Efficacy of Three Antimalarial Regimens for Uncomplicated Plasmodium Falciparum Malaria in Cambodia, 2009 – 2011: A Randomized Control Trial

Background: Antimalarial resistance remains an important public health challenge in Cambodia. The effectiveness of three therapies for uncomplicated Falciparum malaria were evaluated in Oddar Meanchey province in Northern Cambodia from 2009 – 2011.Methods: In this randomized, open-label, parallel group controlled trial, 211 subjects at least 5 years old with uncomplicated Falciparum malaria were treated with directly observed therapy. Over 3 days, 63 received artesunate-mefloquine (AS/MQ), 77 received dihydroartemisinin-piperaquine (DHA/PPQ), and 71 received atovaquone-proguanil (ATQ/PG). Subjects were followed for 42 days or until recurrent parasitemia. Genotyping of msp1, msp2, and glurp among individual parasite isolates distinguished recrudescence from reinfection. Pfmdr1 copy number was measured by real-time PCR and half-maximal parasite inhibitory concentrations (IC50) was measured in vitro by 48-hour isotopic hypoxanthine incorporation assay.Results: The primary outcome of per-protocol PCR-adjusted efficacy at 42 days was analyzed for 190 (90.0%) of the enrolled subjects. PCR-adjusted efficacy (95% confidence interval) at 42 days was 80.6% (70.8 – 90.5%) for AS/MQ, 97.2% (93.3 – 100%) for DHA/PPQ, and 92.9% (86.1 – 99.6%) for ATQ/PG. On day 3, 59.3% remained parasitemic. At baseline, 46.9% had microscopic P. falciparum gametocytemia. Both recurrences in the DHA/PPQ arm lost Pfmdr1 copy number amplification at recrudescence. All four recurrences in the ATQ/PG arm were wild-type for cytochrome bc1. One subject withdrew from the ATQ/PG arm due to drug allergy.Conclusions: This previously unpublished study was conducted at the epicenter of substantial multi-drug resistance that emerged soon thereafter. Occurring early in the national transition from AS/MQ to DHA/PPQ, both DHA/PPQ and ATQ/PG had acceptable efficacy against uncomplicated falciparum malaria. However, efficacy of AS/MQ was only 80% with apparent mefloquine resistance based on elevated Pfmdr1 copy number and IC50. By 2009, there was already significant evidence of artemisinin resistance not previously reported at the Northern Cambodia-Thai border. This study suggests the basis for early development of significant DHA/PPQ failures within 3 years of introduction. Artemisinin resistance likely occurred on the Northern border concurrently with that reported along the Western border in Pailin.Trial Registration: This legacy trial was conducted prior to International Committee of Medical Journal Editors’ requirements for preregistration on ClinicalTrials.gov. The full protocol has been provided.

Usability of Video Observed Therapy with a Notification System to Improve Monitoring of Tuberculosis Treatment in Thailand (Preprint)

BACKGROUND In Thailand, the healthcare system has struggled to cope with the coronavirus disease 2019 (COVID-19), resulting in directly observed therapy (DOT) for tuberculosis (TB) being de-emphasized. Video observed therapy (VOT) or, more specifically, the Thai VOT “TH VOT” system, was then developed to replace DOT. According to the pilot study, the system needed a notification to improve usability and user compliance. The updated version of the TH VOT system thus enabled LINE notifications. OBJECTIVE This study aimed to reassess the user compliance and usability of the updated TH VOT system. METHODS This study was conducted in Hat Yai and Meuang Songkhla districts in Songkhla Province, Southern Thailand. The system was used by not only TB patients but also TB staff as observers in primary health care settings. Some of the observers used the simulated VOT system instead of the actual system due to the lack of participating patients in their jurisdiction. After 30-day usage, VOT session records were analyzed to determine the compliance of the patients and observers. The User Experience Questionnaire (UEQ) was administered to reassess the usability of the system and compare the ratings of the participants with the general benchmark scores of the UEQ. The results were summarized to reveal the user compliance and usability based on three groups: the patient, actual VOT observer, and simulated VOT observer. RESULTS Of the 19 observers, 10 were used the actual VOT, and the remaining 9 used the simulated VOT; there were also 10 TB patients. The patients, actual VOT observers, and simulated observers had about 80%, 65%, and 50% compliance, respectively, in terms of following the standard operating procedures every day. The scores of all groups on all dimensions were well above the average scores. There was no significant difference in any of the dimensional scores among the three groups. CONCLUSIONS The updated version of the TH VOT was deemed usable by both the patients and the healthcare staff. Compliance to use the system was high among the patients but moderate among the observers.

Evaluation of the safety and efficacy of dihydroartemisinin–piperaquine for intermittent preventive treatment of malaria in HIV-infected pregnant women: protocol of a multicentre, two-arm, randomised, placebo-controlled, superiority clinical trial (MAMAH project)

IntroductionMalaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine–pyrimethamine is recommended for malaria prevention in HIV-uninfected women, but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. Dihydroartemisinin–piperaquine (DHA–PPQ) has been shown to improve antimalarial protection, constituting a promising IPTp candidate. This trial’s objective is to determine if monthly 3-day IPTp courses of DHA–PPQ added to daily CTXp are safe and superior to CTXp alone in decreasing the proportion of peripheral malaria parasitaemia at the end of pregnancy.Methods and analysisThis is a multicentre, two-arm, placebo-controlled, individually randomised trial in HIV-infected pregnant women receiving CTXp and antiretroviral treatment. A total of 664 women will be enrolled at the first antenatal care clinic visit in sites from Gabon and Mozambique. Participants will receive an insecticide-treated net, and they will be administered monthly IPTp with DHA-PPQ or placebo (1:1 ratio) as directly observed therapy from the second trimester of pregnancy. Primary study outcome is the prevalence of maternal parasitaemia at delivery. Secondary outcomes include prevalence of malaria-related maternal and infant outcomes and proportion of adverse perinatal outcomes. Participants will be followed until 6 weeks after the end of pregnancy and their infants until 1 year of age to also evaluate the impact of DHA–PPQ on mother-to-child transmission of HIV. The analysis will be done in the intention to treat and according to protocol cohorts, adjusted by gravidity, country, seasonality and other variables associated with malaria.Ethics and disseminationThe protocol was reviewed and approved by the institutional and national ethics committees of Gabon and Mozambique and the Hospital Clinic of Barcelona. Project results will be presented to all stakeholders and published in open-access journals.Trial registration numberNCT03671109.

Provider preferences for delivery of HIV care coordination services: results from a discrete choice experiment

Introduction The PROMISE study was launched in 2018 to assess and document the implementation of changes to an existing HIV Care Coordination Program (CCP) designed to address persistent disparities in care and treatment engagement among persons with HIV in New York City. We evaluated provider endorsement of features of the CCP to identify opportunities for improvement. Methods We used a discrete choice experiment (DCE) to measure provider endorsement of four CCP attributes, including: a) how CCP helps with medication adherence, b) how CCP helps with primary care appointments, c) how CCP helps with issues other than primary care, and d) where CCP visits take place (visit location). Each attribute had three to four levels. Our primary outcomes were relative importance and part-worth utilities, measures of preference for the levels of the four CCP program attributes. Results Visit location (28.6%) had the highest relative importance, followed by how staff help with ART adherence (24.3%), how staff help with issues other than primary care (24.2%), and how staff help with primary care appointments (22.9%). Within each of the above attributes, respectively, the levels with the highest part-worth utilities were home visits 60 minutes from the program or agency (19.9 utiles, 95% CI 10.7-29.0), directly observed therapy (26.1 utiles, 95% CI 19.1-33.1), help with non-HIV specialty medical care (26.5 utiles, 95% CI 21.5-31.6), and reminding clients about and accompanying them to primary care appointments (20.8 utiles, 95% CI 15.6-26.0). Conclusions Ongoing CCP refinements should account for how best to support and evaluate the intensive CCP components endorsed by providers in this study.

“I am afraid that others will feel scared and disgusted with me. So, I will keep it a secret until I die”: A qualitative study among patients with tuberculosis receiving DOTS regimen in Thailand

Background: Tuberculosis (TB) has become a significant public health problem leading to a top ten morality. Directly Observed Therapy, Short-course (DOTS) is recommended as a critical element for curing and preventing TB. However, patients who have been living with TB often receive barriers and challenges, which may lead them to discontinue the DOTS treatment. Objective: This study aimed to understand patients’ experiences living with TB and receiving DOTS regimens. Methods: A qualitative descriptive study was employed. Semi-structured interviews were done among twenty tuberculosis patients selected using convenience sampling from the slum community in Bangkok, Thailand. The thematic approach was used for data analysis. Results: Two main themes were developed: (1) troublesome disease and (2) emotional challenges. The first theme comprises three subthemes: confronting death, accepting lifestyle change, and DOTS challenges. The second theme consists of two subthemes: isolation from others and stigma. Conclusion: The findings could guide nurses and other healthcare professionals to develop the treatment guideline and the DOTS strategy using a holistic approach.

Does optimized adherence support improve treatment outcomes in RR / MDR-TB patients on 18-20 months regimen in Tbilisi, Georgia?

Introduction: Adherence to second-line antituberculosis drug is challenging. A combination of strategies needs to be implemented to achieve adherence. In Georgia an optimized adherence support (OAS) – a package of education, psychosocial support and adherence counselling – was added to the already existing package of adherence support (supervised treatment, adherence incentives, transport cost reimbursement) to improve adherence and increase treatment success. We assessed the additive benefits of OAS on adherence and treatment outcomes. Methodology: This was a before and after cohort study using routine programme data in the National Center for Tuberculosis and Lung Diseases in Tbilisi. All adult rifampicin- and multidrug-resistant tuberculosis (RR/MDR-TB) patients enrolled for treatment under directly observed therapy in the NCTLD during the period before (June 2015 – January 2016) and after (June 2017 – January 2018) were included in the study. Primary outcomes were: i) adequate adherence defined as ≥ 85% of days covered by TB medication during the whole treatment period; ii) final treatment outcomes. Results: Of 221 RR/MDR-TB, most patients were male (76%, N = 167) with a mean age of 41 ± 14 years. Adherence data was available for 111 patients in the ‘before’ and 97 patients in the ‘after’ cohort. Adequate adherence was achieved by 62% (69/111) in the ‘before’ and 70% (68/97) in the ‘after’ cohort (p = 0.290). Overall treatment success was 64% (73/114) and 63% (67/107) in the ‘before’ and ‘after’ cohorts respectively (p = 0.937). Conclusions: Implementation of OAS had modest effect on adherence and had no additive benefits on treatment outcomes among RR/MDR-TB patients on 18-20 months regimen.

The Effect of Incarceration on Tuberculosis Treatment Outcomes in Brazil: a Retrospective Cohort Study

Background: Tuberculosis notifications in Latin American prisons have more than doubled over the past two decades; however, treatment outcomes and their determinants among incarcerated individuals in this region are not well understood. Methods: Newly diagnosed drug-susceptible tuberculosis cases reported to Brazils Sistema de Informação de Agravos de Notificação (SINAN) between January 2015 and December 2017 were included. Multivariate logistic regression was used to assess socioeconomic and clinical factors associated with treatment success among incarcerated individuals. Results: Incarcerated individuals (n=17,776) had greater treatment success than non-incarcerated individuals (n=160,728; 82.2% vs 75.1%, p<0.0001), including after adjusting for demographic and clinical risk factors (adjusted Odds Ratio [aOR]: 1.27; 95% CI: 1.19-1.34). These differences were partially mediated by increased use of directly observed therapy among incarcerated individuals (DOT) (61% vs 47%, p<0.001), which was associated with greater efficacy in the incarcerated population (aOR 2.56 vs aOR 2.17; p<0.001). DOT was associated with improved treatment success among incarcerated subpopulations at elevated risk of poor outcomes. Conclusion: Tuberculosis treatment success among incarcerated individuals in Brazil is higher than non-incarcerated individuals, but both fall below WHO targets. Expanding the use of DOT and services for socially and medically vulnerable individuals may improve outcomes in carceral settings.