , Korte JE , Odero R , van Heerden J , Zemanay W , Kennedy S , Nabeta P , Hanif M , Rodrigues C , Skrahina A , Stevens W , Dietze R , Liu X , Ellner JJ , Alland D , Joloba ML , Schumacher SG , McCarthy KD , Nakiyingi L , Dorman SE . Lancet Microbe 2024 BACKGROUND: Xpert MTB/RIF Ultra (Ultra) is an automated molecular test for the detection of Mycobacterium tuberculosis in sputum. We compared the sensitivity of Ultra to that of mycobacterial growth indicator tube (MGIT) liquid culture, considered the most sensitive assay in routine clinical use. METHODS: In this prospective, multicentre, cross-sectional diagnostic accuracy study, we used a non-inferiority design to assess whether the sensitivity of a single Ultra test was non-inferior to that of a single liquid culture for detection of M tuberculosis in sputum. We enrolled adults (age ≥18 years) with pulmonary tuberculosis symptoms in 11 countries and each adult provided three sputum specimens with a minimum volume of 2 mL over 2 days. Ultra was done directly on sputum 1, and Ultra and MGIT liquid culture were done on resuspended pellet from sputum 2. Results of MGIT and solid media cultures done on sputum 3 were considered the reference standard. The pre-defined non-inferiority margin was 5·0%. FINDINGS: Between Feb 18, 2016, and Dec 4, 2019, we enrolled 2906 participants. 2600 (89%) participants were analysed, including 639 (25%) of 2600 who were positive for tuberculosis by the reference standard. Of the 2357 included in the non-inferiority analysis, 877 (37%) were HIV-positive and 984 (42%) were female. Sensitivity of Ultra performed directly on sputum 1 was non-inferior to that of sputum 2 MGIT culture (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; 95% CI -2·8 to 1·1). Sensitivity of Ultra performed on sputum 2 pellet was also non-inferior to that of sputum 2 MGIT (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; -2·7 to 1·0). INTERPRETATION: For the detection of M tuberculosis in sputum from adults with respiratory symptoms, there was no difference in sensitivity of a single Ultra test to that of a single MGIT culture. Highly sensitive, rapid molecular approaches for M tuberculosis detection, combined with advances in genotypic methods for drug resistance detection, have potential to replace culture. FUNDING: US National Institute of Allergy and Infectious Diseases. |
Early morning anopheline mosquito biting, a potential driver of malaria transmission in Busia County, western Kenya
Odero JI , Abong'o B , Moshi V , Ekodir S , Harvey SA , Ochomo E , Gimnig JE , Achee NL , Grieco JP , Oria PA , Monroe A . Malar J 2024 23 (1) 66 BACKGROUND: Insecticide-treated nets (ITNs) contributed significantly to the decline in malaria since 2000. Their protective efficacy depends not only on access, use, and net integrity, but also location of people within the home environment and mosquito biting profiles. Anopheline mosquito biting and human location data were integrated to identify potential gaps in protection and better understand malaria transmission dynamics in Busia County, western Kenya. METHODS: Direct observation of human activities and human landing catches (HLC) were performed hourly between 1700 to 0700 h. Household members were recorded as home or away; and, if at home, as indoors/outdoors, awake/asleep, and under a net or not. Aggregated data was analysed by weighting hourly anopheline biting activity with human location. Standard indicators of human-vector interaction were calculated using a Microsoft Excel template. RESULTS: There was no significant difference between indoor and outdoor biting for Anopheles gambiae sensu lato (s.l.) (RR = 0.82; 95% CI 0.65-1.03); significantly fewer Anopheles funestus were captured outdoors than indoors (RR = 0.41; 95% CI 0.25-0.66). Biting peaked before dawn and extended into early morning hours when people began to awake and perform routine activities, between 0400-0700 h for An. gambiae and 0300-0700 h for An. funestus. The study population away from home peaked at 1700-1800 h (58%), gradually decreased and remained constant at 10% throughout the night, before rising again to 40% by 0600-0700 h. When accounting for resident location, nearly all bites within the peri-domestic space (defined as inside household structures and surrounding outdoor spaces) occurred indoors for unprotected people (98%). Using an ITN while sleeping was estimated to prevent 79% and 82% of bites for An. gambiae and An. funestus, respectively. For an ITN user, most remaining exposure to bites occurred indoors in the hours before bed and early morning. CONCLUSION: While use of an ITN was estimated to prevent most vector bites in this context, results suggest gaps in protection, particularly in the early hours of the morning when biting peaks and many people are awake and active. Assessment of additional human exposure points, including outside of the peri-domestic setting, are needed to guide supplementary interventions for transmission reduction. |
Impact of the COVID-19 pandemic on routine HIV care and antiretroviral treatment outcomes in Kenya: A nationally representative analysis
Kimanga DO , Makory VNB , Hassan AS , Ngari F , Ndisha MM , Muthoka KJ , Odero L , Omoro GO , Aoko A , Ng'ang'a L . PLoS One 2023 18 (11) e0291479 BACKGROUND: The COVID-19 pandemic adversely disrupted global health service delivery. We aimed to assess impact of the pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and initial virologic non-suppression (VnS) among individuals starting antiretroviral therapy (ART) in Kenya. METHODS: Individual-level longitudinal service delivery data were analysed. Random sampling of individuals aged >15 years starting ART between April 2018 -March 2021 was done. Date of ART initiation was stratified into pre-COVID-19 (April 2018 -March 2019 and April 2019 -March 2020) and COVID-19 (April 2020 -March 2021) periods. Mixed effects generalised linear, survival and logistic regression models were used to determine the effect of COVID-19 pandemic on same-day HIV diagnosis/ART initiation, six-months non-retention and VnS, respectively. RESULTS: Of 7,046 individuals sampled, 35.5%, 36.0% and 28.4% started ART during April 2018 -March 2019, April 2019 -March 2020 and April 2020 -March 2021, respectively. Compared to the pre-COVID-19 period, the COVID-19 period had higher same-day HIV diagnosis/ART initiation (adjusted risk ratio [95% CI]: 1.09 [1.04-1.13], p<0.001) and lower six-months non-retention (adjusted hazard ratio [95% CI]: 0.66 [0.58-0.74], p<0.001). Of those sampled, 3,296 (46.8%) had a viral load test done at a median 6.2 (IQR, 5.3-7.3) months after ART initiation. Compared to the pre-COVID-19 period, there was no significant difference in VnS during the COVID-19 period (adjusted odds ratio [95% CI]: 0.79 [95%% CI: 0.52-1.20], p = 0.264). CONCLUSIONS: In the short term, the COVID-19 pandemic did not have an adverse impact on HIV care and treatment outcomes in Kenya. Timely, strategic and sustained COVID-19 response may have played a critical role in mitigating adverse effects of the pandemic and point towards maturity, versatility and resilience of the HIV program in Kenya. Continued monitoring to assess long-term impact of the COVID-19 pandemic on HIV care and treatment program in Kenya is warranted. |
Leveraging electronic medical records for HIV testing, care, and treatment programming in Kenya-The National Data Warehouse Project
Ndisha M , Hassan AS , Ngari F , Munene E , Gikura M , Kimutai K , Muthoka K , Murie LA , Tolentino H , Odhiambo J , Mwele P , Odero L , Mbaire K , Omoro G , Kimanga DO . BMC Med Inform Decis Mak 2023 23 (1) 183 BACKGROUND: Aggregate electronic data repositories and population-level cross-sectional surveys play a critical role in HIV programme monitoring and surveillance for data-driven decision-making. However, these data sources have inherent limitations including inability to respond to public health priorities in real-time and to longitudinally follow up clients for ascertainment of long-term outcomes. Electronic medical records (EMRs) have tremendous potential to bridge these gaps when harnessed into a centralised data repository. We describe the evolution of EMRs and the development of a centralised national data warehouse (NDW) repository. Further, we describe the distribution and representativeness of data from the NDW and explore its potential for population-level surveillance of HIV testing, care and treatment in Kenya. MAIN BODY: Health information systems in Kenya have evolved from simple paper records to web-based EMRs with features that support data transmission to the NDW. The NDW design includes four layers: data warehouse application programming interface (DWAPI), central staging, integration service, and data visualization application. The number of health facilities uploading individual-level data to the NDW increased from 666 in 2016 to 1,516 in 2020, covering 41 of 47 counties in Kenya. By the end of 2020, the NDW hosted longitudinal data from 1,928,458 individuals ever started on antiretroviral therapy (ART). In 2020, there were 936,869 individuals who were active on ART in the NDW, compared to 1,219,276 individuals on ART reported in the aggregate-level Kenya Health Information System (KHIS), suggesting 77% coverage. The proportional distribution of individuals on ART by counties in the NDW was consistent with that from KHIS, suggesting representativeness and generalizability at the population level. CONCLUSION: The NDW presents opportunities for individual-level HIV programme monitoring and surveillance because of its longitudinal design and its ability to respond to public health priorities in real-time. A comparison with estimates from KHIS demonstrates that the NDW has high coverage and that the data maybe representative and generalizable at the population-level. The NDW is therefore a unique and complementary resource for HIV programme monitoring and surveillance with potential to strengthen timely data driven decision-making towards HIV epidemic control in Kenya. DATABASE LINK: ( https://dwh.nascop.org/ ). |
Uptake and continuation of HIV pre-exposure prophylaxis among women of reproductive age in two health facilities in Kisumu County, Kenya
Ogolla M , Nyabiage OL , Musingila P , Gachau S , Odero TMA , Odoyo-June E , Ochanda B , Appolonia A , Katiku E , Joseph R , Ogolla C , Otieno L , Odhiambo F , Truong HM . J Int AIDS Soc 2023 26 (3) e26069 INTRODUCTION: In 2020, Kenya had 19,000 new HIV infections among women aged 15+ years. Studies have shown sub-optimal oral pre-exposure prophylaxis (PrEP) use among sub-populations of women. We assessed the uptake and continuation of oral PrEP among women 15-49 years in two health facilities in Kisumu County, Kenya. METHODS: A retrospective cohort of 262 women aged 15-49 years, initiated into oral PrEP between 12 November 2019 and 31 March 2021, was identified from two health facilities in the urban setting of Kisumu County, Kenya. Data on baseline characteristics and oral PrEP continuation at months 1, 3 and 6 were abstracted from patient records and summarized using descriptive statistics. Missing data in the predictor variables were imputed within the joint modelling multiple imputation framework. Using logistic regression, we evaluated factors associated with the discontinuation of oral PrEP at month 1. RESULTS: Of the 66,054 women screened, 320 (0.5%) were eligible and 262 (82%) were initiated on oral PrEP. Uptake was higher among women 25-29 years as compared to those 15-24 years (77% vs. 33%). Oral PrEP continuation declined significantly with increasing duration of follow-up; 37% at month 1, 21% at month 3 and 12% at month 6 (p<0.05). In the adjusted analysis, women 15-24 years had lower adjusted odds of continuing at month 1 than women ≥25 years (adjusted odds ratio [aOR]: 0.41, 95% CI: 0.21-0.82). There was no association between being sero-discordant and continuation of oral PrEP at month 1 (aOR; 1.21, 95% CI 0.59-2.50). Women from the sub-county hospital were more likely to continue at month 1 of follow-up compared to women enrolled in the county referral hospital (aOR 5.11; 95% CI 2.24-11.70). CONCLUSIONS: The low eligibility for oral PrEP observed among women 15-49 years in an urban setting with high HIV prevalence calls for a review of the screening process to validate the sensitivity of the screening tool and its proper application. The low uptake and continuation among adolescent girls and young women underscores the need to identify and address specific patient- and facility-level barriers affecting different sub-populations at risk for HIV acquisition. |
Mass testing and treatment on malaria in an area of western Kenya
Samuels AM , Odero NA , Odongo W , Otieno K , Were V , Shi YP , Sang T , Williamson J , Wiegand R , Hamel MJ , Kachur SP , Slutsker L , Lindblade KA , Kariuki SK , Desai MR . Clin Infect Dis 2021 72 (6) 1103-1104 We appreciate the thoughtful commentary provided by Hamer and Miller [1] and are pleased that they arrived at many of the same conclusions that we did; however, we would like to clarify a few points. | | First, we wish to correct the statement that, in our trial, mass testing and treatment (MTaT) was only implemented within the core areas of clusters. Rather, MTaT was implemented throughout intervention clusters, which included a core area ranging between 1 and 3 Km in diameter, and a 300-m buffer. As described, to limit contamination, inclusion criteria for the analytic sample required residence within the core area [2, 3]. |
Impact of intermittent mass testing and treatment on incidence of malaria infection in a high transmission area of western Kenya
Desai M , Samuels A , Odongo W , Williamson J , Odero NA , Otieno K , Shi YP , Kachur SP , Hamel MJ , Kariuki S , Lindblade KA . Am J Trop Med Hyg 2020 103 (1) 369-377 Progress with malaria control in western Kenya has stagnated since 2007. Additional interventions to reduce the high burden of malaria in this region are urgently needed. We conducted a two-arm, community-based, cluster-randomized, controlled trial of active case detection and treatment of malaria infections in all residents mass testing and treatment (MTaT) of 10 village clusters (intervention clusters) for two consecutive years to measure differences in the incidence of clinical malaria disease and malaria infections compared with 20 control clusters where MTaT was not implemented. All residents of intervention clusters, irrespective of history of fever or other malaria-related symptoms, were tested three times per year before the peak malaria season using malaria rapid diagnostic tests. All positive cases were treated with dihydroartemisinin-piperaquine. The incidence of clinical malaria was measured through passive surveillance, whereas the cumulative incidence of malaria infection was measured using active surveillance in a cohort comprising randomly selected residents. The incidence of clinical malaria was 0.19 cases/person-year (p-y, 95% CI: 0.13-0.28) in the intervention arm and 0.24 cases/p-y (95% CI: 0.15-0.39) in the control arm (incidence rate ratio [IRR] 0.79, 95% CI: 0.61-1.02). The cumulative incidence of malaria infections was similar between the intervention (2.08 infections/p-y, 95% CI: 1.93-2.26) and control arms (2.19 infections/p-y, 95% CI: 2.02-2.37) with a crude IRR of 0.95 (95% CI: 0.87-1.04). Six rounds of MTaT over 2 years did not have a significant impact on the incidence of clinical malaria or the cumulative incidence of malaria infection in this area of high malaria transmission. |
Impact of community-based mass testing and treatment on malaria infection prevalence in a high transmission area of western Kenya: A cluster randomized controlled trial
Samuels AM , Odero NA , Odongo W , Otieno K , Were V , Shi YP , Sang T , Williamson J , Wiegand R , Hamel MJ , Kachur SP , Slutsker L , Lindblade KA , Kariuki SK , Desai MR . Clin Infect Dis 2020 72 (11) 1927-1935 BACKGROUND: Global gains towards malaria elimination have been heterogeneous and have recently stalled. Interventions targeting afebrile malaria infections may be needed to address residual transmission. We studied the efficacy of repeated rounds of community-based mass testing and treatment (MTaT) on malaria infection prevalence in western Kenya. METHODS: Twenty clusters were randomly assigned to three rounds of MTaT per year for two years or control (standard-of-care for testing and treatment at public health facilities along with government sponsored mass long-lasting insecticidal net (LLIN) distributions). During rounds community health volunteers visited all households in intervention clusters and tested all consenting individuals with a rapid diagnostic test. Those positive were treated with dihydroartemisinin-piperaquine. Cross-sectional community infection prevalence surveys were performed in both study arms at baseline and each year after three rounds of MTaT. The primary outcome was the effect size of MTaT on parasite prevalence by microscopy between arms by year adjusted for age, reported LLIN use, enhanced vegetative index, and socio-economic status. RESULTS: Demographic and behavioral characteristics, including LLIN usage, were similar between arms at each survey. MTaT coverage ranged between 75.0-77.5% and 81.9-94.3% between the three rounds in year 1 and year 2, respectively. The adjusted effect size of MTaT on the prevalence of parasitemia between arms was 0.93 (CI: 0.79-1.08) and 0.92 (0.76-1.10) after year 1 and 2, respectively. CONCLUSIONS: MTaT performed three times per year over two years did not reduce malaria parasite prevalence in this high-transmission area. |
Impact of 10-valent pneumococcal conjugate vaccine introduction on pneumococcal carriage and antibiotic susceptibility patterns among children aged <5 years and adults with human immunodeficiency virus infection: Kenya, 2009-2013
Kobayashi M , Bigogo G , Kim L , Mogeni OD , Conklin LM , Odoyo A , Odiembo H , Pimenta F , Ouma D , Harris AM , Odero K , Milucky JL , Ouma A , Aol G , Audi A , Onyango C , Cosmas L , Jagero G , Farrar JL , da Gloria Carvalho M , Whitney CG , Breiman RF , Lessa FC . Clin Infect Dis 2020 70 (5) 814-826 BACKGROUND: Kenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) among children <1 year in 2011 with catch-up vaccination among children 1-4 years in some areas. We assessed changes in pneumococcal carriage and antibiotic susceptibility patterns in children <5 years and adults. METHODS: During 2009-2013, we performed annual cross-sectional pneumococcal carriage surveys in 2 sites: Kibera (children <5 years) and Lwak (children <5 years, adults). Only Lwak had catch-up vaccination. Nasopharyngeal and oropharyngeal (adults only) swabs underwent culture for pneumococci; isolates were serotyped. Antibiotic susceptibility testing was performed on isolates from 2009 and 2013; penicillin nonsusceptible pneumococci (PNSP) was defined as penicillin-intermediate or -resistant. Changes in pneumococcal carriage by age (<1 year, 1-4 years, adults), site, and human immunodeficiency virus (HIV) status (adults only) were calculated using modified Poisson regression, with 2009-2010 as baseline. RESULTS: We enrolled 2962 children (2073 in Kibera, 889 in Lwak) and 2590 adults (2028 HIV+, 562 HIV-). In 2013, PCV10-type carriage was 10.3% (Lwak) to 14.6% (Kibera) in children <1 year and 13.8% (Lwak) to 18.7% (Kibera) in children 1-4 years. This represents reductions of 60% and 63% among children <1 year and 52% and 60% among children 1-4 years in Kibera and Lwak, respectively. In adults, PCV10-type carriage decreased from 12.9% to 2.8% (HIV+) and from 11.8% to 0.7% (HIV-). Approximately 80% of isolates were PNSP, both in 2009 and 2013. CONCLUSIONS: PCV10-type carriage declined in children <5 years and adults post-PCV10 introduction. However, PCV10-type and PNSP carriage persisted in children regardless of catch-up vaccination. |
Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: development of study site infrastructure and lessons learned
Odero NA , Samuels AM , Odongo W , Abong'o B , Gimnig J , Otieno K , Odero C , Obor D , Ombok M , Were V , Sang T , Hamel MJ , Kachur SP , Slutsker L , Lindblade KA , Kariuki S , Desai M . Malar J 2019 18 (1) 255 BACKGROUND: Malaria transmission is high in western Kenya and the asymptomatic infected population plays a significant role in driving the transmission. Mathematical modelling and simulation programs suggest that interventions targeting asymptomatic infections through mass testing and treatment (MTaT) or mass drug administration (MDA) have the potential to reduce malaria transmission when combined with existing interventions. OBJECTIVE: This paper describes the study site, capacity development efforts required, and lessons learned for implementing a multi-year community-based cluster-randomized controlled trial to evaluate the impact of MTaT for malaria transmission reduction in an area of high transmission in western Kenya. METHODS: The study partnered with Kenya's Ministry of Health (MOH) and other organizations on community sensitization and engagement to mobilize, train and deploy community health volunteers (CHVs) to deliver MTaT in the community. Within the health facilities, the study availed staff, medical and laboratory supplies and strengthened health information management system to monitor progress and evaluate impact of intervention. RESULTS: More than 80 Kenya MOH CHVs, 13 clinical officers, field workers, data and logistical staff were trained to carry out MTaT three times a year for 2 years in a population of approximately 90,000 individuals. A supply chain management was adapted to meet daily demands for large volumes of commodities despite the limitation of few MOH facilities having ideal storage conditions. Modern technology was adapted more to meet the needs of the high daily volume of collected data. CONCLUSIONS: In resource-constrained settings, large interventions require capacity building and logistical planning. This study found that investing in relationships with the communities, local governments, and other partners, and identifying and equipping the appropriate staff with the skills and technology to perform tasks are important factors for success in delivering an intervention like MTaT. |
Modelling the relationship between malaria prevalence as a measure of transmission and mortality across age groups
Khagayi S , Desai M , Amek N , Were V , Onyango ED , Odero C , Otieno K , Bigogo G , Munga S , Odhiambo F , Hamel MJ , Kariuki S , Samuels AM , Slutsker L , Gimnig J , Vounatsou P . Malar J 2019 18 (1) 247 BACKGROUND: Parasite prevalence has been used widely as a measure of malaria transmission, especially in malaria endemic areas. However, its contribution and relationship to malaria mortality across different age groups has not been well investigated. Previous studies in a health and demographic surveillance systems (HDSS) platform in western Kenya quantified the contribution of incidence and entomological inoculation rates (EIR) to mortality. The study assessed the relationship between outcomes of malaria parasitaemia surveys and mortality across age groups. METHODS: Parasitological data from annual cross-sectional surveys from the Kisumu HDSS between 2007 and 2015 were used to determine malaria parasite prevalence (PP) and clinical malaria (parasites plus reported fever within 24 h or temperature above 37.5 degrees C). Household surveys and verbal autopsy (VA) were used to obtain data on all-cause and malaria-specific mortality. Bayesian negative binomial geo-statistical regression models were used to investigate the association of PP/clinical malaria with mortality across different age groups. Estimates based on yearly data were compared with those from aggregated data over 4 to 5-year periods, which is the typical period that mortality data are available from national demographic and health surveys. RESULTS: Using 5-year aggregated data, associations were established between parasite prevalence and malaria-specific mortality in the whole population (RRmalaria = 1.66; 95% Bayesian Credible Intervals: 1.07-2.54) and children 1-4 years (RRmalaria = 2.29; 1.17-4.29). While clinical malaria was associated with both all-cause and malaria-specific mortality in combined ages (RRall-cause = 1.32; 1.01-1.74); (RRmalaria = 2.50; 1.27-4.81), children 1-4 years (RRall-cause = 1.89; 1.00-3.51); (RRmalaria = 3.37; 1.23-8.93) and in older children 5-14 years (RRall-cause = 3.94; 1.34-11.10); (RRmalaria = 7.56; 1.20-39.54), no association was found among neonates, adults (15-59 years) and the elderly (60+ years). Distance to health facilities, socioeconomic status, elevation and survey year were important factors for all-cause and malaria-specific mortality. CONCLUSION: Malaria parasitaemia from cross-sectional surveys was associated with mortality across age groups over 4 to 5 year periods with clinical malaria more strongly associated with mortality than parasite prevalence. This effect was stronger in children 5-14 years compared to other age-groups. Further analyses of data from other HDSS sites or similar platforms would be useful in investigating the relationship between malaria and mortality across different endemicity levels. |
Medical pluralism and rationalities for HIV care utilization among discordant couples in Siaya County, rural western Kenya
Arego J , Ondenge K , Odero I , Awuonda E , Omoro T , Akelo V , Mudhune V , Gust DA . Int J STD AIDS 2019 30 (9) 956462419843691 Understanding healthcare seeking and utilization of members of discordant couples can help in implementing effective HIV treatment, care, and support. We conducted a qualitative study comprised of in-depth interviews (n = 26) and ten focus group discussions (n = 73) with community members including opinion leaders, healthcare workers, and members of discordant couples. A portion of the latter group had been participants in the HIV Prevention Trials Network (HPTN) 052 study. Themes that emerged from the data were pragmatism and the realities of hospital care, quest for a cure through traditional medicine, and religious dogma. Medical pluralism is practiced by members of discordant couples seeking HIV care through intersections of hospital facility services and traditional and religious therapeutic options. It would be prudent for healthcare policy makers and conventional medical providers to recognize the importance of traditional medicine and religion in the lives of members of HIV discordant couples and make efforts to integrate the positive concepts of both into the couples' overall health plan. |
Community perceptions and personal accounts of HIV discordance in rural western Kenya
Ondenge K , Odero I , Awuonda E , Omoro T , Kibogo M , Otieno G , Ongwena P , Gust DA . Afr J AIDS Res 2018 17 (3) 281-290 Among HIV-discordant couples, the literature is sparse regarding issues related to stigma, relationships and coping. Objectives were to explore: 1) perceptions about discordant HIV status; 2) understanding of HIV discordancy; 3) effects of discordancy on couples; and 4) adaptation and coping strategies for discordant HIV status. A survey was administered to 202 members of heterosexual discordant couples in rural western Kenya. In addition, to understand the community perspective, in-depth interviews (IDI) (n = 26) and focus group discussions (FGD) (n = 10) were conducted with community opinion leaders, healthcare workers and members of discordant couples. More than 70% of men (73.4%) and women (80.4%) surveyed agreed that their relationship changed for the worse when they disclosed their HIV status to their partner. Participants of IDIs and FGDs provided several explanations for discordancy including the perception that discordancy is a lie, the negative partner has "thick blood", HIV infection is a punishment for sexual promiscuity or cultural disobedience, and that HIV is a punishment from God. Members of discordant couples reported experiencing tension and fear, stigma and rejection, and changes in partner support. Adaptation and coping strategies included counselling, sero-sorting and pursuing concordancy with the uninfected partner. HIV discordancy in a relationship can potentially cause long-term negative emotional and physical consequences. There is an acute need to develop and disseminate locally sensitive HIV-discordant couple counselling messages, and to provide couple-centred HIV care and treatment. Communication can help couples rebuild and rebalance their relationship and adjust to a new normal. |
Participant satisfaction with clinical trial experience and post-trial transitioning to HIV care in Kenya
Odero I , Ondeng'e K , Mudhune V , Okola P , Oruko J , Otieno G , Akelo V , Gust DA . Int J STD AIDS 2018 30 (1) 956462418791946 We conducted an exploratory analysis of former HIV Prevention Trials Network 052 (HPTN 052) clinical trial participants in 2016 to assess their (1) satisfaction with the HPTN 052 clinical trial care and treatment, and reasons for joining the trial; and (2) perspectives about the post-trial transition to public HIV care centers. Quantitative data showed that, of the 70 survey participants, 94.3% (n = 66) reported being very satisfied with the care and treatment they received while participating in the clinical trial and 51.4% (n = 36) reported they joined the study because they would receive information to improve their own or their partner's health. Qualitative data (five in-depth interviews and two focus group discussions) analysis revealed the following themes: transition experiences; perceived superior clinical trial care; study benefits not offered at public HIV care centers; and the public HIV care centers' indifference to the uninfected partner. For some HPTN 052 participants, transition to HIV care clinics was disappointing. Clinical trial investigators and local Institutional Review Boards should consider the need for safeguards and oversight of post-trial health care for trial participants after the trial ends, especially in resource-constrained settings, to avoid negative health outcomes. |
Development of colorimetric sensor array for diagnosis of tuberculosis through detection of urinary volatile organic compounds
Sandlund J , Lim S , Queralto N , Huang R , Yun J , Taba B , Song R , Odero R , Ouma G , Sitati R , Murithi W , Cain KP , Banaei N . Diagn Microbiol Infect Dis 2018 92 (4) 299-304 BACKGROUND: Top priorities for tuberculosis control and elimination include a simple, low-cost screening test using sputum and a non-sputum-based test in patients that do not produce sputum. The aim of this study was to evaluate the performance of a colorimetric sensor array (CSA) test, for analysis of volatile organic compounds in urine, in the diagnosis of pulmonary TB. MATERIAL AND METHODS: Urine samples were collected from individuals suspected of having pulmonary TB in Western Kenya. Reference methods included MGIT culture and/or Xpert MTB/RIF nucleic acid amplification test on sputa. Fresh urine samples were tested with the CSA, with acid and base and without an additive. The CSA were digitally imaged, and the resulting colorimetric response patterns were used for chemometric analysis. Sensitivity, specificity, and negative (NPV) and positive predictive (PPV) values were determined for HIV-positive and HIV-negative patients. RESULTS: In HIV-negative patients, the highest accuracy was obtained in urine samples pre-treated with a base, yielding a sensitivity, specificity, PPV, and NPV of 78.3% (65/83), 69.2% (54/78), 73.0% (n/89) and 75.0% (n/72). The highest sensitivity of 79.5% was achieved using sensor data from all three test conditions at a specificity of 65.4%. In HIV-positive subjects, the sensor performance was substantially lower with sensitivity, specificity, PPV, and NPV ranging from 48.3% to 62.3%, 54.1% to 74.0%, 55.9% to 64.2%, and 60.6% to 64.9%, respectively. CONCLUSION: The CSA fingerprint of urine headspace volatiles showed moderate accuracy in diagnosing TB in HIV-negative patients, but the sensor performance dropped substantially in HIV-coinfected patients. Further development of TB-responsive CSA indicators may improve the accuracy of CSA urine assay. |
Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections
Early AM , Lievens M , MacInnis BL , Ockenhouse CF , Volkman SK , Adjei S , Agbenyega T , Ansong D , Gondi S , Greenwood B , Hamel M , Odero C , Otieno K , Otieno W , Owusu-Agyei S , Asante KP , Sorgho H , Tina L , Tinto H , Valea I , Wirth DF , Neafsey DE . Nat Commun 2018 9 (1) 1381 Host immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures. Here, we combine these complementary approaches in an analysis of the malaria parasite Plasmodium falciparum using haplotype sequences from thousands of natural infections in sub-Saharan Africa. We find that parasite genotypes show preferential clustering within multi-strain infections in young children, and identify individual amino acid positions that may contribute to strain-specific immunity. Our results demonstrate that natural host defenses to P. falciparum act in an allele-specific manner to block specific parasite haplotypes from establishing blood-stage infections. This selection partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines targeting such proteins should account for allele-specific immunity. |
Assessment of submicroscopic infections and gametocyte carriage of Plasmodium falciparum during peak malaria transmission season in a community-based cross-sectional survey in western Kenya, 2012.
Zhou Z , Mitchell RM , Kariuki S , Odero C , Otieno P , Otieno K , Onyona P , Were V , Wiegand RE , Gimnig JE , Walker ED , Desai M , Shi YP . Malar J 2016 15 (1) 421 BACKGROUND: Although malaria control intervention has greatly decreased malaria morbidity and mortality in many African countries, further decline in parasite prevalence has stagnated in western Kenya. In order to assess if malaria transmission reservoir is associated with this stagnation, submicroscopic infection and gametocyte carriage was estimated. Risk factors and associations between malaria control interventions and gametocyte carriage were further investigated in this study. METHODS: A total of 996 dried blood spot samples were used from two strata, all smear-positives (516 samples) and randomly selected smear-negatives (480 samples), from a community cross-sectional survey conducted at peak transmission season in 2012 in Siaya County, western Kenya. Plasmodium falciparum parasite presence and density were determined by stained blood smear and by 18S mRNA transcripts using nucleic acid sequence-based amplification assay (NASBA), gametocyte presence and density were determined by blood smear and by Pfs25 mRNA-NASBA, and gametocyte diversity by Pfg377 mRNA RT-PCR and RT-qPCR. RESULTS: Of the randomly selected smear-negative samples, 69.6 % (334/480) were positive by 18S-NASBA while 18S-NASBA detected 99.6 % (514/516) smear positive samples. Overall, 80.2 % of the weighted population was parasite positive by 18S-NASBA vs 30.6 % by smear diagnosis and 44.0 % of the weighted population was gametocyte positive by Pfs25-NASBA vs 2.6 % by smear diagnosis. Children 5-15 years old were more likely to be parasitaemic and gametocytaemic by NASBA than individuals >15 years old or children <5 years old while gametocyte density decreased with age. Anaemia and self-reported fever within the past 24 h were associated with increased odds of gametocytaemia. Fever was also positively associated with parasite density, but not with gametocyte density. Anti-malarial use within the past 2 weeks decreased the odds of gametocytaemia, but not the odds of parasitaemia. In contrast, recent anti-malarial use was associated with lowered parasite density, but not the gametocyte density. Use of ITNs was associated with lower odds for parasitaemia in part of the study area with a longer history of ITN interventions. In the same part of study area, the odds of having multiple gametocyte alleles were also lower in individuals using ITNs than in those not using ITNs and parasite density was positively associated with gametocyte diversity. CONCLUSION: A large proportion of submicroscopic parasites and gametocytes in western Kenya might contribute to the stagnation in malaria prevalence, suggesting that additional interventions targeting the infectious reservoir are needed. As school aged children and persons with anaemia and fever were major sources for gametocyte reservoir, these groups should be targeted for intervention and prevention to reduce malaria transmission. Anti-malarial use was associated with lower parasite density and odds of gametocytaemia, but not the gametocyte density, indicating a limitation of anti-malarial impact on the transmission reservoir. ITN use had a protective role against parasitaemia and gametocyte diversity in western Kenya. |
Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial
Otieno L , Oneko M , Otieno W , Abuodha J , Owino E , Odero C , Mendoza YG , Andagalu B , Awino N , Ivinson K , Heerwegh D , Otsyula N , Oziemkowska M , Usuf EA , Otieno A , Otieno K , Leboulleux D , Leach A , Oyieko J , Slutsker L , Lievens M , Cowden J , Lapierre D , Kariuki S , Ogutu B , Vekemans J , Hamel MJ . Lancet Infect Dis 2016 16 (10) 1134-1144 BACKGROUND: Malaria remains a major global public health concern, especially in sub-Saharan Africa. The RTS,S/AS01 malaria candidate vaccine was reviewed by the European Medicines Agency and received a positive scientific opinion; WHO subsequently recommended pilot implementation in sub-Saharan African countries. Because malaria and HIV overlap geographically, HIV-infected children should be considered for RTS,S/AS01 vaccination. We therefore aimed to assess the safety of RTS,S/AS01 in HIV-infected children at two sites in western Kenya. METHODS: We did a randomised, double-blind, controlled trial at the clinical trial sites of the Kenya Medical Research Institute (KEMRI)-Walter Reed Army Institute of research in Kisumu and the KEMRI/US Centers for Disease Control and Prevention in Siaya. Eligible participants were infants and children aged from 6 weeks to 17 months with WHO stage 1 or 2 HIV disease (documented positive by DNA PCR), whether or not they were receiving antiretroviral therapy (ART). We randomly assigned participants (1:1) to receive three doses of either RTS,S/AS01 or rabies vaccine (both 0.5 mL per dose by intramuscular injection), given once per month at 0, 1, and 2 months. We did the treatment allocation using a web-based central randomisation system stratified by age (6 weeks-4 months, 5-17 months), and by baseline CD4% (<10, 10-14, 15-19, and ≥20). Data were obtained in an observer-blind manner, and the vaccine recipient, their parent or carer, the funder, and investigators responsible for the assessment of endpoints were all masked to treatment allocation (only staff responsible for the preparation and administration of the vaccines were aware of the assignment and these individuals played no other role in the study). We provided ART, even if the participants were not receiving ART before the study, and daily co-trimoxazole for prevention of opportunistic infections. The primary outcome was the occurrence of serious adverse events until 14 months after dose 1 of the vaccine, assessed in the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01148459. FINDINGS: Between July 30, 2010, and May 24, 2013, we enrolled 200 children to our study and randomly assigned 99 to receive RTS,S/AS01 and 101 to receive rabies vaccine. 177 (89%) of the 200 children enrolled completed 14 months of follow-up. Serious adverse events were noted in 41 (41.4%, 95% CI 31.6-51.8) of 99 RTS,S/AS01 recipients and 37 (36.6%, 27.3-46.8) of 101 rabies-vaccine recipients (relative risk 1.1, 95% CI 0.8-1.6). 20 (20.2%, 95% CI 12.8-29.5) of 99 RTS,S/AS01 recipients and 12 (11.9%, 6.3-19.8) of 101 rabies-vaccine recipients had at least one serious adverse event within 30 days after vaccination, mainly pneumonia, febrile convulsions, and salmonella sepsis. Five (5.1%, 95% CI 1.7-11.4) of 99 RTS,S/AS01 recipients and four (4.0%, 1.1-9.8) of 101 rabies-vaccine recipients died, but no deaths were deemed related to vaccination. Mortality was associated with five cases of pneumonia (1% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), five cases of gastroenteritis (3% RTS,S/AS01 recipients vs 2% rabies-vaccine recipients), five cases of malnutrition (2% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), one case of sepsis (1% rabies-vaccine recipients), one case of Haemophilus influenza meningitis (1% rabies-vaccine recipients), and one case of tuberculosis (1% RTS,S/AS01 recipients). INTERPRETATION: RTS, S/AS01 was well tolerated when given to children with WHO clinical stage 1 or 2 HIV disease along with high antiretroviral and co-trimoxazole use. Children with HIV disease could be included in future RTS,S/AS01 vaccination programmes. FUNDING: GlaxoSmithKline Biologicals SA and PATH Malaria Vaccine Initiative. |
A cross-sectional study of water, sanitation, and hygiene-related risk factors for soil-transmitted helminth infection in urban school- and preschool-aged children in Kibera, Nairobi
Worrell CM , Wiegand RE , Davis SM , Odero KO , Blackstock A , Cuellar VM , Njenga SM , Montgomery JM , Roy SL , Fox LM . PLoS One 2016 11 (3) e0150744 Soil-transmitted helminth (STH) infections affect persons living in areas with poor water, sanitation, and hygiene (WASH). Preschool-aged children (PSAC) and school-aged children (SAC) are disproportionately affected by STH infections. We aimed to identify WASH factors associated with STH infection among PSAC and SAC in Kibera, Kenya. In 2012, households containing a PSAC or SAC were randomly selected from those enrolled in the International Emerging Infections Program, a population-based surveillance system. We administered a household questionnaire, conducted environmental assessments for WASH, and tested three stools from each child for STH eggs using the Kato-Katz method. WASH factors were evaluated for associations with STH infection using univariable and multivariable Poisson regression. Any-STH prevalence was 40.8% among 201 PSAC and 40.0% among 475 SAC enrolled. Using the Joint Monitoring Programme water and sanitation classifications, 1.5% of households reported piped water on premises versus 98.5% another improved water source; 1.3% reported improved sanitation facilities, while 81.7% used shared sanitation facilities, 13.9% had unimproved facilities, and 3.1% reported no facilities (open defecation). On univariable analysis, STH infection was significantly associated with a household toilet located off-premises (prevalence ratio (PR) = 1.33; p = 0.047), while always treating water (PR = 0.81; p = 0.04), covering drinking water containers (PR = 0.75; p = 0.02), using clean towels during hand drying (PR = 0.58; p<0.01), having finished household floor material (PR = 0.76; p<0.01), having electricity (PR = 0.70; p<0.01), and increasing household elevation in 10-meter increments (PR = 0.89; p<0.01) were protective against STH infection. On multivariable analysis, usually versus always treating water was associated with increased STH prevalence (adjusted prevalence ratio (aPR) = 1.52; p<0.01), while having finished household floor material (aPR = 0.76; p = 0.03), reported child deworming in the last year (aPR = 0.76; p<0.01), and 10-meter household elevation increases (aPR = 0.89; p<0.01) were protective against infection. The intersection between WASH and STH infection is complex; site-specific WASH interventions should be considered to sustain the gains made by deworming activities. |
Genetic diversity of Plasmodium falciparum parasite by microsatellite markers after scale-up of insecticide-treated bed nets in western Kenya.
Gatei W , Gimnig JE , Hawley W , Ter Kuile F , Odero C , Iriemenam NC , Shah MP , Howard PP , Omosun YO , Terlouw DJ , Nahlen B , Slutsker L , Hamel MJ , Kariuki S , Walker E , Shi YP . Malar J 2014 13 Suppl 1 495 BACKGROUND: An initial study of genetic diversity of Plasmodium falciparum in Asembo, western Kenya showed that the parasite maintained overall genetic stability 5 years after insecticide-treated bed net (ITN) introduction in 1997. This study investigates further the genetic diversity of P. falciparum 10 years after initial ITN introduction in the same study area and compares this with two other neighbouring areas, where ITNs were introduced in 1998 (Gem) and 2004 (Karemo). METHODS: From a cross-sectional survey conducted in 2007, 235 smear-positive blood samples collected from children ≤15-year-old in the original study area and two comparison areas were genotyped employing eight neutral microsatellites. Differences in multiple infections, allele frequency, parasite genetic diversity and parasite population structure between the three areas were assessed. Further, molecular data reported previously (1996 and 2001) were compared to the 2007 results in the original study area Asembo. RESULTS: Overall proportion of multiple infections (MA) declined with time in the original study area Asembo (from 95.9 %-2001 to 87.7 %-2007). In the neighbouring areas, MA was lower in the site where ITNs were introduced in 1998 (Gem 83.7 %) compared to where they were introduced in 2004 (Karemo 96.7 %) in 2007. Overall mean allele count (MAC ~ 2.65) and overall unbiased heterozygosity (H e ~ 0.77) remained unchanged in 1996, 2001 and 2007 in Asembo and was the same level across the two neighbouring areas in 2007. Overall parasite population differentiation remained low over time and in the three areas at FST < 0.04. Both pairwise and multilocus linkage disequilibrium showed limited to no significant association between alleles in Asembo (1996, 2001 and 2007) and between three areas. CONCLUSIONS: This study showed the P. falciparum high genetic diversity and parasite population resilience on samples collected 10 years apart and in different areas in western Kenya. The results highlight the need for long-term molecular monitoring after implementation and use of combined and intensive prevention and intervention measures in the region. |
Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial
RTS S Clinical Trials Partnership , Hamel MJ , Kariuki S , Oneko M , Odero C , Otieno K , Awino N , Muturi-Kioi V , Omoto J , Sang T , Odhiambo S , Laserson KF , Slutsker L . Lancet 2015 386 (9988) 31-45 BACKGROUND: The efficacy and safety of the RTS,S/AS01 candidate malaria vaccine during 18 months of follow-up have been published previously. Herein, we report the final results from the same trial, including the efficacy of a booster dose. METHODS: From March 27, 2009, until Jan 31, 2011, children (age 5-17 months) and young infants (age 6-12 weeks) were enrolled at 11 centres in seven countries in sub-Saharan Africa. Participants were randomly assigned (1:1:1) at first vaccination by block randomisation with minimisation by centre to receive three doses of RTS,S/AS01 at months 0, 1, and 2 and a booster dose at month 20 (R3R group); three doses of RTS,S/AS01 and a dose of comparator vaccine at month 20 (R3C group); or a comparator vaccine at months 0, 1, 2, and 20 (C3C [control group]). Participants were followed up until Jan 31, 2014. Cases of clinical and severe malaria were captured through passive case detection. Serious adverse events (SAEs) were recorded. Analyses were by modified intention to treat and per protocol. The coprimary endpoints were the occurrence of malaria over 12 months after dose 3 in each age category. In this final analysis, we present data for the efficacy of the booster on the occurrence of malaria. Vaccine efficacy (VE) against clinical malaria was analysed by negative binomial regression and against severe malaria by relative risk reduction. This trial is registered with ClinicalTrials.gov, number NCT00866619. FINDINGS: 8922 children and 6537 young infants were included in the modified intention-to-treat analyses. Children were followed up for a median of 48 months (IQR 39-50) and young infants for 38 months (34-41) after dose 1. From month 0 until study end, compared with 9585 episodes of clinical malaria that met the primary case definition in children in the C3C group, 6616 episodes occurred in the R3R group (VE 36·3%, 95% CI 31·8-40·5) and 7396 occurred in the R3C group (28·3%, 23·3-32·9); compared with 171 children who experienced at least one episode of severe malaria in the C3C group, 116 children experienced at least one episode of severe malaria in the R3R group (32·2%, 13·7 to 46·9) and 169 in the R3C group (1·1%, -23·0 to 20·5). In young infants, compared with 6170 episodes of clinical malaria that met the primary case definition in the C3C group, 4993 episodes occurred in the R3R group (VE 25·9%, 95% CI 19·9-31·5) and 5444 occurred in the R3C group (18·3%, 11·7-24·4); and compared with 116 infants who experienced at least one episode of severe malaria in the C3C group, 96 infants experienced at least one episode of severe malaria in the R3R group (17·3%, 95% CI -9·4 to 37·5) and 104 in the R3C group (10·3%, -17·9 to 31·8). In children, 1774 cases of clinical malaria were averted per 1000 children (95% CI 1387-2186) in the R3R group and 1363 per 1000 children (995-1797) in the R3C group. The numbers of cases averted per 1000 young infants were 983 (95% CI 592-1337) in the R3R group and 558 (158-926) in the R3C group. The frequency of SAEs overall was balanced between groups. However, meningitis was reported as a SAE in 22 children: 11 in the R3R group, ten in the R3C group, and one in the C3C group. The incidence of generalised convulsive seizures within 7 days of RTS,S/AS01 booster was 2·2 per 1000 doses in young infants and 2·5 per 1000 doses in children. INTERPRETATION: RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in young infants and children when administered with or without a booster dose. Efficacy was enhanced by the administration of a booster dose in both age categories. Thus, the vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures, especially in areas of high transmission. FUNDING: GlaxoSmithKline Biologicals SA and the PATH Malaria Vaccine Initiative. |
Severe acute respiratory infection in children in a densely populated urban slum in Kenya, 2007-2011
Breiman RF , Cosmas L , Njenga MK , Williamson J , Mott JA , Katz MA , Erdman DD , Schneider E , Oberste MS , Neatherlin JC , Njuguna H , Ondari DM , Odero K , Okoth GO , Olack B , Wamola N , Montgomery JM , Fields BS , Feikin DR . BMC Infect Dis 2015 15 (95) 95 BACKGROUND: Reducing acute respiratory infection burden in children in Africa remains a major priority and challenge. We analyzed data from population-based infectious disease surveillance for severe acute respiratory illness (SARI) among children <5 years of age in Kibera, a densely populated urban slum in Nairobi, Kenya. METHODS: Surveillance was conducted among a monthly mean of 5,874 (range=5,778-6,411) children <5 years old in two contiguous villages in Kibera. Participants had free access to the study clinic and their health events and utilization were noted during biweekly home visits. Patients meeting criteria for SARI (WHO-defined severe or very severe pneumonia, or oxygen saturation <90%) from March 1, 2007-February 28, 2011 had blood cultures processed for bacteria, and naso- and oro-pharyngeal swabs collected for quantitative real-time reverse transcription polymerase chain reaction testing for influenza viruses, parainfluenza viruses (PIV), respiratory syncytial virus (RSV), adenovirus, and human metapneumovirus (hMPV). Swabs collected during January 1, 2009-February 28, 2010 were also tested for rhinoviruses, enterovirus, parechovirus, Mycoplasma pneumoniae, and Legionella species. Swabs were collected for simultaneous testing from a selected group of control-children visiting the clinic without recent respiratory or diarrheal illnesses. RESULTS: SARI overall incidence was 12.4 cases/100 person-years of observation (PYO) and 30.4 cases/100 PYO in infants. When comparing detection frequency in swabs from 815 SARI cases and 115 healthy controls, only RSV and influenza A virus were significantly more frequently detected in cases, although similar trends neared statistical significance for PIV, adenovirus and hMPV. The incidence for RSV was 2.8 cases/100 PYO and for influenza A was 1.0 cases/100 PYO. When considering all PIV, the rate was 1.1 case/100 PYO and the rate per 100 PYO for SARI-associated disease was 1.5 for adenovirus and 0.9 for hMPV. RSV and influenza A and B viruses were estimated to account for 16.2% and 6.7% of SARI cases, respectively; when taken together, PIV, adenovirus, and hMPV may account for >20% additional cases. CONCLUSIONS: Influenza viruses and RSV (and possibly PIV, hMPV and adenoviruses) are important pathogens to consider when developing technologies and formulating strategies to treat and prevent SARI in children. |
Assessment of molecular markers for anti-malarial drug resistance after the introduction and scale-up of malaria control interventions in western Kenya.
Shah M , Omosun Y , Lal A , Odero C , Gatei W , Otieno K , Gimnig JE , Kuile Fter , Hawley WA , Nahlen B , Kariuki S , Walker E , Slutsker L , Hamel M , Shi YP . Malar J 2015 14 (75) 75 BACKGROUND: Although it is well known that drug pressure selects for drug-resistant parasites, the role of transmission reduction by insecticide-treated bed nets (ITNs) on drug resistance remains unclear. In this study, the drug resistance profile of current and previous first-line anti-malarials in Kenya was assessed within the context of drug policy change and scale-up of ITNs. National first-line treatment changed from chloroquine (CQ) to sulphadoxine-pyrimethamine (SP) in 1998 and to artemether-lumefantrine (AL) in 2004. ITN use was scaled-up in the Asembo, Gem and Karemo areas of western Kenya in 1997, 1999 and 2006, respectively. METHODS: Smear-positive samples (N=253) collected from a 2007 cross-sectional survey among children in Asembo, Gem and Karemo were genotyped for mutations in pfcrt and pfmdr1 (CQ), dhfr and dhps (SP), and at pfmdr-N86 and the gene copy number in pfmdr1 (lumefantrine). Results were compared among the three geographic areas in 2007 and to retrospective molecular data from children in Asembo in 2001. RESULTS: In 2007, 69 and 85% of samples harboured the pfmdr1-86Y mutation and dhfr/dhps quintuple mutant, respectively, with no significant differences by study area. However, the prevalence of the pfcrt-76T mutation differed significantly among areas (p <0.02), between 76 and 94%, with the highest prevalence in Asembo. Several 2007 samples carried mutations at dhfr-164 L, dhps-436A, or dhps-613T. From 2001 to 2007, there were significant increases in the pfcrt-76T mutation from 82 to 94% (p <0.03), dhfr/dhps quintuple mutant from 62 to 82% (p <0.03), and an increase in the septuple CQ and SP combined mutant haplotype, K76Y86I51R59N108G437E540, from 28 to 39%. The prevalence of the pfmdr1-86Y mutation remained unchanged. All samples were single copy for pfmdr1. CONCLUSIONS: Molecular markers associated with lumefantrine resistance were not detected in 2007. More recent samples will be needed to detect any selective effects by AL. The prevalence of CQ and SP resistance markers increased from 2001 to 2007 in the absence of changes in transmission intensity. In 2007, only the prevalence of pfcrt-76T mutation differed among study areas of varying transmission intensity. Resistant parasites were most likely selected by sustained drug pressure from the continued use of CQ, SP, and mechanistically similar drugs, such as amodiaquine and cotrimoxazole. There was no clear evidence that differences in transmission intensity, as a result of ITN scale-up, influenced the prevalence of drug resistance molecular markers. |
Unprogrammed deworming in the Kibera slum, Nairobi: implications for control of soil-transmitted helminthiases
Harris JR , Worrell CM , Davis SM , Odero K , Mogeni OD , Deming MS , Mohammed A , Montgomery JM , Njenga SM , Fox LM , Addiss DG . PLoS Negl Trop Dis 2015 9 (3) e0003590 BACKGROUND: Programs for control of soil-transmitted helminth (STH) infections are increasingly evaluating national mass drug administration (MDA) interventions. However, "unprogrammed deworming" (receipt of deworming drugs outside of nationally-run STH control programs) occurs frequently. Failure to account for these activities may compromise evaluations of MDA effectiveness. METHODS: We used a cross-sectional study design to evaluate STH infection and unprogrammed deworming among infants (aged 6-11 months), preschool-aged children (PSAC, aged 1-4 years), and school-aged children (SAC, aged 5-14 years) in Kibera, Kenya, an informal settlement not currently receiving nationally-run MDA for STH. STH infection was assessed by triplicate Kato-Katz. We asked heads of households with randomly-selected children about past-year receipt and source(s) of deworming drugs. Local non-governmental organizations (NGOs) and school staff participating in school-based deworming were interviewed to collect information on drug coverage. RESULTS: Of 679 children (18 infants, 184 PSAC, and 477 SAC) evaluated, 377 (55%) reported receiving at least one unprogrammed deworming treatment during the past year. PSAC primarily received treatments from chemists (48.3%) or healthcare centers (37.7%); SAC most commonly received treatments at school (55.0%). Four NGOs reported past-year deworming activities at 47 of >150 schools attended by children in our study area. Past-year deworming was negatively associated with any-STH infection (34.8% vs 45.4%, p = 0.005). SAC whose most recent deworming medication was sourced from a chemist were more often infected with Trichuris (38.0%) than those who received their most recent treatment from a health center (17.3%) or school (23.1%) (p = 0.05). CONCLUSION: Unprogrammed deworming was received by more than half of children in our study area, from multiple sources. Both individual-level treatment and unprogrammed preventive chemotherapy may serve an important public health function, particularly in the absence of programmed deworming; however, they may also lead to an overestimation of programmed MDA effectiveness. A standardized, validated tool is needed to assess unprogrammed deworming. |
Serological markers for monitoring historical changes in malaria transmission intensity in a highly endemic region of Western Kenya, 1994-2009
Wong J , Hamel MJ , Drakeley CJ , Kariuki S , Shi YP , Lal AA , Nahlen BL , Bloland PB , Lindblade KA , Were V , Otieno K , Otieno P , Odero C , Slutsker L , Vulule JM , Gimnig JE . Malar J 2014 13 (451) 451 BACKGROUND: Monitoring local malaria transmission intensity is essential for planning evidence-based control strategies and evaluating their impact over time. Anti-malarial antibodies provide information on cumulative exposure and have proven useful, in areas where transmission has dropped to low sustained levels, for retrospectively reconstructing the timing and magnitude of transmission reduction. It is unclear whether serological markers are also informative in high transmission settings, where interventions may reduce transmission, but to a level where considerable exposure continues. METHODS: This study was conducted through ongoing KEMRI and CDC collaboration. Asembo, in Western Kenya, is an area where intense malaria transmission was drastically reduced during a 1997-1999 community-randomized, controlled insecticide-treated net (ITN) trial. Two approaches were taken to reconstruct malaria transmission history during the period from 1994 to 2009. First, point measurements were calculated for seroprevalence, mean antibody titre, and seroconversion rate (SCR) against three Plasmodium falciparum antigens (AMA-1, MSP-119, and CSP) at five time points for comparison against traditional malaria indices (parasite prevalence and entomological inoculation rate). Second, within individual post-ITN years, age-stratified seroprevalence data were analysed retrospectively for an abrupt drop in SCR by fitting alternative reversible catalytic conversion models that allowed for change in SCR. RESULTS: Generally, point measurements of seroprevalence, antibody titres and SCR produced consistent patterns indicating that a gradual but substantial drop in malaria transmission (46-70%) occurred from 1994 to 2007, followed by a marginal increase beginning in 2008 or 2009. In particular, proportionate changes in seroprevalence and SCR point estimates (relative to 1994 baseline values) for AMA-1 and CSP, but not MSP-119, correlated closely with trends in parasite prevalence throughout the entire 15-year study period. However, retrospective analyses using datasets from 2007, 2008 and 2009 failed to detect any abrupt drop in transmission coinciding with the timing of the 1997-1999 ITN trial. CONCLUSIONS: In this highly endemic area, serological markers were useful for generating accurate point estimates of malaria transmission intensity, but not for retrospective analysis of historical changes. Further investigation, including exploration of different malaria antigens and/or alternative models of population seroconversion, may yield serological tools that are more informative in high transmission settings. |
Soil-transmitted helminths in pre-school-aged and school-aged children in an urban slum: a cross-sectional study of prevalence, distribution, and associated exposures
Davis SM , Worrell CM , Wiegand RE , Odero KO , Suchdev PS , Ruth LJ , Lopez G , Cosmas L , Neatherlin J , Njenga SM , Montgomery JM , Fox LM . Am J Trop Med Hyg 2014 91 (5) 1002-10 Soil-transmitted helminths (STHs) are controlled by regular mass drug administration. Current practice targets school-age children (SAC) preferentially over pre-school age children (PSAC) and treats large areas as having uniform prevalence. We assessed infection prevalence in SAC and PSAC and spatial infection heterogeneity, using a cross-sectional study in two slum villages in Kibera, Nairobi. Nairobi has low reported STH prevalence. The SAC and PSAC were randomly selected from the International Emerging Infections Program's surveillance platform. Data included residence location and three stools tested by Kato-Katz for STHs. Prevalences among 692 analyzable children were any STH: PSAC 40.5%, SAC 40.7%; Ascaris: PSAC 24.1%, SAC 22.7%; Trichuris: PSAC 24.0%, SAC 28.8%; hookworm < 0.1%. The STH infection prevalence ranged from 22% to 71% between sub-village sectors. The PSAC have similar STH prevalences to SAC and should receive deworming. Small areas can contain heterogeneous prevalences; determinants of STH infection should be characterized and slums should be assessed separately in STH mapping. |
Mortality trends observed in population-based surveillance of an urban slum settlement, Kibera, Kenya, 2007-2010
Olack B , Feikin DR , Cosmas LO , Odero KO , Okoth GO , Montgomery JM , Breiman RF . PLoS One 2014 9 (1) e85913 BACKGROUND: We used population based infectious disease surveillance to characterize mortality rates in residents of an urban slum in Kenya. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
Soil-transmitted helminth infection and nutritional status among urban slum children in Kenya
Suchdev PS , Davis SM , Bartoces M , Ruth LJ , Worrell CM , Kanyi H , Odero K , Wiegand RE , Njenga SM , Montgomery JM , Fox LM . Am J Trop Med Hyg 2013 90 (2) 299-305 To evaluate the nutritional impact of soil-transmitted helminth (STH) infection, we conducted a cross-sectional survey of 205 pre-school- (PSC) and 487 school-aged children (SAC) randomly selected from the surveillance registry of the Centers for Disease Control and Prevention of the Kibera slum in Kenya. Hemoglobin, iron deficiency (ID), vitamin A deficiency (VAD), inflammation, malaria, anthropometry, and STH ova were measured. Poisson regression models evaluated associations between STH and malnutrition outcomes and controlled for confounders. Approximately 40% of PSC and SAC had STH infection, primarily Ascaris and Trichuris; 2.9% of PSC and 1.1% of SAC had high-intensity infection. Malnutrition prevalence among PSC and SAC was anemia (38.3% and 14.0%, respectively), ID (23.0% and 5.0%, respectively), VAD (16.9% and 4.5%, respectively), and stunting (29.7% and 16.9%, respectively). In multivariate analysis, STH in PSC was associated with VAD (PR = 2.2, 95% confidence interval = 1.1-4.6) and ID (PR = 3.3, 95% confidence interval = 1.6-6.6) but not anemia or stunting. No associations were significant in SAC. Integrated deworming and micronutrient supplementation strategies should be evaluated in this population. |
Men who have sex with men in Kisumu, Kenya: support group membership and knowledge of HIV-risk factors
Okall DO , Otieno FO , Nyikuri M , Mills LA , Hardnett F , Odero S , Turner K , Gust DA . Cult Health Sex 2013 15 (8) 968-80 Men who have sex with men are an important yet marginalised population for HIV prevention in Africa. We conducted a two-phase study (individual qualitative interviews and a survey) of men who have sex with men, aged 18-34 years of age and living in Kisumu, Kenya. Approximately half (27/51) of survey respondents reported belonging to a support group. The odds of belonging to support groups were greater for older men (aged 24-34 versus 18-23 years [OR = 5.20; 95% CI = 1.27-26.66]). More than two-thirds (68.6%) of survey respondents were categorised as having high knowledge of HIV-risk factors. Most respondents (94.1%) correctly reported lack of condom use during vaginal sex as a risk factor for HIV, but slightly fewer (82.4%) recognised lack of condom use during anal sex as an HIV risk factor. Among the 15 interviewees, the following were included as greatest needs: health information (n = 5), safe lubricants (n = 5), condoms (n = 4), healthcare facility or men-who-have-sex-with-men-friendly health services (n = 3) and advocacy (n = 2). Kenyan men who have sex with men have developed support groups and have unmet needs for information, lubricants and condoms and services. Partnering with support groups offers an opportunity for organisations to reach men who have sex with men with accurate health information, provision of safe sexual lubricants, condoms and other health and social services. |
A randomized trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated malaria among children in western Kenya
Agarwal A , McMorrow M , Onyango P , Otieno K , Odero C , Williamson J , Kariuki S , Kachur SP , Slutsker L , Desai M . Malar J 2013 12 254 BACKGROUND: Artemether-lumefantrine (AL) was adopted as first-line treatment for uncomplicated malaria in Kenya in 2006. Monitoring drug efficacy at regular intervals is essential to prevent unnecessary morbidity and mortality. The efficacy of AL and dihydroartemisinin-piperaquine (DP) were evaluated for the treatment of uncomplicated malaria in children aged six to 59 months in western Kenya. METHODS: From October 2010 to August 2011, children with fever or history of fever with uncomplicated Plasmodium falciparum mono-infection were enrolled in an in vivo efficacy trial in accordance with World Health Organization (WHO) guidelines. The children were randomized to treatment with a three-day course of AL or DP and efficacy outcomes were measured at 28 and 42 days after treatment initiation. RESULTS: A total of 137 children were enrolled in each treatment arm. There were no early treatment failures and all children except one had cleared parasites by day 3. Polymerase chain reaction (PCR)-uncorrected adequate clinical and parasitological response rate (ACPR) was 61% in the AL arm and 83% in the DP arm at day 28 (p = 0.001). PCR-corrected ACPR at day 28 was 97% in the AL group and 99% in the DP group, and it was 96% in both arms at day 42. CONCLUSIONS: AL and DP remain efficacious for the treatment of uncomplicated malaria among children in western Kenya. The longer half-life of piperaquine relative to lumefantrine may provide a prophylactic effect, accounting for the lower rate of re-infection in the first 28 days after treatment in the DP arm. |
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