Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT.

BACKGROUND: The efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria may be threatened by parasites with reduced responsiveness to artemisinins. Among 298 ACT-treated children from Mbita, Kenya, submicroscopic persistence of P. falciparum on day 3 posttreatment was associated with subsequent microscopically detected parasitemia at days 28 or 42. METHODS: DNA sequences of resistance-associated parasite loci pfcrt, pfmdr1, pfubp1, and pfap2mu were determined in the Mbita cohort before treatment, on days 2 and 3 after initiation of treatment, and on the day of treatment failure. RESULTS: Parasites surviving ACT on day 2 or day 3 posttreatment were significantly more likely than the baseline population to carry the wild-type haplotypes of pfcrt (CVMNK at codons 72-76; P < .001) and pfmdr1 (NFD at codons 86, 184, 1246; P < .001). In contrast, variant alleles of the novel candidate resistance genes pfap2mu (S160N/T; P = .006) and pfubp-1 (E1528D; P < .001) were significantly more prevalent posttreatment. No genetic similarities were found to artemisinin-tolerant parasites recently described in Cambodia. CONCLUSIONS: Among treated children in western Kenya, certain P. falciparum genotypes defined at pfcrt, pfmdr1, pfap2mu, and pfubp1 more often survive ACT at the submicroscopic level, and contribute to onward transmission and subsequent patent recrudescence.

Use of ethanol extract of Mycobacterium bovis for detection of specific antibodies in sera of farmed red deer (Cervus elaphus) with bovine tuberculosis.

BACKGROUND: Bovine tuberculosis (bTB) in wildlife species poses a threat to domestic livestock in many situations. Control programs for bTB in livestock depend on testing and slaughtering the positive animals; however, the currently available diagnostic tests often have poor specificity. In our previous study, we developed a specific and sensitive enzyme linked immunosorbent assay (ELISA) for another mycobacterial disease - Johne's disease, using surface antigens of Mycobacterium avium ssp. paratuberculosis (MAP) extracted by briefly agitating the bacilli in 80% ethanol solution. The ELISA test was named ethanol vortex ELISA (EVELISA). The objective of this study is to examine whether EVELISA technique could be used to specifically detect anti-Mycobacterium bovis (M. bovis) antibodies in the serum of M. bovis-infected farmed red deer (Cervus elaphus). We tested a total of 45 red deer serum samples, divided in 3 groups - uninfected animals (n = 15), experimentally infected with M. bovis (n = 15) and experimentally infected with MAP (n = 15). RESULTS: The presence of anti-M. bovis antibodies was tested using an ethanol extract of M. bovis. Without absorption of anti-MAP cross reactive antibodies, it was found that 13 out of the 15 MAP-infected animals showed high antibody binding. Using heat killed MAP as an absorbent of cross reactive antibodies, anti-M. bovis antibodies were detected in 86.7% of M. bovis-infected animals with minor false positive results caused by MAP infection. CONCLUSIONS: The results from this study suggest that EVELISA may form a basis for a sensitive and specific test for the diagnosis of bTB in farmed red deer.

Association of sexual relationship power with PrEP persistence and other sexual health outcomes among adolescent and young women in Kenya and South Africa.

Introduction: Gendered power inequalities impact adolescent girls' and young women's (AGYW) sexual and reproductive health (SRH) outcomes. We investigated the influence of sexual relationship power on AGYW's SRH outcomes, including HIV pre-exposure prophylaxis (PrEP) persistence. Methods: The POWER study in Kisumu, Kenya, and Cape Town and Johannesburg, South Africa provided PrEP to 2,550 AGYW (aged 16-25). AGYW's perceived power in their primary sexual relationship was measured among the first 596 participants enrolled using the Sexual Relationship Power Scale's (SRPS) relationship control sub-scale. Multivariable regression was used to test for (1) key sociodemographic and relationship characteristics associated with relationship power; and (2) the association of relationship power with SRH outcomes including PrEP persistence. Results: In this cohort, the mean SRPS score was 2.56 (0.49), 542 (90.9%) initiated PrEP; 192 (35.4%) persisted with PrEP at 1 month of which 46 (24.0% of 192) persisted at 6 months. SRPS were significantly lower among AGYW who cohabited with their sex partner (-0.14, 95% CI: -0.24 to -0.04, p = 0.01), or had ≥1 sex partner (-0.10, 95% CI: -0.19 to -0.00, p = 0.05). AGYW with lower SRPS were more likely to not know their partner's HIV status (aOR 2.05, 95% CI: 1.27 to 3.33, p < 0.01), but SRPS was not associated with PrEP persistence, STI infection, condom, or hormonal contraception use. Discussion: AGYW's reasons for initiating PrEP and reasons for continuously using PrEP may be different. While low relationship power was associated with perceived HIV vulnerability, AGYW's PrEP persistence may be influenced by more than relationship power.

Health Care Providers as Agents of Change: Integrating PrEP With Other Sexual and Reproductive Health Services for Adolescent Girls and Young Women.

Background: Successful integration of pre-exposure prophylaxis (PrEP) with existing reproductive health services will require iterative learning and adaptation. The interaction between the problem-solving required to implement new interventions and health worker motivation has been well-described in the public health literature. This study describes structural and motivational challenges faced by health care providers delivering PrEP to adolescent girls and young women (AGYW) alongside other SRH services, and the strategies used to overcome them. Methods: We conducted in-depth interviews (IDIs) and focus group discussions (FGDs) with HCWs from two demonstration projects delivering PrEP to AGYW alongside other SRH services. The Prevention Options for the Women Evaluation Research (POWER) is an open label PrEP study with a focus on learning about PrEP delivery in Kenyan and South African family planning, youth mobile services, and public clinics at six facilities. PrIYA focused on PrEP delivery to AGYW via maternal and child health (MCH) and family planning (FP) clinics in Kenya across 37 facilities. IDIs and FGDs were transcribed verbatim and analyzed using a combination of inductive and deductive methods. Results: We conducted IDIs with 36 participants and 8 FGDs with 50 participants. HCW described a dynamic process of operationalizing PrEP delivery to better respond to patient needs, including modifying patient flow, pill packaging, and counseling. HCWs believed the biggest challenge to sustained integration and scaling of PrEP for AGYW would be lack of health care worker motivation, primarily due to a misalignment of personal and professional values and expectations. HCWs frequently described concerns of PrEP provision being seen as condoning or promoting unprotected sex among young unmarried, sexually active women. Persuasive techniques used to overcome these reservations included emphasizing the social realities of HIV risk, health care worker professional identities, and vocational commitments to keeping young women healthy. Conclusion: Sustained scale-up of PrEP will require HCWs to value and prioritize its incorporation into daily practice. As with the provision of other SRH services, HCWs may have moral reservations about providing PrEP to AGYW. Strategies that strengthen alignment of HCW personal values with professional goals will be important for strengthening motivation to overcome delivery challenges.

The Significance of an MBA Degree for a Podiatric Physician-Is It Worth It? A Survey Study.

BACKGROUND:: The Kent State University College of Podiatric Medicine is negotiating with the College of Business Administration at Kent State University to establish a dual Doctor of Podiatric Medicine (DPM)/Master of Business Administration (MBA) degree. Of the nine colleges of podiatric medicine in the nation, there are two schools that have a joint DPM/MBA program listed in their catalogue, but no joint program was operational at the time this survey was conducted. A telephone survey of the other eight podiatric medical colleges was conducted to obtain that information. This survey was used to assess further data for the exploration of a dual DPM/MBA program at Kent State University College of Podiatric Medicine. METHODS:: A survey was sent out to 38 individuals who possessed both a DPM and an MBA degree. They responded to questions about why they obtained the business degree, how they are using their business degree, what courses in the MBA program are most relevant, and whether they would recommend that DPM students pursue a dual degree. RESULTS:: The majority of respondents indicated that they obtained an MBA degrees to gain a better understanding of the marketplace, to increase their income, and to better manage a podiatric medical practice. The respondents were generally very happy to have obtained their MBA degree and would encourage a dual-degree option. They admitted that a minor or series of courses with a business focus may be helpful to a DPM student who did not opt for an MBA degree. CONCLUSIONS:: The positive survey results from respondents encourage continued research into a dual-degree DPM/MBA program. During research for a DPM/MBA degree, we feel a DPM with an MBA degree will allow our students to be better prepared for leadership roles within their community and administrative positions and to have a deeper understanding of the business of health care.

Pedal Cutaneous Manifestations of Tuberous Sclerosis.

This case report concerns a patient with a painful soft-tissue mass on his fourth toe. He was evaluated for this soft-tissue mass and was diagnosed as having tuberous sclerosis. The podiatric physician should be able to evaluate a patient with a lower-extremity complaint and relate whether this complaint may correlate with a systemic disorder. This case report will make the podiatric physician more aware of tuberous sclerosis and the manifestations of the disorder.

Plantar fasciitis: what is the diagnosis and treatment?

Foot pain, specifically plantar heel pain, is a common complaint among patients in a podiatric or orthopaedic office setting but may be seen in primary care offices, urgent care centers, or emergency departments as well. There are numerous causes for heel pain, but plantar fasciitis is the most frequent cause. The diagnosis of plantar fasciitis is generally made clinically, but there are many diagnostic modalities that may be used to confirm the diagnosis. Treatment of plantar fasciitis ranges from conservative measures to surgical interventions, but most cases of plantar fasciitis can be managed conservatively. There is no definitive treatment proven to be the best option for plantar fasciitis. Treatment is patient dependent and commonly requires a combination of different modalities to successfully alleviate the symptoms. In this article, plantar fasciitis from defining the disorder, diagnosis, and treatment are discussed.

A promoter mutation in the haemagglutinin segment of influenza A virus generates an effective candidate live attenuated vaccine.

BACKGROUND: Annual seasonal and pandemic influenza vaccines need to be produced in a very tight time frame. Haemagglutinin (HA) is the major immunogenic component of influenza vaccines, and there is a lot of interest in improving candidate vaccine viruses. OBJECTIVES: It has been shown elsewhere that mutations introduced in the non-coding region of influenza genome segments can upregulate protein expression. Our objective was to assess a virus based on the laboratory strain A/PR/8/34 (PR8) containing a modified 3' non-coding region of RNA segment 4 (haemagglutinin). METHODS: NIBRG-93 was generated using reverse genetics. HA protein expression and growth properties were assessed. The virus phenotype suggested that it could be a candidate for use as a live attenuated vaccine, so in vivo studies were performed to assess its suitability. RESULTS: NIBRG-93 virus has enhanced haemagglutinin production and is significantly attenuated. Electron microscopy (EM) shows that the modified virus produces a large proportion of 'virus-like particles' that consist of budded cell membrane covered in HA but lacking M1 protein. The virus was shown to be attenuated in mice and offered complete protection against lethal challenge. CONCLUSIONS: We demonstrate that NIBRG-93 is an effective live attenuated vaccine virus protecting mice against lethal challenge and reducing virus shedding.

Case Report on Calciphylaxis: An Early Diagnosis and Treatment May Improve Outcome.

This is a case report of a patient who presented to the wound care center with LE ulcerations that were subsequently diagnosed with calciphylaxis. She was an insulin dependent diabetic with renal disease, but unaware of her critical kidney status. She was treated with local wound care, a partial parathyroidectomy, and started on dialysis. She is currently healed with no recurrence of ulcerations. Her ulcerations were controlled with conservative wound care and no surgical debridement.

Permissible variation in the 3' non-coding region of the haemagglutinin genome segment of the H5N1 candidate influenza vaccine virus NIBRG-14 [corrected].

The candidate H5N1 vaccine virus NIBRG-14 was created in response to a call from the World Health Organisation in 2004 to prepare candidate vaccine viruses (CVVs) to combat the threat of an H5N1 pandemic. NIBRG-14 was created by reverse genetics and is composed of the neuraminidase (NA) and modified haemagglutinin (HA) genes from A/Vietnam/1194/2004 and the internal genes of PR8, a high growing laboratory adapted influenza A(H1N1) strain. Due to time constraints, the non-coding regions (NCRs) of A/Vietnam/1194/2004 HA were not determined prior to creating NIBRG-14. Consequently, the sequence of the primers used to clone the modified A/Vietnam/1194/2004 HA was based upon previous experience of cloning H5N1 viruses. We report here that the HA 3' NCR sequence of NIBRG-14 is different to that of the parental wild type virus A/Vietnam/1194/2004; however this does not appear to impact on its growth or antigen yield. We introduced additional small changes into the 3'NCR of NIBRG-14; these had only minor effects on viral growth and antigen content. These findings may serve to assure the influenza vaccine community that generation of CVVs using best-guess NCR sequences, based on sequence alignments, are likely to produce robust viruses.

Improved haemagglutinin antigen content in H5N1 candidate vaccine viruses with chimeric haemagglutinin molecules.

The candidate vaccine virus NIBRG-14 was derived by reverse genetics and comprises the haemagglutinin (HA) and neuraminidase (NA) genes derived from the clade 1 virus A/Viet Nam/1194/2004 on an A/Puerto Rico/8/34 (PR8) backbone. The HA gene was modified to remove the multibasic cleavage site motif associated with high pathogenicity. Reports from manufacturers, confirmed by data generated in this laboratory, have shown that this virus yields a low amount of HA antigen. We have generated a panel of new viruses using reverse genetics in which each virus consists of the PR8 backbone, the NA gene from A/Viet Nam/1194/2004 and a chimeric HA gene with sequences from both PR8 and A/Viet Nam/1194/2004. Here we show that a number of these viruses have improved HA antigen content and yield and are therefore better candidate vaccine viruses for use in production of H5N1 vaccine.

Evaluation of first unprovoked seizures in children by general paediatricians in New Zealand.

AIM: To determine current practice of general paediatricians in New Zealand in the investigation and management of a first unprovoked seizure in childhood. METHODS: A self-administered questionnaire was emailed to 109 general paediatricians in New Zealand. The questionnaire presented the participant with three hypothetical case scenarios representing a generalised tonic clonic seizure, a complex partial seizure and an episode of non-specific collapse. The participant was asked to indicate what investigations and course of management was required. RESULTS: Forty-seven questionnaires were returned. Primary investigations included an electroencephalogram (EEG) in 47% of cases after a first generalised tonic clonic seizure increasing to 89% after a second. Ninety-one per cent of paediatricians were likely to request an EEG after a complex partial seizure. No paediatrician would request neuroimaging following a first generalised tonic clonic seizure. Neuroimaging was requested by 10% of paediatricians following a second generalised tonic clonic seizure and by 47% following a complex partial seizure. No paediatrician elected to initiate antiepileptic drugs after a first generalised tonic clonic seizure, but 49% would initiate treatment after a second generalised tonic clonic seizure. Eleven per cent of paediatricians would start treatment after a single complex partial seizure. CONCLUSION: Less than 50% of general paediatricians would request an EEG after a first unprovoked seizure. This is an unexpectedly low rate that may reflect accessibility. New Zealand paediatricians had an appropriately low rate of requesting neuroimaging. As currently recommended no general paediatricians began antiepileptic drugs in the scenario of a single uncomplicated seizure in the absence of other risk factors.