Social acceptance of livestock-administered endectocides for malaria control in Vhembe District, Limpopo Province, South Africa.

BACKGROUND: Malaria continues to be a leading cause of morbidity and mortality in Africa and conventional malaria control strategies, such as indoor residual spraying and insecticide-treated bed nets, have limited effectiveness for some malarial vectors. Consequently, the development of alternative or supplementary strategies is required. One potential strategy is the use of livestock-administered endectocides to control vector mosquitoes that feed outdoors on livestock. However, since this strategy requires support from local communities and livestock owners consenting for their animals to be treated, it can only be implemented if agreed to by affected communities. The aim of this study was to assess the social acceptance of the use of livestock-administered endectocides in the malaria endemic villages of Vhembe District, Limpopo Province, South Africa, where malaria incidence is high. METHODS: Questionnaires were administered to 103 livestock-owning households from four villages, namely, Gumbu, Malale, Manenzhe and Bale. The assessment included questions on the acceptability of the strategy, the type and number of livestock owned, distances between houses and kraals (overnight pens) as well as previous use and awareness of endectocides. The results were analysed using descriptive statistics and multinomial logistic regression. RESULTS: The types of livestock owned by the participants comprised, cattle, goats, sheep and donkeys, with the most dominant being goats (n = 1040) and cattle (n = 964). The majority of kraals were less than 10 m from homesteads. Most participants (72.5%) were already using chemicals to treat their livestock for parasites. All participants were amenable to the implementation of the strategy, and would give consent for their animals to be treated by endectocides. CONCLUSIONS: The use of livestock-administered endectocides appears to be a feasible and acceptable approach for control of animal-feeding malaria vector species in the malaria endemic villages of Vhembe District. This is based on a high percentage of rural residents keeping suitable livestock close to their homes and expressing willingness to use endectocides for mosquito control.

Endocrine Disruptors and Health Effects in Africa: A Call for Action.

BACKGROUND: Africa faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa. However, a coordinated approach to identify and monitor these contaminants and to develop strategies for public health interventions has not yet been made. OBJECTIVES: This commentary summarizes the scientific evidence presented by experts at the First African Endocrine Disruptors meeting. We describe a "call to action" to utilize the available scientific knowledge to address the impact of EDCs on human and wildlife health in Africa. DISCUSSION: We identify existing knowledge gaps about exposures to EDCs in Africa and describe how well-designed research strategies are needed to address these gaps. A lack of resources for research and a lag in policy implementation slows down intervention strategies and poses a challenge to advancing future health in Africa. CONCLUSION: To address the many challenges posed by EDCs, we argue that Africans should take the lead in prioritization and evaluation of environmental hazards, including EDCs. We recommend the institution of education and training programs for chemical users, adoption of the precautionary principle, establishment of biomonitoring programs, and funding of community-based epidemiology and wildlife research programs led and funded by African institutes and private companies. https://doi.org/10.1289/EHP1774.

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.

Acceptability and effectiveness of a monofilament, polyethylene insecticide-treated wall lining for malaria control after six months in dwellings in Vhembe District, Limpopo Province, South Africa.

BACKGROUND: South Africa uses indoor residual spraying (IRS) for vector control in its malaria control programme (MCP). Insecticide-treated wall linings (ITWLs) offer possible advantages over IRS and long-lasting, insecticide-treated nets (LLINs). This study assessed the user acceptability and perceived effectiveness, and the durability, including efficacy through bioassays, of a newly developed, monofilament polyethylene ITWL. METHODS: Four ITWL formulations/treatments, two incorporated with deltamethrin and two with alpha-cypermethrin in concentrations ranging from 0.29 to 0.85 wt%, and untreated linings were randomly installed on the inner walls of traditional mud huts (n = 20) and modern brick houses (n = 20) in a community village in Vhembe District, Limpopo Province. The linings were exposed to conditions within these dwellings over 6 months. Data were collected monthly through questionnaires and entomological residual efficacy analysis of ITWL, as part of durability testing, was done bimonthly using WHO prescribed bioassays. RESULTS: Monofilament polyethylene ITWLs were successfully installed in traditional sleeping huts and in bedrooms of modern type brick houses. ITWL remained intact throughout the entire 6 months of the study. Participants did not express any dissatisfaction towards the linings although two participants indicated the product should be fitted at a lower level for better results. User perceived effectiveness was very high with participants reporting observed mortality of mosquitoes and other nuisance insects. This perception coincided with results obtained through residual efficacy bioassays where a 100 % knockdown and mortality of mosquitoes was recorded throughout the trial period. Acceptability regarding appearance, including colour, position and attachment method, was also satisfactory with some participants citing the lining as decorative. All participants opted to keep ITWL and residual long-term efficacy will be determined annually for a further 3 years. CONCLUSIONS: The newly developed ITWLs are highly accepted amongst participants in an unsprayed section of a village in a malaria-endemic area. The perceived effectiveness that coincides with results obtained through bioassays and acceptance of the overall appearance of ITWL will be evaluated over a longer term to determine sustainability. With further developing and testing, this ITWL has the potential to become a sustainable and safer alternative vector control method.

The role of the PCA3 assay in predicting prostate biopsy outcome in a South African setting.

UNLABELLED: What's known on the subject? and What does the study add? The PCA3 assay has shown significant potential amongst the initial studies carried out in Western countries. This assay performed in line with previous studies. We have shown this marker to perform independent of prostatic volume and have identified potential indications for its use in our setting. However, we have not observed the PCA3 assay to outperform the PSA level across the risk spectrum. OBJECTIVES: • To evaluate the investigational role, ideal threshold and indications of the Prostate CAncer gene 3 (PCA3) assay in a South African context. • To better define the universality of the above marker since this is the pioneer study on the continent of Africa. PATIENTS AND METHODS: • We prospectively evaluated 105 consecutive South African men referred for a prostate biopsy at two tertiary centres in the capital city, Pretoria. • Sequentially, PSA levels and post DRE urine samples were taken within 24 h before prostate biopsy. • The urine specimen was tested using the PROGENSA™ PCA3 assay and a score was generated as (PCA3 mRNA/PSA mRNA) × 1000. • The performance of this assay in predicting biopsy outcome was assessed, and compared with that of serum PSA. RESULTS: • Median patient age was 67 years with a positive biopsy incidence of 42.9%. • The higher the PCA3 score the greater the probability of a positive biopsy (P = 0.003). • This score performed independently of prostatic volume (P = 0.3889) or the presence of a concurrent primary malignancy (P = 0.804). • A threshold of 60 revealed a positive predictive value of 60% with an odds ratio of 4, whereas setting a limit of 35 revealed a positive predictive value of 54% and odds ratio of 3.5. • Using receiver operating characteristics for overall performance comparison, the PSA level (area under the curve 0.844) performed better than the PCA3 score (area under the curve 0.705). CONCLUSION: • PCA3 assay has shown consistency and performed in line with previous studies but it did not surpass serum PSA in this population. • A PCA3 assay threshold of 60 performed better than the conventional limit of 35. • This assay may have a potential niche in a certain subset of South African men that includes patients with larger glands, previous negative biopsies and altered baseline PSA levels.

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.

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.

Ultrastructural changes of platelet aggregates and fibrin networks in a patient with renal clear cell adenocarcinoma: a scanning electron microscopy study.

A 47-year-old male patient presented with weight loss, hematuria, and a left renal mass, which proved to be a clear cell renal carcinoma with multiple liver, pulmonary and bone metastases. The platelet count was raised initially (414 x 10(9)/L) but declined 10 weeks after a debulking procedure followed by chemotherapy. Fibrin clots were prepared for scanning electron microscopy (SEM) by adding human thrombin to platelet rich plasma (derived by differential centrifugation of fresh blood samples taken from the patient as well as controls). The clots were washed, fixed in 2.5% glutaraldehyde and Dulbecos phosphate buffered saline and prepared for SEM with a Zeiss Ultra 55 FEG SEM. The SEM photographs revealed an altered morphology of the platelet aggregates with multiple breakages in the platelet membrane, showing a pock-marked, crenated, prune-like appearance as opposed to the smooth rounded globular membrane of the controls. The ultrastructural morphology of the fibrin bound platelet aggregates in this patient with renal carcinoma therefore showed a disrupted cytoskeletal architecture which appears to be similar to the apoptotic changes of programmed cell death as described by Bornman et al. (2007) and Pretorius et al. (2008). These features may well be a distinct ultrastructural hematological manifestation of a previously unidentified paraneoplastic syndrome.

Histopathological changes in the reproductive system (ovaries and testes) of Oreochromis mossambicus following exposure to DDT.

This study assesses the effects of 1,1-bis (4-chlorophenyl)-2,2,2-trichloroethane (DDT) on the reproduction and gonadal histology of adult Mozambique tipalia (Oreochromis mossambicus). The fish were allowed to breed, following exposure to 2 and 5µg/l of waterborne technical-grade DDT for 40 days. Fertilized eggs were artificially incubated. In the 5µg/l exposure, posthatch survival was significantly lower, and prevalence of larval skeletal deformities significantly higher, compared to the control (p<0.05). Incomplete axial development was the common gross deformity in posthatch larvae, caused by failure to develop chondroblasts posterior to the buccopharyngeal cavity. There were no significant differences in the gonadosomatic index of exposed and non-exposed male and female adults. The exposure caused increased oocyte atresia in the ovaries and disorganization of seminiferous lobules in the testes of adults. DDT exposure reduced survival and increased deformities in larvae, at levels that did not cause severe histopathological changes to parental gonads.

Testicular apoptosis in feral Clarias gariepinus using TUNEL and cleaved caspase-3 immunohistochemistry.

This paper reports on the mechanistic basis of cellular death in the testis of Clarias gariepinus using the TUNEL and caspase-3 immunohistochemistry. It was also aimed to determine the testicular zone most suitable for the quantification of testicular apoptosis. The results showed that based on its immuno-expression patterns, activated caspase-3 has a clear and defined role in the progression of germ cell apoptosis in spermatogenically active catfish testis. Caspase-3 activation, and not TUNEL-detected DNA fragmentation, is associated with condensation of chromatin into a single mass. Testes of spermatogenically active catfish consist of spermatogenic, mature and spent tubules. Spermatogenic tubules were concluded to be the most suitable zone for the quantification of testicular cell death ratios as apoptotic events occurred predominantly in the secondary spermatocytes. The findings of this study will form the basis to link apoptotic events in the testes of C. gariepinus with the effects of EDC exposure in future studies.

Impaired semen quality associated with environmental DDT exposure in young men living in a malaria area in the Limpopo Province, South Africa.

The pesticide DDT [1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane] is 1 of the 12 persistent organic pollutants (POPs) under negotiation at the Stockholm Convention to restrict or ban their production and use because of their toxicity, resistance to breakdown, bioaccumulation, and potential for being transported over long distances. DDT has estrogenic potential, and the main metabolite, p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE), is a potent antiandrogen. In response to mounting evidence on the endocrine-disrupting influence of environmental chemicals on human health, this epidemiological study was initiated to test the hypothesis that nonoccupational exposure to DDT affects male reproductive parameters. In a cross-sectional study, healthy male subjects (n=311) between 18 and 40 years (23+/-5) of age were recruited from 3 communities in an endemic malaria area in which DDT is sprayed annually. A semen analysis according to World Health Organization (WHO) standards was performed. The Hamilton Thorne Computer Assisted Sperm Analysis (CASA) system was simultaneously used to determine additional sperm motility parameters. Blood plasma samples were assayed for p,p'-DDT and metabolites as a measure of exposure. The exposure levels were expressed as lipid-adjusted p,p'-DDT and p,p'-DDE values. The mean p,p'-DDT and p,p'-DDE concentrations were 90.23 microg/g(+/-102.4) and 215.47 microg/g(+/-210.6), respectively. The multivariate linear regression analyses indicated that mean CASA motility was lower with a higher p,p'-DDE concentration (beta=-0.02, P=.001) and the CASA parameter beat cross-frequency (BCF) was higher with a higher p,p'-DDT concentration (beta=0.01, P=.000). There was also a statistically significant positive association between percent sperm with cytoplasmic droplets and p,p'-DDT concentration (beta=0.0014, P=.014). The ejaculate volume (mean 1.9+/-1.33 mL) was lower than the normal range (>or=2.0 mL) according to WHO, and a significant decrease with increasing p,p'-DDE values was seen for both square root-transformed volume (beta=-0.0003; P=.024) and count (beta=-0.003; P=.04). Although there were no associations between either p,p'-DDT or p,p'-DDE concentrations and the rest of the seminal parameters, the incidence of teratozoospermia (99%; normal sperm<15%) was high. Twenty-eight percent of the study group presented with oligozoospermia (<20x10(6) sperm/mL), which had a significant positive association with p,p'-DDE (odds ratio [OR]=1.001, P=.03). There was a significant positive association between participants with asthenozoospermia (32%) and p,p'-DDT (OR 1.003, P=.006) and p,p'-DDE (OR 1.001, P=.02). The results imply that nonoccupational exposure to DDT is associated with impaired seminal parameters in men. The high exposure levels of p,p'-DDT and p,p'-DDE are of concern because these levels could have far-reaching implications for reproductive and general health.