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4.
Trop Med Int Health ; 6(6): 429-34, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11422956

ABSTRACT

Since 1993 sulphadoxine/pyrimethamine (SP) has been used as the first-line drug for uncomplicated Plasmodium falciparum malaria in Malawi. To investigate the current efficacy of SP and other antimalarial drug resistance, we studied in vivo and in vitro responses to SP, chloroquine (CQ), mefloquine (MF), quinine (QN), and halofantrine (HF) in Salima, central Malawi. In a follow-up of 14 days, nine (13.8%) of 65 children under five showed RII/RIII parasitological resistance, and in in vitro microtests 18 (62.1%) of 29 isolates showed < 90% inhibition of schizont maturation at pyrimethamine 75 nmol/l blood medium mixture, indicating resistance. The discrepancy between in vivo and in vitro results might be partially explained by acquired immunity in this holoendemic area. In vitro one (3.4%) of 29 isolates failed schizont inhibition at 1.6 micromol/l blood of CQ, indicating resistance. Compared with an in vitro study conducted in 1988 in another region of Malawi using the same cut-off point, the proportion of resistant isolates had decreased significantly (P < 0.01). Although 31% of isolates were borderline, showing schizont maturation at 0.8 micromol/l blood but no schizonts at 1.6 micromol/l in our study, the results suggest possible recovery of CQ sensitivity after long-term absence of drug pressure. Resistance remains a major problem in malaria control. Monitoring resistance patterns in vitro provides early warning signs of impending loss of therapeutic efficacy of the standard treatment, and may detect changing patterns in alternative drug resistance.


Subject(s)
Antimalarials/pharmacology , Malaria, Falciparum/drug therapy , Plasmodium falciparum/drug effects , Pyrimethamine/pharmacology , Sulfadoxine/pharmacology , Animals , Antimalarials/therapeutic use , Child, Preschool , Drug Monitoring , Drug Resistance , Drug Therapy, Combination , Humans , In Vitro Techniques , Infant , Infant, Newborn , Logistic Models , Malaria, Falciparum/parasitology , Malawi , Parasitic Sensitivity Tests , Pyrimethamine/therapeutic use , Sulfadoxine/therapeutic use , Treatment Outcome
5.
Acta Trop ; 63(4): 195-207, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9088434

ABSTRACT

A malaria study area in the Philippines is described. It consists of the municipality of Morong, Bataan on the Island of Luzon. In January 1992, the population was 19454 in 106 villages located on a narrow coastal plain, or in valleys of streams running from the mountainous interior. This is an area of low level but persistent seasonal transmission of malaria with approximately one thousand cases reported each year, mainly from February to July. In spite of the low level of malaria, it is apparently quite stable. The study site has been used to investigate parameters leading to stable malaria. Hypotheses tested were that there was substantial under reporting of cases; that there was strain specific immunity stabilising the incidence of malaria and that malaria transmission in this area is highly localised in small regions with a high enough malaria prevalence to account for the year to year stability. The study plan included cross sectional surveys of parasite prevalence and seropositivity, longitudinal surveys, passive case detection, entomological surveys, anthropological surveys to assess knowledge of malaria and documentation of the health-seeking behaviour of the population.


Subject(s)
Malaria/epidemiology , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Cross-Sectional Studies , Demography , Disease Notification , Health Services Accessibility , Humans , Immunity, Active , Infant , Infant, Newborn , Longitudinal Studies , Malaria/immunology , Malaria/transmission , Middle Aged , Philippines/epidemiology , Prevalence , Seasons , Seroepidemiologic Studies
6.
Acta Trop ; 63(4): 241-56, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9088437

ABSTRACT

Field epidemiological studies were conducted to examine factors affecting endemicity in an area with a low prevalence of malaria. Two annual cross sectional surveys were done to estimate parasite prevalence rates at two periods in time, to determine the distribution of the parasitemic population and to describe the serological status of the population. A longitudinal study of a sample of infected people was used to measure reinfection rates and antibody dynamics. A 2 year passive case detection was done to estimate the number and distribution of people with symptomatic infections. Malaria was found in all age groups, with marked clustering of cases. Active and passive case detection and serological surveys all gave a similar pattern of malaria distribution: generally low prevalence with small foci of relatively high endemicity. The infection frequencies were generally similar in all age groups, measured by both active and passive case detection. There was a high frequency of P. falciparum gametocytemic infections in the asymptomatic cases found through active case detection. Twenty to 39 year old males had the highest frequency of infection by active case detection, and 10-19 year old males by passive case detection. These two groups were also more likely to be gametocyte positive than their female counterparts, suggesting that in this community, this portion of the population acts as the main reservoir of infection.


Subject(s)
Malaria/epidemiology , Adolescent , Adult , Age Factors , Aged , Animals , Antibodies, Protozoan/analysis , Child , Child, Preschool , Cross-Sectional Studies , Female , Fluorescent Antibody Technique, Indirect , Humans , Infant , Infant, Newborn , Longitudinal Studies , Malaria/immunology , Malaria, Falciparum/epidemiology , Male , Middle Aged , Philippines/epidemiology , Plasmodium/isolation & purification , Prevalence , Recurrence , Seroepidemiologic Studies , Sex Factors
7.
Acta Trop ; 63(4): 257-65, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9088438

ABSTRACT

The patterns of malaria morbidity and mortality can vary with the level of malaria transmission in a given area. We carried out two annual cross-sectional surveys in the hypoendemic malarious community of Morong, the Philippines, to examine epidemiologic and sociobehavioural risk factors for infection. In both surveys, the greatest risk of having malaria was associated with place of residence. For example, in the first survey, living in an area where more than 50% of the community had a high IFAT titer had an adjusted odds ratio (OR) of 33.7. A range of activities thought to be associated with risk were examined, but in the first survey, only frequent nocturnal visits to the forest were found to be a significant risk factor overall (adjusted OR; 2.65; 95% CI 1.48, 4.73), but this phenomenon was primarily observed among individuals residing in the lowest prevalence areas. In the second survey, where only the area with a relatively high prevalence of malaria was sampled, no association with activities was found. In this survey, significant factors associated with malarial infection were: being a migrant (adjusted OR 1.97; 95% CI 1.33, 2.92), being male (adjusted OR 1.63; 95% CI 1.10, 2.43) and age 30 years or less (adjusted OR 0.29 for age > 30 years; 95% CI 0.16, 0.52). The data suggest that in low-endemic communities like Morong, Bataan, control efforts should be primarily directed to focal areas identified by serology, particularly among migrants and among male young adults.


Subject(s)
Malaria/epidemiology , Malaria/transmission , Adult , Age Factors , Aged , Antibodies, Protozoan/analysis , Cross-Sectional Studies , Female , Fluorescent Antibody Technique, Indirect , Humans , Male , Middle Aged , Philippines/epidemiology , Prevalence , Residence Characteristics , Risk Factors , Seroepidemiologic Studies , Sex Factors , Social Behavior , Transients and Migrants , Trees
8.
Acta Trop ; 63(4): 267-73, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9088439

ABSTRACT

Malaria in Morong, Bataan, The Philippines, a municipality with relatively low level, but stable malaria is associated with small foci of relatively high endemicity. Although there is little association between age and symptomatic malaria, there is a reservoir of asymptomatic cases which are present throughout the year. Risk analysis suggests that the greatest risk factor in acquiring malaria depends on place of residence and not on occupation, including those associated with forest activities such as charcoal making. Foci of infection and the timing of symptomatic cases is closely correlated with breeding sites and abundance of adult Anopheles flavirostris. In spite of this close association, widely held views in the community that malaria is not related to mosquito transmission are likely to make better malaria control based on vector control difficult to sustain. Observation of treatment practices in the community and estimates of the number of apparently asymptomatic carriers from active case detection illustrate the importance of delayed treatment in providing a continuing reservoir of infection. These results highlight the need for improved early case detection and treatment.


Subject(s)
Communicable Disease Control/methods , Malaria/prevention & control , Antibodies, Protozoan/analysis , Carrier State/parasitology , Disease Reservoirs , Drug Therapy/psychology , Fluorescent Antibody Technique, Indirect , Humans , Malaria/drug therapy , Malaria/epidemiology , Mosquito Control , Philippines/epidemiology , Residence Characteristics , Risk Assessment , Seroepidemiologic Studies , Trees
9.
Trop Med Parasitol ; 45(2): 83-6, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7939166

ABSTRACT

Chloroquine prophylaxis was administered to 3 healthy male volunteers at 100 mg base/day for 25 days, followed by the curative dose at 25 mg base/kg for 3 days. Subjects attained effective chloroquine (mean = 50 micrograms/l) and desethylchloroquine (mean = 17 micrograms/l) concentrations by the 3rd week of prophylaxis, underlining the need to start chloroquine prophylaxis two weeks before travel. On the second day of the treatment period, hourly electrocardiographic monitoring showed a diminution of the T wave and prolongation of the QTc interval, manifesting cumulatively during the 3 days' curative dose, but with no cardiac symptoms. A dose-dependent cumulative effect of chloroquine was demonstrated with higher blood concentrations during the treatment period. Electrocardiographic readings spontaneously normalized after the treatment period as drug concentrations diminished progressively.


Subject(s)
Chloroquine/pharmacology , Chloroquine/pharmacokinetics , Electrocardiography/drug effects , Heart/drug effects , Adult , Chloroquine/adverse effects , Chloroquine/analogs & derivatives , Chloroquine/blood , Follow-Up Studies , Humans , Male
11.
Bull World Health Organ ; 72(5): 729-35, 1994.
Article in English | MEDLINE | ID: mdl-7955021

ABSTRACT

In-vitro drug sensitivity tests were performed on Philippine isolates of Plasmodium falciparum between 1991 and 1993, using the radioisotope microdilution method. The success of the tests varied significantly with the level of parasitaemia, the source of the strains, the period that elapsed before culturing, and the detectable concentrations of antimalarials in the blood. There was a significant positive correlation between the IC50 values for chloroquine and artesunate and the level of chloroquine in the blood before testing. In the Philippines the sensitivity profiles of the standard antimalarials (chloroquine, quinine, mefloquine, and halofantrine) were less severe than those in other south-east Asian countries. Fairly low IC50 values were obtained for the qinghaosu derivatives artemisinin, artemether, arteether and artesunate. There was a positive correlation between quinine, mefloquine, halofantrine and some of the qinghaosu derivatives, and between the qinghaosu compounds themselves, raising the possibility of either cross-resistance or possible drug associations.


Subject(s)
Antimalarials/pharmacology , Artemisinins , Plasmodium falciparum/drug effects , Sesquiterpenes/pharmacology , Adolescent , Adult , Aged , Animals , Antimalarials/blood , Child , Child, Preschool , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Humans , Microbial Sensitivity Tests , Middle Aged , Radioisotope Dilution Technique
14.
Am J Trop Med Hyg ; 47(3): 372-7, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1524151

ABSTRACT

The study was designed to evaluate how exposure of Plasmodium falciparum to mefloquine modifies the sensitivity of the parasite to four major antimalarial drugs. A recently culture-adapted strain of P. falciparum was subjected to intermittent drug pressure at three different mefloquine concentrations (2.34, 4.68, and 9.37 ng/ml). Growth was monitored by daily evaluation of parasitemia on thin smears. Drug sensitivity tests were done weekly, using a radioisotope microdilution method. Mefloquine was removed from culture media when decreasing parasitemia was observed, and reintroduced when multiplication reoccurred. Parasite survival was inversely proportional to drug concentrations. The parasites tolerated progressively higher concentrations of mefloquine with prolonged exposure to the drug. Throughout this adaptation, the 50% inhibitory concentration for chloroquine and quinine showed no modification, but it increased considerably for mefloquine, exceeding known levels of resistance. Furthermore, a parallel increased resistance to halofantrine was observed, surpassing the normal range of sensitivity. Cross-resistance between mefloquine and halofantrine shown in this study has now been confirmed by epidemiologic in vitro surveys and clone analysis. These findings may have important in vivo consequences and eventually affect the choice of antimalarial therapy.


Subject(s)
Antimalarials/pharmacology , Mefloquine/pharmacology , Phenanthrenes/pharmacology , Plasmodium falciparum/drug effects , Animals , Chloroquine/pharmacology , Drug Resistance , Humans , Plasmodium falciparum/growth & development , Quinine/pharmacology
15.
Bull Soc Pathol Exot ; 83(1): 43-5, 1990.
Article in French | MEDLINE | ID: mdl-2190703

ABSTRACT

Malaria caused by P. falciparum occurred during prophylaxis with mefloquine upon return from Sierra Leone (zone II). A typical and not recognized, with negative results of initial hematological examinations. Diagnosed on D.26 with parasitemia of 0.2%. Successful treatment of clinical symptoms with halofantrine but increased anemia and positive parasitemia at D.7. Successful treatment with chloroquine. Chemosensitivity tests confirmed sensitivity to chloroquine, threshold sensitivity to quinine (IC50 = 297), resistance to mefloquine (IC50 = 76) despite high levels in bloods, and to halofantrine (IC50 = 7-laboratory normal value = 1). This cross-resistance of P. falciparum originating from Sierra Leone to mefloquine-halofantrine seems to be the first observation of this danger in Africa. Prescription of chloroquine is still imperative in zone 11 countries.


Subject(s)
Antimalarials/therapeutic use , Malaria/parasitology , Mefloquine/therapeutic use , Plasmodium falciparum/drug effects , Adult , Animals , Chloroquine/therapeutic use , Cross Reactions , Drug Resistance , Humans , Malaria/drug therapy , Male , Mefloquine/pharmacology , Phenanthrenes/pharmacology , Phenanthrenes/therapeutic use
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