Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs

BACKGROUND: There is renewed acknowledgement that targeting gametocytes is essential for malaria control and elimination efforts. Simple mathematical models were fitted to data from clinical trials in order to determine the mean gametocyte circulation time and duration of gametocyte carriage in treated malaria patients. METHODS: Data were used from clinical trials from East Africa. The first trial compared non-artemisinin combination therapy (non-ACT: sulphadoxine-pyrimethamine (SP) plus amodiaquine) and artemisinin-based combination therapy (ACT: SP plus artesunate (AS) or artemether-lumefantrine). The second trial compared ACT (SP+AS) with ACT in combination with a single dose of primaquine (ACT-PQ: SP+AS+PQ). Mature gametocytes were quantified in peripheral blood samples by nucleic acid sequence based amplification. A simple deterministic compartmental model was fitted to gametocyte densities to estimate the circulation time per gametocyte; a similar model was fitted to gametocyte prevalences to estimate the duration of gametocyte carriage after efficacious treatment. RESULTS: The mean circulation time of gametocytes was 4.6-6.5 days. After non-ACT treatment, patients were estimated to carry gametocytes for an average of 55 days (95% CI 28.7 - 107.7). ACT reduced the duration of gametocyte carriage fourfold to 13.4 days (95% CI 10.2-17.5). Addition of PQ to ACT resulted in a further fourfold reduction of the duration of gametocyte carriage. CONCLUSIONS: These findings confirm previous estimates of the circulation time of gametocytes, but indicate a much longer duration of (low density) gametocyte carriage after apparently successful clearance of asexual parasites. ACT shortened the period of gametocyte carriage considerably, and had the most pronounced effect on mature gametocytes when combined with PQ

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children

Background Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T‐helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre‐dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1‐stimulating infection. Objective To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. Methods Three‐hundred and fifty‐nine randomly selected children aged 6–14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris‐specific IgE (Ascaris‐sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. Results were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris‐sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris‐sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy‐related bronchial hyper‐responsiveness. In children with negative TST (<10 mm), elevated Ascaris‐sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (ORadj) 6.5; 95% confidence interval (CI) 1.9–22.4), whereas in those with positive TST (10 mm) this association disappeared (ORadj 0.96; 95% CI 0.4–2.8). Conclusions These results suggest that immune response to Ascaris (Ascaris‐sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti‐inflammatory networks.We thank all the parents and children who participated in this study. We are indebted to Prof. P.C. Potter (Allergy Diagnostic and Clinical Research Unit, University of Cape Town, South Africa) for the serum IgE analyses and allergy diagnostics. We are also indebted to Ann Toerien for carrying out the allergy and tuberculin skin tests, Jerome Cornelius for the successful fieldwork and Dr Vera Adams (Nutritional Intervention Research Unit, Medical Research Council of South Africa, Cape Town, South Africa). We also thank Edwin Videler and Johan Mouton (Lung Function Laboratory of the Department of Respiratory Medicine, Stellenbosch University), and Rita van Deventer (Parasitology Reference Unit, National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa). Sources of support and grants: C.C.O is a recipient of a grant from the Ter Meulen Fund, Royal Netherlands Academy of Arts and Sciences. This study was funded by the Stellenbosch University (through funding from the South African Department of Trade and Industry, THRIP fund) and the Wilhelmina Children’s Hospital, University Medical Center Utrecht, the Netherlands