Effect of chemotherapy on malaria transmission among Yanomami Amerindians: simulated consequences of placebo treatment.

Abstract

Abstract. To determine whether chemotherapy effectively reduces Plasmodium falciparum malaria transmission in isolated human populations, we followed two abrupt sequential outbreaks of malaria infection among Yanomami Amerindians and modeled the effect of chemotherapy and the consequences if no drug was available. A Macdonaldtype mathematical model demonstrated that both outbreaks comprised a single epidemic event linked by an invisible outbreak in vector mosquitoes. The basic reproductive number, R 0 , from fitted values based on the treated epidemic was 2 during the initial phase of the epidemic, and waned as vector density decreased with the onset of the dry season. In the observed epidemic, 60 (45%) of 132 village residents were affected, and the treated outbreak ended after two months. Although the initial chemotherapy regimen was only marginally effective, the duration of human infectivity was reduced from an expected nine months to two weeks. In the absence of this intervention, the initial R 0 value would have been 40, more than 60% of the population would have been infected, and more than 30% would have remained parasitemic until the next rainy season (about six months later). Another outbreak would then have ensued, and malaria probably would have remained endemic in this village. Our simulated placebo treatment permits us to conclude that even partially effective chemotherapeutic interventions, such as those in our study, interrupt serial transmission of P. falciparum among isolated human populations that are exposed to infection seasonally.Although mass administration of antimalarial drugs reduces prevalence of malaria infection, such interventions may not sustainably reduce transmission. [1][2][3][4][5] In certain endemic sites, the basic reproductive number (R 0 ) of malaria appears to be so great (80-100) that the cycle of transmission could not be broken unless drugs were administered to the entire affected human population. 5,6 The resulting requirement for an apparently impractical level of drug coverage persuaded the directors of the now discontinued malaria eradication campaigns, for example, to depend entirely on anti-vector interventions. 3 The effect of drugs on transmission of passively detected Plasmodium falciparum malaria infections, those discovered when symptomatic people seek health care, has not rigorously been evaluated. Such a definitive study would require simultaneous, longitudinal comparison of spatially separated human populations exposed to real and placebo chemotherapy, but any such placebo treatment of this debilitating and frequently fatal disease would violate ethical standards. Modeling techniques that facilitate such analyses, however, recently have become available.Chemotherapeutic intervention administered to passively detected cases of P. falciparum malaria may suppress transmission occurring in episodically infected human populations. To investigate this possibility, we explored malaria transmission in a population of nonimmune Yanomami Amerindians that was experie...

Parameterization and Sensitivity Analysis of a Complex Simulation Model for Mosquito Population Dynamics, Dengue Transmission, and Their Control

“…These results are consistent with other modeling studies reporting the importance of mosquito survival or mortality, [14][15][16][17][18][19][20][21] biting rate, 6,14,15,17,18,22 and length of the infectious period in the host 6,14,21,[23][24][25][26][27] in determining the dynamics of mosquitoborne diseases. However, our results go one step further by identifying specific causes of mosquito mortality and the aspects of biting behaviors that may be most influential.…”

Historical review: Does falciparum malaria destroy isolated tribal populations?

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