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1.
Nat Commun ; 12(1): 2635, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976132

RESUMO

The scale-up of malaria control efforts has led to marked reductions in malaria burden over the past twenty years, but progress has slowed. Implementation of indoor residual spraying (IRS) of insecticide, a proven vector control intervention, has been limited and difficult to sustain partly because questions remain on its added impact over widely accepted interventions such as bed nets. Using data from 14 enhanced surveillance health facilities in Uganda, a country with high bed net coverage yet high malaria burden, we estimate the impact of starting and stopping IRS on changes in malaria incidence. We show that stopping IRS was associated with a 5-fold increase in malaria incidence within 10 months, but reinstating IRS was associated with an over 5-fold decrease within 8 months. In areas where IRS was initiated and sustained, malaria incidence dropped by 85% after year 4. IRS could play a critical role in achieving global malaria targets, particularly in areas where progress has stalled.

2.
PLoS Med ; 18(5): e1003630, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33945526

RESUMO

BACKGROUND: Frequent retesting for HIV among persons at increased risk of HIV infection is critical to early HIV diagnosis of persons and delivery of combination HIV prevention services. There are few evidence-based interventions for promoting frequent retesting for HIV. We sought to determine the effectiveness of financial incentives and deposit contracts in promoting quarterly HIV retesting among adults at increased risk of HIV. METHODS AND FINDINGS: In peri-urban Ugandan communities from October to December 2018, we randomized HIV-negative adults with self-reported risk to 1 of 3 strategies to promote HIV retesting: (1) no incentive; (2) cash incentives (US$7) for retesting at 3 and 6 months (total US$14); or (3) deposit contracts: participants could voluntarily deposit US$6 at baseline and at 3 months that would be returned with interest (total US$7) upon retesting at 3 and 6 months (total US$14) or lost if participants failed to retest. The primary outcome was retesting for HIV at both 3 and 6 months. Of 1,482 persons screened for study eligibility following community-based recruitment, 524 participants were randomized to either no incentive (N = 180), incentives (N = 172), or deposit contracts (N = 172): median age was 25 years (IQR: 22 to 30), 44% were women, and median weekly income was US$13.60 (IQR: US$8.16 to US$21.76). Among participants randomized to deposit contracts, 24/172 (14%) made a baseline deposit, and 2/172 (1%) made a 3-month deposit. In intent-to-treat analyses, HIV retesting at both 3 and 6 months was significantly higher in the incentive arm (89/172 [52%]) than either the control arm (33/180 [18%], odds ratio (OR) 4.8, 95% CI: 3.0 to 7.7, p < 0.001) or the deposit contract arm (28/172 [16%], OR 5.5, 95% CI: 3.3 to 9.1, p < 0.001). Among those in the deposit contract arm who made a baseline deposit, 20/24 (83%) retested at 3 months; 11/24 (46%) retested at both 3 and 6 months. Among 282 participants who retested for HIV during the trial, three (1%; 95%CI: 0.2 to 3%) seroconverted: one in the incentive group and two in the control group. Study limitations include measurement of retesting at the clinic where baseline enrollment occurred, only offering clinic-based (rather than community-based) HIV retesting and lack of measurement of retesting after completion of the trial to evaluate sustained retesting behavior. CONCLUSIONS: Offering financial incentives to high-risk adults in Uganda resulted in significantly higher HIV retesting. Deposit contracts had low uptake and overall did not increase retesting. As part of efforts to increase early diagnosis of HIV among high-risk populations, strategic use of incentives to promote retesting should receive greater consideration by HIV programs. TRIAL REGISTRATION: clinicaltrials.gov: NCT02890459.

3.
AIDS ; 35(6): 911-919, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33821821

RESUMO

OBJECTIVE: Sub-Saharan Africa faces twin epidemics of HIV and noncommunicable diseases including hypertension. Integrating hypertension care into chronic HIV care is a global priority, but cost estimates are lacking. In the SEARCH Study, we performed population-level HIV/hypertension testing, and offered integrated streamlined chronic care. Here, we estimate costs for integrated hypertension/HIV care for HIV-positive individuals, and costs for hypertension care for HIV-negative individuals in the same clinics. DESIGN: Microcosting analysis of healthcare expenditures within Ugandan HIV clinics. METHODS: SEARCH (NCT: 01864603) conducted community health campaigns for diagnosis and linkage to care for both HIV and hypertension. HIV-positive patients received hypertension/HIV care jointly including blood pressure monitoring and medications; HIV-negative patients received hypertension care at the same clinics. Within 10 Ugandan study communities during 2015-2016, we estimated incremental annual per-patient hypertension care costs using micro-costing techniques, time-and-motion personnel studies, and administrative/clinical records review. RESULTS: Overall, 70 HIV-positive and 2355 HIV-negative participants received hypertension care. For HIV-positive participants, average incremental cost of hypertension care was $6.29 per person per year, a 2.1% marginal increase over prior estimates for HIV care alone. For HIV-negative participants, hypertension care cost $11.39 per person per year, a 3.8% marginal increase over HIV care costs. Key costs for HIV-positive patients included hypertension medications ($6.19 per patient per year; 98% of total) and laboratory testing ($0.10 per patient per year; 2%). Key costs for HIV-negative patients included medications ($5.09 per patient per year; 45%) and clinic staff salaries ($3.66 per patient per year; 32%). CONCLUSION: For only 2-4% estimated additional costs, hypertension care was added to HIV care, and also expanded to all HIV-negative patients in prototypic Ugandan clinics, demonstrating substantial synergy. Our results should encourage accelerated scale-up of hypertension care into existing clinics.


Assuntos
Infecções por HIV , Hipertensão , Doenças não Transmissíveis , Instituições de Assistência Ambulatorial , Infecções por HIV/complicações , Infecções por HIV/terapia , Humanos , Hipertensão/epidemiologia , Hipertensão/terapia , População Rural
4.
Malar J ; 20(1): 187, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858434

RESUMO

BACKGROUND: Uganda's clinical management guidelines recommend a malaria laboratory test in all patients presenting with fever (history of fever or an axillary temperature ≥ 37.5 °C), and only those with a positive test receive anti-malarial treatment. However, the current practice in areas with declining malaria transmission remains unknown. This study assessed the clinicians' diagnostic practices, the factors associated with recommending a test, and the risk of missing a malaria case when a test is not recommended in patients presenting with fever in Kampala, an area of declining malaria transmission in Uganda. METHODS: Between January and March 2020, 383 participants aged ≥ 12 years and presenting to Kisenyi Health Centre IV in Kampala district with fever were enrolled in the study. A questionnaire was administered during exit interviews, routine diagnostic practices were recorded from participant clinical notes, and a research blood slide was obtained for later reading. RESULTS: Of the enrolled participants, 356 (93%) had a malaria diagnostic test recommended by the clinician. Factors associated with increasing prevalence of having a test recommended included; history of overnight travel (adjusted prevalence ratio [aPR] 1.07, 95% confidence interval [CI] 1.02-1.13, p = 0.011), being married (aPR = 1.07, 95% CI 1.01-1.13, p = 0.022), and having tertiary education (aPR = 1.09 95% CI 1.01-1.17, p = 0.031). Among the 27 participants where a malaria diagnostic test was not recommended, 4 (14.8%) had a positive study smear. CONCLUSION: Despite having significant declines in malaria transmission in Kampala in the last decade, clinicians at the study health facility highly adhered to the clinical management guidelines, recommending a malaria test in almost all patients presenting with fever. However, a significant proportion of malaria cases was missed when a test was not recommended. These results highlight the importance of laboratory testing for malaria in all patients who present with fevers and live in endemic settings even when the transmission has significantly declined.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33770065

RESUMO

BACKGROUND: The SEARCH study provided community-based HIV and multi-disease testing and antiretroviral therapy (ART) to 32 communities in East Africa and reported no statistically significant difference in three-year HIV incidence. We used mathematical modelling to estimate the effect of control arm viral suppression and community mixing on SEARCH trial outcomes. SETTING: Uganda and Kenya. METHODS: Using the individual-based HIV modeling software EMOD-HIV, we configured a new model of SEARCH communities. The model was parameterized using demographic, HIV prevalence, male circumcision, and viral suppression data, and calibrated to HIV prevalence, ART coverage, and population size. Using assumptions about ART scale-up in the control arm, degree of community mixing, and effect of baseline testing, we estimated comparative HIV incidence under multiple scenarios. RESULTS: Prior to the trial results, we predicted that SEARCH would report a 4-40% reduction between arms, depending on control arm ART linkage rates and community mixing. With universal baseline testing followed by rapidly expanded ART eligibility and uptake, modelled effect sizes were smaller than the study was powered to detect. Using interim viral suppression data, we estimated three-year cumulative incidence would have been reduced by up to 27% in the control arm and 43% in the intervention arm compared to a counterfactual without universal baseline testing. CONCLUSIONS: Our model suggests that the active control arm substantially reduced expected effect size and power of the SEARCH study. However, compared to a counterfactual "true control" without increased ART linkage due to baseline testing, SEARCH reduced HIV incidence by up to 43%.

6.
Clin Infect Dis ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783495

RESUMO

BACKGROUND: We tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing. METHODS: In the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years. Comparisons between study arms used a cluster-level analysis with survival estimates from Kaplan-Meier; estimates of ART start among ART-naive persons treated death as a competing risk. RESULTS: Among 13 266 adults with HIV, 2973 (22.4%) had CD4 ≤ 350/uL. Of these, 33% were new diagnoses, and 10% were diagnosed but ART-naive. Men with HIV were almost twice as likely as women with HIV to have CD4 ≤ 350/uL and be untreated (15% vs 8%, respectively). Streamlined care reduced mortality by 28% versus control (risk ratio [RR] = 0.72; 95% confidence interval [CI]: .56, .93; P = .02). Despite eligibility in both arms, persons with CD4 ≤ 350/uL started ART faster under streamlined care versus control (76% vs 43% by 12 months, respectively; P < .001). Mortality was reduced substantially more among men (RR = 0.61; 95% CI: .43, .86; P = .01) than among women (RR = 0.90; 95% CI: .62, 1.32; P = .58). CONCLUSIONS: After population-based HIV testing, streamlined care reduced population-level mortality among persons with HIV and CD4 ≤ 350/uL, particularly among men. Streamlined HIV care models may play a key role in global efforts to reduce AIDS deaths.

7.
Health Res Policy Syst ; 19(1): 14, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557828

RESUMO

BACKGROUND: In Uganda and other resource-poor countries, relevant research findings face a tortuous path to translation into policy and routine practice. Implementation science (ImSc) research could facilitate faster translation. Presently it is unclear what ImSc research capacity and possible training needs exist among Ugandan researchers. To assess both components, we interviewed potential trainees in Kampala, Uganda. METHODS: We used a cross-sectional design to survey potential ImSc trainees who had some research training and involvement in generating or utilizing research. Using a questionnaire, we documented eligibility for ImSc training, knowledge and interest in training, existing self-assessed confidence in initiating clinical research (SCICR) and self-assessed confidence in initiating ImSc research (SCIIR), availability for training and preferred modes of training. We developed scores from the Likert scales and used descriptive statistics, logistic regression and ordinal logistic regression to evaluate predictors of SCIIR. RESULTS: Between November 2016 and April 2017, we interviewed 190 participants; 60% were men, with a median age of 37 years. Among participants, 33% comprised faculty, 37% were graduate students and 30% were project staff. The majority of respondents knew about ImSc (73%) and were research-trained (80%). Only 9% reported any ImSc-related training. Previous ImSc training was associated with higher odds of a SCIIR score ≥ 75th percentile. Previous ImSc training compared to not having any training was associated with higher odds of reporting abilities in behaviour change theory integration (OR: 3.3, 95% CI: 1.3-8.5, p = 0.01) and framework use in intervention design and implementation (OR: 2.9, 95% CI: 1.1-7.4, p = 0.03), accounting for age, sex and current employment. In addition, 53% of participants preferred in-person (face-to-face) short ImSc courses compared to a year-long training, while 33% preferred online courses. Participants reported median availability of 6 hours per week (IQR: 4, 10) for training. CONCLUSION: Most participants had some understanding of ImSc research, had research training and were interested in ImSc training. Those with previous ImSc training had better skills and SCIIR, compared to those without previous training. A hybrid approach with modular face-to-face training and online sessions would suit the preferences of most potential trainees.

8.
Malar J ; 20(1): 111, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632228

RESUMO

BACKGROUND: Malaria is one of the most serious infectious diseases in the world. The malaria burden is greatly affected by human immunity, and immune responses vary between populations. Genetic diversity in KIR and HLA-C genes, which are important in immunity to infectious diseases, is likely to play a role in this heterogeneity. Several studies have shown that KIR and HLA-C genes influence the immune response to viral infections, but few studies have examined the role of KIR and HLA-C in malaria infection, and these have used low-resolution genotyping. The aim of this study was to determine whether genetic variation in KIR and their HLA-C ligands differ in Ugandan populations with historically varied malaria transmission intensity using more comprehensive genotyping approaches. METHODS: High throughput multiplex quantitative real-time PCR method was used to genotype KIR genetic variants and copy number variation and a high-throughput real-time PCR method was developed to genotype HLA-C1 and C2 allotypes for 1344 participants, aged 6 months to 10 years, enrolled from Ugandan populations with historically high (Tororo District), medium (Jinja District) and low (Kanungu District) malaria transmission intensity. RESULTS: The prevalence of KIR3DS1, KIR2DL5, KIR2DS5, and KIR2DS1 genes was significantly lower in populations from Kanungu compared to Tororo (7.6 vs 13.2%: p = 0.006, 57.2 vs 66.4%: p = 0.005, 33.2 vs 46.6%: p < 0.001, and 19.7 vs 26.7%: p = 0.014, respectively) or Jinja (7.6 vs 18.1%: p < 0.001, 57.2 vs 63.8%: p = 0.048, 33.2 vs 43.5%: p = 0.002, and 19.7 vs 30.4%: p < 0.001, respectively). The prevalence of homozygous HLA-C2 was significantly higher in populations from Kanungu (31.6%) compared to Jinja (21.4%), p = 0.043, with no significant difference between Kanungu and Tororo (26.7%), p = 0.296. CONCLUSIONS: The KIR3DS1, KIR2DL5, KIR2DS5 and KIR2DS1 genes may partly explain differences in transmission intensity of malaria since these genes have been positively selected for in places with historically high malaria transmission intensity. The high-throughput, multiplex, real-time HLA-C genotyping PCR method developed will be useful in disease-association studies involving large cohorts.

9.
JMIR Mhealth Uhealth ; 9(2): e23737, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33605886

RESUMO

BACKGROUND: Lack of trained health care workers and nonadherence to national guidelines are key barriers to achieving high-quality newborn care in health care facilities in low- and middle-income countries. Traditional didactic approaches addressing these barriers fail to account for high staff turnover rates and result in temporary behavior change. NoviGuide, a clinical decision support software designed to standardize neonatal care through point-of-care assessments, has the potential to align bedside practice to national guidelines in settings lacking subspecialty neonatal providers. OBJECTIVE: This study aims to determine the adaptation, adoption, feasibility, acceptability, and sustainability of NoviGuide and its impact on nurse-midwives' knowledge in a rural hospital in eastern Uganda. METHODS: This mixed methods observational study was guided by the Proctor framework. Experts reviewed the clinical content of NoviGuide to ensure fidelity to Uganda guidelines. We enrolled nurses and midwives providing newborn care at Tororo District Hospital, trained them on NoviGuide use, and followed them for 12 months. We assessed adoption, feasibility, acceptability, and sustainability by analyzing NoviGuide use data, comparing it with maternity registry data and administering the System Usability Scale (SUS) and the Center for Health Care Evaluation Provider Satisfaction Questionnaire. We compared the mean knowledge assessment score at baseline, 6 months, and 12 months using a two-tailed t test. RESULTS: Five Ugandan experts suggested two minor changes to NoviGuide: the inclusion of an unsterile birth environment as an indication for empiric antibiotics and the addition of a reminder to follow-up with newborns with temperatures between 37.7°C and 37.9°C. Of the 19 nurse-midwives enrolled in February 2017, 74% (n=14) completed the follow-up in March 2018. The participants entered a total of 1705 assessments of varying newborn characteristics into NoviGuide throughout the day, evening, and night nursing shifts. The SUS score at the end of the study was very high (93.5, above the average of 68). Participants had a positive perception about NoviGuide, reporting that NoviGuide saved time (mean 5, SD 0) and prevented mistakes (mean 5, SD 0), and that they felt more confident in taking care of newborns when they used NoviGuide (mean 5, SD 0). Participants were highly satisfied with NoviGuide (mean 4.86, SD 0.36), although they lacked medical supplies and materials needed to follow NoviGuide recommendations (mean 3.3, SD 1.22). The participants' knowledge scores improved by a mean change of 3.7 (95% CI 2.6-4.8) at 6 months and 6.7 (95% CI 4.6-8.2) at 12 months (P<.001). CONCLUSIONS: NoviGuide was easily adapted to the Uganda guidelines. Nurse-midwives used NoviGuide frequently and reported high levels of satisfaction despite challenges with medical supplies and high staff turnover. NoviGuide improved knowledge and confidence in newborn care without in-person didactic training. NoviGuide use has the potential to scale up quality newborn care by facilitating adherence to national guidelines.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Hospitais Rurais , Estudos de Viabilidade , Feminino , Hospitais de Distrito , Humanos , Recém-Nascido , Gravidez , Software , Uganda
10.
PLoS One ; 16(2): e0246113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33539400

RESUMO

A 12-dose weekly regimen of rifapentine plus isoniazid (3HP) is recommended for the prevention of active tuberculosis (TB); however, it is unclear whether 3HP should be provided by directly observed therapy (DOT) or self-administered therapy (SAT). In addition, the introduction of patient informed choice between delivery modalities may have a positive impact on factors leading to treatment completion. The authors randomized 252 participants with HIV to a hypothetical scenario of providing preventive therapy by either DOT or an informed choice between DOT and SAT. Out of 104 participants who were randomized to a choice between DOT and SAT, 103 chose therapy by SAT. Participants rated their level of confidence and intention to complete therapy. Compared to those assigned to the DOT scenario, patients assigned to the choice scenario expressed greater confidence and intention to complete preventive therapy. Convenience and travel required to complete 3HP therapy were important factors in deciding between delivery modalities. Those assigned to DOT identified more barriers to completing therapy than those given a choice. Empowering patients to make informed decisions about how they receive TB preventive therapy may improve completion rates.

11.
PLoS One ; 16(2): e0243167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33544717

RESUMO

BACKGROUND: Additional progress towards HIV epidemic control requires understanding who remains at risk of HIV infection in the context of high uptake of universal testing and treatment (UTT). We sought to characterize seroconverters and risk factors in the SEARCH UTT trial (NCT01864603), which achieved high uptake of universal HIV testing and ART coverage in 32 communities of adults (≥15 years) in rural Uganda and Kenya. METHODS: In a pooled cohort of 117,114 individuals with baseline HIV negative test results, we described those who seroconverted within 3 years, calculated gender-specific HIV incidence rates, evaluated adjusted risk ratios (aRR) for seroconversion using multivariable targeted maximum likelihood estimation, and assessed potential infection sources based on self-report. RESULTS: Of 704 seroconverters, 63% were women. Young (15-24 years) men comprised a larger proportion of seroconverters in Western Uganda (18%) than Eastern Uganda (6%) or Kenya (10%). After adjustment for other risk factors, men who were mobile [≥1 month of prior year living outside community] (aRR:1.68; 95%CI:1.09,2.60) or who HIV tested at home vs. health fair (aRR:2.44; 95%CI:1.89,3.23) were more likely to seroconvert. Women who were aged ≤24 years (aRR:1.91; 95%CI:1.27,2.90), mobile (aRR:1.49; 95%CI:1.04,2.11), or reported a prior HIV test (aRR:1.34; 95%CI:1.06,1.70), or alcohol use (aRR:2.07; 95%CI:1.34,3.22) were more likely to seroconvert. Among survey responders (N = 607, 86%), suspected infection source was more likely for women than men to be ≥10 years older (28% versus 8%) or a spouse (51% vs. 31%) and less likely to be transactional sex (10% versus 16%). CONCLUSION: In the context of universal testing and treatment, additional strategies tailored to regional variability are needed to address HIV infection risks of young women, alcohol users, mobile populations, and those engaged in transactional sex to further reduce HIV incidence rates.

12.
PLoS Med ; 18(2): e1003492, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33561143

RESUMO

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP. METHODS AND FINDINGS: During population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (<1,000 c/ml based on available assays) after ART start. Using Poisson regression with cluster-robust standard errors, we compared HIV incidence among PrEP initiators to incidence among propensity score-matched recent historical controls (from the year before PrEP availability) in 8 of the 16 communities, adjusted for risk group. Among 74,541 individuals who tested negative for HIV, 15,632/74,541 (21%) were assessed to be at elevated HIV risk; 5,447/15,632 (35%) initiated PrEP (49% female; 29% 15-24 years; 19% in serodifferent partnerships), of whom 79% engaged in ≥1 follow-up visit and 61% self-reported PrEP adherence at ≥1 visit. Over 7,150 person-years of follow-up, HIV incidence was 0.35 per 100 person-years (95% confidence interval [CI] 0.22-0.49) among PrEP initiators. Among matched controls, HIV incidence was 0.92 per 100 person-years (95% CI 0.49-1.41), corresponding to 74% lower incidence among PrEP initiators compared to matched controls (adjusted incidence rate ratio [aIRR] 0.26, 95% CI 0.09-0.75; p = 0.013). Among women, HIV incidence was 76% lower among PrEP initiators versus matched controls (aIRR 0.24, 95% CI 0.07-0.79; p = 0.019); among men, HIV incidence was 40% lower, but not significantly so (aIRR 0.60, 95% CI 0.12-3.05; p = 0.54). Of 25 participants with incident HIV infection (68% women), 7/25 (28%) reported taking PrEP ≤30 days before HIV diagnosis, and 24/25 (96%) started ART. Of those with repeat HIV RNA after ART start, 18/19 (95%) had <1,000 c/ml. One participant with viral non-suppression was found to have transmitted viral resistance, as well as emtricitabine resistance possibly related to PrEP use. Limitations include the lack of contemporaneous controls to assess HIV incidence without PrEP and that plasma samples were not archived to assess for baseline acute infection. CONCLUSIONS: Population-level offer of PrEP with rapid start and flexible service delivery was associated with 74% lower HIV incidence among PrEP initiators compared to matched recent controls prior to PrEP availability. HIV infections were significantly lower among women who started PrEP. Universal HIV testing with linkage to treatment and prevention, including PrEP, is a promising approach to accelerate reductions in new infections in generalized epidemic settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.

13.
Malar J ; 20(1): 42, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441121

RESUMO

BACKGROUND: Malaria surveillance is critical for monitoring changes in malaria morbidity over time. National Malaria Control Programmes often rely on surrogate measures of malaria incidence, including the test positivity rate (TPR) and total laboratory confirmed cases of malaria (TCM), to monitor trends in malaria morbidity. However, there are limited data on the accuracy of TPR and TCM for predicting temporal changes in malaria incidence, especially in high burden settings. METHODS: This study leveraged data from 5 malaria reference centres (MRCs) located in high burden settings over a 15-month period from November 2018 through January 2020 as part of an enhanced health facility-based surveillance system established in Uganda. Individual level data were collected from all outpatients including demographics, laboratory test results, and village of residence. Estimates of malaria incidence were derived from catchment areas around the MRCs. Temporal relationships between monthly aggregate measures of TPR and TCM relative to estimates of malaria incidence were examined using linear and exponential regression models. RESULTS: A total of 149,739 outpatient visits to the 5 MRCs were recorded. Overall, malaria was suspected in 73.4% of visits, 99.1% of patients with suspected malaria received a diagnostic test, and 69.7% of those tested for malaria were positive. Temporal correlations between monthly measures of TPR and malaria incidence using linear and exponential regression models were relatively poor, with small changes in TPR frequently associated with large changes in malaria incidence. Linear regression models of temporal changes in TCM provided the most parsimonious and accurate predictor of changes in malaria incidence, with adjusted R2 values ranging from 0.81 to 0.98 across the 5 MRCs. However, the slope of the regression lines indicating the change in malaria incidence per unit change in TCM varied from 0.57 to 2.13 across the 5 MRCs, and when combining data across all 5 sites, the R2 value reduced to 0.38. CONCLUSIONS: In high malaria burden areas of Uganda, site-specific temporal changes in TCM had a strong linear relationship with malaria incidence and were a more useful metric than TPR. However, caution should be taken when comparing changes in TCM across sites.

14.
Nat Commun ; 12(1): 132, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420104

RESUMO

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.


Assuntos
Poluentes Ambientais/efeitos adversos , Feto/imunologia , Exposição Materna/efeitos adversos , Sarampo/sangue , Praguicidas/efeitos adversos , Adulto , Anticorpos Antivirais/sangue , Pré-Escolar , Ensaios Clínicos Fase III como Assunto , Feminino , Sangue Fetal/química , Seguimentos , Humanos , Sistema Imunitário/efeitos dos fármacos , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Malária/prevenção & controle , Troca Materno-Fetal/imunologia , Sarampo/imunologia , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Controle de Mosquitos/métodos , Praguicidas/análise , Fenilcarbamatos/efeitos adversos , Fenilcarbamatos/análise , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Malar J ; 20(1): 4, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33386076

RESUMO

BACKGROUND: Rapid diagnostic tests (RDTs) play a key role in malaria case management. The most widely used RDT identifies Plasmodium falciparum based on immunochromatographic recognition of P. falciparum histidine-rich protein 2 (PfHRP2). Deletion of the paralogous pfhrp2 and pfhrp3 genes leads to false-negative PfHRP2-based RDTs, and has been reported in P. falciparum infections from South America and Africa. However, identification of pfhrp2/pfhrp3 deletions has usually been based only on failure to amplify these genes using PCR, without confirmation based on PfHRP2 protein expression, and understanding of the true prevalence of deletions is incomplete. METHODS: Deletions of pfhrp2/pfhrp3 in blood samples were investigated from cross-sectional surveys in 2012-13 in three regions of varied malaria transmission intensity in Uganda. Samples with positive Giemsa-stained thick blood smears, but negative PfHRP2-based RDTs were evaluated by PCR amplification of conserved subunit ribosomal DNA for Plasmodium species, PCR amplification of pfhrp2 and pfhrp3 genes to identify deletions, and bead-based immunoassays for expression of PfHRP2. RESULTS: Of 3516 samples collected in cross-sectional surveys, 1493 (42.5%) had positive blood smears, of which 96 (6.4%) were RDT-negative. Of these 96 RDT-negative samples, P. falciparum DNA was identified by PCR in 56 (58%) and only non-falciparum plasmodial DNA in 40 (42%). In all 56 P. falciparum-positive samples there was a failure to amplify pfhrp2 or pfhrp3: in 25 (45%) pfhrp2 was not amplified, in 39 (70%) pfhrp3 was not amplified, and in 19 (34%) neither gene was amplified. For the 39 P. falciparum-positive, RDT-negative samples available for analysis of protein expression, PfHRP2 was not identified by immunoassay in only four samples (10.3%); these four samples all had failure to amplify both pfhrp2 and pfhrp3 by PCR. Thus, only four of 96 (4.2%) smear-positive, RDT-negative samples had P. falciparum infections with deletion of pfhrp2 and pfhrp3 confirmed by failure to amplify the genes by PCR and lack of expression of PfHRP2 demonstrated by immunoassay. CONCLUSION: False negative RDTs were uncommon. Deletions in pfhrp2 and pfhrp3 explained some of these false negatives, but most false negatives were not due to deletion of the pfhrp2 and pfhrp3 genes.

16.
J Int AIDS Soc ; 23(12): e25647, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33283986

RESUMO

INTRODUCTION: The rollout of antiretroviral therapy (ART) has been associated with reductions in HIV-related stigma, but pathways through which this reduction occurs are poorly understood. In the newer context of universal test and treat (UTT) interventions, where rapid diffusion of ART uptake takes place, there is an opportunity to understand the processes through which HIV-related stigma can decline, and how UTT strategies may precipitate more rapid and widespread changes in stigma. This qualitative study sought to evaluate how a UTT intervention influenced changes in beliefs, attitudes and behaviours related to HIV. METHODS: Longitudinal qualitative in-depth semi-structured interview data were collected within a community-cluster randomized UTT trial, the Sustainable East Africa Research in Community Health (SEARCH) study, annually over three rounds (2014 to 2016) from two cohorts of adults (n = 32 community leaders, and n = 112 community members) in eight rural communities in Uganda and Kenya. Data were inductively analysed to develop new theory for understanding the pathways of stigma decline. RESULTS: We present an emergent theoretical model of pathways through which HIV-related stigma may decline: internalized stigma may be reduced by two processes accelerated through the uptake and successful usage of ART: first, a reduced fear of dying and increased optimism for prolonged and healthy years of life; second, a restoration of perceived social value and fulfilment of subjective role expectations via restored physical strength and productivity. Anticipated stigma may be reduced in response to widespread engagement in HIV testing, leading to an increasing number of HIV status disclosures in a community, "normalizing" disclosure and reducing fears. Improvements in the perceived quality of HIV care lead to people living with HIV (PLHIV) seeking care in nearby facilities, seeing other known community members living with HIV, reducing isolation and facilitating opportunities for social support and "solidarity." Finally, enacted stigma may be reduced in response to the community viewing the healthy bodies of PLHIV successfully engaged in treatment, which lessens the fears that trigger enacted stigma; it becomes no longer socially normative to stigmatize PLHIV. This process may be reinforced through public health messaging and anti-discrimination laws. CONCLUSIONS: Declines in HIV-related stigma appear to underway and explained by social processes accelerated by UTT efforts. Widespread implementation of UTT shows promise for reducing multiple dimensions of stigma, which is critical for improving health outcomes among PLHIV.

17.
Malar J ; 19(1): 445, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267886

RESUMO

BACKGROUND: Accurate measures of malaria incidence are essential to track progress and target high-risk populations. While health management information system (HMIS) data provide counts of malaria cases, quantifying the denominator for incidence using these data is challenging because catchment areas and care-seeking behaviours are not well defined. This study's aim was to estimate malaria incidence using HMIS data by adjusting the population denominator accounting for travel time to the health facility. METHODS: Outpatient data from two public health facilities in Uganda (Kihihi and Nagongera) over a 3-year period (2011-2014) were used to model the relationship between travel time from patient village of residence (available for each individual) to the facility and the relative probability of attendance using Poisson generalized additive models. Outputs from the model were used to generate a weighted population denominator for each health facility and estimate malaria incidence. Among children aged 6 months to 11 years, monthly HMIS-derived incidence estimates, with and without population denominators weighted by probability of attendance, were compared with gold standard measures of malaria incidence measured in prospective cohorts. RESULTS: A total of 48,898 outpatient visits were recorded across the two sites over the study period. HMIS incidence correlated with cohort incidence over time at both study sites (correlation in Kihihi = 0.64, p < 0.001; correlation in Nagongera = 0.34, p = 0.045). HMIS incidence measures with denominators unweighted by probability of attendance underestimated cohort incidence aggregated over the 3 years in Kihihi (0.5 cases per person-year (PPY) vs 1.7 cases PPY) and Nagongera (0.3 cases PPY vs 3.0 cases PPY). HMIS incidence measures with denominators weighted by probability of attendance were closer to cohort incidence, but remained underestimates (1.1 cases PPY in Kihihi and 1.4 cases PPY in Nagongera). CONCLUSIONS: Although malaria incidence measured using HMIS underestimated incidence measured in cohorts, even when adjusting for probability of attendance, HMIS surveillance data are a promising and scalable source for tracking relative changes in malaria incidence over time, particularly when the population denominator can be estimated by incorporating information on village of residence.

18.
Malar J ; 19(1): 449, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272281

RESUMO

BACKGROUND: Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM. METHODS: Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (> 0-20% high powered fields [HPFs] with pigment), or severe past PM (> 20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM. RESULTS: There were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p = 0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p = 0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p < 0.001), but not female infants (aIRR 0.74, 95% CI 0.46-1.20, p = 0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM. CONCLUSION: PM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk. Trial registration ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622.

19.
BMJ Glob Health ; 5(11)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33257417

RESUMO

INTRODUCTION: Interventions informed by behavioural economics, such as planning prompts, have the potential to increase HIV testing at minimal or no cost. Planning prompts have not been previously evaluated for HIV testing uptake. We conducted a randomised clinical trial to evaluate the effectiveness of low-cost planning prompts to promote HIV testing among men. METHODS: We randomised adult men in rural Ugandan parishes to receive a calendar planning prompt that gave them the opportunity to make a plan to get tested for HIV at health campaigns held in their communities. Participants received either a calendar showing the dates when the community health campaign would be held (control group) or a calendar showing the dates and prompting them to select a date and time when they planned to attend (planning prompt group). Participants were not required to select a date and time or to share their selection with study staff. The primary outcome was HIV testing uptake at the community health campaign. RESULTS: Among 2362 participants, 1796 (76%) participants tested for HIV. Men who received a planning prompt were 2.2 percentage points more likely to test than the control group, although the difference was not statistically significant (77.1% vs 74.9%; 95% CI -1.2 to 5.7 percentage points, p=0.20). The planning prompt was more effective among men enrolled ≤40 days before the campaigns (3.6 percentage-point increase in testing; 95% CI -2.9 to 10.1, p=0.27) than among men enrolled >40 days before the campaigns (1.8 percentage-point increase; 95% CI -2.3 to 5.8, p=0.39), although the effects within the subgroups were not significant. CONCLUSION: These findings suggest that planning prompts may be an effective behavioural intervention to promote HIV testing at minimal or no cost. Large-scale studies should further assess the impact and cost-effectiveness of such interventions.

20.
PLoS One ; 15(12): e0244457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382787

RESUMO

BACKGROUND: Plasmodium falciparum histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) are exclusively recommended for malaria diagnosis in Uganda; however, their functionality can be affected by parasite-related factors that have not been investigated in field settings. METHODS: Using a cross-sectional design, we analysed 219 RDT-/microscopy+ and 140 RDT+/microscopy+ dried blood spots obtained from symptomatic children aged 2-10 years from 48 districts in Uganda between 2017 and 2019. We aimed to investigate parasite-related factors contributing to false RDT results by molecular characterization of parasite isolates. ArcGIS software was used to map the geographical distribution of parasites. Statistical analysis was performed using chi-square or Fisher's exact tests, with P ≤ 0.05 indicating significance. Odds ratios (ORs) were used to assess associations, while logistic regression was performed to explore possible factors associated with false RDT results. RESULTS: The presence of parasite DNA was confirmed in 92.5% (332/359) of the blood samples. The levels of agreement between the HRP2 RDT and PCR assay results in the (RDT+/microscopy+) and (RDT-/microscopy+) sample subsets were 97.8% (137/140) and 10.9% (24/219), respectively. Factors associated with false-negative RDT results in the (RDT-/microscopy+) samples were parasite density (<1,000/µl), pfhrp2/3 gene deletion and non-P. falciparum species (aOR 2.65, 95% CI: 1.62-4.38, P = 0.001; aOR 4.4, 95% CI 1.72-13.66, P = 0.004; and aOR 18.65, 95% CI: 5.3-38.7, P = 0.001, respectively). Overall, gene deletion and non-P. falciparum species contributed to 12.3% (24/195) and 19.0% (37/195) of false-negative RDT results, respectively. Of the false-negative RDTs results, 80.0% (156/195) were from subjects with low-density infections (< 25 parasites per 200 WBCs or <1,000/µl). CONCLUSION: This is the first evaluation and report of the contributions of pfhrp2/3 gene deletion, non-P. falciparum species, and low-density infections to false-negative RDT results under field conditions in Uganda. In view of these findings, the use of HRP2 RDTs should be reconsidered; possibly, switching to combination RDTs that target alternative antigens, particularly in affected areas, may be beneficial. Future evaluations should consider larger and more representative surveys covering other regions of Uganda.


Assuntos
Antígenos de Protozoários/isolamento & purificação , Malária Falciparum/diagnóstico , Plasmodium falciparum/isolamento & purificação , Proteínas de Protozoários/isolamento & purificação , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Estudos Transversais , DNA de Protozoário/isolamento & purificação , Teste em Amostras de Sangue Seco/instrumentação , Teste em Amostras de Sangue Seco/estatística & dados numéricos , Monitoramento Epidemiológico , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Masculino , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Reação em Cadeia da Polimerase/estatística & dados numéricos , Prevalência , Proteínas de Protozoários/imunologia , Uganda/epidemiologia
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