A Multicenter Study of Azithromycin, Alone and in Combination with Chloroquine, for the Treatment of Acute Uncomplicated<i>Plasmodium falciparum</i>Malaria in India

Dunne, Michael; Singh, Niraj Kumar; Shukla, Man Mohan; Valecha, Neena; Bhattacharyya, P. C.; Dev, Vas; Patel, Kanta; Mohapatra, Manoranjan; Lakhani, Jitendra D.; Benner, Rebecca J.; Lele, Chitra; Patki, Kiran C.

doi:10.1086/429343

Cited by 93 publications

(99 citation statements)

References 16 publications

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“…This study, with the aim of detecting and characterizing PfCRT haplotype distribution, was conducted from September 2004 to July 2006 as part of a series of double-blind, randomized clinical trials which investigated the efficacy of CQ plus azithromycin combination therapy in the treatment of P. falciparum infections in Uganda (Kampala and Kakira), Suriname, and India (states of Goa, Maharasthtra, Madhya Pradesh, Orissa, and Assam) (10).…”

Section: Methodsmentioning

confidence: 99%

“…Adults of Ͼ18 years of age were enrolled in the study upon meeting eligibility criteria and providing informed consent (10). At each site, the informed consent was translated into the local language.…”

Section: Methodsmentioning

confidence: 99%

“…Based on this assumption, we hypothesized that the CRPF isolates in India should possess the CVIET haplotype and that the prevalence of CRPF may be higher than appreciated. However, there are currently limited data available on the distribution and prevalence of CQ resistance and the Pfcrt haplotypes present in P. falciparum isolates from India (2,10,18,23,26).…”

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confidence: 99%

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Real-Time PCR Assay for Rapid Detection and Analysis of PfCRT Haplotypes of Chloroquine-Resistant Plasmodium falciparum Isolates from India

Keen¹,

Farcas²,

Zhong

et al. 2007

J Clin Microbiol

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Chloroquine-resistant Plasmodium falciparum (CRPF) malaria isolates in Southeast Asia and sub-Saharan Africa share the same Plasmodium falciparum chloroquine resistance transporter (PfCRT) haplotype (CVIET; amino acids 72 to 76). It is believed that CRPF malaria emerged in Southeast Asia and spread to sub-Saharan Africa via the Indian subcontinent. Based on this assumption, we hypothesized that CRPF isolates in India should possess the same drug resistance haplotype (PfCRT haplotype CVIET) as P. falciparum isolates in Southeast Asia and Africa and that the prevalence of CRPF may be higher and more widespread in India than appreciated. To test this postulate, we utilized a standardized real-time PCR assay to assess the prevalence and distribution of PfCRT haplotypes in P. falciparum isolates (n ‫؍‬ 406) collected from Western, Central, and Eastern states in India and compared them to isolates from South America and Africa. Based on the proportion of isolates possessing the molecular marker K76T, the prevalence of chloroquine resistance was high in all five regions of India studied (91%), as well as in Uganda (98%) and Suriname (100%). All isolates from Suriname contained the chloroquine-resistant SVMNT haplotype typical of South American isolates, and 98% of isolates from Uganda possessed the chloroquine-resistant CVIET haplotype characteristic of Southeast Asian/African strains. However, of 246 P. falciparum isolates from across India that contained the molecular marker for chloroquine resistance, 81% contained the SVMNT haplotype. In conclusion, the prevalence of CRPF malaria was high in geographically dispersed regions of India, and the primary haplotype observed, SVMNT, did not support a presumed geographic spread from contiguous Southeast Asia.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Real-Time PCR Assay for Rapid Detection and Analysis of PfCRT Haplotypes of Chloroquine-Resistant Plasmodium falciparum Isolates from India

Keen¹,

Farcas²,

Zhong

et al. 2007

J Clin Microbiol

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“…Interestingly, when animals received azithromycin prophylaxis during sporozoite exposure, lower liver loads and superior protection were observed (Friesen & Matuschewski, 2011). The combination of azithromycin and chloroquine has demonstrated synergistic effect against parasite growth in vitro (Nakornchai & Konthiang, 2006) and has shown substantially improved clinical and parasitological outcomes compared to azithromycin or chloroquine monotherapy in vivo (Dunne et al, 2005). In treatment trials with azithromycin-chloroquine in Africa, this drug combination showed non-inferiority compared to mefloquine (van Eijk & Terlouw, 2011).…”

Section: Innovative Application Of Drug Use In the Fieldmentioning

confidence: 99%

Enhancement of naturally acquired immunity against malaria by drug use

Bijker

Sauerwein

2012

Journal of Medical Microbiology

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Combination of chemoprophylaxis with chloroquine and so-called 'controlled human malaria infections' has been shown to induce sustained and fully protective immunity against malaria in experimental settings. This opens possibilities of translating this approach into an effective and applicable strategy for the field. We review the different ways in which antimalarial drugs have been used for prevention of malaria in endemic settings and discuss the possibilities and challenges of applying a strategy of drug use and naturally acquired infection in the field. IntroductionMalaria remains one of the most important infectious diseases worldwide, causing almost 655 000 deaths per year, of which the majority are children under 5 years of age. Intense malaria control interventions during the past decade have successfully established a reduction of more than 50 % in either confirmed cases of malaria or malaria admissions and deaths in 11 countries of the WHO African region (WHO, 2011a). However, increases in the number of malaria cases in 2009 in Rwanda, Sao Tome and Principe and Zambia, which previously reported reductions, illustrate the fragility of the current successes. This underlines the need for additional and innovative strategies.Availability of an effective vaccine would greatly contribute to malaria control and elimination. It is well known that clinical immunity is acquired in endemic areas after a number of years and a sufficient number of naturally acquired infections (Snow & Marsh, 1995). The search for malaria vaccines against Plasmodium falciparum has been pursued for decades, with the main focus on the development of subunit-vaccines, but with limited success. Twenty candidate vaccines are currently under clinical investigation but only one product, RTS,S, has progressed into a phase 3 field trial having recently shown encouraging indications of protection in an interim evaluation (RTS,S Clinical Trials Partnership, 2011; WHO, 2011b).One of the shortcomings of subunit-vaccines is the inability to appropriately address the significant antigenic diversity of target epitopes and the often-observed poor immunogenicity of the soluble parasite-derived proteins used. Against that background a whole-parasite approach may perform better. Indeed, immunization with sporozoite forms has consistently been shown to induce .90 % protection in rodents and humans in experimental set-ups (Friesen & Matuschewski, 2011;Hoffman et al., 2002).Transmission intensity varies greatly in sub-Saharan Africa where individuals can be subjected to up to 10 infectious bites per night at certain periods of the year. Here, we explore the idea that using medicines together with naturally acquired infection could result in the induction of protective immunity. We will review the different ways in which antimalarial drugs have been used for prevention of malaria in endemic areas and reflect on the possibilities and challenges of applying a strategy of drug use together with naturally acquired infection in the field (see Table 1 for an ov...

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“…In accordance with these findings, increasing the dose and frequency of administration of chloroquine can increase plasma concentrations to levels higher than the IC 50 values of chloroquine-resistant parasites. Similar to the artemisinin derivatives, prospects for long-term chloroquine efficacy will be enhanced if it can be used in combination, such as chloroquine-azithromycin (Dunne et al, 2005). With the right combination therapy, the prospects for a chloroquine comeback are good.…”

Section: Status Of Resistancementioning

confidence: 99%

Is chloroquine making a comeback?

Saifi

Beg²,

Harrath³

et al. 2012

Afr. J. Pharm. Pharmacol.

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Malaria remains one of the leading causes of disease and death in the tropics, mainly of children under 5 years of age. Chloroquine began as a first-line antimalarial in 1946; it became the corner stone of antimalarial chemotherapy for the next 40 years. It is one of the least expensive antimalarials available and is still in widespread use. Chloroquine can be taken both as prophylactic and as a treatment. For decades, chloroquine was a remarkably effective, safe, and inexpensive antimalarial. Optimism about effectiveness of chloroquine led public health professionals to predict the eradication of malaria by 2000. Despite much research during the last 40 years, the exact mechanism by which the chloroquine kills the malaria parasite remains controversial. Biochemical analyses suggest that this class of compounds enter acidic vacuoles of host cells, where they inhibit the growth of parasites by forming a complex with haematin. Unfortunately, Plasmodium falciparum gradually became resistant to chloroquine. After first appearing in Southeast Asia and South America in the late 1950s, resistance spread throughout Africa by the 1980s. Resistance to chloroquine was slow to develop, taking almost 20 years, despite extensive use of the drug, suggesting that mutations in several genes were required to produce the resistance phenotype. The mechanism of chloroquine resistance also is uncertain. Similar to the artemisinin derivatives, prospects for long-term chloroquine efficacy will be enhanced if it can be used in combination, such as chloroquine-azithromycin. With the right dosage and combination, the prospects for a chloroquine comeback are good.

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A Multicenter Study of Azithromycin, Alone and in Combination with Chloroquine, for the Treatment of Acute UncomplicatedPlasmodium falciparumMalaria in India

Cited by 93 publications

References 16 publications

Real-Time PCR Assay for Rapid Detection and Analysis of PfCRT Haplotypes of Chloroquine-Resistant Plasmodium falciparum Isolates from India

Real-Time PCR Assay for Rapid Detection and Analysis of PfCRT Haplotypes of Chloroquine-Resistant Plasmodium falciparum Isolates from India

Enhancement of naturally acquired immunity against malaria by drug use

Is chloroquine making a comeback?

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