Publications (8)21.58 Total impact
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Article: Antimalarial drug sensitivity profile of western Kenya Plasmodium falciparum field isolates determined by a SYBR Green I in vitro assay and molecular analysis.
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ABSTRACT: In vitro drug sensitivity and molecular analyses of Plasmodium falciparum track drug resistance. DNA-binding fluorescent dyes like SYBR Green I may allow field laboratories, proximal to P. falciparum collection sites, to conduct drug assays. In 2007-2008, we assayed 121 P. falciparum field isolates from western Kenya for 50% inhibitory concentrations (IC(50)) against 6 antimalarial drugs using a SYBR Green I in vitro assay: 91 immediate ex vivo (IEV) and 30 culture-adapted, along with P. falciparum reference clones D6 (chloroquine [CQ] sensitive) and W2 (CQ resistant). We also assessed P. falciparum mdr1 (Pfmdr1) copy number and single nucleotide polymorphisms (SNPs) at four codons. The IC(50)s for IEV and culture-adapted P. falciparum isolates were similar, and approximated historical IC(50)s. For Pfmdr1, mean copy number was 1, with SNPs common at codons 86 and 184. The SYBR Green I assay adapted well to our field-based laboratory, for both IEV and culture-adapted P. falciparum, warranting continued use.The American journal of tropical medicine and hygiene 07/2011; 85(1):34-41. · 2.59 Impact Factor -
Article: Capacity-building efforts by the AFHSC-GEIS program.
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ABSTRACT: Capacity-building initiatives related to public health are defined as developing laboratory infrastructure, strengthening host-country disease surveillance initiatives, transferring technical expertise and training personnel. These initiatives represented a major piece of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) contributions to worldwide emerging infectious disease (EID) surveillance and response. Capacity-building initiatives were undertaken with over 80 local and regional Ministries of Health, Agriculture and Defense, as well as other government entities and institutions worldwide. The efforts supported at least 52 national influenza centers and other country-specific influenza, regional and U.S.-based EID reference laboratories (44 civilian, eight military) in 46 countries worldwide. Equally important, reference testing, laboratory infrastructure and equipment support was provided to over 500 field sites in 74 countries worldwide from October 2008 to September 2009. These activities allowed countries to better meet the milestones of implementation of the 2005 International Health Regulations and complemented many initiatives undertaken by other U.S. government agencies, such as the U.S. Department of Health and Human Services, the U.S. Agency for International Development and the U.S. Department of State.BMC Public Health 01/2011; 11 Suppl 2:S4. · 2.00 Impact Factor -
Article: A growing global network's role in outbreak response: AFHSC-GEIS 2008-2009.
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ABSTRACT: A cornerstone of effective disease surveillance programs comprises the early identification of infectious threats and the subsequent rapid response to prevent further spread. Effectively identifying, tracking and responding to these threats is often difficult and requires international cooperation due to the rapidity with which diseases cross national borders and spread throughout the global community as a result of travel and migration by humans and animals. From Oct.1, 2008 to Sept. 30, 2009, the United States Department of Defense's (DoD) Armed Forces Health Surveillance Center Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) identified 76 outbreaks in 53 countries. Emerging infectious disease outbreaks were identified by the global network and included a wide spectrum of support activities in collaboration with host country partners, several of which were in direct support of the World Health Organization's (WHO) International Health Regulations (IHR) (2005). The network also supported military forces around the world affected by the novel influenza A/H1N1 pandemic of 2009. With IHR (2005) as the guiding framework for action, the AFHSC-GEIS network of international partners and overseas research laboratories continues to develop into a far-reaching system for identifying, analyzing and responding to emerging disease threats.BMC Public Health 01/2011; 11 Suppl 2:S3. · 2.00 Impact Factor -
Article: Molecular epidemiology of influenza A/H3N2 viruses circulating in Uganda.
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ABSTRACT: The increasing availability of complete influenza virus genomes is deepening our understanding of influenza evolutionary dynamics and facilitating the selection of vaccine strains. However, only one complete African influenza virus sequence is available in the public domain. Here we present a complete genome analysis of 59 influenza A/H3N2 viruses isolated from humans in Uganda during the 2008 and 2009 season. Isolates were recovered from hospital-based sentinel surveillance for influenza-like illnesses and their whole genome sequenced. The viruses circulating during these two seasons clearly differed from each other phylogenetically. They showed a slow evolution away from the 2009/10 recommended vaccine strain (A/Brisbane/10/07), instead clustering with the 2010/11 recommended vaccine strain (A/Perth/16/09) in the A/Victoria/208/09 clade, as observed in other global regions. All of the isolates carried the adamantane resistance marker S31N in the M2 gene and carried several markers of enhanced transmission; as expected, none carried any marker of neuraminidase inhibitor resistance. The hemagglutinin gene of the 2009 isolates differed from that of the 2008 isolates in antigenic sites A, B, D, and to a lesser extent, C and E indicating evidence of an early phylogenetic shift from the 2008 to 2009 viruses. The internal genes of the 2009 isolates were similar to those of one 2008 isolate, A/Uganda/MUWRP-050/2008. Another 2008 isolate had a truncated PB1-F2 protein. Whole genome sequencing can enhance surveillance of future seasonal changes in the viral genome which is crucial to ensure that selected vaccine strains are protective against the strains circulating in Eastern Africa. This data provides an important baseline for this surveillance. Overall the influenza virus activity in Uganda appears to mirror that observed in other regions of the southern hemisphere.PLoS ONE 01/2011; 6(11):e27803. · 4.09 Impact Factor -
Article: Influenza and respiratory disease surveillance: the US military's global laboratory-based network.
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ABSTRACT: The US Department of Defense influenza surveillance system now spans nearly 500 sites in 75 countries, including active duty US military and dependent populations as well as host-country civilian and military personnel. This system represents a major part of the US Government's contributions to the World Health Organization's Global Influenza Surveillance Network and addresses Presidential Directive NSTC-7 to expand global surveillance, training, research and response to emerging infectious disease threats. Since 2006, the system has expanded significantly in response to rising pandemic influenza concerns. The expanded system has played a critical role in the detection and monitoring of ongoing H5N1 outbreaks worldwide as well as in the initial detection of, and response to, the current (H1N1) 2009 influenza pandemic. This article describes the system, details its contributions and the critical gaps that it is filling, and discusses future plans.Influenza and Other Respiratory Viruses 05/2010; 4(3):155-61. · 4.16 Impact Factor -
Article: Short report: Clinical and molecular evidence for a case of Buruli ulcer (Mycobacterium ulcerans infection) in Kenya.
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ABSTRACT: Mycobacterium ulcerans infection is an emerging disease that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU) and occasional contiguous or metastatic bone lesions. Buruli ulcer is named after Buruli County in Uganda (east Africa), where an epidemic occurred in the 1960s. Today, BU is most common in central and west Africa. We describe clinical and molecular evidence for a case of BU in Kenya.The American journal of tropical medicine and hygiene 12/2009; 81(6):1110-3. · 2.59 Impact Factor -
Article: of Tropical Medicine and Hygiene 1110 * Address correspondence to Short Report: Clinical and Molecular Evidence for a Case of Buruli Ulcer ( Mycobacterium ulcerans Infection) in Kenya
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ABSTRACT: Mycobacterium ulcerans infection is an emerging disease that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU) and occasional contiguous or metastatic bone lesions. Buruli ulcer is named after Buruli County in Uganda (east Africa), where an epidemic occurred in the 1960s. Today, BU is most common in central and west Africa. We describe clinical and molecular evidence for a case of BU in Kenya. Mycobacterium ulcerans is an emerging infection that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU). 1 Reactive osteitis or osteomyelitis beneath skin lesions, or met-astatic osteomyelitis from lymphohematogenous spread of M. ulcerans , develops in approximately 10% of infected patients. 2 The most plausible mode of transmission is by trauma at cutane-ous sites superficially contaminated by M. ulcerans . Mycolactones elaborated by M. ulcerans are probably the most important pathogenic factors in lesions of BU. 3,4 Incidence of BU is high-est in children ≤ 15 years of age, and is a public health prob-lem in disease-endemic countries because of disabling sequelae that may include scarring contractures, bone destruction, and amputations. 2 The prevalence of BU is highest in west and cen-tral Africa, but the disease has also been reported in more than 30 countries, including several countries in east Africa, such as Sudan. 2 We describe clinical and molecular evidence in support of the first confirmed case of BU in Kenya. A 34-year-old woman (FO) who lived in a village approxi-mately 10–15 km from Kisumu (Lake Victoria region in west-ern Kenya) came to the outpatient clinic of New Nyanza Provincial General Hospital with four annular, painless, pris-tine ulcers with undermined borders and cotton-like necrotic centers on the right thigh (Figure 1). Each ulcer was sur-rounded by induration, mild hyperpigmentation, and scaling. The lesions had been present for 6–12 months and described as non-healing and slowly progressive. The hip area was tender on palpation and the patient walked with a limp. She did not recall antecedent trauma to the site. There was no evidence of previous treatment. Social history was notable for man-ual work in the family garden, and exposure to natural water sources when washing clothes. Serologic status for infection with human immunodeficiency virus was unknown. Gram and Ziehl-Neelsen stainings of swab smears of exu-date from the undermined areas of the ulcers showed gram-positive cocci and numerous, scattered, acid-fast bacilli (AFB) (Figure 2). Swab samples of exudate were placed in 70% eth-anol for molecular analysis. Bacterial cultures or a lesional biopsy were not done. The patient was referred for a right hip radiograph to establish possible bone involvement, but she absconded and the procedure was not done. Upon completionClinical and Molecular Evidence for a Case of Buruli Ulcer ( Mycobacterium ulcerans Infection) in Kenya. 01/2009; 81:1110-1113. -
Article: Genetic analysis of H3N2 influenza A viruses isolated in 2006-2007 in Nairobi, Kenya.
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ABSTRACT: Minimal influenza surveillance has been carried out in sub-Saharan Africa to provide information on circulating influenza subtypes for the purpose of vaccine production and monitoring trends in virus spread and mutations. The aim of this study was to investigate a surveillance program in Kenya to isolate and characterize influenza viruses. In the 2006-2007 influenza season, nine influenza A viruses were isolated. All were of H3N2 subtype with key amino acid (aa) changes indicating that they were more closely related to recent World Health Organization recommended vaccine strains than to older vaccine strains, and mirroring the evolution of circulating influenza A globally. Hemagglutination inhibition data showed that the 2006 Kenya isolates had titers identical to the 2005-2006 H3N2 vaccine strain but two- to threefold lower titers to the 2006-2007 vaccine strain, suggesting that the isolates were antigenic variants of the 2006-2007 vaccine strains. Analysis of aa substitutions of hemagglutinin-1 (HA1) protein of the 2006 Kenyan viruses revealed unique genetic variations with several aa substitutions located at immunodominant epitopes of the HA1 protein. These mutations included the V112I change at site E, the K 173 E substitution at site D and N 278 K change at site C, mutations that may result in conformational change on the HA molecule to expose novel epitopes thus abrogating binding of pre-existing antibodies at these sites. Characterization of these important genetic variations in influenza A viruses isolated from Kenya highlights the importance of continuing surveillance and characterization of emerging influenza drift variants in sub-Saharan Africa.Influenza and Other Respiratory Viruses 06/2008; 2(3):107-13. · 4.16 Impact Factor
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2010
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US Army Medical Research Unit Kenya
Nairobi, Nairobi Province, Kenya
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