Browsing by Author "Greenhouse, Bryan"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study
    (Malaria Journal, 2020) Kakande, Elijah; Greenhouse, Bryan; Bajunirwe, Francis; Drakeley, Chris; Nankabirwa, Joaniter I.; Walakira, Andrew; Nsobya, Samuel L.; Katureebe, Agaba; Rek, John; Arinaitwe, Emmanuel; Rosenthal, Philip J.; Kamya, Moses R.; Dorsey, Grant; Rodriguez‑Barraquer, Isabel
    Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A—(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes.
  • Thumbnail Image
    Item
    Impact of Antimalarial Treatment and Chemoprevention on the Drug Sensitivity of Malaria Parasites Isolated from Ugandan Children
    (Antimicrobial agents and chemotherapy, 2015) Tumwebaze, Patrick; Conrad, Melissa D.; Walakira, Andrew; LeClair, Norbert; Byaruhanga, Oswald; Nakazibwe, Christine; Okiring, Jaffer; Kakuru, Abel; Bigira, Victor; Kapisi, James; Kamya, Moses R.; Greenhouse, Bryan; Nsobya, Samuel L.; Rosenthal, Philip J.
    Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. Over time, ex vivo sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of pfcrt K76 and pfmdr1 N86 and D1246 increased, and the prevalences of pfdhfr and pfdhps polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased ex vivo lumefantrine sensitivity and increased prevalence of pfcrt K76 and pfmdr1 N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of pfmdr1 86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively.
  • Thumbnail Image
    Item
    Measures of Malaria Burden after Long- Lasting Insecticidal Net Distribution and Indoor Residual Spraying at Three Sites in Uganda: A Prospective Observational Study
    (PLoS medicine, 2016) Katureebe, Agaba; Zinszer, Kate; Arinaitwe, Emmanuel; Rek, John; Kakande, Elijah; Charland, Katia; Kigozi, Ruth; Kilama, Maxwell; Nankabirwa, Joaniter; Yeka, Adoke; Mawejje, Henry; Mpimbaza, Arthur; Katamba, Henry; Donnelly, Martin J.; Rosenthal, Philip J.; Drakeley, Chris; Lindsay, Steve W.; Staedke, Sarah G.; Smith, David L.; Greenhouse, Bryan; Kamya, Moses R.; Dorsey, Grant
    Long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are the primary vector control interventions used to prevent malaria in Africa. Although both interventions are effective in some settings, high-quality evidence is rarely available to evaluate their effectiveness following deployment by a national malaria control program. In Uganda, we measured changes in key malaria indicators following universal LLIN distribution in three sites, with the addition of IRS at one of these sites. Methods and Findings Comprehensive malaria surveillance was conducted from October 1, 2011, to March 31, 2016, in three sub-counties with relatively low (Walukuba), moderate (Kihihi), and high transmission (Nagongera). Between 2013 and 2014, universal LLIN distribution campaigns were conducted in all sites, and in December 2014, IRS with the carbamate bendiocarb was initiated in Nagongera. High-quality surveillance evaluated malaria metrics and mosquito exposure before and after interventions through (a) enhanced health-facility-based surveillance to estimate malaria test positivity rate (TPR), expressed as the number testing positive for malaria/number tested for malaria (number of children tested for malaria: Walukuba = 42,833, Kihihi = 28,790, and Nagongera = 38,690); (b) cohort studies to estimate the incidence of malaria, expressed as the number of episodes per person-year [PPY] at risk (number of children observed: Walukuba = 340, Kihihi = 380, and Nagongera = 361); and (c) entomology surveys to estimate household-level human biting rate (HBR), expressed as the number of female Anopheles mosquitoes collected per house-night of collection (number of households observed: Walukuba = 117, Kihihi = 107, and Nagongera = 107). The LLIN distribution campaign substantially increased LLIN coverage levels at the three sites to between 65.0% and 95.5% of households with at least one LLIN. In Walukuba, over the 28-mo post-intervention period, universal LLIN distribution was associated with no change in the incidence of malaria (0.39 episodes PPY pre-intervention versus 0.20 post-intervention; adjusted rate ratio [aRR] = 1.02, 95% CI 0.36±2.91, p = 0.97) and nonsignificant reductions in the TPR (26.5% pre-intervention versus 26.2% post-intervention; aRR = 0.70, 95% CI 0.46±1.06, p = 0.09) and HBR (1.07 mosquitoes per house-night preintervention versus 0.71 post-intervention; aRR = 0.41, 95% CI 0.14±1.18, p = 0.10). In Kihihi, over the 21-mo post-intervention period, universal LLIN distribution was associated with a reduction in the incidence of malaria (1.77 pre-intervention versus 1.89 post-intervention; aRR = 0.65, 95% CI 0.43±0.98, p = 0.04) but no significant change in the TPR (49.3% pre-intervention versus 45.9% post-intervention; aRR = 0.83, 95% 0.58±1.18, p = 0.30) or HBR (4.06 pre-intervention versus 2.44 post-intervention; aRR = 0.71, 95% CI 0.30±1.64, p = 0.40). In Nagongera, over the 12-mo post-intervention period, universal LLIN distribution was associated with a reduction in the TPR (45.3% pre-intervention versus 36.5% post-intervention; aRR = 0.82, 95% CI 0.76±0.88, p < 0.001) but no significant change in the incidence of malaria (2.82 pre-intervention versus 3.28 post-intervention; aRR = 1.10, 95% 0.76±1.59, p = 0.60) or HBR (41.04 pre-intervention versus 20.15 postintervention; aRR = 0.87, 95% CI 0.31±2.47, p = 0.80). The addition of three rounds of IRS at ~6-mo intervals in Nagongera was followed by clear decreases in all outcomes: incidence of malaria (3.25 pre-intervention versus 0.63 post-intervention; aRR = 0.13, 95% CI 0.07±0.27, p < 0.001), TPR (37.8% pre-intervention versus 15.0% post-intervention; aRR = 0.54, 95% CI 0.49±0.60, p < 0.001), and HBR (18.71 pre-intervention versus 3.23 postintervention; aRR = 0.29, 95% CI 0.17±0.50, p < 0.001). High levels of pyrethroid resistance were documented at all three study sites. Limitations of the study included the observational study design, the lack of contemporaneous control groups, and that the interventions were implemented under programmatic conditions. Conclusions Universal distribution of LLINs at three sites with varying transmission intensity was associated with modest declines in the burden of malaria for some indicators, but the addition of IRS at the highest transmission site was associated with a marked decline in the burden of malaria for all indicators. In highly endemic areas of Africa with widespread pyrethroid resistance, IRS using alternative insecticide formulations may be needed to achieve substantial gains in malaria control.
  • Thumbnail Image
    Item
    Rapid shifts in the age‑specific burden of malaria following successful control interventions in four regions of Uganda
    (Malaria journal, 2020) Kigozi, Simon P.; Kigozi, Ruth N.; Epstein, Adrienne; Mpimbaza, Arthur; Sserwanga, Asadu; Yeka, Adoke; Nankabirwa, Joaniter I.; Halliday, Katherine; Pullan, Rachel L.; Rutazaana, Damian; Sebuguzi, Catherine M.; Opigo, Jimmy; Kamya, Moses R.; Staedke, Sarah G.; Dorsey, Grant; Greenhouse, Bryan; Rodriguez‑Barraquer, Isabel
    Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear. Methods: Over a 10-year period (January 2009 to July 2018), outpatient surveillance data from four health facilities in Uganda were used to estimate the impact of control interventions on temporal changes in the age distribution of malaria cases using multinomial regression. Interventions included mass distribution of LLINs at all sites and IRS at two sites. Results: Overall, 896,550 patient visits were included in the study; 211,632 aged < 5 years, 171,166 aged 5–15 years and 513,752 > 15 years. Over time, the age distribution of patients not suspected of malaria and those malaria negative either declined or remained the same across all sites. In contrast, the age distribution of suspected and confirmed malaria cases increased across all four sites. In the two LLINs-only sites, the proportion of malaria cases in < 5 years decreased from 31 to 16% and 35 to 25%, respectively. In the two sites receiving LLINs plus IRS, these proportions decreased from 58 to 30% and 64 to 47%, respectively. Similarly, in the LLINs-only sites, the proportion of malaria cases > 15 years increased from 40 to 61% and 29 to 39%, respectively. In the sites receiving LLINs plus IRS, these proportions increased from 19 to 44% and 18 to 31%, respectively. Conclusions: These findings demonstrate a shift in the burden of malaria from younger to older individuals following implementation of successful control interventions, which has important implications for malaria prevention, surveillance, case management and control strategies.
  • Thumbnail Image
    Item
    Urban malaria: primary caregivers’ knowledge, attitudes, practices and predictors of malaria incidence in a cohort of Ugandan children
    (Tropical medicine & international health, 2003) Njama, Denise; Dorsey, Grant; Guwatudde, David; Kigonya, Kate; Greenhouse, Bryan; Musisi, Stephen; Kamya, Moses R.
    To assess malaria-related knowledge, attitude and practices (KAP) among primary caregivers, to identify associations between primary caregivers characteristics and positive KAP towards malaria, and to identify independent predictors of childhood malaria incidence in an urban setting. methods Children aged 6 months to 5 years living in Kampala, Uganda were enrolled as part of a longitudinal study on antimalarial therapy. Primary caregivers of 307 children were interviewed and information was collected on demographics, malaria-related KAP, environmental and household factors. Malaria incidence was measured prospectively using passive surveillance. results A total of 90% of respondents reported mosquitoes and/or malaria as the cause of fever. Caregivers reported that if their child had fever, 63% would go to a clinic or hospital as their first action and 97% as their first or second action. Only 38% knew that chloroquine was the recommended firstline treatment for malaria and 29% knew the correct dose. Preventive measures for malaria were reported in 45% of households but only 25% reported using bednets. Higher levels of education for the caregiver were associated with positive malaria-related KAP. Malaria incidence varied widely. The following were independent predictors of malaria incidence: (1) Children aged 24–41 months at enrolment had a higher incidence of malaria. (2) Reported bednet or chemoprophylaxis use reduced the incidence of malaria. (3) A child’s place of residence was associated with incidence. (4) Children from households using open water sources had a higher incidence than those using closed sources. conclusion Primary caregivers were knowledgeable about malaria and used modern health care facilities but knew less about the proper administration of antimalarials and had limited use of preventive measures. Malaria incidence was associated with child’s age at enrolment, geography, source of water and the use of preventive measures.