Adherence to a Six-Dose Regimen of Artemether-Lumefantrine for Treatment of Uncomplicated Plasmodium Falciparum Malaria in Uganda.

Measuring baseline levels of adherence and identifying risk factors for non-adherence are important steps before the introduction of new antimalarials. In Mbarara in southwestern Uganda, we assessed adherence to artemether-lumefantrine (Coartem) in its latest World Health Organization blister formulation. Patients with uncomplicated Plasmodium falciparum malaria were prescribed artemether-lumefantrine and received an explanation of how to take the following five doses at home. A tablet count was made and a questionnaire was completed during a home visit. Among 210 analyzable patients, 21 (10.0%) were definitely or probably non-adherent, whereas 189 (90.0%) were probably adherent. Age group was not associated with adherence. Lack of formal education was the only factor associated with non-adherence after controlling for confounders (odds ratio = 3.1, 95% confidence interval [CI] = 1.1-9.7). Mean lumefantrine blood levels were lower among non-adherent (n = 16) (2.76 microg/mL, 95% CI = 1.06-4.45) than among adherent (n = 171) (3.19 microg/mL, 95% CI = 2.84-3.54) patients, but this difference was not statistically significant. The high adherence to artemether-lumefantrine found in our study suggest that this drug is likely to be very effective in Mbarara provided that patients receive clear dosage explanations

Circulating B-lymphocytes as potential biomarkers of tuberculosis infection activity.

Accurate biomarkers of Mycobacterium tuberculosis infection activity would significantly improve early diagnosis, treatment and management of M. tuberculosis infection. We hypothesised that circulating B-lymphocytes may be useful biomarkers of tuberculosis (TB) infection status in highly TB-endemic settings. Ex-vivo and in-vitro mycobacteria-specific B-cell ELISPOT assays were used to examine the plasmablast (PB) and memory B-cell (MBC) responses in the peripheral blood of adult, healthy, community controls (n = 151) and of active TB patients (n = 48) living in Uganda. Frequencies of mycobacteria-specific PBs were markedly higher in active TB patients compared to healthy controls, and, conversely, MBCs were markedly higher in the healthy controls compared to active TB patients. In addition, the community controls with evidence of latent TB infection had higher peripheral blood PB and MBC responses than those without evidence of TB infection. These data demonstrate that peripheral blood B-cell responses are differentially modulated during latent and active M. tuberculosis infection, and suggest that the PB to MBC ratio may be a useful biomarker of TB infection activity

Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.

BACKGROUND: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data. METHODS: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa. RESULTS: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001). CONCLUSION: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination

The general population cohort in rural south-western Uganda: a platform for communicable and non-communicable disease studies.

The General Population Cohort (GPC) was set up in 1989 to examine trends in HIV prevalence and incidence, and their determinants in rural south-western Uganda. Recently, the research questions have included the epidemiology and genetics of communicable and non-communicable diseases (NCDs) to address the limited data on the burden and risk factors for NCDs in sub-Saharan Africa. The cohort comprises all residents (52% aged ≥13years, men and women in equal proportions) within one-half of a rural sub-county, residing in scattered houses, and largely farmers of three major ethnic groups. Data collected through annual surveys include; mapping for spatial analysis and participant location; census for individual socio-demographic and household socioeconomic status assessment; and a medical survey for health, lifestyle and biophysical and blood measurements to ascertain disease outcomes and risk factors for selected participants. This cohort offers a rich platform to investigate the interplay between communicable diseases and NCDs. There is robust infrastructure for data management, sample processing and storage, and diverse expertise in epidemiology, social and basic sciences. For any data access enquiries you may contact the director, MRC/UVRI, Uganda Research Unit on AIDS by email to [email protected] or the corresponding author

The health system burden of chronic disease care: an estimation of provider costs of selected chronic diseases in Uganda.

OBJECTIVE: To explore the chronic disease services in Uganda: their level of utilisation, the total service costs and unit costs per visit. METHODS: Full financial and economic cost data were collected from 12 facilities in two districts, from the provider's perspective. A combination of ingredients-based and step-down allocation costing approaches was used. The diseases under study were diabetes, hypertension, chronic obstructive pulmonary disease (COPD), epilepsy and HIV infection. Data were collected through a review of facility records, direct observation and structured interviews with health workers. RESULTS: Provision of chronic care services was concentrated at higher-level facilities. Excluding drugs, the total costs for NCD care fell below 2% of total facility costs. Unit costs per visit varied widely, both across different levels of the health system, and between facilities of the same level. This variability was driven by differences in clinical and drug prescribing practices. CONCLUSION: Most patients reported directly to higher-level facilities, bypassing nearby peripheral facilities. NCD services in Uganda are underfunded particularly at peripheral facilities. There is a need to estimate the budget impact of improving NCD care and to standardise treatment guidelines

Effect of HSV-2 on population-level trends in HIV incidence in Uganda between 1990 and 2007.

OBJECTIVE: To assess the long-term effects of population-level HSV-2 infection on HIV incidence. METHODS: Data from a population-based cohort in south-western Uganda were used to estimate HIV incidence from 1990 to 2007. Stored blood samples were tested for HSV-2, and the impact of HSV-2 prevalence and incidence on HIV incidence was estimated by calculating population attributable fractions (PAFs). The association between population-level annual HIV incidence and annual HSV-2 incidence/prevalence was analysed using linear regression. RESULTS: HIV incidence declined over time among men, from 8.72/1000 person-years (pyr) in 1990 to 4.85/1000 pyr in 2007 (P-trend <0.001). In contrast, there was no decline in HIV incidence among women (4.86/1000 pyr in 1990 to 6.74/1000 pyr in 2007, P-trend = 0.18). PAFs of incident HIV attributable to HSV-2 were high (60% in males; 70% in females). There was no evidence of an association between long-term trends in HIV incidence and HSV-2 prevalence or incidence. CONCLUSION: Assuming a causal relationship, a substantial proportion of new HIV infections in this population are attributable to HSV-2. The study did not find an effect of HSV-2 prevalence/incidence on trends in HIV incidence. HIV incidence did not vary much during the study period. This may partly explain the lack of association

Effect of isoniazid preventive therapy on immune responses to mycobacterium tuberculosis: an open label randomised, controlled, exploratory study.

BACKGROUND: With the renewed emphasis to implement isoniazid preventive therapy (IPT) in Sub-Saharan Africa, we investigated the effect of IPT on immunological profiles among household contacts with latent tuberculosis. METHODS: Household contacts of confirmed tuberculosis patients were tested for latent tuberculosis using the QuantiFERON®-TB Gold In-Tube (QFN) assay and tuberculin skin test (TST). HIV negative contacts aged above 5 years, positive to both QFN and TST, were randomly assigned to IPT and monthly visits or monthly visits only. QFN culture supernatants from enrolment and six months' follow-up were analysed for M.tb-specific Th1, Th2, Th17, and regulatory cytokines by Luminex assay, and for M.tb-specific IgG antibody concentrations by ELISA. Effects of IPT were assessed as the net cytokine and antibody production at the end of six months. RESULTS: Sixteen percent of contacts investigated (47/291) were randomised to IPT (n = 24) or no IPT (n = 23). After adjusting for baseline cytokine or antibody responses, and for presence of a BCG scar, IPT (compared to no IPT) resulted in a relative decline in M.tb-specific production of IFN gamma (adjusted mean difference at the end of six months (bootstrap 95% confidence interval (CI), p-value) -1488.6 pg/ml ((-2682.5, -294.8), p = 0.01), and IL- 2 (-213.1 pg/ml (-419.2, -7.0), p = 0.04). A similar decline was found in anti-CFP-10 antibody levels (adjusted geometric mean ratio (bootstrap 95% CI), p-value) 0.58 ((0.35, 0.98), p = 0.04). We found no effect on M.tb-specific Th2 or regulatory or Th17 cytokine responses, or on antibody concentrations to PPD and ESAT-6. CONCLUSIONS: IPT led to a decrease in Th1 cytokine production, and also in the anti CFP-10 antibody concentration. This could be secondary to a reduction in mycobacterial burden or as a possible direct effect of isoniazid induced T cell apoptosis, and may have implications for protective immunity following IPT in tuberculosis-endemic countries. TRIAL REGISTRATION: ISRCTN registry, ISRCTN15705625. Registered on 30(th) September 2015

Readiness of Ugandan health services for the management of outpatients with chronic diseases.

OBJECTIVE: Traditionally, health systems in sub-Saharan Africa have focused on acute conditions. Few data exist on the readiness of African health facilities (HFs) to address the growing burden of chronic diseases (CDs), specifically chronic, non-communicable diseases (NCDs). METHODS: A stratified random sample of 28 urban and rural Ugandan HFs was surveyed to document the burden of selected CDs by analysing the service statistics, service availability and service readiness using a modified WHO Service Availability and Readiness Assessment questionnaire. Knowledge, skills and practice in the management of CDs of 222 health workers were assessed through a self-completed questionnaire. RESULTS: Among adult outpatient visits at hospitals, 33% were for CDs including HIV vs. 14% and 4% at medium-sized and small health centres, respectively. Many HFs lacked guidelines, diagnostic equipment and essential medicines for the primary management of CDs; training and reporting systems were weak. Lower-level facilities routinely referred patients with hypertension and diabetes. HIV services accounted for most CD visits and were stronger than NCD services. Systems were weaker in lower-level HFs. Non-doctor clinicians and nurses lacked knowledge and experience in NCD care. CONCLUSION: Compared with higher level HFs, lower-level ones are less prepared and little used for CD care. Health systems in Uganda, particularly lower-level HFs, urgently need improvement in managing common NCDs to cope with the growing burden. This should include the provision of standard guidelines, essential diagnostic equipment and drugs, training of health workers, supportive supervision and improved referral systems. Substantially better HIV basic service readiness demonstrates that improved NCD care is feasible

Explaining Adherence Success in Sub-Saharan Africa: An Ethnographic Study

Background: Individuals living with HIV/AIDS in sub-Saharan Africa generally take more than 90% of prescribed doses of antiretroviral therapy (ART). This number exceeds the levels of adherence observed in North America and dispels early scale-up concerns that adherence would be inadequate in settings of extreme poverty. This paper offers an explanation and theoretical model of ART adherence success based on the results of an ethnographic study in three sub-Saharan African countries. Methods and Findings: Determinants of ART adherence for HIV-infected persons in sub-Saharan Africa were examined with ethnographic research methods. 414 in-person interviews were carried out with 252 persons taking ART, their treatment partners, and health care professionals at HIV treatment sites in Jos, Nigeria; Dar es Salaam, Tanzania; and Mbarara, Uganda. 136 field observations of clinic activities were also conducted. Data were examined using category construction and interpretive approaches to analysis. Findings indicate that individuals taking ART routinely overcome economic obstacles to ART adherence through a number of deliberate strategies aimed at prioritizing adherence: borrowing and “begging” transport funds, making “impossible choices” to allocate resources in favor of treatment, and “doing without.” Prioritization of adherence is accomplished through resources and help made available by treatment partners, other family members and friends, and health care providers. Helpers expect adherence and make their expectations known, creating a responsibility on the part of patients to adhere. Patients adhere to promote good will on the part of helpers, thereby ensuring help will be available when future needs arise. Conclusion: Adherence success in sub-Saharan Africa can be explained as a means of fulfilling social responsibilities and thus preserving social capital in essential relationships

Linkage to HIV care after home-based HIV counselling and testing in sub-Saharan Africa: A systematic review.

Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA) but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA. Five databases were searched for studies published between 1(st) January 2000 and 19(th) August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines. 14 studies from six countries met the eligibility criteria; 9 used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic, and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8%-9.8%] to 99.1% (95% CI, 96.9%-99.9%). Linkage was generally lower (&lt;33%) if HBHCT was followed by referral only, and higher (&gt;80%) if additional strategies were used. Only 1 study assessed linkage by means of a randomised trial. 5 studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36%-57.9%) to 94.9% (95% CI, 91.3%-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting, and the key variable definitions. Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials. This article is protected by copyright. All rights reserved