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Inoculum size, incubation period and severity of malaria. Analysis of data from malaria therapy records
1Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine.
Abstract:
The size of the infecting inoculum may influence the severity of malaria, but evidence is scarce. Malaria therapy records provide a unique source of information on induced malaria in people. The therapy was given to large numbers of neurosyphilis patients and the malaria was left untreated as long as possible. Data from patients treated at the Horton Hospital, Epsom 1923-60 with a single strain of vivax malaria were analysed to assess the influence of inoculum size on severity of disease. Malaria was induced by mosquito bite, blood inoculation or direct sporozoite inoculation. The different measures of inoculum size were inversely correlated with pre-patent period, as expected. Overall, information was available on a total of 563 non-immune patients who were not treated during the first 5 days of patent parasitaemia. No strong or consistent relationships were found between measures of inoculum size and any of the measures of severity used: neither parasitaemia levels, nor peak fevers, nor number of paroxysms of fever. In the largest data set, longer pre-patent periods were associated with tertian fever, spontaneous recovery and less use of modifying treatment. Difficulties in interpreting the results are discussed, particularly with respect to misclassification of both exposure and outcome variables. While an inoculum size-severity relationship cannot be ruled out, a strong relationship is very unlikely.
Insights
Infecting malaria parasite inoculum size did not strongly correlate with disease severity in treated patients. This study suggests a large inoculum size is unlikely to cause more severe malaria infections.
Area of Science:
- Infectious Diseases
- Tropical Medicine
- Malariology
Background:
- The relationship between malaria inoculum size and disease severity is not well-established.
- Malaria therapy, using induced Plasmodium vivax malaria, was historically administered to neurosyphilis patients.
- Historical records offer a unique dataset for studying induced malaria.
Purpose of the Study:
- To investigate the influence of infectious inoculum size on the severity of induced Plasmodium vivax malaria.
- To analyze data from malaria therapy patients to assess the inoculum size-severity relationship.
Main Methods:
- Analysis of historical malaria therapy records from Horton Hospital, Epsom (1923-1960).
- Inclusion of 563 non-immune patients infected with a single strain of P. vivax malaria.
- Assessment of severity using parasitemia levels, peak fevers, and fever paroxysms, with inoculum size measured by induction method (mosquito bite, blood, or sporozoite inoculation).
Main Results:
- Inoculum size measures were inversely correlated with the pre-patent period, as anticipated.
- No significant or consistent association was found between inoculum size and measures of disease severity.
- Longer pre-patent periods correlated with tertian fever, spontaneous recovery, and reduced need for treatment.
Conclusions:
- A strong relationship between infectious inoculum size and malaria severity is unlikely.
- Potential misclassification of exposure and outcome variables complicates definitive interpretation.
- Further research is needed to fully elucidate the inoculum size-severity dynamic in malaria.