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Fulltext The prevalence of simian malaria in wild long-tailed macaques throughout Peninsular Malaysia

Shahari S, Bin Abdullah ML, Binti Isman Rohimly AA, Binti Ashrat N, Amir A, Atroosh WMM, et al.

Sci Rep, 2024 Mar 12;14(1):6023.
PMID: 38472278 DOI: 10.1038/s41598-024-54981-2

The parasite Plasmodium knowlesi has been the sole cause of malaria in Malaysia from 2018 to 2022. The persistence of this zoonotic species has hampered Malaysia's progress towards achieving the malaria-free status awarded by the World Health Organisation (WHO). Due to the zoonotic nature of P. knowlesi infections, it is important to study the prevalence of the parasite in the macaque host, the long-tailed macaque (Macaca fascicularis). Apart from P. knowlesi, the long-tailed macaque is also able to harbour Plasmodium cynomolgi, Plasmodium inui, Plasmodium caotneyi and Plasmodium fieldi. Here we report the prevalence of the 5 simian malaria parasites in the wild long-tailed macaque population in 12 out of the 13 states in Peninsular Malaysia using a nested PCR approach targeting the 18s ribosomal RNA (18s rRNA) gene. It was found that all five Plasmodium species were widely distributed throughout Peninsular Malaysia except for states with major cities such as Kuala Lumpur and Putrajaya. Of note, Pahang reported a malaria prevalence of 100% in the long-tailed macaque population, identifying it as a potential hotspot for zoonotic transmission. Overall, this study shows the distribution of the 5 simian malaria parasite species throughout Peninsular Malaysia, the data of which could be used to guide future malaria control interventions to target zoonotic malaria.
Natural Plasmodium infection in wild macaques of three states in peninsular Malaysia

Amir A, Shahari S, Liew JWK, de Silva JR, Khan MB, Lai MY, et al.

Acta Trop, 2020 Nov;211:105596.
PMID: 32589995 DOI: 10.1016/j.actatropica.2020.105596

Zoonotic cases of Plasmodium knowlesi account for most malaria cases in Malaysia, and humans infected with P. cynomolgi, another parasite of macaques have recently been reported in Sarawak. To date the epidemiology of malaria in its natural Macaca reservoir hosts remains little investigated. In this study we surveyed the prevalence of simian malaria in wild macaques of three states in Peninsular Malaysia, namely Pahang, Perak and Johor using blood samples from 103 wild macaques (collected by the Department of Wildlife and National Parks Peninsular Malaysia) subjected to microscopic examination and nested PCR targeting the Plasmodium small subunit ribosomal RNA gene. As expected, PCR analysis yielded significantly higher prevalence (64/103) as compared to microscopic examination (27/103). No relationship between the age and/or sex of the macaques with the parasitaemia and the Plasmodium species infecting the macaques could be identified. Wild macaques in Pahang had the highest prevalence of Plasmodium parasites (89.7%), followed by those of Perak (69.2%) and Johor (28.9%). Plasmodium inui and P. cynomolgi were the two most prevalent species infecting the macaques from all three states. Half of the macaques (33/64) harboured two or more Plasmodium species. These data provide a baseline survey, which should be extended by further longitudinal investigations that should be associated with studies on the bionomics of the anopheline vectors. This information will allow an accurate evaluation of the risk of zoonotic transmission to humans, and to elaborate effective strategies to control simian malaria.
The value of small mangrove patches

Curnick DJ, Pettorelli N, Amir AA, Balke T, Barbier EB, Crooks S, et al.

Science, 2019 01 18;363(6424):239.
PMID: 30655434 DOI: 10.1126/science.aaw0809
Fulltext Reduced red blood cell deformability in Plasmodium knowlesi malaria

Barber BE, Russell B, Grigg MJ, Zhang R, William T, Amir A, et al.

Blood Adv, 2018 02 27;2(4):433-443.
PMID: 29487058 DOI: 10.1182/bloodadvances.2017013730

The simian parasite Plasmodium knowlesi can cause severe and fatal human malaria. However, little is known about the pathogenesis of this disease. In falciparum malaria, reduced red blood cell deformability (RBC-D) contributes to microvascular obstruction and impaired organ perfusion. In P knowlesi infection, impaired microcirculatory flow has been observed in Macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. However, RBC-D has not been measured in human infection or in the natural host M fascicularis (long-tailed macaques). Using ektacytometry, we measured RBC-D in adults with severe and non-severe knowlesi and falciparum malaria and in healthy controls. In addition, we used micropipette aspiration to determine the relative stiffness of infected RBCs (iRBCs) and uninfected RBCs (uRBCs) in P knowlesi-infected humans and M fascicularis Ektacytometry demonstrated that RBC-D overall was reduced in human knowlesi malaria in proportion to disease severity, and in severe knowlesi malaria, it was comparable to that of severe falciparum malaria. RBC-D correlated inversely with parasitemia and lactate in knowlesi malaria and HRP2 in falciparum malaria, and it correlated with hemoglobin nadir in knowlesi malaria. Micropipette aspiration confirmed that in humans, P knowlesi infection increased stiffness of both iRBCs and uRBCs, with the latter mostly the result of echinocytosis. In contrast, in the natural host M fascicularis, echinocyte formation was not observed, and the RBC-D of uRBCs was unaffected. In unnatural primate hosts of P knowlesi, including humans, reduced deformability of iRBCs and uRBCs may represent a key pathogenic mechanism leading to microvascular accumulation, impaired organ perfusion, and anemia.
Fulltext Effects of immunonutrition on biomarkers in traumatic brain injury patients in Malaysia: a prospective randomized controlled trial

Rai VRH, Phang LF, Sia SF, Amir A, Veerakumaran JS, Kassim MKA, et al.

BMC Anesthesiol, 2017 06 15;17(1):81.
PMID: 28619005 DOI: 10.1186/s12871-017-0369-4

BACKGROUND: Head injury is one of the top three diagnosis leading to intensive care unit (ICU) admission in Malaysia. There has been growing interest in using immunonutrition as a mode of modulating the inflammatory response to injury or infection with the aim of improving clinical outcome. The aim of the present study was to evaluate the effect of an immunonutrition on biomarkers (IL-6, glutathione, CRP, total protein and albumin) in traumatic brain injury patients.
METHODS: Thirty six patients with head injury admitted to neurosurgical ICU in University Malaya Medical Centre were recruited for this study, over a 6-month period from July 2014 to January 2015. Patients were randomized to receive either an immunonutrition (Group A) or a standard (Group B) enteral feed. Levels of biomarkers were measured at day 1, 5 and 7 of enteral feeding.
RESULTS: Patients in Group A showed significant reduction of IL-6 at day 5 (p
Fulltext Antibiotic consumption at community pharmacies: A multicenter repeated prevalence surveillance using WHO methodology

Saleem Z, Faller EM, Godman B, Malik MSA, Iftikhar A, Iqbal S, et al.

Med Access Point Care, 2021 12 16;5:23992026211064714.
PMID: 36204499 DOI: 10.1177/23992026211064714

Background: Antibiotics are losing their effectiveness because of the rapid emergence of resistant bacteria. Unnecessary antimicrobial use increases antimicrobial resistance (AMR). There are currently no published data on antibiotic consumption in Pakistan at the community level. This is a concern given high levels of self-purchasing of antibiotics in Pakistan and variable knowledge regarding antibiotics and AMR among physicians and pharmacists.
Objective: The objective of this repeated prevalence survey was to assess the pattern of antibiotic consumption data among different community pharmacies to provide a baseline for developing future pertinent initiatives.
Methods: A multicenter repeated prevalence survey conducted among community pharmacies in Lahore, a metropolitan city with a population of approximately 10 million people, from October to December 2017 using the World Health Organization (WHO) methodology for a global program on surveillance of antimicrobial consumption.
Results: The total number of defined daily doses (DDDs) dispensed per patient ranged from 0.1 to 50.0. In most cases, two DDDs per patient were dispensed from pharmacies. Co-amoxiclav was the most commonly dispensed antibiotic with a total number of DDDs at 1018.15. Co-amoxiclav was followed by ciprofloxacin with a total number of 486.6 DDDs and azithromycin with a total number of 472.66 DDDs. The least consumed antibiotics were cefadroxil, cefotaxime, amikacin, and ofloxacin, with overall consumption highest in December.
Conclusion: The study indicated high antibiotic usage among community pharmacies in Lahore, Pakistan particularly broad-spectrum antibiotics, which were mostly dispensed inappropriately. The National action plan of Pakistan on AMR should be implemented by policymakers including restrictions on the dispensing of antimicrobials.
Case report: recurrence of Plasmodium vivax malaria due to defective cytochrome P450 2D6 function in Pos Lenjang, Pahang, Malaysia

Mat Salleh NH, Rahman MFA, Samsusah S, De Silva JR, Ng DC, Ghozali AH, et al.

Trans R Soc Trop Med Hyg, 2020 Sep 01;114(9):700-703.
PMID: 32511702 DOI: 10.1093/trstmh/traa042

Five children in Pos Lenjang, Pahang, Malaysia were PCR-positive for vivax malaria and were admitted to the hospital from 5 to 26 July 2019. One of the patients experienced three episodes of recurrence of vivax malaria. Microsatellite analysis showed that reinfection is unlikely. Drug resistance analysis indicated that Riamet (artemether-lumefantrine) is effective. Cytochrome P450 2D6 (CYP2D6) testing showed that this patient has defective CYP2D6 function. Primaquine failure to clear the Plasmodium vivax hypnozoites may be the cause of recurring infections in this patient. This report highlights the need for the development of liver-stage curative antimalarials that do not require metabolism by the CYP2D6 enzyme.
Simian malaria: a narrative review on emergence, epidemiology and threat to global malaria elimination

Fornace KM, Zorello Laporta G, Vythilingham I, Chua TH, Ahmed K, Jeyaprakasam NK, et al.

Lancet Infect Dis, 2023 Dec;23(12):e520-e532.
PMID: 37454671 DOI: 10.1016/S1473-3099(23)00298-0

Simian malaria from wild non-human primate populations is increasingly recognised as a public health threat and is now the main cause of human malaria in Malaysia and some regions of Brazil. In 2022, Malaysia became the first country not to achieve malaria elimination due to zoonotic simian malaria. We review the global distribution and drivers of simian malaria and identify priorities for diagnosis, treatment, surveillance, and control. Environmental change is driving closer interactions between humans and wildlife, with malaria parasites from non-human primates spilling over into human populations and human malaria parasites spilling back into wild non-human primate populations. These complex transmission cycles require new molecular and epidemiological approaches to track parasite spread. Current methods of malaria control are ineffective, with wildlife reservoirs and primarily outdoor-biting mosquito vectors urgently requiring the development of novel control strategies. Without these, simian malaria has the potential to undermine malaria elimination globally.
Fulltext Enterobius vermicularis salpingitis seen in the setting of ectopic pregnancy in a Malaysian patient

Ngui R, Ravindran S, Ong DB, Chow TK, Low KP, Nureena ZS, et al.

J Clin Microbiol, 2014 Sep;52(9):3468-70.
PMID: 24989613 DOI: 10.1128/JCM.01191-14

We report a rare and unusual case of invasive Enterobius vermicularis infection in a fallopian tube. The patient was a 23-year-old Malaysian woman who presented with suprapubic pain and vaginal bleeding. A clinical diagnosis of ruptured right ovarian ectopic pregnancy was made. She underwent a laparotomy with a right salpingo-oophorectomy. Histopathological examination of the right fallopian tube showed eggs and adult remnants of E. vermicularis, and the results were confirmed using PCR and DNA sequencing.
Progress on the national action plan of Pakistan on antimicrobial resistance (AMR): a narrative review and the implications

Saleem Z, Godman B, Azhar F, Kalungia AC, Fadare J, Opanga S, et al.

Expert Rev Anti Infect Ther, 2022 Jan;20(1):71-93.
PMID: 34038294 DOI: 10.1080/14787210.2021.1935238

INTRODUCTION: The emergence of antimicrobial resistance (AMR) is a threat to public health. In 2015, the World Health Organization (WHO) introduced a global action plan to tackle AMR in the World Health Assembly. Pakistan's national action plan (NAP) for AMR was released in May 2017 by the Ministry of National Health Services. Based on the NAP, strategies have been initiated on a national and provincial scale in Pakistan.
AREAS COVERED: This narrative review of the five components of the Pakistan NAP has been undertaken to discuss some of the challenges in implementation of the NAP for AMR in Pakistan including different opinions and views of key stakeholders, combined with suggestions on potential ways to reduce the burden of the AMR.
EXPERT OPINION: Going forward, healthcare authorities should focus on screening and monitoring of all the objectives of the NAP by establishing proper policies as well as promoting antimicrobial stewardship interventions and Infection prevention and control (IPC) practices. Overall, the comprehensive strengthening of the healthcare system is required to adequately implement the NAP, tackle continued inappropriate antimicrobial use and high AMR rates in Pakistan.
Fulltext Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi

Moon RW, Sharaf H, Hastings CH, Ho YS, Nair MB, Rchiad Z, et al.

Proc Natl Acad Sci U S A, 2016 Jun 28;113(26):7231-6.
PMID: 27303038 DOI: 10.1073/pnas.1522469113

The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.
Fulltext Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data

Cannarella R, Shah R, Hamoda TAA, Boitrelle F, Saleh R, Gul M, et al.

World J Mens Health, 2024 Jan;42(1):92-132.
PMID: 37382284 DOI: 10.5534/wjmh.230034

PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles.
MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies).
RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864.
CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.
Fulltext Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations

Rambhatla A, Shah R, Ziouziou I, Kothari P, Salvio G, Gul M, et al.

World J Mens Health, 2024 Apr 04.
PMID: 38606867 DOI: 10.5534/wjmh.230339

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA.
MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit.
CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
Fulltext Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations

Shah R, Rambhatla A, Atmoko W, Martinez M, Ziouziou I, Kothari P, et al.

World J Mens Health, 2024 Apr 03.
PMID: 38606865 DOI: 10.5534/wjmh.230333

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations.
MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations.
RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate.
CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

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