Retention and mortality outcomes from a community-supported public–private HIV treatment programme in Myanmar

Introduction: There is a growing interest in the potential contribution the private sector can make towards increasing access to antiretroviral therapy (ART) in low- and middle-income settings. This article describes a public–private partnership that was developed to expand HIV care capacity in Yangon, Myanmar. The partnership was between private sector general practitioners (GPs) and a community-based non-governmental organization (International HIV/AIDS Alliance). Methods: Retrospective analysis of 2119 patient records dating from March 2009 to April 2015 was conducted. Outcomes assessed were immunological response, loss to follow-up, all-cause mortality, and alive and retained in care. Follow-up time was calculated from the date of registration to the date of death, loss to follow-up, transfer out, or if still alive and known to be in care, until April 2015. Cox proportional hazards model was used to identify predictors of loss to follow-up and mortality. Kaplan–Meier survival analysis was used to estimate survival function of being alive and retained in care. Results: The median number of patients for each of the 16 GPs was 42 (interquartile range (IQR): 25–227), and the median follow-up period was 13 months. The median patient age was 35 years (IQR: 30–41); 56.6% were men, 62 and 11.8% were in WHO Stage III and Stage IV at registration, respectively; median CD4 count at registration was 177 cells/mm3; and 90.7% were on ART in April 2015. The median CD4 count at registration increased from 122 cells/mm3 in 2009 to 194 cells/mm3 in 2014. Among patients on ART, CD4 counts increased from a median of 187 cells/mm3 at registration to 436 cells/mm3 at 36 months. The median time to initiation of ART among eligible patients was 29 days, with 93.8% of eligible patients being initiated on ART within 90 days. Overall, 3.3% patients were lost to follow-up, 4.2% transferred out to other health facilities, and 8.3% died during the follow-up period. Crude mortality rate was 48.6/1000 person-years; 42% (n=74) of deaths occurred during the pre-ART period and 39.8% (n=70) occurred during the first six months of ART. Of those who died during the pre-ART period, 94.5% were eligible for ART. In multivariate regression, baseline CD4 count and ART status were independent predictors of mortality, whereas ART status, younger age and patient volumes per provider were predictors of loss to follow-up. Probability of being alive and retained in care at six months was 96.8% among those on ART, 38.5% among pre-ART but eligible patients, and 20.0% among ART-ineligible patients. Conclusions: Effectively supported private sector GPs successfully administered and monitored ART in Myanmar, suggesting that community-supported private sector partnerships can contribute to expansion of HIV treatment and care capacity. To further improve patient outcomes, early testing and initiation of ART, combined with close clinical monitoring and support during the initial periods of enrolling in treatment and care, are required

Treatment efficacy of artesunate-amodiaquine and prevalence of Plasmodium falciparum drug resistance markers in Zanzibar, 2002-2017

Introduction: Emergence of resistance to artemisinin-based combination therapy (ACT) is a major threat to combat Plasmodium falciparum malaria. Regular therapeutic studies to monitor treatment efficacy is essential, and genotyping of molecular makers is useful for mapping development and spread of resistance. Aims: The study aims are to assess efficacy of artesunate-amodiquine (ASAQ) and prevalence of molecular markers of drug resistance in Zanzibar in 2017. Methods: Treatment efficacy of the clinical trial conducted in 2017 was compared with efficacies in 2002 and 2005. A total of 142 samples were genotyped for single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter gene (pfcrt) gene, the P. falciparum multi drug resistance 1 (pfmdr1) gene, and in the P. falciparum Kelch 13 (PfK13) propeller region. Prevalence of SNPs were assessed during the period 2002-2017. Results: Cure rate was 100% in 2017, compared to 94% and 96%, in 2002-2003 and 2005, respectively. Day 3 fever clearance rate were also high 93% (2002-3), 99% (2005) and 98% (2017) in all studies. Prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y and pfmdr1 (86Y, 184Y and 1246Y) YYY haplotypes were significantly decreased between 2002-3 and 2017 (p &lt; 0.001). No SNP in the PfK13 gene related to artemisinin resistance was identified. Conclusion: Efficacy of ASAQ remains high after fourteen years as first-line treatment, despite the wide-scale use of ASAQ, and there is no evidence of selection of resistance markers in Zanzibar. Continuous monitoring of drug efficacy and resistance markers is recommended.This master thesis is a collaboration project between Institutionen för kvinnors och barns hälsa, Department of Women's and Children's Health, Uppsala Universtiy and Anders Björkman group, Department of Microbiology, Tumor and Cell Biology (MTC), C1, Karolinska Institutet. Laboratory examinations were mainly conducted at MTC house, Karolinska Institutet.</p

Una storia di Stato? Leggi memoriali, religione civile, conflitto

In the southern Bago Yoma mountain range in Myanmar, Asian elephants are being killed at a disturbing rate. This emerging crisis was identified initially through a telemetry study when 7 of 19 of collared elephants were poached within a year of being fitted with a satellite-GPS collar. Subsequent follow up of ground teams confirmed the human caused death or disappearance of at least 19 elephants, including the seven collared individuals, within a 35 km2 area in less than two years. The carcasses of 40 additional elephants were found in areas located across south-central Myanmar once systematic surveys began by our team and collaborators. In addition to the extreme rate of loss, this study documents the targeting of elephants for their skin instead of the more common ivory, an increasing trend in Myanmar. Intensive research programs focused on other conservation problems identified this issue and are now encouraging local authorities to prioritize anti-poaching efforts and improve conservation policies within the country. Myanmar represents one of the last remaining countries in Asia with substantial wildlands suitable for elephants. Increasing rates of human-elephant conflict and poaching events in this country pose a dire threat to the global population

Parasite clearance, cure rate, post-treatment prophylaxis and safety of standard 3-day versus an extended 6-day treatment of artemether-lumefantrine and a single low-dose primaquine for uncomplicated Plasmodium falciparum malaria in Bagamoyo district, Tanzania– a randomized controlled trial.

Background: Artemisinin-based combination therapy (ACT) resistant Plasmodium falciparum represents an increasing threat to Africa. Extended ACT regimens from standard 3 to 6 days may represent a means to prevent its development and potential spread in Africa. Methods:  Standard 3-day treatment with artemether-lumefantrine (control) was compared to extended 6-day treatment and single low-dose primaquine (intervention); in a randomized controlled, parallel group, superiority clinical trial of patients aged 1-65 years with microscopy confirmed uncomplicated P. falciparum malaria, enrolled in Bagamoyo district, Tanzania. The study evaluated parasite clearance, including proportion of PCR detectable P. falciparum on days 5 and 7 (primary endpoint), cure rate, post-treatment prophylaxis, safety and tolerability. Clinical, and laboratory assessments, including ECG were conducted during 42 days of follow-up. Blood samples were collected for parasite detection (by microscopy and PCR), molecular genotyping and pharmacokinetic analyses. Kaplan-Meier survival analyses were done for both parasite clearance and recurrence. Results. A total of 280 patients were enrolled, 141 and 139 in the control and intervention arm, respectively, of whom 121 completed 42 days follow-up in each arm. There was no difference in proportion of PCR positivity across the arms at day 5 (80/130 (61.5%) vs 89/134 (66.4%), p=0.44), or day 7 (71/129 (55.0%) vs 70/134 (52.2%), p=0.71). Day 42 microscopy determined cure rates (PCR adjusted) were 97.4% (100/103) and 98.3% (110/112), p=0.65, in the control and intervention arm, respectively. Microscopy determined crude recurrent parasitemia during follow-up was 21/121 (17.4%) in the control and 14/121 (11.6%) in the intervention arm, p=0.20, and it took 34 days and 42 days in the respective arms for 90% of the patients to remain without recurrent parasitemia. Lumefantrine exposure was significantly higher in intervention arm from D3 to D42, but cardiac, biochemical and hematological safety was high and similar in both arms. Conclusion: Extended 6-day artemether-lumefantrine treatment and a single low-dose of primaquine was not superior to standard 3-day treatment for ACT sensitive P. falciparum infections, but importantly equally efficacious and safe. Thus, extended artemether-lumefantrine treatment may be considered as a future treatment regimen for ACT resistant P. falciparum, to prolong the therapeutic lifespan of ACT in Africa

Effectiveness of repellent delivered through village health volunteers on malaria incidence in villages in South-East Myanmar: a stepped-wedge cluster-randomised controlled trial protocol

Abstract Background To combat emerging drug resistance in the Greater Mekong Sub-region (GMS) the World Health Organization and GMS countries have committed to eliminating malaria in the region by 2030. The overall approach includes providing universal access to diagnosis and treatment of malaria, and sustainable preventive measures, including vector control. Topical repellents are an intervention that can be used to target residual malaria transmission not covered by long lasting insecticide nets and indoor residual spraying. Although there is strong evidence that topical repellents protect against mosquito bites, evidence is not well established for the effectiveness of repellents distributed as part of malaria control activities in protecting against episodes of malaria. A common approach to deliver malaria services is to assign Village Health Volunteers (VHVs) to villages, particularly where limited or no services exist. The proposed trial aims to provide evidence for the effectiveness of repellent distributed through VHVs in reducing malaria. Methods The study is an open stepped-wedge cluster-randomised controlled trial randomised at the village level. Using this approach, repellent (N,N-diethyl-benzamide – 12% w/w, cream) is distributed by VHVs in villages sequentially throughout the malaria transmission season. Villages will be grouped into blocks, with blocks transitioned monthly from control (no repellent) to intervention states (to receive repellent) across 14 monthly intervals in random order). This follows a 4-week baseline period where all villages do not receive repellent. The primary endpoint is defined as the number of individuals positive for Plasmodium falciparum and Plasmodium vivax infections diagnosed by a rapid diagnostic test. Secondary endpoints include symptomatic malaria, Polymerase Chain Reaction (PCR)-detectable Plasmodium spp. infections, molecular markers of drug resistance and antibodies specific for Plasmodium spp. parasites. Discussion This study has been approved by relevant institutional ethics committees in Myanmar and Australia. Results will be disseminated through workshops, conferences and peer-reviewed publications. Findings will contribute to a better understanding of the optimal distribution mechanisms of repellent, context specific effectiveness and inform policy makers and implementers of malaria elimination programs in the GMS. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12616001434482). Retrospectively registered 14th October 2016

Evaluation of the effectiveness of topical repellent distributed by village health volunteer networks against Plasmodium spp. infection in Myanmar: A stepped-wedge cluster randomised trial.

BackgroundThe World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination.Methods and findingsBetween April 2015 and June 2016, a 15-month stepped-wedge cluster randomised trial was conducted in 116 villages in Myanmar (stepped monthly in blocks) to test the effectiveness of 12% N,N-diethylbenzamide w/w cream distributed by VHVs, on Plasmodium spp. infection. The median age of participants was 18 years, approximately half were female, and the majority were either village residents (46%) or forest dwellers (40%). No adverse events were reported during the study. Generalised linear mixed modelling estimated the effect of repellent on infection detected by rapid diagnostic test (RDT) (primary outcome) and polymerase chain reaction (PCR) (secondary outcome). Overall Plasmodium infection detected by RDT was low (0.16%; 50/32,194), but infection detected by PCR was higher (3%; 419/13,157). There was no significant protection against RDT-detectable infection (adjusted odds ratio [AOR] = 0.25, 95% CI 0.004-15.2, p = 0.512). In Plasmodium-species-specific analyses, repellent protected against PCR-detectable P. falciparum (adjusted relative risk ratio [ARRR] = 0.67, 95% CI 0.47-0.95, p = 0.026), but not P. vivax infection (ARRR = 1.41, 95% CI 0.80-2.47, p = 0.233). Repellent effects were similar when delayed effects were modelled, across risk groups, and regardless of village-level and temporal heterogeneity in malaria prevalence. The incremental cost-effectiveness ratio was US$256 per PCR-detectable infection averted. Study limitations were a lower than expected Plasmodium spp. infection rate and potential geographic dilution of the intervention.ConclusionsIn this study, we observed apparent protection against new infections associated with the large-scale distribution of repellent by VHVs. Incorporation of repellent into national strategies, particularly in areas where bed nets are less effective, may contribute to the interruption of malaria transmission. Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform WHO public health policy on the deployment of topical repellents for malaria prevention.Trial registrationAustralian and New Zealand Clinical Trials Registry (ACTRN12616001434482)

Skinned elephant cacass.

<p>The skinned carcass of an elephant found in April in Ayeyarwady. Credit: Dr. Zaw Min Oo.</p

Poaching for elephant body parts.

<p>Elephant skin and trunks removed by poachers in Ayeyarwady. Credit: Dr. Zaw Min Oo.</p

Bago Yoma elephant population survival estimation.

<p>Population survival estimation over time utilizing data from the Bago Yoma collared elephant study.</p

Locations of the study sites in Myanmar.

<p>1) Ayeryarwady Delta, 2) southern Bago Yoma mountain range, and 3) southern Tanintharyi region. Myanmar elephant range from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194113#pone.0194113.ref018" target="_blank">18</a>]. Image source: World Imagery: Esri, DigitalGlobe, Earthstar Geographics, CNES/Airbus DS, GeoEye, USDA FSA, USGS, Getmapping, Aerogrid, IGN, IGP, and the GIS User Community (accessed November 2017).</p