Showing papers by "Moses R. Kamya published in 2009"
TL;DR: A significant early mortality in a cohort of patients who initiated antiretroviral therapy in Uganda is shown that is driven by advanced human immunodeficiency virus disease and characterized by low CD4 cell counts.
Abstract: Background. Although many studies have reported high early mortality among patients enrolled in antiretroviral therapy (ART) programs in sub-Saharan Africa―particularly among those individuals with advanced immunodeficiency―few studies have reported the most common causes of these early deaths Methods. We determined cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome (IRIS) in a well-characterized patient cohort in Kampala, Uganda, over a 36-month period of ART. Results. In a cohort of patients who initiated antiretroviral therapy in Uganda, we observed a high early mortality rate among patients with advanced disease. The most common causes of death were tuberculosis and cryptococcal meningitis. The contribution of immune reconstitution inflammatory syndrome to mortality was limited. Conclusions. We show a significant early mortality in our ART cohort in resource-limited settings that is driven by advanced human immunodeficiency virus disease and characterized by low CD4 cell counts. In our experience, the contribution of IRIS to this observed early mortality is limited.
129 citations
TL;DR: Artemether-lumefantrine and dihydroartemisinin-piperaquine were both efficacious and had similar long-term effects on the risk of recurrent malaria.
Abstract: Background Artemisinin-based combination therapies are now widely recommended as first-line treatment for uncomplicated malaria. However, which therapies are optimal is a matter of debate. We aimed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ugandan children. Methods A total of 351 children aged 6 weeks to 12 months were enrolled and followed up for up to 1 year. Children who were at least 4 months of age, weighted at least 5 kg, and had been diagnosed as having their first episode of uncomplicated malaria were randomized to receive artemether-lumefantrine or dihydroartemisinin-piperaquine. The same treatment was given for all subsequent episodes of uncomplicated malaria. Recrudescent and new infections were distinguished by polymerase chain reaction genotyping. Outcomes included the risk of recurrent malaria after individual treatments and the incidence of malaria treatments for individual children after randomization. Results A total of 113 children were randomized to artemether-lumefantrine and 119 to dihydroartemisinin-piperaquine, resulting in 320 and 351 treatments for uncomplicated falciparum malaria, respectively. Artemether-lumefantrine was associated with a higher risk of recurrent malaria after 28 days (35% vs 11%; P = .001]). When the duration of follow-up was extended, differences in the risk of recurrent malaria decreased such that the overall incidence of malaria treatments was similar for children randomized to artemether-lumefantrine, compared with those randomized to dihydroartemisinin-piperaquine (4.82 vs 4.61 treatments per person-year; P = .63). The risk of recurrent malaria due to recrudescent parasites was similarly low in both treatment arms. Conclusions Artemether-lumefantrine and dihydroartemisinin-piperaquine were both efficacious and had similar long-term effects on the risk of recurrent malaria. Clinical trials registration. NCT00527800.
121 citations
TL;DR: The effectiveness of a seven day course of quinine for the treatment of uncomplicated malaria in Ugandan children was significantly lower than that of artemether-lumefantrine, and these findings question the advisability of the recommendation forQuinine therapy for uncomplication malaria in Africa.
Abstract: Objective To compare the effectiveness of oral quinine with that of artemether-lumefantrine in treating uncomplicated malaria in children. Design Randomised, open label effectiveness study. Setting Outpatient clinic of Uganda’s national referral hospital in Kampala. Participants 175 children aged 6 to 59 months with uncomplicated malaria. Interventions Participants were randomised to receive oral quinine or artemether-lumefantrine administered by care givers at home. Main outcome measures Primary outcomes were parasitological cure rates after 28 days of follow-up unadjusted and adjusted by genotyping to distinguish recrudescence from new infections. Secondary outcomes were adherence to study drug, presence of gametocytes, recovery of haemoglobin concentration from baseline at day 28, and safety profiles. Results Using survival analysis the cure rate unadjusted by genotyping was 96% for the artemether-lumefantrine group compared with 64% for the quinine group (hazard ratio 10.7, 95% confidence interval 3.3 to 35.5, P=0.001). In the quinine group 69% (18/26) of parasitological failures were due to recrudescence compared with none in the artemether-lumefantrine group. The mean adherence to artemether-lumefantrine was 94.5% compared with 85.4% to quinine (P=0.0008). Having adherence levels of 80% or more was associated with a decreased risk of treatment failure (0.44, 0.19 to 1.02, P=0.06). Adverse events did not differ between the two groups. Conclusions The effectiveness of a seven day course of quinine for the treatment of uncomplicated malaria in Ugandan children was significantly lower than that of artemether-lumefantrine. These findings question the advisability of the recommendation for quinine therapy for uncomplicated malaria in Africa. Trial registration ClinicalTrials.gov NCT00540202.
93 citations
TL;DR: Changes in SPR provided a useful estimate of changes in the incidence of malaria in a well defined cohort; however, a gradual decline in the occurrence of non-malaria fevers introduced some bias in these estimates.
Abstract: As malaria control efforts intensify, it is critical to monitor trends in disease burden and measure the impact of interventions. A key surveillance indicator is the incidence of malaria. Yet measurement of incidence is challenging. The slide positivity rate (SPR) has been used as a surrogate measure of malaria incidence, but limited data exist on the relationship between SPR and the incidence of malaria. A cohort of 690 children aged 1-10 years at enrollment were followed for all their health care needs over a four-year period in Kampala, Uganda. All children with fever underwent laboratory testing, allowing us to measure the incidence of malaria and non-malaria fevers. A formula was derived to estimate relative changes in the incidence of malaria (rΔIm) based on changes in the SPR and the assumption that the incidence of non-malaria fevers was consistent over time. Observed and estimated values of rΔIm were compared over two, six, and 12 month time intervals after restricting the analysis to children contributing observation time between the ages of 4-10 years to control for aging of the cohort. Over the four-year observation period the incidence of malaria declined significantly from 0.93 episodes per person-year in 2005 to 0.39 episodes per person-year in 2008 (p < 0.0001) and the incidence of non-malaria fevers declined significantly from 2.31 episodes per person-year in 2005 to 1.31 episodes per person-year in 2008 (p < 0.0001). Younger age was associated with a significantly greater incidence of malaria and the incidence of malaria was significantly higher during seasonal peaks occurring each January-February and May-June. Changes in SPR produced reasonably accurate estimates of rΔIm over all time intervals. The average absolute difference in observed and estimated values of rΔIm was lower for six-month intervals (0.13) than it was for two-month (0.21) or 12 month intervals (0.21). Changes in SPR provided a useful estimate of changes in the incidence of malaria in a well defined cohort; however, a gradual decline in the incidence of non-malaria fevers introduced some bias in these estimates.
49 citations
TL;DR: Although home management of malaria led to prompt treatment of fever, there was little effect on clinical outcomes, and a substantial over-treatment suggests that artemether-lumefantrine provided in the home might not be appropriate for large urban areas or settings with fairly low malaria transmission.
46 citations
TL;DR: IRS was effective in reducing malaria morbidity, but this effect waned over the subsequent 12 months and was not sustained beyond 1 year for the proportion of blood smears read as positive.
Abstract: A single round of indoor residual spraying (IRS) using lambda-cyhalothrin was implemented in a district of Uganda with moderate transmission intensity in 2007. Individual patient data were collected from one health facility within the district 8 months before and 16 months after IRS. There was a consistent decrease in the proportion of patients diagnosed with clinical malaria after IRS for patients 5 years of age (52% versus 26%, P 5 (26% versus 9%, P < 0.001) years of age, but this effect waned over the subsequent 12 months. IRS was effective in reducing malaria morbidity, but this was not sustained beyond 1 year for the proportion of blood smears read as positive.
46 citations
TL;DR: Unprotected receptive anal intercourse (URAI) was associated with identifying as gay, being younger and having had an HIV test in the past 6 months, and perceptions of being low risk to acquire or transmit HIV infection were paradoxically associated with higher likelihood of URAI.
Abstract: We conducted a respondent-driven sampling survey (N = 215) to characterize correlates of risk for HIV infection among gay and bisexual men in Kampala, Uganda. We used RDSAT software to produce population estimates for measures and created exportable weights for multivariable analysis. Overall, 60.5% of gay/bi men identify as gay and 39.5% as bisexual; 91.6% are Ugandans. Unprotected receptive anal intercourse (URAI) was associated with identifying as gay, being younger and having had an HIV test in the past 6 months. Perceptions of being low risk to acquire or transmit HIV infection were paradoxically associated with higher likelihood of URAI. Programs to address risk of HIV infection among gay and bisexual men in Kampala need to address perceptions of risk among gay identified men.
41 citations
TL;DR: Declining immunity in the study population appeared to be the primary factor underlying decreased efficacy of amodiaquine plus sulfadoxine-pyrimethamine, and with improved malaria-control efforts, decreasing immunity may unmask resistance to partially efficacious drugs.
Abstract: Background. Improved control efforts are reducing the burden of malaria in Africa but may result in decreased antimalarial immunity. Methods. A cohort of 129 children aged 1-10 years in Kampala, Uganda, were treated with amodiaquine plus sulfadoxine-pyrimethamine for 396 episodes of uncomplicated malaria over a 29-month period as part of a longitudinal clinical trial. Results. The risk of treatment failure increased over the course of the study from 5% to 21% (hazard ratio [HR], 2.4 per year [95% confidence interval {CI}, 1.3-4.3]). Parasite genetic polymorphisms were associated with an increased risk of failure, but their prevalence did not change over time. Three markers of antimalarial immunity were associated with a decreased risk of treatment failure: increased age (HR, 0.5 per 5-year increase [95% CI, 0.2-1.2]), living in an area of higher malaria incidence (HR, 0.26 [95% CI, 0.11-0.64]), and recent asymptomatic parasitemia (HR, 0.06 [95% CI, 0.01-0.36]). In multivariate analysis, adjustment for recent asymptomatic parasitemia, but not parasite polymorphisms, removed the association between calendar time and the risk of treatment failure (HR, 1.5 per year [95% CI, 0.7-3.4]), suggesting that worsening treatment efficacy was best explained by decreasing host immunity. Conclusion. Declining immunity in our study population appeared to be the primary factor underlying decreased efficacy of amodiaquine plus sulfadoxine-pyrimethamine. With improved malaria-control efforts, decreasing immunity may unmask resistance to partially efficacious drugs.
36 citations
TL;DR: HCT for hospitalised children and their caretakers in Mulago teaching hospital in Uganda was introduced to assess its feasibility and to identify opportunities for HIV diagnosis and appropriate treatment.
Abstract: Summary objectives Early diagnosis of HIV-infected children remains a major challenge in Africa. Children who are hospitalised represent an opportunity for HIV diagnosis and appropriate treatment. We introduced HIV Counselling and Testing (HCT) for hospitalised children and their caretakers in Mulago teaching hospital in Uganda to assess its feasibility. methods We analysed routine program data for children and caretakers who were tested between February 2005 and February 2008 to assess the proportion of children and caretakers who were HIVinfected. We also assessed the level of immune suppression (CD4 percentage) in a subset of HIV infected children tested between January 2007 and December 2007. results Caretakers agreed to HIV testing for 8990 (92.8%) of the 9687 children who were offered HIV testing. Among the caretakers, 89.8% agreed to be tested. At the time of hospitalization, 41.3% of the caretakers had previously tested for HIV. Although 313 parents (mothers and fathers) reported that they had previously tested HIV positive, only 113 (36.3%) of these had tested their children prior to hospitalization. Overall HIV prevalence among caretakers was 16.7%. HIV prevalence among children was 12.4%, highest on the nutrition ward (30.8%). Of those children who underwent CD4 counts, 56.4% had a CD4 percentage of <20%. conclusion HCT for hospitalized children and their caretakers identified a significant number of HIV infected children and caretakers. More than half of the children had advanced HIV disease. More intensive efforts are needed to ensure earlier diagnosis and linkage to care for HIV infected children.
34 citations
TL;DR: This study confirms lopinavir/ ritonavir-based second-line regimen but with a high rate of toxicities, as a safe and effective treatment after failing a first line NNRTI based regimen.
Abstract: Objective: To evaluate the safety and virological response to lopinavir/ritonavir containing second-line therapy after failing a first line nonnucleoside reverse transcriptase inhibitor NNRTI) based regimen. Design. Prospective 36 months cohort study of patients switched to zidovudine/stavudine plusdidanosine plus lopinavir/ritonavir capsules as second-line regimen. Methodology. Structured interview medical examination and laboratory assessment performed every 6 months. Results. We enrolled 40 patients; 1 died and 3 were lost to follow-up. Median CD4+count at baseline was 108cell/microL median log viral load was 4.8 copies/mL. Sixteen (40%) patients had baseline genotypic resistant test 14 (87%) had lamivudine resistance mutations and all had NNRTIs resistance mutations. At month 36 82% of the patients achieved viral suppression (<400copies/mL) and the median increase in CD4+count was 214 cell/microL (interquartile range: 128-295). Twenty-five patients (62%) experienced at least one adverse event. Conclusions. Our study confirms lopinavir/ritonavir-based second-line regimen but with a high rate of toxicities.
33 citations
TL;DR: Both AL and DP were safe and well tolerated for the treatment of uncomplicated malaria in young HIV-infected and uninfected children.
Abstract: Background: Artemisinin combination therapy has become the standard of care for uncomplicated malaria in most of Africa. However, there is limited data on the safety and tolerability of these drugs, especially in young children and patients co-infected with HIV. Methods: A longitudinal, randomized controlled trial was conducted in a cohort of HIV-infected and uninfected children aged 4-22 months in Tororo, Uganda. Participants were randomized to treatment with artemetherlumefantrine (AL) or dihydroartemisinin-piperaquine (DP) upon diagnosis of their first episode of uncomplicated malaria and received the same regimen for all subsequent episodes. Participants were actively monitored for adverse events for 28 days and then passively for up to 63 days after treatment. This study was registered in ClinicalTrials.gov (registration # NCT00527800). Results: A total of 122 children were randomized to AL and 124 to DP, resulting in 412 and 425 treatments, respectively. Most adverse events were rare, with only cough, diarrhoea, vomiting, and anaemia occurring in more than 1% of treatments. There were no differences in the risk of these events between treatment groups. Younger age was associated with an increased risk of diarrhoea in both the AL and DP treatment arms. Retreatment for malaria within 17-28 days was associated with an increased risk of vomiting in the DP treatment arm (HR = 6.47, 95% CI 2.31-18.1, p < 0.001). There was no increase in the risk of diarrhoea or vomiting for children who were HIV-infected or on concomitant therapy with antiretrovirals or trimethoprim-sulphamethoxazole prophylaxis. Conclusion: Both AL and DP were safe and well tolerated for the treatment of uncomplicated malaria in young HIV-infected and uninfected children.
Journal Article•
TL;DR: Key strategies to optimize HIV treatment outcomes include scaling up HIV testing to identify all in need of HIV treatment, strengthening the links between HIV diagnosis and comprehensive HIV/AIDS care, and timely initiation of antiretroviral therapy.
Abstract: Although the availability of antiretroviral therapy has increased rapidly to reach over three million people in low- and middle-income countries, coverage remains low as only 31% of people in need were receiving antiretroviral therapy in sub-Saharan Africa. Antiretroviral therapy scale-up needs to continue to grow exponentially to meet the need for universal access and keep pace with or exceed the new HIV infections. This calls for strategies that will have the greatest impact on the reduction of opportunistic infections, toxicities, and early mortality after antiretroviral therapy initiation as well improve adherence, clinical, immunological, and virologic responses, patient retention in antiretroviral therapy programs, and overall quality of life of people living with HIV/AIDS. Expanding antiretroviral therapy to all those eligible requires evidence-based decisions about how, when, and where expansion should occur. In this article we highlight some of the strategies that have optimized HIV treatment outcomes within the constraints of limited resources in sub-Saharan Africa. Key strategies to optimize HIV treatment outcomes include, i) scaling up HIV testing to identify all in need of HIV treatment, ii) strengthening the links between HIV diagnosis and comprehensive HIV/AIDS care, iii) timely initiation of antiretroviral therapy, iv) optimal diagnosis and treatment of opportunistic infections and comorbidities, v) investing in laboratory tests to support clinical monitoring of patients on antiretroviral therapy, vi) maximizing adherence to antiretroviral medication and retention of patients in HIV/AIDS care, viii) improving the health infrastructure, and increasing the human resources to handle the growing numbers of people in need of HIV treatment.
TL;DR: Differences in activation between naive and memory T cells in HIV-infected Ugandan children are explored and PD-1 expression on CD8(+) T cells is assessed as a measure of immune dysfunction.
Abstract: T cell activation is an important mechanism in HIV-associated immune depletion. We have previously demonstrated an association between the hyperactivation of CD4+ and CD8+ T cells and low CD4 status in HIV-infected Ugandan children. In this study, we explore differences in activation between naive and memory T cells in HIV-infected Ugandan children. A significant correlation between CD4- and CD8-mediated immune activation and CD4 status was observed only in the memory T cells. Antiretroviral (ART) untreated and treated HIV-positive and HIV-negative children displayed similar profiles of activation and distribution within the CD4+ naive T cells. In contrast, significantly higher immune activation of the memory CD4+ T cell subset was seen in ART-untreated children when compared to ART-treated or HIV-negative children. ART-mediated viral suppression led to the correction of CD4+ immune activation to levels seen in uninfected children but did not increase the size of the memory CD4+ T cell population...
TL;DR: Is well known at a biological and health systems level, but often ignored.
Abstract: This editorial focuses on the biological interaction between malaria and HIV. It states that the evidence for a biological interaction in people who are co-infected has grown but operational programs for malaria and HIV/AIDS continue to be planned separately despite the substantial impact on one another. It concludes that it is time for the development of a comprehensive operational research and policy strategy to tackle key knowledge gaps regarding malaria and HIV co-infection.
TL;DR: The data suggest that significant decreases in T cell activation accompany CD4 recovery in ART-treated HIV-infected African children, to levels that approach but do not reach those of uninfected children.