Christiaan de Jager

The pine river statement: human health consequences of DDT use.

Objectives Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.

Changes in malaria morbidity and mortality in Mpumalanga Province, South Africa (2001- 2009): a retrospective study

BackgroundMalaria remains a serious epidemic threat in Mpumalanga Province. In order to appropriately target interventions to achieve substantial reduction in the burden of malaria and ultimately eliminate the disease, there is a need to track progress of malaria control efforts by assessing the time trends and evaluating the impact of current control interventions. This study aimed to assess the changes in the burden of malaria in Mpumalanga Province during the past eight malaria seasons (2001/02 to 2008/09) and whether indoor residual spraying (IRS) and climate variability had an effect on these changes.MethodsThis is a descriptive retrospective study based on the analysis of secondary malaria surveillance data (cases and deaths) in Mpumalanga Province. Data were extracted from the Integrated Malaria Information System. Time series model (Autoregressive Integrated Moving Average) was used to assess the association between climate and malaria.ResultsWithin the study period, a total of 35,191 cases and 164 deaths due to malaria were notified in Mpumalanga Province. There was a significant decrease in the incidence of malaria from 385 in 2001/02 to 50 cases per 100,000 population in 2008/09 (P < 0.005). The incidence and case fatality (CFR) rates for the study period were 134 cases per 100,000 and 0.54%, respectively. Mortality due to malaria was lower in infants and children (CFR < 0.5%) and higher in those >65 years, with the mean CFR of 2.1% as compared to the national target of 0.5%. A distinct seasonal transmission pattern was found to be significantly related to changes in rainfall patterns (P = 0.007). A notable decline in malaria case notification was observed following apparent scale-up of IRS coverage from 2006/07 to 2008/09 malaria seasons.ConclusionsMpumalanga Province has achieved the goal of reducing malaria morbidity and mortality by over 70%, partly as a result of scale-up of IRS intervention in combination with other control strategies. These results highlight the need to continue with IRS together with other control strategies until interruption in local malaria transmission is completely achieved. However, the goal to eliminate malaria as a public health problem requires efforts to be directed towards the control of imported malaria cases; development of strategies to interrupt local transmission; and maintaining high quality surveillance and reporting system.

Immunohistochemical study of nuclear changes associated with male germ cell death and spermiogenesis

In a previous study on the effects of gestational and lactational exposure of para-nonylphenol on male rats, we noted in both induced and uninduced rats, that variations in cleaved caspase-3 immunostaining patterns were associated with distinct nuclear alterations in mainly basally located germ cells (spermatogonia and preleptotene spermatocytes). These were re-analysed and compared with cleaved caspase-3-labeled germ cells in the aging human and the spermatogenically active catfish testis. In the rat testes, cytoplasmic immunostaining was progressively associated with lateral compression of the nucleus, its break up into large pieces which can contain immunostained marginated chromatin masses. The pale remnants of the nucleus continued to shrink in size concomitant with the appearance of blue-purplish stained regions in the cytoplasm similar in color to the condensed chromatin in spermatids, a condition which was TUNEL-negative. These large clumps of chromatin also eventually disappeared, giving rise to cells resembling cytoplasmic ghosts, a condition which was TUNEL-positive. By contrast, the immunolabeled nuclei of human and catfish germ cells condensed into a single mass, after which they lost immunoreactivity. To exclude the possibility that these observations could reflect alterations in Sertoli nuclei, rat testicular sections were probed with a mouse anti-human GATA-4 monoclonal (MHM) antibody. The MHM was, however, the second of two GATA-4 antibodies tested, with a goat anti-mouse polyclonal (GMP) initially used to label the rat Sertoli nuclei. GMP unexpectedly, but distinctly labeled the complete development of the acrosome in the rat testis, a fortuitous finding with utility for staging of the seminiferous epithelium.

Changes in retinol-binding protein concentrations and thyroid homeostasis with nonoccupational exposure to DDT.

Background The insecticide dichlorodiphenyltrichloroethane (DDT) has been used for malaria vector control in the northern and eastern parts of the Vhembe District of Limpopo Province, South Africa, since 1945. Bioaccumulation of DDT raises concern because it reportedly affects thyroid function. Objective Our objective was to investigate the association between DDT uptake (as reflected in plasma concentrations) and thyroid homeostasis while considering related factors. Methods We compared dietary intake, serum retinol-binding protein (RBP), transthyretin (TTR) and albumin concentrations, and liver and thyroid function between cases with evidence of a body burden of DDT in the circulation (concentration of any DDT isomer ≥ 0.02 μg/g lipid; n = 278) and controls (concentration of all DDT isomers < 0.02 μg/g lipid; n = 40) in a cross-sectional study. Further analyses were performed to assess the relevance of changes in RBP status associated with DDT uptake. Results RBP concentrations below the reference range were more prevalent in cases (54% vs. 10% in controls; χ2 = 27.4; p < 0.001), which could not be explained by nutrient intake. We observed significantly lower thyroid hormone concentrations among cases (p ≤ 0.01). We also observed a significant linear trend for serum concentrations of free thyroxine and free triiodothyronine (p < 0.001) and a significant quadratic trend for serum thyroid-stimulating hormone (p = 0.025) and TTR (p < 0.001) across the control group and case groups with normal and relatively low RBP concentrations. Relatively low RBP concentrations were associated with significantly higher DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) isomer concentrations and with a higher DDE/DDT ratio (p ≤ 0.01), which signifies long-term exposure. Inadequate intake of vitamin A and zinc were observed in 84% and 58%, respectively, of the total study population. Conclusion RBP concentrations appear to decrease in the presence of long-term DDT uptake, which may have deleterious effects on thyroid function and vitamin A nutritional status. This is of major concern in a population with poor vitamin A and zinc intake.

Sustainable malaria control: transdisciplinary approaches for translational applications

With the adoption of the Global Malaria Action Plan, several countries are moving from malaria control towards elimination and eradication. However, the sustainability of some of the approaches taken may be questionable. Here, an overview of malaria control and elimination strategies is provided and the sustainability of each in context of vector- and parasite control is assessed. From this, it can be concluded that transdisciplinary approaches are essential for sustained malaria control and elimination in malaria-endemic communities.

Morbidity and mortality due to malaria in Est Mono district, Togo, from 2005 to 2010: a times series analysis

BackgroundIn 2004, Togo adopted a regional strategy for malaria control that made use of insecticide-treated nets (ITNs), followed by the use of rapid diagnostic tests (RDTs), artemisinin-based combination therapy (ACT). Community health workers (CHWs) became involved in 2007. In 2010, the impact of the implementation of these new malaria control strategies had not yet been evaluated. This study sought to assess the trends of malaria incidence and mortality due to malaria in Est Mono district from 2005 to 2010.MethodsSecondary data on confirmed and suspected malaria cases reported by health facilities from 2005 to 2010 were obtained from the district health information system. Rainfall and temperature data were provided by the national Department of Meteorology. Chi square test or independent student’s t-test were used to compare trends of variables at a 95% confidence interval. An interrupted time series analysis was performed to assess the effect of meteorological factors and the use of ACT and CHWs on morbidity and mortality due to malaria.ResultsFrom January 2005 to December 2010, 114,654 malaria cases (annual mean 19,109 ± 6,622) were reported with an increase of all malaria cases from 10,299 in 2005 to 26,678 cases in 2010 (p<0.001). Of the 114,654 malaria cases 52,539 (45.8%) were confirmed cases. The prevalence of confirmed malaria cases increased from 23.1 per 1,000 in 2005 to 257.5 per 1,000 population in 2010 (p <0.001). The mortality rate decreased from 7.2 per 10,000 in 2005 to 3.6 per 10,000 in 2010 (p <0.001), with a significant reduction of 43.9% of annual number of death due to malaria. Rainfall (β-coefficient = 1.6; p = 0.05) and number of CHWs trained (β-coefficient = 6.8; p = 0.002) were found to be positively correlated with malaria prevalence.ConclusionThis study showed an increase of malaria prevalence despite the implementation of the use of ACT and CHW strategies. Multicentre data analysis over longer periods should be carried out in similar settings to assess the impact of malaria control strategies on the burden of the disease. Integrated malaria vector control management should be implemented in Togo to reduce malaria transmission.

Mosquito-borne arboviruses of African origin: review of key viruses and vectors

Key aspects of 36 mosquito-borne arboviruses indigenous to Africa are summarized, including lesser or poorly-known viruses which, like Zika, may have the potential to escape current sylvatic cycling to achieve greater geographical distribution and medical importance. Major vectors are indicated as well as reservoir hosts, where known. A series of current and future risk factors is addressed. It is apparent that Africa has been the source of most of the major mosquito-borne viruses of medical importance that currently constitute serious global public health threats, but that there are several other viruses with potential for international challenge. The conclusion reached is that increased human population growth in decades ahead coupled with increased international travel and trade is likely to sustain and increase the threat of further geographical spread of current and new arboviral disease.

Effect of rotation on the generation of reactive oxygen species in human semen

Summary. Rotation of semen after liquefaction is a standard procedure in an Andrology laboratory. During rotation under aerobic conditions the semen is exposed to oxygen. Oxygen toxicity induces lipid peroxidation which is responsible for the loss of sperm function. The generation of reactive oxygen species was significantly increased after rotation. This may have a detrimental effect on sperm function during assisted reproduction.

Changing the policy for intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy in Malawi

BackgroundThe growing resistance of Plasmodium falciparum to sulfadoxine–pyrimethamine (SP) treatment for uncomplicated malaria led to a recommendation by the World Health Organization for the use of artemisinin-based combination therapy. Inevitably, concerns were also raised surrounding the use of SP for intermittent prevention treatment of malaria during pregnancy (IPTp) amidst the lack of alternative drugs. Malawi was the first country to adopt intermittent prevention treatment with SP in 1993, and updated in 2013. This case study examines the policy updating process and the contribution of research and key stakeholders to this process. The findings support the development of a malaria research-to-policy framework in Malawi.MethodsDocuments and evidence published from 1993 to 2012 were systematically reviewed in addition to key informant interviews.ResultsThe online search identified 170 potential publications, of which eight from Malawi met the inclusion criteria. Two published studies from Malawi were instrumental in the WHO policy recommendation which in turn led to the updating of national policies. The updated policy indicates that more than two SP doses, as informed by research, overcome the challenges of the first policy of two SP doses only because of ineffectiveness by P. falciparum resistance and the global lack of replacement drugs to SP for IPTp.ConclusionInternational WHO recommendations facilitated a smooth policy change driven by motivated local leadership with technical and financial support from development partners. Policy development and implementation should include key stakeholders and use local malaria research in a research-to-policy framework.

Effects of environmental endocrine disruptors, including insecticides used for malaria vector control on reproductive parameters of male rats.

The male reproductive system is sensitive to endocrine disrupting chemicals (EDCs) during critical developmental windows. Male Sprague-Dawley rats were exposed in utero-, during lactation- and directly to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and a mixture of DDT, deltamethrin (DM), p-nonylphenol (p-NP) and phytoestrogens, at concentrations found in a malaria-area. After dosing for 104 days, histological assessments and reproductive-endpoints were assessed. The anogenital distance (AGD) (P=0.005) was shorter in the mixture-exposed group, while the prostate mass (P=0.018) was higher in the DDT-exposed group. A higher testicular mass and abnormal histology was observed in the DDT-(P=0.019), DDE-(P=0.047) and mixture-exposed (P<0.005) groups. This study shows that in utero-, lactational- and direct exposure to EDCs present in a malaria-area negatively affects male reproductive parameters in rats. These findings raise concerns to EDC-exposures to mothers living in malaria-areas and the reproductive health of their male offspring.