Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial.

BACKGROUND: Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance. METHODS: In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries. Eligible patients were aged 2-65 years, with acute, uncomplicated P falciparum malaria alone or mixed with non-falciparum species, and a temperature of 37·5°C or higher, or a history of fever in the past 24 h. Patients were randomly assigned (1:1) to one of two treatments using block randomisation, depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar patients were assigned to either dihydroartemisinin-piperaquine or dihydroartemisinin-piperaquine plus mefloquine; at three sites in Cambodia they were assigned to either artesunate-mefloquine or dihydroartemisinin-piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo they were assigned to either artemether-lumefantrine or artemether-lumefantrine plus amodiaquine. All drugs were administered orally and doses varied by drug combination and site. Patients were followed-up weekly for 42 days. The primary endpoint was efficacy, defined by 42-day PCR-corrected adequate clinical and parasitological response. Primary analysis was by intention to treat. A detailed assessment of safety and tolerability of the study drugs was done in all patients randomly assigned to treatment. This study is registered at ClinicalTrials.gov, NCT02453308, and is complete. FINDINGS: Between Aug 7, 2015, and Feb 8, 2018, 1100 patients were given either dihydroartemisinin-piperaquine (183 [17%]), dihydroartemisinin-piperaquine plus mefloquine (269 [24%]), artesunate-mefloquine (73 [7%]), artemether-lumefantrine (289 [26%]), or artemether-lumefantrine plus amodiaquine (286 [26%]). The median age was 23 years (IQR 13 to 34) and 854 (78%) of 1100 patients were male. In Cambodia, Thailand, and Vietnam the 42-day PCR-corrected efficacy after dihydroartemisinin-piperaquine plus mefloquine was 98% (149 of 152; 95% CI 94 to 100) and after dihydroartemisinin-piperaquine was 48% (67 of 141; 95% CI 39 to 56; risk difference 51%, 95% CI 42 to 59; p<0·0001). Efficacy of dihydroartemisinin-piperaquine plus mefloquine in the three sites in Myanmar was 91% (42 of 46; 95% CI 79 to 98) versus 100% (42 of 42; 95% CI 92 to 100) after dihydroartemisinin-piperaquine (risk difference 9%, 95% CI 1 to 17; p=0·12). The 42-day PCR corrected efficacy of dihydroartemisinin-piperaquine plus mefloquine (96% [68 of 71; 95% CI 88 to 99]) was non-inferior to that of artesunate-mefloquine (95% [69 of 73; 95% CI 87 to 99]) in three sites in Cambodia (risk difference 1%; 95% CI -6 to 8; p=1·00). The overall 42-day PCR-corrected efficacy of artemether-lumefantrine plus amodiaquine (98% [281 of 286; 95% CI 97 to 99]) was similar to that of artemether-lumefantrine (97% [279 of 289; 95% CI 94 to 98]; risk difference 2%, 95% CI -1 to 4; p=0·30). Both TACTs were well tolerated, although early vomiting (within 1 h) was more frequent after dihydroartemisinin-piperaquine plus mefloquine (30 [3·8%] of 794) than after dihydroartemisinin-piperaquine (eight [1·5%] of 543; p=0·012). Vomiting after artemether-lumefantrine plus amodiaquine (22 [1·3%] of 1703) and artemether-lumefantrine (11 [0·6%] of 1721) was infrequent. Adding amodiaquine to artemether-lumefantrine extended the electrocardiogram corrected QT interval (mean increase at 52 h compared with baseline of 8·8 ms [SD 18·6] vs 0·9 ms [16·1]; p<0·01) but adding mefloquine to dihydroartemisinin-piperaquine did not (mean increase of 22·1 ms [SD 19·2] for dihydroartemisinin-piperaquine vs 20·8 ms [SD 17·8] for dihydroartemisinin-piperaquine plus mefloquine; p=0·50). INTERPRETATION: Dihydroartemisinin-piperaquine plus mefloquine and artemether-lumefantrine plus amodiaquine TACTs are efficacious, well tolerated, and safe treatments of uncomplicated P falciparum malaria, including in areas with artemisinin and ACT partner-drug resistance. FUNDING: UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and US National Institutes of Health.

Helicobacter pylori infection in dyspeptic patients in an industrial belt of India.

The present study is done to study different aspects of Helicobacter pylori (H. pylori) such as its prevalence, association with upper gastrointestinal pathology, diagnosis and treatment outcome. Gastric antral biopsy and serology for H. pylori was done for all dyspeptic patients. Histopathology, gram stain and biopsy urease test was done from the gastric biopsy specimen. The prevalence of H. pylori infection was 58.8%. The sensitivity, specificity, positive and negative predictive value for histopathology was 96.9%, 100%, 100% and 95.8%, respectively; for biopsy urease test 80.4%, 100%, 100% and 78.2%, respectively; for gram stain 85.6%, 97.1%, 97.6% and 82.5%, respectively, and for serology 94.8%, 77.9%, 86% and 91.4%, respectively. Mostly peptic ulcer and duodenitis cases followed by chronic active gastritis were associated with H. pylori infection. Repeat biopsy revealed eradication of H. pylori in 90.7% cases. In dyspeptic patients, endoscopic biopsy not only detects H. pylori infection, but also reveals different gastric pathologies.

Comparing Leishman and Giemsa staining for the assessment of peripheral blood smear preparations in a malaria-endemic region in India.

BACKGROUND: Microscopy of peripheral blood thin and thick films remains the reference for malaria diagnosis. Although Giemsa staining is most commonly used, the Leishman staining method provides better visualization of the nuclear chromatin pattern of cells. It is less well known whether accuracy of parasitaemia assessment is equally accurate with the latter method. METHODS: Peripheral blood thin and thick smears from consecutive febrile patients admitted to Ispat General hospital, Rourkela, Odhisa, India, were stained with Giemsa and Leishman stain. Methods were compared for species identification, parasite quantification, and ability for identification of alternative diagnoses. RESULTS: Blood films from 1,180 fever patients were compared according to staining method, of which 111 were identified as parasitaemic using Giemsa and 110 with Leishman staining. The Kappa value as a measure of agreement between methods was 0.995 (p < 0.001), and the log10parasitaemia between methods were strongly correlated (r2 = 0.9981). In parasite negative patients, thin smear assessment contributed to making a diagnosis in 276/1,180 (23%) of cases. These assessments were better made in Leishman-stained preparations, especially for the assessment of morphological changes in red and white cells. CONCLUSION: Leishman's staining method for thin and thick smears is a good alternative to Giemsa's stain for identifying Plasmodium parasites. The Leishman method is superior for visualization of red and white blood cell morphology.