The suppression of malarial parasitaemia by pyrimethamine in combination with dapsone or sulphormethoxine.
ABSTRACT The antimalarial activity of pyrimethamine in combination either with dapsone or with sulphormethoxine, was compared with that of pyrimethamine alone. In this double-blind controlled study, 280 children, living in an area of stable P. falciparum malaria, were observed during one year. With pyrimethamine alone there was incomplete suppression of parasitaemia with crude parasite rates ranging from 2 to 25%. The first dose of the drug combinations produced a rapid clearance of parasitaemia, and weekly administration of the drug combinations sustained a virtually complete suppression of parasitaemia throughout the year. The drugs were well tolerated and no serious side-effects were encountered among the treated children.
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ABSTRACT: The immune response against the Plasmodium falciparum variant surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against falciparum malaria. In this study, we used sera from human volunteers who had been infected with the P. falciparum 3D7 strain to investigate the development, specificity, and dynamics of anti-PfEMP1 antibodies measured against six different strain 3D7 Duffy binding-like domain 1alpha (DBL1alpha) fusion proteins. We observed that a parasitemia of 20 to 200 infected erythrocytes per mul was required to trigger an antibody response to DBL1alpha and that antibodies against one DBL1alpha variant cross-react with other DBL1alpha variants. Both serum and purified immunoglobulin Gs (IgGs) were able to agglutinate infected erythrocytes, and purified anti-DBL1alpha IgGs bound to the live infected red blood cell surface in a punctate surface pattern, confirming that the IgGs recognize native PfEMP1. Analysis of sera from tourists naturally infected with P. falciparum suggests that the anti-PfEMP1 antibodies often persisted for more than 100 days after a single infection. These results help to further our understanding of the development of acquired immunity to P. falciparum infections.Infection and immunity 01/2008; 75(12):5967-73. · 4.21 Impact Factor
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ABSTRACT: We describe the epidemiology of malaria in San Dulakudar, a village in Sundargarh District in the state of Orissa in eastern India. Malaria transmission is perennial with Plasmodium falciparum, accounting for greater than 80% of malaria cases. Transmission intensity varies with season with high transmission after the monsoon rains in autumn and winter, low transmission in summer, and intermediate transmission in spring. The anthropophagic mosquito Anopheles fluviatilis was identified as the main vector for malaria transmission. Based on observations of spleen rates and supported by data on malaria parasite prevalence and malaria incidence, San Dulakudar can be classified as a hyperendemic area for P. falciparum malaria. Parasite prevalence and malaria incidence rates decrease with age, suggesting that residents of San Dulakudar develop immunity to malaria. The study demonstrates the presence of regions in the Indian subcontinent such as Sundargarh District where P. falciparum is the primary cause of malaria and where malaria transmission rates are comparable to those found in many parts of Africa.The American journal of tropical medicine and hygiene 11/2004; 71(4):457-65. · 2.53 Impact Factor
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ABSTRACT: Malaria chemoprophylaxis concerns prescribing healthy individuals medication for an infection they have an unknown chance of getting. Sensible use of malaria chemoprophylaxis is a balance between the risk of infection and death, and the risk of side effects. The risk of infection can be broken down into the risk of being bitten by a malaria-infected mosquito and the risk of the malaria parasites being resistant to the drug used for prophylaxis. Our knowledge of these parameters is patchy. The risk of infection is not uniform at a given location and the standard of living will greatly influence risk. It is suggested that chemoprophylaxis should not be recommended in areas with less than ten reported cases of P. falciparum malaria per 1000 inhabitants per year. The resistance pattern is known to a certain extent but, for instance, diverging opinion of how much resistance to chloroquine there is in West Africa illustrates the lack of data. There is much debate on rare adverse events, which usually escape Phase III studies prior to registration and are only picked up by passive, postmarketing surveillance. The lessons over the past 20 years with the introduction of amodiaquine, pyrimethamine/dapsone (Maloprim, GlaxoSmithKline) and pyrimethamine/sulfadoxine (Fansidar, Roche), which were all withdrawn for prophylaxis after a few years, show how sensitive drugs for chemoprophylaxis are to side effects. Three levels of chemoprophylaxis are used: chloroquine in areas with sensitive P. falciparum, chloroquine plus proguanil in areas with low level chloroquine resistance, and atovaquone/proguanil (Malarone, GlaxoSmithKline), doxycycline or mefloquine (Lariam, Roche) in areas with extensive resistance against chloroquine and proguanil. Primaquine and the primaquone analog tafenoquine may be future alternatives but otherwise there are few new drugs for chemoprophylaxis on the horizon.Expert Review of Anticancer Therapy 03/2004; 2(1):119-32. · 3.22 Impact Factor