Browsing by Author "Millard, Monica"

Now showing 1 - 9 of 9
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    Contraceptive Use in Women Enrolled into Preventive HIV Vaccine Trials: Experience from a Phase I/II Trial in East Africa
    (PLoS ONE, 2009) Kibuuka, Hannah; Guwatudde, David; Kimutai, Robert; Maganga, Lucas; Maboko, Leonard; Watyema, Cecilia; Sawe, Fredrick; Shaffer, Douglas; Matsiko, Dickson; Millard, Monica; Michael, Nelson; Wabwire-Mangen, Fred; Robb, Merlin
    HIV vaccine trials generally require that pregnant women are excluded from participation, and contraceptive methods must be used to prevent pregnancy during the trial. However, access to quality services and misconceptions associated with contraceptive methods may impact on their effective use in developing countries. We describe the pattern of contraceptive use in a multi-site phase I/IIa HIV Vaccine trial in East Africa (Uganda, Kenya and Tanzania) and factors that may have influenced their use during the trial. Methods: Pregnancy prevention counseling was provided to female participants during informed consent process and at each study visit. Participants’ methods of contraception used were documented. Methods of contraceptives were provided on site. Pregnancy testing was done at designated visits during the trial. Obstacles to contraceptive use were identified and addressed at each visit. Results: Overall, 103 (31.8%) of a total of 324 enrolled volunteers were females. Female participants were generally young with a mean age of 29(67.2), married (49.5%) and had less than high school education (62.1%). Hormonal contraceptives were the most common method of contraception (58.3%) followed by condom use (22.3%). The distribution of methods of contraception among the three sites was similar except for more condom use and less abstinence in Uganda. The majority of women (85.4%) reported to contraceptive use prior to screening. The reasons for not using contraception included access to quality services, insufficient knowledge of certain methods, and misconceptions. Conclusion: Although hormonal contraceptives were frequently used by females participating in the vaccine trial, misconceptions and their incorrect use might have led to inconsistent use resulting in undesired pregnancies. The study underscores the need for an integrated approach to pregnancy prevention counseling during HIV vaccine trials.
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    Epidemiology and Surveillance of Influenza Viruses in Uganda between 2008 and 2014
    (PLoS ONE, 2016) Wabwire-Mangen, Fred; Mimbe, Derrick E.; Erima, Bernard; Mworozi, Edison A.; Millard, Monica; Kibuuka, Hannah; Lukwago, Luswa; Bwogi, Josephine; Kiconco, Jocelyn; Tugume, Titus; Mulei, Sophia; Ikomera, Christine; Tsui, Sharon; Malinzi, Stephen; Kasasa, Simon; Coldren, Rodney; Byarugaba, Denis K.
    Influenza surveillance was conducted in Uganda from October 2008 to December 2014 to identify and understand the epidemiology of circulating influenza strains in out-patient clinic attendees with influenza-like illness and inform control strategies. Methodology Surveillance was conducted at five hospital-based sentinel sites. Nasopharyngeal and/or oropharyngeal samples, epidemiological and clinical data were collected from enrolled patients. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to identify and subtype influenza strains. Data were double-entered into an Epi Info 3.5.3 database and exported to STATA 13.0 software for analysis. Results Of the 6,628 patient samples tested, influenza virus infection was detected in 10.4% (n = 687/ 6,628) of the specimens. Several trends were observed: influenza circulates throughout the year with two peaks; the major one from September to November and a minor one from March to June. The predominant strains of influenza varied over the years: Seasonal Influenza A(H3) virus was predominant from 2008 to 2009 and from 2012 to 2014; Influenza A (H1N1)pdm01 was dominant in 2010; and Influenza B virus was dominant in 2011. The peaks generally coincided with times of higher humidity, lower temperature, and higher rainfall. Conclusion Influenza circulated throughout the year in Uganda with two major peaks of outbreaks with similar strains circulating elsewhere in the region. Data on the circulating strains of influenza and its patterns of occurrence provided critical insights to informing the design and timing of influenza vaccines for influenza prevention in tropical regions of sub-Saharan Africa.
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    Genetic analysis of influenza B viruses isolated in Uganda during the 2009–2010 seasons
    (Virology Journal, 2013) Byarugaba, Denis K.; Erima, Bernard; Millard, Monica; Kibuuka, Hannah; Lukwago, L.; Bwogi, Josephine; Mimbe, Derrick; Mworozi, Edison A.; Sharp, Bridget; Krauss, Scott; Webby, Richard J.; Webster, Robert G.; Martin, Samuel K.; Wabwire-Mangen, Fred; Ducatez, Mariette F.
    Influenza B viruses can cause morbidity and mortality in humans but due to the lack of an animal reservoir are not associated with pandemics. Because of this, there is relatively limited genetic sequences available for influenza B viruses, especially from developing countries. Complete genome analysis of one influenza B virus and several gene segments of other influenza B viruses isolated from Uganda from May 2009 through December 2010 was therefore undertaken in this study. Methods: Samples were collected from patients showing influenza like illness and screened for influenza A and B by PCR. Influenza B viruses were isolated on Madin-Darby Canine Kidney cells and selected isolates were subsequently sequenced and analyzed phylogenetically.
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    Molecular Epidemiology of Influenza A/H3N2 Viruses Circulating in Uganda
    (PLoS ONE, 2011) Byarugaba, Denis K.; Ducatez, Mariette F.; Erima, Bernard; Mworozi, Edison A.; Millard, Monica; Kibuuka, Hannah; Lukwago, Luswa; Bwogi, Josephine; Kaira, Blanche B.; Mimbe, Derrick; Schnabel, David C.; Krauss, Scott; Darnell, Daniel; Webby, Richard J.; Webster, Robert G.; Wabwire-Mangen, Fred
    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.
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    Pre-positioned Outbreak Research: The Joint Medical Emerging Diseases Intervention Clinical Capability Experience in Uganda
    (Health security, 2020) Martins, Karen A.; Ayebare, Rodgers R.; Bhadelia, Nahid; Kiweewa, Francis; Waitt, Peter; Mimbe, Derrick; Okello, Stephen; Naluyima, Prossy; Brett-Major, David M.; Lawler, James V.; Millard, Monica; Walwema, Richard; Cardile, Anthony P.; Ritchie, Chi; Kwiecien, Antonia; Badu, Helen; Espinosa, Benjamin J.; Beckett, Charmagne; Bavari, Sina; Zaman, Saima; Christopher, George; Clark, Danielle V.; Lamorde, Mohammed; Kibuuka, Hannah
    The West Africa Ebola virus disease outbreak of 2014-2016 demonstrated that responses to viral hemorrhagic fever epidemics must go beyond emergency stopgap measures and should incorporate high-quality medical care and clinical research. Optimal patient management is essential to improving outcomes, and it must be implemented regardless of geographical location or patient socioeconomic status. Coupling clinical research with improved care has a significant added benefit: Improved data quality and management can guide the development of more effective supportive care algorithms and can support regulatory approvals of investigational medical countermeasures (MCMs), which can alter the cycle of emergency response to reemerging pathogens. However, executing clinical research during outbreaks of high-consequence pathogens is complicated and comes with ethical and research regulatory challenges. Aggressive care and excellent quality control must be balanced by the requirements of an appropriate infection prevention and control posture for healthcare workers and by overcoming the resource limitations inherent in many outbreak settings. The Joint Mobile Emerging Disease Intervention Clinical Capability was established in 2015 to develop a high-quality clinical trial capability in Uganda to support rigorous evaluation of MCMs targeting high-consequence pathogens like Ebola virus. This capability assembles clinicians, laboratorians, clinical researchers, logisticians, and regulatory professionals trained in infection prevention and control and in good clinical and good clinical laboratory practices. The resulting team is prepared to provide high-quality medical care and clinical research during high-consequence outbreaks.
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    Prevalence of influenza A viruses in livestock and free-living waterfowl in Uganda
    (BMC Veterinary Research, 2014) Kirunda, Halid; Erima, Bernard; Tumushabe, Agnes; Kiconco, Jocelyn; Tugume, Titus; Mulei, Sophia; Mimbe, Derrick; Mworozi, Edison; Bwogi, Josephine; Luswa, Lukwago; Kibuuka, Hannah; Millard, Monica; Byaruhanga, Achilles; Ducatez, Mariette F.; Krauss, Scott; Webby, Richard J.; Webster, Robert G.; Wurapa, Kofi; Byarugaba, Denis K.; Wabwire-Mangen, Fred
    Avian influenza viruses may cause severe disease in a variety of domestic animal species worldwide, with high mortality in chickens and turkeys. To reduce the information gap about prevalence of these viruses in animals in Uganda, this study was undertaken. Results: Influenza A virus prevalence by RT-PCR was 1.1% (45/4,052) while sero prevalence by ELISA was 0.8% (24/2,970). Virus prevalence was highest in domestic ducks (2.7%, 17/629) and turkeys (2.6%, 2/76), followed by free-living waterfowl (1.3%, 12/929) and swine (1.4%, 7/511). A lower proportion of chicken samples (0.4%, 7/1,865) tested positive. No influenza A virus was isolated. A seasonal prevalence of these viruses in waterfowl was 0.7% (4/561) for the dry and 2.2% (8/368) for the wet season. In poultry, prevalence was 0.2% (2/863) for the dry and 1.4% (24/1,713) for the wet season, while that of swine was 0.0% (0/159) and 2.0% (7/352) in the two seasons, respectively. Of the 45 RT-PCR positive samples, 13 (28.9%) of them were H5 but none was H7. The 19 swine sera positive for influenza antibodies by ELISA were positive for H1 antibodies by HAI assay, but the subtype(s) of ELISA positive poultry sera could not be determined. Antibodies in the poultry sera could have been those against subtypes not included in the HAI test panel. Conclusions: The study has demonstrated occurrence of influenza A viruses in animals in Uganda. The results suggest that increase in volumes of migratory waterfowl in the country could be associated with increased prevalence of these viruses in free-living waterfowl and poultry.
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    Rapid establishment of a frontline field laboratory in response to an imported outbreak of Ebola virus disease in western Uganda, June 2019
    (PLOS Neglected Tropical Diseases, 2021) Schuh, Amy J.; Kyondo, Jackson; Graziano, James; Balinandi, Stephen; Kainulainen, Markus H.; Tumusiime, Alex; Nyakarahuka, Luke; Mulei, Sophia; Baluku, Jimmy; Lonergan, William; Mayer, Oren; Masereka, Rastus; Masereka, Fredrick; Businge, Esther; Gatare, Alphonse; Kabyanga, Loice; Muhindo, Samuel; Mugabe, Raymond; Makumbi, Issa; Kayiwa, Joshua; Makoba Wetaka, Milton; Brown, Vance; Ojwang, Joseph; Nelson, Lisa; Millard, Monica; Nichol, Stuart T.; Montgomery, Joel M.; Taboy, Celine H.; Lutwama, Julius J.; Klena, John D.
    The Democratic Republic of the Congo (DRC) declared an Ebola virus disease (EVD) outbreak in North Kivu in August 2018. By June 2019, the outbreak had spread to 26 health zones in northeastern DRC, causing >2,000 reported cases and >1,000 deaths. On June 10, 2019, three members of a Congolese family with EVD-like symptoms traveled to western Uganda’s Kasese District to seek medical care. Shortly thereafter, the Viral Hemorrhagic Fever Surveillance and Laboratory Program (VHF program) at the Uganda Virus Research Institute (UVRI) confirmed that all three patients had EVD. The Ugandan Ministry of Health declared an outbreak of EVD in Uganda’s Kasese District, notified the World Health Organization, and initiated a rapid response to contain the outbreak. As part of this response, UVRI and the United States Centers for Disease Control and Prevention, with the support of Uganda’s Public Health Emergency Operations Center, the Kasese District Health Team, the Superintendent of Bwera General Hospital, the United States Department of Defense’s Makerere University Walter Reed Project, and the United States Mission to Kampala’s Global Health Security Technical Working Group, jointly established an Ebola Field Laboratory in Kasese District at Bwera General Hospital, proximal to an Ebola Treatment Unit (ETU). The laboratory consisted of a rapid containment kit for viral inactivation of patient specimens and a GeneXpert Instrument for performing Xpert Ebola assays. Laboratory staff tested 76 specimens from alert and suspect cases of EVD; the majority were admitted to the ETU (89.3%) and reported recent travel to the DRC (58.9%). Although no EVD cases were detected by the field laboratory, it played an important role in patient management and epidemiological surveillance by providing diagnostic results in <3 hours. The integration of the field laboratory into Uganda’s National VHF Program also enabled patient specimens to be referred to Entebbe for confirmatory EBOV testing and testing for other hemorrhagic fever viruses that circulate in Uganda.
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    Relatively Low HIV Infection Rates in Rural Uganda, but with High Potential for a Rise: A Cohort Study in Kayunga District, Uganda
    (PLoS ONE, 2009) Guwatudde, David; Wabwire-Mangen, Fred; Eller, Leigh Anne; Eller, Michael; McCutchan, Francine; Kibuuka, Hannah; Millard, Monica; Sewankambo, Nelson; Serwadda, David; Michael, Nelson; Robb, Merlin
    Few studies have been conducted in Uganda to identify and quantify the determinants of HIV-1 infection. We report results from a community-based cohort study, whose primary objectives were to determine HIV-1 prevalence, incidence, and determinants of these infections, among other objectives. Methodology: Consenting volunteers from the rural district of Kayunga in Uganda aged 15–49 years were enrolled between March and July 2006. Participants were evaluated every six months. A questionnaire that collected information on behavioral and other HIV-1 risk factors was administered, and a blood sample obtained for laboratory analysis at each study visit. Principal Findings: HIV-1 prevalence among the 2025 participants was 9.9% (95% CI = 8.6%–11.2%). By the end of 12 months of follow-up, 1689.7 person-years had been accumulated, with a median follow-up time of 11.97 months. Thirteen HIV-1 incident cases were detected giving an annual HIV-1 incidence of 0.77% (95% CI = 0.35–1.19). Prevalence of HSV-2 infection was 57% and was strongly associated with prevalent HIV-1 infection (adjusted Odds Ratio = 3.9, 95% CI = 2.50–6.17); as well as incident HIV-1 infection (adjusted Rate Ratio (RR) = 8.7, 95% CI = 1.11–67.2). The single most important behavioral characteristic associated with incident HIV infection was the number of times in the past 6 months, a participant had sex with person(s) they suspected/knew were having sex with others; attaining statistical significance at 10 times and higher (adjusted RR = 6.3, 95% CI = 1.73–23.1). By the end of 12 months of follow-up, 259 participants (13%) were lost to follow-up, 13 (0.6%) had died, and 2 (0.1%) had withdrawn consent. Conclusions: Despite relatively low HIV-1 incidence observed in this community, prevalence remains relatively high. In the presence of high prevalence of HSV-2 infection and the behavioral characteristic of having sex with more than one partner, there is potential for increase in HIV-1 incidence.
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    Whole-genome analysis of influenza A(H1N1)pdm09 viruses isolated in Uganda from 2009 to 2011
    (Influenza and Other Respiratory Viruses, 2016) Byarugaba, Denis K.; Erima, Bernard; Millard, Monica; Kibuuka, Hannah; Lukwago, Luswa; Bwogi, Josephine; Mimbe, Derrick; Kiconco, Jocelyn B.; Tugume, Titus; Mworozi, Edison A.; Turner, Jasmine; Mckenzie, Pamela P.; Webby, Richard R. J.; Webster, Robert G.; Foret, Charlotte; Ducatez, Mariette F.; Coldren, Rodney; Wabwire-Mangen, Fred; Krauss, Scott
    We report a whole-genome analysis of 19 influenza A(H1N1)pdm09 isolates from four Ugandan hospitals between 2009 and 2011. The isolates differed from the vaccine strain A/California/07/2009 by three amino acid substitutions P100S, S220T, and I338V in the hemagglutinin and by two amino acid substitutions V106I and N248D in the neuraminidase proteins with consistent mutations in all gene segments distinguishing isolates from the 2009/2010 to 2010/2011 seasons. Phylogenetic analysis showed low genetic evolution, with genetic distances of 0%–1.3% and 0.1%–1.6% for HA and NA genes, respectively. The amino acid substitutions did not lead to antigenic differences from the reference strains.