Chloroquine treatment of falciparum malaria in an area of Kenya of intermediate chloroquine resistance

Abstract

106 children aged 1-10 years who had pure Plasmodium falciparum infections and temperatures greater than or equal to 38 degrees C were treated with chloroquine base, 25 mg/kg body weight. 29% of the infections were sensitive in vivo, 41% recurred within 4 weeks (RI), 26% were RII resistant, and 4% were RII resistant. Rieckmann micro in vitro tests were successful in 64% of isolates obtained from these children; 63% were resistant to chloroquine. In 58 paired isolates obtained before and after treatment, the level of chloroquine sensitivity was lower in the parasites persisting or recurring after treatment. All children except 2 of the 4 with RIII resistance became afebrile an average of 1.4 d after starting treatment and their other symptoms resolved in an average of 1.8 d. By day 28, 57% of the children with RI resistance and 78% of those with RII resistance had recurrence of fever and other symptoms, compared with 19% of children with sensitive infections. No relationship was observed between the clinical or parasitological response and age, nutritional status, haematocrit, splenomegaly, presence of sickle-cell trait, or seropositivity to malaria by enzyme-linked immunosorbent assay. The study demonstrates that, in most children with malaria in an area of intermediate chloroquine resistance, fever and other symptoms resolve at least temporarily when treated with chloroquine.

The public health impact of chloroquine resistance in Africa

“…Because most patients improved clinically within a few days, even in the case of parasitological failure, the assumption was that chloroquine retained sufficient efficacy to justify its use even though a majority of patients remained parasitemic. 1,37 To explain this paradox, it is necessary to consider the potential lethality of each malaria attack occurring among patients living in highly malaria-endemic areas. The daily clinical monitoring of cohorts of children in Congo and Senegal has shown that most individuals suffer several dozens of malaria attacks during childhood.…”

Predictors of chloroquine treatment failure in children and adults with falciparum malaria in Kampala, Uganda.

“…These resistance levels are considerably higher than earlier reports from Uganda, 28,29 but consistent with the 58% risk of parasitological resistance more recently reported from an urban Ugandan setting 30 and reports of resistance from countries neighboring Uganda. [1][2][3][4][5][6][7] Our study identified simple host-related characteristics that were independent predictors of chloroquine treatment failure. Young age was a strong predictor of treatment failure.…”

“…Resistance levels have risen alarmingly over the last 20 years, and in recent studies chloroquine has failed to clear parasites in up to 80% of EastAfrican patients. [1][2][3][4][5][6][7] Chloroquine resistance has also been linked to increased malaria-specific mortality. 8 Despite the spread of resistance, most African countries continue to designate chloroquine as the first-line drug for uncomplicated malaria.…”

“…8 Despite the spread of resistance, most African countries continue to designate chloroquine as the first-line drug for uncomplicated malaria. 9 Arguing against the abandonment of chloroquine as a first-line agent are observations that many patients experience symptomatic relief with chloroquine despite failure to clear parasites from the blood, 3,10,11 the appreciation that chloroquine resistance rates may vary considerably within a country, 12 a lack of ideal alternatives to chloroquine, 12 and the realization that increased use of other agents will lead to increased resistance to these drugs. 13 Sulfadoxine-pyrimethamine (S/P, Fansidar) is generally considered the most appropriate replacement for chloroquine in Africa, and is recommended as first-line therapy for uncomplicated malaria in Malawi and Kenya.…”

“…17 Interpretation of results from the few available studies that report predictors for chloroquine resistance in Africa is limited by small numbers, differing methodologies, and in some cases, failure to control for confounding effects. 3,[18][19][20][21][22] In this report, we analyze the predictive value of hostrelated factors for chloroquine treatment failure in an urban East-African setting. A small set of easily recognized hostrelated features offered strong predictive value in identifying patients at increased risk for clinical failure after treatment with chloroquine for uncomplicated falciparum malaria.…”