Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 35 Records) |
Query Trace: Sang T[original query] |
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Could less be more? Accounting for fractional-dose regimens and different number of vaccine doses when measuring the impact of the RTS, S/AS01E malaria vaccine
Westercamp N , Osei-Tutu L , Schuerman L , Kariuki SK , Bollaerts A , Lee CK , Samuels AM , Ockenhouse C , Bii DK , Adjei S , Oneko M , Lievens M , Attobrah Sarfo MA , Atieno C , Bakari A , Sang T , Kotoh-Mortty MF , Otieno K , Roman F , Buabeng PBY , Ntiamoah Y , Ansong D , Agbenyega T , Ofori-Anyinam O . J Infect Dis 2024 BACKGROUND: The RTS, S/AS01E malaria vaccine (RTS, S) is recommended for children in moderate-to-high Plasmodium falciparum malaria transmission areas. This phase 2b trial (NCT03276962) evaluates RTS, S fractional- and full-dose regimens in Ghana and Kenya. METHODS: 1500 children aged 5-17 months were randomised (1:1:1:1:1) to receive RTS, S or rabies control vaccine. RTS, S groups received two full RTS, S doses at month (M)0/M1 followed by either full (groups R012-20, R012-14-26) or fractional (1/5) doses (groups Fx012-14-26, Fx017-20-32). RESULTS: At M32 post-first dose, vaccine efficacy (VE) against clinical malaria (all episodes) ranged from 38% (R012-20; 95%CI: 24-49) to 53% (R012-14-26; 95%CI: 42-62). Vaccine impact estimates (cumulative number of malaria cases averted/1000 children vaccinated) were 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional- versus full-dose), in a post-hoc analysis, we also estimated cases averted/1000 RTS, S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), 880 (Fx017-20-32). CONCLUSIONS: VE against clinical malaria was similar in all RTS, S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If borne out through trial end (M50), these observations underscore the means to reduce cost per regimen with a goal of maximising impact and optimising supply. |
Climate and urbanization drive mosquito preference for humans (preprint)
Rose NH , Sylla M , Badolo A , Lutomiah J , Ayala D , Aribodor OB , Ibe N , Akorli J , Otoo S , Mutebi JP , Kriete AL , Ewing EG , Sang R , Gloria-Soria A , Powell JR , Baker RE , White BJ , Crawford JE , McBride CS . bioRxiv 2020 2020.02.12.939041 The majority of mosquito-borne illness is spread by a few mosquito species that have evolved to specialize in biting humans, yet the precise causes of this behavioral shift are poorly understood. We address this gap in the arboviral vector Aedes aegypti. We first characterize the behaviour of mosquitoes from 27 sites scattered across the species’ ancestral range in sub-Saharan Africa, revealing previously unrecognized diversity in female preference for human versus animal odor. We then use modelling to show that this diversity can be almost fully predicted by two ecological factors – dry season intensity and human population density. Finally we integrate this information with whole genome sequence data from 345 individual mosquitoes to identify a single underlying ancestry component linked to human preference, with genetic changes concentrated in a few key chromosomal regions. Our findings strongly suggest that human-biting in this important disease vector originally evolved as a by-product of breeding in human-stored water in areas where doing so provided the only means to survive the long, hot dry season. Our model also predicts that changes in human population density are likely to drive future mosquito evolution. Rapid urbanization may drive a shift to human-biting in many cities across Africa by 2050. |
First cases of SARS-CoV-2 infection and secondary transmission in Kisumu, Kenya
Tippett Barr Beth A , Herman-Roloff Amy , Mburu Margaret , Murnane Pamela M , Sang Norton , Bukusi Elizabeth , Oele Elizabeth , Odhiambo Albert , Lewis-Kulzer Jayne , Onyango Clayton O , Hunsperger Elizabeth , Odhiambo Francesca , Joseph Rachel H , Munyua Peninah , Othieno Kephas , Mulwa Edwin , Akelo Victor , Muok Erick , Bulterys Marc , Nzioka Charles , Cohen Craig R . PLoS Glob Public Health 2022 2 (9) e0000951 We investigated the first 152 laboratory-confirmed SARS-CoV-2 cases (125 primary and 27 secondary) and their 248 close contacts in Kisumu County, Kenya. Conducted June 10–October 8, 2020, this study included interviews and sample collection at enrolment and 14–21 days later. Median age was 35 years (IQR 28–44); 69.0% reported COVID-19 related symptoms, most commonly cough (60.0%), headache (55.2%), fever (53.3%) and loss of taste or smell (43.8%). One in five were hospitalized, 34.4% >25 years of age had at least one comorbidity, and all deaths had comorbidities. Adults ≥25 years with a comorbidity were 3.15 (95% CI 1.37–7.26) times more likely to have been hospitalized or died than participants without a comorbidity. Infectious comorbidities included HIV, tuberculosis, and malaria, but no current cases of influenza, respiratory syncytial virus, dengue fever, leptospirosis or chikungunya were identified. Thirteen (10.4%) of the 125 primary infections transmitted COVID-19 to 27 close contacts, 158 (63.7%) of whom resided or worked within the same household. Thirty-one percent (4 of 13) of those who transmitted COVID-19 to secondary cases were health care workers; no known secondary transmissions occurred between health care workers. This rapid assessment early in the course of the COVID-19 pandemic identified some context-specific characteristics which conflicted with the national line-listing of cases, and which have been substantiated in the year since. These included over two-thirds of cases reporting the development of symptoms during the two weeks after diagnosis, compared to the 7% of cases reported nationally; over half of cases reporting headaches, and nearly half of all cases reporting loss of taste and smell, none of which were reported at the time by the World Health Organization to be common symptoms. This study highlights the importance of rapid in-depth assessments of outbreaks in understanding the local epidemiology and response measures required. |
Efficacy of RTS,S/AS01(E) malaria vaccine administered according to different full, fractional, and delayed third or early fourth dose regimens in children aged 5-17 months in Ghana and Kenya: an open-label, phase 2b, randomised controlled trial
Samuels AM , Ansong D , Kariuki SK , Adjei S , Bollaerts A , Ockenhouse C , Westercamp N , Lee CK , Schuerman L , Bii DK , Osei-Tutu L , Oneko M , Lievens M , Attobrah Sarfo MA , Atieno C , Morelle D , Bakari A , Sang T , Jongert E , Kotoh-Mortty MF , Otieno K , Roman F , Buabeng PBY , Ntiamoah Y , Ofori-Anyinam O , Agbenyega T . Lancet Infect Dis 2022 22 (9) 1329-1342 BACKGROUND: Controlled infection studies in malaria-naive adults suggest increased vaccine efficacy for fractional-dose versus full-dose regimens of RTS,S/AS01. We report first results of an ongoing trial assessing different fractional-dose regimens in children, in natural exposure settings. METHODS: This open-label, phase 2b, randomised controlled trial is conducted at the Malaria Research Center, Agogo, Ashanti Region (Ghana), and the Kenya Medical Research Institute and the US Centers for Disease Control and Prevention site in Siaya County (Kenya). We enrolled children aged 5-17 months without serious acute or chronic illness who had previously received three doses of diphtheria, tetanus, pertussis, and hepatitis B vaccine and at least three doses of oral polio vaccine. Children were randomly assigned (1:1:1:1:1) using a web-based randomisation system with a minimisation procedure accounting for centre to receive rabies control vaccine (M012 schedule) or two full doses of RTS,S/AS01(E) at month 0 and month 1, followed by either full doses at months 2 and 20 (group R012-20 [standard regimen]), full doses at months 2, 14, 26, and 38 (R012-14), fractional doses at months 2, 14, 26, and 38 (Fx012-14), or fractional doses at months 7, 20, and 32 (Fx017-20). The fractional doses were administered as one fifth (0·1 mL) of the full RTS,S dose (0·5 mL) after reconstitution. All vaccines were administered by intramuscular injection in the left deltoid. The primary outcome was occurrence of clinical malaria cases from month 2·5 until month 14 for the Fx012-14 group versus the pooled R012-14 and R012-20 groups in the per-protocol set. We assessed incremental vaccine efficacy of the Fx012-14 group versus the pooled R012-14 and R012-20 group over 12 months after dose three. Safety was assessed in all children who received at least one vaccine dose. This trial is registered with ClinicalTrials.gov, NCT03276962. FINDINGS: Between Sept 28, 2017, and Sept 25, 2018, 2157 children were enrolled, of whom 1609 were randomly assigned to a treatment group (322 to each RTS,S/AS01(E) group and 321 to the rabies vaccine control group). 1500 children received at least one study vaccine dose and the per-protocol set comprised 1332 children. Over 12 months after dose three, the incremental vaccine efficacy in the Fx012-14 group versus the pooled R012-14 and R12-20 groups was -21% (95% CI -57 to 7; p=0·15). Up to month 21, serious adverse events occurred in 48 (16%) of 298 children in the R012-20 group, 45 (15%) of 294 in the R012-14 group, 47 (15%) of 304 in the Fx012-14 group, 62 (20%) of 311 in the Fx017-20 group, and 71 (24%) of 293 in the control group, with no safety signals observed. INTERPRETATION: The Fx012-14 regimen was not superior to the standard regimen over 12 months after dose three. All RTS,S/AS01(E) regimens provided substantial, similar protection against clinical malaria, suggesting potential flexibility in the recommended dosing regimen and schedule. This, and the effect of annual boosters, will be further evaluated through 50 months of follow-up. FUNDING: GlaxoSmithKline Biologicals; PATH's Malaria Vaccine Initiative. |
Baseline assessment findings of the Africa Society for Blood Transfusion Step-Wise Accreditation Programme in 10 sub-Saharan African countries, 2016-2018
Kanagasabai U , Qualls M , Shiraishi RW , Eno L , Zungu I , Bust L , Drammeh B , Selenic D . Vox Sang 2022 117 (6) 839-846 BACKGROUND AND OBJECTIVES: The accreditation of blood services promotes continuous quality improvement in blood and transfusion services. The Africa Society for Blood Transfusion (AfSBT) conducted 20 baseline assessments of National Blood Transfusion Services (NBTS) or blood banks as part of the Step-Wise Accreditation Programme (SWAP) in 10 sub-Saharan African (SSA) countries from 2016 to 2018. This paper aims to elucidate the process and findings of the baseline assessments. MATERIALS AND METHODS: This is a descriptive study of 20 baseline assessments of NBTS. Eleven sections of the AfSBT assessment were reviewed, and 48 out of 68 standards and 356 out of 466 criteria were assessed. Each standard was assigned a value of 1 if it was fully achieved, 0.5 if partially achieved and 0 if not achieved. We defined average section scores >75% as having 'met AfSBT Standards', 25% as not meeting standards, 26%-50% as needs major improvement, and 51%-75% as needs some improvement and >75% as meets standards. RESULTS: The AfSBT SWAP standards were met in 4 out of the 11 sections: donor management, blood collection, component production and compatibility testing. Three sections were determined to need some improvement (quality system; handling, transport and storage and testing of donated blood), and three sections were determined to need major improvement (haemovigilance, blood administration and national blood service accreditation). One section (receipt, ordering, and issuing of blood) did not meet standards. CONCLUSION: Despite improvements in the quality of blood services in SSA over the past two decades, governments may consider the importance of prioritizing investments in NBTS, ensuring these institutions meet international accreditation standards that are aligned with safe blood transfusion services. |
Safety, immunogenicity and efficacy of PfSPZ vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial
Oneko M , Steinhardt LC , Yego R , Wiegand RE , Swanson PA , Kc N , Akach D , Sang T , Gutman JR , Nzuu EL , Dungani A , Kim Lee Sim B , Oloo PN , Otieno K , Bii DK , Billingsley PF , James ER , Kariuki S , Samuels AM , Jongo S , Chebore W , Abdulla S , Daubenberger C , Mpina M , Styers D , Potter GE , Abarbanell G , Richie TL , Hoffman SL , Seder RA . Nat Med 2021 27 (9) 1636-1645 The radiation-attenuated Plasmodium falciparum sporozoite (PfSPZ) vaccine provides protection against P. falciparum infection in malaria-naïve adults. Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. We hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. We conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5-12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya ( NCT02687373 ). Groups of 84 infants each received 4.5 × 10(5), 9.0 × 10(5) or 1.8 × 10(6) PfSPZ Vaccine or saline three times at 8-week intervals. The vaccine was well tolerated; 52 (20.6%) children in the vaccine groups and 20 (23.8%) in the placebo group experienced related solicited adverse events (AEs) within 28 d postvaccination and most were mild. There was 1 grade 3-related solicited AE in the vaccine group (0.4%) and 2 in the placebo group (2.4%). Seizures were more common in the highest-dose group (14.3%) compared to 6.0% of controls, with most being attributed to malaria. There was no significant protection against P. falciparum infection in any dose group at 6 months (VE in the 9.0 × 10(5) dose group = -6.5%, P = 0.598, the primary statistical end point of the study). VE against clinical malaria 3 months after the last dose in the highest-dose group was 45.8% (P = 0.027), an exploratory end point. There was a dose-dependent increase in antibody responses that correlated with VE at 6 months in the lowest- and highest-dose groups. T cell responses were undetectable across all dose groups. Detection of Vδ2(+)Vγ9(+) T cells, which have been correlated with induction of PfSPZ Vaccine T cell immunity and protection in adults, were infrequent. These data suggest that PfSPZ Vaccine-induced T cell immunity is age-dependent and may be influenced by Vδ2(+)Vγ9(+) T cell frequency. Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group. |
2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.
Kuhn JH , Adkins S , Agwanda BR , Al Kubrusli R , Alkhovsky Aльxoвcкий Cepгeй Bлaдимиpoвич SV , Amarasinghe GK , Avšič-Županc T , Ayllón MA , Bahl J , Balkema-Buschmann A , Ballinger MJ , Basler CF , Bavari S , Beer M , Bejerman N , Bennett AJ , Bente DA , Bergeron É , Bird BH , Blair CD , Blasdell KR , Blystad DR , Bojko J , Borth WB , Bradfute S , Breyta R , Briese T , Brown PA , Brown JK , Buchholz UJ , Buchmeier MJ , Bukreyev A , Burt F , Büttner C , Calisher CH , Cao 曹孟籍 M , Casas I , Chandran K , Charrel RN , Cheng Q , Chiaki 千秋祐也 Y , Chiapello M , Choi IR , Ciuffo M , Clegg JCS , Crozier I , Dal Bó E , de la Torre JC , de Lamballerie X , de Swart RL , Debat H , Dheilly NM , Di Cicco E , Di Paola N , Di Serio F , Dietzgen RG , Digiaro M , Dolnik O , Drebot MA , Drexler JF , Dundon WG , Duprex WP , Dürrwald R , Dye JM , Easton AJ , Ebihara 海老原秀喜 H , Elbeaino T , Ergünay K , Ferguson HW , Fooks AR , Forgia M , Formenty PBH , Fránová J , Freitas-Astúa J , Fu 付晶晶 J , Fürl S , Gago-Zachert S , Gāo 高福 GF , García ML , García-Sastre A , Garrison AR , Gaskin T , Gonzalez JJ , Griffiths A , Goldberg TL , Groschup MH , Günther S , Hall RA , Hammond J , Han 韩彤 T , Hepojoki J , Hewson R , Hong 洪健 J , Hong 洪霓 N , Hongo 本郷誠治 S , Horie 堀江真行 M , Hu JS , Hu T , Hughes HR , Hüttner F , Hyndman TH , Ilyas M , Jalkanen R , Jiāng 姜道宏 D , Jonson GB , Junglen S , Kadono 上遠野冨士夫 F , Kaukinen KH , Kawate M , Klempa B , Klingström J , Kobinger G , Koloniuk I , Kondō 近藤秀樹 H , Koonin EV , Krupovic M , Kubota 久保田健嗣 K , Kurath G , Laenen L , Lambert AJ , Langevin SL , Lee B , Lefkowitz EJ , Leroy EM , Li 李邵蓉 S , Li 李龙辉 L , Lǐ 李建荣 J , Liu 刘华珍 H , Lukashevich IS , Maes P , de Souza WM , Marklewitz M , Marshall SH , Marzano SL , Massart S , McCauley JW , Melzer M , Mielke-Ehret N , Miller KM , Ming TJ , Mirazimi A , Mordecai GJ , Mühlbach HP , Mühlberger E , Naidu R , Natsuaki 夏秋知英 T , Navarro JA , Netesov Heтёcoв Cepгeй Bиктopoвич SV , Neumann G , Nowotny N , Nunes MRT , Olmedo-Velarde A , Palacios G , Pallás V , Pályi B , Papa Άννα Παπά A , Paraskevopoulou Σοφία Παρασκευοπούλου S , Park AC , Parrish CR , Patterson DA , Pauvolid-Corrêa A , Pawęska JT , Payne S , Peracchio C , Pérez DR , Postler TS , Qi 亓立莹 L , Radoshitzky SR , Resende RO , Reyes CA , Rima BK , Luna GR , Romanowski V , Rota P , Rubbenstroth D , Rubino L , Runstadler JA , Sabanadzovic S , Sall AA , Salvato MS , Sang R , Sasaya 笹谷孝英 T , Schulze AD , Schwemmle M , Shi 施莽 M , Shí 石晓宏 X , Shí 石正丽 Z , Shimomoto 下元祥史 Y , Shirako Y , Siddell SG , Simmonds P , Sironi M , Smagghe G , Smither S , Song 송진원 JW , Spann K , Spengler JR , Stenglein MD , Stone DM , Sugano J , Suttle CA , Tabata A , Takada 高田礼人 A , Takeuchi 竹内繁治 S , Tchouassi DP , Teffer A , Tesh RB , Thornburg NJ , Tomitaka 冨高保弘 Y , Tomonaga 朝長啓造 K , Tordo N , Torto B , Towner JS , Tsuda 津田新哉 S , Tu 涂长春 C , Turina M , Tzanetakis IE , Uchida J , Usugi 宇杉富雄 T , Vaira AM , Vallino M , van den Hoogen B , Varsani A , Vasilakis Νίκος Βασιλάκης N , Verbeek M , von Bargen S , Wada 和田治郎 J , Wahl V , Walker PJ , Wang 王林发 LF , Wang 王国平 G , Wang 王雁翔 Y , Wang 王亚琴 Y , Waqas M , Wèi 魏太云 T , Wen 温少华 S , Whitfield AE , Williams JV , Wolf YI , Wu 吴建祥 J , Xu 徐雷 L , Yanagisawa 栁澤広宣 H , Yang 杨彩霞 C , Yang 杨作坤 Z , Zerbini FM , Zhai 翟立峰 L , Zhang 张永振 YZ , Zhang 张松 S , Zhang 张靖国 J , Zhang 张哲 Z , Zhou 周雪平 X . Arch Virol 2021 166 (12) 3513-3566 ![]() In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. |
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]. |
Enhanced Zika virus susceptibility of globally invasive Aedes aegypti populations.
Aubry F , Dabo S , Manet C , Filipović I , Rose NH , Miot EF , Martynow D , Baidaliuk A , Merkling SH , Dickson LB , Crist AB , Anyango VO , Romero-Vivas CM , Vega-Rúa A , Dusfour I , Jiolle D , Paupy C , Mayanja MN , Lutwama JJ , Kohl A , Duong V , Ponlawat A , Sylla M , Akorli J , Otoo S , Lutomiah J , Sang R , Mutebi JP , Cao-Lormeau VM , Jarman RG , Diagne CT , Faye O , Faye O , Sall AA , McBride CS , Montagutelli X , Rašić G , Lambrechts L . Science 2020 370 (6519) 991-996 ![]() ![]() The drivers and patterns of zoonotic virus emergence in the human population are poorly understood. The mosquito Aedes aegypti is a major arbovirus vector native to Africa that invaded most of the world's tropical belt over the past four centuries, after the evolution of a "domestic" form that specialized in biting humans and breeding in water storage containers. Here, we show that human specialization and subsequent spread of A. aegypti out of Africa were accompanied by an increase in its intrinsic ability to acquire and transmit the emerging human pathogen Zika virus. Thus, the recent evolution and global expansion of A. aegypti promoted arbovirus emergence not solely through increased vector-host contact but also as a result of enhanced vector susceptibility. |
Evaluation of the WHO global database on blood safety
Kanagasabai U , Selenic D , Chevalier MS , Drammeh B , Qualls M , Shiraishi RW , Bock N , Benech I , Mili FD . Vox Sang 2020 116 (2) 197-206 OBJECTIVE: While the Global Database on Blood Safety (GDBS) helps to monitor the status of adequate and safe blood availability, its presence alone does not serve as a solution to existing challenges. The objective of this evaluation was to determine the GDBS usefulness in improving the availability of adequate safe blood and its ability to function as a surveillance system. METHODS: The GDBS was evaluated using methods set out by the Centers for Disease Control and Prevention (CDC) Guidelines for assessing surveillance systems. Six recommended tasks were used to evaluate if the GDBS met the requirements of a surveillance system in a public health context. RESULTS: The majority of stakeholders engaged with GDBS found it was unique and useful. The GDBS answered all six questions essential for determining a blood safety surveillance system's usefulness. The GDBS fully met the needs to six of the eleven attributes used for evaluating the usefulness of a surveillance system. CONCLUSION: The GDBS is a unique global activity that provides vital data on safety of blood transfusion services across countries and regions. However, aspects of the GDBS such as timeliness of reporting and improvement of WHO Member States national blood information systems could enhance its effectiveness and potential to serve as a global surveillance system for blood safety. |
Climate and Urbanization Drive Mosquito Preference for Humans.
Rose NH , Sylla M , Badolo A , Lutomiah J , Ayala D , Aribodor OB , Ibe N , Akorli J , Otoo S , Mutebi JP , Kriete AL , Ewing EG , Sang R , Gloria-Soria A , Powell JR , Baker RE , White BJ , Crawford JE , McBride CS . Curr Biol 2020 30 (18) 3570-3579 e6 ![]() The majority of mosquito-borne illness is spread by a few mosquito species that have evolved to specialize in biting humans, yet the precise causes of this behavioral shift are poorly understood. We address this gap in the arboviral vector Aedes aegypti. We first collect and characterize the behavior of mosquitoes from 27 sites scattered across the species' ancestral range in sub-Saharan Africa, revealing previously unrecognized variation in preference for human versus animal odor. We then use modeling to show that over 80% of this variation can be predicted by two ecological factors-dry season intensity and human population density. Finally, we integrate this information with whole-genome sequence data from 375 individual mosquitoes to identify a single underlying ancestry component linked to human preference. Genetic changes associated with human specialist ancestry were concentrated in a few chromosomal regions. Our findings suggest that human-biting in this important disease vector originally evolved as a by-product of breeding in human-stored water in areas where doing so provided the only means to survive the long, hot dry season. Our model also predicts that the rapid urbanization currently taking place in Africa will drive further mosquito evolution, causing a shift toward human-biting in many large cities by 2050. |
Feasibility of direct venous inoculation of the radiation-attenuated Plasmodium falciparum whole sporozoite vaccine in children and infants in Siaya, western Kenya
Oneko M , Cherop YR , Sang T , Gutman JR , Wiegand R , Nyang'au EM , Odila AD , Akach D , Hamel MJ , Samuels AM , Kariuki S , Abebe Y , Nzuu EL , Wijayalath W , James ER , Sim BKL , Billingsley PF , Richie TL , Hoffman SL , Seder RA , Steinhardt LC . Vaccine 2020 38 (29) 4592-4600 PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, is administered by direct venous inoculation (DVI) for maximal efficacy against malaria. A critical issue for advancing vaccines that are administered intravenously is the ability to efficiently administer them across multiple age groups. As part of a pediatric safety, immunogenicity, and efficacy trial in western Kenya, we evaluated the feasibility and tolerability of DVI, including ease of venous access, injection time, and crying during the procedure across age groups. Part 1 was an age de-escalation, dose escalation trial in children aged 13 months-5 years and infants aged 5-12 months; part 2 was a vaccine efficacy trial including only infants, using the most skilled injectors from part 1. Injectors could use a vein viewer, if needed. A total of 1222 injections (target 0.5 mL) were initiated by DVI in 511 participants (36 were 5-9-year-olds, 65 were 13-59-month-olds, and 410 infants). The complete volume was injected in 1185/1222 (97.0%) vaccinations, 1083/1185 (91.4%) achieved with the first DVI. 474/511 (92.8%) participants received only complete injections, 27/511 (5.3%) received at least one partial injection (<0.5 mL), and in 10/511 (2.0%) venous access was not obtained. The rate of complete injections by single DVI for infants improved from 77.1% in part 1 to 92.8% in part 2. No crying occurred in 51/59 (86.4%) vaccinations in 5-9-year-olds, 25/86 (29.1%) vaccinations in 13-59-month-olds and 172/1067 (16.1%) vaccinations in infants. Mean administration time ranged from 2.6 to 4.6 minutes and was longer for younger age groups. These data show that vaccination by DVI was feasible and well tolerated in infants and children in this rural hospital in western Kenya, when performed by skilled injectors. We also report that shipping and storage in liquid nitrogen vapor phase was simple and efficient. (Clinicaltrials.gov NCT02687373). |
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. |
Safety, tolerability, and immunogenicity of PfSPZ Vaccine administered by direct venous inoculation to infants and young children: findings from an age de-escalation, dose-escalation double-blinded randomized, controlled study in western Kenya
Steinhardt LC , Richie TL , Yego R , Akach D , Hamel MJ , Gutman JR , Wiegand RE , Nzuu EL , Dungani A , Kc N , Murshedkar T , Church LWP , Sim BKL , Billingsley PF , James ER , Abebe Y , Kariuki S , Samuels AM , Otieno K , Sang T , Kachur SP , Styers D , Schlessman K , Abarbanell G , Hoffman SL , Seder RA , Oneko M . Clin Infect Dis 2019 71 (4) 1063-1071 BACKGROUND: The whole sporozoite PfSPZ Vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ Vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited. METHODS: We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (5-9 years, 13-59 months, and 5-12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35x105, 2.7x105, 4.5x105, 9.0x105, and 1.8x106Plasmodium falciparum sporozoites (PfSPZ), with the two highest doses given twice, 8 weeks apart. Solicited adverse events (AEs) were monitored for eight days after vaccination; unsolicited AEs for 29 days; and serious AEs (SAEs) throughout the study. Blood taken pre-vaccination and one-week post-vaccination was tested for IgG antibodies to Pf circumsporozoite protein (PfCSP) using enzyme-linked immunosorbent assay (ELISA). RESULTS: Rates of AEs were similar in vaccinees and controls for solicited (35.7% vs. 41.5%) and unsolicited (83.9% vs. 92.5%) AEs, respectively. No related grade 3 AEs, SAEs, or grade 3 laboratory abnormalities occurred. Most (79.0%) vaccinations were administered by a single DVI. Among those in the 9.0x105 and 1.8x106 PfSPZ groups, 36/45 (80.0%) vaccinees and 4/21 (19.0%) placebo controls developed antibodies to PfCSP, p<0.001. CONCLUSIONS: PfSPZ Vaccine in doses as high as 1.8x106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic. |
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. |
Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial
Samuels AM , Awino N , Odongo W , Abong'o B , Gimnig J , Otieno K , Shi YP , Were V , Allen DR , Were F , Sang T , Obor D , Williamson J , Hamel MJ , Patrick Kachur S , Slutsker L , Lindblade KA , Kariuki S , Desai M . Malar J 2017 16 (1) 240 Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices. |
Dengue outbreak in Mombasa City, Kenya, 2013-2014: Entomologic investigations
Lutomiah J , Barrera R , Makio A , Mutisya J , Koka H , Owaka S , Koskei E , Nyunja A , Eyase F , Coldren R , Sang R . PLoS Negl Trop Dis 2016 10 (10) e0004981 Dengue outbreaks were first reported in East Africa in the late 1970s to early 1980s including the 1982 outbreak on the Kenyan coast. In 2011, dengue outbreaks occurred in Mandera in northern Kenya and subsequently in Mombasa city along the Kenyan coast in 2013-2014. Following laboratory confirmation of dengue fever cases, an entomologic investigation was conducted to establish the mosquito species, and densities, causing the outbreak. Affected parts of the city were identified with the help of public health officials. Adult Ae. aegypti mosquitoes were collected using various tools, processed and screened for dengue virus (DENV) by cell culture and RT-PCR. All containers in every accessible house and compound within affected suburbs were inspected for immatures. A total of 2,065 Ae. aegypti adults were collected and 192 houses and 1,676 containers inspected. An overall house index of 22%, container index, 31.0% (indoor = 19; outdoor = 43) and Breteau index, 270.1, were observed, suggesting that the risk of dengue transmission was high. Overall, jerry cans were the most productive containers (18%), followed by drums (17%), buckets (16%), tires (14%) and tanks (10%). However, each site had specific most-productive container-types such as tanks (17%) in Kizingo; Drums in Nyali (30%) and Changamwe (33%), plastic basins (35%) in Nyali-B and plastic buckets (81%) in Ganjoni. We recommend that for effective control of the dengue vector in Mombasa city, all container types would be targeted. Measures would include proper covering of water storage containers and eliminating discarded containers outdoors through a public participatory environmental clean-up exercise. Providing reliable piped water to all households would minimize the need for water storage and reduce aquatic habitats. Isolation of DENV from male Ae. aegypti mosquitoes is a first observation in Kenya and provides further evidence that transovarial transmission may have a role in DENV circulation and/or maintenance in the environment. |
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. |
Orthobunyavirus antibodies among humans in selected parts of the Rift Valley and northeastern Kenya
Odhiambo C , Venter M , Swanepoel R , Sang R . Vector Borne Zoonotic Dis 2015 15 (5) 329-32 Ngari, Bunyamwera, Ilesha, and Germiston viruses are among the mosquito-borne human pathogens in the Orthobunyavirus genus, family Bunyaviridae, associated with febrile illness. Although the four orthobunyaviruses have been isolated from mosquito and/or tick vectors sampled from different geographic regions in Kenya, little is known of human exposure in such areas. We conducted a serologic investigation to determine whether orthobunyaviruses commonly infect humans in Kenya. Orthobunyavirus-specific antibodies were detected by plaque reduction neutralization tests in 89 (25.8%) of 345 persons tested. Multivariable analysis revealed age and residence in northeastern Kenya as risk factors. Implementation of acute febrile illness surveillance in northeastern Kenya will help to detect such infections. |
A household serosurvey to estimate the magnitude of a dengue outbreak in Mombasa, Kenya, 2013
Ellis EM , Neatherlin JC , Delorey M , Ochieng M , Mohamed AH , Mogeni DO , Hunsperger E , Patta S , Gikunju S , Waiboic L , Fields B , Ofula V , Konongoi SL , Torres-Velasquez B , Marano N , Sang R , Margolis HS , Montgomery JM , Tomashek KM . PLoS Negl Trop Dis 2015 9 (4) e0003733 Dengue appears to be endemic in Africa with a number of reported outbreaks. In February 2013, several individuals with dengue-like illnesses and negative malaria blood smears were identified in Mombasa, Kenya. Dengue was laboratory confirmed and an investigation was conducted to estimate the magnitude of local transmission including a serologic survey to determine incident dengue virus (DENV) infections. Consenting household members provided serum and were questioned regarding exposures and medical history. RT-PCR was used to identify current DENV infections and IgM anti-DENV ELISA to identify recent infections. Of 1,500 participants from 701 households, 210 (13%) had evidence of current or recent DENV infection. Among those infected, 93 (44%) reported fever in the past month. Most (68, 73%) febrile infected participants were seen by a clinician and all but one of 32 participants who reportedly received a diagnosis were clinically diagnosed as having malaria. Having open windows at night (OR = 2.3; CI: 1.1-4.8), not using daily mosquito repellent (OR = 1.6; CI: 1.0-2.8), and recent travel outside of Kenya (OR = 2.5; CI: 1.1-5.4) were associated with increased risk of DENV infection. This survey provided a robust measure of incident DENV infections in a setting where cases were often unrecognized and misdiagnosed. |
Genome sequence analysis of in vitro and in vivo phenotypes of Bunyamwera and Ngari virus isolates from northern Kenya
Odhiambo C , Venter M , Limbaso K , Swanepoel R , Sang R . PLoS One 2014 9 (8) e105446 ![]() Biological phenotypes of tri-segmented arboviruses display characteristics that map to mutation/s in the S, M or L segments of the genome. Plaque variants have been characterized for other viruses displaying varied phenotypes including attenuation in growth and/or pathogenesis. In order to characterize variants of Bunyamwera and Ngari viruses, we isolated individual plaque size variants; small plaque (SP) and large plaque (LP) and determined in vitro growth properties and in vivo pathogenesis in suckling mice. We performed gene sequencing to identify mutations that may be responsible for the observed phenotype. The LP generally replicated faster than the SP and the difference in growth rate was more pronounced in Bunyamwera virus isolates. Ngari virus isolates were more conserved with few point mutations compared to Bunyamwera virus isolates which displayed mutations in all three genome segments but majority were silent mutations. Contrary to expectation, the SP of Bunyamwera virus killed suckling mice significantly earlier than the LP. The LP attenuation may probably be due to a non-synonymous substitution (T858I) that mapped within the active site of the L protein. In this study, we identify natural mutations whose exact role in growth and pathogenesis need to be determined through site directed mutagenesis studies. |
Ticks and tick-borne viruses from livestock hosts in arid and semiarid regions of the eastern and northeastern parts of Kenya
Lutomiah J , Musila L , Makio A , Ochieng C , Koka H , Chepkorir E , Mutisya J , Mulwa F , Khamadi S , Miller BR , Bast J , Schnabel D , Wurapa EK , Sang R . J Med Entomol 2014 51 (1) 269-277 Biodiversity and relative abundance of ticks and associated arboviruses in Garissa (northeastern) and Isiolo (eastern) provinces of Kenya were evaluated. Ticks were collected from livestock, identified to species, pooled, and processed for virus isolation. In Garissa, Rhipicephalus pulchellus Gerstacker (57.8%) and Hyalomma truncatum Koch (27.8%) were the most abundant species sampled, whereas R. pulchellus (80.4%) and Amblyomma gemma Donitz (9.6%) were the most abundant in Isiolo. Forty-four virus isolates, comprising Dugbe virus (DUGV; n = 22) and Kupe virus (n = 10; Bunyaviridae: Nirovirus), Dhori virus (DHOV; n = 10; Orthomyxoviridae: Thogotovirus), and Ngari virus (NRIV; n = 2; Bunyaviridae: Orthobunyavirus), were recovered mostly from R. pulchellus sampled in Isiolo. DUGV was mostly recovered from R. pulchellus from sheep and cattle, and DHOV from R. pulchellus from sheep. All Kupe virus isolates were from Isiolo ticks, including R. pulchellus from all the livestock, A. gemma and Amblyomma variegatum F. from cattle, and H. truncatum from goat. NRIV was obtained from R. pulchellus and A. gemma sampled from cattle in Isiolo and Garissa, respectively, while all DHOV and most DUGV (n = 12) were from R. pulchellus sampled from cattle in Garissa. DUGV was also recovered from H. truncatum and Amblyomma hebraeum Koch from cattle and from Rhipicephalus annulatus Say from camel. This surveillance study has demonstrated the circulation of select tick-borne viruses in parts of eastern and northeastern provinces of Kenya, some of which are of public health importance. The isolation of NRIV from ticks is particularly significant because it is usually known to be a mosquito-borne virus affecting humans. |
Increased immunogenicity of avian influenza DNA vaccine delivered to the skin using a microneedle patch.
Kim YC , Song JM , Lipatov AS , Choi SO , Lee JW , Donis RO , Compans RW , Kang SM , Prausnitz MR . Eur J Pharm Biopharm 2012 81 (2) 239-47 ![]() Effective public health responses to an influenza pandemic require an effective vaccine that can be manufactured and administered to large populations in the shortest possible time. In this study, we evaluated a method for vaccination against avian influenza virus that uses a DNA vaccine for rapid manufacturing and delivered by a microneedle skin patch for simplified administration and increased immunogenicity. We prepared patches containing 700-mcm long microneedles coated with an avian H5 influenza hemagglutinin DNA vaccine from A/Viet Nam/1203/04 influenza virus. The coating DNA dose increased with DNA concentration in the coating solution and the number of dip-coating cycles. Coated DNA was released into the skin tissue by dissolution within minutes. Vaccination of mice using microneedles induced higher levels of antibody responses and hemagglutination inhibition titers, and improved protection against lethal infection with avian influenza as compared to conventional intramuscular delivery of the same dose of the DNA vaccine. Additional analysis showed that the microneedle coating solution containing carboxymethylcellulose and a surfactant may have negatively affected the immunogenicity of the DNA vaccine. Overall, this study shows that DNA vaccine delivery by microneedles can be a promising approach for improved vaccination to mitigate an influenza pandemic. |
Outbreak of tuberculosis among Guatemalan immigrants in rural Minnesota, 2008
Lowther SA , Miramontes R , Navara B , Sabuwala N , Brueshaber M , Solarz S , Haddad MB , Sodt D , Lynfield R . Public Health Rep 2011 126 (5) 726-32 OBJECTIVES: We described the outbreak investigation and control measures after the Minnesota Department of Health identified a cluster of tuberculosis (TB) cases among Guatemalan immigrants within three rural Minnesota counties in August 2008. METHODS: TB cases were diagnosed by tuberculin skin test followed by chest radiography and sputum testing for Mycobacterium tuberculosis (M. tuberculosis). We reviewed medical records, interviewed patients, and completed a contact investigation for each infectious case. We used isolate genotyping to confirm epidemiologic links between cases. RESULTS: The index case was a six-month-old U.S.-born male with Guatemalan parents. Although he experienced four months of cough and fever, TB was not considered at two medical visits but was diagnosed upon hospitalization in May 2008. The presumed source of infection was a Guatemalan male aged 25 years who sang in a band that practiced in the infant's house and whose pulmonary TB was diagnosed at hospitalization in June 2008, despite his having sought medical attention for symptoms seven months earlier. Among the 16 identified TB cases, 14 were outbreak-related. Three genetically distinct M. tuberculosis strains circulated. Of 150 contacts of the singer, 62 (41%) had latent TB infection and 13 (9%), including 10 children, had TB disease. CONCLUSIONS: In this outbreak, delayed diagnoses contributed to M. tuberculosis transmission. Isolate genotyping corroborated the social links between outbreak-related patients. More timely diagnosis of TB among immigrants and their children can prevent TB transmission among communities in rural, low-incidence areas that might have limited resources for contact investigations. |
Crimean-Congo hemorrhagic fever virus in hyalommid ticks, northeastern Kenya
Sang R , Lutomiah J , Koka H , Makio A , Chepkorir E , Ochieng C , Yalwala S , Mutisya J , Musila L , Richardson JH , Miller BR , Schnabel D . Emerg Infect Dis 2011 17 (8) 1502-5 As part of ongoing arbovirus surveillance, we screened ticks obtained from livestock in northeastern Kenya in 2008 to assess the risk for human exposure to tick-borne viruses. Of 1,144 pools of 8,600 Hyalomma spp. ticks screened for Congo-Crimean hemorrhagic fever virus by reverse transcription PCR, 23 pools were infected, demonstrating a potential for human exposure. |
Malaria in Kakuma refugee camp, Turkana, Kenya: facilitation of Anopheles arabiensis vector populations by installed water distribution and catchment systems
Nabie Bayoh M , Akhwale W , Ombok M , Sang D , Engoki SC , Koros D , Walker ED , Williams HA , Burke H , Armstrong GL , Cetron MS , Weinberg M , Breiman R , Hamel MJ . Malar J 2011 10 149 BACKGROUND: Malaria is a major health concern for displaced persons occupying refugee camps in sub-Saharan Africa, yet there is little information on the incidence of infection and nature of transmission in these settings. Kakuma Refugee Camp, located in a dry area of north-western Kenya, has hosted ca. 60,000 to 90,000 refugees since 1992, primarily from Sudan and Somalia. The purpose of this study was to investigate malaria prevalence and attack rate and sources of Anopheles vectors in Kakuma refugee camp, in 2005-2006, after a malaria epidemic was observed by staff at camp clinics. METHODS: Malaria prevalence and attack rate was estimated from cases of fever presenting to camp clinics and the hospital in August 2005, using rapid diagnostic tests and microscopy of blood smears. Larval habitats of vectors were sampled and mapped. Houses were sampled for adult vectors using the pyrethrum knockdown spray method, and mapped. Vectors were identified to species level and their infection with Plasmodium falciparum determined. RESULTS: Prevalence of febrile illness with P. falciparum was highest among the 5 to 17 year olds (62.4%) while malaria attack rate was highest among the two to 4 year olds (5.2/1,000/day). Infected individuals were spatially concentrated in three of the 11 residential zones of the camp. The indoor densities of Anopheles arabiensis, the sole malaria vector, were similar during the wet and dry seasons, but were distributed in an aggregated fashion and predominantly in the same zones where malaria attack rates were high. Larval habitats and larval populations were also concentrated in these zones. Larval habitats were man-made pits of water associated with tap-stands installed as the water delivery system to residents with year round availability in the camp. Three percent of A. arabiensis adult females were infected with P. falciparum sporozoites in the rainy season. CONCLUSIONS: Malaria in Kakuma refugee camp was due mainly to infection with P. falciparum and showed a hyperendemic age-prevalence profile, in an area with otherwise low risk of malaria given prevailing climate. Transmission was sustained by A. arabiensis, whose populations were facilitated by installation of man-made water distribution and catchment systems. |
Rift Valley fever virus epidemic in Kenya, 2006/2007: the entomologic investigations
Sang R , Kioko E , Lutomiah J , Warigia M , Ochieng C , O'Guinn M , Lee JS , Koka H , Godsey M , Hoel D , Hanafi H , Miller B , Schnabel D , Breiman RF , Richardson J . Am J Trop Med Hyg 2010 83 28-37 ![]() In December 2006, Rift Valley fever (RVF) was diagnosed in humans in Garissa Hospital, Kenya and an outbreak reported affecting 11 districts. Entomologic surveillance was performed in four districts to determine the epidemic/epizootic vectors of RVF virus (RVFV). Approximately 297,000 mosquitoes were collected, 164,626 identified to species, 72,058 sorted into 3,003 pools and tested for RVFV by reverse transcription-polymerase chain reaction. Seventy-seven pools representing 10 species tested positive for RVFV, including Aedes mcintoshi/circumluteolus (26 pools), Aedes ochraceus (23 pools), Mansonia uniformis (15 pools); Culex poicilipes, Culex bitaeniorhynchus (3 pools each); Anopheles squamosus, Mansonia africana (2 pools each); Culex quinquefasciatus, Culex univittatus, Aedes pembaensis (1 pool each). Positive Ae. pembaensis, Cx. univittatus, and Cx. bitaeniorhynchus was a first time observation. Species composition, densities, and infection varied among districts supporting hypothesis that different mosquito species serve as epizootic/epidemic vectors of RVFV in diverse ecologies, creating a complex epidemiologic pattern in East Africa. |
Prediction, assessment of the Rift Valley fever activity in East and Southern Africa 2006-2008 and possible vector control strategies
Anyamba A , Linthicum KJ , Small J , Britch SC , Pak E , de La Rocque S , Formenty P , Hightower AW , Breiman RF , Chretien JP , Tucker CJ , Schnabel D , Sang R , Haagsma K , Latham M , Lewandowski HB , Magdi SO , Mohamed MA , Nguku PM , Reynes JM , Swanepoel R . Am J Trop Med Hyg 2010 83 43-51 Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Nino/Southern Oscillation (ENSO) phenomenon, which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and regional elevated sea surface temperatures, elevated rainfall, and satellite derived-normalized difference vegetation index data, we predicted with lead times of 2-4 months areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to March 2008. Predictions were confirmed by entomological field investigations of virus activity and by reported cases of RVF in human and livestock populations. This represents the first series of prospective predictions of RVF outbreaks and provides a baseline for improved early warning, control, response planning, and mitigation into the future. |
An investigation of a major outbreak of Rift Valley fever in Kenya: 2006-2007
Nguku PM , Sharif SK , Mutonga D , Amwayi S , Omolo J , Mohammed O , Farnon EC , Gould LH , Lederman E , Rao C , Sang R , Schnabel D , Feikin DR , Hightower A , Njenga MK , Breiman RF . Am J Trop Med Hyg 2010 83 5-13 An outbreak of Rift Valley fever (RVF) occurred in Kenya during November 2006 through March 2007. We characterized the magnitude of the outbreak through disease surveillance and serosurveys, and investigated contributing factors to enhance strategies for forecasting to prevent or minimize the impact of future outbreaks. Of 700 suspected cases, 392 met probable or confirmed case definitions; demographic data were available for 340 (87%), including 90 (26.4%) deaths. Male cases were more likely to die than females, Case Fatality Rate Ratio 1.8 (95% Confidence Interval [CI] 1.3-3.8). Serosurveys suggested an attack rate up to 13% of residents in heavily affected areas. Genetic sequencing showed high homology among viruses from this and earlier RVF outbreaks. Case areas were more likely than non-case areas to have soil types that retain surface moisture. The outbreak had a devastatingly high case-fatality rate for hospitalized patients. However, there were up to 180,000 infected mildly ill or asymptomatic people within highly affected areas. Soil type data may add specificity to climate-based forecasting models for RVF. |
Blood donors in Kenya: a comparison of voluntary and family replacement donors based on a population-based survey
Kimani D , Mwangi J , Mwangi M , Bunnell R , Kellogg TA , Oluoch T , Gichangi A , Kaiser R , Mugo N , Odongo T , Oduor M , Marum L . Vox Sang 2010 100 (2) 212-8 BACKGROUND AND OBJECTIVES: Blood safety and sufficiency are major challenges in Kenya and other sub-Saharan African countries forcing many countries to rely on family replacement donors (FRD). We analysed data from a national AIDS indicator survey to describe blood donors in Kenya and potential risks of transfusion transmissible infections (TTI) comparing voluntary donors and FRD. MATERIALS AND METHODS: A population-based, cross-sectional survey was conducted in 2007 among 15- to 64- year-olds. Consenting participants were interviewed about blood donation history and were tested for HIV, HSV-2 and syphilis. RESULTS: Of the 17 940 people surveyed, 445 (2.3%) reported donating blood in the prior 12 months. Sixty-four per cent were voluntary donors, and the rest were FRD. Compared to FRD, the majority of voluntary donors were < 25 years old (59% versus 18%), from the highest wealth quintile (57% versus 42%) and single (64% versus 23%). In addition, voluntary donors were less likely to have been sexually active than replacement donors (43% versus 13%). HIV prevalence was lower among voluntary donors than among FRD (2.6% versus 7.4%, P-value = 0.07). CONCLUSIONS: The majority of blood donors in Kenya are voluntary with lower potential risk of TTI. |
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