The effectiveness of non-pyrethroid insecticide-treated durable wall lining to control malaria in rural Tanzania: study protocol for a two-armed cluster randomized trial.

Background: Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide-treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance.

Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria.

Background: Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated Plasmodium falciparum malaria in the Amazon region of Peru.

Surveillance for adverse drug reactions to combination antimalarial therapy with sulfadoxine-pyrimethamine plus artesunate in Peru.

In 2001, Peru changed its treatment policy for uncomplicated Plasmodium falciparum malaria on the northern Pacific Coast to sulfadoxine-pyrimethamine with atresunate (SP-AS). Because Peru was the first country in the Americas to adopt this combination therapy, we established a surveillance system in the region to assess the frequency of new or worsening symptoms after starting therapy. Over a period of two years, 1,552, or approximately two-thirds of all patients with uncomplicated P.

Adaptation of a multi-drug resistant strain of Plasmodium falciparum from Peru to Aotus lemurinus griseimembra, A. nancymaae, and A. vociferans monkeys.

A strain of Plasmodium falciparum from Peru was adapted to splenectomized Aotus nancymaae and Aotus vociferans monkeys. The Peru 134/CDC strain of P. falciparum was shown to be resistant to treatment with chloroquine in monkeys and partially resistant to mefloquine and malarone.

Unusual pattern of Plasmodium falciparum drug resistance in the northwestern Peruvian Amazon region.

High levels of Plasmodium falciparum resistance to both chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) have been documented throughout the Amazon Basin of South America. Because of reports about the persistent efficacy of both of these drugs in the northwestern Peruvian Amazon region, we carried out an evaluation of the therapeutic efficacy of chloroquine (25 mg/kg) and SP (25 mg/kg of the sulfadoxine component) for the treatment of uncomplicated P. falciparum infections at two sites: Ullpayacu and Pampa Hermoza/Alianza.

Efficacy and tolerability of artesunate plus sulfadoxine-pyrimethamine and sulfadoxine-pyrimethamine alone for the treatment of uncomplicated Plasmodium falciparum malaria in Peru.

To assist the Peruvian Ministry of Health in modifying the malaria treatment policy for their north Pacific coastal region, we conducted an in vivo efficacy trial of sulfadoxine-pyrimethamine (SP) and SP plus artesunate (SP-AS) for the treatment for uncomplicated Plasmodium falciparum infections. A total of 197 patients were randomized to therapy with either SP (25 mg/kg of the sulfadoxine component in a single dose on day 0) or a combination of SP plus AS (4 mg/kg on days 0, 1, and 2) and were followed for 28 days for symptoms and recurrence of parasitemia. No statistically significant differences between the two groups were observed on enrollment with respect to age, sex, history of malaria, or geometric mean parasite density.

Modifying national malaria treatment policies in Peru.

Between 1998 and 2001, the Peruvian Ministry of Health made sweeping changes in its malaria treatment policies in response to a resurgence of disease and the spread and intensification of antimalarial drug resistance. On the Pacific Coast, the first-line treatment for uncomplicated Plasmodium falciparum malaria was changed to combination therapy with sulfadoxine-pyrimethamine plus artesunate; in the Amazon region, mefloquine-artesunate combination therapy was introduced. With these changes in treatment policy, Peru became the first country in the Americas to use combination therapy with an artemisinin drug as its first-line treatment for falciparum malaria and the first country in the world to use two different drug combination therapy regimens based on an artemisinin drug in different regions of the country.

Efficacy of sulfadoxine-pyrimethamine and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon basin of Peru.

In vivo antimalarial drug efficacy studies of uncomplicated Plasmodium falciparum malaria at an isolated site in the Amazon basin of Peru bordering Brazil and Colombia showed >50% RII/RIII resistance to sulfadoxine-pyrimethamine but no evidence of resistance to mefloquine.

Efficacy of mefloquine and mefloquine-artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon region of Bolivia.

We assessed the efficacy of mefloquine monotherapy and mefloquine-artesunate (MQ-AS) combination therapy for the treatment of Plasmodium falciparum malaria at four sites in the Bolivian Amazon region. Patients with uncomplicated P. falciparum infections between 5 and 60 years of age were randomly assigned to be treated with either MQ (15 mg/kg in a single oral dose) or MQ (15 mg/kg) plus AS (4 mg/kg daily for 3 days).

Chloroquine-resistant Plasmodium vivax malaria in Peru.

Reports from several sites in South America suggest the presence of isolated cases of chloroquine-resistant Plasmodium vivax malaria. To investigate the possibility of chloroquine-resistant P. vivax in Peru, we conducted 28-day in vivo drug efficacy trials at three sites in the Amazon region and one site on the northern Pacific Coast between 1998 and 2001.

Evaluation of a simple operational approach for monitoring resistance to antimalarial drugs in Peru.

Since 1994, the Peruvian Malaria Control Program has used a simplified operational approach for monitoring antimalarial drug efficacy, in which blood smears are taken 7 and 14 days after treatment from all patients diagnosed with malaria at Ministry of Health facilities. The proportion of patients with parasitaemia on one of their return visits provides an indication of the efficacy of the drug being administered. We compared this approach for antimalarial drug resistance monitoring to the more labour-intensive and expensive World Health Organization (WHO) 14-day in vivo efficacy trial at six sites in the Amazon Basin and the north coast of Peru.

The mortality consequences of the continued use of chloroquine in Africa: experience in Siaya, western Kenya.

In spite of increasing resistance, chloroquine remains the primary drug for treatment of malaria in most sub-Saharan African countries. We evaluated the effect of drug treatment policy on the case-fatality rates of children, adjusting for differing distributions of malaria and severe anemia. In 1991, 63% of children were treated with chloroquine while the remaining 37% were treated with a regimen that would eliminate and clear parasitemia.

Practical aspects of in vivo antimalarial drug efficacy testing in the Americas.

The World Health Organization (WHO) has developed guidelines for in vivo antimalarial drug efficacy testing for Plasmodium falciparum and Plasmodium vivax in areas with low-to-moderate transmission, such as the Americas. These guidelines are used widely by ministries of health and national malaria control programs to assess the efficacy of their first-line and second-line drugs for the treatment of malaria and to provide the information necessary to update national malaria treatment policies. Following the WHO guidelines, we have conducted in vivo efficacy trials with a variety of drugs and drug combinations against P.

Efficacy of mefloquine and a mefloquine-artesunate combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon Basin of Peru.

In the Amazon Basin of Peru, more than 50% of patients with uncomplicated Plasmodium falciparum malaria fail to respond to treatment with chloroquine or sulfadoxine-pyrimethamine. To assist the National Malaria Control Program in identifying an alternative first-line therapy for this region, we conducted a trial of the safety and efficacy of mefloquine (MQ) compared with mefloquine-artesunate (MQ-AS) combination therapy. Patients with uncomplicated P.

Efficacy of chloroquine, sulfadoxine-pyrimethamine, and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria on the north coast of Peru.

As part of an effort to assess antimalarial drug resistance in Peru, we carried out 14-day in vivo efficacy trials of chloroquine (CQ; 25 mg/kg) and sulfadoxine-pyrimethamine (SP; 25 mg/kg of the sulfadoxine component) for the treatment of uncomplicated Plasmodium falciparum infections at three sites on the northern coast of Peru. Mefloquine (MQ; 15 mg/kg) also was evaluated at one site. The results from all three sites were similar.

Lack of prediction of mefloquine and mefloquine-artesunate treatment outcome by mutations in the Plasmodium falciparum multidrug resistance 1 (pfmdr1) gene for P. falciparum malaria in Peru.

We assessed whether mutations in the Plasmodium falciparum multidrug-resistance gene 1 (pfmdr1) (C1034S, D1042N, and Y1246D) would predict treatment outcome during a 28-day in vivo treatment trial in the Peruvian Amazon. Mefloquine (MQ) was compared with mefloquine-artesunate (MQ-AS) in a randomized, multi-clinic protocol for the first time in the Americas. Of 115 patients enrolled in the in vivo arm, 97 patients were eligible for molecular analysis.

Efficacy of mefloquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum infection in Machinga District, Malawi, 1998.

In response to the spread of chloroquine-resistant Plasmodium falciparum, Malaŵi changed its first-line antimalarial drug in 1993 from chloroquine to sulfadoxine-pyrimethamine (SP). Surveillance data has suggested that resistance to SP may be increasing. We compared the efficacy of SP with a potential successor, mefloquine (MQ).

Dracunculiasis eradication: delayed, not denied.

By the end of 1998, Asia was free of dracunculiasis (Guinea worm disease), with Pakistan, India, and Yemen having interrupted transmission in 1993, 1996, and 1997, respectively. Transmission of the disease was also interrupted in Cameroon and Senegal during 1997. Chad reported only 3 cases during 1998.

Assessment of therapeutic response of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine in an area of low malaria transmission in Colombia.

Although chloroquine (CQ) resistance was first reported in Colombia in 1961 and sulfadoxine-pyrimethamine (SP) resistance in 1981, the frequency of treatment failures to these drugs in Colombia is unclear. A modified World Health Organization 14-day in vivo drug efficacy test for uncomplicated Plasmodium falciparum malaria in areas with intense malaria transmission was adapted to reflect the clinical and epidemiologic features of a low-intensity malaria transmission area in the Pacific Coast Region of Colombia. Patients > or =1 year of age with a parasite density > or =1,000 asexual parasites per microliter were enrolled in this study.

Maintenance and sustained use of insecticide-treated bednets and curtains three years after a controlled trial in western Kenya.

In large experimental trials throughout Africa, insecticide-treated bednets and curtains have reduced child mortality in malaria-endemic communities by 15%-30%. While few questions remain about the efficacy of this intervention, operational issues around how to implement and sustain insecticide-treated materials (ITM) projects need attention. We revisited the site of a small-scale ITM intervention trial, 3 years after the project ended, to assess how local attitudes and practices had changed.

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children.

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. Between June 1992 and July 1994, 1,848 children less than 15 years of age were monitored prospectively for a mean of 236 days. During this period, 12,035 blood smears were examined for malaria and only 34% were found to be negative.

Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission I. Description of study site, general methodology, and study population.

A large-scale longitudinal cohort project was initiated in western Kenya in June 1992. The primary purpose of the project was to study Plasmodium falciparum malaria in a highly endemic area using a comprehensive and multidisciplinary approach, which included epidemiology, entomology, and immunology. Between June 1992 and July 1994, pregnant women living in 15 rural villages were identified during a monthly census and 1,164 were enrolled.