Clinical trial of extended-dose chloroquine for treatment of resistant falciparum malaria among Afghan refugees in Pakistan

BACKGROUND: Falciparum malaria is a significant problem for Afghan refugees in Pakistan. Refugee treatment guidelines recommended standard three-day chloroquine treatment (25 mg/kg) for first episodes and extended five-day treatment (40 mg/kg) for recrudescent infections, based on the assumption that a five-day course would more likely achieve a cure. An in-vivo randomized controlled trial was conducted among refugees with uncomplicated falciparum malaria to determine whether five-day treatment (CQ40) was more effective than standard treatment (CQ25). METHODS: 142 falciparum patients were recruited into CQ25 or CQ40 treatment arms and followed up to 60 days with regular blood smears. The primary outcome was parasitological cure without recrudescence. Treatment failures were retreated with CQ40. PCR genotyping of 270 samples, from the same and nearby sites, was used to support interpretation of outcomes. RESULTS: 84% of CQ25 versus 51% of CQ40 patients experienced parasite recrudescence during follow-up (adjusted odds ratio 0.17, 95%CI 0.08-0.38). Cure rates were significantly improved with CQ40, particularly among adults. Fever clearance time, parasite clearance time, and proportions gametocytaemic post-treatment were similar between treatment groups. Second-line CQ40 treatment resulted in higher failure rates than first-line CQ40 treatment. CQ-resistance marker pfcrt 76T was found in all isolates analysed, while pfmdr1 86Y and 184Y were found in 18% and 37% of isolates respectively. CONCLUSIONS: CQ is not suitable for first-line falciparum treatment in Afghan refugee communities. The extended-dose CQ regimen can overcome 39% of resistant infections that would recrudesce under the standard regimen, but the high failure rate after directly observed treatment demonstrates its use is inappropriate

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

INTRODUCTION: Antimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown. METHODS: A single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure. FINDINGS: A total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced. CONCLUSIONS: CQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single-dose PQ for reducing gametocyte carriage. TRIAL REGISTRATION: ClinicalTrials.gov NCT00959517

Cost-effectiveness of adding indoor residual spraying to case management in Afghan refugee settlements in Northwest Pakistan during a prolonged malaria epidemic.

INTRODUCTION: Financing of malaria control for displaced populations is limited in scope and duration, making cost-effectiveness analyses relevant but difficult. This study analyses cost-effectiveness of adding prevention through targeted indoor residual spraying (IRS) to case management in Afghan refugee settlements in Pakistan during a prolonged malaria epidemic. METHODS/FINDINGS: An intervention study design was selected, taking a societal perspective. Provider and household costs of vector control and case management were collected from provider records and community survey. Health outcomes (e.g. cases and DALYs averted) were derived and incremental cost-effectiveness ratios (ICERs) for cases prevented and DALYs averted calculated. Population, treatment cost, women's time, days of productivity lost, case fatality rate, cases prevented, and DALY assumptions were tested in sensitivity analysis. Malaria incidence peaked at 44/1,000 population in year 2, declining to 14/1,000 in year 5. In total, 370,000 malaria cases, 80% vivax, were diagnosed and treated and an estimated 67,988 vivax cases and 18,578 falciparum and mixed cases prevented. Mean annual programme cost per capita was US$0.56. The additional cost of including IRS over five years per case prevented was US$39; US$50 for vivax (US$43 in years 1-3, US$80 in years 4-5) and US$182 for falciparum (US$139 in years 1-3 and US$680 in years 4-5). Per DALY averted this was US$266 (US$220 in years 1-3 and US$486 in years 4-5) and thus 'highly cost-effective' or cost-effective using WHO and comparison thresholds. CONCLUSIONS: Adding IRS was cost-effective in this moderate endemicity, low mortality setting. It was more cost-effective when transmission was highest, becoming less so as transmission reduced. Because vivax was three times more common than falciparum and the case fatality rate was low, cost-effectiveness estimations for cases prevented appear reliable and more definitive for vivax malaria

Cushing syndrome due to ectopic ACTH secreting pheochromocytoma

In this case report, we present a case of a woman in her late 30s who presented with bilateral motor weakness, headache, hyperglycaemia and hypertension. Investigations revealed very high 24-hour urine cortisol of 90 524, ectopic adrenocorticotropic hormone secreting pheochromocytoma, normal metanephrine levels and empty sella, which has never been reported. CT chest and abdomen revealed enlarged left adrenal gland with large necrotic mass 4.7×4.0 cm most likely neoplastic lesion. The patient was cured after surgical removal of the left adrenal mass. Histological examination revealed 3.5×2.5×2 cm mass consistent with pheochromocytoma. After surgery and a short stay in the intensive care unit, the patient started improving and both antihypertensive treatment and insulin injections were withdrawn

Impact of Digital Marketing on the Tourism Industry Business Profitability of UAE through the role of Effectiveness

This Paper explores the influence of digital marketing impact and tourism attraction on business profitability through the mediating role of effectiveness. Researcher use a structured questionnaire as the primary instrument for collecting quantitative data and analyzing numerical data methodically, a researcher using a quantitative research design can better understand the connection between UAE businesses' success in the tourism industry and their use of digital marketing. Data were investigated through SPSS Version 26 and SEM (structural equation modeling) using Smart PLS Version 4 software. The results show that digital marketing impact has positive influence on digital marketing effectiveness and business profitability, Tourism attraction has impact on tourism industry effectiveness and business profitability, Perceived Digital Marketing Effectiveness has positive impact on business profitability. The results provide practical implications for organizations seeking to increase business profitability. Organizations can improve digital marketing effectiveness and business profitability by using digital marketing impact and tourism attraction

Afghan refugees and the temporal and spatial distribution of malaria in Pakistan.

Influx of refugees and establishment of camps or settlements in malaria endemic areas can affect the distribution and burden of malaria in the host country. Within a decade of the Soviet invasion of Afghanistan and the arrival of 2.3 million Afghan refugees in Pakistan's North West Frontier Province, the annual burden of malaria among refugees had risen ten fold from 11,200 cases in 1981 to 118,000 cases in 1991, a burden greater than the one reported by the Pakistan Ministry of Health for the entire Pakistani population. Political developments in the 1990s led to over half the refugee population repatriating to Afghanistan, and the Afghan Refugee Health Programme (ARHP) was scaled down proportionately. Districts in which the ARHP recorded a reduced incidence of malaria began to show an increased incidence in the statistics of the Pakistan government health programme. This and other evidence pointed to a change in health seeking practices of the refugees who remained in Pakistan, with many turning from ARHP to Pakistani health services as aid declined. Comparison of the two sources of data produced no evidence for the spatial distribution of malaria in NWFP having changed during the 1990s. Nor was there any evidence for the presence of refugees having increased the malaria burden in the Pakistani population, as is sometimes alleged. This highlights the risk of misinterpreting health trends when parallel health services are operating. Over the decade incidence in the refugee camps decreased by 25% as a result of control activities, and by 1997 the burden among remaining refugees had fallen to 26,856 cases per annum. These trends indicate that the burden would continue to fall if political conditions in Afghanistan were to improve and more refugees returned to their homeland

Cost-effectiveness of adding indoor residual spraying to case management in Afghan refugee settlements in Northwest Pakistan during a prolonged malaria epidemic

10.1371/journal.pntd.0005935PLOS NEGLECTED TROPICAL DISEASES111

IMPACTS OF UNTREATED EFFLUENT MIXING ON SURFACE AND GROUND WATER QUALITY

During this research water quality in Ravi River was assessed properly through site surveying and sampling. Untreated effluent from communal and industrial sectors is seriously damaging the surface water quality in Ravi River. Analyses of effluent from Lahore city was showing very high rate of pollutants. During the investigation period the Biological Oxygen Demand (BOD-5) of effluent had been increased from 410 mg/L to 495 mg/L, Chemical Oxygen Demand (COD) from 815 mg/L to 870 mg/L and Total Solids (TS) from 1280 mg/L to 1400 mg/L. This might be due to the fact that there is a rapid growth of urbanization in Lahore City and the municipality conditions are becoming worse day by day. Samples were also collected from selected location along river and as well as groundwater reservoir in the study area. Collected samples were analyzed for different water quality parameters like pH, Total Dissolve Salts (TDS), Electric Conductivity (EC), temperature, hardness, magnesium, calcium, chloride, sulfate etc. Laboratory results of these analyses from selected locations indicates that low flow conditions in Ravi River along with high rate of contaminants are also damaging the ground water sources in the study area. Investigations show that unhygienic condition of Ravi River is seriously increasing the negative impacts on surrounding environment and aquatic life of the river. Proper treatment of communal and industrial wastewater is necessary to improve the surface and ground water conditions in the area studied

A REVIEW OF WASTEWATER TREATMENT PROCESS MODELING

Modeling of Wastewater Treatment Process (WWTP) has gained much attention and a lot of research has been focused toward this area. This review paper includes a detailed discussion on different aspects of wastewater treatment process modeling considering white-box and black-box modeling techniques. Initially basic model steps are discussed for the better understanding of modeling concepts. Basic Activated Sludge Models (ASM) developed by International Water Association (IWA) task group are contributing considerablyin wastewater treatment modeling. Different factors related to the model performance like model selection, model functions and model calibration are discussed in detail. The applications of ASM1, ASM2, ASM2d, ASM3, ASM3_2N, ASM3 bio-P model etc. are also studied. The white-box modeling techniques in this area are more significant. The importance of black-box models under special conditions where white-box models are not able to predict accurate results are also investigated. It was also found that use of hybrid, linearizationand Artificial Intelligence (AI) techniques in wastewater treatment modeling can be more useful for process optimization and control