Harparkash Kaur

London School of Hygiene and Tropical Medicine | LSHTM · Faculty of Infectious and Tropical Diseases

Background: Insecticide-treated nets and indoor residual spraying of insecticides are used as the vector control interventions in the fight against malaria. Measuring the actual amount of deposits of insecticides on bed nets and walls is essential for evaluating the quality and effectiveness of the intervention. A colorimetric "Test Kit" designed...

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and is capable of causing severe symptoms, such as pseudomembranous colitis and toxic megacolon. An unusual feature of C. difficile is the distinctive production of high levels of the antimicrobial compound para -cresol. p -Cresol production provides C. difficile with a...

Background Pyronaridine–artesunate is the most recently licensed artemisinin-based combination therapy. WHO has recommended that a single low dose of primaquine could be added to artemisinin-based combination therapies to reduce Plasmodium falciparum transmission in areas aiming for elimination of malaria or areas facing artemisinin resistance. We...

Background Long-lasting efficacy of insecticide-treated nets is a balance between adhesion, retention and migration of insecticide to the surface of netting fibres. ICON ® Maxx is a twin-sachet ‘home-treatment kit’ of pyrethroid plus binding agent, recommended by the World Health Organization (WHO) for long-lasting, wash-fast treatment of polyester...

Background Long-lasting efficacy of insecticide treated nets is a balance between adhesion, retention and migration of insecticide to the surface of netting fibres. ICON® Maxx is a twin-sachet ‘home-treatment kit’ of pyrethroid plus binding agent, recommended by the World Health Organization for long-lasting, wash-fast treatment of polyester nets....

Since the introduction of antibiotics into mainstream health care, resistance to these drugs has become a widespread issue that continues to increase worldwide. Policy decisions to mitigate the development of antimicrobial resistance are hampered by the current lack of surveillance data on antibiotic product availability and use in low-income count...

Background Insecticide-treated nets and indoor residual spraying of insecticides are used as the major vector control interventions in the fight against malaria. Measuring the actual amount of deposits of insecticides on bed nets and walls is essential for evaluating the quality and effectiveness of the intervention. A colorimetric “Test Kit” desig...

Background Insecticides used in vector control mostly rely on vectors being exposed through contact with treated surfaces, yet little is known about the amount picked up by the insect. Measuring this amount is relevant not only for determining the actual doses that are lethal to the mosquito, but also for understanding effects on the physiology and...

Clostridioides difficile infection results from antibiotic-associated dysbiosis. para -Cresol, a phenolic compound produced by C. difficile , selectively targets gammaproteobacteria in the gut, facilitating dysbiosis. Here, we demonstrate that expression of the hpdBCA operon, encoding the HpdBCA decarboxylase which converts p -HPA to p -cresol, is...

Background: Widespread access to good quality antihypertensive medicines is a critical component for reducing premature cardiovascular disease (CVD) mortality. Poor-quality medicines pose serious health concerns; however, there remains a knowledge gap about the quality of cardiovascular medicines available in low-and middle-income countries.

Background: Widespread access to good quality antihypertensive medicines is a critical component for reducing premature cardiovascular disease (CVD) mortality. Poor-quality medicines pose serious health concerns; however, there remains a knowledge gap about the quality of cardiovascular medicines available in low- and middle-income countries. Obj...

Background: We assessed the impact of exposure to P. falciparum on parasite kinetics, clinical symptoms, and functional immunity after controlled human malaria infection (CHMI) in two cohorts with different levels of previous malarial exposure. Methods: Nine adult males with high (sero-high) and ten with low (sero-low) previous exposure received...

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recove...

Comparison of the metabolite profiles in medium supplemented with 0.1% and 0.2% pHPA. 1H NMR spectroscopy was used to determine the metabolite profiles of co-culture samples in media containing 0.1% and 0.2% p-HPA. a) PCA demonstrating metabolic variation across the profiles in media containing 0.1% or 0.2% (v/v) p-HPA. b) Loading plots of the PCA...

Gut intestinal microbes used in this study. (XLSX)

Statistical analysis of growth curves in BHIS with exogenous p-cresol. The top table shows the output of a Linear Regression analysis to compare the growth of a particular strain of bacteria, at a given concentration of p-cresol against the reference strain, C. difficile. Grey shading indicates analyses where the p<0.05. The bottom table indicates...

Differential growth rates in BHIS. Growth curves were performed in BHIS media under anaerobic conditions to determine the differential growth rate between C. difficile strains 630Δerm, hpdC::CT and the complemented mutant (hpdC::CT::phpdC-A and the intestinal microbiota species a) E. coli and K. oxytoca, and b) E. faecium and L. fermentum. The time...

Detection of p-cresol by 1H NMR. a) 1H NMR spectra doublet of pHPA (δ6.867ppm) and p-cresol (δ6.831ppm), with C. difficile strains highlighted in different colours 630Δerm (black), hpdC::CT (red) and the complemented mutant hpdC::CT::phpdC-A (blue). Each line represents an individual 1H NMR spectrum of the culture supernatants. The arrows on the ri...

Colony counts for different bacterial strains at OD 0.5. (XLSX)

Colony counts for extrinsic p-cresol co-culture experiments. CFU/ml was determined each bacterial species grown in co-culture in the presence or absence of extrinsic p-cresol. (XLSX)

Modulating p-cresol production and the effect on competitive co-culture. Relative fitness of C. difficile 630Δerm, hpdC::CT and hpdC::CT complement in competitive co-culture for 24 hours with gut commensal species was performed in media supplemented with p-HPA (0.3% v/v). Expression of the hpdCA in trans from a plasmid-borne tetracycline-inducible...

Sporulation assay of C. difficile strains. The sporulation frequency of strains 630Δerm, hpdC::CT and the complemented mutant hpdC::CT::phpdC-A, were determine in BHIS media grown for 72 hours in BHIS broth. a) total cell counts were enumerated on BHIS plates containing 0.1% taurocholate and spore counts were determined by heat inactivation of vege...

ANOSIM population analysis of the microbiota. ANOSIM was performed to identify differences in bacterial population between 630Δerm and hpdC::CT infected animals across the experiment as well as at given time points, D7, D0R, D2R and D4R. Significant differences are indicated with a circle p<0.001. (TIF)

Strains, plasmids and primers. (XLSX)

Minimum inhibitory concentrations of vancomycin and cefoperazone. (XLSX)

Diversity of the microbiome at Day 7. A table demonstrating the relative abundance of families comprising the faecal microbiome at day 7 for the wild-type infected, hpdC::CT infected and naïve mice. (XLSX)

Introduction Poor-quality artemisinin-containing antimalarials (ACAs), including falsified and substandard formulations, pose serious health concerns in malaria endemic countries. They can harm patients, contribute to the rise in drug resistance and increase the public’s mistrust of health systems. Systematic assessment of drug quality is needed to...

Background Management of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite susceptibility to ACT in Africa have now been well documented....

Background Assessing the quality of medicines in low-middle income countries (LMICs) relies primarily on human inspection and screening technologies, where available. Field studies and surveys have frequently utilized screening tests to analyse medicines sampled at the point of care, such as health care facilities and medicine outlets, to provide a...

Poor-quality medicines are a major problem for health-care systems in resource-poor settings as identifying falsified medicines requires a complex laboratory infrastructure such as a Medicines Quality Control Laboratory. We report here an evaluation of a low-cost, handheld near-infrared spectrometer (NIRS) device by analyzing a library of artemisin...

We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015-16. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitaemia within 6 weeks of treatment with no intervening travel to malarious countries. Parasite isolates, all of African origin, harbour...

Case histories are presented for four patients with malaria treated with artemether-lumefantrine in UK hospitals. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitaemia within 6 weeks of treatment. Parasite isolates, all of African origin, were genotyped at candidate resistance loci. No evidence of pfk13-mediated...

This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representati...

Dihydroartemisinin-piperaquine (DP) is recommended for the treatment of uncomplicated malaria, used in efforts to contain artemisinin resistance, and increasingly considered for mass drug administration. Because of the narrow therapeutic dose range and available tablet strengths, the manufacturers and World Health Organization recommended regimens...

Background Ghana changed their antimalarial drug policy from monotherapies to Artemisinin-based Combination Therapies in 2004 in order to provide more efficacious medicines for treatment of malaria. The policy change can be eroded if poor quality Artemisinin-based Combination Therapies are allowed to remain on the Ghanaian market unchecked by regul...

Background: The dengue and Zika viruses are primarily transmitted by Aedes aegypti mosquitoes, which are most active during day light hours and feed both in and outside of the household. Personal protection technologies such as insecticide-treated clothing could provide individual protection. Here we assessed the efficacy of permethrin-treated clo...

Poor quality antimalarials, including falsified, substandard, and degraded drugs, are a serious health concern in malaria-endemic countries. Guidelines are lacking on how to distinguish between substandard and degraded drugs. "Forced degradation" in an oven was carried out on three common artemisinin-based combination therapy (ACT) brands to detect...

Background Prevention and optimal management of hypertension in the general population is paramount to the achievement of the World Heart Federation (WHF) goal of reducing premature cardiovascular disease (CVD) mortality by 25% by the year 2025 and widespread access to good quality antihypertensive medicines is a critical component for achieving th...

Introduction: Dengue transmission by the mosquito vector, Aedes aegypti, occurs indoors and outdoors during the day. Personal protection of individuals, particularly when outside, is challenging. Here we assess the efficacy and durability of different types of insecticide-treated clothing on laboratory-reared Ae. aegypti. Methods: Standardised W...

Published in Medicine Maker as an invited opinion piece When you think about counterfeit and falsified medicines in developing countries, antimalarials are likely to spring to mind first – but we shouldn't forget that antibiotics are also important targets for fraudsters. In either case, more quality control testing is needed.

Recent studies alluded to the alarming scale of poor anti-malarial drug quality in malaria-endemic countries, but also illustrated the major geographical gaps in data on anti-malarial drug quality from endemic countries. Data are particularly scarce from Central Africa, although it carries the highest burden of malaria. The aim of this medicine qua...

Insecticide-treated nets are the primary method of preventing malaria. To remain effective, the pyrethroid insecticide must withstand multiple washes over the lifetime of the net. ICON® Maxx is a 'dip-it-yourself' kit for long-lasting treatment of polyester nets. The twin-sachet kit contains a slow-release capsule suspension of lambda-cyhalothrin p...

Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from...

In 2003, a stratified random sample survey was conducted in the Lao People's Democratic Republic (Laos) to study the availability and quality of antimalarials in the private sector. In 2012, this survey was repeated to allow a statistically valid analysis of change through time. The counterfeit detection device 3 (CD-3) was used to assess packaging...

Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open s...

Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open s...

In 2003, a stratified random sample survey was conducted in the Lao People's Democratic Republic (Laos) to study the availability and quality of antimalarials in the private sector. In 2012, this survey was repeated to allow a statistically valid analysis of change through time. The counterfeit detection device 3 (CD-3) was used to assess packaging...

Ensuring that artemisinin-containing antimalarials (ACAs) are of good quality is a key component of effective malaria treatment. There are concerns that a high proportion of ACAs are falsified or substandard, though estimates are rarely based on representative data. During a nationally representative survey in Tanzania, ACAs were purchased from pri...

Little is known about the quality of antibiotics despite being in high demand globally. Thirty five samples (27 brands) of the antibiotics amoxicillin (N = 20; 16 brands) and co-trimoxazole (N = 15; 11 brands), manufactured in six countries (China, Ghana, India, Ireland, Nigeria, and United Kingdom), were purchased in Ghana, Nigeria, and the United...

Miltefosine, an effective oral treatment of visceral leishmaniasis (VL), was selected in May 2005, by the governments of India, Nepal, and Bangladesh for the elimination of VL. However, abnormally high treatment failure rates reported in patients in Bangladesh, given a miltefosine generic product ("Miltefos", Popular Pharmaceuticals Ltd.) during 20...

Good-quality antimalarials are crucial for the effective treatment and control of malaria. A total of 7,740 individual and packaged tablets, ampoules, and syrups were obtained from 60 randomly selected public (N = 35) and private outlets (N = 25) in Afghanistan. Of these, 134 samples were screened using the Global Pharma Health Fund (GPHF) MiniLab(...

Malaria is a curable disease, provided timely access to efficacious drugs is sought. Poor quality and, in particular, falsified antimalarial drugs harm the population of malaria endemic areas; they put lives in peril, cause economic losses to patients, families, industry, and generally undermine the trust in health systems. The extent of the proble...

Pharmaceutical counterfeiting is a global threat that can kill patients, contributes to the rise of drug resistance, and increases citizens’ mistrust of health systems. To monitor drug quality, governments and health programs must invest in regulations, technologies, and infrastructure, including anti-counterfeiting measures, specialised analytical...

Although many malaria control programmes in sub-Saharan Africa use indoor residual spraying with long-lasting insecticidal nets (LLINs), the two studies assessing the benefit of the combination of these two interventions gave conflicting results. We aimed to assess whether the addition of indoor residual spraying to LLINs provided a significantly d...

Background The quality of routine indoor residual spraying (IRS) operations is rarely assessed because of the limited choice of methods available for quantifying insecticide content in the field. This study, therefore, evaluated a user-friendly, rapid colorimetric assay for detecting insecticide content after routine IRS operations were conducted....

Long-lasting insecticide treated blankets (LLIBs) may provide additional protection against malaria where use of long lasting insecticidal nets (LLIN) is low or impractical such as in disaster or emergency situations. Initial efficacy testing of a new candidate LLIB was carried out at LSHTM and KCMUCo, before and after washing, in cone and ball bio...

The invention relates to an assay to test for pyrethroids in a sample. The assay is particularly useful for testing material treated with pyrethroids, such as bed netting and the like.