Antimalarial drug efficacy and resistance in malaria-endemic countries in HANMAT-PIAM_net countries of the Eastern Mediterranean Region 2016-2020: Clinical and genetic studies.

INTRODUCTION: The World Health Organization recommends regular monitoring of the efficacy of nationally recommended antimalarial drugs. We present the results of studies on the efficacy of recommended antimalarials and molecular markers of artemisinin and partner resistance in Afghanistan, Pakistan, Somalia, Sudan and Yemen. METHODS: Single-arm prospective studies were conducted to evaluate the efficacy of artesunate-sulfadoxine-pyrimethamine (ASSP) in Afghanistan and Pakistan, artemether-lumefantrine (AL) in all countries, or dihydroartemisinin-piperaquine (DP) in Sudan for the treatment of Plasmodium falciparum. The efficacy of chloroquine (CQ) and AL for the treatment of Plasmodium vivax was evaluated in Afghanistan and Somalia, respectively. Patients were treated and monitored for 28 (CQ, ASSP and AL) or 42 (DP) days. Polymerase chain reaction (PCR)-corrected cure rate and parasite positivity rate at Day 3 were estimated. Mutations in the P. falciparum kelch 13 (Pfk13) gene and amplifications of plasmepsin (Pfpm2) and multidrug resistance-1 (Pfmdr-1) genes were also studied. RESULTS: A total of 1680 (249 for ASSP, 1079 for AL and 352 for DP) falciparum cases were successfully assessed. A PCR-adjusted ASSP cure rate of 100% was observed in Afghanistan and Pakistan. For AL, the cure rate was 100% in all but four sites in Sudan, where cure rates ranged from 92.1% to 98.8%. All but one patient were parasite-free at Day 3. For P. vivax, cure rates were 98.2% for CQ and 100% for AL. None of the samples from Afghanistan, Pakistan and Yemen had a Pfk13 mutation known to be associated with artemisinin resistance. In Sudan, the validated Pfk13 R622I mutation accounted for 53.8% (14/26) of the detected non-synonymous Pfk13 mutations, most of which were repeatedly detected in Gadaref. A prevalence of 2.7% and 9.3% of Pfmdr1 amplification was observed in Pakistan and Yemen, respectively. CONCLUSION: High efficacy of ASSP, AL and DP in the treatment of uncomplicated falciparum infection and of CQ and AL in the treatment of P. vivax was observed in the respective countries. The repeated detection of a relatively high rate of Pfk13 R622I mutation in Sudan underscores the need for close monitoring of the efficacy of recommended ACTs, parasite clearance rates and Pfk13 mutations in Sudan and beyond. Registration numbers of the trials: ACTRN12622000944730 and ACTRN12622000873729 for Afghanistan, ACTRN12620000426987 and ACTRN12617001025325 for Pakistan, ACTRN12618001224213 for Somalia, ACTRN12617000276358, ACTRN12622000930785 and ACTRN12618001800213 for Sudan and ACTRN12617000283370 for Yemen.

Trends in malaria indicators after scale-up of community-based malaria management in Afghanistan.

BACKGROUND: The Community-Based Malaria Management (CBMM) strategy, introduced in 2013 and expanded to all health facilities and health posts in Afghanistan by 2016, aimed to deliver rapid diagnostic testing and more timely treatment to all communities nationwide. In this study, trends for several malaria outcome indicators were compared before and after the expansion of the CBMM strategy, using cross-sectional analysis of surveillance data. METHODS: Generalized estimating equation (GEE) models with a Poisson distribution were used to assess trends of three key outcomes before (2012-2015) and after (2016-2019) CBMM expansion. These outcomes were annual malaria incidence rate (both all and confirmed malaria incidence), malaria death rate, and malaria test positivity rate. Additional variables assessed included annual blood examination rates (ABER) and malaria confirmation rate. RESULTS: Average malaria incidence rates decreased from 13.1 before CBMM expansion to 10.0 per 1000 persons per year after CBMM expansion (P < 0.001). The time period after CBMM was expanded witnessed a 339% increase in confirmed malaria incidence as compared to the period before (IRR 3.39, 95% CI 2.18, 5.27; P < 0.001). In the period since the expansion of CBMM (2016-2019), overall malaria incidence rate declined by 19% each year (IRR 0.81, 95% CI 0.71,0.92; P = 0.001) and the malaria death rate declined by 85% each year (IRR 0.15, 95% CI 0.12, 0.20; P < 0.001). In comparing the before period to the after period, the ABER increased from 2.3 to 3.5 per 100 person/year, the malaria test positivity rate increased from 12.2 to 20.5%, and the confirmation rate increased from 21% before to 71% after CBMM. CONCLUSIONS: Afghanistan's CBMM expansion to introduce rapid diagnostic tests and provide more timely treatment for malaria through all levels of care temporally correlates with significant improvement in multiple indicators of malaria control.

The Ross procedure in children: preoperative haemodynamic manifestation has significant effect on late autograft re-operation.

OBJECTIVES: The Ross procedure is the aortic valve-replacement procedure of choice in children. Nonetheless, late autograft re-operation for dilatation and/or valve regurgitation is of concern. We examined whether preoperative haemodynamic manifestation (e.g., stenosis, regurgitation and mixed aortic valve disease) affected late re-operation risk. METHODS: Medical records of 227 children who underwent the Ross procedure (1991-2004) were reviewed. Competing-risks methodology determined time-related prevalence and associated factors for two mutually exclusive end-states after the Ross procedure: (1) death prior to subsequent autograft re-operation and (2) autograft re-operation, with the remainder of patients being alive and free from subsequent autograft re-operation. RESULTS: There were 162 male patients (71%) in this study. Median age at surgery was 12.1 years (range: 1 week-18 years). The haemodynamic aortic valve dysfunction was primarily stenosis (n=40, 18%), primarily regurgitation (n=109, 48%) and mixed disease (n=78, 35%). Underlying pathology was rheumatic fever (n=104, 46%), congenital heart disease (n=113, 50%) and endocarditis (n=8, 3%). Competing-risks analysis showed that, at 10 years following the Ross procedure, ∼5% of patients had died, 16% had undergone autograft re-operation with aortic valve replacement and 79% were alive and free from autograft re-operation. Ten-year freedom from autograft re-operation for patients with preoperative stenosis, regurgitation and mixed disease was 97%, 69% and 93%, respectively, (p<0.001 for regurgitation vs others). Risk factors for increased risk of autograft re-operation were rheumatic fever (parameter estimates (PEs): 2.09 ± 0.75, p=0.006), and earlier year of surgery (PE: 0.20 ± 0.06, p=0.001). Ten-year freedom from homograft replacement was 81% and was not dependent on haemodynamic manifestation (PE: -0.16 ± 0.38, p=0.68). Significant factors for homograft replacement included fresh homografts (PE: 2.2 ± 0.63, p=0.01) and annular enlargement (PE: 1.11 ± 0.3, p=0.01). Ten-year freedom from cardiac re-operation other than auto-/homograft was 85%, higher in patients with preoperative aortic regurgitation (PE: 1.01 ± 0.42, p=0.02). Concomitant cardiac surgery was a significant factor for late cardiac re-operation other than auto-/homograft replacement (PE: 1.79 ± 0.39, p<0.001). CONCLUSIONS: The Ross procedure in children is associated with excellent survival. Late autograft re-operation may be required; however, it is more common in children with preoperative aortic regurgitation, especially those with rheumatic fever. Better patient selection in later era has mitigated the risk of autograft re-operation. Continued improved candidate selection, along with modifications in autograft implantation and root/sinotubular stabilisation techniques, may further decrease late autograft failure.

Is isolation of outborn infants required at admission to the neonatal intensive care unit?

BACKGROUND: To measure the rate of colonization of outborn infants with methicillin-resistant Staphylococcus aureus (MRSA) to evaluate the need for Contact Precautions (including isolation) at the time of admission to the neonatal intensive care unit (NICU). METHODS: All 239 consecutive infants referred from the neonatal units of other hospitals to a tertiary NICU in Al Ain, United Arab Emirates, between January 2000 and December 2007 were screened for MRSA colonization. Swabs from the ear, nose, rectum, axillae, and groin were obtained from each patient, and the rates of colonization were calculated retrospectively. RESULTS: Some 72% of newborns were admitted to our NICU in the first week. Only 1 patient, admitted from Oman, grew MRSA from the ear swab (rate, 0.4%; 95% confidence interval = 0.01% approximately 2.3%). CONCLUSION: This study from a tertiary NICU in a developing country shows that outborn infants are unlikely to harbor MRSA, and thus their routine admission in a single-bed isolation room is not justified. MRSA screening on admission has a very low yield and does not appear to be cost-effective. Contact Precautions should be reserved for those newborns transferred from general pediatric wards and those admitted from home.