Abstract.The relationship between quantitative Plasmodium falciparum or P. vivax parasitemia and clinical illness has not been defined in Pakistan or in other areas where malaria transmission is not highly endemic. Standardized questionnaires were given to and physical examinations and parasitologic tests were performed in 8,941 subjects seen in outpatient clinics in 4 villages for 13 consecutive months in the Punjab region of Pakistan. The results, based on multivariable analysis, showed that a clinical diagnosis of malaria, a history of fever, rigors, headache, myalgia, elevated temperature, and a palpable spleen among children were all strongly associated with the presence and density of P. falciparum or P. vivax malaria in a monotonic dose-response fashion. The malaria attributable fraction of a clinical diagnosis of malaria, and the same symptoms and signs also increased with increasing P. falciparum and, to a lesser extent, P. vivax, parasitemia. Unlike in sub-Saharan Africa, clinical illness due to malaria often occurs in the Punjab among adolescents and adults and in patients with parasite densities less than 1,000/l. Clinical guidelines based upon parasitemia and symptomatology must be adjusted according to the intensity of transmission and be specific for each geographic area. Morbidity and mortality have been strongly linked toPlasmodium falciparum parasite density and guidelines have been introduced for etiologic classification of febrile illnesses and for therapeutic regimens based upon density of parasites in the blood. While P. falciparum is the predominant species in sub-Saharan Africa, where most of the studies comparing clinical illness with intensity of infection have been conducted, 1-6 malaria in southern Asia and many other endemic areas is caused by both P. falciparum and P. vivax and is characterized by a much lower sporozoite inoculation rate. The relationship between parasite density and clinical illness in such an environment has not been defined as it has been in Africa. Also, the impact of increasing P. vivax parasite density on clinical disease has not been studied as rigorously as has P. falciparum.

The prevalence of malaria in 4 villages 60 km south of Lahore, Punjab, where Anopheles culicifacies is the vector was estimated from blood films made during three mass malaria surveys (MS) and at 204 clinics (CS) held over 18 consecutive months. The highest parasite rate occurred during October 1984 when 43% of the CS population had parasitaemias. Plasmodium vivax predominated early in the major transmission season (23% and 15% vivax parasitaemias in August 1983 and 1984 respectively) whereas P. falciparum was the most common species later in the transmission season (an average falciparum prevalence of 37% in October and November 1984) and following the transmission season through March. Despite the proximity and habitat similarity of the 4 villages, both total and species malaria prevalence rates showed inter-village differences. Asexual stage and gametocyte parasite rates in children were 2 to 5 times higher than in adults. No increased mortality due to malaria was detected among the 4000 study population. Malaria was stable and endemic, albeit seasonally transmitted, in these 4 villages during 1983 and 1984.

Analysis of data obtained from Giemsa-stained blood films from patients with mixed Plasmodium vivax and P. falciparum parasitaemias seen in outpatient clinics held over 20 consecutive months in 4 villages in the Pakistani Punjab suggest that infections with P. falciparum and P. vivax were independent of each other. There was no evidence to support the hypothesis that P. falciparum suppressed P. vivax. A likely explanation for the seasonal variation in species parasitaemia rates in the Punjab is that P. vivax was predominant early in the transmission season due to late relapses, while P. falciparum was predominant later in the transmission season because of community-wide development of immunity to P. vivax.

No abstract

We evaluated amodiaquine as a replacement drug for treating falciparum malaria in an area of Pakistani Punjab where chloroquine-resistant Plasmodium falciparum has recently emerged. Amodiaquine appeared to be 4 to 8 times more effective than chloroquine when P. falciparum isolates were tested in vitro. However, the recrudescence rate was greater than 50% after oral treatment with 20 mg/kg amodiaquine given over two successive days. This lack of therapeutic response from amodiaquine may have been due to selection of resistant parasites in the villages where the study was performed through extensive use of chloroquine for presumptive malaria treatment during the preceding 18 months. We conclude that amodiaquine is not a suitable replacement for chloroquine for treating falciparum malaria in our study area despite in vitro sensitivity data suggesting that it would be efficacious. Baseline in vitro sensitivity to mefloquine is also reported.