Should DDT be banned by international treaty?

The insecticide DDT has been an effective and affordable means of malaria control in many countries, but pressure for its use to be banned is mounting. Here, Chris Curtis and Jo Lines take a critical look at evidence that links house spraying by DDT with harm to the environment and human health, and stress the need for resources for alternatives to DDT to be made available to countries that would be affected by a DDT ban.     

Can Wolbachia be used to control malaria?

Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites transmitted by the infectious bite of Anopheles mosquitoes. Vector control of malaria has predominantly focused on targeting the adult mosquito through insecticides and bed nets. However, current vector control methods are often not sustainable for long periods so alternative methods are needed. A novel biocontrol approach for mosquito-borne diseases has recently been proposed, it uses maternally inherited endosymbiotic Wolbachia bacteria transinfected into mosquitoes in order to interfere with pathogen transmission. Transinfected Wolbachia strains in Aedes aegypti mosquitoes, the primary vector of dengue fever, directly inhibit pathogen replication, including Plasmodium gallinaceum, and also affect mosquito reproduction to allow Wolbachia to spread through mosquito populations. In addition, transient Wolbachia infections in Anopheles gambiae significantly reduce Plasmodium levels. Here we review the prospects of using a Wolbachia-based approach to reduce human malaria transmission through transinfection of Anopheles mosquitoes.     

Should colonoscopy be the first investigation for colonic disease?

Many patients with suspected colonic disease undergo rigid sigmoidoscopy, barium enema examination, and ultimately total colonoscopy, but the need for preliminary radiology has not been formally assessed. A total of 168 patients requiring large bowel investigation were therefore randomised to undergo either rigid sigmoidoscopy plus double contrast barium enema examination or total colonoscopy. Disease was found in 56 patients, including 14 with a carcinoma, 11 with polyps, and 16 with inflammatory bowel disease, the remainder having diverticular disease alone. Of the 89 patients allocated to double contrast barium enema examination, nine required a subsequent colonoscopy for suspected tumour or polyps, three because of incomplete radiological examination, and 12 for rectal bleeding for which no cause was found at the radiological examination. In 16 patients this yielded further information or altered treatment. Of the 79 patients undergoing total colonoscopy, only six required subsequent radiology.As both procedures were well tolerated with no major complications total colonoscopy may be the preferred initial investigation where facilities allow.     

Roll Back Malaria? The scarcity of international aid for malaria control

Background

Intraerythrocytic malaria parasites actively import obligate nutrients from serum and export proteins and lipids to erythrocyte cytoplasm and membrane. The import of macromolecules in the malaria parasite has been the subject of many debates. To understand the import of macromolecules by the parasite, we studied the uptake of proteins by Plasmodium falciparum infected human erythrocyte.

Methods

Proteins were biotin labelled individually, purified on a gel filtration column and added to uninfected and infected asynchronized culture. The uptake of these proteins by malaria parasites was determined by western blot analysis of parasite pellet and their different fractions using streptavidin-horseradish conjugate. To further confirm this import, we studied the uptake of¹²⁵I-labelled proteins by western blot analysis as well as used direct immunofluorescence method.

Results

Here we show that biotin labelled and radio-iodinated polypeptides of molecular sizes in the range of 45 to 206 kDa, when added in the culture medium, get direct access to the parasite membrane through a membrane network by by-passing the erythrocyte cytosol. The import of these polypeptides is ATP-dependent as sodium azide treatment blocks this uptake. We also show that malaria parasites have the ability to take up and degrade biotin labelled human serum albumin, which has been shown to be essential for the parasite growth.

Conclusions

These results can be used, as a basis to explore the role of human serum albumin in the intraerythrocytic development of parasites, and this in turn can be an important adjunct to the development of novel antimalarial drugs.     

Can primaquine therapy for vivax malaria be improved?

The incidence and range of endemic malaria caused by Plasmodium vivax has expanded during the past 30 years. This parasite forms hypnozoites in the liver, creating a persistent reservoir of infection. Primaquine (PQ), introduced 50 years ago, is the only drug available to eliminate hypnozoites. However, lengthy treatment courses and follow-up periods are not conducive to assessing the effectiveness of this drug in preventing relapses. Resistance to standard therapy could be widespread. Studies are urgently needed to gauge this problem and to determine the safety, tolerability and efficacy of shorter courses and higher doses of PQ.     

Should consent be required for organ procurement?

Must we obtain a patient's consent before posthumously removing her organs? According to the consent requirement, in order to permissibly remove organs from a deceased person, it is necessary that her prior consent be obtained. If the consent requirement is true, then this seems to rule out policies that do not seek and obtain a patient's prior consent to organ donation, while at the same time vindicating policies that do seek and obtain patient consent. In this paper, however, I argue that once we recognize the difference between consent, on the one hand, and wishing or desiring, on the other, we will see that obtaining consent before organ removal is neither necessary nor sufficient to respect patient autonomy in organ procurement.     

The decline of malaria in Finland – the impact of the vector and social variables

Background

Resistance to anti-malarial drugs hampers control efforts and increases the risk of morbidity and mortality from malaria. The efficacy of standard therapies for uncomplicated Plasmodium falciparum and Plasmodium vivax malaria was assessed in Chumkiri, Kampot Province, Cambodia.

Methods

One hundred fifty-one subjects with uncomplicated falciparum malaria received directly observed therapy with 12 mg/kg artesunate (over three days) and 25 mg/kg mefloquine, up to a maximum dose of 600 mg artesunate/1,000 mg mefloquine. One hundred nine subjects with uncomplicated vivax malaria received a total of 25 mg/kg chloroquine, up to a maximum dose of 1,500 mg, over three days. Subjects were followed for 42 days or until recurrent parasitaemia was observed. For P. falciparum infected subjects, PCR genotyping of msp1, msp2, and glurp was used to distinguish treatment failures from new infections. Treatment failure rates at days 28 and 42 were analyzed using both per protocol and Kaplan-Meier survival analysis. Real Time PCR was used to measure the copy number of the pfmdr1 gene and standard 48-hour isotopic hypoxanthine incorporation assays were used to measure IC₅₀ for anti-malarial drugs.

Results

Among P. falciparum infected subjects, 47.0% were still parasitemic on day 2 and 11.3% on day 3. The PCR corrected treatment failure rates determined by survival analysis at 28 and 42 days were 13.1% and 18.8%, respectively. Treatment failure was associated with increased pfmdr1 copy number, higher initial parasitaemia, higher mefloquine IC₅₀, and longer time to parasite clearance. One P. falciparum isolate, from a treatment failure, had markedly elevated IC₅₀ for both mefloquine (130 nM) and artesunate (6.7 nM). Among P. vivax infected subjects, 42.1% suffered recurrent P. vivax parasitaemia. None acquired new P. falciparum infection.

Conclusion

The results suggest that artesunate-mefloquine combination therapy is beginning to fail in southern Cambodia and that resistance is not confined to the provinces at the Thai-Cambodian border. It is unclear whether the treatment failures are due solely to mefloquine resistance or to artesunate resistance as well. The findings of delayed clearance times and elevated artesunate IC₅₀ suggest that artesunate resistance may be emerging on a background of mefloquine resistance.     

Should edentulous patients be constrained to removable complete dentures? The use of dental implants to improve the quality of life for edentulous patients

doi:10.1111/j.1741‐2358.2009.00294.x
Should edentulous patients be constrained to removable complete dentures? The use of dental implants to improve the quality of life for edentulous patients Background: Nowadays, there is some speculation among dental educators that the need for complete dentures will significantly decrease in the future and that training in their provision should be removed from the dental curriculum. Objective: To sensitise the reader to the functional shortcomings of complete denture therapy in the edentulous patient and present restorative options including implants to improve edentulous quality of life in these patients. Methods: Information retrieval followed a systematic approach using PubMed. English articles published from 1964 to 2008, in which the masticatory performance of patients with implant‐supported dentures was assessed by objective methods and compared with performance with conventional dentures, were included. Results: National epidemiological survey data suggested that the adult population in need of one or two complete dentures will increase from 35.4 million adults in 2000 to 37.9 million adults in 2020. Clinical studies have showed that the ratings of general satisfaction were significantly better in the patients treated with implant overdentures post‐delivery compared with the complete denture users. In addition, the implant group gave significantly higher ratings on comfort, stability and ability to chew. Furthermore, patients who received mandibular implant overdentures had significantly fewer oral health‐related quality of life problems than did the conventional group. Conclusion: Implant‐supported dentures including either complete overdentures or a hybrid prosthesis significantly improve the quality of life for edentulous patients compared with conventional removable complete dentures. Therefore, the contemporary dental practitioner should consider other options as well as conventional removable complete dentures to restore edentulous patients.     

Should Deceased Donors be Tested for vCJD?

The 1997 Bovine Spongiform Encephalopathy enquiry and the 2001 Hepatitis C litigation judgement set the UK scene for evoking the precautionary principle and the legal precedent that liability for defective transfusion products should not be dependent on medical negligence, but on the mere fact of defectiveness. Animal models indicate that vCJD in humans, with infection via the oral route, is likely to be associated with infectivity within the lymphoreticular system (LRS). This is likely to appear prior to the involvement of the central nervous system and thus infectivity is likely to be present in the LRS before the onset of clinical disease. A number of relevant epidemiological studies using LRS tissue have shown a low, but measurable, existence of the carrier state in vCJD. Two possible cases of transmission of the abnormal prion of vCJD by blood transfusion suggested that tissues might also transmit and that testing of LRS tissue from deceased potential tissue donors should be considered as a first measure towards the prevention of vCJD transmission by tissues designated for use in transplantation. A variety of different tissues could be used as representative of the LRS, but each is associated with problems of feasibility and practicality. Assays for vCJD have not been validated in the context of donor screening rather than epidemiological studies nor on deceased donors. However, given the number of vCJD cases in the UK, significant attention should be paid to the logistical, ethical, social and other issues associated with undertaking vCJD testing of tissue donors, with a view to introducing testing of deceased tissue donors for vCJD disease or latency.     

Can fungal biopesticides control malaria?

Recent research has raised the prospect of using insect fungal pathogens for the control of vector-borne diseases such as malaria. In the past, microbial control of insect pests in both medical and agricultural sectors has generally had limited success. We propose that it might now be possible to produce a cheap, safe and green tool for the control of malaria, which, in contrast to most chemical insecticides, will not eventually be rendered useless by evolution of resistance. Realizing this potential will require lateral thinking by biologists, technologists and development agencies.     

Can the resurgence of malaria be partially attributed to structural adjustment programmes?

Structural Adjustment Programmes (SAPs) (restrictive fiscal and monetary policies and extensive public sector reforms) were implemented in many developing countries during the 1980s. Their socio-economic impact on the poor has been widely discussed. Antimalarial efforts could have been affected by this economic reform process, and the resurgence of malaria during the past twenty years could be partially attributed to the socio-economic hardship generated by these programmes.     

Should the draft chimpanzee sequence be finished?

Owing to the availability of genome working drafts (WDs), current comparative-sequence studies are frequently performed on a genome-wide scale. In this article, we appraise the utility of WD sequences in the detection of genomic differences in closely related species. We compared human DNA sequences with draft and high-quality versions of the corresponding chimpanzee loci to reveal the overall high quality of the chimp WD sequence. Nevertheless, a significant proportion of the differences between WD and high-quality sequences we observed can be attributed to sequencing errors in the draft. Although we suggest methods to reduce the number of such false positives efficiently, our study emphasizes the benefit expected from finishing the chimpanzee genome sequence.