Burden of bacterial antimicrobial resistance in low-income and middle-income countries avertible by existing interventions: an evidence review and modelling analysis.

National action plans enumerate many interventions as potential strategies to reduce the burden of bacterial antimicrobial resistance (AMR). However, knowledge of the benefits achievable by specific approaches is needed to inform policy making, especially in low-income and middle-income countries (LMICs) with substantial AMR burden and low health-care system capacity. In a modelling analysis, we estimated that improving infection prevention and control programmes in LMIC health-care settings could prevent at least 337 000 (95% CI 250 200-465 200) AMR-associated deaths annually. Ensuring universal access to high-quality water, sanitation, and hygiene services would prevent 247 800 (160 000-337 800) AMR-associated deaths and paediatric vaccines 181 500 (153 400-206 800) AMR-associated deaths, from both direct prevention of resistant infections and reductions in antibiotic consumption. These estimates translate to prevention of 7·8% (5·6-11·0) of all AMR-associated mortality in LMICs by infection prevention and control, 5·7% (3·7-8·0) by water, sanitation, and hygiene, and 4·2% (3·4-5·1) by vaccination interventions. Despite the continuing need for research and innovation to overcome limitations of existing approaches, our findings indicate that reducing global AMR burden by 10% by the year 2030 is achievable with existing interventions. Our results should guide investments in public health interventions with the greatest potential to reduce AMR burden.

Heterogeneity in prevalence of subclinical Plasmodium falciparum and Plasmodium vivax infections but no parasite genomic clustering in the Chittagong Hill Tracts, Bangladesh.

BACKGROUND: Malaria remains endemic in Bangladesh, with the majority of cases occurring in forested, mountainous region in the Chittagong Hill Tracts (CHT). This area is home to Bengali and diverse groups of indigenous people (Pahari) residing largely in mono-ethnic villages. METHODS: 1002 individuals of the 9 most prominent Pahari and the Bengali population were randomly selected and screened by RDT and qPCR. Parasites were genotyped by msp2 and deep sequencing of 5 amplicons (ama1-D3, cpmp, cpp, csp, and msp7) for Plasmodium falciparum (n = 20), and by microsatellite (MS) typing of ten loci and amplicon sequencing of msp1 for Plasmodium vivax (n = 21). Population structure was analysed using STRUCTURE software. Identity-by-state (IBS) was calculated as a measure of parasite relatedness and used to generate relatedness networks. RESULTS: The prevalence of P. falciparum and P. vivax infection was 0.7% by RDT (P. falciparum 6/1002; P. vivax 0/1002, mixed: 1/1002) and 4% by qPCR (P. falciparum 21/1002; P. vivax 16/1002, mixed: 5/1002). Infections were highly clustered, with 64% (27/42) of infections occurring in only two Pahari groups, the Khumi and Mro. Diversity was high; expected heterozygosity was 0.93 for P. falciparum and 0.81 for P. vivax. 85.7% (18/21) of P. vivax and 25% (5/20) of P. falciparum infections were polyclonal. No population structure was evident for either species, suggesting high transmission and gene flow among Pahari groups. CONCLUSIONS: High subclinical infection prevalence and genetic diversity mirror ongoing transmission. Control activities should be specifically directed to Pahari groups at greatest risk.

Glucose-6-phosphate dehydrogenase activity in individuals with and without malaria: Analysis of clinical trial, cross-sectional and case-control data from Bangladesh.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) activity is dependent upon G6PD genotype and age of the red blood cell (RBC) population, with younger RBCs having higher activity. Peripheral parasitemia with Plasmodium spp. induces hemolysis, replacing older RBCs with younger cells with higher G6PD activity. This study aimed to assess whether G6PD activity varies between individuals with and without malaria or a history of malaria. METHODS AND FINDINGS: Individuals living in the Chittagong Hill Tracts of Bangladesh were enrolled into 3 complementary studies: (i) a prospective, single-arm clinical efficacy trial of patients (n = 175) with uncomplicated malaria done between 2014 and 2015, (ii) a cross-sectional survey done between 2015 and 2016 (n = 999), and (iii) a matched case-control study of aparasitemic individuals with and without a history of malaria done in 2020 (n = 506). G6PD activity was compared between individuals with and without malaria diagnosed by microscopy, rapid diagnostic test (RDT), or polymerase chain reaction (PCR), and in aparasitemic participants with and without a history of malaria. In the cross-sectional survey and clinical trial, 15.5% (182/1,174) of participants had peripheral parasitemia detected by microscopy or RDT, 3.1% (36/1,174) were positive by PCR only, and 81.4% (956/1,174) were aparasitemic. Aparasitemic individuals had significantly lower G6PD activity (median 6.9 U/g Hb, IQR 5.2-8.6) than those with peripheral parasitemia detected by microscopy or RDT (7.9 U/g Hb, IQR 6.6-9.8, p < 0.001), but G6PD activity similar to those with parasitemia detected by PCR alone (submicroscopic parasitemia) (6.1 U/g Hb, IQR 4.8-8.6, p = 0.312). In total, 7.7% (14/182) of patients with malaria had G6PD activity < 70% compared to 25.0% (248/992) of participants with submicroscopic or no parasitemia (odds ratio [OR] 0.25, 95% CI 0.14-0.44, p < 0.001). In the case-control study, the median G6PD activity was 10.3 U/g Hb (IQR 8.8-12.2) in 253 patients with a history of malaria and 10.2 U/g Hb (IQR 8.7-11.8) in 253 individuals without a history of malaria (p = 0.323). The proportion of individuals with G6PD activity < 70% was 11.5% (29/253) in the cases and 15.4% (39/253) in the controls (OR 0.7, 95% CI 0.41-1.23, p = 0.192). Limitations of the study included the non-contemporaneous nature of the clinical trial and cross-sectional survey. CONCLUSIONS: Patients with acute malaria had significantly higher G6PD activity than individuals without malaria, and this could not be accounted for by a protective effect of G6PD deficiency. G6PD-deficient patients with malaria may have higher than expected G6PD enzyme activity and an attenuated risk of primaquine-induced hemolysis compared to the risk when not infected.

Correction: Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1003084.].

Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

BACKGROUND: The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. METHODS AND FINDINGS: Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3-14.0) for the Trinity assay and 8.3 U/g Hb (6.8-15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%-94%) to 100% (95% CI: 96%-100%) and specificity from 96% (95% CI: 89%-99%) to 100% (100%-100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%-75%) and specificity to 35% (95% CI: 24%-46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies. CONCLUSIONS: Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.

Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group.

The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness.

Barriers to routine G6PD testing prior to treatment with primaquine.

BACKGROUND: Primaquine is essential for the radical cure of vivax malaria, however its broad application is hindered by the risk of drug-induced haemolysis in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. Rapid diagnostic tests capable of diagnosing G6PD deficiency are now available, but these are not used widely. METHODS: A series of qualitative interviews were conducted with policy makers and healthcare providers in four vivax-endemic countries. Routine G6PD testing is not part of current policy in Bangladesh, Cambodia or China, but it is in Malaysia. The interviews were analysed with regard to respondents perceptions of vivax malaria, -primaquine based treatment for malaria and the complexities of G6PD deficiency. RESULTS: Three barriers to the roll-out of routine G6PD testing were identified in all sites: (a) a perceived low risk of drug-induced haemolysis; (b) the perception that vivax malaria was benign and accordingly treatment with primaquine was not regarded as a priority; and, (c) the additional costs of introducing routine testing. In Malaysia, respondents considered the current test and treat algorithm suitable and the need for an alternative approach was only considered relevant in highly mobile and hard to reach populations. CONCLUSIONS: Greater efforts are needed to increase awareness of the benefits of the radical cure of Plasmodium vivax and this should be supported by economic analyses exploring the cost effectiveness of routine G6PD testing.

Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group.

The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia-Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by  the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.

Reduction in malaria prevalence and increase in malaria awareness in endemic districts of Bangladesh.

BACKGROUND: Malaria is endemic in 13 districts of Bangladesh. A baseline malaria prevalence survey across the endemic districts of Bangladesh was conducted in 2007, when the prevalence was reported around 39.7 per 1000 population. After two rounds of Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)-funded intervention by the National Malaria Control Programme (NMCP) and a BRAC-led NGO consortium, a follow-up survey was conducted across the malaria-endemic districts of Bangladesh to measure the change in prevalence rate and in people's knowledge of malaria. METHODS: The survey was carried out from August to November 2013 in 70 upazilas (sub-districts) of 13 malaria-endemic districts of Bangladesh, following the same multi-stage cluster sampling design and the same number of households enrolled during the baseline prevalence survey in 2007, to collect 9750 randomly selected blood samples. For on-the-spot diagnosis of malaria, a rapid diagnostic test was used. The household head or eldest person available was interviewed using a pre-coded structured questionnaire to collect data on the knowledge and awareness of malaria in the household. RESULTS: Based on a weighted calculation, the overall malaria prevalence was found to be 1.41 per 1000 population. The proportion of Plasmodium falciparum mono-infection was 77.78% while both Plasmodium vivax mono-infection and mixed infection of the two species were found to be 11.11%. Bandarban had the highest prevalence (6.67 per 1000 population). Knowledge of malaria signs, symptoms and mode of transmission were higher in the follow-up survey (97.26%) than the baseline survey. Use of bed nets for prevention of malaria was found to be high (90.15%) at respondent level. People's knowledge of selected parameters increased significantly during the follow-up survey compared to the baseline survey conducted in 2007. CONCLUSIONS: A reduced prevalence rate of malaria and increased level of knowledge were observed in the present malaria prevalence survey in Bangladesh.

The challenges of introducing routine G6PD testing into radical cure: a workshop report.

The only currently available drug that effectively removes malaria hypnozoites from the human host is primaquine. The use of 8-aminoquinolines is hampered by haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Recently a number of qualitative and a quantitative rapid diagnostic test (RDT) format have been developed that provide an alternative to the current standard G6PD activity assays. The WHO has recently recommended routine testing of G6PD status prior to primaquine radical cure whenever possible. A workshop was held in the Philippines in early 2015 to discuss key challenges and knowledge gaps that hinder the introduction of routine G6PD testing. Two point-of-care (PoC) test formats for the measurement of G6PD activity are currently available: qualitative tests comparable to malaria RDT as well as biosensors that provide a quantitative reading. Qualitative G6PD PoC tests provide a binomial test result, are easy to use and some products are comparable in price to the widely used fluorescent spot test. Qualitative test results can accurately classify hemizygous males, heterozygous females, but may misclassify females with intermediate G6PD activity. Biosensors provide a more complex quantitative readout and are better suited to identify heterozygous females. While associated with higher costs per sample tested biosensors have the potential for broader use in other scenarios where knowledge of G6PD activity is relevant as well. The introduction of routine G6PD testing is associated with additional costs on top of routine treatment that will vary by setting and will need to be assessed prior to test introduction. Reliable G6PD PoC tests have the potential to play an essential role in future malaria elimination programmes, however require an improved understanding on how to best integrate routine G6PD testing into different health settings.

A systematic analysis of commonly used antibodies in cancer diagnostics.

AIMS: Immunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. METHODS AND RESULTS: A tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. CONCLUSIONS: The results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer.

High prevalence and genetic diversity of Plasmodium malariae and no evidence of Plasmodium knowlesi in Bangladesh.

Although the prevalence of malaria remains high in parts of Bangladesh, there continues to be a substantial shortage of information regarding the less common malaria parasites such as Plasmodium malariae or Plasmodium knowlesi. Recent studies indicate that P. malariae may be extremely rare, and so far, there are no data on the presence (or absence) of P. knowlesi in southeastern Bangladesh. Genus- and species-specific nested polymerase chain reaction (PCR) analysis of the small subunit ribosomal RNA gene was performed to assess the presence and prevalence of P. malariae and P. knowlesi in 2,246 samples originating from asymptomatic and febrile participants of a cross-sectional and a febrile illnesses study in the Chittagong Hill Tracts in southeastern Bangladesh. P. malariae was detected in 60 samples (2.7%) corresponding to 8% of the 746 samples giving positive PCR results for Plasmodium sp., mainly because of the high prevalence (9.5%) among asymptomatic study participants testing positive for malaria. Symptomatic cases were more common (4.3% of all symptomatic malaria cases) during the dry season. Parasitemias were low (1,120-2,560/µl in symptomatic and 120-520/µl in asymptomatic carriers). Symptomatic patients presented mild to moderate symptoms like fever, chills, headache, dizziness, fatigue and myalgia.Although both the intermediate as well as the definite host are known to be endemic in southeastern Bangladesh, no evidence for the presence of P. knowlesi was found. We conclude that the role of P. malariae is highly underestimated in rural Bangladesh with major implications for malaria control and elimination strategies.

Diagnosis of pneumonia in children with dehydrating diarrhoea.

The World Health Organization (WHO) guidelines for diagnosis of pneumonia are based on the history of cough or difficult breathing and age-adjusted respiration rates. Metabolic acidosis associated with dehydrating diarrhoea also influences the respiration rate. Two hundred and four children, aged 2 to 59 months, with dehydrating diarrhoea and a history of cough and/or fast breathing, were enrolled in a prospective study. Pneumonia diagnoses were made on enrollment and again 6 hours post-enrollment (after initial rehydration), using the WHO guidelines. These were compared with investigators' clinical diagnosis based on history and findings of physical examination and a chest x-ray at the same time points. Using the WHO guidelines, 149/152 (98%) infants in the 2-11 months age-group and 38/40 (95%) children in the 12-59 months age-group were diagnosed to have pneumonia on enrollment, which dropped to 107 (70%) and 30 (75%) respectively at 6 hours post-enrollment. The specificity of the WHO guidelines for diagnosis of pneumonia was very low (6.9%) at enrollment but increased to 65.5% at 6 hours post-enrollment, after initial rehydration. The specificity of the WHO guidelines for diagnosis of pneumonia in young children is significantly reduced in dehydrating diarrhoea. For young children with dehydrating diarrhoea, rehydration, clinical and radiological assessments are useful in identifying those with true pneumonia.

Primary Burkitt's lymphoma of endometrium and bilateral ovaries in a 6-year-old female: report of a rare entity and review of the published work.

We report a case of a 6-year-old girl with primary Burkitt's lymphoma (BL) of endometrium and bilateral ovaries of 1-month duration. To the best of our knowledge, few cases of childhood primary BL of bilateral ovaries have been reported worldwide. However, extensive search of the published work did not reveal any case of primary BL of endometrium and both ovaries. Although rare, BL is a potentially curable malignancy with good prognosis.

Giant cell interstitial pneumonia: an unusual finding in a case of preoperative death.

Giant cell interstitial pneumonia (GIP) is an exceedingly rare, debatable, perplexing, occupational lung disease, which most commonly affects individuals exposed to hard metal dust. We report a case of GIP in a 60-year-old man, scheduled for coronary artery bypass graft surgery and died during induction of general anesthesia despite all efforts to resuscitate him. Patient's relatives lodged complaint with the police alleging the negligence by the attending physicians. Despite inaccessible data pertaining to the occupation, clinical history, and radiographic findings, the diagnosis was GIP due to the presence of intra-alveolar, bizarre, "cannibalistic" multinucleated giant cells-the histologic sine qua non of GIP. To the best of our knowledge, this is the first case report of GIP in the world literature that was diagnosed on histopathologic examination of lung tissue obtained at medicolegal autopsy.

Bangladesh in the era of malaria elimination.

Bangladesh has dramatically reduced malaria by 93% from 2008 to 2020. The strategy has been district-wise, phased elimination; however, the last districts targeted for elimination include remote, forested regions which present several challenges for prevention, detection, and treatment of malaria. These districts border Myanmar which harbors Plasmodium falciparum malaria parasites resistant to artemisinins, key drugs used in artemisinin-based combination therapies (ACTs) that have been vital for control programs. Challenges in monitoring emergence of artemisinin resistance (AR), tracking parasite reservoirs, changes in vector behavior and responses to insecticides, as well as other environmental and host factors (including the migration of Forcibly Displaced Myanmar Nationals; FDMNs) may pose added hazards in the final phase of eliminating malaria in Bangladesh.

Is this pill an antibiotic or a painkiller? Improving the identification of oral antibiotics for better use.

In this Viewpoint, we discuss how the identification of oral antibiotics and their distinction from other commonly used medicines can be challenging for consumers, suppliers, and health-care professionals. There is a large variation in the names that people use to refer to antibiotics and these often relate to their physical appearance, although antibiotics come in many different physical presentations. We also reflect on how the physical appearance of medicine influences health care and public health by affecting communication between patients and health-care professionals, dispensing , medicine use, and the public understanding of health campaigns. Furthermore, we report expert and stakeholder consultations on improving the identification of oral antibiotics and discuss next steps towards a new identification system for antibiotics. We propose to use the physical appearance as a tool to support and nudge awareness about antibiotics and their responsible use.

Adherence to Anti-Malarial Treatment in Malaria Endemic Areas of Bangladesh.

Ensuring adherence to antimalarial treatment is crucial for achieving a radical cure and elimination of malaria, especially in hard-to-reach areas. We conducted this study to assess the current scenario of drug adherence in four endemic sub-districts of Bangladesh. Among 110 enrolled participants, 70% were mono-infected with Plasmodium falciparum and the remaining 30% with P. vivax. The overall treatment adherence frequency was 92.7% (95% CI: 83.0-96.3%). A total of eight participants were found to be nonadherent to treatment and all of them were from Bandarban. Level of nonadherence was equally observed in two age groups: 11-17 and 18+ years. However, male participants (n = 6) were found to be more nonadherent than females (n = 2). Among 7.3% with nonadherence to treatment, a single participant with P. falciparum mono-infection refused to take medication and became nonadherent. Remaining participants stated that they were feeling well and going to work, thus leaving treatment course uncompleted. Although overall compliance with malaria medication seems good, a gradual increase in noncompliance to P. vivax malaria treatment suggests that the National Malaria Elimination Program must be enhanced and monitored to fulfil the projected malaria elimination goal before 2030 from Bangladesh.

Antiplasmodial activity of flavonol quercetin and its analogues in Plasmodium falciparum: evidence from clinical isolates in Bangladesh and standardized parasite clones.

Malaria is still a major threat in many parts of the world with resistance spreading to almost all classes of antimalarials. The limited arsenal of available antimalarial drugs emphasizes the urgent need for novel antimalarial compounds. Owing to the fact that novel leads from nature have traditionally played a pivotal role in the development of various classes of antimalarials, we investigated a set of eight naturally occurring dietary flavonoids and their analogues for their antiplasmodial activity on clinical field isolates in southeastern Bangladesh and culture-adapted chloroquine-sensitive and chloroquine-resistant parasite clones. Except for taxifolin, all the other flavonoids had 50% inhibitory concentrations below 14 µM, both in the field and laboratory-adapted parasites. Neither of the flavonoids showed any activity correlation with chloroquine. The quercetin analogue rutin (7.10 ± 10.32 µM) was the most active substance in field isolates as well as laboratory-adapted cultures (3.53 ± 13.34 µM in 3D7 and 10.38 ± 15.08 µM in K1), providing the first evidence of its activity against Plasmodium falciparum parasites. Thus, our results provide important evidence of the antimalarial activity of flavonoids in traditional use and thus warrant further investigation of these compounds as potential antiplasmodial agents.

Ovarian ligament adenomyoma: report of a rare entity with review of the literature.

Adenomyoma is a benign tumor composed of endometrial glands, specialized endometrioid stroma, and smooth muscle. These tumors typically originate within the uterus. An extrauterine adenomyoma is an extremely rare entity. We present the case of a 56-year-old perimenopausal woman with a right adnexal mass, diagnosed histopathologically as an ovarian ligament adenomyoma. This report documents a fourth case of an extrauterine adenomyoma and only the second case in ovarian ligament. The differential diagnosis includes endometrioma, leiomyomatosis peritonealis disseminata, uterus-like mass lesion and extrauterine leiomyoma with entrapped endometrioid glands and stroma. Two theories for the etiology of adenomyoma have been proposed: (i) Müllerian duct fusion defect and (ii) metaplasia.