Levels of DDT and metabolites in breast milk from Kwa-Zulu mothers after DDT application for malaria control

Concentrations of DDT, DDE and DDD were determined in the breast milk of Kwa-Zulu mothers residing in two different areas--with and without annual intra-domiciliary applications of DDT for the interruption of malaria transmission (exposed and control groups, respectively). While no significant change in levels with time was found in the control group, both DDT and DDE in breast milk of the exposed group increased after DDT application and this continued for three more months, after which it did not decrease appreciably. Percentage DDT increased from 42.57% (sigma DDT = 12.21 mg/kg milk fat) before spraying to 50.87% (sigma DDT = 13.79 mg/kg milk fat) following DDT application. At 6 and 9 months after the application it was 45.85% (sigma DDT = 19.49 mg/kg milk fat) and 43.27% (sigma DDT = 18.34 mg/kg milk fat), respectively. These results suggest a risk to the health of the infants in the exposed group.     

Worldwide trends in DDT levels in human breast milk.

BACKGROUND: Concern over human breast milk contamination with the pesticide DDT (1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane) has prompted numerous studies around the world during the last five decades. This article examines trends in reported DDT levels, and the apparent effect of restrictions on DDT use. METHODS: More than 130 published values for DDT in human milk since 1951 were compiled, and trend lines were fit for regions of the world. RESULTS: Population means have declined in much of the world, from 5000-10000 microg DDT/kg milk fat to around 1000 today in many areas. Although different regions have different means, the decline seen in various countries corresponds to their restricting DDT use. DISCUSSION: DDT concentrations in human milk have declined in most areas of the world, consistent with restrictions on its use. Nevertheless, levels can be high in areas still using DDT, even higher than the World Health Organization's recommended limit for infants. These results indicate that population averages can be reduced by a predictable amount as DDT use is restricted.     

Exposure assessment for workers applying DDT to control malaria in Veracruz, Mexico.

DDT has systematically been used in sanitation campaigns against malaria in Mexico. To assess chronic occupational exposure, we studied a group of workers dedicated to spraying houses to control malaria vectors in the state of Veracruz. Exposure was directly estimated for a subgroup of 40 workers by measuring DDT metabolites in adipose tissue samples and indirectly estimated for 331 workers by using a questionnaire to determine their occupational history. Participants ranged in age from 20 to 70 years, and 80% of the workers had been employed in the sanitation campaign for at least 20 years. The mean concentrations of extractable lipids found in adipose tissue samples were as follows: total DDT, 104.48 micrograms/g; p,p'-DDE, 60.98 micrograms/g; p,p'-DDT, 31.0 micrograms/g; o,p'-DDT, 2.10 micrograms/g; and p,p'-DDD, 0.95 microgram/g. The DDT metabolite p,p'-DDE was selected as the indicator of chronic exposure. An index of chronic occupational exposure was constructed according to worker position and based on the historical duration and intensity of DDT application. A linear model including this index, the use of protective gear, and recent weight loss explained 55% of the variation of p,p'-DDE concentrations in adipose tissue. By this model, the predicted values of p,p'-DDE concentration in adipose tissue for the 331 workers are between 9.56 micrograms/g and 298.4 micrograms/g of fat, with a geometric mean of 67.41 micrograms/g. These high levels of DDT in adipose tissue call for exposure prevention programs and the promotion of more secure application measures and hygiene. We also discuss the use of indirect measures of DDT exposure in epidemiological studies of health effects.     

Cooperative actions to achieve malaria control without the use of DDT

The success of regional networks to provide incentives and mechanisms for sharing information is illustrated through the North American Regional Action Plan on DDT (NARAP). This NARAP was designed to reduce human and environmental exposure to DDT and its metabolites in North America through cooperative efforts. The increasing role of environmental concerns in the planning and design of Mexico's DDT phase-out program motivated the Mexican Ministry of Health to undertake an alternative program for malaria control maximizing community participation without negatively affecting human and ecosystem health. This program relies on: 1) elimination of parasites in people, 2) improvement of personal and household hygiene, and 3) use of environmental management practices to eliminate mosquito breeding sites. This new strategy resulted in the elimination of DDT for malaria control in Mexico in the year 2000. While malaria and its corresponding vectors show considerable variability within a single country and certainly around the globe, the case example of Mexico provides a methodology for developing alternatives to DDT.     

Transmission of methicillin-resistant Staphylococcus aureus to preterm infants through breast milk.

OBJECTIVE: To determine a potential source of MRSA colonization and infection among preterm infants in a neonatal intensive care unit (NICU) using molecular analysis of breast milk samples. DESIGN: Case report, outbreak investigation. RESULTS: Preterm triplets were delivered at 26 weeks' gestation via cesarean section when routine active surveillance for MRSA was performed for all infants in a NICU. Surveillance consisted of swabbing the throat, nose, and umbilicus (TNU) weekly. Although infants A and B initially had negative TNU swabs, repeat cultures were positive for MRSA on day of life (DOL) 10 and DOL 18, respectively. Surveillance and clinical cultures for infant C were negative. Infant A developed sepsis, and multiple blood cultures were positive for MRSA beginning on DOL 14. Infant B developed conjunctivitis and a conjunctival exudate culture was positive for MRSA on DOL 70. Both infants were fed breast milk via nasogastric tube. Cultures of breast milk samples for infants A and B dated prior to either infant's first positive surveillance culture were positive for MRSA. All MRSA isolates had identical results on antibiotic susceptibility testing. PFGE demonstrated identical banding patterns for the MRSA isolates from the blood culture of infant A, breast milk for infants A and B, and a surveillance swab from infant B. At no time did the mother develop evidence of mastitis or other local breast infection. CONCLUSIONS: MRSA can be passed from mother to preterm infant through contaminated breast milk, even in the absence of maternal infection. Colonization and clinical disease can result.     

Transfer of antibody via mother's milk

Differing from humans, IgG from breast milk in many animal species (rodents, bovines, cats, ferrets, etc.) are transported across the intestinal epithelium into the neonatal circulation. This transport is located at the duodenal and jejunal level where enterocytes express a surface membrane receptor able to bind Fc of IgG and to facilitate transcytosis of these immunoglobulins. Fcgamma-R, which is very similar to the placenta receptor responsible for active transplacental transfer of IgG in humans, binds IgG but not other isotypes. Maternal milk antibodies represent an important part of circulating IgG in these animals, as they are involved in the negative feedback of endogenous IgG synthesis. This phenomenon stops abruptly as soon as weaning takes place. Neonatal calves that have a defect in such transfer of maternal immunoglobulins are at high risk of systemic infectious diseases. In humans, in whom gut closure occurs precociously, breast milk antibodies do not enter neonatal/infant circulation. A large part of immunoglobulins excreted in milk are IgA that protect mainly against enteric infections. The specificity of maternal milk IgA is driven by an entero-mammary cell circulation. Human milk also contains anti-idiotypic antibodies capable of enhancing infant antibody response. Maternal milk antibodies coat infant mucosal surfaces and some have a clear protective role. This has been studied extensively in infectious disease models such as rotavirus, E. coli, poliovirus, and retroviruses. In the rotavirus model, antirotaviral IgA can be detected in stools of breast-fed but not bottle-fed neonates. In a large cohort of lactating women infected with HIV-1 in Rwanda, anti-HIV milk antibodies of the IgG isotype were more frequently detected followed by secretory IgM. Surprisingly, anti-HIV-1 SIgA were less frequently found. The presence of milk SIgA at 15 days as well as the persistence of a SIgM response during the whole lactation period was associated with lower risk of HIV transmission from the mother to the infant. Recently, HIV-1 antibodies from maternal milk have been shown to block transcytosis in vitro in a monolayer enterocyte model. Among these antibodies, those directed against the ELDKWA epitope had higher neutralising activity than serum antibodies.In humans, milk excreted antibodies play a major role in protecting infants from infection by pathogens having a mucosal portal of entry.     

DDT and its metabolites in breast milk from two regions in Saudi Arabia.

A cross sectional study was designed to measure DDT residues and its metabolites in breast milk samples collected randomly from Saudi lactating mothers living in Al-Ehssa region; which was under leishmania control until 1995, and compare them to samples from mothers living in Riyadh region where no spraying activities was involved. p,p'-DDE, p,p'-DDD and p,p'-DDT residues were measured in 878 breast milk samples by Gas Chromatography/Electron Capture Detector (GC/ECD) and confirmed by Gas Chromatography/Mass Spectrometer Detector (GC/MSD). Variation in the DDT and its metabolites levels were investigated with respect to regional distribution. Wilcoxon rank sum tests showed that the average ranks of p,p'-DDE, p,p'-DDD, p,p'-DDT and sigma p,p'-DDT in lactating mothers from Al-Ehssa region were significantly higher than those living in Riyadh region. These differences supported our hypothesis that the implications of the spraying activities to control vector borne diseases in Al-Ehssa region are obvious. We estimated that 99.2% of infants of lactating mothers living in Al-Ehssa region had sigma p,p'-DDT daily intakes that exceeded 20 micrograms/Kg-day of body weight, the WHO/UNEP Acceptable Daily Intakes for a 5-Kg infant. Exposure of infants to these chemicals through breast-feeding is clearly a public health concern. Because the bulk of literature highlights the adverse health effects of DDT and its metabolites on children and infants, public health polices should enforce the ban of DDT use and advise pregnant and lactating women to avoid DDT containing food or any other type of exposure.     

An evaluation of the residual lifespan of DDT in malaria control

The insecticide lifespan of DDT was assessed in huts sprayed for malaria control. The age of the spray deposits ranged from 3 up to 22 months. Blood-fed female Anopheles arabiensis were either released into the huts or exposed on sprayed surfaces by a bioassay technique. Mosquitoes released were recovered in exit traps fitted on windows or dead on the floor. Only 50% or less of mosquitoes released in sprayed huts were recovered. Mortality figures for recovered mosquitoes ranged from 94% at 3 months, declining to 19% for huts sprayed 18 months previously. Of the recovered mosquitoes, 60% or more attempted to escape from sprayed huts within two hours postrelease up to 15 months postspray. Bioassays gave average mortalities of 95 and 76% on thatch and mud walls, respectively. Analysis of mud samples from test huts showed that target dose of 2 g AI/m2 of DDT was not being achieved. The results support the need for an annual spraying cycle.     

Nonmalarial infant deaths and DDT use for malaria control

Although dichlorodiphenyl trichloroethane (DDT) is being banned worldwide, countries in sub-Saharan Africa have sought exemptions for malaria control. Few studies show illness in children from the use of DDT, and the possibility of risks to them from DDT use has been minimized. However, plausible if inconclusive studies associate DDT with more preterm births and shorter duration of lactation, which raise the possibility that DDT does indeed have such toxicity. Assuming that these associations are causal, we estimated the increase in infant deaths that might result from DDT spraying. The estimated increases are of the same order of magnitude as the decreases from effective malaria control. Unintended consequences of DDT use need to be part of the discussion of modern vector control policy.     

DDT, global strategies, and a malaria control crisis in South America.

Malaria is reemerging in endemic-disease countries of South America. We examined the rate of real growth in annual parasite indexes (API) by adjusting APIs for all years to the annual blood examination rate of 1965 for each country. The standardized APIs calculated for Brazil, Peru, Guyana, and for 18 other malaria-endemic countries of the Americas presented a consistent pattern of low rates up through the late 1970s, followed by geometric growth in malaria incidence in subsequent years. True growth in malaria incidence corresponds temporally with changes in global strategies for malaria control. Underlying the concordance of these events is a causal link between decreased spraying of homes with DDT and increased malaria; two regression models defining this link showed statistically significant negative relationships between APIs and house-spray rates. Separate analyses of data from 1993 to 1995 showed that countries that have recently discontinued their spray programs are reporting large increases in malaria incidence. Ecuador, which has increased use of DDT since 1993, is the only country reporting a large reduction (61%) in malaria rates since 1993. DDT use for malaria control and application of the Global Malaria Control Strategy to the Americas should be subjects of urgent national and international debate. We discuss the recent actions to ban DDT, the health costs of such a ban, perspectives on DDT use in agriculture versus malaria control, and costs versus benefits of DDT and alternative insecticides.     

Reproductive effects of occupational DDT exposure among male malaria control workers

To assess potential effects of human DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] exposure, we evaluated the reproductive history of 2,033 workers in the antimalaria campaign of Mexico. Data on occupational exposure to DDT and reproductive outcomes were gathered through a questionnaire, and workers provided information about 9,187 pregnancies. We estimated paternal exposure to DDT before each pregnancy using three approaches: a) a dichotomous indicator for pregnancies before and after exposure began, b) a qualitative index of four exposure categories, and c) an estimation of the DDT metabolite DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] accumulated in fat. To assess associations, we used logistic regression models that accounted for correlated observations and adjusted for parents' age at each child's birth, exposure to other pesticides, exposure to chemical substances in other employment, smoking, and alcohol consumption. The odds ratio for birth defects comparing pregnancies after and before the first exposure was 3.77 [95% confidence interval (95% CI), 1.19-9.52]. Compared with the lowest quartile of estimated DDE in fat, the ORs were 2.48 (95% CI, 0.75-8.11), 4.15 (95% CI, 1.38-12.46), and 3.76 (95% CI, 1.23-11.44) for quartiles 2, 3, and 4, equivalent to p,p -DDE in fat of 50, 82, and 298 microg/g fat, respectively. No significant association was found for spontaneous abortion or sex ratio. We found an increased risk of birth defects associated with high occupational exposure to DDT in this group of workers. The significance of this association at lower exposure levels found in the general population remains uncertain.     

PCB exposure in utero and via breast milk. A review

A review of the literature was conducted to investigate the importance to offspring of in utero and breast milk polychlorinated biphenyl (PCB) exposure. All reports that we could identify (n=25) were included, representing 16 study populations. Tissue-specific PCB concentrations in human placenta, breast milk, maternal blood and cord blood were compared to determine accumulation ratios between tissue compartments. On a lipid basis, the highest concentration of PCB in placenta (5027 ng/g fat) was 2.8 times higher than the highest concentration of PCB in breast milk ( 1770 ng/g fat). While there are limitations with regard to quantitation methods and statistical methods utilized by the reviewed studies, our results suggest that PCBs may be capable of crossing the placenta to a greater extent than previously believed. Future studies of PCB body burden in the perinatal period should include placenta, breast milk, maternal and cord blood specimens. In order to compare PCB concentrations in various tissues and with other studies, concentrations should be determined on a lipid basis.     

Parachuting cats and crushed eggs the controversy over the use of DDT to control malaria

The use of DDT to control malaria has been a contentious practice for decades. This controversy centers on concerns over the ecological harm caused by DDT relative to the gains in public health from its use to prevent malaria. Given the World Health Organization's recent policy decisions concerning the use of DDT to control malaria, it is worth reviewing the historical context of DDT use. Ecological concerns focused on evidence that DDT ingestion by predatory birds resulted in eggs with shells so thin they were crushed by adult birds. In addition, DDT spraying to control malaria allegedly resulted in cats being poisoned in some areas, which led to increased rodent populations and, in turn, the parachuting of cats into the highlands of the island of Borneo to kill the rodents, a story that influenced the decision to ban DDT spraying. I focus on this story with the intention of grounding the current debate on lessons from the past.