Chloroquine-Resistant Plasmodium Falciparum: Now in Pakistani Punjab

Fox, Emile; Sarwar, Mohammad; Khaliq, AmirA.; Strickland, G. Thomas

doi:10.1016/s0140-6736(85)91855-0

Cited by 23 publications

(6 citation statements)

References 7 publications

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“…The complete failure of chloroquine (which at the time of the study remained the officially sanctioned first line treatment) convinced policy makers of the need to redefine treatment practices in South Asia. The new data demonstrated higher levels of resistance than in previous studies dating back to the 1980s and 1990s [2] , [3] , [5] , [48] , [49] and emphasised the need for change to national treatment guidelines. The addition of artesunate to chloroquine did reduce treatment failure rates, but if this regimen was used as policy it would, in effect, constitute artesunate monotherapy in the majority of infections and accelerate the development of artesunate tolerance, as reported in South East Asia [50] .…”

Section: Discussionmentioning

confidence: 83%

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

Kolaczinski

Leslie

Ali³

et al. 2012

PLoS ONE

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IntroductionAntimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown.MethodsA single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure.FindingsA total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced.ConclusionsCQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single-dose PQ for reducing gametocyte carriage.Trial Registration ClinicalTrials.gov bold>

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Section: Discussionmentioning

confidence: 83%

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

Kolaczinski

Leslie

Ali³

et al. 2012

PLoS ONE

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“…Besides previous evidence of enlargement of parasite clearance time associated to the upsurge of resistance either in vivo or in vitro (Fox et al 1985, Barkakaty et al 1992) no correlation has been found when quantitative parameters are directly compared, such as minimum inhibitory concentration versus parasite clearance time or IC 50 versus parasite clearance time (Sowonmi et al 1992, Alin et al 1995. It can be in part explained by the complex host-parasite relationship.…”

Section: Discussionmentioning

confidence: 96%

Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method

Cerutti

Marques

Alencar

et al. 1999

Mem. Inst. Oswaldo Cruz

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“…Xerostomia (dry mouth) and xerophthalmia (conjunctivitis sicca, dry eyes) are hallmarks of Sjögren's syndrome [1]. The mechanism associated with Sjögren's syndrome is unclear however, immunologically-activated or apoptotic glandular epithelial cells may present novel autoantigens in predisposed individuals driving autoimmune-mediated tissue injury [2,3].…”

Section: Introductionmentioning

confidence: 99%

Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland function in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjögren's syndrome

et al. 2012

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IntroductionCytotoxic T-lymphocyte antigen 4 (CTLA-4) is a key negative costimulatory molecule that displays a wide range of anti-inflammatory properties and is currently approved to treat rheumatoid arthritis as a recombinant fusion protein (CTLA4IgG). To better understand the role of CTLA4IgG in primary Sjögren's syndrome (pSS), we generated a recombinant adeno-associated virus vector serotype 2 (AAV2) expressing a chimera of mouse CTLA-4 fused with a human immunoglobulin (AAV2-CTLA4IgG) and observed the effect of this molecule in C57BL/6.NOD-Aec1Aec2 mice, an animal model of pSS.MethodsA recombinant adeno-associated virus-2 (AAV-2) vector was constructed encoding a CTLA4IgG fusion protein. The AAV2-CTLA4IgG vector and an AAV2 control vector encoding beta galactosidase (LacZ) were administered by retrograde cannulation of the submandibular glands of C57BL/6.NOD-Aec1Aec2 mice. Protein expression was measured by ELISA and salivary glands were assessed for inflammation and activity.ResultsRecombinant CTLA4IgG blocked B7 expression on macrophages in vitro. In vivo, localized expression of CTLA4IgG in the salivary glands of C57BL/6.NOD-Aec1Aec2 mice inhibited the loss of salivary gland activity and decreased T and B cell infiltration as well as dendritic cells and macrophages in the glands compared with control mice. In addition a decrease in several proinflammatory cytokines and an increase in transforming growth factor beta-1 (TGF-β1) expression were also observed.ConclusionsThese data suggest expression of CTLA4IgG in the salivary gland can decrease the inflammation and improve the xerostomia reported in these mice.

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Chloroquine-Resistant Plasmodium Falciparum: Now in Pakistani Punjab

Cited by 23 publications

References 7 publications

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method

Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland function in the C57BL/6.NOD-Aec1Aec2 mouse model of Sjögren's syndrome

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