In Zambia the first-line treatment for uncomplicated malaria is artemisinin combination therapy (ACT), with artemether-lumefantrine currently being used. However, the antifolate regimen, ...sulphadoxine-pyrimethamine (SP), remains the treatment of choice in children weighing less than 5 kg and also in expectant mothers. SP is also the choice drug for intermittent preventive therapy in pregnancy and serves as stand-by treatment during ACT stock outs. The current study assessed the status of Plasmodium falciparum point mutations associated with antifolate drug resistance in the area around Macha.
A representative sample of 2,780 residents from the vicinity of Macha was screened for malaria by microscopy. At the same time, blood was collected onto filter paper and dried for subsequent P. falciparum DNA analysis. From 188 (6.8%) individuals that were thick film-positive, a simple random sub-set of 95 P. falciparum infections were genotyped for DHFR and DHPS antifolate resistance mutations, using nested PCR and allele-specific restriction enzyme digestion.
Plasmodium falciparum field samples exhibited a high prevalence of antifolate resistance mutations, including the DHFR triple (Asn-108 + Arg-59 + Ile-51) mutant (41.3%) and DHPS double (Gly-437 + Glu-540) mutant (16%). The quintuple (DHFR triple + DHPS double) mutant was found in 4 (6.5%) of the samples. Levels of mutated parasites showed a dramatic escalation, relative to previous surveys since 1988. However, neither of the Val-16 and Thr-108 mutations, which jointly confer resistance to cycloguanil, was detectable among the human infections. The Leu-164 mutation, associated with high grade resistance to both pyrimethamine and cycloguanil, as a multiple mutant with Asn-108, Arg-59 and (or) Ile-51, was also absent.
This study points to escalating levels of P. falciparum antifolate resistance in the vicinity of Macha. Continued monitoring is recommended to ensure timely policy revisions before widespread resistance exacts a serious public health toll.
Plasmodium falciparum genotyping with molecular polymorphic markers is widely employed to distinguish recrudescence from re-infection in antimalarial drug efficacy monitoring programmes. However, ...limitations occur on agarose gel DNA measurements used to resolve the polymorphisms. Without empirical data, the current distinction of pre- and post-treatment bands, as persistent or new infection, is subjective and often varying by author. This study measures empirical tolerance limits for classifying different-sized bands as same or different alleles during MSP2 genotyping.
P. falciparum field samples from 161 volunteers were genotyped by nested PCR using polymorphic MSP2 family-specific primers. Data were analysed to determine variability of band size measurements between identical MSP2 alleles randomized into different agarose lanes.
The mean (95% CI) paired difference in band size between identical alleles was 9.8 bp (1.48 - 18.16 bp, p = 0.022) for 3D7/IC and 2.54 (-3.04 - 8.05 bp, p = 0.362) for FC27. Based on these findings, pre- and post-treatment samples with 3D7/IC alleles showing less than 18 bp difference corresponded to recrudescence, with 95% confidence, while greater difference indicated new infection. FC27 allele differences were much narrower. For both 3D7/IC and FC27 amplicon, allele detection sensitivity was significantly higher with 13 mul compared to 20 mul or 30 mul lane loading volumes.
During MSP genotyping, it is useful to standardize classifications against measurement of background variability on identical alleles, in order to obtain reliable findings. It is critical to use a fixed optimal lane loading volume for constant allele patency, to avoid the disappearance or false appearance of new infection.
Intimate partner violence (IPV) during pregnancy has been associated with multiple negative health outcomes including emotional distress during pregnancy. However, little is known about IPV during ...pregnancy and its association with emotional distress among South African women. The objectives of this study were to determine the prevalence of both emotional distress and IPV during pregnancy, to identify whether different exposures of violence were associated with emotional distress and to assess whether social support attenuated the relationship between IPV and emotional distress. Pregnant women enrolled in the South Africa HIV Antenatal and Posttest Support Study (SAHAPS) who completed the baseline survey were included in this cross sectional analysis. We used logistic regression models to explore bivariate and multivariate relationships between the proposed covariates and emotional distress. Nearly a quarter of women experienced some type of IPV during the current pregnancy, with psychological violence being the most prevalent. The odds of emotional distress was 1.41 times (95% CI: 1.26, 1.57) higher for each additional episode of psychological violence and 2.01 times (95% CI: 1.16, 3.77) higher for each additional episode of sexual violence during pregnancy, adjusting for other covariates. Physical violence was only marginally associated with increased odds of emotional distress. Finally, social support was marginally significant as a main effect but did not attenuate the relationship between IPV and emotional distress. The high prevalence of IPV among South African women and its association with emotional distress during pregnancy suggest that interventions that reduce violence during or prior to pregnancy are needed.
PDF
